WorldWideScience

Sample records for exhibit differential sensitivity

  1. Superconductive microstrip exhibiting negative differential resistivity

    International Nuclear Information System (INIS)

    Huebener, R.P.; Gallus, D.E.

    1975-01-01

    A device capable of exhibiting negative differential electrical resistivity over a range of values of current and voltage is formed by vapor-depositing a thin layer of a material capable of exhibiting superconductivity on an insulating substrate, establishing electrical connections at opposite ends of the deposited strip, and cooling the alloy into its superconducting range. The device will exhibit negative differential resistivity when biased in the current-induced resistive state

  2. Sensitivity analysis and design optimization through automatic differentiation

    International Nuclear Information System (INIS)

    Hovland, Paul D; Norris, Boyana; Strout, Michelle Mills; Bhowmick, Sanjukta; Utke, Jean

    2005-01-01

    Automatic differentiation is a technique for transforming a program or subprogram that computes a function, including arbitrarily complex simulation codes, into one that computes the derivatives of that function. We describe the implementation and application of automatic differentiation tools. We highlight recent advances in the combinatorial algorithms and compiler technology that underlie successful implementation of automatic differentiation tools. We discuss applications of automatic differentiation in design optimization and sensitivity analysis. We also describe ongoing research in the design of language-independent source transformation infrastructures for automatic differentiation algorithms

  3. Differential sensitivity of long-sleep and short-sleep mice to high doses of cocaine.

    Science.gov (United States)

    de Fiebre, C M; Ruth, J A; Collins, A C

    1989-12-01

    The cocaine sensitivity of male and female long-sleep (LS) and short-sleep (SS) mice, which have been selectively bred for differential ethanol-induced "sleep-time," was examined in a battery of behavioral and physiological tests. Differences between these two mouse lines were subtle and were seen primarily at high doses. At high doses, SS mice were more sensitive than LS mice, particularly to cocaine-induced hypothermia; however, significant hypothermia was not seen except at doses which were very near to the seizure threshold. During a 60-min test of locomotor activity, LS mice showed greater stimulation of Y-maze activity by 20 mg/kg cocaine than SS mice. Consistent with the finding of subtle differences in sensitivity to low doses of cocaine. LS and SS mice did not differ in sensitivity to cocaine inhibition of synaptosomal uptake of [3H]-dopamine, [3H]-norepinephrine or [3H]-5-hydroxytryptamine. However, consistent with the finding of differential sensitivity to high doses of cocaine, SS mice were more sensitive to the seizure-producing effects of the cocaine and lidocaine, a local anesthetic. It is hypothesized that the differential sensitivity of these mouse lines to high doses of cocaine is due to differential sensitivity to cocaine's actions on systems that regulate local anesthetic effects. Selective breeding for differential duration of alcohol-induced "sleep-time" may have resulted in differential ion channel structure or function in these mice.

  4. Graphene nanomesh-based devices exhibiting a strong negative differential conductance effect

    International Nuclear Information System (INIS)

    Hung Nguyen, V; Mazzamuto, F; Saint-Martin, J; Bournel, A; Dollfus, P

    2012-01-01

    Using atomistic quantum simulation based on a tight binding model, we have investigated the transport characteristics of graphene nanomesh-based devices and evaluated the possibilities of observing negative differential conductance. It is shown that by taking advantage of bandgap opening in the graphene nanomesh lattice, a strong negative differential conductance effect can be achieved at room temperature in pn junctions and n-doped structures. Remarkably, the effect is improved very significantly (with a peak-to-valley current ratio of a few hundred) and appears to be weakly sensitive to the transition length in graphene nanomesh pn hetero-junctions when inserting a pristine (gapless) graphene section in the transition region between n and p zones. The study therefore suggests new design strategies for graphene electronic devices which may offer strong advantages in terms of performance and processing over the devices studied previously. (paper)

  5. Toward Analytic Solution of Nonlinear Differential Difference Equations via Extended Sensitivity Approach

    International Nuclear Information System (INIS)

    Darmani, G.; Setayeshi, S.; Ramezanpour, H.

    2012-01-01

    In this paper an efficient computational method based on extending the sensitivity approach (SA) is proposed to find an analytic exact solution of nonlinear differential difference equations. In this manner we avoid solving the nonlinear problem directly. By extension of sensitivity approach for differential difference equations (DDEs), the nonlinear original problem is transformed into infinite linear differential difference equations, which should be solved in a recursive manner. Then the exact solution is determined in the form of infinite terms series and by intercepting series an approximate solution is obtained. Numerical examples are employed to show the effectiveness of the proposed approach. (general)

  6. [DIFFERENTIAL SENSITIVITY OF MICROORGANISMS TO POLYHEXAMETHYLENEGUANIDINE].

    Science.gov (United States)

    Lysytsya, A V; Mandygra, Y M; Bojko, O P; Romanishyna, O O; Mandygra, M S

    2015-01-01

    Factors identified that affect the sensitivity of microorganisms to polyhexamethyleneguanidine (PHMG). Salts of PHMG chloride, valerate, maleate, succinate was to use. Test strains of Esherichia coli, Staphylococcus aureus, Bacillus cereus, Leptospira interrogans, Paenibacillus larvae, Mycobacterium bovis, M. avium, M. fortuitum, Aspergillus niger and some strains of viruses are taken as objects of research. We have determined that the cytoplasm membrane phospholipids is main "target" for the polycation molecules of PHMG. A differential sensitivity of the microorganisms to this drug is primarily determined by relative amount of lipids in membrane and their accessibility. Such trends exist: increase the relative contents of anionic lipids and more negative surface electric potential of membrane, and reduction of the sizes fat acid remainder of lipids bring to increase of microorganism sensitivity. Types of anion salt PHMG just have a certain value. Biocide activity of PHMG chloride is more, than its salts with organic acid. Feasibility of combining PHMG with other biocides in the multicomponent disinfectants studied and analyzed. This combination does not lead to a significant increase in the sensitivity of microorganisms tested in most cases. Most species of pathogenic bacteria can be quickly neutralized by aqueous solutions of PHMG in less than 1% concentrations.

  7. CONSTRUCTION OF A DIFFERENTIAL ISOTHERMAL CALORIMETER OF HIGH SENSITIVITY AND LOW COST.

    OpenAIRE

    Trinca, RB; Perles, CE; Volpe, PLO

    2009-01-01

    CONSTRUCTION OF A DIFFERENTIAL ISOTHERMAL CALORIMETER OF HIGH SENSITIVITY AND LOW COST The high cost of sensitivity commercial calorimeters may represent an obstacle for many calorimetric research groups. This work describes (fie construction and calibration of a batch differential heat conduction calorimeter with sample cells volumes of about 400 mu L. The calorimeter was built using two small high sensibility square Peltier thermoelectric sensors and the total cost was estimated to be about...

  8. Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ke, E-mail: dingke@med.uestc.edu.cn [Department of Pediatric Surgery, School of medicine, University of Electronic Science and Technology of China, Chengdu 610072 (China); Sichuan Academy of Medical Sciences & Sichuan Provincial People' s Hospital, Chengdu 610072 (China); Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Liu, Wen-ying; Zeng, Qiang; Hou, Fang [Department of Pediatric Surgery, School of medicine, University of Electronic Science and Technology of China, Chengdu 610072 (China); Sichuan Academy of Medical Sciences & Sichuan Provincial People' s Hospital, Chengdu 610072 (China); Xu, Jian-zhong, E-mail: xjzspine@163.com [Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Yang, Zhong, E-mail: zyang1999@163.com [Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2017-03-01

    Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering.

  9. Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation

    International Nuclear Information System (INIS)

    Ding, Ke; Liu, Wen-ying; Zeng, Qiang; Hou, Fang; Xu, Jian-zhong; Yang, Zhong

    2017-01-01

    Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering.

  10. Msx1-modulated muscle satellite cells retain a primitive state and exhibit an enhanced capacity for osteogenic differentiation.

    Science.gov (United States)

    Ding, Ke; Liu, Wen-Ying; Zeng, Qiang; Hou, Fang; Xu, Jian-Zhong; Yang, Zhong

    2017-03-01

    Multipotent muscle satellite cells (MuSCs) have been identified as potential seed cells for bone tissue engineering. However, MuSCs exhibit a rapid loss of stemness after in vitro culturing, thereby compromising their therapeutic efficiency. Muscle segment homeobox gene 1 (msx1) has been found to induce the dedifferentiation of committed progenitor cells, as well as terminally differentiated myotubes. In this study, a Tet-off retroviral gene delivery system was used to modulate msx1 expression. After ten passages, MuSCs that did not express msx-1 (e.g., the non-msx1 group) were compared with MuSCs with induced msx-1 expression (e.g., the msx1 group). The latter group exhibited a more juvenile morphology, it contained a significantly lower percentage of senescent cells characterized by positive β-galactosidase staining, and it exhibited increased proliferation and a higher proliferation index. Immunocytochemical stainings further detected a more primitive gene expression profile for the msx1 group, while osteogenic differentiation assays and ectopic bone formation assays demonstrated an improved capacity for the msx1 group to undergo osteogenic differentiation. These results suggest that transient expression of msx1 in MuSCs can retain a primitive state, thereby enhancing their capacity for osteogenic differentiation and restoring the potential for MuSCs to serve as seed cells for bone tissue engineering. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Application of differential sensitivity theory to transients with scram

    International Nuclear Information System (INIS)

    Parks, C.V.; Maudlin, P.J.; Weber, C.F.

    1980-01-01

    Differential sensitivity theory (DST) based on adjoint functions has been applied to various reactor safety problems. The most comprehensive application of DST sensitivity analysis has addressed the coupled thermal-hydraulic equations of the MELT-III fast reactor safety code, where a power ramp was imposed to eliminate the neutron point kinetics equations. In extending the above work to include realistic neutronic coupling, a DST procedure was developed for dealing with parameter discontinuities induced by dependent variables

  12. Differential Search Coils Based Magnetometers: Conditioning, Magnetic Sensitivity, Spatial Resolution

    Directory of Open Access Journals (Sweden)

    Timofeeva Maria

    2012-03-01

    Full Text Available A theoretical and experimental comparison of optimized search coils based magnetometers, operating either in the Flux mode or in the classical Lenz-Faraday mode, is presented. The improvements provided by the Flux mode in terms of bandwidth and measuring range of the sensor are detailed. Theory, SPICE model and measurements are in good agreement. The spatial resolution of the sensor is studied which is an important parameter for applications in non destructive evaluation. A general expression of the magnetic sensitivity of search coils sensors is derived. Solutions are proposed to design magnetometers with reduced weight and volume without degrading the magnetic sensitivity. An original differential search coil based magnetometer, made of coupled coils, operating in flux mode and connected to a differential transimpedance amplifier is proposed. It is shown that this structure is better in terms of volume occupancy than magnetometers using two separated coils without any degradation in magnetic sensitivity. Experimental results are in good agreement with calculations.

  13. Evaluation of the Sensitivity and Specificity of Immunohistochemical Markers in the Differential Diagnosis of Effusion Cytology

    Directory of Open Access Journals (Sweden)

    Zahraa Mohammed Yahya

    2013-11-01

    Full Text Available Objective: To evaluate the sensitivity and specificity of Calretinin and Carcinoembryonic antigen as immunocytochemical markers in distinguishing mesothelial cells from metastatic adenocarcinoma cells in effusion cytology.Methods: This study included 50 patients who presented with effusions (26 pleural and 24 peritoneal, at Al-Kadhimya Teaching Hospital who were selected according to their preliminary diagnosis from 1st December 2010 to 30th June 2011. Effusion fluids were aspirated and processed for both conventional cytological methods using Papanicolaou-stain and immunocytochemical staining with anti Calretinin and Carcinoembryonic antigen.Results: The sensitivity of cytology for detection of malignant cells was 77%, with 100% specificity and 86% accuracy. Calretinin was observed to be a specific (100% and sensitive (90% marker for mesothelial cells (of benign etiology. Carcinoembryonic antigen exhibited 70% sensitivity and 100% specificity for adenocarcinoma cells. When the results of both cytology and immunocytochemistry were considered in conjunction, the sensitivity for the detection of malignancy increased to 97%, with 100% specificity and 98% accuracy.Conclusion: Calretinin and Carcinoembryonic antigen were found to be useful markers for differentiating reactive mesothelial cells from metastatic adenocarcinoma cells in smears prepared from body fluids. Also, the combination of both cytology and immunocytochemical studies using the two markers can greatly enhance the diagnostic accuracy, sensitivity and specificity in malignant effusions.

  14. DDASAC, Double-Precision Differential or Algebraic Sensitivity Analysis

    International Nuclear Information System (INIS)

    Caracotsios, M.; Stewart, W.E.; Petzold, L.

    1997-01-01

    1 - Description of program or function: DDASAC solves nonlinear initial-value problems involving stiff implicit systems of ordinary differential and algebraic equations. Purely algebraic nonlinear systems can also be solved, given an initial guess within the region of attraction of a solution. Options include automatic reconciliation of inconsistent initial states and derivatives, automatic initial step selection, direct concurrent parametric sensitivity analysis, and stopping at a prescribed value of any user-defined functional of the current solution vector. Local error control (in the max-norm or the 2-norm) is provided for the state vector and can include the sensitivities on request. 2 - Method of solution: Reconciliation of initial conditions is done with a damped Newton algorithm adapted from Bain and Stewart (1991). Initial step selection is done by the first-order algorithm of Shampine (1987), extended here to differential-algebraic equation systems. The solution is continued with the DASSL predictor- corrector algorithm (Petzold 1983, Brenan et al. 1989) with the initial acceleration phase detected and with row scaling of the Jacobian added. The backward-difference formulas for the predictor and corrector are expressed in divide-difference form, and the fixed-leading-coefficient form of the corrector (Jackson and Sacks-Davis 1980, Brenan et al. 1989) is used. Weights for error tests are updated in each step with the user's tolerances at the predicted state. Sensitivity analysis is performed directly on the corrector equations as given by Catacotsios and Stewart (1985) and is extended here to the initialization when needed. 3 - Restrictions on the complexity of the problem: This algorithm, like DASSL, performs well on differential-algebraic systems of index 0 and 1 but not on higher-index systems; see Brenan et al. (1989). The user assigns the work array lengths and the output unit. The machine number range and precision are determined at run time by a

  15. PDASAC, Partial Differential Sensitivity Analysis of Stiff System

    International Nuclear Information System (INIS)

    Caracotsios, M.; Stewart, W.E.

    2001-01-01

    1 - Description of program or function: PDASAC solves stiff, nonlinear initial-boundary-value problems in a timelike dimension t and a space dimension x. Plane, circular cylindrical or spherical boundaries can be handled. Mixed-order systems of partial differential and algebraic equations can be analyzed with members of order or 0 or 1 in t, 0, 1 or 2 in x. Parametric sensitivities of the calculated states are computed simultaneously on request, via the Jacobian of the state equations. Initial and boundary conditions are efficiently reconciled. Local error control (in the max-norm or the 2-norm) is provided for the state vector and can include the parametric sensitivities if desired. 2 - Method of solution: The method of lines is used, with a user- selected x-grid and a minimum-bandwidth finite-difference approximations of the x-derivatives. Starting conditions are reconciled with a damped Newton algorithm adapted from Bain and Stewart (1991). Initial step selection is done by the first-order algorithms of Shampine (1987), extended here to differential- algebraic equation systems. The solution is continued with the DASSL predictor-corrector algorithm (Petzold 1983, Brenan et al. 1989) with the initial acceleration phase deleted and with row scaling of the Jacobian added. The predictor and corrector are expressed in divided-difference form, with the fixed-leading-coefficient form of corrector (Jackson and Sacks-Davis 1989; Brenan et al. 1989). Weights for the error tests are updated in each step with the user's tolerances at the predicted state. Sensitivity analysis is performed directly on the corrector equations of Caracotsios and Stewart (1985) and is extended here to the initialization when needed. 3 - Restrictions on the complexity of the problem: This algorithm, like DASSL, performs well on differential-algebraic equation systems of index 0 and 1 but not on higher-index systems; see Brenan et al. (1989). The user assigned the work array lengths and the output

  16. A combination of differential method and perturbation theory for the calculation of sensitivity coefficients

    International Nuclear Information System (INIS)

    Santos, Adimir dos; Borges, A.A.

    2000-01-01

    A new method for the calculation of sensitivity coefficients is developed. The new method is a combination of two methodologies used for calculating these coefficients, which are the differential and the generalized perturbation theory methods. The proposed method utilizes as integral parameter the average flux in an arbitrary region of the system. Thus, the sensitivity coefficient contains only the component corresponding to the neutron flux. To obtain the new sensitivity coefficient, the derivates of the integral parameter, φ(ξ), with respect to σ are calculated using the perturbation method and the functional derivates of this generic integral parameter with respect to σ and φ are calculated using the differential method. The new method merges the advantages of the differential and generalized perturbation theory methods and eliminates their disadvantages. (author)

  17. Theoretical foundations for traditional and generalized sensitivity functions for nonlinear delay differential equations.

    Science.gov (United States)

    Banks, H Thomas; Robbins, Danielle; Sutton, Karyn L

    2013-01-01

    In this paper we present new results for differentiability of delay systems with respect to initial conditions and delays. After motivating our results with a wide range of delay examples arising in biology applications, we further note the need for sensitivity functions (both traditional and generalized sensitivity functions), especially in control and estimation problems. We summarize general existence and uniqueness results before turning to our main results on differentiation with respect to delays, etc. Finally we discuss use of our results in the context of estimation problems.

  18. A combination between the differential and the perturbation theory methods for calculating sensitivity coefficients

    International Nuclear Information System (INIS)

    Borges, Antonio Andrade

    1998-01-01

    A new method for the calculation of sensitivity coefficients is developed. The new method is a combination of two methodologies used for calculating theses coefficients, which are the differential and the generalized perturbation theory methods. The method utilizes as integral parameter the average flux in an arbitrary region of the system. Thus, the sensitivity coefficient contains only the component corresponding to the neutron flux. To obtain the new sensitivity coefficient, the derivatives of the integral parameter, Φ, with respect to σ are calculated using the perturbation method and the functional derivatives of this generic integral parameter with respect to σ and Φ are calculated using the differential method. (author)

  19. Stress Sensitivity Is Associated with Differential Accumulation of Reactive Oxygen and Nitrogen Species in Maize Genotypes with Contrasting Levels of Drought Tolerance

    Science.gov (United States)

    Yang, Liming; Fountain, Jake C.; Wang, Hui; Ni, Xinzhi; Ji, Pingsheng; Lee, Robert D.; Kemerait, Robert C.; Scully, Brian T.; Guo, Baozhu

    2015-01-01

    Drought stress decreases crop growth, yield, and can further exacerbate pre-harvest aflatoxin contamination. Tolerance and adaptation to drought stress is an important trait of agricultural crops like maize. However, maize genotypes with contrasting drought tolerances have been shown to possess both common and genotype-specific adaptations to cope with drought stress. In this research, the physiological and metabolic response patterns in the leaves of maize seedlings subjected to drought stress were investigated using six maize genotypes including: A638, B73, Grace-E5, Lo964, Lo1016, and Va35. During drought treatments, drought-sensitive maize seedlings displayed more severe symptoms such as chlorosis and wilting, exhibited significant decreases in photosynthetic parameters, and accumulated significantly more reactive oxygen species (ROS) and reactive nitrogen species (RNS) than tolerant genotypes. Sensitive genotypes also showed rapid increases in enzyme activities involved in ROS and RNS metabolism. However, the measured antioxidant enzyme activities were higher in the tolerant genotypes than in the sensitive genotypes in which increased rapidly following drought stress. The results suggest that drought stress causes differential responses to oxidative and nitrosative stress in maize genotypes with tolerant genotypes with slower reaction and less ROS and RNS production than sensitive ones. These differential patterns may be utilized as potential biological markers for use in marker assisted breeding. PMID:26492235

  20. Stress Sensitivity Is Associated with Differential Accumulation of Reactive Oxygen and Nitrogen Species in Maize Genotypes with Contrasting Levels of Drought Tolerance

    Directory of Open Access Journals (Sweden)

    Liming Yang

    2015-10-01

    Full Text Available Drought stress decreases crop growth, yield, and can further exacerbate pre-harvest aflatoxin contamination. Tolerance and adaptation to drought stress is an important trait of agricultural crops like maize. However, maize genotypes with contrasting drought tolerances have been shown to possess both common and genotype-specific adaptations to cope with drought stress. In this research, the physiological and metabolic response patterns in the leaves of maize seedlings subjected to drought stress were investigated using six maize genotypes including: A638, B73, Grace-E5, Lo964, Lo1016, and Va35. During drought treatments, drought-sensitive maize seedlings displayed more severe symptoms such as chlorosis and wilting, exhibited significant decreases in photosynthetic parameters, and accumulated significantly more reactive oxygen species (ROS and reactive nitrogen species (RNS than tolerant genotypes. Sensitive genotypes also showed rapid increases in enzyme activities involved in ROS and RNS metabolism. However, the measured antioxidant enzyme activities were higher in the tolerant genotypes than in the sensitive genotypes in which increased rapidly following drought stress. The results suggest that drought stress causes differential responses to oxidative and nitrosative stress in maize genotypes with tolerant genotypes with slower reaction and less ROS and RNS production than sensitive ones. These differential patterns may be utilized as potential biological markers for use in marker assisted breeding.

  1. Quartz crystal microbalance-based system for high-sensitivity differential sputter yield measurements

    International Nuclear Information System (INIS)

    Rubin, B.; Topper, J. L.; Farnell, C. C.; Yalin, A. P.

    2009-01-01

    We present a quartz crystal microbalance-based system for high sensitivity differential sputter yield measurements of different target materials due to ion bombardment. The differential sputter yields can be integrated to find total yields. Possible ion beam conditions include ion energies in the range of 30-350 eV and incidence angles of 0 deg. - 70 deg. from normal. A four-grid ion optics system is used to achieve a collimated ion beam at low energy (<100 eV) and a two-grid ion optics is used for higher energies (up to 750 eV). A complementary weight loss approach is also used to measure total sputter yields. Validation experiments are presented that confirm high sensitivity and accuracy of sputter yield measurements.

  2. Automatic differentiation for design sensitivity analysis of structural systems using multiple processors

    Science.gov (United States)

    Nguyen, Duc T.; Storaasli, Olaf O.; Qin, Jiangning; Qamar, Ramzi

    1994-01-01

    An automatic differentiation tool (ADIFOR) is incorporated into a finite element based structural analysis program for shape and non-shape design sensitivity analysis of structural systems. The entire analysis and sensitivity procedures are parallelized and vectorized for high performance computation. Small scale examples to verify the accuracy of the proposed program and a medium scale example to demonstrate the parallel vector performance on multiple CRAY C90 processors are included.

  3. Differentiation of the insulin-sensitive glucose transporter in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Frost, S.C.; Baly, D.L.; Cushman, S.W.; Lane, M.D.; Simpson, I.A.

    1986-01-01

    3T3-L1 fibroblasts differentiate in culture to resemble adipocytes both morphologically and biochemically. Insulin-sensitive glucose transport, as measured by 2-deoxy-[1- 14 C]- glucose uptake in the undifferentiated cell is small (2X). In contrast, the rate of glucose transport in fully differentiated cells is elevated 15-fold over basal in the presence of insulin. To determine if this is due to an increase in the number of transporters/cell or accessibility to the transporters, the number of transporters was measured in subcellular fractions over differentiation using a 3 H-cytochalasin B binding assay. The increase in the rate of insulin-sensitive glucose transport directly parallels an increase in the number of transporters which reside in an insulin-responsive intracellular compartment. This observation was confirmed by identifying the transporters by immunoblotting using an antibody generated against the human erythrocyte transporter. The molecular weight of this transporter increases over differentiation from a single band of 40kDa to a heterogeneous triplet of 40, 44 and 48kDa. These data suggest that the transporter undergoes differential processing and that the functional, insulin-responsive transporter may be different from the insulin-insensitive (basal) transporter

  4. Improving sensitivity of linear regression-based cell type-specific differential expression deconvolution with per-gene vs. global significance threshold.

    Science.gov (United States)

    Glass, Edmund R; Dozmorov, Mikhail G

    2016-10-06

    The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from blood samples suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. Combined with cell counts, heterogeneous gene expression may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression, and a global cutoff to judge significance, such as False Discovery Rate (FDR). Yet, they do not consider many artifacts hidden in high-dimensional gene expression data that may negatively affect linear regression. In this paper we quantify the parameter space affecting the performance of linear regression (sensitivity of cell type-specific differential expression detection) on a per-gene basis. We evaluated the effect of sample sizes, cell type-specific proportion variability, and mean squared error on sensitivity of cell type-specific differential expression detection using linear regression. Each parameter affected variability of cell type-specific expression estimates and, subsequently, the sensitivity of differential expression detection. We provide the R package, LRCDE, which performs linear regression-based cell type-specific differential expression (deconvolution) detection on a gene-by-gene basis. Accounting for variability around cell type-specific gene expression estimates, it computes per-gene t-statistics of differential detection, p-values, t-statistic-based sensitivity, group-specific mean squared error, and several gene-specific diagnostic metrics. The sensitivity of linear regression-based cell type-specific differential expression detection differed for each gene as a function of mean squared error, per group sample sizes, and variability of the proportions

  5. Paratingent Derivative Applied to the Measure of the Sensitivity in Multiobjective Differential Programming

    Directory of Open Access Journals (Sweden)

    F. García

    2013-01-01

    Full Text Available We analyse the sensitivity of differential programs of the form subject to where and are maps whose respective images lie in ordered Banach spaces. Following previous works on multiobjective programming, the notion of -optimal solution is used. The behaviour of some nonsingleton sets of -optimal solutions according to changes of the parameter in the problem is analysed. The main result of the work states that the sensitivity of the program is measured by a Lagrange multiplier plus a projection of its derivative. This sensitivity is measured by means of the paratingent derivative.

  6. Differential sensitivity of Chironomus and human hemoglobin to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gaikwad, Pallavi S. [Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007 (India); Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Panicker, Lata [Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Mohole, Madhura; Sawant, Sangeeta [Bioinformatics Center, Savitribai Phule Pune University, Pune, 411007 (India); Mukhopadhyaya, Rita [Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085 (India); Nath, Bimalendu B., E-mail: bbnath@gmail.com [Stress Biology Research Laboratory, Department of Zoology, Savitribai Phule University, Pune, 411007 (India)

    2016-08-05

    Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. -- Highlights: •Comparison of radiation tolerant Chironomus Hb and radiation sensitive Human Hb. •Amino acid composition of midge and human heme confer differential hydrophobicity. •Heme pocket of evolutionarily ancient midge Hb provide gamma radiation resistivity.

  7. Differential sensitivity of Chironomus and human hemoglobin to gamma radiation

    International Nuclear Information System (INIS)

    Gaikwad, Pallavi S.; Panicker, Lata; Mohole, Madhura; Sawant, Sangeeta; Mukhopadhyaya, Rita; Nath, Bimalendu B.

    2016-01-01

    Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. -- Highlights: •Comparison of radiation tolerant Chironomus Hb and radiation sensitive Human Hb. •Amino acid composition of midge and human heme confer differential hydrophobicity. •Heme pocket of evolutionarily ancient midge Hb provide gamma radiation resistivity.

  8. Differential Effects of Intermittent versus Continuous Haloperidol Treatment throughout Adolescence on Haloperidol Sensitization and Social Behavior in Adulthood

    Science.gov (United States)

    Gao, Jun; Li, Ming

    2014-01-01

    Animal work on the behavioral effects of antipsychotic treatment suggests that different dosing regimens could affect drug sensitivity differently, with an intermittent treatment regimen tending to cause a sensitization effect, while a continuous treatment causing a tolerance. In this study, we explored how haloperidol (HAL) sensitization induced throughout adolescence and tested in adulthood was differentially impacted by these two dosing regimens in the conditioned avoidance response (CAR) test. We also examined how these two dosing regiments affected social interaction and social memory in adulthood. Male adolescent Sprague-Dawley rats were treated with HAL via either osmotic minipump (HAL-0.25 CONT; 0.25 mg/kg/day, n = 14) or daily injection (HAL-0.05 INT; 0.05 mg/kg/injection/day, sc, n = 14), or sterile water (n = 14) from postnatal days (PND) 44 to 71. HAL sensitization was assessed in a challenge test in which all rats were injected with HAL (0.025 and 0.05 mg/kg, sc) on PND 80 and PND 82. Two days later, half of the rats from each group (n = 7/group) were assayed in two 4-trial social interaction tests in which a subject rat was given four 5-min social encounters with a familiar or novel juvenile rat (PND 35–40) at 10 min intervals. Another half were tested in a quinpirole-induced hyperlocomotion assay to assess the potential HAL-induced change in D2-mediated function. Results show that only the intermittent dosing group under the HAL 0.05 mg/kg challenge showed a robust sensitization effect as rats in this group made significantly fewer avoidance responses than those in the vehicle and HAL-0.25 CONT groups. Adolescent HAL treatment did not affect social behavior and social memory, as rats from all 3 groups exhibited a similar level of social interaction and showed a similar level of sensitivity to the change of social stimuli. Similarly, adolescent HAL treatment also did not produce a long-lasting change in D2 function, as all 3 groups exhibited a

  9. Differential Privacy for Relational Algebra: Improving the Sensitivity Bounds via Constraint Systems

    Directory of Open Access Journals (Sweden)

    Catuscia Palamidessi

    2012-07-01

    Full Text Available Differential privacy is a modern approach in privacy-preserving data analysis to control the amount of information that can be inferred about an individual by querying a database. The most common techniques are based on the introduction of probabilistic noise, often defined as a Laplacian parametric on the sensitivity of the query. In order to maximize the utility of the query, it is crucial to estimate the sensitivity as precisely as possible. In this paper we consider relational algebra, the classical language for queries in relational databases, and we propose a method for computing a bound on the sensitivity of queries in an intuitive and compositional way. We use constraint-based techniques to accumulate the information on the possible values for attributes provided by the various components of the query, thus making it possible to compute tight bounds on the sensitivity.

  10. A Posteriori Finite Element Bounds for Sensitivity Derivatives of Partial-Differential-Equation Outputs. Revised

    Science.gov (United States)

    Lewis, Robert Michael; Patera, Anthony T.; Peraire, Jaume

    1998-01-01

    We present a Neumann-subproblem a posteriori finite element procedure for the efficient and accurate calculation of rigorous, 'constant-free' upper and lower bounds for sensitivity derivatives of functionals of the solutions of partial differential equations. The design motivation for sensitivity derivative error control is discussed; the a posteriori finite element procedure is described; the asymptotic bounding properties and computational complexity of the method are summarized; and illustrative numerical results are presented.

  11. Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon

    Directory of Open Access Journals (Sweden)

    Po-Chang Wu

    2013-08-01

    Conclusion: The nailfold capillaroscopic (NC patterns may be useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD patterns exhibit high specificity but relatively low sensitivity.

  12. Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration.

    Science.gov (United States)

    Li, P; Tian, H; Li, Z; Wang, L; Gao, F; Ou, Q; Lian, C; Li, W; Jin, C; Zhang, J; Xu, J-Y; Wang, J; Zhang, J; Wang, F; Lu, L; Xu, G-T

    2016-01-01

    Bone marrow mesenchymal stem cells (BMSCs) have a therapeutic role in retinal degeneration (RD). However, heterogeneity of BMSCs may be associated with differential therapeutic effects in RD. In order to confirm this hypothesis, two subsets of rat BMSCs, termed rBMSC1 and rBMSC2, were obtained, characterized and functionally evaluated in the treatment of RD of Royal College of Surgeons (RCS) rats. Both subpopulations expressed mesenchymal stem cells (MSC) markers CD29 and CD90, but were negative for hemacyte antigen CD11b and CD45 expression. In comparison with rBMSC2, rBMSC1 showed higher rate of proliferation, stronger colony formation, and increased adipogenic potential, whereas rBMSC2 exhibited higher osteogenic potential. Microarray analysis showed differential gene expression patterns between rBMSC1 and rBMSC2, including functions related to proliferation, differentiation, immunoregulation, stem cell maintenance and division, survival and antiapoptosis. After subretinal transplantation in RCS rats, rBMSC1 showed stronger rescue effect than rBMSC2, including increased b-wave amplitude, restored retinal nuclear layer thickness, and decreased number of apoptotic photoreceptors, whereas the rescue function of rBMSC2 was essentially not better than the control. Histological analysis also demonstrated that rBMSC1 possessed a higher survival rate than rBMSC2 in subretinal space. In addition, treatment of basic fibroblast growth factor, an accompanying event in subretinal injection, triggered more robust increase in secretion of growth factors by rBMSC1 as compared to rBMSC2. Taken together, these results have suggested that the different therapeutic functions of BMSC subpopulations are attributed to their distinct survival capabilities and paracrine functions. The underlying mechanisms responsible for the different functions of BMSC subpopulation may lead to a new strategy for the treatment of RD.

  13. Differential sensitivity to natural ultraviolet radiation among phytoplankton species in Arctic lakes (Spitsbergen, Norway)

    NARCIS (Netherlands)

    Donk, van E.; Faafeng, B.A.; Lange, de H.J.

    2001-01-01

    Incubation experiments demonstrated a differential sensitivity to natural UV-radiation among the dominant phytoplankton species from three Arctic lakes, situated near Ny-Ålesund, Spitsbergen (79° N). The growth of small chlorophytes, diatoms and picocyanobacteria from two oligotrophic lakes was

  14. Ethylene regulates Apple (Malus x domestica) fruit softening through a dose x time-dependent mechanism and through differential sensitivities and dependencies of cell wall-modifying genes.

    Science.gov (United States)

    Ireland, Hilary S; Gunaseelan, Kularajathevan; Muddumage, Ratnasiri; Tacken, Emma J; Putterill, Jo; Johnston, Jason W; Schaffer, Robert J

    2014-05-01

    In fleshy fruit species that have a strong requirement for ethylene to ripen, ethylene is synthesized autocatalytically, producing increasing concentrations as the fruits ripen. Apple fruit with the ACC OXIDASE 1 (ACO1) gene suppressed cannot produce ethylene autocatalytically at ripening. Using these apple lines, an ethylene sensitivity dependency model was previously proposed, with traits such as softening showing a high dependency for ethylene as well as low sensitivity. In this study, it is shown that the molecular control of fruit softening is a complex process, with different cell wall-related genes being independently regulated and exhibiting differential sensitivities to and dependencies on ethylene at the transcriptional level. This regulation is controlled through a dose × time mechanism, which results in a temporal transcriptional response that would allow for progressive cell wall disassembly and thus softening. This research builds on the sensitivity dependency model and shows that ethylene-dependent traits can progress over time to the same degree with lower levels of ethylene. This suggests that a developmental clock measuring cumulative ethylene controls the fruit ripening process.

  15. Differentiated human midbrain-derived neural progenitor cells express excitatory strychnine-sensitive glycine receptors containing α2β subunits.

    Directory of Open Access Journals (Sweden)

    Florian Wegner

    Full Text Available BACKGROUND: Human fetal midbrain-derived neural progenitor cells (NPCs may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson's disease. While glutamate and GABA(A receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing α2β subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na(+-K(+-Cl(- co-transporter 1 (NKCC1-inhibitor bumetanide did not significantly influence cell proliferation and differentiation in vitro. CONCLUSIONS/SIGNIFICANCE: These data indicate that NPCs derived from human fetal midbrain tissue acquire essential glycine receptor properties during neuronal maturation. However, glycine receptors seem to have a limited functional impact on neurogenesis and dopaminergic differentiation of NPCs in vitro.

  16. Deterministic phase measurements exhibiting super-sensitivity and super-resolution

    DEFF Research Database (Denmark)

    Schäfermeier, Clemens; Ježek, Miroslav; Madsen, Lars S.

    2018-01-01

    Phase super-sensitivity is obtained when the sensitivity in a phase measurement goes beyond the quantum shot noise limit, whereas super-resolution is obtained when the interference fringes in an interferometer are narrower than half the input wavelength. Here we show experimentally that these two...

  17. Innate immune defenses exhibit circadian rhythmicity and differential temporal sensitivity to a bacterial endotoxin in Nile tilapia (Oreochromis niloticus)

    DEFF Research Database (Denmark)

    Lazado, Carlo Cabacang; Skov, Peter Vilhelm; Pedersen, Per Bovbjerg

    2016-01-01

    The present study investigated the daily dynamics of humoral immune defenses and the temporal influence in the sensitivity of these responses to a bacterial endotoxin in Nile tilapia (Oreochromis niloticus). The first experiment subjected the fish to two photoperiod conditions, 12L:12D (LD) and 0L...... experiment, fish were injected with bacterial endotoxin lipopolysaccharide (LPS) either at ZT3 (day) or at ZT15 (night) to evaluate the temporal sensitivity of humoral immunity to a pathogen-associated molecular pattern. The results demonstrated that responses to LPS were gated by the time of day. LPS...... significantly modulated serum ALP and ANTI activities but only when the endotoxin was administered at ZT3. Serum LYZ and PER were stimulated at both injection times but with differing response profiles. Modulated LYZ activity was persistent when injected at ZT3 but transient when LPS was applied at ZT15...

  18. S36. DIFFERENTIAL ENCODING OF SENSITIZATION AND CROSS SENSITIZATION TO PSYCHOSTIMULANTS AND ANTIPSYCHOTICS IN NUCLEUS ACCUMBENS D1- AND D2- RECEPTOR EXPRESSING MEDIUM SPINY NEURONS

    Science.gov (United States)

    Amato, Davide; Heinsbroek, Jasper; Kalivas, Peter W

    2018-01-01

    Abstract Background Nearly half of all individuals diagnosed with schizophrenia abuse addictive substances such as cocaine. Currently, the neurobiological mechanisms in patients with schizophrenia that lead to cocaine abuse are unknown. A possible explanation for the co-morbidity between schizophrenia and addiction is that the rewarding properties of cocaine reverse the diminished motivational drive caused by chronic antipsychotic regimen. Moreover, chronic antipsychotic treatment can sensitize and amplify cocaine rewarding effects and exacerbate psychoses. Methods The rewarding properties of cocaine are attributed to the differential effects of dopamine on D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc). Using in vivo Ca2+ miniature microscopic imaging, we characterize the role of D1 and D2 MSN in mono- and a cross- sensitization paradigms. D1- and D2-Cre mice were injected with a Cre dependent calcium indicator (gCaMP6f) and implanted with a gradient index (GRIN) lens above the nucleus accumbens and calcium activity was recorded using a head mounted miniature microscope. Cocaine sensitization was measured after a classic repeated cocaine regiment and antipsychotic and psychostimulant cross-sensitization was measured by a single cocaine injection after chronic pre-treatment with haloperidol. Results We found that both D1-MSN and D2-MSN populations are modulated by initial cocaine experience and further modulated during the expression of cocaine sensitization. A subpopulation of D1-MSN displayed initial activation, but reduced activity during the expression of sensitization. By contrast, the majority of D2-MSNs were suppressed by initial cocaine experience, but became active during the expression of sensitization. Furthermore, activity of D1- and D2-MSNs bidirectionally related with the observed behavioral responses to cocaine. Cross-sensitization following haloperidol treatment led to increased behavioral responses to

  19. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

    Science.gov (United States)

    Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

    2014-08-05

    The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Bovine ocular squamous cell carcinoma: UV sensitivity in lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lavin, M.F.; Jennings, P.A.; Hughes, D.J. (Queensland Univ., Brisbane (Australia))

    1982-05-01

    Increased sensitivity to UV light has been demonstrated in Phytohaemagglutinin stimulated lymphocytes from normal and tumour-bearing Hereford cattle when compared to lymphocytes from other breeds. Trypan blue exclusion and inhibition of DNA synthesis were used to determine cell viability. The results obtained from time course and radiation dose experiments demonstrate biphasic survival kinetics. This is indicative of at least two separate cell populations, exhibiting differential sensitivity to UV. The increased sensitivity to UV observed in Herefords may reflect a general sensitivity to UV or alternatively a different cellular constitution in the mitogen stimulated cultures. DNA repair synthesis, measured in the presence of hydroxyurea, was of similar levels in cell cultures from Herefords and one of the control breeds.

  1. Offspring of prenatal IV nicotine exposure exhibit increased sensitivity to the reinforcing effects of methamphetamine

    Directory of Open Access Journals (Sweden)

    Steven Brown Harrod

    2012-06-01

    Full Text Available Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH in offspring using a low dose, intravenous (IV exposure method. Pregnant dams were administered nicotine (0.05 mg/kg/injection or prenatal saline (PS 3×/day on gestational days 8-21, and adult offspring were tested using METH self-administration (experiment 1 or METH-induced conditioned taste aversion (CTA; experiment 2 procedures. For METH self-administration, animals were trained to respond for IV METH (0.05 mg/kg/injection; fixed-ratio 3 and they were tested on varying doses the reinforcer (0.0005-1.0 mg/kg/injection. For METH CTA, rats received three saccharin and METH pairings (0, 0.3, or 0.5 mg/kg, sc followed by fourteen daily extinction trials. Experiment 1: PN and PS animals exhibited inverted U-shaped dose-response curves; however, the PN animal’s curve was shifted to the left, suggesting PN animals were more sensitive to the reinforcing effects of METH. Experiment 2: METH CTA was acquired in a dose-dependent manner and the factor of PN exposure was not related to the acquisition or extinction of METH-induced CTA. There were no sex differences in either experiment. These results indicate that adult offspring of IV PN exposure exhibited altered motivation for the reinforcing effects of METH. This suggests that PN exposure, via maternal smoking, will alter the reinforcing effects of METH during later stages of development, and furthermore, will influence substance use vulnerability in adult human offspring.

  2. Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

    DEFF Research Database (Denmark)

    Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia

    2013-01-01

    Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and human skin......, MSC populations obtained from different tissues exhibit significant differences in their proliferation, differentiation and molecular phenotype, which should be taken into consideration when planning their use in clinical protocols....

  3. Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

    Science.gov (United States)

    Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

    2016-06-01

    Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

  4. Differential sensitivity of coral larvae to natural levels of ultraviolet radiation during the onset of larval competence.

    KAUST Repository

    Aranda, Manuel

    2011-07-01

    Scleractinian corals are the major builders of the complex structural framework of coral reefs. They live in tropical waters around the globe where they are frequently exposed to potentially harmful ultraviolet radiation (UVR). The eggs and early embryonic stages of some coral species are highly buoyant and remain near the sea surface for prolonged periods of time and may therefore be the most sensitive life stages with respect to UVR. Here, we analysed gene expression changes in five developmental stages of the Caribbean coral Montastraea faveolata to natural levels of UVR using high-density cDNA microarrays (10 930 clones). We found that larvae exhibit low sensitivity to natural levels of UVR during early development as reflected by comparatively few transcriptomic changes in response to UVR. However, we identified a time window of high UVR sensitivity that coincides with the motile planula stage and the onset of larval competence. These processes have been shown to be affected by UVR exposure, and the transcriptional changes we identified explain these observations well. Our analysis of differentially expressed genes indicates that UVR alters the expression of genes associated with stress response, the endoplasmic reticulum, Ca(2+) homoeostasis, development and apoptosis during the motile planula stage and affects the expression of neurogenesis-related genes that are linked to swimming and settlement behaviour at later stages. Taken together, our study provides further data on the impact of natural levels of UVR on coral larvae. Furthermore, our results might allow a better prediction of settlement and recruitment rates after coral spawning events if UVR climate data are taken into account.

  5. Differential housing and novelty response: Protection and risk from locomotor sensitization.

    Science.gov (United States)

    Garcia, Erik J; Haddon, Tara N; Saucier, Donald A; Cain, Mary E

    2017-03-01

    High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3mg/kg) or saline and then either stayed in or switched housing environments for 30days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce

  6. Bovine ocular squamous cell carcinoma: UV sensitivity in lymphocytes

    International Nuclear Information System (INIS)

    Lavin, M.F.; Jennings, P.A.; Hughes, D.J.

    1982-01-01

    Increased sensitivity to UV light has been demonstrated in Phytohaemagglutinin stimulated lymphocytes from normal and tumour-bearing Hereford cattle when compared to lymphocytes from other breeds. Trypan blue exclusion and inhibition of DNA synthesis were used to determine cell viability. The results obtained from time course and radiation dose experiments demonstrate biphasic survival kinetics. This is indicative of at least two separate cell populations, exhibiting differential sensitivity to UV. The increased sensitivity to UV observed in Herefords may reflect a general sensitivity to UV or alternatively a different cellular constitution in the mitogen stimulated cultures. DNA repair synthesis, measured in the presence of hydroxyurea, was of similar levels in cell cultures from Herefords and one of the control breeds. (author)

  7. Altered sensitivity to ellagic acid in neuroblastoma cells undergoing differentiation with 12-O-tetradecanoylphorbol-13-acetate and all-trans retinoic acid.

    Science.gov (United States)

    Alfredsson, Christina Fjæraa; Rendel, Filip; Liang, Qui-Li; Sundström, Birgitta E; Nånberg, Eewa

    2015-12-01

    Ellagic acid has previously been reported to induce reduced proliferation and activation of apoptosis in several tumor cell lines including our own previous data from non-differentiated human neuroblastoma SH-SY5Y cells. The aim of this study was now to investigate if in vitro differentiation with the phorbol ester 12-O- tetradecanoylphorbol-13-acetate or the vitamin A derivative all-trans retinoic acid altered the sensitivity to ellagic acid in SH-SY5Y cells. The methods used were cell counting and LDH-assay for evaluation of cell number and cell death, flow cytometric analysis of SubG1- and TUNEL-analysis for apoptosis and western blot for expression of apoptosis-associated proteins. In vitro differentiation was shown to reduce the sensitivity to ellagic acid with respect to cell detachment, loss of viability and activation of apoptosis. The protective effect was phenotype-specific and most prominent in all-trans retinoic acid-differentiated cultures. Differentiation-dependent up-regulation of Bcl-2 and integrin expression is introduced as possible protective mechanisms. The presented data also point to a positive correlation between proliferative activity and sensitivity to ellagic-acid-induced cell detachment. In conclusion, the presented data emphasize the need to consider degree of neuronal differentiation and phenotype of neuroblastoma cells when discussing a potential pharmaceutical application of ellagic acid in tumor treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Lonely adolescents exhibit heightened sensitivity for facial cues of emotion.

    Science.gov (United States)

    Vanhalst, Janne; Gibb, Brandon E; Prinstein, Mitchell J

    2017-02-01

    Contradicting evidence exists regarding the link between loneliness and sensitivity to facial cues of emotion, as loneliness has been related to better but also to worse performance on facial emotion recognition tasks. This study aims to contribute to this debate and extends previous work by (a) focusing on both accuracy and sensitivity to detecting positive and negative expressions, (b) controlling for depressive symptoms and social anxiety, and (c) using an advanced emotion recognition task with videos of neutral adolescent faces gradually morphing into full-intensity expressions. Participants were 170 adolescents (49% boys; M age  = 13.65 years) from rural, low-income schools. Results showed that loneliness was associated with increased sensitivity to happy, sad, and fear faces. When controlling for depressive symptoms and social anxiety, loneliness remained significantly associated with sensitivity to sad and fear faces. Together, these results suggest that lonely adolescents are vigilant to negative facial cues of emotion.

  9. Mars approach for global sensitivity analysis of differential equation models with applications to dynamics of influenza infection.

    Science.gov (United States)

    Lee, Yeonok; Wu, Hulin

    2012-01-01

    Differential equation models are widely used for the study of natural phenomena in many fields. The study usually involves unknown factors such as initial conditions and/or parameters. It is important to investigate the impact of unknown factors (parameters and initial conditions) on model outputs in order to better understand the system the model represents. Apportioning the uncertainty (variation) of output variables of a model according to the input factors is referred to as sensitivity analysis. In this paper, we focus on the global sensitivity analysis of ordinary differential equation (ODE) models over a time period using the multivariate adaptive regression spline (MARS) as a meta model based on the concept of the variance of conditional expectation (VCE). We suggest to evaluate the VCE analytically using the MARS model structure of univariate tensor-product functions which is more computationally efficient. Our simulation studies show that the MARS model approach performs very well and helps to significantly reduce the computational cost. We present an application example of sensitivity analysis of ODE models for influenza infection to further illustrate the usefulness of the proposed method.

  10. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    International Nuclear Information System (INIS)

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha; Beisiegel, Ulrike; Heeren, Joerg

    2008-01-01

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor γ (PPARγ) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPARγ agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARγ-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake

  11. Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer:

    DEFF Research Database (Denmark)

    Giovanella, Luca; Clark, Penelope M; Chiovato, Luca

    2014-01-01

    Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source...... at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians...

  12. Differentiation-associated decrease in muscarinic receptor sensitivity in human neuroblastoma cells

    International Nuclear Information System (INIS)

    Heikkilae, J.E.; Scott, J.G.; Suominen, L.A.; Akerman, K.E.O.

    1987-01-01

    Muscarinic receptor-linked increases in intracellular free Ca 2+ as measured with quin-2 and Ca 2+ release from monolayers of cells have been measured in the human neuroblastoma cell line SH-SY5Y. Induction of differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) leads to a decrease in the sensitivity of the cells to low concentrations of agonists with respect to the induced increase in cytosolic free Ca 2+ and stimulation of Ca 2+ efflux. No decrease in agonist binding affinity was observed when the displacement of a labelled antagonist, 3 H-NMS, by a non-labelled agonist was studied

  13. Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells.

    Science.gov (United States)

    Topoluk, Natasha; Hawkins, Richard; Tokish, John; Mercuri, Jeremy

    2017-09-01

    Therapeutic efficacy of various mesenchymal stromal cell (MSC) types for orthopaedic applications is currently being investigated. While the concept of MSC therapy is well grounded in the basic science of healing and regeneration, little is known about individual MSC populations in terms of their propensity to promote the repair and/or regeneration of specific musculoskeletal tissues. Two promising MSC sources, adipose and amnion, have each demonstrated differentiation and extracellular matrix (ECM) production in the setting of musculoskeletal tissue regeneration. However, no study to date has directly compared the differentiation potential of these 2 MSC populations. To compare the ability of human adipose- and amnion-derived MSCs to undergo osteogenic and chondrogenic differentiation. Controlled laboratory study. MSC populations from the human term amnion were quantified and characterized via cell counting, histologic assessment, and flow cytometry. Differentiation of these cells in comparison to commercially purchased human adipose-derived mesenchymal stromal cells (hADSCs) in the presence and absence of differentiation media was evaluated via reverse transcription polymerase chain reaction (PCR) for bone and cartilage gene transcript markers and histology/immunohistochemistry to examine ECM production. Analysis of variance and paired t tests were performed to compare results across all cell groups investigated. The authors confirmed that the human term amnion contains 2 primary cell types demonstrating MSC characteristics-(1) human amniotic epithelial cells (hAECs) and (2) human amniotic mesenchymal stromal cells (hAMSCs)-and each exhibited more than 90% staining for MSC surface markers (CD90, CD105, CD73). Average viable hAEC and hAMSC yields at harvest were 2.3 × 10 6 ± 3.7 × 10 5 and 1.6 × 10 6 ± 4.7 × 10 5 per milliliter of amnion, respectively. As well, hAECs and hAMSCs demonstrated significantly greater osteocalcin ( P = .025), aggrecan ( P

  14. Amygdala and auditory cortex exhibit distinct sensitivity to relevant acoustic features of auditory emotions.

    Science.gov (United States)

    Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha

    2016-12-01

    Discriminating between auditory signals of different affective value is critical to successful social interaction. It is commonly held that acoustic decoding of such signals occurs in the auditory system, whereas affective decoding occurs in the amygdala. However, given that the amygdala receives direct subcortical projections that bypass the auditory cortex, it is possible that some acoustic decoding occurs in the amygdala as well, when the acoustic features are relevant for affective discrimination. We tested this hypothesis by combining functional neuroimaging with the neurophysiological phenomena of repetition suppression (RS) and repetition enhancement (RE) in human listeners. Our results show that both amygdala and auditory cortex responded differentially to physical voice features, suggesting that the amygdala and auditory cortex decode the affective quality of the voice not only by processing the emotional content from previously processed acoustic features, but also by processing the acoustic features themselves, when these are relevant to the identification of the voice's affective value. Specifically, we found that the auditory cortex is sensitive to spectral high-frequency voice cues when discriminating vocal anger from vocal fear and joy, whereas the amygdala is sensitive to vocal pitch when discriminating between negative vocal emotions (i.e., anger and fear). Vocal pitch is an instantaneously recognized voice feature, which is potentially transferred to the amygdala by direct subcortical projections. These results together provide evidence that, besides the auditory cortex, the amygdala too processes acoustic information, when this is relevant to the discrimination of auditory emotions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Programmable differential capacitance-to-voltage converter for MEMS accelerometers

    Science.gov (United States)

    Royo, G.; Sánchez-Azqueta, C.; Gimeno, C.; Aldea, C.; Celma, S.

    2017-05-01

    Capacitive MEMS sensors exhibit an excellent noise performance, high sensitivity and low power consumption. They offer a huge range of applications, being the accelerometer one of its main uses. In this work, we present the design of a capacitance-to-voltage converter in CMOS technology to measure the acceleration from the capacitance variations. It is based on a low-power, fully-differential transimpedance amplifier with low input impedance and a very low input noise.

  16. Withanolide D Exhibits Similar Cytostatic Effect in Drug-Resistant and Drug-Sensitive Multiple Myeloma Cells

    Directory of Open Access Journals (Sweden)

    Mark E. Issa

    2017-09-01

    Full Text Available In spite of recent therapeutic advances, multiple myeloma (MM remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs. MM-CSCs are equipped with the necessary tools that render them highly resistant to virtually all conventional therapies. In this study, the growth inhibitory effects of withanolide D (WND, a steroidal lactone isolated from Withania somnifera, on drug-sensitive tumoral plasma cells and drug-resistant MM cells have been investigated. In MTT/XTT assays, WND exhibited similar cytostatic effects between drug-resistant and drug-sensitive cell lines in the nM range. WND also induced cell death and apoptosis in MM-CSCs and RPMI 8226 cells, as examined by the calcein/ethidium homodimer and annexin V/propidium iodide stainings, respectively. To determine whether P-glycoprotein (P-gp efflux affected the cytostatic activity of WND, P-gp was inhibited with verapamil and results indicated that the WND cytostatic effect in MM-CSCs was independent of P-gp efflux. Furthermore, WND did not increase the accumulation of the fluorescent P-gp substrate rhodamine 123 in MM-CSCs, suggesting that WND may not inhibit P-gp at the tested relevant doses. Therefore, the WND-induced cytostatic effect may be independent of P-gp efflux. These findings warrant further investigation of WND in MM-CSC animal models.

  17. Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects.

    Science.gov (United States)

    Dresch, Jacqueline M; Liu, Xiaozhou; Arnosti, David N; Ay, Ahmet

    2010-10-24

    Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context. We apply local and global sensitivity analyses to two recent transcriptional models to determine the sensitivity of individual parameters. We show that in one case, values for repressor efficiencies are very sensitive, while values for protein cooperativities are not, and provide insights on why these differential sensitivities stem from both biological effects and the structure of the applied models. In a second case, we demonstrate that parameters that were thought to prove the system's dependence on activator-activator cooperativity are relatively insensitive. We show that there are numerous parameter sets that do not satisfy the relationships proferred as the optimal solutions, indicating that structural differences between the two types of transcriptional enhancers analyzed may not be as simple as altered activator cooperativity. Our results emphasize the need for sensitivity analysis to examine model construction and forms of biological data used for modeling transcriptional processes, in order to determine the significance of estimated parameter values for thermodynamic models. Knowledge of parameter sensitivities can provide the necessary

  18. Temperature sensitivity of differential absorption lidar measurements of water vapor in the 720-nm region

    Science.gov (United States)

    Browell, Edward V.; Ismail, Syed; Grossmann, Benoist E.

    1991-01-01

    Recently measured properties of water vapor (H2O) absorption lines have been used in calculations to evalute the temperature sensitivity of differential absorption lidar (Dial) H2O measurements. This paper estimates the temperature sensitivity of H2O lines in the 717-733-nm region for both H2O mixing ratio and number density measurements, and discusses the influence of the H2O line ground state energies E-double-prime, the H2O absorption linewidths, the linewidth temperature dependence parameter, and the atmospheric temperature and pressure variations with altitude and location on the temperature sensitivity calculations. Line parameters and temperature sensitivity calculations for 67 H2O lines in the 720-nm band are given which can be directly used in field experiments. Water vapor lines with E-double-prime values in the 100-300/cm range were found to be optimum for Dial measurements of H2O number densities, while E-double-prime values in the 250-500/cm range were found to be optimum for H2O mixing ratio measurements.

  19. Energy-Based Yield Criteria for Orthotropic Materials, Exhibiting Strength-Differential Effect. Specification for Sheets under Plane Stress State

    Directory of Open Access Journals (Sweden)

    Szeptyński P.

    2017-06-01

    Full Text Available A general proposition of an energy-based limit condition for anisotropic materials exhibiting strength-differential effect (SDE based on spectral decomposition of elasticity tensors and the use of scaling pressure-dependent functions is specified for the case of orthotropic materials. A detailed algorithm (based on classical solutions of cubic equations for the determination of elastic eigenstates and eigenvalues of the orthotropic stiffness tensor is presented. A yield condition is formulated for both two-dimensional and three-dimensional cases. Explicit formulas based on simple strength tests are derived for parameters of criterion in the plane case. The application of both criteria for the description of yielding and plastic deformation of metal sheets is discussed in detail. The plane case criterion is verified with experimental results from the literature.

  20. RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Salehzada, T; Lambert, K

    2012-01-01

    Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role...... is associated with CHOP10 mRNA and regulates its stability. CHOP10 expression is conserved in RNase L(-/-)-MEFs, maintaining preadipocyte state while impairing their terminal differentiation. RNase L(-/-)-MEFs have decreased lipids storage capacity, insulin sensitivity and glucose uptake. Expression of ectopic...... RNase L in RNase L(-/-)-MEFs triggers CHOP10 mRNA instability, allowing increased lipids storage, insulin response and glucose uptake. Similarly, downregulation of CHOP10 mRNA with CHOP10 siRNA in RNase L(-/-)-MEFs improves their differentiation in adipocyte. In vivo, aged RNase L(-)/(-) mice present...

  1. A Sensitive Tg Assay or rhTSH Stimulated Tg : What's the Best in the Long-Term Follow-Up of Patients with Differentiated Thyroid Carcinoma?

    NARCIS (Netherlands)

    Persoon, Adrienne C. M.; Jager, Pieter L.; Sluiter, Wim J.; Plukker, John T. M.; Wolffenbuttel, Bruce H. R.; Links, Thera P.

    2007-01-01

    Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the

  2. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

    Science.gov (United States)

    Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

    2016-04-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  3. Applicability of the two-angle differential method to response measurement of neutron-sensitive devices at the RCNP high-energy neutron facility

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, Akihiko, E-mail: aki-masuda@aist.go.jp [National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Matsumoto, Tetsuro [National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Iwamoto, Yosuke [Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai, Naka, Ibaraki 319-1195 (Japan); Hagiwara, Masayuki [High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Satoh, Daiki; Sato, Tatsuhiko [Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai, Naka, Ibaraki 319-1195 (Japan); Iwase, Hiroshi [High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Yashima, Hiroshi [Research Reactor Institute, Kyoto University, 2-1010 Asashiro-nishi, Kumatori, Sennan, Osaka 590-0494 (Japan); Nakane, Yoshihiro [Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai, Naka, Ibaraki 319-1195 (Japan); Nishiyama, Jun [Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8550 (Japan); Shima, Tatsushi; Tamii, Atsushi; Hatanaka, Kichiji [Research Center for Nuclear Physics (RCNP), Osaka University, 10-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Harano, Hideki [National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Nakamura, Takashi [Cyclotron and Radioisotope Center (CYRIC), Tohoku University, 6-3 Aramaki, Aoba, Sendai, Miyagi 980-8578 (Japan)

    2017-03-21

    Quasi-monoenergetic high-energy neutron fields induced by {sup 7}Li(p,n) reactions are used for the response evaluation of neutron-sensitive devices. The quasi-monoenergetic high-energy field consists of high-energy monoenergetic peak neutrons and unwanted continuum neutrons down to the low-energy region. A two-angle differential method has been developed to compensate for the effect of the continuum neutrons in the response measurements. In this study, the two-angle differential method was demonstrated for Bonner sphere detectors, which are typical examples of moderator-based neutron-sensitive detectors, to investigate the method's applicability and its dependence on detector characteristics. Experiments were performed under 96–387 MeV quasi-monoenergetic high-energy neutron fields at the Research Center for Nuclear Physics (RCNP), Osaka University. The measurement results for large high-density polyethylene (HDPE) sphere detectors agreed well with Monte Carlo calculations, which verified the adequacy of the two-angle differential method. By contrast, discrepancies were observed in the results for small HDPE sphere detectors and metal-induced sphere detectors. The former indicated that detectors that are particularly sensitive to low-energy neutrons may be affected by penetrating neutrons owing to the geometrical features of the RCNP facility. The latter discrepancy could be consistently explained by a problem in the evaluated cross-section data for the metals used in the calculation. Through those discussions, the adequacy of the two-angle differential method was experimentally verified, and practical suggestions were made pertaining to this method.

  4. The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats differ in sensitivity to nicotine.

    Science.gov (United States)

    de Fiebre, NancyEllen C; Dawson, Ralph; de Fiebre, Christopher M

    2002-06-01

    Studies in rodents selectively bred to differ in alcohol sensitivity have suggested that nicotine and ethanol sensitivities may cosegregate during selective breeding. This suggests that ethanol and nicotine sensitivities may in part be genetically correlated. Male and female high alcohol sensitivity (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were tested for nicotine-induced alterations in locomotor activity, body temperature, and seizure activity. Plasma and brain levels of nicotine and its primary metabolite, cotinine, were measured in these animals, as was the binding of [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin in eight brain regions. Both replicate HAS lines were more sensitive to nicotine-induced locomotor activity depression than the replicate LAS lines. No consistent HAS/LAS differences were seen on other measures of nicotine sensitivity; however, females were more susceptible to nicotine-induced seizures than males. No HAS/LAS differences in nicotine or cotinine levels were seen, nor were differences seen in the binding of nicotinic ligands. Females had higher levels of plasma cotinine and brain nicotine than males but had lower brain cotinine levels than males. Sensitivity to a specific action of nicotine cosegregates during selective breeding for differential sensitivity to a specific action of ethanol. The differential sensitivity of the HAS/LAS rats is due to differences in central nervous system sensitivity and not to pharmacokinetic differences. The differential central nervous system sensitivity cannot be explained by differences in the numbers of nicotinic receptors labeled in ligand-binding experiments. The apparent genetic correlation between ethanol and nicotine sensitivities suggests that common genes modulate, in part, the actions of both ethanol and nicotine and may explain the frequent coabuse of these agents.

  5. Sensitivity and specificity of monochromatic photography of the ocular fundus in differentiating optic nerve head drusen and optic disc oedema: optic disc drusen and oedema.

    Science.gov (United States)

    Gili, Pablo; Flores-Rodríguez, Patricia; Yangüela, Julio; Orduña-Azcona, Javier; Martín-Ríos, María Dolores

    2013-03-01

    Evaluation of the efficacy of monochromatic photography of the ocular fundus in differentiating optic nerve head drusen (ONHD) and optic disc oedema (ODE). Sixty-six patients with ONHD, 31 patients with ODE and 70 healthy subjects were studied. Colour and monochromatic fundus photography with different filters (green, red and autofluorescence) were performed. The results were analysed blindly by two observers. The sensitivity, specificity and interobserver agreement (k) of each test were assessed. Colour photography offers 65.5 % sensitivity and 100 % specificity for the diagnosis of ONHD. Monochromatic photography improves sensitivity and specificity and provides similar results: green filter (71.20 % sensitivity, 96.70 % specificity), red filter (80.30 % sensitivity, 96.80 % specificity), and autofluorescence technique (87.8 % sensitivity, 100 % specificity). The interobserver agreement was good with all techniques used: autofluorescence (k = 0.957), green filter (k = 0.897), red filter (k = 0.818) and colour (k = 0.809). Monochromatic fundus photography permits ONHD and ODE to be differentiated, with good sensitivity and very high specificity. The best results were obtained with autofluorescence and red filter study.

  6. Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

    Science.gov (United States)

    Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

    2013-09-01

    Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction. Copyright © 2013 Wiley Periodicals, Inc.

  7. Inhibition of WNT signaling reduces differentiation and induces sensitivity to doxorubicin in human malignant neuroblastoma SH-SY5Y cells.

    Science.gov (United States)

    Suebsoonthron, Junjira; Jaroonwitchawan, Thiranut; Yamabhai, Montarop; Noisa, Parinya

    2017-06-01

    Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme. XAV939 treatment led to the reduction of β-catenin within the cells, confirming its inhibitory effect of WNT. The inhibition of WNT signaling by XAV939 did not affect cell morphology, survival, and proliferation; however, the differentiation and sensitivity to anticancer drugs of human neuroblastoma cells were altered. The treatment of XAV939 resulted in the downregulation of mature neuronal markers, including β-tubulin III, PHOX2A, and PHOX2B, whereas neural progenitor markers (PAX6, TFAP2α, and SLUG) were upregulated. In addition, the combination of XAV939 significantly enhanced the sensitivity of SH-SY5Y and IMR-32 cells to doxorubicin in both 2D and 3D culture systems. Microarray gene expression profiling suggested numbers of candidate target genes of WNT inhibition by XAV939, in particular, p21, p53, ubiquitin C, ZBED8, MDM2, CASP3, and FZD1, and this explained the enhanced sensitivity of SH-SY5Y cells to doxorubicin. Altogether, these results proposed that the altered differentiation of human malignant neuroblastoma cells by inhibiting WNT signaling sensitized the cells to anticancer drugs. This approach could thus serve as an effective treatment option for aggressive brain malignancy.

  8. ADC as a useful diagnostic tool for differentiating benign and malignant vertebral bone marrow lesions and compression fractures: a systematic review and meta-analysis.

    Science.gov (United States)

    Suh, Chong Hyun; Yun, Seong Jong; Jin, Wook; Lee, Sun Hwa; Park, So Young; Ryu, Chang-Woo

    2018-07-01

    To assess the sensitivity and specificity of quantitative assessment of the apparent diffusion coefficient (ADC) for differentiating benign and malignant vertebral bone marrow lesions (BMLs) and compression fractures (CFs) METHODS: An electronic literature search of MEDLINE and EMBASE was conducted. Bivariate modelling and hierarchical summary receiver operating characteristic modelling were performed to evaluate the diagnostic performance of ADC for differentiating vertebral BMLs. Subgroup analysis was performed for differentiating benign and malignant vertebral CFs. Meta-regression analyses according to subject, study and diffusion-weighted imaging (DWI) characteristics were performed. Twelve eligible studies (748 lesions, 661 patients) were included. The ADC exhibited a pooled sensitivity of 0.89 (95% confidence interval [CI] 0.80-0.94) and a pooled specificity of 0.87 (95% CI 0.78-0.93) for differentiating benign and malignant vertebral BMLs. In addition, the pooled sensitivity and specificity for differentiating benign and malignant CFs were 0.92 (95% CI 0.82-0.97) and 0.91 (95% CI 0.87-0.94), respectively. In the meta-regression analysis, the DWI slice thickness was a significant factor affecting heterogeneity (p benign and malignant vertebral BMLs and CFs. • Quantitative assessment of ADC is useful in differentiating vertebral BMLs. • Quantitative ADC assessment for BMLs had sensitivity of 89%, specificity of 87%. • Quantitative ADC assessment for CFs had sensitivity of 92%, specificity of 91%. • The specificity is highest (95%) with thinner (< 5 mm) DWI slice thickness.

  9. Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

    DEFF Research Database (Denmark)

    Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

    2003-01-01

    of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

  10. Automatic differentiation bibliography

    Energy Technology Data Exchange (ETDEWEB)

    Corliss, G.F. [comp.

    1992-07-01

    This is a bibliography of work related to automatic differentiation. Automatic differentiation is a technique for the fast, accurate propagation of derivative values using the chain rule. It is neither symbolic nor numeric. Automatic differentiation is a fundamental tool for scientific computation, with applications in optimization, nonlinear equations, nonlinear least squares approximation, stiff ordinary differential equation, partial differential equations, continuation methods, and sensitivity analysis. This report is an updated version of the bibliography which originally appeared in Automatic Differentiation of Algorithms: Theory, Implementation, and Application.

  11. Nonintrusive Polynomial Chaos Expansions for Sensitivity Analysis in Stochastic Differential Equations

    KAUST Repository

    Jimenez, M. Navarro; Le Maî tre, O. P.; Knio, Omar

    2017-01-01

    A Galerkin polynomial chaos (PC) method was recently proposed to perform variance decomposition and sensitivity analysis in stochastic differential equations (SDEs), driven by Wiener noise and involving uncertain parameters. The present paper extends the PC method to nonintrusive approaches enabling its application to more complex systems hardly amenable to stochastic Galerkin projection methods. We also discuss parallel implementations and the variance decomposition of the derived quantity of interest within the framework of nonintrusive approaches. In particular, a novel hybrid PC-sampling-based strategy is proposed in the case of nonsmooth quantities of interest (QoIs) but smooth SDE solution. Numerical examples are provided that illustrate the decomposition of the variance of QoIs into contributions arising from the uncertain parameters, the inherent stochastic forcing, and joint effects. The simulations are also used to support a brief analysis of the computational complexity of the method, providing insight on the types of problems that would benefit from the present developments.

  12. Nonintrusive Polynomial Chaos Expansions for Sensitivity Analysis in Stochastic Differential Equations

    KAUST Repository

    Jimenez, M. Navarro

    2017-04-18

    A Galerkin polynomial chaos (PC) method was recently proposed to perform variance decomposition and sensitivity analysis in stochastic differential equations (SDEs), driven by Wiener noise and involving uncertain parameters. The present paper extends the PC method to nonintrusive approaches enabling its application to more complex systems hardly amenable to stochastic Galerkin projection methods. We also discuss parallel implementations and the variance decomposition of the derived quantity of interest within the framework of nonintrusive approaches. In particular, a novel hybrid PC-sampling-based strategy is proposed in the case of nonsmooth quantities of interest (QoIs) but smooth SDE solution. Numerical examples are provided that illustrate the decomposition of the variance of QoIs into contributions arising from the uncertain parameters, the inherent stochastic forcing, and joint effects. The simulations are also used to support a brief analysis of the computational complexity of the method, providing insight on the types of problems that would benefit from the present developments.

  13. Proteomic Dissection of Nanotopography-Sensitive Mechanotransductive Signaling Hubs that Foster Neuronal Differentiation in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Elisa Maffioli

    2018-01-01

    Full Text Available Neuronal cells are competent in precisely sensing nanotopographical features of their microenvironment. The perceived microenvironmental information will be “interpreted” by mechanotransductive processes and impacts on neuronal functioning and differentiation. Attempts to influence neuronal differentiation by engineering substrates that mimic appropriate extracellular matrix (ECM topographies are hampered by the fact that profound details of mechanosensing/-transduction complexity remain elusive. Introducing omics methods into these biomaterial approaches has the potential to provide a deeper insight into the molecular processes and signaling cascades underlying mechanosensing/-transduction but their exigence in cellular material is often opposed by technical limitations of major substrate top-down fabrication methods. Supersonic cluster beam deposition (SCBD allows instead the bottom-up fabrication of nanostructured substrates over large areas characterized by a quantitatively controllable ECM-like nanoroughness that has been recently shown to foster neuron differentiation and maturation. Exploiting this capacity of SCBD, we challenged mechanosensing/-transduction and differentiative behavior of neuron-like PC12 cells with diverse nanotopographies and/or changes of their biomechanical status, and analyzed their phosphoproteomic profiles in these settings. Versatile proteins that can be associated to significant processes along the mechanotransductive signal sequence, i.e., cell/cell interaction, glycocalyx and ECM, membrane/f-actin linkage and integrin activation, cell/substrate interaction, integrin adhesion complex, actomyosin organization/cellular mechanics, nuclear organization, and transcriptional regulation, were affected. The phosphoproteomic data suggested furthermore an involvement of ILK, mTOR, Wnt, and calcium signaling in these nanotopography- and/or cell mechanics-related processes. Altogether, potential nanotopography-sensitive

  14. A single enhancer regulating the differential expression of duplicated red-sensitive opsin genes in zebrafish.

    Directory of Open Access Journals (Sweden)

    Taro Tsujimura

    2010-12-01

    Full Text Available A fundamental step in the evolution of the visual system is the gene duplication of visual opsins and differentiation between the duplicates in absorption spectra and expression pattern in the retina. However, our understanding of the mechanism of expression differentiation is far behind that of spectral tuning of opsins. Zebrafish (Danio rerio have two red-sensitive cone opsin genes, LWS-1 and LWS-2. These genes are arrayed in a tail-to-head manner, in this order, and are both expressed in the long member of double cones (LDCs in the retina. Expression of the longer-wave sensitive LWS-1 occurs later in development and is thus confined to the peripheral, especially ventral-nasal region of the adult retina, whereas expression of LWS-2 occurs earlier and is confined to the central region of the adult retina, shifted slightly to the dorsal-temporal region. In this study, we employed a transgenic reporter assay using fluorescent proteins and P1-artificial chromosome (PAC clones encompassing the two genes and identified a 0.6-kb "LWS-activating region" (LAR upstream of LWS-1, which regulates expression of both genes. Under the 2.6-kb flanking upstream region containing the LAR, the expression pattern of LWS-1 was recapitulated by the fluorescent reporter. On the other hand, when LAR was directly conjugated to the LWS-2 upstream region, the reporter was expressed in the LDCs but also across the entire outer nuclear layer. Deletion of LAR from the PAC clones drastically lowered the reporter expression of the two genes. These results suggest that LAR regulates both LWS-1 and LWS-2 by enhancing their expression and that interaction of LAR with the promoters is competitive between the two genes in a developmentally restricted manner. Sharing a regulatory region between duplicated genes could be a general way to facilitate the expression differentiation in duplicated visual opsins.

  15. Adaptive Epigenetic Differentiation between Upland and Lowland Rice Ecotypes Revealed by Methylation-Sensitive Amplified Polymorphism.

    Directory of Open Access Journals (Sweden)

    Hui Xia

    Full Text Available The stress-induced epimutations could be inherited over generations and play important roles in plant adaption to stressful environments. Upland rice has been domesticated in water-limited environments for thousands of years and accumulated drought-induced epimutations of DNA methylation, making it epigenetically differentiated from lowland rice. To study the epigenetic differentiation between upland and lowland rice ecotypes on their drought-resistances, the epigenetic variation was investigated in 180 rice landraces under both normal and osmotic conditions via methylation-sensitive amplified polymorphism (MSAP technique. Great alterations (52.9~54.3% of total individual-locus combinations of DNA methylation are recorded when rice encountering the osmotic stress. Although the general level of epigenetic differentiation was very low, considerable level of ΦST (0.134~0.187 was detected on the highly divergent epiloci (HDE. The HDE detected in normal condition tended to stay at low levels in upland rice, particularly the ones de-methylated in responses to osmotic stress. Three out of four selected HDE genes differentially expressed between upland and lowland rice under normal or stressed conditions. Moreover, once a gene at HDE was up-/down-regulated in responses to the osmotic stress, its expression under the normal condition was higher/lower in upland rice. This result suggested expressions of genes at the HDE in upland rice might be more adaptive to the osmotic stress. The epigenetic divergence and its influence on the gene expression should contribute to the higher drought-resistance in upland rice as it is domesticated in the water-limited environment.

  16. Adaptive Epigenetic Differentiation between Upland and Lowland Rice Ecotypes Revealed by Methylation-Sensitive Amplified Polymorphism.

    Science.gov (United States)

    Xia, Hui; Huang, Weixia; Xiong, Jie; Tao, Tao; Zheng, Xiaoguo; Wei, Haibin; Yue, Yunxia; Chen, Liang; Luo, Lijun

    2016-01-01

    The stress-induced epimutations could be inherited over generations and play important roles in plant adaption to stressful environments. Upland rice has been domesticated in water-limited environments for thousands of years and accumulated drought-induced epimutations of DNA methylation, making it epigenetically differentiated from lowland rice. To study the epigenetic differentiation between upland and lowland rice ecotypes on their drought-resistances, the epigenetic variation was investigated in 180 rice landraces under both normal and osmotic conditions via methylation-sensitive amplified polymorphism (MSAP) technique. Great alterations (52.9~54.3% of total individual-locus combinations) of DNA methylation are recorded when rice encountering the osmotic stress. Although the general level of epigenetic differentiation was very low, considerable level of ΦST (0.134~0.187) was detected on the highly divergent epiloci (HDE). The HDE detected in normal condition tended to stay at low levels in upland rice, particularly the ones de-methylated in responses to osmotic stress. Three out of four selected HDE genes differentially expressed between upland and lowland rice under normal or stressed conditions. Moreover, once a gene at HDE was up-/down-regulated in responses to the osmotic stress, its expression under the normal condition was higher/lower in upland rice. This result suggested expressions of genes at the HDE in upland rice might be more adaptive to the osmotic stress. The epigenetic divergence and its influence on the gene expression should contribute to the higher drought-resistance in upland rice as it is domesticated in the water-limited environment.

  17. Differential gene expression responses distinguish contact and respiratory sensitizers and nonsensitizing irritants in the local lymph node assay.

    Science.gov (United States)

    Adenuga, David; Woolhiser, Michael R; Gollapudi, B Bhaskar; Boverhof, Darrell R

    2012-04-01

    Genomic approaches have the potential to enhance the specificity and predictive accuracy of existing toxicology endpoints, including those for chemical sensitization. The present study was conducted to determine whether gene expression responses can distinguish contact sensitizers (1-chloro-2,4-dinitrobenzene [DNCB] and hexyl cinnamic aldehyde [HCA]), respiratory sensitizers (ortho-phthalaldehyde and trimellitic anhydride [TMA]), and nonsensitizing irritants (methyl salicylate [MS] and nonanoic acid [NA]) in the local lymph node assay (LLNA). Female Balb/c mice received doses of each chemical as per the standard LLNA dosing regimen on days 1, 2, and 3. Auricular lymph nodes were analyzed for tritiated thymidine ((3)HTdR) incorporation on day 6 and for gene expression responses on days 6 and 10. All chemicals induced dose-dependent increases in stimulation index, which correlated strongly with the number of differentially expressed genes. A majority of genes modulated by the irritants were similarly altered by the sensitizers, consistent with the irritating effects of the sensitizers. However, a select number of responses involved with immune-specific functions, such as dendritic cell activation, were unique to the sensitizers and may offer the ability to distinguish sensitizers from irritants. Genes for the mast cell proteases 1 and 8, Lgals7, Tim2, Aicda, Il4, and Akr1c18 were more strongly regulated by respiratory sensitizers compared with contact sensitizers and may represent potential biomarkers for discriminating between contact and respiratory sensitizers. Collectively, these data suggest that gene expression responses may serve as useful biomarkers to distinguish between respiratory and contact sensitizers and nonsensitizing irritants in the LLNA.

  18. Species-Specific Antimonial Sensitivity in Leishmania Is Driven by Post-Transcriptional Regulation of AQP1

    Science.gov (United States)

    Mandal, Goutam; Mandal, Srotoswati; Sharma, Mansi; Charret, Karen Santos; Papadopoulou, Barbara; Bhattacharjee, Hiranmoy; Mukhopadhyay, Rita

    2015-01-01

    Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans. The different clinical forms of leishmaniasis are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating leishmaniasis. Recent studies suggest that pentavalent antimony (Sb(V)) acts as a pro-drug, which is converted to the more active trivalent form (Sb(III)). However, sensitivity to trivalent antimony varies among different Leishmania species. In general, Leishmania species causing cutaneous leishmaniasis (CL) are more sensitive to Sb(III) than the species responsible for visceral leishmaniasis (VL). Leishmania aquaglyceroporin (AQP1) facilitates the adventitious passage of antimonite down a concentration gradient. In this study, we show that Leishmania species causing CL accumulate more antimonite, and therefore exhibit higher sensitivity to antimonials, than the species responsible for VL. This species-specific differential sensitivity to antimonite is directly proportional to the expression levels of AQP1 mRNA. We show that the stability of AQP1 mRNA in different Leishmania species is regulated by their respective 3’-untranslated regions. The differential regulation of AQP1 mRNA explains the distinct antimonial sensitivity of each species. PMID:25714343

  19. Evoked Pressure Pain Sensitivity Is Associated with Differential Analgesic Response to Verum and Sham Acupuncture in Fibromyalgia.

    Science.gov (United States)

    Zucker, Noah A; Tsodikov, Alex; Mist, Scott D; Cina, Stephen; Napadow, Vitaly; Harris, Richard E

    2017-08-01

    Fibromyalgia is a chronic pain condition with few effective treatments. Many fibromyalgia patients seek acupuncture for analgesia; however, its efficacy is limited and not fully understood. This may be due to heterogeneous pathologies among participants in acupuncture clinical trials. We hypothesized that pressure pain tenderness would differentially classify treatment response to verum and sham acupuncture in fibromyalgia patients. Baseline pressure pain sensitivity at the thumbnail at baseline was used in linear mixed models as a modifier of differential treatment response to sham versus verum acupuncture. Similarly, needle-induced sensation was also analyzed to determine its differential effect of treatment on clinical pain. A cohort of 114 fibromyalgia patients received baseline pressure pain testing and were randomized to either verum (N = 59) or sham (N = 55) acupuncture. Participants received treatments from once a week to three times a week, increasing in three-week blocks for a total of 18 treatments. Clinical pain was measured on a 101-point visual analog scale, and needle sensation was measured by questionnaire throughout the trial. Participants who had higher pain pressure thresholds had greater reduction in clinical pain following verum acupuncture while participants who had lower pain pressure thresholds showed better analgesic response to sham acupuncture. Moreover, patients with lower pressure pain thresholds had exacerbated clinical pain following verum acupuncture. Similar relationships were observed for sensitivity to acupuncture needling. These findings suggest that acupuncture efficacy in fibromyalgia may be underestimated and a more personalized treatment for fibromyalgia may also be possible. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  20. On the achievable field sensitivity of a segmented annular detector for differential phase contrast measurements

    International Nuclear Information System (INIS)

    Schwarzhuber, Felix; Melzl, Peter; Zweck, Josef

    2017-01-01

    Highlights: • Practical guide to calibrate a DPC setup considering geometrical parameters. • Optimizing the field sensitivity of a segmented annular DPC detector. • Determination of maximum electric and magnetic field sensitivity of a DPC setup. - Abstract: Differential phase contrast microscopy measures minute deflections of the electron probe due to electric and/or magnetic fields, using a position sensitive device. Although recently, pixelated detectors have become available which also serve as a position sensitive device, the most frequently used detector is a four-segmented annular semiconducting detector ring (or variations thereof), where the difference signals of opposing detector elements represent the components of the deflection vector. This deflection vector can be used directly to quantitatively determine the deflecting field, provided the specimen’s thickness is known. While there exist many measurements of both electric and magnetic fields, even at an atomic level, until now the question of the smallest clearly resolvable field value for this detector has not yet been answered. This paper treats the problem theoretically first, leading to a calibration factor κ which depends solely on simple, experimentally accessible parameters and relates the deflecting field to the measured deflection vector. In a second step, the calibration factor for our combination of microscope and detector is determined experimentally for various combinations of camera length, condenser aperture and spot size to determine the optimum setup. From this optimized condition we determine the minimum change in field which leads to a clearly measurable signal change for both HMSTEM and LMSTEM operation. A strategy is described which allows the experimenter to choose the setup giving the highest field sensitivity. Quantification problems due to scattering processes in the specimen are addressed and ways are shown to choose a setup which is less sensitive to these artefacts.

  1. On the achievable field sensitivity of a segmented annular detector for differential phase contrast measurements

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzhuber, Felix, E-mail: felix.schwarzhuber@ur.de; Melzl, Peter; Zweck, Josef

    2017-06-15

    Highlights: • Practical guide to calibrate a DPC setup considering geometrical parameters. • Optimizing the field sensitivity of a segmented annular DPC detector. • Determination of maximum electric and magnetic field sensitivity of a DPC setup. - Abstract: Differential phase contrast microscopy measures minute deflections of the electron probe due to electric and/or magnetic fields, using a position sensitive device. Although recently, pixelated detectors have become available which also serve as a position sensitive device, the most frequently used detector is a four-segmented annular semiconducting detector ring (or variations thereof), where the difference signals of opposing detector elements represent the components of the deflection vector. This deflection vector can be used directly to quantitatively determine the deflecting field, provided the specimen’s thickness is known. While there exist many measurements of both electric and magnetic fields, even at an atomic level, until now the question of the smallest clearly resolvable field value for this detector has not yet been answered. This paper treats the problem theoretically first, leading to a calibration factor κ which depends solely on simple, experimentally accessible parameters and relates the deflecting field to the measured deflection vector. In a second step, the calibration factor for our combination of microscope and detector is determined experimentally for various combinations of camera length, condenser aperture and spot size to determine the optimum setup. From this optimized condition we determine the minimum change in field which leads to a clearly measurable signal change for both HMSTEM and LMSTEM operation. A strategy is described which allows the experimenter to choose the setup giving the highest field sensitivity. Quantification problems due to scattering processes in the specimen are addressed and ways are shown to choose a setup which is less sensitive to these artefacts.

  2. Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity

    NARCIS (Netherlands)

    Harkany, Tibor; Varga, Csaba; Grosche, Jens; Mulder, Jan; Luiten, Paul G.M.; Hortobágyi, Tibor; Penke, Botond; Härtig, Wolfgang

    2002-01-01

    Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a significant damage of cholinergic neurons concomitant with increased amyloid precursor protein (APP) expression in the cerebral cortex. However, the sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP

  3. Nucleotide excision repair in differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Wees, Caroline van der [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Jansen, Jacob [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Laarse, Arnoud van der [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Zeeland, Albert van [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Mullenders, Leon [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands)]. E-mail: l.mullenders@lumc.nl

    2007-01-03

    Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions and operates via two NER subpathways, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Although detailed information is available on expression and efficiency of NER in established mammalian cell lines, little is known about the expression of NER pathways in (terminally) differentiated cells. The majority of studies in differentiated cells have focused on repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4PP) because of the high frequency of photolesions at low level of toxicity and availability of sensitive technologies to determine photolesions in defined regions of the genome. The picture that emerges from these studies is blurred and rather complex. Fibroblasts and terminally differentiated myocytes of the rat heart display equally efficient GGR of 6-4PP but poor repair of CPD due to the absence of p48 expression. This repair phenotype is clearly different from human terminal differentiated neurons. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. In contrast, in intact rat spermatogenic cells repair was very inefficient at the genome overall level and in transcriptionally active genes indicating that GGR and TCR are non-functional. Also, non-differentiated mouse embryonic stem (ES) cells exhibit low levels of NER after UV irradiation. However, the mechanisms that lead to low NER activity are clearly different: in differentiated spermatogenic cells differences in chromatin compaction and sequestering of NER proteins may underlie the lack of NER activity in pre-meiotic cells, whereas in non-differentiated ES cells NER is impaired by a strong apoptotic response.

  4. Rock-dwelling lizards exhibit less sensitivity of sprint speed to increases in substrate rugosity.

    Science.gov (United States)

    Collins, Clint E; Self, Jessica D; Anderson, Roger A; McBrayer, Lance D

    2013-06-01

    Effectively moving across variable substrates is important to all terrestrial animals. The effects of substrates on lizard performance have ecological ramifications including the partitioning of habitat according to sprinting ability on different surfaces. This phenomenon is known as sprint sensitivity, or the decrease in sprint speed due to change in substrate. However, sprint sensitivity has been characterized only in arboreal Anolis lizards. Our study measured sensitivity to substrate rugosity among six lizard species that occupy rocky, sandy, and/or arboreal habitats. Lizards that use rocky habitats are less sensitive to changes in substrate rugosity, followed by arboreal lizards, and then by lizards that use sandy habitats. We infer from comparative phylogenetic analysis that forelimb, chest, and tail dimensions are important external morphological features related to sensitivity to changes in substrate rugosity. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. Human sensitivity to vertical self-motion.

    Science.gov (United States)

    Nesti, Alessandro; Barnett-Cowan, Michael; Macneilage, Paul R; Bülthoff, Heinrich H

    2014-01-01

    Perceiving vertical self-motion is crucial for maintaining balance as well as for controlling an aircraft. Whereas heave absolute thresholds have been exhaustively studied, little work has been done in investigating how vertical sensitivity depends on motion intensity (i.e., differential thresholds). Here we measure human sensitivity for 1-Hz sinusoidal accelerations for 10 participants in darkness. Absolute and differential thresholds are measured for upward and downward translations independently at 5 different peak amplitudes ranging from 0 to 2 m/s(2). Overall vertical differential thresholds are higher than horizontal differential thresholds found in the literature. Psychometric functions are fit in linear and logarithmic space, with goodness of fit being similar in both cases. Differential thresholds are higher for upward as compared to downward motion and increase with stimulus intensity following a trend best described by two power laws. The power laws' exponents of 0.60 and 0.42 for upward and downward motion, respectively, deviate from Weber's Law in that thresholds increase less than expected at high stimulus intensity. We speculate that increased sensitivity at high accelerations and greater sensitivity to downward than upward self-motion may reflect adaptations to avoid falling.

  6. Investigation of a redox-sensitive predictive model of mouse embryonic stem cells differentiation using quantitative nuclease protection assays and glutathione redox status

    Science.gov (United States)

    Investigation of a redox-sensitive predictive model of mouse embryonic stem cell differentiation via quantitative nuclease protection assays and glutathione redox status Chandler KJ,Hansen JM, Knudsen T,and Hunter ES 1. U.S. Environmental Protection Agency, Research Triangl...

  7. Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides

    Directory of Open Access Journals (Sweden)

    Liu Qiang

    2012-12-01

    Full Text Available Abstract Background β-amyloid (Aβ accumulation is described as a hallmark of Alzheimer’s disease (AD. Aβ perturbs a number of synaptic components including nicotinic acetylcholine receptors containing α7 subunits (α7-nAChRs, which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric α7β2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Aβ exposure. To extend our previous work, we evaluated the expression and pharmacology of α7β2-nAChRs in hippocampal interneurons and their sensitivity to Aβ. Results GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional α7β2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-β-erythroidine (DHβE, a nAChR β2* subunit selective blocker, and α7 and β2 subunit interaction using immunoprecipitation assay. In addition, α7β2-nAChRs were sensitive to 1 nM oligomeric Aβ. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. Conclusion These findings suggest that Aβ modulation of cholinergic signaling in hippocampal GABAergic interneurons via α7β2-nAChRs could be an early and critical event in Aβ-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.

  8. The Sensitivity of State Differential Game Vessel Traffic Model

    Directory of Open Access Journals (Sweden)

    Lisowski Józef

    2016-04-01

    Full Text Available The paper presents the application of the theory of deterministic sensitivity control systems for sensitivity analysis implemented to game control systems of moving objects, such as ships, airplanes and cars. The sensitivity of parametric model of game ship control process in collision situations have been presented. First-order and k-th order sensitivity functions of parametric model of process control are described. The structure of the game ship control system in collision situations and the mathematical model of game control process in the form of state equations, are given. Characteristics of sensitivity functions of the game ship control process model on the basis of computer simulation in Matlab/Simulink software have been presented. In the end, have been given proposals regarding the use of sensitivity analysis to practical synthesis of computer-aided system navigator in potential collision situations.

  9. Analysis of the sensitivity and sample-furnace thermal-lag of a differential thermal analyzer

    International Nuclear Information System (INIS)

    Roura, P.; Farjas, J.

    2005-01-01

    The heat exchange between the horizontal furnace of a differential thermal analyzer (DTA) and the sample is analyzed with the aim of understanding the parameters governing the thermal signal. The resistance due to radiation and conduction through the gas has been calculated and compared to the experimental values of the thermal-lag between the sample and furnace and apparatus sensitivity. The overall evolution of these parameters with the temperature and their relative values are well understood by considering the temperature differences that arise between the sample and holder. Two RC thermal models are used for describing the apparatus performance at different temperature ranges. Finally, the possibility of improving the signal quality through the control of the leak resistances is stressed

  10. The Compton Camera - medical imaging with higher sensitivity Exhibition LEPFest 2000

    CERN Multimedia

    2000-01-01

    The Compton Camera reconstructs the origin of Compton-scattered X-rays using electronic collimation with Silicon pad detectors instead of the heavy conventional lead collimators in Anger cameras - reaching up to 200 times better sensitivity and a factor two improvement in resolution. Possible applications are in cancer diagnosis, neurology neurobiology, and cardiology.

  11. Automated differentiation of computer models for sensitivity analysis

    International Nuclear Information System (INIS)

    Worley, B.A.

    1990-01-01

    Sensitivity analysis of reactor physics computer models is an established discipline after more than twenty years of active development of generalized perturbations theory based on direct and adjoint methods. Many reactor physics models have been enhanced to solve for sensitivities of model results to model data. The calculated sensitivities are usually normalized first derivatives although some codes are capable of solving for higher-order sensitivities. The purpose of this paper is to report on the development and application of the GRESS system for automating the implementation of the direct and adjoint techniques into existing FORTRAN computer codes. The GRESS system was developed at ORNL to eliminate the costly man-power intensive effort required to implement the direct and adjoint techniques into already-existing FORTRAN codes. GRESS has been successfully tested for a number of codes over a wide range of applications and presently operates on VAX machines under both VMS and UNIX operating systems

  12. Automated differentiation of computer models for sensitivity analysis

    International Nuclear Information System (INIS)

    Worley, B.A.

    1991-01-01

    Sensitivity analysis of reactor physics computer models is an established discipline after more than twenty years of active development of generalized perturbations theory based on direct and adjoint methods. Many reactor physics models have been enhanced to solve for sensitivities of model results to model data. The calculated sensitivities are usually normalized first derivatives, although some codes are capable of solving for higher-order sensitivities. The purpose of this paper is to report on the development and application of the GRESS system for automating the implementation of the direct and adjoint techniques into existing FORTRAN computer codes. The GRESS system was developed at ORNL to eliminate the costly man-power intensive effort required to implement the direct and adjoint techniques into already-existing FORTRAN codes. GRESS has been successfully tested for a number of codes over a wide range of applications and presently operates on VAX machines under both VMS and UNIX operating systems. (author). 9 refs, 1 tab

  13. Differential reconstructed gene interaction networks for deriving toxicity threshold in chemical risk assessment.

    Science.gov (United States)

    Yang, Yi; Maxwell, Andrew; Zhang, Xiaowei; Wang, Nan; Perkins, Edward J; Zhang, Chaoyang; Gong, Ping

    2013-01-01

    Pathway alterations reflected as changes in gene expression regulation and gene interaction can result from cellular exposure to toxicants. Such information is often used to elucidate toxicological modes of action. From a risk assessment perspective, alterations in biological pathways are a rich resource for setting toxicant thresholds, which may be more sensitive and mechanism-informed than traditional toxicity endpoints. Here we developed a novel differential networks (DNs) approach to connect pathway perturbation with toxicity threshold setting. Our DNs approach consists of 6 steps: time-series gene expression data collection, identification of altered genes, gene interaction network reconstruction, differential edge inference, mapping of genes with differential edges to pathways, and establishment of causal relationships between chemical concentration and perturbed pathways. A one-sample Gaussian process model and a linear regression model were used to identify genes that exhibited significant profile changes across an entire time course and between treatments, respectively. Interaction networks of differentially expressed (DE) genes were reconstructed for different treatments using a state space model and then compared to infer differential edges/interactions. DE genes possessing differential edges were mapped to biological pathways in databases such as KEGG pathways. Using the DNs approach, we analyzed a time-series Escherichia coli live cell gene expression dataset consisting of 4 treatments (control, 10, 100, 1000 mg/L naphthenic acids, NAs) and 18 time points. Through comparison of reconstructed networks and construction of differential networks, 80 genes were identified as DE genes with a significant number of differential edges, and 22 KEGG pathways were altered in a concentration-dependent manner. Some of these pathways were perturbed to a degree as high as 70% even at the lowest exposure concentration, implying a high sensitivity of our DNs approach

  14. Regulating Chondrogenesis of Human Mesenchymal Stromal Cells with a Retinoic Acid Receptor-Beta Inhibitor: Differential Sensitivity of Chondral Versus Osteochondral Development

    Directory of Open Access Journals (Sweden)

    Solvig Diederichs

    2014-05-01

    Full Text Available Aim: Main objective was to investigate whether the synthetic retinoic acid receptor (RAR-β antagonist LE135 is able to drive in vitro chondrogenesis of human mesenchymal stromal cells (MSCs or improve differentiation by suppressing hypertrophic chondrocyte development. Methods: Chondrogenesis of human bone marrow and adipose tissue-derived MSCs was induced in micromass pellet culture for six weeks. Effects of LE135 alone and in combinatorial treatment with TGF-β on deposition of cartilaginous matrix including collagen type II and glycosaminoglycans, on deposition of non-hyaline cartilage collagens type I and X, and on hypertrophy markers including alkaline phosphatase (ALP, indian hedghehog (IHH and matrix metalloproteinase (MMP-13 were assessed. Results: LE135 was no inducer of chondrogenesis and failed to stimulate deposition of collagen type II and glycosaminoglycans. Moreover, addition of LE135 to TGF-β-treated pellets inhibited cartilaginous matrix deposition and gene expression of COL2A1. In contrast, non-hyaline cartilage collagens were less sensitive to LE135 and hypertrophy markers remained unaffected. Conclusion: This demonstrates a differential sensitivity of chondral versus endochondral differentiation pathways to RARβ signaling; however, opposite to the desired direction. The relevance of trans-activating versus trans-repressing RAR signaling, including effects on activator protein (AP-1 is discussed and implications for overcoming current limits of hMSC chondrogenesis are considered.

  15. Regulating chondrogenesis of human mesenchymal stromal cells with a retinoic Acid receptor-Beta inhibitor: differential sensitivity of chondral versus osteochondral development.

    Science.gov (United States)

    Diederichs, Solvig; Zachert, Kerstin; Raiss, Patric; Richter, Wiltrud

    2014-01-01

    Main objective was to investigate whether the synthetic retinoic acid receptor (RAR)-β antagonist LE135 is able to drive in vitro chondrogenesis of human mesenchymal stromal cells (MSCs) or improve differentiation by suppressing hypertrophic chondrocyte development. Chondrogenesis of human bone marrow and adipose tissue-derived MSCs was induced in micromass pellet culture for six weeks. Effects of LE135 alone and in combinatorial treatment with TGF-β on deposition of cartilaginous matrix including collagen type II and glycosaminoglycans, on deposition of non-hyaline cartilage collagens type I and X, and on hypertrophy markers including alkaline phosphatase (ALP), indian hedghehog (IHH) and matrix metalloproteinase (MMP)-13 were assessed. LE135 was no inducer of chondrogenesis and failed to stimulate deposition of collagen type II and glycosaminoglycans. Moreover, addition of LE135 to TGF-β-treated pellets inhibited cartilaginous matrix deposition and gene expression of COL2A1. In contrast, non-hyaline cartilage collagens were less sensitive to LE135 and hypertrophy markers remained unaffected. This demonstrates a differential sensitivity of chondral versus endochondral differentiation pathways to RARβ signaling; however, opposite to the desired direction. The relevance of trans-activating versus trans-repressing RAR signaling, including effects on activator protein (AP)-1 is discussed and implications for overcoming current limits of hMSC chondrogenesis are considered. © 2014 S. Karger AG, Basel.

  16. Computational Analysis of Epidermal Growth Factor Receptor Mutations Predicts Differential Drug Sensitivity Profiles toward Kinase Inhibitors.

    Science.gov (United States)

    Akula, Sravani; Kamasani, Swapna; Sivan, Sree Kanth; Manga, Vijjulatha; Vudem, Dashavantha Reddy; Kancha, Rama Krishna

    2018-05-01

    A significant proportion of patients with lung cancer carry mutations in the EGFR kinase domain. The presence of a deletion mutation in exon 19 or L858R point mutation in the EGFR kinase domain has been shown to cause enhanced efficacy of inhibitor treatment in patients with NSCLC. Several less frequent (uncommon) mutations in the EGFR kinase domain with potential implications in treatment response have also been reported. The role of a limited number of uncommon mutations in drug sensitivity was experimentally verified. However, a huge number of these mutations remain uncharacterized for inhibitor sensitivity or resistance. A large-scale computational analysis of clinically reported 298 point mutants of EGFR kinase domain has been performed, and drug sensitivity profiles for each mutant toward seven kinase inhibitors has been determined by molecular docking. In addition, the relative inhibitor binding affinity toward each drug as compared with that of adenosine triphosphate was calculated for each mutant. The inhibitor sensitivity profiles predicted in this study for a set of previously characterized mutants correlated well with the published clinical, experimental, and computational data. Both the single and compound mutations displayed differential inhibitor sensitivity toward first- and next-generation kinase inhibitors. The present study provides predicted drug sensitivity profiles for a large panel of uncommon EGFR mutations toward multiple inhibitors, which may help clinicians in deciding mutant-specific treatment strategies. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  17. Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin

    International Nuclear Information System (INIS)

    Lopez-Larraza, Daniel M.; Padron, Juan; Ronci, Natalia E.; Vidal Rioja, Lidia A.

    2006-01-01

    Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 o C. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells

  18. Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Larraza, Daniel M. [IMBICE, C.C. 403, 1900 La Plata (Argentina)]. E-mail: danielop@imbice.org.ar; Padron, Juan [IMBICE, C.C. 403, 1900 La Plata (Argentina); Ronci, Natalia E. [IMBICE, C.C. 403, 1900 La Plata (Argentina); Vidal Rioja, Lidia A. [IMBICE, C.C. 403, 1900 La Plata (Argentina)

    2006-08-30

    Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 {sup o}C. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells.

  19. Identifying group-sensitive physical activities: a differential item functioning analysis of NHANES data.

    Science.gov (United States)

    Gao, Yong; Zhu, Weimo

    2011-05-01

    The purpose of this study was to identify subgroup-sensitive physical activities (PA) using differential item functioning (DIF) analysis. A sub-unweighted sample of 1857 (men=923 and women=934) from the 2003-2004 National Health and Nutrition Examination Survey PA questionnaire data was used for the analyses. Using the Mantel-Haenszel, the simultaneous item bias test, and the ANOVA DIF methods, 33 specific leisure-time moderate and/or vigorous PA (MVPA) items were analyzed for DIF across race/ethnicity, gender, education, income, and age groups. Many leisure-time MVPA items were identified as large DIF items. When participating in the same amount of leisure-time MVPA, non-Hispanic blacks were more likely to participate in basketball and dance activities than non-Hispanic whites (NHW); NHW were more likely to participated in golf and hiking than non-Hispanic blacks; Hispanics were more likely to participate in dancing, hiking, and soccer than NHW, whereas NHW were more likely to engage in bicycling, golf, swimming, and walking than Hispanics; women were more likely to participate in aerobics, dancing, stretching, and walking than men, whereas men were more likely to engage in basketball, fishing, golf, running, soccer, weightlifting, and hunting than women; educated persons were more likely to participate in jogging and treadmill exercise than less educated persons; persons with higher incomes were more likely to engage in golf than those with lower incomes; and adults (20-59 yr) were more likely to participate in basketball, dancing, jogging, running, and weightlifting than older adults (60+ yr), whereas older adults were more likely to participate in walking and golf than younger adults. DIF methods are able to identify subgroup-sensitive PA and thus provide useful information to help design group-sensitive, targeted interventions for disadvantaged PA subgroups. © 2011 by the American College of Sports Medicine

  20. Differential response of nNOS knockout mice to MDMA ("ecstasy")- and methamphetamine-induced psychomotor sensitization and neurotoxicity.

    Science.gov (United States)

    Itzhak, Yossef; Anderson, Karen L; Ali, Syed F

    2004-10-01

    It has been shown that mice deficient in neuronal nitric oxide synthase (nNOS) gene are resistant to cocaine-induced psychomotor sensitization and methamphetamine (METH)-induced dopaminergic neurotoxicity. The present study was undertaken to investigate the hypothesis that nNOS has a major role in dopamine (DA)- but not serotonin (5-hydroxytryptamine; 5-HT)-mediated effects of psychostimulants. The response of nNOS knockout (KO) and wild-type (WT) mice to the psychomotor-stimulating and neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and METH were investigated. Repeated administration of MDMA for 5 days resulted in psychomotor sensitization in both WT and nNOS KO mice, while repeated administration of METH caused psychomotor sensitization in WT but not in KO mice. Sensitization to both MDMA and METH was persistent for 40 days in WT mice, but not in nNOS KO mice. These findings suggest that the induction of psychomotor sensitization to MDMA and METH is NO independent and NO dependent, respectively, while the persistence of sensitization to both drugs is NO dependent. For the neurochemical studies, a high dose of MDMA caused marked depletion of 5-HT in several brain regions of both WT and KO mice, suggesting that the absence of the nNOS gene did not afford protection against MDMA-induced depletion of 5-HT. Striatal dopaminergic neurotoxicity caused by high doses of MDMA and METH in WT mice was partially prevented in KO mice administered with MDMA, but it was fully precluded in KO mice administered with METH. The differential response of nNOS KO mice to the behavioral and neurotoxic effects of MDMA and METH suggests that the nNOS gene is required for the expression and persistence of DA-mediated effects of METH and MDMA, while 5-HT-mediated effects of MDMA (induction of sensitization and 5-HT depletion) are not dependent on nNOS.

  1. Differential Processing of Consonance and Dissonance within the Human Superior Temporal Gyrus

    Directory of Open Access Journals (Sweden)

    Francine eFoo

    2016-04-01

    Full Text Available The auditory cortex is well known to be critical for music perception, including the perception of consonance and dissonance. Studies on the neural correlates of consonance and dissonance perception have largely employed non-invasive electrophysiological and functional imaging techniques in humans as well as neurophysiological recordings in animals, but the fine-grained spatiotemporal dynamics within the human auditory cortex remain unknown. We recorded electrocorticographic (ECoG signals directly from the lateral surface of either the left or right temporal lobe of 8 patients undergoing neurosurgical treatment as they passively listened to highly consonant and highly dissonant musical chords. We assessed ECoG activity in the high gamma (γhigh, 70-150 Hz frequency range within the superior temporal gyrus (STG and observed two types of cortical sites of interest in both hemispheres: one type showed no significant difference in γhigh activity between consonant and dissonant chords, and another type showed increased γhigh responses to dissonant chords between 75-200ms post-stimulus onset. Furthermore, a subset of these sites exhibited additional sensitivity towards different types of dissonant chords. We also observed a distinct spatial organization of cortical sites in the right STG, with dissonant-sensitive sites located anterior to non-sensitive sites. In sum, these findings demonstrate differential processing of consonance and dissonance in bilateral STG with the right hemisphere exhibiting robust and spatially organized sensitivity towards dissonance.

  2. Nano-CL-20/HMX Cocrystal Explosive for Significantly Reduced Mechanical Sensitivity

    Directory of Open Access Journals (Sweden)

    Chongwei An

    2017-01-01

    Full Text Available Spray drying method was used to prepare cocrystals of hexanitrohexaazaisowurtzitane (CL-20 and cyclotetramethylene tetranitramine (HMX. Raw materials and cocrystals were characterized using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, Raman spectroscopy, and Fourier transform infrared spectroscopy. Impact and friction sensitivity of cocrystals were tested and analyzed. Results show that, after preparation by spray drying method, microparticles were spherical in shape and 0.5–5 µm in size. Particles formed aggregates of numerous tiny plate-like cocrystals, whereas CL-20/HMX cocrystals had thicknesses of below 100 nm. Cocrystals were formed by C–H⋯O bonding between –NO2 (CL-20 and –CH2– (HMX. Nanococrystal explosives exhibited drop height of 47.3 cm, and friction demonstrated explosion probability of 64%. Compared with raw HMX, cocrystals displayed significantly reduced mechanical sensitivity.

  3. Serum inflammatory markers in the elderly: are they useful in differentiating sepsis from SIRS?

    Directory of Open Access Journals (Sweden)

    Mahshid Talebi-Taher

    2014-06-01

    Full Text Available Differentiating sepsis from other noninfectious causes of systemic inflammation is often difficult in the elderly. The aim of this study was to evaluate the ability of C-reactive protein (CRP, Erythrocyte Sedimentation Rate (ESR, procalcitonin (PCT, and Interleukin-6 (IL-6 to identify elderly patients with sepsis. In this single center prospective observational study, we included all consecutive elderly patients admitted with suspected sepsis and systemic inflammatory response syndrome (SIRS in an emergency department. Blood samples for measuring CRP, PCT, IL-6, ESR and white blood cells (WBC count were taken at first day of admission. Sensitivity, specificity, positive and negative predictive values were calculated for each inflammatory markers being studied. A total of 150 elderly patients aged 65 and older, 50 with sepsis and 50 with SIRS, and fifty individuals in a normal health status were included. CRP exhibited the greatest sensitivity (98% and negative predictive value (98.6% and performed best in differentiating patients with sepsis from those with SIRS. In a receiver operating characteristic curve analysis, IL-6 performed best in distinguishing between SIRS and the control group (AUC 0.75, 95% CI. On the other hand, both CRP and ESR appeared to be a more accurate diagnostic parameter for differentiating sepsis from SIRS among elderly patients.

  4. Chromonic liquid crystalline nematic phase exhibited in binary mixture of two liquid crystals

    Energy Technology Data Exchange (ETDEWEB)

    Govindaiah, T. N., E-mail: tngovi.phy@gmail.com; Sreepad, H. R. [Post-Graduate Department of Physics, Government College (Autonomous), Mandya-571401 (India); Sridhar, K. N.; Sridhara, G. R.; Nagaraja, N. [Government College for Boys, Kolar-563101 (India)

    2015-06-24

    A binary mixture of abietic acid and orthophosphoric acid (H{sub 3}PO{sub 4}) exhibits co-existence of biphasic region of Nematic+Isotropic (N+I), lyotropic Nematic (ND) and Smectic-G (SmG) phases. The mixture exhibits N+I, N and SmG phases at different concentrations and at different temperatures. Mixtures with all concentrations of abietic acid exhibit I→N+I→N→SmG phases sequentially when the specimen is cooled from its isotropic melt. These phases have been characterized by using differential scanning calorimetric, X-ray diffraction, and optical texture studies.

  5. Determination of the interatomic potential from elastic differential cross sections at fixed energy: Functional sensitivity analysis approach

    International Nuclear Information System (INIS)

    Ho, T.; Rabitz, H.

    1989-01-01

    Elastic differential cross sections in atomic crossed beam experiments contain detailed information about the underlying interatomic potentials. The functional sensitivity density of the cross sections with respect to the potential δσ(θ)/δV(R) reveals such information and has been implemented in an iterative inversion procedure, analogous to that of the Newton--Raphson technique. The stability of the inversion is achieved with the use of the regularization method of Tikhonov and Miller. It is shown that given a set of well resolved and noise-free differential cross section data within a limited angular range and given a reasonable starting reference potential, the recovered potential accurately resembles the desired one in the important region, i.e., the region to which the scattering data are sensitive. The region of importance depends upon the collision energy relative to the well depth of the potential under study; usually a higher collision energy penetrates deeper into the repulsive part of the potential and thus accordingly yields a more accurate potential in that part. The inversion procedure produces also a quality function indicating the well determined radial region. Moreover, the extracted potential is quite independent of the functional form of the reference potential in contrast to curve fitting approaches. As illustrations, the model inert gas systems He--Ne and Ne--Ar have been considered. For collision energies within an order of magnitude of the associated potential well depth, the attractive part of the potential can be determined to high precision provided that scattering data at small enough angles are available

  6. Differential proteomic and tissue expression analyses identify valuable diagnostic biomarkers of hepatocellular differentiation and hepatoid adenocarcinomas.

    Science.gov (United States)

    Reis, Henning; Padden, Juliet; Ahrens, Maike; Pütter, Carolin; Bertram, Stefanie; Pott, Leona L; Reis, Anna-Carinna; Weber, Frank; Juntermanns, Benjamin; Hoffmann, Andreas-C; Eisenacher, Martin; Schlaak, Joörg F; Canbay, Ali; Meyer, Helmut E; Sitek, Barbara; Baba, Hideo A

    2015-10-01

    The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candidates were immunohistochemically validated in 14 paired samples of hepatocellular carcinoma (HCC) and non-tumourous liver tissue (NT). The candidates and HepPar1/Arginase1 were afterwards tested for consistency in a large cohort of hepatocellular lesions and NT (n = 290), non-hepatocellular malignancies (n = 383) and HAC (n = 13). Eight non-redundant, differentially expressed proteins were suitable for further immunohistochemical validation and four (ABAT, BHMT, FABP1, HAOX1) for further evaluation. Sensitivity and specificity rates for HCC/HAC were as follows: HepPar1 80.2%, 94.3% / 80.2%, 46.2%; Arginase1 82%, 99.4% / 82%, 69.2%; BHMT 61.4%, 93.8% / 61.4%, 100%; ABAT 84.4%, 33.7% / 84.4%, 30.8%; FABP1 87.2%, 95% / 87.2%, 69.2%; HAOX1 95.5%, 36.3% / 95.5%, 46.2%. The best 2×/3× biomarker panels for the diagnosis of HCC consisted of Arginase1/HAOX1 and BHMT/Arginase1/HAOX1 and for HAC consisted of Arginase1/FABP1 and BHMT/Arginase1/FABP1. In summary, we successfully identified, validated and benchmarked protein biomarker candidates of hepatocellular differentiation. BHMT in particular exhibited superior diagnostic characteristics in hepatocellular lesions and specifically in HAC. BHMT is therefore a promising (panel based) biomarker candidate in the differential diagnostic process of lesions with hepatocellular aspect.

  7. Differential sensitivity of Src-family kinases to activation by SH3 domain displacement.

    Directory of Open Access Journals (Sweden)

    Jamie A Moroco

    Full Text Available Src-family kinases (SFKs are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12 to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo.

  8. Few items in the thyroid-related quality of life instrument ThyPRO exhibited differential item functioning

    DEFF Research Database (Denmark)

    Watt, Torquil; Grønvold, Mogens; Hegedüs, Laszlo

    2014-01-01

    To evaluate the extent of differential item functioning (DIF) within the thyroid-specific quality of life patient-reported outcome measure, ThyPRO, according to sex, age, education and thyroid diagnosis.......To evaluate the extent of differential item functioning (DIF) within the thyroid-specific quality of life patient-reported outcome measure, ThyPRO, according to sex, age, education and thyroid diagnosis....

  9. A combination between the differential and the perturbation theory methods for calculating sensitivity coefficients; Uma combinacao entre os metodos diferencial e da teoria de pertubacao para o calculo dos coeficientes de sensibilidade

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Antonio Andrade

    1998-07-01

    A new method for the calculation of sensitivity coefficients is developed. The new method is a combination of two methodologies used for calculating theses coefficients, which are the differential and the generalized perturbation theory methods. The method utilizes as integral parameter the average flux in an arbitrary region of the system. Thus, the sensitivity coefficient contains only the component corresponding to the neutron flux. To obtain the new sensitivity coefficient, the derivatives of the integral parameter, {phi}, with respect to {sigma} are calculated using the perturbation method and the functional derivatives of this generic integral parameter with respect to {sigma} and {phi} are calculated using the differential method. (author)

  10. Differential Processing of Consonance and Dissonance within the Human Superior Temporal Gyrus

    Science.gov (United States)

    Foo, Francine; King-Stephens, David; Weber, Peter; Laxer, Kenneth; Parvizi, Josef; Knight, Robert T.

    2016-01-01

    The auditory cortex is well-known to be critical for music perception, including the perception of consonance and dissonance. Studies on the neural correlates of consonance and dissonance perception have largely employed non-invasive electrophysiological and functional imaging techniques in humans as well as neurophysiological recordings in animals, but the fine-grained spatiotemporal dynamics within the human auditory cortex remain unknown. We recorded electrocorticographic (ECoG) signals directly from the lateral surface of either the left or right temporal lobe of eight patients undergoing neurosurgical treatment as they passively listened to highly consonant and highly dissonant musical chords. We assessed ECoG activity in the high gamma (γhigh, 70–150 Hz) frequency range within the superior temporal gyrus (STG) and observed two types of cortical sites of interest in both hemispheres: one type showed no significant difference in γhigh activity between consonant and dissonant chords, and another type showed increased γhigh responses to dissonant chords between 75 and 200 ms post-stimulus onset. Furthermore, a subset of these sites exhibited additional sensitivity towards different types of dissonant chords, and a positive correlation between changes in γhigh power and the degree of stimulus roughness was observed in both hemispheres. We also observed a distinct spatial organization of cortical sites in the right STG, with dissonant-sensitive sites located anterior to non-sensitive sites. In sum, these findings demonstrate differential processing of consonance and dissonance in bilateral STG with the right hemisphere exhibiting robust and spatially organized sensitivity toward dissonance. PMID:27148011

  11. Immersive Exhibitions

    DEFF Research Database (Denmark)

    Achiam, Marianne

    2015-01-01

    The immersive exhibition is a specialized exhibition genre in museums, which creates the illusion of time and place by representing key characteristics of a reference world and by integrating the visitor in this three-dimensionally reconstructed world (Mortensen 2010). A successful representation...... of the reference world depends on three criteria: whether the exhibition is staged as a coherent whole with all the displayed objects supporting the representation, whether the visitor is integrated as a component of the exhibition, and whether the content and message of the exhibition become dramatized...

  12. Epigenetic differentiation and relationship to adaptive genetic divergence in discrete populations of the violet Viola cazorlensis.

    Science.gov (United States)

    Herrera, Carlos M; Bazaga, Pilar

    2010-08-01

    *In plants, epigenetic variations based on DNA methylation are often heritable and could influence the course of evolution. Before this hypothesis can be assessed, fundamental questions about epigenetic variation remain to be addressed in a real-world context, including its magnitude, structuring within and among natural populations, and autonomy in relation to the genetic context. *Extent and patterns of cytosine methylation, and the relationship to adaptive genetic divergence between populations, were investigated for wild populations of the southern Spanish violet Viola cazorlensis (Violaceae) using the methylation-sensitive amplified polymorphism (MSAP) technique, a modification of the amplified fragment length polymorphism method (AFLP) based on the differential sensitivity of isoschizomeric restriction enzymes to site-specific cytosine methylation. *The genome of V. cazorlensis plants exhibited extensive levels of methylation, and methylation-based epigenetic variation was structured into distinct between- and within- population components. Epigenetic differentiation of populations was correlated with adaptive genetic divergence revealed by a Bayesian population-genomic analysis of AFLP data. Significant associations existed at the individual genome level between adaptive AFLP loci and the methylation state of methylation-susceptible MSAP loci. *Population-specific, divergent patterns of correlated selection on epigenetic and genetic individual variation could account for the coordinated epigenetic-genetic adaptive population differentiation revealed by this study.

  13. Detection and quantitation of trace phenolphthalein (in pharmaceutical preparations and in forensic exhibits) by liquid chromatography-tandem mass spectrometry, a sensitive and accurate method.

    Science.gov (United States)

    Sharma, Kakali; Sharma, Shiba P; Lahiri, Sujit C

    2013-01-01

    Phenolphthalein, an acid-base indicator and laxative, is important as a constituent of widely used weight-reducing multicomponent food formulations. Phenolphthalein is an useful reagent in forensic science for the identification of blood stains of suspected victims and for apprehending erring officials accepting bribes in graft or trap cases. The pink-colored alkaline hand washes originating from the phenolphthalein-smeared notes can easily be determined spectrophotometrically. But in many cases, colored solution turns colorless with time, which renders the genuineness of bribe cases doubtful to the judiciary. No method is known till now for the detection and identification of phenolphthalein in colorless forensic exhibits with positive proof. Liquid chromatography-tandem mass spectrometry had been found to be most sensitive, accurate method capable of detection and quantitation of trace phenolphthalein in commercial formulations and colorless forensic exhibits with positive proof. The detection limit of phenolphthalein was found to be 1.66 pg/L or ng/mL, and the calibration curve shows good linearity (r(2) = 0.9974). © 2012 American Academy of Forensic Sciences.

  14. Exhibition: Life and Achievements of Maria Sklodowska-Curie

    CERN Multimedia

    CERN Bulletin

    2011-01-01

    The exhibition "Life and Achievements of Maria Sklodowska-Curie” will be held at CERN (Pas Perdus Corridor, 1st floor, building 61) from the 8 to 24 March.   It is organised under the auspices of the Ambassador R. Henczel, Permanent Representative of the Republic of Poland to the UN Office at Geneva to celebrate the 100th anniversary of the Nobel Prize in Chemistry given to Maria Sklodowska-Curie. The exhibition is also one of the events celebrating the 20th anniversary of Poland joining CERN as a Member State. Maria Sklodowska-Curie, Nobel Prize winner both in physics and chemistry, is one of the greatest scientists of Polish origin. The exhibition, consisting of 20 posters, presents her not only as a brilliant scientist, but also an exceptional woman of great heart, character and organizational talents, sensitive to contemporary problems. The authors are Mrs M. Sobieszczak-Marciniak, the director of the Maria Sklodowska-Curie Museum in Warsaw and Mrs H. Krajewska, the direct...

  15. Benzoylformate analogues exhibit differential rate-determining steps in the benzoylformate decarboxylase reaction

    International Nuclear Information System (INIS)

    Garcia, G.A.; Weiss, P.M.; Cook, P.F.; Kenyon, G.L.; Cleland, W.W.

    1987-01-01

    Benzoylformate decarboxylase from Pseudomonas putida is a thiamine pyrophosphate (TPP)-dependent enzyme which converts benzoylformate to benzaldehyde and CO 2 . The rate-determining step(s) in the benzoylformate decarboxylase reaction for a series of substituted benzoylformates (p-CH 3 O, p-CH 3 , p-Cl, and m-F) were studied using solvent deuterium and 13 C kinetic isotope effects. The normal substrate was found to have two partially rate-determining steps; initial tetrahedral adduct formation (D 2 O-sensitive) and decarboxylation ( 13 C-sensitive). D 2 O and 13 C isotope effects indicate that electron-withdrawing substituents (p-Cl and m-F) remove the rate dependence upon decarboxylation such that only a D 2 O effect on (V/K) is observed. Conversely, electron-donating substituents increase the rate-dependence upon decarboxylation such that a larger 13 (V/K) is seen while the D 2 O effects on (V) and (V/K) are not dramatically different from those for benzoylformate. All of the data are consistent with substituent stabilization or destabilization of the carbanionic intermediate formed upon decarboxylation

  16. Neutron importance calculation in an equivalent cell using the age approximation and differential thermalization models. Determination of the cross section sensitivity to the parameters of a differential model in the thermal range

    International Nuclear Information System (INIS)

    Sidorenko, V.D.

    1978-01-01

    The equations are discussed for calculating the importance of neutron function in heterogeneous media obtained with the integral transport theory method. The thermalization effect in the thermal range is described using the differential model. The account of neutron slowing-down in the epithermal range is accomplished in the age approximation. The fast range is described in the 3-group approximation. On the basis of the equations derived the share of delayed neutrons and lifetimes of prompt neutrons are calculated and compared with available experimental data. In the thermal range the sensitivity of cross sections to some parameters of the differential model is analyzed for reactor cells typical for WWER type reactor cores. The models and approximations used are found to be adequate for the calculations

  17. Calcium imaging shows differential sensitivity to cooling and communication in luminous transgenic plants.

    Science.gov (United States)

    Campbell, A K; Trewavas, A J; Knight, M R

    1996-03-01

    Imaging of a recombinant bioluminescent Ca2+ indicator, aequorin, in an entire organism showed three novel features of Ca2+ signals in plants. First, cooling the plant from 25 degrees C to 2 degrees C demonstrated differential sensitivities between organs, the roots firing a Ca2+ signal at some 8-10 degrees C higher than the cotyledons. Secondly, prolonged cooling provoked Ca2+ oscillations, but only in the cotyledons. These oscillations occurred with a frequency of 100 s and damped down within 800 s. Thirdly, cooling the roots of mature plants triggered a Ca2+ signal in the leaves, as a result of organ-organ communication. However, warming and then recooling the roots did not generate a second Ca2+ signal in these leaves. This desensitisation was not due to down-regulation in the leaf since this was able to generate a Ca2+ signal of its own when cooled directly. Thus a combination of a recombinant bioluminescent indicator with photon counting imaging reveals startling new aspects of signalling in intact organs and whole organisms.

  18. Pairing virtual reality with dynamic posturography serves to differentiate between patients experiencing visual vertigo

    Directory of Open Access Journals (Sweden)

    Streepey Jefferson

    2007-07-01

    Full Text Available Abstract Background To determine if increased visual dependence can be quantified through its impact on automatic postural responses, we have measured the combined effect on the latencies and magnitudes of postural response kinematics of transient optic flow in the pitch plane with platform rotations and translations. Methods Six healthy (29–31 yrs and 4 visually sensitive (27–57 yrs subjects stood on a platform rotated (6 deg of dorsiflexion at 30 deg/sec or translated (5 cm at 5 deg/sec for 200 msec. Subjects either had eyes closed or viewed an immersive, stereo, wide field of view virtual environment (scene moved in upward pitch for a 200 msec period for three 30 sec trials at 5 velocities. RMS values and peak velocities of head, trunk, and head with respect to trunk were calculated. EMG responses of 6 trunk and lower limb muscles were collected and latencies and magnitudes of responses determined. Results No effect of visual velocity was observed in EMG response latencies and magnitudes. Healthy subjects exhibited significant effects (p p Conclusion Differentiation of postural kinematics in visually sensitive subjects when exposed to the combined perturbations suggests that virtual reality technology could be useful for differential diagnosis and specifically designed interventions for individuals whose chief complaint is sensitivity to visual motion.

  19. Soya bean Gα proteins with distinct biochemical properties exhibit differential ability to complement Saccharomyces cerevisiae gpa1 mutant.

    Science.gov (United States)

    Roy Choudhury, Swarup; Wang, Yuqi; Pandey, Sona

    2014-07-01

    Signalling pathways mediated by heterotrimeric G-proteins are common to all eukaryotes. Plants have a limited number of each of the G-protein subunits, with the most elaborate G-protein network discovered so far in soya bean (Glycine max, also known as soybean) which has four Gα, four Gβ and ten Gγ proteins. Biochemical characterization of Gα proteins from plants suggests significant variation in their properties compared with the well-characterized non-plant proteins. Furthermore, the four soya bean Gα (GmGα) proteins exhibit distinct biochemical activities among themselves, but the extent to which such biochemical differences contribute to their in vivo function is also not known. We used the yeast gpa1 mutant which displays constitutive signalling and growth arrest in the pheromone-response pathway as an in vivo model to evaluate the effect of distinct biochemical activities of GmGα proteins. We showed that specific GmGα proteins can be activated during pheromone-dependent receptor-mediated signalling in yeast and they display different strengths towards complementation of yeast gpa1 phenotypes. We also identified amino acids that are responsible for differential complementation abilities of specific Gα proteins. These data establish that specific plant Gα proteins are functional in the receptor-mediated pheromone-response pathway in yeast and that the subtle biochemical differences in their activity are physiologically relevant.

  20. Statins and PPARα agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    International Nuclear Information System (INIS)

    Johnson, Timothy E.; Zhang, Xiaohua; Shi, Shu; Umbenhauer, Diane R.

    2005-01-01

    Statins and fibrates (weak PPARα agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPARα agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPARα compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPARγ agonist Rosiglitazone caused little or no cell death at up to 10 μM and the PPARδ ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPARα agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPARα agonism mediates in part the toxicity response to PPARα compounds. Furthermore, PPARα agonists and statins cause myotoxicity through distinct and independent pathways

  1. N-acetylaspartate (NAA) induces neuronal differentiation of SH-SY5Y neuroblastoma cell line and sensitizes it to chemotherapeutic agents.

    Science.gov (United States)

    Mazzoccoli, Carmela; Ruggieri, Vitalba; Tataranni, Tiziana; Agriesti, Francesca; Laurenzana, Ilaria; Fratello, Angelo; Capitanio, Nazzareno; Piccoli, Claudia

    2016-05-03

    Neuroblastoma is the most commonly extra-cranial solid tumor of childhood frequently diagnosed. The nervous system-specific metabolite N-acetylaspartate (NAA) is synthesized from aspartate and acetyl-CoA in neurons, it is among the most abundant metabolites present in the central nervous system (CNS) and appears to be involved in many CNS disorders. The functional significance of the high NAA concentration in the brain remains uncertain, but it confers to NAA a unique clinical significance exploited in magnetic resonance spectroscopy. In the current study, we show that treatment of SH-SY5Y neuroblastoma-derived cell line with sub-cytotoxic physiological concentrations of NAA inhibits cell growth. This effect is partly due to enhanced apoptosis, shown by decrease of the anti-apoptotic factors survivin and Bcl-xL, and partly to arrest of the cell-cycle progression, linked to enhanced expression of the cyclin-inhibitors p53, p21Cip1/Waf1 and p27Kip1. Moreover, NAA-treated SH-SY5Y cells exhibited morphological changes accompanied with increase of the neurogenic markers TH and MAP2 and down-regulation of the pluripotency markers OCT4 and CXCR4/CD184. Finally, NAA-pre-treated SH-SY5Y cells resulted more sensitive to the cytotoxic effect of the chemotherapeutic drugs Cisplatin and 5-fluorouracil.To our knowledge, this is the first study demonstrating the neuronal differentiating effects of NAA in neuroblastoma cells. NAA may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment.

  2. Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing.

    Science.gov (United States)

    Hennessy, Michael B; Chun, Katie; Capitanio, John P

    2017-02-01

    Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1β showed increased responsiveness to immune challenge, and IL-1β and TNF-α showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects.

  3. The psychometrics of mental workload: multiple measures are sensitive but divergent.

    Science.gov (United States)

    Matthews, Gerald; Reinerman-Jones, Lauren E; Barber, Daniel J; Abich, Julian

    2015-02-01

    A study was run to test the sensitivity of multiple workload indices to the differing cognitive demands of four military monitoring task scenarios and to investigate relationships between indices. Various psychophysiological indices of mental workload exhibit sensitivity to task factors. However, the psychometric properties of multiple indices, including the extent to which they intercorrelate, have not been adequately investigated. One hundred fifty participants performed in four task scenarios based on a simulation of unmanned ground vehicle operation. Scenarios required threat detection and/or change detection. Both single- and dual-task scenarios were used. Workload metrics for each scenario were derived from the electroencephalogram (EEG), electrocardiogram, transcranial Doppler sonography, functional near infrared, and eye tracking. Subjective workload was also assessed. Several metrics showed sensitivity to the differing demands of the four scenarios. Eye fixation duration and the Task Load Index metric derived from EEG were diagnostic of single-versus dual-task performance. Several other metrics differentiated the two single tasks but were less effective in differentiating single- from dual-task performance. Psychometric analyses confirmed the reliability of individual metrics but failed to identify any general workload factor. An analysis of difference scores between low- and high-workload conditions suggested an effort factor defined by heart rate variability and frontal cortex oxygenation. General workload is not well defined psychometrically, although various individual metrics may satisfy conventional criteria for workload assessment. Practitioners should exercise caution in using multiple metrics that may not correspond well, especially at the level of the individual operator.

  4. Differential ontogenetic patterns of levocabastine-sensitive neurotensin NT2 receptors and of NT1 receptors in the rat brain revealed by in situ hybridization.

    Science.gov (United States)

    Lépée-Lorgeoux, I; Betancur, C; Rostène, W; Pélaprat, D

    1999-03-12

    The postnatal ontogeny of the levocabastine-sensitive neurotensin receptor (NT2) mRNA was studied by in situ hybridization in the rat brain and compared with the distribution of the levocabastine-insensitive NT1 receptor. NT2 receptor mRNA was absent at birth from all brain structures except the ependymal cell layer lining the ventricles. The development of NT2 receptor mRNA followed three ontogenetic patterns. The first pattern, involving the majority of the cerebral gray matter, was characterized by a continuous increase from postnatal day 5 (P5) to P30. The second one, involving regions rich in myelinated fibers such as the corpus callosum and lacunosum moleculare layer of the hippocampus, exhibited a pronounced increase between P5 and P10, peaked at P15 and was followed by a plateau or a slight decrease. The third pattern was observed in the ependymal cell layer lining the olfactory and lateral ventricles, where the high labeling already present at birth continued to increase during development. These different developmental patterns could reflect the variety of cells expressing NT2 receptor mRNA, including neurons, protoplasmic astrocytes in gray matter, fibrous astrocytes present in myelinated fibers tracts, and ependymal cells. In contrast, NT1 receptor mRNA, which seems to be associated only with neurons, was highly and transiently expressed during the perinatal period in the cerebral cortex, hippocampus and striatal neuroepithelium. Other regions, notably the ventral tegmental area and substantia nigra compacta, exhibited a gradual increase in NT1 receptor signal, reaching adult levels by P21. Both the differential localization and ontogenetic profiles of NT1 and NT2 receptor mRNAs suggest different involvement of these two receptors in brain functions and development. Copyright 1999 Elsevier Science B.V.

  5. Homologous Recombination Defective Arabidopsis Mutants Exhibit Enhanced Sensitivity to Abscisic Acid.

    Directory of Open Access Journals (Sweden)

    Sujit Roy

    Full Text Available Abscisic acid (ABA acts as an important plant hormone in regulating various aspects of plant growth and developmental processes particularly under abiotic stress conditions. An increased ABA level in plant cells inhibits DNA replication and cell division, causing plant growth retardation. In this study, we have investigated the effects of ABA on the growth responses of some major loss-of-function mutants of DNA double-stand break (DSB repair genes in Arabidopsis during seed germination and early stages of seedling growth for understanding the role of ABA in the induction of genome instability in plants. A comparative analysis of ABA sensitivity of wild-type Arabidopsis and the knockout mutant lines related to DSB sensors, including atatm, atatr, the non-homologous end joining (NHEJ pathway genes, and mutants related to homologous recombination (HR pathway genes showed relatively enhanced sensitivity of atatr and HR-related mutants to ABA treatment. The expression levels of HR-related genes were increased in wild-type Arabidopsis (Col-0 during seed germination and early stages of seedling growth. Immunoblotting experiments detected phosphorylation of histone H2AX in wild-type (Col-0 and DSB repair gene mutants after ABA treatment, indicating the activation of DNA damage response due to ABA treatment. Analyses of DSB repair kinetics using comet assay under neutral condition have revealed comparatively slower DSB repair activity in HR mutants. Overall, our results have provided comprehensive information on the possible effect of ABA on DNA repair machinery in plants and also indicated potential functional involvement of HR pathway in repairing ABA induced DNA damage in Arabidopsis.

  6. Exhibit Engineering

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    Science museums define the objectives of their exhibitions in terms of visitor learning outcomes. Yet, exhibit designers lack theoretical and empirical research findings on which to base the creation of such educational environments. Here, this shortcoming is addressed through the development...... of tools and processes to guide the design of educational science exhibits. The guiding paradigm for this development is design-based research, which is characterised by an iterative cycle of design, enactment, and analysis. In the design phase, an educational intervention is planned and carried out based...... on the generation of theoretical ideas for exhibit design is offered in a fourth and parallel research undertaking, namely the application of the notion of cultural border-crossing to a hypothetical case of exhibit design....

  7. Salivary Proteome Patterns Affecting Human Salt Taste Sensitivity.

    Science.gov (United States)

    Stolle, Theresa; Grondinger, Freya; Dunkel, Andreas; Meng, Chen; Médard, Guillaume; Kuster, Bernhard; Hofmann, Thomas

    2017-10-25

    To investigate the role of perireceptor events in inter-individual variability in salt taste sensitivity, 31 volunteers were monitored in their detection functions for sodium chloride (NaCl) and classified into sensitive (0.6-1.7 mmol/L), medium-sensitive (1.8-6.9 mmol/L), and nonsensitive (7.0-11.2 mmol/L) subjects. Chemosensory intervention of NaCl-sensitive (S + ) and nonsensitive (S - ) panellists with potassium chloride, ammonium chloride, and sodium gluconate showed the salt taste sensitivity to be specific for NaCl. As no significant differences were found between S + and S - subjects in salivary sodium and protein content, salivary proteome differences and their stimulus-induced dynamic changes were analyzed by tryptic digestion, iTRAQ labeling, and liquid chromatography-tandem mass spectrometry analysis. Differences in the salivary proteome between S + and S - subjects were found primarily in resting saliva and were largely independent of the dynamic alterations observed upon salt stimulation. Gene ontology enrichment analysis of key proteins, i.e., immunoglobulin heavy constant y1, myeloblastin, cathepsin G, and kallikrein, revealed significantly increased serine-type endopeptidase activity for the S + group, while the S - group exhibited augmented cysteine-type endopeptidase inhibitor activity by increased abundances in lipocalin-1 and cystatin-D, -S, and -SN, respectively. As proteases have been suggested to facilitate transepithelial sodium transport by cleaving the y-subunit of the epithelial sodium channel (ENaC) and protease inhibitors have been shown to reduce ENaC-mediated sodium transport, the differentially modulated proteolytic activity patterns observed in vivo for S + and S - subjects show evidence of them playing a crucial role in affecting human NaCl sensitivity.

  8. Differentiation grade for extrahepatic bile duct adenocarcinoma: Assessed by diffusion-weighted imaging at 3.0-T MR

    International Nuclear Information System (INIS)

    Huang, Xin-Qiao; Shu, Jian; Luo, Li; Jin, Ming-Li; Lu, Xiao-Fei; Yang, Shu-Gen

    2016-01-01

    Highlights: • DWI can assess the prognostic of extrahepatic bile duct adenocarcinomas (EBDA). • The ADC value of EBDA lesion descended as the differentiation grade decreased. • The cut off value from ROC Curve of ADC can predict EBDA differentiation grade. • To some extend, it is reliable as we analysed a relatively large number of EBDAs. - Abstract: Purpose—: To assess the pathological differentiation grade in the patients with extrahepatic bile duct adenocarcinoma (EBDA) using diffusion-weighted imaging (DWI) at 3.0-T MR. Methods—: Sixty-eight patients who were clinically and histologically diagnosed with EBDA underwent abdominal DWI within 2 weeks before surgery. The lesion signal intensity, signal intensity ratio of the lesion and hepar (SIR-LH) value, and apparent diffusion coefficient (ADC) value in patients with EBDA were retrospectively analysed. Results: —In the 68 patients, 22 well-differentiated, 36 moderately-differentiated, and 10 poorly-differentiated EBDAs were histopathological confirmed. These EBDAs exhibited hyper-intensity on DWI in 95.59% of patients. Hyper-intensity lesions were found in 90.91% of patients with good-differentiation, in 97.22% with moderate-differentiation and in 100% with poor-differentiation. There showed no statistical difference for the lesion signal intensity (P = 0.426) and SIR-LH value (P = 0.766) on DWI among three groups. The median ADC value of the well-differentiated, moderately-differentiated and poorly-differentiated EBDAs were 1.506 × 10 −3 mm 2 /s, 1.275 × 10 −3 mm 2 /s and 1.154 × 10 −3 mm 2 /s, respectively. As the pathological differentiation grade decreased, the lesion ADC value of EBDA gradually declined (x 2 = 51.220, P = 0.000). The ADC value <1.184 × 10 −3 mm 2 /s can predict the poorly-differentiated EBDA with a sensitivity of 100% and a specificity of 94.83%. The ADC value >1.316 × 10 −3 mm 2 / s can forecast the well-differentiated EBDA with a sensitivity of 100% and a

  9. Differentiation grade for extrahepatic bile duct adenocarcinoma: Assessed by diffusion-weighted imaging at 3.0-T MR

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xin-Qiao, E-mail: 1109489147@qq.com; Shu, Jian, E-mail: shujiannc@163.com; Luo, Li, E-mail: 23857275@qq.com; Jin, Ming-Li, E-mail: 1242037853@qq.com; Lu, Xiao-Fei, E-mail: 82901782@qq.com; Yang, Shu-Gen, E-mail: 82587849@qq.com

    2016-11-15

    Highlights: • DWI can assess the prognostic of extrahepatic bile duct adenocarcinomas (EBDA). • The ADC value of EBDA lesion descended as the differentiation grade decreased. • The cut off value from ROC Curve of ADC can predict EBDA differentiation grade. • To some extend, it is reliable as we analysed a relatively large number of EBDAs. - Abstract: Purpose—: To assess the pathological differentiation grade in the patients with extrahepatic bile duct adenocarcinoma (EBDA) using diffusion-weighted imaging (DWI) at 3.0-T MR. Methods—: Sixty-eight patients who were clinically and histologically diagnosed with EBDA underwent abdominal DWI within 2 weeks before surgery. The lesion signal intensity, signal intensity ratio of the lesion and hepar (SIR-LH) value, and apparent diffusion coefficient (ADC) value in patients with EBDA were retrospectively analysed. Results: —In the 68 patients, 22 well-differentiated, 36 moderately-differentiated, and 10 poorly-differentiated EBDAs were histopathological confirmed. These EBDAs exhibited hyper-intensity on DWI in 95.59% of patients. Hyper-intensity lesions were found in 90.91% of patients with good-differentiation, in 97.22% with moderate-differentiation and in 100% with poor-differentiation. There showed no statistical difference for the lesion signal intensity (P = 0.426) and SIR-LH value (P = 0.766) on DWI among three groups. The median ADC value of the well-differentiated, moderately-differentiated and poorly-differentiated EBDAs were 1.506 × 10{sup −3} mm{sup 2}/s, 1.275 × 10{sup −3} mm{sup 2}/s and 1.154 × 10{sup −3} mm{sup 2}/s, respectively. As the pathological differentiation grade decreased, the lesion ADC value of EBDA gradually declined (x{sup 2} = 51.220, P = 0.000). The ADC value <1.184 × 10{sup −3} mm{sup 2}/s can predict the poorly-differentiated EBDA with a sensitivity of 100% and a specificity of 94.83%. The ADC value >1.316 × 10{sup −3} mm{sup 2}/ s can forecast the well-differentiated

  10. Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways

    Directory of Open Access Journals (Sweden)

    Young Daniel L

    2006-08-01

    Full Text Available Abstract Nonassociative learning is a basic neuroadaptive behavior exhibited across animal phyla and sensory modalities but its role in brain intelligence is unclear. Current literature on habituation and sensitization, the classic "dual process" of nonassociative learning, gives highly incongruous accounts between varying experimental paradigms. Here we propose a general theory of nonassociative learning featuring four base modes: habituation/primary sensitization in primary stimulus-response pathways, and desensitization/secondary sensitization in secondary stimulus-response pathways. Primary and secondary modes of nonassociative learning are distinguished by corresponding activity-dependent recall, or nonassociative gating, of neurotransmission memory. From the perspective of brain computation, nonassociative learning is a form of integral-differential calculus whereas nonassociative gating is a form of Boolean logic operator – both dynamically transforming the stimulus-response relationship. From the perspective of sensory integration, nonassociative gating provides temporal filtering whereas nonassociative learning affords low-pass, high-pass or band-pass/band-stop frequency filtering – effectively creating an intelligent sensory firewall that screens all stimuli for attention and resultant internal model adaptation and reaction. This unified framework ties together many salient characteristics of nonassociative learning and nonassociative gating and suggests a common kernel that correlates with a wide variety of sensorimotor integration behaviors such as central resetting and self-organization of sensory inputs, fail-safe sensorimotor compensation, integral-differential and gated modulation of sensorimotor feedbacks, alarm reaction, novelty detection and selective attention, as well as a variety of mental and neurological disorders such as sensorimotor instability, attention deficit hyperactivity, sensory defensiveness, autism

  11. An immuno-wall microdevice exhibits rapid and sensitive detection of IDH1-R132H mutation specific to grade II and III gliomas

    Science.gov (United States)

    Yamamichi, Akane; Kasama, Toshihiro; Ohka, Fumiharu; Suzuki, Hiromichi; Kato, Akira; Motomura, Kazuya; Hirano, Masaki; Ranjit, Melissa; Chalise, Lushun; Kurimoto, Michihiro; Kondo, Goro; Aoki, Kosuke; Kaji, Noritada; Tokeshi, Manabu; Matsubara, Toshio; Senga, Takeshi; Kaneko, Mika K.; Suzuki, Hidenori; Hara, Masahito; Wakabayashi, Toshihiko; Baba, Yoshinobu; Kato, Yukinari; Natsume, Atsushi

    2016-01-01

    World Health Organization grade II and III gliomas most frequently occur in the central nervous system (CNS) in adults. Gliomas are not circumscribed; tumor edges are irregular and consist of tumor cells, normal brain tissue, and hyperplastic reactive glial cells. Therefore, the tumors are not fully resectable, resulting in recurrence, malignant progression, and eventual death. Approximately 69-80% of grade II and III gliomas harbor mutations in the isocitrate dehydrogenase 1 gene (IDH1), of which 83-90% are found to be the IDH1-R132H mutation. Detection of the IDH1-R132H mutation should help in the differential diagnosis of grade II and III gliomas from other types of CNS tumors and help determine the boundary between the tumor and normal brain tissue. In this study, we established a highly sensitive antibody-based device, referred to as the immuno-wall, to detect the IDH1-R132H mutation in gliomas. The immuno-wall causes an immunoreaction in microchannels fabricated using a photo-polymerizing polymer. This microdevice enables the analysis of the IDH1 status with a small sample within 15 min with substantially high sensitivity. Our results suggested that 10% content of the IDH1-R132H mutation in a sample of 0.33 μl volume, with 500 ng protein, or from 500 cells is theoretically sufficient for the analysis. The immuno-wall device will enable the rapid and highly sensitive detection of the IDH1-R132H mutation in routine clinical practice.

  12. Highly repeatable room temperature negative differential resistance in AlN/GaN resonant tunneling diodes grown by molecular beam epitaxy

    International Nuclear Information System (INIS)

    Growden, Tyler A.; Fakhimi, Parastou; Berger, Paul R.; Storm, David F.; Meyer, David J.; Zhang, Weidong; Brown, Elliott R.

    2016-01-01

    AlN/GaN resonant tunneling diodes grown on low dislocation density semi-insulating bulk GaN substrates via plasma-assisted molecular-beam epitaxy are reported. The devices were fabricated using a six mask level, fully isolated process. Stable room temperature negative differential resistance (NDR) was observed across the entire sample. The NDR exhibited no hysteresis, background light sensitivity, or degradation of any kind after more than 1000 continuous up-and-down voltage sweeps. The sample exhibited a ∼90% yield of operational devices which routinely displayed an average peak current density of 2.7 kA/cm 2 and a peak-to-valley current ratio of ≈1.15 across different sizes.

  13. Highly repeatable room temperature negative differential resistance in AlN/GaN resonant tunneling diodes grown by molecular beam epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Growden, Tyler A.; Fakhimi, Parastou; Berger, Paul R., E-mail: pberger@ieee.org [Department of Electrical and Computer Engineering, The Ohio State University, Columbus, Ohio 43210 (United States); Storm, David F.; Meyer, David J. [U.S. Naval Research Laboratory, Washington, DC 20375 (United States); Zhang, Weidong; Brown, Elliott R. [Departments of Physics and Electrical Engineering, Wright State University, Dayton, Ohio 45435 (United States)

    2016-08-22

    AlN/GaN resonant tunneling diodes grown on low dislocation density semi-insulating bulk GaN substrates via plasma-assisted molecular-beam epitaxy are reported. The devices were fabricated using a six mask level, fully isolated process. Stable room temperature negative differential resistance (NDR) was observed across the entire sample. The NDR exhibited no hysteresis, background light sensitivity, or degradation of any kind after more than 1000 continuous up-and-down voltage sweeps. The sample exhibited a ∼90% yield of operational devices which routinely displayed an average peak current density of 2.7 kA/cm{sup 2} and a peak-to-valley current ratio of ≈1.15 across different sizes.

  14. Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

    Science.gov (United States)

    Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

    2015-05-01

    Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

  15. Mycobacterium tuberculosis strains exhibit differential and strain-specific molecular signatures in pulmonary epithelial cells.

    Science.gov (United States)

    Mvubu, Nontobeko Eunice; Pillay, Balakrishna; Gamieldien, Junaid; Bishai, William; Pillay, Manormoney

    2016-12-01

    Although pulmonary epithelial cells are integral to innate and adaptive immune responses during Mycobacterium tuberculosis infection, global transcriptomic changes in these cells remain largely unknown. Changes in gene expression induced in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11, F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq). The Illumina HiSeq 2000 platform generated 50 bp reads that were mapped to the human genome (Hg19) using Tophat (2.0.10). Differential gene expression induced by the different strains in infected relative to the uninfected cells was quantified and compared using Cufflinks (2.1.0) and MeV (4.0.9), respectively. Gene expression varied among the strains with the total number of genes as follows: F15/LAM4/KZN (1187), Beijing (1252), F11 (1639), F28 (870), Unique (886) and H37Rv (1179). A subset of 292 genes was commonly induced by all strains, where 52 genes were down-regulated while 240 genes were up-regulated. Differentially expressed genes were compared among the strains and the number of induced strain-specific gene signatures were as follows: F15/LAM4/KZN (138), Beijing (52), F11 (255), F28 (55), Unique (186) and H37Rv (125). Strain-specific molecular gene signatures associated with functional pathways were observed only for the Unique and H37Rv strains while certain biological functions may be associated with other strain signatures. This study demonstrated that strains of M. tuberculosis induce differential gene expression and strain-specific molecular signatures in pulmonary epithelial cells. Specific signatures induced by clinical strains of M. tuberculosis can be further explored for novel host-associated biomarkers and adjunctive immunotherapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Technology Exhibition

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1979-09-15

    Linked to the 25th Anniversary celebrations, an exhibition of some of CERN's technological achievements was opened on 22 June. Set up in a new 600 m{sup 2} Exhibition Hall on the CERN site, the exhibition is divided into eight technology areas — magnets, vacuum, computers and data handling, survey and alignment, radiation protection, beam monitoring and handling, detectors, and workshop techniques.

  17. Eugenics visualized: the exhibit of the Third International Congress of Eugenics, 1932.

    Science.gov (United States)

    Stillwell, Devon

    2012-01-01

    This article investigates the exhibit of the Third International Congress of Eugenics, which was organized by Harry Hamilton Laughlin and showcased at the American Museum of Natural History in 1932. It argues that the exhibit's displays shaped popular eugenic ideology by connecting particular eugenic principles to specific visual representations that were experienced in relation to binaries such as the artistically traditional and the modern, the classical and the grotesque, and the scientific and the spectacle (or the "freak" and the medical specimen). These dichotomies were, in turn, experienced within the context of the exhibit's overall theme of eugenics as anchored in the past and the future and concern over the differential birthrate. The exhibit to the Third Congress provides insight into growing tensions within the eugenics movement of the 1930s, the importance of positive eugenics, the aesthetics of heredity, and how the "scientific truths" of a given era are publicized and perpetuated.

  18. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

    Directory of Open Access Journals (Sweden)

    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  19. Gene regulatory and signaling networks exhibit distinct topological distributions of motifs

    Science.gov (United States)

    Ferreira, Gustavo Rodrigues; Nakaya, Helder Imoto; Costa, Luciano da Fontoura

    2018-04-01

    The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.

  20. Functional Analysis and Treatment of Human-Directed Undesirable Behavior Exhibited by a Captive Chimpanzee

    Science.gov (United States)

    Martin, Allison L.; Bloomsmith, Mollie A.; Kelley, Michael E.; Marr, M. Jackson; Maple, Terry L.

    2011-01-01

    A functional analysis identified the reinforcer maintaining feces throwing and spitting exhibited by a captive adult chimpanzee ("Pan troglodytes"). The implementation of a function-based treatment combining extinction with differential reinforcement of an alternate behavior decreased levels of inappropriate behavior. These findings further…

  1. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    International Nuclear Information System (INIS)

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.

    2013-01-01

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level

  2. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

    2013-08-15

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

  3. Statins and PPAR{alpha} agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Timothy E [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States); Zhang, Xiaohua [Department of Biometrics Research, Merck Research Laboratories, West Point, PA 19486 (United States); Shi, Shu [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States); Umbenhauer, Diane R [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States)

    2005-11-01

    Statins and fibrates (weak PPAR{alpha} agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPAR{alpha} agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPAR{alpha} compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPAR{gamma} agonist Rosiglitazone caused little or no cell death at up to 10 {mu}M and the PPAR{delta} ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPAR{alpha} agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPAR{alpha} agonism mediates in part the toxicity response to PPAR{alpha} compounds. Furthermore, PPAR{alpha} agonists and statins cause myotoxicity through distinct and independent pathways.

  4. Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens

    Energy Technology Data Exchange (ETDEWEB)

    Montani, Claudia [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Steimberg, Nathalie; Boniotti, Jennifer [Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia (Italy); Biasiotto, Giorgio; Zanella, Isabella [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Diafera, Giuseppe [Integrated Systems Engineering (ISE), Milan (Italy); Biunno, Ida [IRGB-CNR, Milan (Italy); IRCCS-Multimedica, Milan (Italy); Caimi, Luigi [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Mazzoleni, Giovanna [Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia (Italy); Di Lorenzo, Diego, E-mail: diego.dilorenzo@yahoo.it [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy)

    2014-11-01

    Cell differentiation and response to hormonal signals were studied in a 3D environment on an in-house generated mouse fibroblast cell line expressing a reporter gene under the control of estrogen responsive sequences (EREs). 3D cell culture conditions were obtained in a Rotary Cell Culture System; (RCCS™), a microgravity based bioreactor that promotes the aggregation of cells into multicellular spheroids (MCS). In this bioreactor the cells maintained a better differentiated phenotype and more closely resembled in vivo tissue. The RCCS™ cultured fibroblasts showed higher expression of genes regulating cell assembly, differentiation and hormonal functions. Microarray analysis showed that genes related to cell cycle, proliferation, cytoskeleton, migration, adhesion and motility were all down-regulated in 3D as compared to 2D conditions, as well as oncogene expression and inflammatory cytokines. Controlled remodeling of ECM, which is an essential aspect of cell organization, homeostasis and tissue was affected by the culture method as assessed by immunolocalization of β-tubulin. Markers of cell organization, homeostasis and tissue repair, metalloproteinase 2 (MMP2) and its physiological inhibitor (TIMP4) changed expression in association with the relative formation of cell aggregates. The fibroblasts cultured in the RCCS™ maintain a better responsiveness to estrogens, measured as expression of ERα and regulation of an ERE-dependent reporter and of the endogenous target genes CBP, Rarb, MMP1 and Dbp. Our data highlight the interest of this 3D culture model for its potential application in the field of cell response to hormonal signals and the pharmaco-toxicological analyses of chemicals and natural molecules endowed of estrogenic potential. - Highlights: • We here characterized the first cell line derived from an estrogen reporter mouse. • In the RCCS cells express an immortalized behavior but not a transformed phenotype. • The RCCS provides a system for

  5. Differential biological effects of iodoacetate in mammalian cell lines; radio sensitization and radio protection

    International Nuclear Information System (INIS)

    Yadav, Usha; Anjaria, K.B.; Desai, Utkarsha N.; Chaurasia, Rajesh K.; Shirsath, K.B.; Bhat, Nagesh N.; Balakrishnan, Sreedevi; Sapra, B.K.; Nairy, Rajesha

    2014-01-01

    There are several studies where it has been shown that Iodoacetate (IA) possesses in vivo anti-tumor activity. The fact that it is a model glycolytic inhibitor makes it more interesting. As seen in recent trends, glycolytic inhibitors are emerging as new strategy for cancer therapeutic research taking advantage of glycolytic phenotype of cancerous tissues. IA has been reported to have radioprotective effects in yeast cells and human lymphocytes. Biological effects of IA in response to radiation in mammalian cell lines are not well documented. We screened IA for cytotoxicity using clonogenic assay at different concentrations ranging from 0.1 to 2.5 μg/ml using three different mammalian cell lines; A-549 (human lung carcinoma cell line), MCF-7 (human mammary cancer cell line) and a noncancerous CHO (Chinese hamster ovary cell line). For studying radioprotective/radio sensitizing efficacy, cells were exposed to 4 Gy of 60 Co-γ radiation using a teletherapy source at a dose rate of 1 Gy/min, following which IA post-treatment was carried out. Clonogenic and micronucleus assay were performed to assess radioprotection/sensitization. The results indicated that IA was highly cytotoxic in cancerous cell lines A-549 (IC 50 =1.25 μg/ml) and MCF-7 (IC 50 = 1.9 μg/ml). In contrast, it was totally non-toxic in non-cancerous cell line, viz. CHO, in the same concentration range. In addition, IA exhibited radio protective effect in CHO cell line, whereas in other two cancer cell lines, viz. A-549 and MCF-7, radio sensitizing effect was seen as judged by induction of cell killing and micronuclei. In conclusion, lA, a model glycolytic inhibitor, was found to be selectively cytotoxic in cancer cells as compared to normal cells. Further, it reduced radiation induced damage (micronuclei and cell killing) in normal cells but increased it in cancer cells indicating its potential use in cancer therapy. (author)

  6. Role of the mitochondrial amino acid pool in the differential sensitivity of erythroid and myeloid cells to chloramphenicol

    International Nuclear Information System (INIS)

    Abou-Khalil, S.; Abou-Khalil, W.H.; Whitney, P.L.; Yunis, A.A.

    1986-01-01

    Previous studies in the authors laboratory have suggested that mitochondrial amino acid (AA) pool is involved in the differential sensitivity of erythroid and myeloid cells to chloramphenicol (CAP). The present study examines the role of AA pool by analysis of its composition and testing the effects of its major components. The endogenous AA composition of isolated mitochondria protein was determined using a JEOL 5AH AA analyzer. L-( 14 C) leucine incorporation into mitochondrial protein was used to measure the rate of protein synthesis. Analysis of the endogenous pool in erythroleukemia (EM) and chloroleukemia (CM) mitochrondria showed similar total amount of AAs. However, some AAs were present in significantly higher or lower quantity within EM and CM (i.e. EM had about 2-fold higher glycine content). When compensating for each low AA addition of that particular acid to the reaction medium, only glycine and serine had significant effect. Thus, the addition of increasing concentrations of glycine or serine enhanced the sensitivity to CAP from 14% to 49-51% in CM but not in EM. Other AAs gave little or no effect. Since glycine is one of the first reactants in heme biosynthesis within mitochondria and is interconvertible with serine, it would appear that erythroid cells sensitivity to CAP is determined by the mitochondrial glycine-serine pool and may be somehow related of the pathway to heme biosynthesis in these cells

  7. Parametric Sensitivity Analysis of Oscillatory Delay Systems with an Application to Gene Regulation.

    Science.gov (United States)

    Ingalls, Brian; Mincheva, Maya; Roussel, Marc R

    2017-07-01

    A parametric sensitivity analysis for periodic solutions of delay-differential equations is developed. Because phase shifts cause the sensitivity coefficients of a periodic orbit to diverge, we focus on sensitivities of the extrema, from which amplitude sensitivities are computed, and of the period. Delay-differential equations are often used to model gene expression networks. In these models, the parametric sensitivities of a particular genotype define the local geometry of the evolutionary landscape. Thus, sensitivities can be used to investigate directions of gradual evolutionary change. An oscillatory protein synthesis model whose properties are modulated by RNA interference is used as an example. This model consists of a set of coupled delay-differential equations involving three delays. Sensitivity analyses are carried out at several operating points. Comments on the evolutionary implications of the results are offered.

  8. Evaluation of tumor markers for the differential diagnosis of benign and malignant ascites.

    Science.gov (United States)

    Liu, Fang; Kong, Xinjuan; Dou, Qian; Ye, Jin; Xu, Dong; Shang, Haitao; Xu, Keshu; Song, Yuhu

    2014-01-01

    The diagnosis of malignant ascites is a challenging problem in clinical practice, non-invasive techniques should be developed to improve diagnostic accuracy. The diagnostic performances of tumor markers in malignant ascites remained unsettled. Our aim was to evaluate diagnostic performance of tumor markers in differential diagnosis of benign and malignant ascites. A total of 437 patients were enrolled, and the relevant parameters of the patients were analyzed for the differentiation of benign ascites from malignant ascites. At the predetermined cutoff values of tumor makers, tumor markers in ascitic fluid showed better diagnostic performance than those in serum. Combined use of tumor markers and the cytology increased the diagnostic yield of the latter by 37%. In cytologically negative malignant ascites, tumor markers provided assistance in differentiating malignant ascites from benign ascites, and the combination of ascitic tumor markers yielded 86% sensitivity, 97% specificity. Use of a panel of tumor markers exhibited excellent diagnostic performance in diagnosing malignant ascites, which indicated the detection of tumor markers may represent a beneficial adjunct to cytology, thus guiding the selection of patients who might benefit from further invasive procedures.

  9. The fetal/neonatal mouse liver exhibits transcriptional features of the adult pancreas.

    Science.gov (United States)

    Metabolic homeostasis of the organism is maintained by the liver’s ability to detoxify and eliminate xenobiotics through the expression of xenobiotic metabolism enxymes (XME). The fetus and neonate have been hypothesized to exhibit increased sensitivity to xenobiotic toxicity. T...

  10. Sensitivity and fidelity of DNA microarray improved with integration of Amplified Differential Gene Expression (ADGE

    Directory of Open Access Journals (Sweden)

    Ile Kristina E

    2003-07-01

    Full Text Available Abstract Background The ADGE technique is a method designed to magnify the ratios of gene expression before detection. It improves the detection sensitivity to small change of gene expression and requires small amount of starting material. However, the throughput of ADGE is low. We integrated ADGE with DNA microarray (ADGE microarray and compared it with regular microarray. Results When ADGE was integrated with DNA microarray, a quantitative relationship of a power function between detected and input ratios was found. Because of ratio magnification, ADGE microarray was better able to detect small changes in gene expression in a drug resistant model cell line system. The PCR amplification of templates and efficient labeling reduced the requirement of starting material to as little as 125 ng of total RNA for one slide hybridization and enhanced the signal intensity. Integration of ratio magnification, template amplification and efficient labeling in ADGE microarray reduced artifacts in microarray data and improved detection fidelity. The results of ADGE microarray were less variable and more reproducible than those of regular microarray. A gene expression profile generated with ADGE microarray characterized the drug resistant phenotype, particularly with reference to glutathione, proliferation and kinase pathways. Conclusion ADGE microarray magnified the ratios of differential gene expression in a power function, improved the detection sensitivity and fidelity and reduced the requirement for starting material while maintaining high throughput. ADGE microarray generated a more informative expression pattern than regular microarray.

  11. A voltage-sensitive dye-based assay for the identification of differentiated neurons derived from embryonic neural stem cell cultures.

    Directory of Open Access Journals (Sweden)

    Richardson N Leão

    Full Text Available BACKGROUND: Pluripotent and multipotent stem cells hold great therapeutical promise for the replacement of degenerated tissue in neurological diseases. To fulfill that promise we have to understand the mechanisms underlying the differentiation of multipotent cells into specific types of neurons. Embryonic stem cell (ESC and embryonic neural stem cell (NSC cultures provide a valuable tool to study the processes of neural differentiation, which can be assessed using immunohistochemistry, gene expression, Ca(2+-imaging or electrophysiology. However, indirect methods such as protein and gene analysis cannot provide direct evidence of neuronal functionality. In contrast, direct methods such as electrophysiological techniques are well suited to produce direct evidence of neural functionality but are limited to the study of a few cells on a culture plate. METHODOLOGY/PRINCIPAL FINDINGS: In this study we describe a novel method for the detection of action potential-capable neurons differentiated from embryonic NSC cultures using fast voltage-sensitive dyes (VSD. We found that the use of extracellularly applied VSD resulted in a more detailed labeling of cellular processes compared to calcium indicators. In addition, VSD changes in fluorescence translated precisely to action potential kinetics as assessed by the injection of simulated slow and fast sodium currents using the dynamic clamp technique. We further demonstrate the use of a finite element model of the NSC culture cover slip for optimizing electrical stimulation parameters. CONCLUSIONS/SIGNIFICANCE: Our method allows for a repeatable fast and accurate stimulation of neurons derived from stem cell cultures to assess their differentiation state, which is capable of monitoring large amounts of cells without harming the overall culture.

  12. The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid

    Directory of Open Access Journals (Sweden)

    Aiken Christopher

    2004-06-01

    Full Text Available Abstract Background Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast, SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB, we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4+ T cells. Results Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to DSB, but the mutant virus replicated with reduced efficiency. Conversely, replication of an SIV mutant containing three amino acid substitutions in the CA-SP1 cleavage site was highly sensitive to DSB, and the mutations resulted in delayed cleavage of the CA-SP1 junction in the presence of the drug. Conclusions These results demonstrate that the CA-SP1 junction in Pr55Gag represents the primary viral target of DSB. They further suggest that the therapeutic application of DSB will be accompanied by emergence of mutant viruses that are highly resistant to the drug but which exhibit reduced fitness relative to wild type HIV-1.

  13. Sensitivity Analysis of a Proposed Novel Opto-Nano-Mechanical Photodetector for Improving the Performance of LIDAR and Local Optical Sensors

    International Nuclear Information System (INIS)

    Berman, Gennady P; Bishop, Alan R; Chernobrod, Boris M; Hawley, Marilyn E; Brown, Geoffrey W

    2006-01-01

    We propose a novel approach to the development of a new generation of optical sensors with enhanced detection sensitivity for chemical species. The novelty comes from combining an extremely high Q cantilever sensor with an already well established very sensitive technique, frequency modulation (FM) spectroscopy. In existing implementations, this inherent sensitivity is limited by the inadequacy of current state-of-the-art electronic filters to differentiate the weak amplitude modulated (AM) signal from the inevitable high-frequency laser noise, a consequence of the deterioration in the quality factor with increasing frequency exhibited by these filters. Our approach combines FM techniques with the rapidly advancing technology of nano-mechanical resonator (cantilever) development. Here a cantilever functions as both a sensitive photodetector and a high-quality spectral or temporal filter. These ultra-low mass devices enable detection of the photon momentum rather than conventional detection by photon energy. At least one order of magnitude enhancement appears feasible with existing cantilever technology

  14. Sensitivity Analysis of a Proposed Novel Opto-Nano-Mechanical Photodetector for Improving the Performance of LIDAR and Local Optical Sensors

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Gennady P; Bishop, Alan R; Chernobrod, Boris M; Hawley, Marilyn E; Brown, Geoffrey W [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    2006-05-15

    We propose a novel approach to the development of a new generation of optical sensors with enhanced detection sensitivity for chemical species. The novelty comes from combining an extremely high Q cantilever sensor with an already well established very sensitive technique, frequency modulation (FM) spectroscopy. In existing implementations, this inherent sensitivity is limited by the inadequacy of current state-of-the-art electronic filters to differentiate the weak amplitude modulated (AM) signal from the inevitable high-frequency laser noise, a consequence of the deterioration in the quality factor with increasing frequency exhibited by these filters. Our approach combines FM techniques with the rapidly advancing technology of nano-mechanical resonator (cantilever) development. Here a cantilever functions as both a sensitive photodetector and a high-quality spectral or temporal filter. These ultra-low mass devices enable detection of the photon momentum rather than conventional detection by photon energy. At least one order of magnitude enhancement appears feasible with existing cantilever technology.

  15. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

    Directory of Open Access Journals (Sweden)

    Pernilla Lång

    2008-03-01

    Full Text Available Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer.Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity.Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  16. Differential inhibition of calmodulin-sensitive phosphodiesterase and Ca++-adenosine triphosphatase by chlorpromazine-linked calmodulin

    International Nuclear Information System (INIS)

    Prozialeck, W.C.; Wallace, T.L.; Weiss, B.

    1987-01-01

    Upon irradiation with UV light, chlorpromazine binds irreversibly to calmodulin and inactivates it. To determine whether this chlorpromazine-calmodulin (CPZ-CaM) complex can inhibit the actions of native calmodulin, we examined its effects on the activity of calmodulin-sensitive cyclic nucleotide phosphodiesterase from rat brain and on the Ca++-adenosine triphosphatase (ATPase) of human erythrocyte membranes. The CPZ-CaM complex was prepared by irradiating purified bovine brain calmodulin in the presence of chlorpromazine and Ca++. The sample was then dialyzed extensively to remove reversibly bound chlorpromazine and then assayed for its ability to activate calmodulin-sensitive phosphodiesterase and Ca++-ATPase, and for its ability to block the stimulatory effects of native calmodulin on these enzymes. The CPZ-CaM complex had no effect on the basal activity of either enzyme; it neither activated nor inhibited the enzymes when assayed in the absence of calmodulin. However, it affected differentially the activation of the two enzymes by native calmodulin. The CPZ-CaM complex totally inhibited calmodulin-stimulated phosphodiesterase but had no effect on the activation of the ATPase by calmodulin. Other studies showed that CPZ-CaM increased the activation constant (Ka) for the interaction of calmodulin with phosphodiesterase but did not affect the maximal activation (Vmax) of the enzyme by calmodulin. Neither calmodulin nor CPZ-CaM altered the Km for the interaction between phosphodiesterase and cyclic AMP. These results suggest that CPZ-CaM inhibits the calmodulin-induced activation of phosphodiesterase by competing with calmodulin for regulatory sites on the enzyme and not by interacting with calmodulin itself or by blocking the interaction of cyclic AMP with the enzyme

  17. Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon.

    Science.gov (United States)

    Wu, Po-Chang; Huang, Min-Nung; Kuo, Yu-Min; Hsieh, Song-Chou; Yu, Chia-Li

    2013-08-01

    Nailfold capillaroscopy is a useful tool to distinguish primary from secondary Raynaud's phenomenon (RP) by examining the morphology of nailfold capillaries but its role in disease diagnosis is not clearly established. The purpose of this study was to evaluate the roles of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases (CTDs) with RP. The data between the year 2005 and 2009 were retrieved from the nailfold capillaroscopic database of National Taiwan University Hospital (NTUH). Only the data from the patients with RP were analyzed. The criteria for interpretation of capillaroscopic findings were predefined. The final diagnoses of the patients were based on the American College of Rheumatology classification criteria for individual diseases, independent of nailfold capillaroscopic findings. The sensitivity and the specificity of each capillaroscopic pattern to the diseases were determined. The data from a total of 67 patients were qualified for the current study. We found the sensitivity and specificity of scleroderma pattern for systemic sclerosis (SSc) were 89.47% and 80%, and the specificity of the early, active, and late scleroderma patterns for SSc reached 87.5%, 97.5%, and 95%, respectively. The sensitivity/specificity of systemic lupus erythematosus (SLE) pattern for SLE and polymyositis/dermatomyositis (PM/DM) pattern for PM/DM were 33.33%/95.45% and 60%/96.3%, respectively. The sensitivity/specificity of mixed connective tissue disease (MCTD) pattern for MCTD were 20%/100%. The nailfold capillaroscopic (NC) patterns may be useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD patterns exhibit high specificity but relatively low sensitivity. Copyright © 2012. Published by Elsevier B.V.

  18. Apoptosis in differentiating C2C12 muscle cells selectively targets Bcl-2-deficient myotubes

    Science.gov (United States)

    Schoneich, Christian; Dremina, Elena; Galeva, Nadezhda; Sharov, Victor

    2014-01-01

    Muscle cell apoptosis accompanies normal muscle development and regeneration, as well as degenerative diseases and aging. C2C12 murine myoblast cells represent a common model to study muscle differentiation. Though it was already shown that myogenic differentiation of C2C12 cells is accompanied by enhanced apoptosis in a fraction of cells, either the cell population sensitive to apoptosis or regulatory mechanisms for the apoptotic response are unclear so far. In the current study we characterize apoptotic phenotypes of different types of C2C12 cells at all stages of differentiation, and report here that myotubes of differentiated C2C12 cells with low levels of anti-apoptotic Bcl-2 expression are particularly vulnerable to apoptosis even though they are displaying low levels of pro-apoptotic proteins Bax, Bak and Bad. In contrast, reserve cells exhibit higher levels of Bcl-2 and high resistance to apoptosis. The transfection of proliferating myoblasts with Bcl-2 prior to differentiation did not protect against spontaneous apoptosis accompanying differentiation of C2C12 cell but led to Bcl-2 overexpression in myotubes and to significant protection from apoptotic cell loss caused by exposure to hydrogen peroxide. Overall, our data advocate for a Bcl-2-dependent mechanism of apoptosis in differentiated muscle cells. However, downstream processes for spontaneous and hydrogen peroxide induced apoptosis are not completely similar. Apoptosis in differentiating myoblasts and myotubes is regulated not through interaction of Bcl-2 with pro-apoptotic Bcl-2 family proteins such as Bax, Bak, and Bad. PMID:24129924

  19. Environmental policies in a differentiated oligopoly revisited

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Kenji [School of Economics, Kwansei Gakuin Univ., Uegahara 1-1-155, Nishinomiya, Hyogo 662-8501 (Japan)

    2009-08-15

    Constructing a model of polluting oligopoly with product differentiation, we consider how product differentiation, together with the presence and absence of free entry, affects optimal pollution tax/subsidy policies. The sign of the short- and long-run optimal pollution taxes are highly sensitive to the parameter measuring product differentiation as well as the presence of free entry. How they are affected by a change in product differentiation, which is not addressed in the existing literature, is also made clear. (author)

  20. Scanning differential polarization microscope: Its use to image linear and circular differential scattering

    International Nuclear Information System (INIS)

    Mickols, W.; Maestre, M.F.

    1988-01-01

    A differential polarization microscope that couples the sensitivity of single-beam measurement of circular dichroism and circular differential scattering with the simultaneous measurement of linear dichroism and linear differential scattering has been developed. The microscope uses a scanning microscope stage and single-point illumination to give the very shallow depth of field found in confocal microscopy. This microscope can operate in the confocal mode as well as in the near confocal condition that can allow one to program the coherence and spatial resolution of the microscope. This microscope has been used to study the change in the structure of chromatin during the development of sperm in Drosophila

  1. Mannheimia haemolytica serotype A1 exhibits differential pathogenicity in two related species, Ovis canadensis and Ovis aries.

    Science.gov (United States)

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Herndon, Caroline N; Lawrence, Paulraj K; Frances Cassirer, E; Potter, Kathleen A; Foreyt, William J; Clinkenbeard, Kenneth D; Srikumaran, Subramaniam

    2009-02-02

    Mannheimia haemolytica causes pneumonia in both bighorn sheep (BHS, Ovis canadensis) and domestic sheep (DS, Ovis aries). Under experimental conditions, co-pasturing of BHS and DS results in fatal pneumonia in BHS. It is conceivable that certain serotypes of M. haemolytica carried by DS are non-pathogenic to them, but lethal for BHS. M. haemolytica serotypes A1 and A2 are carried by DS in the nasopharynx. However, it is the serotype A2 that predominantly causes pneumonia in DS. The objectives of this study were to determine whether serotype A1 exhibits differential pathogenicity to BHS and DS, and to determine whether leukotoxin (Lkt) secreted by this organism is its primary virulence factor. Three groups each of BHS and DS were intra-tracheally administered either 1 x 10(9)cfu of serotype A1 wild-type (lktA-Wt group), Lkt-deletion mutant of serotype A1-(lktA-Mt group), or saline (control group), respectively. In the lktA-Wt groups, all four BHS died within 48h while none of the DS died during the 2-week study period. In the lktA-Mt groups, none of the BHS or DS died. In the control groups, one DS died due to an unrelated cause. Necropsy and histopathological findings revealed that death of BHS in the lktA-Wt group was due to bilateral, fibrinohemorrhagic pneumonia. Although the A1-Mt-inoculated BHS were clinically normal, on necropsy, lungs of two BHS showed varying degrees of mild chronic pneumonia. These results indicate that M. haemolytica serotype A1 is non-pathogenic to DS, but highly lethal to BHS, and that Lkt is the primary virulence factor of M. haemolytica.

  2. Mutations at the mei-41, mus(1)101, mus(1)103, mus(2)205 and mus(3)310 loci of Drosophila exhibit differential UDS responses with different DNA-damaging agents

    International Nuclear Information System (INIS)

    Dusenbery, R.L.

    1987-01-01

    5 mutagen-sensitive mutants of Drosophila melanogaster, reported to perform normal or only slightly reduced excision repair of UV damage, were examined by an unscheduled DNA synthesis (UDS) assay. 2 mutants, classified as completely or partially proficient for both excision and postreplication repair of UV damage, mus(1)103 and mus(2)205, were found to give positive UDS responses only for UV damage. These mutants exhibit no measurable UDS activity following DNA damage by several different alkylating agents and X-rays. 3 mutants, classified as having no defect in excision repair, but measurable defects in postreplication repair of UV damage, exhibit 3 different response patterns. The mutant mei-41 exhibits a highly positive UDS response following damage by all agents, consistent with its prior classification as excision-repair-proficient, but postreplication-repair-deficient for UV damage. The mutant mus(1)101, however, exhibits a strong positive UDS response following only UV damage and appears to be blocked in the excision repair of damage produced by both alkylating agents and X-irradiation. Finally, mus(3)310 exhibits no UDS response to alkylation, X-ray or UV damage. This is not consistent with its previous classification. Results obtained w0272the qualitative in vitro UDS assay are entirely consistent with the results from two separate in vivo measures of excision repair deficiency followign DNA damage, larval hypersensitivity to killing and hypermutability in the sex-linked recessive lethal test. (Auth.)

  3. Simulation, optimal control and parametric sensitivity analysis of a molten carbonate fuel cell using a partial differential algebraic dynamic equation system; Simulation, Optimale Steuerung und Sensitivitaetsanalyse einer Schmelzkarbonat-Brennstoffzelle mithilfe eines partiellen differential-algebraischen dynamischen Gleichungssystems

    Energy Technology Data Exchange (ETDEWEB)

    Sternberg, K

    2007-02-08

    Molten carbonate fuel cells (MCFCs) allow an efficient and environmentally friendly energy production by converting the chemical energy contained in the fuel gas in virtue of electro-chemical reactions. In order to predict the effect of the electro-chemical reactions and to control the dynamical behavior of the fuel cell a mathematical model has to be found. The molten carbonate fuel cell (MCFC) can indeed be described by a highly complex,large scale, semi-linear system of partial differential algebraic equations. This system includes a reaction-diffusion-equation of parabolic type, several reaction-transport-equations of hyperbolic type, several ordinary differential equations and finally a system of integro-differential algebraic equations which describes the nonlinear non-standard boundary conditions for the entire partial differential algebraic equation system (PDAE-system). The existence of an analytical or the computability of a numerical solution for this high-dimensional PDAE-system depends on the kind of the differential equations and their special characteristics. Apart from theoretical investigations, the real process has to be controlled, more precisely optimally controlled. Hence, on the basis of the PDAE-system an optimal control problem is set up, whose analytical and numerical solvability is closely linked to the solvability of the PDAE-system. Moreover the solution of that optimal control problem is made more difficult by inaccuracies in the underlying database, which does not supply sufficiently accurate values for the model parameters. Therefore the optimal control problem must also be investigated with respect to small disturbances of model parameters. The aim of this work is to analyze the relevant dynamic behavior of MCFCs and to develop concepts for their optimal process control. Therefore this work is concerned with the simulation, the optimal control and the sensitivity analysis of a mathematical model for MCDCs, which can be characterized

  4. Exhibition

    CERN Document Server

    Staff Association

    2017-01-01

    A Look of Hope Islam Mahmoud Sweity From 19 to 30 June 2017 CERN Meyrin, Main Building Islam Mahmoud Sweity Islam Mahmoud Sweity was born in 1997 at Beit Awwa, Palestine. She is currently following a course to get an Art diploma of Painting at the college of Fine Arts at An-Najah National University under the supervision of Esmat Al As'aad. Her portraits, landscapes and still life paintings are full of life and shining colours. Charged of emotional empathy they catch the attention of the viewer and are reminding us that life is beautiful and worth living in spite of all difficulties we have to go through. She participated in many exhibitions and has exposed her drawings in 2015 at CERN and in France in the framework of the exhibition "The Origin“, and in 2017 in the Former Yugoslav Republic of Macedonia, Palestina and Jordan. In this exhibition the oil paintings made in the past year will be presented. For more information : staff.association@cern.ch | T&eacu...

  5. SigEMD: A powerful method for differential gene expression analysis in single-cell RNA sequencing data.

    Science.gov (United States)

    Wang, Tianyu; Nabavi, Sheida

    2018-04-24

    Differential gene expression analysis is one of the significant efforts in single cell RNA sequencing (scRNAseq) analysis to discover the specific changes in expression levels of individual cell types. Since scRNAseq exhibits multimodality, large amounts of zero counts, and sparsity, it is different from the traditional bulk RNA sequencing (RNAseq) data. The new challenges of scRNAseq data promote the development of new methods for identifying differentially expressed (DE) genes. In this study, we proposed a new method, SigEMD, that combines a data imputation approach, a logistic regression model and a nonparametric method based on the Earth Mover's Distance, to precisely and efficiently identify DE genes in scRNAseq data. The regression model and data imputation are used to reduce the impact of large amounts of zero counts, and the nonparametric method is used to improve the sensitivity of detecting DE genes from multimodal scRNAseq data. By additionally employing gene interaction network information to adjust the final states of DE genes, we further reduce the false positives of calling DE genes. We used simulated datasets and real datasets to evaluate the detection accuracy of the proposed method and to compare its performance with those of other differential expression analysis methods. Results indicate that the proposed method has an overall powerful performance in terms of precision in detection, sensitivity, and specificity. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. ALVIN, Diffusion and Integral Data Comparison and Sensitivity Analysis

    International Nuclear Information System (INIS)

    Harris, D.R.; Reupke, W.A.; Wilson, W.B.

    1982-01-01

    1 - Description of problem or function: ALVIN analyzes the consistency of a set of differential and integral nuclear data, adjusts the differential nuclear data to improve agreement with integral observations, and identifies inconsistent data. ALVIN also computes required sensitivities and related quantities such as sensitivity profiles. 2 - Method of solution: Linear perturbation theory is used for the sensitivity calculations. Data consistency and adjustment computations use least squares techniques. 3 - Restrictions on the complexity of the problem: The DAFT2 consistency and adjustment subroutine treats fully or partially correlated differential and integral parameters, but only as many as the order of the largest matrix that can be inverted. The DAFT3 consistency and adjustment subroutine treats arbitrarily large differential data sets, but only if they are uncorrelated with the integral data. Due to the current dimensions of some arrays, maxima of 75 spatial mesh points, 41 groups, and 6. order Legendre polynomials are allowed. This can be changed by increasing the dimensions of the LCM arrays and the arrays in the labeled COMMON block S1 and blank COMMON

  7. Exhibiting Epistemic Objects

    DEFF Research Database (Denmark)

    Tybjerg, Karin

    2017-01-01

    of exhibiting epistemic objects that utilize their knowledge-generating potential and allow them to continue to stimulate curiosity and generate knowledge in the exhibition. The epistemic potential of the objects can then be made to work together with the function of the exhibition as a knowledge-generating set...

  8. Mouse Embryonic Fibroblasts (MEF) Exhibit a Similar but not Identical Phenotype to Bone Marrow Stromal Stem Cells (BMSC)

    DEFF Research Database (Denmark)

    Saeed, Hamid; Taipaleenmäki, Hanna; Aldahmash, Abdullah M

    2012-01-01

    Mouse embryonic fibroblasts have been utilized as a surrogate stem cell model for the postnatal bone marrow-derived stromal stem cells (BMSC) to study mesoderm-type cell differentiation e.g. osteoblasts, adipocytes and chondrocytes. However, no formal characterization of MEF phenotype has been...... by real-time PCR analysis. Compared to BMSC, MEF exhibited a more enhanced differentiation into adipocyte and chondrocyte lineages. Interestingly, both MEF and BMSC formed the same amount of heterotopic bone and bone marrow elements upon in vivo subcutaneous implantation with hydroxyapatite...... and differentiation to osteoblasts, adipocytes and chondrocytes....

  9. First order sensitivity analysis of flexible multibody systems using absolute nodal coordinate formulation

    International Nuclear Information System (INIS)

    Pi Ting; Zhang Yunqing; Chen Liping

    2012-01-01

    Design sensitivity analysis of flexible multibody systems is important in optimizing the performance of mechanical systems. The choice of coordinates to describe the motion of multibody systems has a great influence on the efficiency and accuracy of both the dynamic and sensitivity analysis. In the flexible multibody system dynamics, both the floating frame of reference formulation (FFRF) and absolute nodal coordinate formulation (ANCF) are frequently utilized to describe flexibility, however, only the former has been used in design sensitivity analysis. In this article, ANCF, which has been recently developed and focuses on modeling of beams and plates in large deformation problems, is extended into design sensitivity analysis of flexible multibody systems. The Motion equations of a constrained flexible multibody system are expressed as a set of index-3 differential algebraic equations (DAEs), in which the element elastic forces are defined using nonlinear strain-displacement relations. Both the direct differentiation method and adjoint variable method are performed to do sensitivity analysis and the related dynamic and sensitivity equations are integrated with HHT-I3 algorithm. In this paper, a new method to deduce system sensitivity equations is proposed. With this approach, the system sensitivity equations are constructed by assembling the element sensitivity equations with the help of invariant matrices, which results in the advantage that the complex symbolic differentiation of the dynamic equations is avoided when the flexible multibody system model is changed. Besides that, the dynamic and sensitivity equations formed with the proposed method can be efficiently integrated using HHT-I3 method, which makes the efficiency of the direct differentiation method comparable to that of the adjoint variable method when the number of design variables is not extremely large. All these improvements greatly enhance the application value of the direct differentiation

  10. Risk-sensitivity in Bayesian sensorimotor integration.

    Directory of Open Access Journals (Sweden)

    Jordi Grau-Moya

    Full Text Available Information processing in the nervous system during sensorimotor tasks with inherent uncertainty has been shown to be consistent with Bayesian integration. Bayes optimal decision-makers are, however, risk-neutral in the sense that they weigh all possibilities based on prior expectation and sensory evidence when they choose the action with highest expected value. In contrast, risk-sensitive decision-makers are sensitive to model uncertainty and bias their decision-making processes when they do inference over unobserved variables. In particular, they allow deviations from their probabilistic model in cases where this model makes imprecise predictions. Here we test for risk-sensitivity in a sensorimotor integration task where subjects exhibit Bayesian information integration when they infer the position of a target from noisy sensory feedback. When introducing a cost associated with subjects' response, we found that subjects exhibited a characteristic bias towards low cost responses when their uncertainty was high. This result is in accordance with risk-sensitive decision-making processes that allow for deviations from Bayes optimal decision-making in the face of uncertainty. Our results suggest that both Bayesian integration and risk-sensitivity are important factors to understand sensorimotor integration in a quantitative fashion.

  11. Diclofenac and triamcinolone acetonide impair tenocytic differentiation and promote adipocytic differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Fredriksson, Maritha; Li, Yan; Stålman, Anders; Haldosén, Lars-Arne; Felländer-Tsai, Li

    2013-09-02

    Tendinopathies are often empirically treated with oral/topical nonsteroidal anti-inflammatory medications and corticosteroid injections despite their unclear effects on tendon regeneration. Recent studies indicate that tendon progenitors exhibit stem cell-like properties, i.e., differentiation to osteoblasts, adipocytes, and chondrocytes, in addition to tenocytes. Our present study aims at understanding the effects of triamcinolone acetonide and diclofenac on tenocytic differentiation of mesenchymal stem cells. The murine fibroblast C3H10T1/2 cell line was induced to tenocytic differentiation by growth differentiation factor-7. Cell proliferation and differentiation with the exposure of different concentrations of triamcinolone acetonide and diclofenac were measured by WST-1 assay and real-time polymerase chain reaction analysis, respectively. Cell proliferation was decreased in a concentration-dependent manner when exposed to triamcinolone acetonide and diclofenac. In addition to tenocytic differentiation, adipocyte formation was observed, both at gene expression and microscopic level, when the cells were exposed to triamcinolone acetonide or high concentrations of diclofenac. Our results indicate that triamcinolone acetonide and diclofenac might alter mesenchymal stem cell differentiation in a nonfavorable way regarding tendon regeneration; therefore, these medications should be used with more caution clinically.

  12. Differential sensitivity of regulatory and effector T cells to cell death: a prerequisite for transplant tolerance

    Directory of Open Access Journals (Sweden)

    Sylvaine eYou

    2015-05-01

    Full Text Available Despite significant progress achieved in transplantation, immunosuppressive therapies currently used to prevent graft rejection are still endowed with severe side effects impairing their efficiency over the long term. Thus, the development of graft-specific, non toxic innovative therapeutic strategies has become a major challenge, the goal being to selectively target alloreactive effector T cells while sparing CD4+Foxp3+ regulatory T cells (Tregs to promote operational tolerance. Various approaches, notably the one based on monoclonal antibodies or fusion proteins directed against the TCR/CD3 complex, TCR coreceptors, or costimulatory molecules, have been proposed to reduce the alloreactive T cell pool which is an essential prerequisite to create a therapeutic window allowing Tregs to induce and maintain allograft tolerance. In this minireview, we focus on the differential sensitivity of Tregs and effector T cells to the depleting and inhibitory effect of these immunotherapies, with a particular emphasis on CD3-specific antibodies that beyond their immunosuppressive effect, also express potent tolerogenic capacities.

  13. Highly sensitive quantitative PCR for the detection and differentiation of Pseudogymnoascus destructans and other Pseudogymnoascus species.

    Science.gov (United States)

    Shuey, Megan M; Drees, Kevin P; Lindner, Daniel L; Keim, Paul; Foster, Jeffrey T

    2014-03-01

    White-nose syndrome is a fungal disease that has decimated bat populations across eastern North America. Identification of the etiologic agent, Pseudogymnoascus destructans (formerly Geomyces destructans), in environmental samples is essential to proposed management plans. A major challenge is the presence of closely related species, which are ubiquitous in many soils and cave sediments and often present in high abundance. We present a dual-probe real-time quantitative PCR assay capable of detecting and differentiating P. destructans from closely related fungi in environmental samples from North America. The assay, based on a single nucleotide polymorphism (SNP) specific to P. destructans, is capable of rapid low-level detection from various sampling media, including sediment, fecal samples, wing biopsy specimens, and skin swabs. This method is a highly sensitive, high-throughput method for identifying P. destructans, other Pseudogymnoascus spp., and Geomyces spp. in the environment, providing a fundamental component of research and risk assessment for addressing this disease, as well as other ecological and mycological work on related fungi.

  14. Shot Noise in Negative-Differential-Conductance Devices

    National Research Council Canada - National Science Library

    Song, W

    2003-01-01

    The authors have compared the shot-noise properties at T = 4.2 K of a double-barrier resonant-tunneling diode and a superlattice tunnel diode, both of which exhibit negative differential-conductance (NDC...

  15. Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis.

    Science.gov (United States)

    Yüksel, Melih; Power, Jeffrey J; Ribbe, Jan; Volkmann, Thorsten; Maier, Berenike

    2016-01-01

    In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off.

  16. Improved Sensitivity Relations in State Constrained Optimal Control

    International Nuclear Information System (INIS)

    Bettiol, Piernicola; Frankowska, Hélène; Vinter, Richard B.

    2015-01-01

    Sensitivity relations in optimal control provide an interpretation of the costate trajectory and the Hamiltonian, evaluated along an optimal trajectory, in terms of gradients of the value function. While sensitivity relations are a straightforward consequence of standard transversality conditions for state constraint free optimal control problems formulated in terms of control-dependent differential equations with smooth data, their verification for problems with either pathwise state constraints, nonsmooth data, or for problems where the dynamic constraint takes the form of a differential inclusion, requires careful analysis. In this paper we establish validity of both ‘full’ and ‘partial’ sensitivity relations for an adjoint state of the maximum principle, for optimal control problems with pathwise state constraints, where the underlying control system is described by a differential inclusion. The partial sensitivity relation interprets the costate in terms of partial Clarke subgradients of the value function with respect to the state variable, while the full sensitivity relation interprets the couple, comprising the costate and Hamiltonian, as the Clarke subgradient of the value function with respect to both time and state variables. These relations are distinct because, for nonsmooth data, the partial Clarke subdifferential does not coincide with the projection of the (full) Clarke subdifferential on the relevant coordinate space. We show for the first time (even for problems without state constraints) that a costate trajectory can be chosen to satisfy the partial and full sensitivity relations simultaneously. The partial sensitivity relation in this paper is new for state constraint problems, while the full sensitivity relation improves on earlier results in the literature (for optimal control problems formulated in terms of Lipschitz continuous multifunctions), because a less restrictive inward pointing hypothesis is invoked in the proof, and because

  17. Cytotoxicity of Vitex agnus-castus fruit extract and its major component, casticin, correlates with differentiation status in leukemia cell lines.

    Science.gov (United States)

    Kikuchi, Hidetomo; Yuan, Bo; Nishimura, Yoshio; Imai, Masahiko; Furutani, Ryota; Kamoi, Saki; Seno, Misako; Fukushima, Shin; Hazama, Shingo; Hirobe, Chieko; Ohyama, Kunio; Hu, Xiao-Mei; Takagi, Norio; Hirano, Toshihiko; Toyoda, Hiroo

    2013-12-01

    We have demonstrated that an extract from the ripe fruit of Vitex agnus-castus (Vitex) exhibits cytotoxic activities against various types of solid tumor cells, whereas its effects on leukemia cells has not been evaluated to date. In this study, the effects of Vitex and its major component, casticin, on leukemia cell lines, HL-60 and U-937, were investigated by focusing on proliferation, induction of apoptosis and differentiation. Identification and quantitation by NMR spectroscopy showed that casticin accounted for approximate 1% weight of Vitex. Dose-dependent cytotoxicity of Vitex and casticin was observed in both cell lines, and HL-60 cells were more sensitive to the cytotoxicity of Vitex/casticin compared to U-937 cells. Furthermore, compared to unstimulated HL-60 cells, phorbol 12-myristate 13-acetate (PMA)- and 1,25-dihydroxyvitamin D₃ (VD₃)-differentiated HL-60 cells acquired resistance to Vitex/casticin based on the results from cell viability and apoptosis induction analysis. Since the HL-60 cell line is more immature than the U-937 cell line, these results suggested that the levels of cytotoxicity of Vitex/casticin were largely attributed to the degree of differentiation of leukemia cells; that is, cell lines with less differentiated phenotype were more susceptible than the differentiated ones. RT-PCR analysis demonstrated that PMA upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) in HL-60 cells, and that anti-ICAM-1 monoclonal antibody not only abrogated PMA-induced aggregation and adhesion of the cells but also restored its sensitivity to Vitex. These results suggested that ICAM-1 plays a crucial role in the acquired resistance in PMA-differentiated HL-60 cells by contributing to cell adhesion. These findings provide fundamental insights into the clinical application of Vitex/casticin for hematopoietic malignancy.

  18. Celiac disease or non-celiac gluten sensitivity? An approach to clinical differential diagnosis.

    Science.gov (United States)

    Kabbani, Toufic A; Vanga, Rohini R; Leffler, Daniel A; Villafuerte-Galvez, Javier; Pallav, Kumar; Hansen, Joshua; Mukherjee, Rupa; Dennis, Melinda; Kelly, Ciaran P

    2014-05-01

    Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is important for appropriate management but is often challenging. We retrospectively reviewed records from 238 patients who presented for the evaluation of symptoms responsive to gluten restriction without prior diagnosis or exclusion of CD. Demographics, presenting symptoms, serologic, genetic, and histologic data, nutrient deficiencies, personal history of autoimmune diseases, and family history of CD were recorded. NCGS was defined as symptoms responsive to a gluten-free diet (GFD) in the setting of negative celiac serology and duodenal biopsies while on a gluten-containing diet or negative human leukocyte antigen (HLA) DQ2/DQ8 testing. Of the 238 study subjects, 101 had CD, 125 had NCGS, 9 had non-celiac enteropathy, and 3 had indeterminate diagnosis. CD subjects presented with symptoms of malabsorption 67.3% of the time compared with 24.8% of the NCGS subjects (Pdiseases (P=0.002), or nutrient deficiencies (P2× upper limit of normal IgA trans-glutaminase antibody (tTG) or IgA/IgG deaminated gliadan peptide antibody (DGP) with clinical response to GFD was 130 (confidence interval (CI): 18.5-918.3). The positive likelihood ratio of the combination of gluten-responsive symptoms and negative IgA tTG or IgA/IgG DGP on a regular diet for NCGS was 9.6 (CI: 5.5-16.9). When individuals with negative IgA tTG or IgA/IgG DGP also lacked symptoms of malabsorption (weight loss, diarrhea, and nutrient deficiencies) and CD risk factors (personal history of autoimmune diseases and family history of CD), the positive likelihood ratio for NCGS increased to 80.9. On the basis of our findings, we have developed a diagnostic algorithm to differentiate CD from NCGS. Subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) on a regular diet are unlikely to have CD. Those with negative serology who also lack clinical evidence of malabsorption and CD risk factors are highly likely to have

  19. Council Chamber exhibition

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    To complete the revamp of CERN’s Council Chamber, a new exhibition is being installed just in time for the June Council meetings.   Panels will showcase highlights of CERN’s history, using some of the content prepared for the exhibitions marking 50 years of the PS, which were displayed in the main building last November. The previous photo exhibition in the Council Chamber stopped at the 1970s. To avoid the new panels becoming quickly out of date, photos are grouped together around specific infrastructures, rather than following a classic time-line. “We have put the focus on the accelerators – the world-class facilities that CERN has been offering researchers over the years, from the well-known large colliders to the lesser-known smaller facilities,” says Emma Sanders, who worked on the content. The new exhibition will be featured in a future issue of the Bulletin with photos and an interview with Fabienne Marcastel, designer of the exhibit...

  20. Position sensitive x-ray detector

    International Nuclear Information System (INIS)

    Macchione, E.L.A.

    1990-01-01

    A multi ware position sensitive gas counter for X-ray detection was developed in our laboratory, making use of commercial delay-lines for position sensing. Six delay-line chips (50 ns delay each, 40 Mhz cut-off frequency) cover a total sensitive length of 150 mm leading to a delay-risetime ratio that allows for a high-resolution position detection. Tests using the 5,9 keV X-ray line from a 55 Fe source and integral linearity better than 0,1% and a maximal differential linearity of ±4,0% were obtained operating the detector with an Ar-C H 4 (90%-10%) gas mixture at 700 torr. Similar tests were performed, using the 8,04 keV line from a Cu x-ray tube. A total resolution of 330 μm, and the same integral and differential linearities were obtained. (author)

  1. Differential Effect of Plant Lipids on Membrane Organization

    Science.gov (United States)

    Grosjean, Kevin; Mongrand, Sébastien; Beney, Laurent; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

    2015-01-01

    The high diversity of the plant lipid mixture raises the question of their respective involvement in the definition of membrane organization. This is particularly the case for plant plasma membrane, which is enriched in specific lipids, such as free and conjugated forms of phytosterols and typical phytosphingolipids, such as glycosylinositolphosphoceramides. This question was here addressed extensively by characterizing the order level of membrane from vesicles prepared using various plant lipid mixtures and labeled with an environment-sensitive probe. Fluorescence spectroscopy experiments showed that among major phytosterols, campesterol exhibits a stronger ability than β-sitosterol and stigmasterol to order model membranes. Multispectral confocal microscopy, allowing spatial analysis of membrane organization, demonstrated accordingly the strong ability of campesterol to promote ordered domain formation and to organize their spatial distribution at the membrane surface. Conjugated sterol forms, alone and in synergy with free sterols, exhibit a striking ability to order membrane. Plant sphingolipids, particularly glycosylinositolphosphoceramides, enhanced the sterol-induced ordering effect, emphasizing the formation and increasing the size of sterol-dependent ordered domains. Altogether, our results support a differential involvement of free and conjugated phytosterols in the formation of ordered domains and suggest that the diversity of plant lipids, allowing various local combinations of lipid species, could be a major contributor to membrane organization in particular through the formation of sphingolipid-sterol interacting domains. PMID:25575593

  2. GSK-3 Inhibition Sensitizes Acute Myeloid Leukemia Cells to 1,25D-Mediated Differentiation

    Science.gov (United States)

    Gupta, Kalpana; Stefan, Tammy; Ignatz-Hoover, James; Moreton, Stephen; Parizher, Gary; Saunthararajah, Yogen; Wald, David N.

    2017-01-01

    1,25-dihydroxyvitamin D3 (1,25D), the biologically active form of vitamin D, is widely considered a promising therapy for acute myeloid leukemia (AML) based on its ability to drive differentiation of leukemic cells. However, clinical trials have been disappointing in part to dose-limiting hypercalcemia. Here we show how inhibiting glycogen synthase kinase 3 (GSK3) can improve the differentiation response of AML cells to 1,25D-mediated differentiation. GSK3 inhibition in AML cells enhanced the differentiating effects of low concentrations of 1,25D. In addition, GSK3 inhibition augmented the ability of 1,25D to induce irreversible growth inhibition and slow the progression of AML in mouse models. Mechanistic studies revealed that GSK3 inhibition led to the hyperphosphorylation of the vitamin D receptor (VDR), enabling an interaction between VDR and the coactivator, SRC-3 (NCOA3), thereby increasing transcriptional activity. We also found that activation of JNK-mediated pathways in response to GSK3 inhibition contributed to the potentiation of 1,25D-induced differentiation. Taken together, our findings offer a preclinical rationale to explore the repositioning of GSK3 inhibitors to enhance differentiation-based therapy for AML treatment. PMID:26964622

  3. Orbital benign and malignant lymphoproliferative disorders: Differentiation using semi-quantitative and quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging

    International Nuclear Information System (INIS)

    Hu, Hao; Xu, Xiao-Quan; Liu, Hu; Hong, Xun-Ning; Shi, Hai-Bin; Wu, Fei-Yun

    2017-01-01

    Objectives: To assess the value of dynamic contrast-enhanced MR imaging (DCE-MRI) in differentiating benign from malignant orbital lymphoproliferative disorders (OLPDs). Methods: Thirty-nine patients with orbital lymphoproliferative disorders (21 malignant and 18 benign) underwent DCE-MRI scan for pre-treatment evaluation from March 2013 to December 2015. Both semi-quantitative (TTP, AUC, Slope max ) and quantitative (K trans , k ep , v e ) parameters were calculated, and compared between two groups. Receiver operating characteristic (ROC) curve analyses were used to determine the diagnostic value of each significant parameter. Results: Malignant OLPDs showed significantly higher k ep , lower v e , and lower AUC than benign OLPDs, while no significant differences were found on K trans , TTP and Slope max . ROC analyses indicated that v e exhibited the best diagnostic performance in predicting malignant OLPDs (cutoff value, 0.211; area under the curve, 0.896; sensitivity, 76.2%; specificity, 94.9%), followed by k ep (cutoff value, 0.853; area under the curve, 0.839; sensitivity, 85.7%; specificity, 89.9%). Conclusion: DCE-MRI and specially its derived quantitative parameters of k ep and v e are promising metrics for differentiating malignant from benign OLPDs.

  4. Oxidative stress status, antioxidant metabolism and polypeptide patterns in Juncus maritimus shoots exhibiting differential mercury burdens in Ria de Aveiro coastal lagoon (Portugal).

    Science.gov (United States)

    Anjum, Naser A; Duarte, Armando C; Pereira, Eduarda; Ahmad, Iqbal

    2014-05-01

    This study assessed the oxidative stress status, antioxidant metabolism and polypeptide patterns in salt marsh macrophyte Juncus maritimus shoots exhibiting differential mercury burdens in Ria de Aveiro coastal lagoon at reference and the sites with highest, moderate and the lowest mercury contamination. In order to achieve these goals, shoot-mercury burden and the responses of representative oxidative stress indices, and the components of both non-glutathione- and glutathione-based H2O2-metabolizing systems were analyzed and cross-talked with shoot-polypeptide patterns. Compared to the reference site, significant elevations in J. maritimus shoot mercury and the oxidative stress indices such as H2O2, lipid peroxidation, electrolyte leakage and reactive carbonyls were maximum at the site with highest followed by moderate and the lowest mercury contamination. Significantly elevated activity of non-glutathione-based H2O2-metabolizing enzymes such as ascorbate peroxidase and catalase accompanied the studied damage-endpoint responses, whereas the activity of glutathione-based H2O2-scavenging enzymes glutathione peroxidase and glutathione sulfo-transferase was inhibited. Concomitantly, significantly enhanced glutathione reductase activity and the contents of both reduced and oxidized glutathione were perceptible in high mercury-exhibiting shoots. It is inferred that high mercury-accrued elevations in oxidative stress indices were obvious, where non-glutathione-based H2O2-decomposing enzyme system was dominant over the glutathione-based H2O2-scavenging enzyme system. In particular, the glutathione-based H2O2-scavenging system failed to coordinate with elevated glutathione reductase which in turn resulted into increased pool of oxidized glutathione and the ratio of oxidized glutathione-to-reduced glutathione. The substantiation of the studied oxidative stress indices and antioxidant metabolism with approximately 53-kDa polypeptide warrants further studies.

  5. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's 50th anniversary celebrations. Fifty candles for CERN, an international laboratory renowned for fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting exhibitions of plastic arts and performances entitled: Accelerated Particles. Several works will be exhibited and performed in two 'salons'. Salon des matières: An exhibition of plastic arts From Tues 12 October to Wed 3 November 2004 Tuesdays to Fridays: 16:00 to 19:00 Saturdays: 14:00 to 18:00 Exhibition open late on performance nights, entrance free Salon des particules: Musical and visual performances Tues 12 and Mon 25 October from 20:00 to 23:00 Preview evening for both events: Tues 12 October from 18:...

  6. Modulation of DNA base excision repair during neuronal differentiation

    DEFF Research Database (Denmark)

    Sykora, Peter; Yang, Jenq-Lin; Ferrarelli, Leslie K

    2013-01-01

    DNA damage susceptibility and base excision DNA repair (BER) capacity in undifferentiated and differentiated human neural cells. The results show that undifferentiated human SH-SY5Y neuroblastoma cells are less sensitive to oxidative damage than their differentiated counterparts, in part because...

  7. A measure-valued differentiation approach to sensitivities of quantiles

    NARCIS (Netherlands)

    Heidergott, B.F.; Volk-Makarewicz, W.

    2016-01-01

    Quantiles play an important role in modelling quality of service in the service industry and in modelling risk in the financial industry. The recent discovery that efficient simulation-based estimators can be obtained for quantile sensitivities has led to an intensive search for sample-path

  8. Differentially Private Confidence Intervals for Empirical Risk Minimization

    OpenAIRE

    Wang, Yue; Kifer, Daniel; Lee, Jaewoo

    2018-01-01

    The process of data mining with differential privacy produces results that are affected by two types of noise: sampling noise due to data collection and privacy noise that is designed to prevent the reconstruction of sensitive information. In this paper, we consider the problem of designing confidence intervals for the parameters of a variety of differentially private machine learning models. The algorithms can provide confidence intervals that satisfy differential privacy (as well as the mor...

  9. Differential neural representation of oral ethanol by central taste-sensitive neurons in ethanol-preferring and genetically heterogeneous rats.

    Science.gov (United States)

    Lemon, Christian H; Wilson, David M; Brasser, Susan M

    2011-12-01

    In randomly bred rats, orally applied ethanol stimulates neural substrates for appetitive sweet taste. To study associations between ethanol's oral sensory characteristics and genetically mediated ethanol preference, we made electrophysiological recordings of oral responses (spike density) by taste-sensitive nucleus tractus solitarii neurons in anesthetized selectively bred ethanol-preferring (P) rats and their genetically heterogeneous Wistar (W) control strain. Stimuli (25 total) included ethanol [3%, 5%, 10%, 15%, 25%, and 40% (vol/vol)], a sucrose series (0.01, 0.03, 0.1, 0.3, 0.5, and 1 M), and other sweet, salt, acidic, and bitter stimuli; 50 P and 39 W neurons were sampled. k-means clustering applied to the sucrose response series identified cells showing high (S(1)) or relatively low (S(0)) sensitivity to sucrose. A three-way factorial analysis revealed that activity to ethanol was influenced by a neuron's sensitivity to sucrose, ethanol concentration, and rat line (P = 0.01). Ethanol produced concentration-dependent responses in S(1) neurons that were larger than those in S(0) cells. Although responses to ethanol by S(1) cells did not differ between lines, neuronal firing rates to ethanol in S(0) cells increased across concentration only in P rats. Correlation and multivariate analyses revealed that ethanol evoked responses in W neurons that were strongly and selectively associated with activity to sweet stimuli, whereas responses to ethanol by P neurons were not easily associated with activity to representative sweet, sodium salt, acidic, or bitter stimuli. These findings show differential central neural representation of oral ethanol between genetically heterogeneous rats and P rats genetically selected to prefer alcohol.

  10. Line pressure effects on differential pressure measurements

    International Nuclear Information System (INIS)

    Neff, G.G.; Evans, R.P.

    1982-01-01

    The performance of differential pressure transducers in experimental pressurized water reactor (PWR) systems was evaluated. Transient differential pressure measurements made using a simple calibration proportionality relating differential pressure to output voltage could have large measurement uncertainties. A more sophisticated calibration equation was derived to incorporate the effects of zero shifts and sensitivity shifts as pressure in the pressure sensing line changes with time. A comparison made between the original calibration proportionality equation and the derived compensation equation indicates that potential measurement uncertainties can be reduced

  11. Sensitivity analysis in remote sensing

    CERN Document Server

    Ustinov, Eugene A

    2015-01-01

    This book contains a detailed presentation of general principles of sensitivity analysis as well as their applications to sample cases of remote sensing experiments. An emphasis is made on applications of adjoint problems, because they are more efficient in many practical cases, although their formulation may seem counterintuitive to a beginner. Special attention is paid to forward problems based on higher-order partial differential equations, where a novel matrix operator approach to formulation of corresponding adjoint problems is presented. Sensitivity analysis (SA) serves for quantitative models of physical objects the same purpose, as differential calculus does for functions. SA provides derivatives of model output parameters (observables) with respect to input parameters. In remote sensing SA provides computer-efficient means to compute the jacobians, matrices of partial derivatives of observables with respect to the geophysical parameters of interest. The jacobians are used to solve corresponding inver...

  12. Detection and differentiation of wild-type and vaccine strains of canine distemper virus by a duplex reverse transcription polymerase chain reaction.

    Science.gov (United States)

    Dong, X Y; Li, W H; Zhu, J L; Liu, W J; Zhao, M Q; Luo, Y W; Chen, J D

    2015-01-01

    Canine distemper virus (CDV) is the cause of canine distemper (CD) which is a severe and highly contagious disease in dogs. In the present study, a duplex reverse transcription polymerase chain reaction (RT-PCR) method was developed for the detection and differentiation of wild-type and vaccine strains of CDV. Four primers were designed to detect and discriminate the two viruses by generating 638- and 781-bp cDNA products, respectively. Furthermore, the duplex RT-PCR method was used to detect 67 field samples suspected of CD from Guangdong province in China. Results showed that, 33 samples were to be wild-type-like. The duplex RT-PCR method exhibited high specificity and sensitivity which could be used to effectively detect and differentiate wild-type and vaccine CDV, indicating its use for clinical detection and epidemiological surveillance.

  13. Britain exhibition at CERN

    CERN Multimedia

    Bertin; CERN PhotoLab

    1969-01-01

    The United Kingdom inaugurated the Industrial Exhibitions in 1968, and it wasn't till 1971 that other countries staged exhibitions at CERN. This photo was taken in 1969, at the second British exhibition, where 16 companies were present.

  14. Mesh refinement and numerical sensitivity analysis for parameter calibration of partial differential equations

    Science.gov (United States)

    Becker, Roland; Vexler, Boris

    2005-06-01

    We consider the calibration of parameters in physical models described by partial differential equations. This task is formulated as a constrained optimization problem with a cost functional of least squares type using information obtained from measurements. An important issue in the numerical solution of this type of problem is the control of the errors introduced, first, by discretization of the equations describing the physical model, and second, by measurement errors or other perturbations. Our strategy is as follows: we suppose that the user defines an interest functional I, which might depend on both the state variable and the parameters and which represents the goal of the computation. First, we propose an a posteriori error estimator which measures the error with respect to this functional. This error estimator is used in an adaptive algorithm to construct economic meshes by local mesh refinement. The proposed estimator requires the solution of an auxiliary linear equation. Second, we address the question of sensitivity. Applying similar techniques as before, we derive quantities which describe the influence of small changes in the measurements on the value of the interest functional. These numbers, which we call relative condition numbers, give additional information on the problem under consideration. They can be computed by means of the solution of the auxiliary problem determined before. Finally, we demonstrate our approach at hand of a parameter calibration problem for a model flow problem.

  15. Differentiation of human mesenchymal stem cell spheroids under microgravity conditions

    Directory of Open Access Journals (Sweden)

    Wolfgang H Cerwinka

    2012-01-01

    Full Text Available To develop and characterize a novel cell culture method for the generation of undifferentiated and differentiated human mesenchymal stem cell 3D structures, we utilized the RWV system with a gelatin-based scaffold. 3 × 106 cells generated homogeneous spheroids and maximum spheroid loading was accomplished after 3 days of culture. Spheroids cultured in undifferentiated spheroids of 3 and 10 days retained expression of CD44, without expression of differentiation markers. Spheroids cultured in adipogenic and osteogenic differentiation media exhibited oil red O staining and von Kossa staining, respectively. Further characterization of osteogenic lineage, showed that 10 day spheroids exhibited stronger calcification than any other experimental group corresponding with significant expression of vitamin D receptor, alkaline phosphatase, and ERp60 . In conclusion this study describes a novel RWV culture method that allowed efficacious engineering of undifferentiated human mesenchymal stem cell spheroids and rapid osteogenic differentiation. The use of gelatin scaffolds holds promise to design implantable stem cell tissue of various sizes and shapes for future regenerative treatment.

  16. Digital collections and exhibits

    CERN Document Server

    Denzer, Juan

    2015-01-01

    Today's libraries are taking advantage of cutting-edge technologies such as flat panel displays using touch, sound, and hands-free motions to design amazing exhibits using everything from simple computer hardware to advanced technologies such as the Microsoft Kinect. Libraries of all types are striving to add new interactive experiences for their patrons through exciting digital exhibits, both online and off. Digital Collections and Exhibits takes away the mystery of designing stunning digital exhibits to spotlight library trea

  17. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink.

    Science.gov (United States)

    Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

    2017-01-16

    Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. As expected, adult offspring fed the S diet post weaning became obese (body weight: Peffect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.

  18. Sensitivity of tissue differentiation and bone healing predictions to tissue properties

    NARCIS (Netherlands)

    Isaksson, H.E.; Donkelaar, van C.C.; Ito, K.

    2009-01-01

    Computational models are employed as tools to investigate possible mechano-regulation pathways for tissue differentiation and bone healing. However, current models do not account for the uncertainty in input parameters, and often include assumptions about parameter values that are not yet

  19. Effects of naltrexone on pain sensitivity and mood in fibromyalgia: no evidence for endogenous opioid pathophysiology.

    Directory of Open Access Journals (Sweden)

    Jarred W Younger

    Full Text Available The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.

  20. D-π-A-A-π-D prototype 2,2'-bipyridine dyads exhibiting large structure and environment-sensitive fluorescence: synthesis, photophysics, and computation.

    Science.gov (United States)

    Sarma, Monima; Chatterjee, Tanmay; Ghanta, Susanta; Das, Samar K

    2012-01-06

    A series of 4,4'-π-conjugated-2,2'-bipyridine chromophores (MS 1-8) were synthesized, and their photophysical and thermal properties were investigated. The title "push-pull' chromophores", except MS 1, were integrated with both alkoxy and alkylamino donor functionalities that differ in their donation capabilities. The oligophenylenevinylene (OPV) chromophores MS 4-8 are associated with a π-extended backbone in which the position and the number of alkoxy donors were systematically varied. All of the studied systems possess a D-π-A-A-π-D dyad archetype in which the A-A is the central 2,2'-bipyridine acceptor core that is electronically attached with the donor termini through π-linkers. The fluorescence quantum yields of the synthesized chromophores are found to be sensitive to the molecular archetype and the solvent medium. Out of the eight fluorescent compounds reported in this article, the compound MS 5 exhibits fluorescence in the solid state also. The modulating effect of the nature, position, and number of donor functionalities on the optical properties of these classes of compounds has further been comprehended on the basis of DFT and TD-DFT computation in a solvent reaction field.

  1. Genetic variation for lettuce seed thermoinhibition is associated with temperature-sensitive expression of abscisic Acid, gibberellin, and ethylene biosynthesis, metabolism, and response genes.

    Science.gov (United States)

    Argyris, Jason; Dahal, Peetambar; Hayashi, Eiji; Still, David W; Bradford, Kent J

    2008-10-01

    Lettuce (Lactuca sativa 'Salinas') seeds fail to germinate when imbibed at temperatures above 25 degrees C to 30 degrees C (termed thermoinhibition). However, seeds of an accession of Lactuca serriola (UC96US23) do not exhibit thermoinhibition up to 37 degrees C in the light. Comparative genetics, physiology, and gene expression were analyzed in these genotypes to determine the mechanisms governing the regulation of seed germination by temperature. Germination of the two genotypes was differentially sensitive to abscisic acid (ABA) and gibberellin (GA) at elevated temperatures. Quantitative trait loci associated with these phenotypes colocated with a major quantitative trait locus (Htg6.1) from UC96US23 conferring germination thermotolerance. ABA contents were elevated in Salinas seeds that exhibited thermoinhibition, consistent with the ability of fluridone (an ABA biosynthesis inhibitor) to improve germination at high temperatures. Expression of many genes involved in ABA, GA, and ethylene biosynthesis, metabolism, and response was differentially affected by high temperature and light in the two genotypes. In general, ABA-related genes were more highly expressed when germination was inhibited, and GA- and ethylene-related genes were more highly expressed when germination was permitted. In particular, LsNCED4, a gene encoding an enzyme in the ABA biosynthetic pathway, was up-regulated by high temperature only in Salinas seeds and also colocated with Htg6.1. The temperature sensitivity of expression of LsNCED4 may determine the upper temperature limit for lettuce seed germination and may indirectly influence other regulatory pathways via interconnected effects of increased ABA biosynthesis.

  2. ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy

    NARCIS (Netherlands)

    Wielenga, Mattheus C. B.; Colak, Selcuk; Heijmans, Jarom; van Lidth de Jeude, Jooske F.; Rodermond, Hans M.; Paton, James C.; Paton, Adrienne W.; Vermeulen, Louis; Medema, Jan Paul; van den Brink, Gijs R.

    2015-01-01

    Colon cancer stem cells (colon-CSCs) are more resistant to conventional chemotherapy than differentiated cancer cells. This subset of therapy refractory cells is therefore believed to play an important role in post-therapeutic tumor relapse. In order to improve the rate of sustained response to

  3. Discrimination? - Exhibition of posters

    OpenAIRE

    Jakimovska, Jana

    2017-01-01

    Participation in the exhibition with the students form the Art Academy. The exhibition consisted of 15 posters tackling the subjects of hate speech and discrimination. The exhibition happened thanks to the invitation of the Faculty of Law at UGD, and it was a part of a larger event of launching books on the aforementioned subjects.

  4. Role for early-differentiated natural killer cells in infectious mononucleosis.

    Science.gov (United States)

    Azzi, Tarik; Lünemann, Anna; Murer, Anita; Ueda, Seigo; Béziat, Vivien; Malmberg, Karl-Johan; Staubli, Georg; Gysin, Claudine; Berger, Christoph; Münz, Christian; Chijioke, Obinna; Nadal, David

    2014-10-16

    A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56(dim) NKG2A(+) immunoglobulin-like receptor(-) NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus. © 2014 by The American Society of Hematology.

  5. Differential effects of exogenous and endogenous attention on second-order texture contrast sensitivity

    Science.gov (United States)

    Barbot, Antoine; Landy, Michael S.; Carrasco, Marisa

    2012-01-01

    The visual system can use a rich variety of contours to segment visual scenes into distinct perceptually coherent regions. However, successfully segmenting an image is a computationally expensive process. Previously we have shown that exogenous attention—the more automatic, stimulus-driven component of spatial attention—helps extract contours by enhancing contrast sensitivity for second-order, texture-defined patterns at the attended location, while reducing sensitivity at unattended locations, relative to a neutral condition. Interestingly, the effects of exogenous attention depended on the second-order spatial frequency of the stimulus. At parafoveal locations, attention enhanced second-order contrast sensitivity to relatively high, but not to low second-order spatial frequencies. In the present study we investigated whether endogenous attention—the more voluntary, conceptually-driven component of spatial attention—affects second-order contrast sensitivity, and if so, whether its effects are similar to those of exogenous attention. To that end, we compared the effects of exogenous and endogenous attention on the sensitivity to second-order, orientation-defined, texture patterns of either high or low second-order spatial frequencies. The results show that, like exogenous attention, endogenous attention enhances second-order contrast sensitivity at the attended location and reduces it at unattended locations. However, whereas the effects of exogenous attention are a function of the second-order spatial frequency content, endogenous attention affected second-order contrast sensitivity independent of the second-order spatial frequency content. This finding supports the notion that both exogenous and endogenous attention can affect second-order contrast sensitivity, but that endogenous attention is more flexible, benefitting performance under different conditions. PMID:22895879

  6. Differential effects of exogenous and endogenous attention on second-order texture contrast sensitivity.

    Science.gov (United States)

    Barbot, Antoine; Landy, Michael S; Carrasco, Marisa

    2012-08-15

    The visual system can use a rich variety of contours to segment visual scenes into distinct perceptually coherent regions. However, successfully segmenting an image is a computationally expensive process. Previously we have shown that exogenous attention--the more automatic, stimulus-driven component of spatial attention--helps extract contours by enhancing contrast sensitivity for second-order, texture-defined patterns at the attended location, while reducing sensitivity at unattended locations, relative to a neutral condition. Interestingly, the effects of exogenous attention depended on the second-order spatial frequency of the stimulus. At parafoveal locations, attention enhanced second-order contrast sensitivity to relatively high, but not to low second-order spatial frequencies. In the present study we investigated whether endogenous attention-the more voluntary, conceptually-driven component of spatial attention--affects second-order contrast sensitivity, and if so, whether its effects are similar to those of exogenous attention. To that end, we compared the effects of exogenous and endogenous attention on the sensitivity to second-order, orientation-defined, texture patterns of either high or low second-order spatial frequencies. The results show that, like exogenous attention, endogenous attention enhances second-order contrast sensitivity at the attended location and reduces it at unattended locations. However, whereas the effects of exogenous attention are a function of the second-order spatial frequency content, endogenous attention affected second-order contrast sensitivity independent of the second-order spatial frequency content. This finding supports the notion that both exogenous and endogenous attention can affect second-order contrast sensitivity, but that endogenous attention is more flexible, benefitting performance under different conditions.

  7. Sensitivity analysis of reactive ecological dynamics.

    Science.gov (United States)

    Verdy, Ariane; Caswell, Hal

    2008-08-01

    Ecological systems with asymptotically stable equilibria may exhibit significant transient dynamics following perturbations. In some cases, these transient dynamics include the possibility of excursions away from the equilibrium before the eventual return; systems that exhibit such amplification of perturbations are called reactive. Reactivity is a common property of ecological systems, and the amplification can be large and long-lasting. The transient response of a reactive ecosystem depends on the parameters of the underlying model. To investigate this dependence, we develop sensitivity analyses for indices of transient dynamics (reactivity, the amplification envelope, and the optimal perturbation) in both continuous- and discrete-time models written in matrix form. The sensitivity calculations require expressions, some of them new, for the derivatives of equilibria, eigenvalues, singular values, and singular vectors, obtained using matrix calculus. Sensitivity analysis provides a quantitative framework for investigating the mechanisms leading to transient growth. We apply the methodology to a predator-prey model and a size-structured food web model. The results suggest predator-driven and prey-driven mechanisms for transient amplification resulting from multispecies interactions.

  8. Cercospora zeina from Maize in South Africa Exhibits High Genetic Diversity and Lack of Regional Population Differentiation.

    Science.gov (United States)

    Muller, Mischa F; Barnes, Irene; Kunene, Ncobile T; Crampton, Bridget G; Bluhm, Burton H; Phillips, Sonia M; Olivier, Nicholas A; Berger, Dave K

    2016-10-01

    South Africa is one of the leading maize-producing countries in sub-Saharan Africa. Since the 1980s, Cercospora zeina, a causal agent of gray leaf spot of maize, has become endemic in South Africa, and is responsible for substantial yield reductions. To assess genetic diversity and population structure of C. zeina in South Africa, 369 isolates were collected from commercial maize farms in three provinces (KwaZulu-Natal, Mpumalanga, and North West). These isolates were evaluated with 14 microsatellite markers and species-specific mating type markers that were designed from draft genome sequences of C. zeina isolates from Africa (CMW 25467) and the United States (USPA-4). Sixty alleles were identified across 14 loci, and gene diversity values within each province ranged from 0.18 to 0.35. High levels of gene flow were observed (Nm = 5.51), and in a few cases, identical multilocus haplotypes were found in different provinces. Overall, 242 unique multilocus haplotypes were identified with a low clonal fraction of 34%. No distinct population clusters were identified using STRUCTURE, principal coordinate analysis, or Weir's theta θ statistic. The lack of population differentiation was supported by analysis of molecular variance tests, which indicated that only 2% of the variation was attributed to variability between populations from each province. Mating type ratios of MAT1-1 and MAT1-2 idiomorphs from 335 isolates were not significantly different from a 1:1 ratio in all provinces, which provided evidence for sexual reproduction. The draft genome of C. zeina CMW 25467 exhibited a complete genomic copy of the MAT1-1 idiomorph as well as exonic fragments of MAT genes from both idiomorphs. The high level of gene diversity, shared haplotypes at different geographical locations within South Africa, and presence of both MAT idiomorphs at all sites indicates widespread dispersal of C. zeina between maize fields in the country as well as evidence for sexual recombination. The

  9. Diclofenac and triamcinolone acetonide impair tenocytic differentiation and promote adipocytic differentiation of mesenchymal stem cells

    OpenAIRE

    Fredriksson, Maritha; Li, Yan; St?lman, Anders; Haldos?n, Lars-Arne; Fell?nder-Tsai, Li

    2013-01-01

    Background Tendinopathies are often empirically treated with oral/topical nonsteroidal anti-inflammatory medications and corticosteroid injections despite their unclear effects on tendon regeneration. Recent studies indicate that tendon progenitors exhibit stem cell-like properties, i.e., differentiation to osteoblasts, adipocytes, and chondrocytes, in addition to tenocytes. Our present study aims at understanding the effects of triamcinolone acetonide and diclofenac on tenocytic differentiat...

  10. Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.

    Science.gov (United States)

    Rudolph, Christiane; Melau, Cecilie; Nielsen, John E; Vile Jensen, Kristina; Liu, Dekang; Pena-Diaz, Javier; Rajpert-De Meyts, Ewa; Rasmussen, Lene Juel; Jørgensen, Anne

    2017-08-01

    Testicular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. The expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2, were investigated during testis development and in the pathogenesis of TGCT, including germ cell neoplasia in situ (GCNIS). The TGCT-derived cell line NTera2 was differentiated using retinoic acid (10 μM, 6 days) after which MMR protein expression and activity, as well as cisplatin sensitivity, were investigated in both undifferentiated and differentiated cells. Finally, the expression of MSH2 was knocked down by siRNA in NTera2 cells after which the effect on cisplatin sensitivity was examined. MMR proteins were expressed in proliferating cells in the testes, while in malignant germ cells MMR protein expression was found to coincide with the expression of the pluripotency factor OCT4, with no or low expression in the more differentiated yolk sac tumours, choriocarcinomas and teratomas. In differentiated NTera2 cells we found a significantly (p cisplatin sensitivity, compared to undifferentiated NTera2 cells. Also, we found that partial knockdown of MSH2 expression in undifferentiated NTera2 cells resulted in a significantly (p cisplatin sensitivity. This study reports, for the first time, expression of the MMR system in fetal gonocytes, from which GCNIS cells are derived. Our findings in primary TGCT specimens and TGCT-derived cells suggest that a reduced sensitivity to cisplatin in differentiated TGCT components could result from a reduced expression of MMR proteins, in

  11. Assessing geomorphic sensitivity in relation to river capacity for adjustment

    Science.gov (United States)

    Reid, H. E.; Brierley, G. J.

    2015-12-01

    River sensitivity describes the nature and rate of channel adjustments. An approach to analysis of geomorphic river sensitivity outlined in this paper relates potential sensitivity based on the expected capacity of adjustment for a river type to the recent history of channel adjustment. This approach was trialled to assess low, moderate and high geomorphic sensitivity for four different types of river (10 reaches in total) along the Lower Tongariro River, North Island, New Zealand. Building upon the River Styles framework, river types were differentiated based upon valley setting (width and confinement), channel planform, geomorphic unit assemblages and bed material size. From this, the behavioural regime and potential for adjustment (type and extent) were determined. Historical maps and aerial photographs were geo-rectified and the channel planform digitised to assess channel adjustments for each reach from 1928 to 2007. Floodplain width controlled by terraces, exerted a strong influence upon reach scale sensitivity for the partly-confined, wandering, cobble-bed river. Although forced boundaries occur infrequently, the width of the active channel zone is constrained. An unconfined braided river reach directly downstream of the terrace-confined section was the most geomorphically sensitive reach. The channel in this reach adjusted recurrently to sediment inputs that were flushed through more confined, better connected upstream reaches. A meandering, sand-bed river in downstream reaches has exhibited negligible rates of channel migration. However, channel narrowing in this reach and the associated delta indicate that the system is approaching a threshold condition, beyond which channel avulsion is likely to occur. As this would trigger more rapid migration, this reach is considered to be more geomorphically sensitive than analysis of its low migration rate alone would indicate. This demonstrates how sensitivity is fashioned both by the behavioural regime of a reach

  12. Differential neuropsychological test sensitivity to left temporal lobe epilepsy.

    Science.gov (United States)

    Loring, David W; Strauss, Esther; Hermann, Bruce P; Barr, William B; Perrine, Kenneth; Trenerry, Max R; Chelune, Gordon; Westerveld, Michael; Lee, Gregory P; Meador, Kimford J; Bowden, Stephen C

    2008-05-01

    We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohen's d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohen's d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE.

  13. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's fiftieth anniversary celebrations. The fiftieth anniversary of a world famous organization like CERN, an international laboratory specializing in fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting two "salons" consisting of an exhibition of plastic arts and evenings of music and visual arts performances with the collective title of "Accelerated Particles". Several works will be exhibited and performed. Salon des matières: An exhibition of plastic arts Until Wednesday 3 November 2004. Tuesdays to Fridays: 4.00 p.m. to 7.00 p.m. Saturdays: 2.00 p.m. to 6.00 p.m. Doors open late on the evening of the performances. Salon des ...

  14. Exhibiting the Human/Exhibiting the Cyborg: “Who Am I?”

    Directory of Open Access Journals (Sweden)

    Sophia C. Vackimes

    2013-08-01

    Full Text Available The role of the museum in shaping our relationship to science and technology, particularly cyborgization, is illuminated by a close examination of the Who Am I permanent exhibition in the Wellcome Wing of the Science Museum of London. This innovative exhibition raises real questions both about the human-technology-science relationship but also about museography. In the context of the history and current practices of museums engaging contemporary technological developments the evidence suggest that even as the Who am I? exhibit did break somewhat from previous approaches, especially the didactic presentation of the socially useful, it has not changed the feld as a whole.

  15. Highly efficient and stable cyclometalated ruthenium(II) complexes as sensitizers for dye-sensitized solar cells

    International Nuclear Information System (INIS)

    Huang, Jian-Feng; Liu, Jun-Min; Su, Pei-Yang; Chen, Yi-Fan; Shen, Yong; Xiao, Li-Min; Kuang, Dai-Bin; Su, Cheng-Yong

    2015-01-01

    Highlights: • Four novel thiocyanate-free cyclometalated ruthenium sensitizer were conveniently synthesized. • The D-CF 3 -sensitized DSSCs show higher efficiency compared to N719 based cells. • The DSSCs based on D-CF 3 and D-bisCF 3 sensitizers exhibit excellent long-term stability. • The diverse cyclometalated Ru complexes can be developed as high-performance sensitizers for use in DSSC. - Abstract: Four novel thiocyanate-free cyclometallted Ru(II) complexes, D-bisCF 3 , D-CF 3 , D-OMe, and D-DPA, with two 4,4′-dicarboxylic acid-2,2′-bipyridine together with a functionalized phenylpyridine ancillary ligand, have been designed and synthesized. The effect of different substituents (R = bisCF 3 , CF 3 , OMe, and DPA) on the ancillary C^N ligand on the photophysical properties and photovoltaic performance is investigated. Under standard global AM 1.5 solar conditions, the device based on D-CF 3 sensitizer gives a higher conversion efficiency of 8.74% than those based on D-bisCF 3 , D-OMe, and D-DPA, which can be ascribed to its broad range of visible light absorption, appropriate localization of the frontier orbitals, weak hydrogen bonds between -CF 3 and -OH groups at the TiO 2 surface, moderate dye loading on TiO 2 , and high charge collection efficiency. Moreover, the D-bisCF 3 and D-CF 3 based DSSCs exhibit good stability under 100 mW cm −2 light soaking at 60 °C for 400 h

  16. A rank-based algorithm of differential expression analysis for small cell line data with statistical control.

    Science.gov (United States)

    Li, Xiangyu; Cai, Hao; Wang, Xianlong; Ao, Lu; Guo, You; He, Jun; Gu, Yunyan; Qi, Lishuang; Guan, Qingzhou; Lin, Xu; Guo, Zheng

    2017-10-13

    To detect differentially expressed genes (DEGs) in small-scale cell line experiments, usually with only two or three technical replicates for each state, the commonly used statistical methods such as significance analysis of microarrays (SAM), limma and RankProd (RP) lack statistical power, while the fold change method lacks any statistical control. In this study, we demonstrated that the within-sample relative expression orderings (REOs) of gene pairs were highly stable among technical replicates of a cell line but often widely disrupted after certain treatments such like gene knockdown, gene transfection and drug treatment. Based on this finding, we customized the RankComp algorithm, previously designed for individualized differential expression analysis through REO comparison, to identify DEGs with certain statistical control for small-scale cell line data. In both simulated and real data, the new algorithm, named CellComp, exhibited high precision with much higher sensitivity than the original RankComp, SAM, limma and RP methods. Therefore, CellComp provides an efficient tool for analyzing small-scale cell line data. © The Author 2017. Published by Oxford University Press.

  17. Relationship between RDX properties and sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Doherty, Ruth M. [Research, Development, Test and Evaluation Directorate, Naval Surface Warfare Center Indian Head Division, Indian Head, MD 20640-5102 (United States); Watt, Duncan S. [Novare, Level 6 80 Petrie Terrace, Brisbane 4000 (Australia)

    2008-02-15

    An interlaboratory comparison of seven lots of commercially available RDX was conducted to determine what properties of the nitramine particles can be used to assess whether the RDX has relatively high or relatively low sensitivity. The materials chosen for the study were selected to give a range of HMX content, manufacturing process and reported shock sensitivity. The results of two different shock sensitivity tests conducted on a PBX made with the RDX lots in the study showed that there are measurable differences in the shock sensitivity of the PBXs, but the impact sensitivity for all of the lots is essentially the same. Impact sensitivity is not a good predictor of shock sensitivity for these types of RDX. Although most RDX that exhibits RS has low HMX content, that characteristic alone is not sufficient to guarantee low sensitivity. A range of additional analytical chemistry tests were conducted on the material; two of these (HPLC and DSC) are discussed within. (Abstract Copyright [2008], Wiley Periodicals, Inc.)

  18. Application of an imaging system to a museum exhibition for developing interactive exhibitions

    Science.gov (United States)

    Miyata, Kimiyoshi; Inoue, Yuka; Takiguchi, Takahiro; Tsumura, Norimichi; Nakaguchi, Toshiya; Miyake, Yoichi

    2009-10-01

    In the National Museum of Japanese History, 215,759 artifacts are stored and used for research and exhibitions. In museums, due to the limitation of space in the galleries, a guidance system is required to satisfy visitors' needs and to enhance their understanding of the artifacts. We introduce one exhibition using imaging technology to improve visitors' understanding of a kimono (traditional Japanese clothing) exhibition. In the imaging technology introduced, one data projector, one display with touch panel interface, and magnifiers were used as exhibition tools together with a real kimono. The validity of this exhibition method was confirmed by results from a visitors' interview survey. Second, to further develop the interactive guidance system, an augmented reality system that consisted of cooperation between the projector and a digital video camera was also examined. A white paper board in the observer's hand was used as a projection screen and also as an interface to control the images projected on the board. The basic performance of the proposed system was confirmed; however continuous development was necessary for applying the system to actual exhibitions.

  19. Orbital benign and malignant lymphoproliferative disorders: Differentiation using semi-quantitative and quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Hao; Xu, Xiao-Quan [Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Liu, Hu [Department of Ophthalmology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Hong, Xun-Ning; Shi, Hai-Bin [Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Wu, Fei-Yun, E-mail: wfydd_njmu@163.com [Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2017-03-15

    Objectives: To assess the value of dynamic contrast-enhanced MR imaging (DCE-MRI) in differentiating benign from malignant orbital lymphoproliferative disorders (OLPDs). Methods: Thirty-nine patients with orbital lymphoproliferative disorders (21 malignant and 18 benign) underwent DCE-MRI scan for pre-treatment evaluation from March 2013 to December 2015. Both semi-quantitative (TTP, AUC, Slope{sub max}) and quantitative (K{sup trans}, k{sub ep}, v{sub e}) parameters were calculated, and compared between two groups. Receiver operating characteristic (ROC) curve analyses were used to determine the diagnostic value of each significant parameter. Results: Malignant OLPDs showed significantly higher k{sub ep}, lower v{sub e}, and lower AUC than benign OLPDs, while no significant differences were found on K{sup trans}, TTP and Slope{sub max}. ROC analyses indicated that v{sub e} exhibited the best diagnostic performance in predicting malignant OLPDs (cutoff value, 0.211; area under the curve, 0.896; sensitivity, 76.2%; specificity, 94.9%), followed by k{sub ep} (cutoff value, 0.853; area under the curve, 0.839; sensitivity, 85.7%; specificity, 89.9%). Conclusion: DCE-MRI and specially its derived quantitative parameters of k{sub ep} and v{sub e} are promising metrics for differentiating malignant from benign OLPDs.

  20. Exhibition; Image display agency

    International Nuclear Information System (INIS)

    Normazlin Ismail

    2008-01-01

    This article touches on the role of Malaysian Nuclear Agency as nuclear research institutions to promote, develop and encourage the peaceful uses of nuclear technology in its agricultural, medical, manufacturing, industrial, health and environment for the development of the country running successfully. Maturity of Malaysian Nuclear Agency in dealing with nuclear technology that are very competitive and globalization cannot be denied. On this basis Malaysian Nuclear Agency was given the responsibility to strengthen the nuclear technology in Malaysia. One way is through an exhibition featuring the research, discoveries and new technology products of the nuclear technology. Through this exhibition is to promote the nuclear technology and introduce the image of the agency in the public eye. This article also states a number of exhibits entered by the Malaysian Nuclear Agency and achievements during the last exhibition. Authors hope that the exhibition can be intensified further in the future.

  1. Effects of the differentiating agents sodium butyrate and N-methylformamide on the oxygen enhancement ratio of human colon tumor cells

    International Nuclear Information System (INIS)

    Hallows, K.R.; Bliven, S.F.; Leith, J.T.

    1988-01-01

    We have previously shown that chronic adaptation of human tumor cells to the differentiation-inducing agents N-methylformamide (NMF) and sodium butyrate (NAB) increases the sensitivity of oxic cells to graded single doses of X rays. These studies were carried out to define the sensitivity of hypoxic cells after adaptation. Clone A colon tumor cells were grown for three passages in medium containing 170 mM NMF or 2 mM NAB and irradiated in suspension culture, after gassing with either oxygen (60 min) or ultrapure nitrogen (90 min), and complete survival curves were generated. Using the linear-quadratic equation to describe the data, it was found that NMF and NAB produced increased X-ray killing of hypoxic cells. At the 10% level of survival, the dose-modifying factors were about 1.20 and 1.25 for NMF- and NAB-adapted hypoxic cells, respectively, as compared to hypoxic control cells. However, since both oxic and hypoxic cells exhibited increased sensitivity after NMF and NAB adaptation, there was no major change in the oxygen enhancement ratio

  2. Responses to cholinergic agonists of rats selectively bred for differential sensitivity to ethanol.

    Science.gov (United States)

    de Fiebre, C M; Romm, E; Collins, J T; Draski, L J; Deitrich, R A; Collins, A C

    1991-03-01

    Alcoholics are almost invariably heavy users of tobacco. Both alcoholism and smoking appear to be influenced by genetic factors but it is not known whether the same or different genes regulate the abuse of ethanol and nicotine. Recent studies have demonstrated that the long-sleep (LS) and short-sleep (SS) mouse lines, which were selectively bred for differences in ethanol-induced anesthesia ("sleep-time"), also differ in several effects of nicotine and the muscarinic agonist, oxotremorine. In order to determine whether or not these differences are due to chance, the relative sensitivities of rat lines which were selectively bred for differences in ethanol-induced sleep-time were determined. The high alcohol sensitivity (HAS) rat line was more sensitive to the locomotor and body temperature depressant effects of nicotine than was the low alcohol sensitivity (LAS) rat line. The control line (CAS) was intermediate in sensitivity. The rat lines did not differ in sensitivity to oxotremorine's hypothermia-producing effects. The numbers and affinities of two classes of brain nicotinic receptors were measured in eight brain regions. No differences among the rat lines were detected. These results suggest that ethanol elicits some of its depressant actions via an effect on brain nicotinic systems, but the differences in sensitivity to ethanol and nicotine are probably not due to differences in the number of brain nicotinic receptors. Perhaps this interaction explains the high correlation between alcoholism and smoking in humans.

  3. Difference in root K+ retention ability and reduced sensitivity of K+-permeable channels to reactive oxygen species confer differential salt tolerance in three Brassica species.

    Science.gov (United States)

    Chakraborty, Koushik; Bose, Jayakumar; Shabala, Lana; Shabala, Sergey

    2016-08-01

    Brassica species are known to possess significant inter and intraspecies variability in salinity stress tolerance, but the cell-specific mechanisms conferring this difference remain elusive. In this work, the role and relative contribution of several key plasma membrane transporters to salinity stress tolerance were evaluated in three Brassica species (B. napus, B. juncea, and B. oleracea) using a range of electrophysiological assays. Initial root growth assay and viability staining revealed that B. napus was most tolerant amongst the three species, followed by B. juncea and B. oleracea At the mechanistic level, this difference was conferred by at least three complementary physiological mechanisms: (i) higher Na(+) extrusion ability from roots resulting from increased expression and activity of plasma membrane SOS1-like Na(+)/H(+) exchangers; (ii) better root K(+) retention ability resulting from stress-inducible activation of H(+)-ATPase and ability to maintain more negative membrane potential under saline conditions; and (iii) reduced sensitivity of B. napus root K(+)-permeable channels to reactive oxygen species (ROS). The last two mechanisms played the dominant role and conferred most of the differential salt sensitivity between species. Brassica napus plants were also more efficient in preventing the stress-induced increase in GORK transcript levels and up-regulation of expression of AKT1, HAK5, and HKT1 transporter genes. Taken together, our data provide the mechanistic explanation for differential salt stress sensitivity amongst these species and shed light on transcriptional and post-translational regulation of key ion transport systems involved in the maintenance of the root plasma membrane potential and cytosolic K/Na ratio as a key attribute for salt tolerance in Brassica species. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  4. Intrinsic Sex-Linked Variations in Osteogenic and Adipogenic Differentiation Potential of Bone Marrow Multipotent Stromal Cells.

    Science.gov (United States)

    Bragdon, Beth; Burns, Robert; Baker, Amelia H; Belkina, Anna C; Morgan, Elise F; Denis, Gerald V; Gerstenfeld, Louis C; Schlezinger, Jennifer J

    2015-02-01

    Bone formation and aging are sexually dimorphic. Yet, definition of the intrinsic molecular differences between male and female multipotent mesenchymal stromal cells (MSCs) in bone is lacking. This study assessed sex-linked differences in MSC differentiation in 3-, 6-, and 9-month-old C57BL/6J mice. Analysis of tibiae showed that female mice had lower bone volume fraction and higher adipocyte content in the bone marrow compared to age-matched males. While both males and females lost bone mass in early aging, the rate of loss was higher in males. Similar expression of bone- and adipocyte-related genes was seen in males and females at 3 and 9 months, while at 6 months, females exhibited a twofold greater expression of these genes. Under osteogenic culture conditions, bone marrow MSCs from female 3- and 6-month-old mice expressed similar levels of bone-related genes, but significantly greater levels of adipocyte-related genes, than male MSCs. Female MSCs also responded to rosiglitazone-induced suppression of osteogenesis at a 5-fold lower (10 nM) concentration than male MSCs. Female MSCs grown in estrogen-stripped medium showed similar responses to rosiglitazone as MSCs grown in serum containing estrogen. MSCs from female mice that had undergone ovariectomy before sexual maturity also were sensitive to rosiglitazone-induced effects on osteogenesis. These results suggest that female MSCs are more sensitive to modulation of differentiation by PPARγ and that these differences are intrinsic to the sex of the animal from which the MSCs came. These results also may explain the sensitivity of women to the deleterious effects of rosiglitazone on bone. © 2014 Wiley Periodicals, Inc.

  5. Spectral differential imaging detection of planets about nearby stars

    International Nuclear Information System (INIS)

    Smith, W.H.

    1987-01-01

    Direct ground-based optical imaging of planets in orbit about nearby stars may be accomplished by spectral differential imaging using multiple passband acoustooptic filters with a CCD. This technique provides two essential results. First, it provides a means to modulate the stellar flux reflected from a planet while leaving the flux from the star and other sources in the same field of view unmodulated. Second, spectral differential imaging enables the CCD detector to achieve a sufficiently high dynamic range to locate planets near a star in spite of an integrated brightness differential of 5 x 10 8 . Spectral differential imaging at nearby diffraction limited imaging conditions with telescope apodization can reduce the time to conduct a sensitive planetary search to a few hours in some cases. The feasibility of this idea is discussed here and shown to provide, in principle, the discrimination and sensitivity to detect a Jovian-class planet about stars at distances of about 10 parsecs. The detection of brown dwarfs is shown to be feasible as well. 31 references

  6. Zero-birefringence pressure-sensitive adhesives

    Directory of Open Access Journals (Sweden)

    Hiroto Ito

    2012-06-01

    Full Text Available We have developed zero-birefringence pressure-sensitive adhesives (PSAs that exhibit almost no birefringence at any orientation of polymer chains. To evaluate the birefringence of PSAs quantitatively, we report a novel birefringence-measurement method utilizing zero–zero-birefringence polymers that exhibit no birefringence at any orientation of polymer chains and in elastic deformation. By employing this method, we designed and synthesized poly(butyl acrylate/phenoxyethyl acrylate/acrylic acid/hydroxyethyl acrylate = 80.0:20.0:1.5:1.0 (by weight that contains 1.8 wt% isocyanate-type crosslinker that exhibited almost zero birefringence. Furthermore, we demonstrated that after the accelerated aging test by applying heat, this zero-birefringence PSA almost completely prevented light leakage through crossed polarizers.

  7. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Hu, Huimin; Qiu, Weimin

    2018-01-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte...... differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating h...

  8. Application of the perturbation theory for sensitivity calculations in thermalhydraulics reactor calculations

    International Nuclear Information System (INIS)

    Andrade Lima, F.R. de

    1986-01-01

    The sensitivity of non linear responses associated with physical quantities governed by non linear differential systems can be studied using perturbation theory. The equivalence and formal differences between the differential and GPT formalisms are shown and both are used for sensitivity calculations of transient problems in a typical PWR coolant channel. The results obtained are encouraging with respect to the potential of the method for thermalhydraulics calculations normally performed for reactor design and safety analysis. (Author) [pt

  9. Oxytocin Neurons Exhibit Extensive Functional Plasticity Due To Offspring Age in Mothers and Fathers.

    Science.gov (United States)

    Kelly, Aubrey M; Hiura, Lisa C; Saunders, Alexander G; Ophir, Alexander G

    2017-09-01

    The needs of offspring change as they develop. Thus, parents should concomitantly change their investment based on the age-related needs of the offspring as they mature. Due to the high costs of parental care, it is optimal for parents to exhibit a shift from intense caregiving of young offspring to promoting independence in older offspring. Yet, the neural mechanisms that underlie shifts in parental behavior are poorly understood, and little is known about how the parental brain responds to offspring of different ages. To elucidate mechanisms that relate to shifts in parental behavior as offspring develop, we examined behavioral and neural responses of male and female prairie voles (Microtus ochrogaster), a biparental rodent, to interactions with offspring at different stages of development (ranging from neonatal to weaning age). Importantly, in biparental species, males and females may adjust their behavior differentially as offspring develop. Because the nonapeptides, vasopressin (VP) and oxytocin (OT), are well known for modulating aspects of parental care, we focused on functional activity of distinct VP and OT cell groups within the maternal and paternal brain in response to separation from, reunion (after a brief period of separation) with, or no separation from offspring of different ages. We found several differences in the neural responses of individual VP and OT cell groups that varied based on the age of pups and sex of the parent. Hypothalamic VP neurons exhibit similar functional responses in both mothers and fathers. However, hypothalamic and amygdalar OT neurons exhibit differential functional responses to being separated from pups based on the sex of the parent. Our results also reveal that the developmental stage of offspring significantly impacts neural function within OT, but not VP, cell groups of both mothers and fathers. These findings provide insight into the functional plastic capabilities of the nonapeptide system, specifically in relation

  10. DNA replication and post-replication repair in U.V.-sensitive mouse neuroblastoma cells

    International Nuclear Information System (INIS)

    Lavin, M.F.; McCombe, P.; Kidson, C.

    1976-01-01

    Mouse neuroblastoma cells differentiated when grown in the absence of serum; differentiation was reversed on the addition of serum. Differentiated cells were more sensitive to U.V.-radiation than proliferating cells. Whereas addition of serum to differentiated neuroblastoma cells normally resulted in immediate, synchronous entry into S phase, irradiation just before the addition of serum resulted in a long delay in the onset of DNA replication. During this lag period, incorporated 3 H-thymidine appeared in the light density region of CsCl gradients, reflecting either repair synthesis or abortive replication. Post-replication repair (gap-filling) was found to be present in proliferating cells and at certain times in differentiated cells. It is suggested that the sensitivity of differentiated neuroblastoma cells to U.V.-radiation may have been due to ineffective post-replication repair or to deficiencies in more than one repair mechanism, with reduction in repair capacity beyond a critical threshold. (author)

  11. Phase reduction and synchronization of a network of coupled dynamical elements exhibiting collective oscillations

    Science.gov (United States)

    Nakao, Hiroya; Yasui, Sho; Ota, Masashi; Arai, Kensuke; Kawamura, Yoji

    2018-04-01

    A general phase reduction method for a network of coupled dynamical elements exhibiting collective oscillations, which is applicable to arbitrary networks of heterogeneous dynamical elements, is developed. A set of coupled adjoint equations for phase sensitivity functions, which characterize the phase response of the collective oscillation to small perturbations applied to individual elements, is derived. Using the phase sensitivity functions, collective oscillation of the network under weak perturbation can be described approximately by a one-dimensional phase equation. As an example, mutual synchronization between a pair of collectively oscillating networks of excitable and oscillatory FitzHugh-Nagumo elements with random coupling is studied.

  12. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Hu, Huimin; Qiu, Weimin

    2018-01-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte...

  13. An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression.

    Directory of Open Access Journals (Sweden)

    Tokiho Akiyama

    Full Text Available Humans show various responses to the environmental stimulus in individual levels as "physiological variations." However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05. The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05, and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.

  14. Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus.

    Science.gov (United States)

    Rosário, Pedro Weslley; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa Maria Z; Maia, Ana Luiza; Vaisman, Mário

    2013-06-01

    Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.

  15. Viability, biofilm formation, and MazEF expression in drug-sensitive and drug-resistant Mycobacterium tuberculosis strains circulating in Xinjiang, China.

    Science.gov (United States)

    Zhao, Ji-Li; Liu, Wei; Xie, Wan-Ying; Cao, Xu-Dong; Yuan, Li

    2018-01-01

    was increased in drug-sensitive and drug-resistant strains compared to H37Rv, while drug-resistant strains exhibited reduced mazF9 expression compared to drug-sensitive strains. Compared to H37Rv, H37RvΔ mazEF 3,6,9-deletion mutants grew more slowly under both stress conditions, and their ability to survive in host macrophages was also weaker. Furthermore, the host macrophage-apoptosis rate was higher after infection with any of the H37RvΔ mazE F3,6,9 mutants than with the H37Rv strain. The increased viability of MTB drug-resistant strains compared with drug-sensitive strains is likely to be related to differential MazEF mRNA and protein expression. mazEF 3,6,9 TASs contribute to MTB viability under stress conditions.

  16. Differentiation of strains of yellow fever virus in γ-irradiated mice

    International Nuclear Information System (INIS)

    Fitzgeorge, R.; Bradish, C.J.

    1980-01-01

    The mouse sensitized by optimal, sub-lethal γ-irradiation has been used for the differentiation of strains of yellow fever virus and for the resolution of their immunogenicity and pathogenicity as distinct characteristics. For different strains of yellow fever virus, the patterns of antibody-synthesis, regulatory immunity (pre-challenge) and protective immunity (post-challenge) are differentially sensitive to γ-irradiation. These critical differentiations of strains of yellow fever virus in γ-irradiated mice have been compared with those shown in normal athymic and immature mice in order to elucidate the range of quantifiable in vivo characteristics and the course of the virus-host interaction. This is discussed as a basis for the comparisons of the responses of model and principal hosts to vaccines and pathogens. (author)

  17. Three-dimensional piezoelectric fibrous scaffolds selectively promote mesenchymal stem cell differentiation.

    Science.gov (United States)

    Damaraju, Sita M; Shen, Yueyang; Elele, Ezinwa; Khusid, Boris; Eshghinejad, Ahmad; Li, Jiangyu; Jaffe, Michael; Arinzeh, Treena Livingston

    2017-12-01

    The discovery of electric fields in biological tissues has led to efforts in developing technologies utilizing electrical stimulation for therapeutic applications. Native tissues, such as cartilage and bone, exhibit piezoelectric behavior, wherein electrical activity can be generated due to mechanical deformation. Yet, the use of piezoelectric materials have largely been unexplored as a potential strategy in tissue engineering, wherein a piezoelectric biomaterial acts as a scaffold to promote cell behavior and the formation of large tissues. Here we show, for the first time, that piezoelectric materials can be fabricated into flexible, three-dimensional fibrous scaffolds and can be used to stimulate human mesenchymal stem cell differentiation and corresponding extracellular matrix/tissue formation in physiological loading conditions. Piezoelectric scaffolds that exhibit low voltage output, or streaming potential, promoted chondrogenic differentiation and piezoelectric scaffolds with a high voltage output promoted osteogenic differentiation. Electromechanical stimulus promoted greater differentiation than mechanical loading alone. Results demonstrate the additive effect of electromechanical stimulus on stem cell differentiation, which is an important design consideration for tissue engineering scaffolds. Piezoelectric, smart materials are attractive as scaffolds for regenerative medicine strategies due to their inherent electrical properties without the need for external power sources for electrical stimulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines

    Science.gov (United States)

    Franco, Domenico; Trusso, Sebastiano; Fazio, Enza; Allegra, Alessandro; Musolino, Caterina; Speciale, Antonio; Cimino, Francesco; Saija, Antonella; Neri, Fortunato; Nicolò, Marco S.; Guglielmino, Salvatore P. P.

    2017-12-01

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM.1R and U266/BTZ-R subtypes, resistant to dexamethasone and bortezomib, respectively. Then, micro-Raman spectroscopy provides an easily accurate and noninvasive method for cancer detection for both research and clinical environments. Characteristic peaks, mostly due to different DNA/RNA ratio, nucleic acids, lipids and protein concentrations, allow for discerning the sensitive and resistant subtypes. We also explored principal component analysis (PCA) for resistant cell identification and classification. Sensitive and resistant cells form distinct clusters that can be defined using just two principal components. The identification of drug-resistant cells by confocal micro-Raman spectroscopy is thus proposed as a clinical tool to assess the development of resistance to glucocorticoids and proteasome inhibitors in myeloma cells.

  19. Reversal of apomorphine locomotor sensitization by a single post-conditioning trial treatment with a low autoreceptor dose of apomorphine: a memory re-consolidation approach.

    Science.gov (United States)

    Carrera, Marinete Pinheiro; Carey, Robert J; Dias, Flávia Regina Cruz; de Matos, Liana Wermelinger

    2011-07-01

    Sensitization is a common feature of psychostimulants and sensitization effects are generally considered to be linked to the addictive properties of these drugs. We used a conventional paired/unpaired Pavlovian protocol to induce a context specific sensitization to the locomotor stimulant effect of a high dose of apomorphine (2.0mg/kg). Two days following a 5 session sensitization induction phase, a brief 5min non-drug test for conditioning was conducted. Only the paired groups exhibited locomotor stimulant conditioned response effects. Immediately following this brief test for conditioning, the paired and the unpaired groups received injections of 0.05mg/kg apomorphine, 2.0mg/kg apomorphine or vehicle designed to differentially impact memory re-consolidation of the conditioning. Two days later, all groups received a sensitization challenge test with 2.0mg/kg apomorphine. The 2.0mg/kg apomorphine post-trial treatment potentiated sensitization while the 0.05mg/kg eliminated sensitization. These effects were only observed in the paired groups. The activation of dopaminergic systems by the high dose of apomorphine strengthened the drug/environment association whereas the inhibition of dopamine activity by the low auto-receptor dose eliminated this association. The results point to the importance of conditioning to context specific sensitization and targeting memory re-consolidation of conditioning as a paradigm to modify sensitization. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Automatic differentiation as a tool in engineering design

    Science.gov (United States)

    Barthelemy, Jean-Francois; Hall, Laura E.

    1992-01-01

    Automatic Differentiation (AD) is a tool that systematically implements the chain rule of differentiation to obtain the derivatives of functions calculated by computer programs. AD is assessed as a tool for engineering design. The forward and reverse modes of AD, their computing requirements, as well as approaches to implementing AD are discussed. The application of two different tools to two medium-size structural analysis problems to generate sensitivity information typically necessary in an optimization or design situation is also discussed. The observation is made that AD is to be preferred to finite differencing in most cases, as long as sufficient computer storage is available; in some instances, AD may be the alternative to consider in lieu of analytical sensitivity analysis.

  1. Redox-sensitive self-assembled nanoparticles based on alpha-tocopherol succinate-modified heparin for intracellular delivery of paclitaxel.

    Science.gov (United States)

    Yang, Xiaoye; Cai, Xiaoqing; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

    2017-06-15

    To remedy the problems riddled in cancer chemotherapy, such as poor solubility, low selectivity, and insufficient intra-cellular release of drugs, novel heparin-based redox-sensitive polymeric nanoparticles were developed. The amphiphilic polymer, heparin-alpha-tocopherol succinate (Hep-cys-TOS) was synthesized by grafting hydrophobic TOS to heparin using cystamine as the redox-sensitive linker, which could self-assemble into nanoparticles in phosphate buffer saline (PBS) with low critical aggregation concentration (CAC) values ranging from 0.026 to 0.093mg/mL. Paclitaxel (PTX)-loaded Hep-cys-TOS nanoparticles were prepared via a dialysis method, exhibiting a high drug-loading efficiency of 18.99%. Physicochemical properties of the optimized formulation were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM) and differential scanning calorimetry (DSC). Subsequently, the redox-sensitivity of Hep-cys-TOS nanoparticles was confirmed by the changes in size distribution, morphology and appearance after dithiothreitol (DTT) treatment. Besides, the in vitro release of PTX from Hep-cys-TOS nanoparticles also exhibited a redox-triggered profile. Also, the uptake behavior and pathways of coumarin 6-loaded Hep-cys-TOS nanoparticles were investigated, suggesting the nanoparticles could be taken into MCF-7 cells in energy-dependent, caveolae-mediated and cholesterol-dependent endocytosis manners. Later, MTT assays of different PTX-free and PTX-loaded formulations revealed the desirable safety of PTX-free nanoparticles and the enhanced anti-cancer activity of PTX-loaded Hep-cys-TOS nanoparticles (IC 50 =0.79μg/mL). Apoptosis study indicated the redox-sensitive formulation could induce more apoptosis of MCF-7 cells than insensitive one (55.2% vs. 41.7%), showing the importance of intracellular burst release of PTX. Subsequently, the hemolytic toxicity confirmed the safety of the nanoparticles for intravenous administration. The results

  2. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha

    2008-01-01

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged...

  3. Vortex dynamics in a pipe T-junction: Recirculation and sensitivity

    Science.gov (United States)

    Chen, Kevin K.; Rowley, Clarence W.; Stone, Howard A.

    2015-03-01

    In the last few years, many researchers have noted that regions of recirculating flow often exhibit particularly high sensitivity to spatially localized feedback. We explore the flow through a T-shaped pipe bifurcation—a simple and ubiquitous, but generally poorly understood flow configuration—and provide a complex example of the relation between recirculation and sensitivity. When Re ≥ 320, a phenomenon resembling vortex breakdown occurs in four locations in the junction, with internal stagnation points appearing on vortex axes and causing flow reversal. The structure of the recirculation is similar to the traditional bubble-type breakdown. These recirculation regions are highly sensitive to spatially localized feedback in the linearized Navier-Stokes operator. The flow separation at the corners of the "T," however, does not exhibit this kind of sensitivity. We focus our analysis on the Reynolds number of 560, near the first Hopf bifurcation of the flow.

  4. Differential Auger spectrometry

    International Nuclear Information System (INIS)

    Strongin, M.; Varma, M.N.; Anne, J.

    1976-01-01

    A differential Auger spectroscopy method is given for increasing the sensitivity of micro-Auger spectroanalysis of the surfaces of dilute alloys, by alternately periodically switching an electron beam back and forth between an impurity free reference sample and a test sample containing a trace impurity. The Auger electrons from the samples produce representative Auger spectrum signals which cancel to produce an Auger test sample signal corresponding to the amount of the impurity in the test samples

  5. A survey of Sertoli cell differentiation in men after gonadotropin suppression and in testicular cancer

    DEFF Research Database (Denmark)

    Tarulli, Gerard A; Stanton, Peter G; Loveland, Kate L

    2013-01-01

    It is widely held that the somatic cell population that is responsible for sperm development and output (Sertoli cells) is terminally differentiated and unmodifiable in adults. It is postulated, with little evidence, that Sertoli cells are not terminally differentiated in some phenotypes of infer...... tubules with CIS and the emergence of strong JAM-A reactivity in seminoma. These findings indicate that adult human Sertoli cells exhibit characteristics of an undifferentiated state in oligospermic men and patients with CIS and seminoma in the presence of germ cell neoplasia....... of infertility and testicular cancer. This study sought to compare markers of Sertoli cell differentiation in normospermic men, oligospermic men (undergoing gonadotropin suppression) and testicular carcinoma in situ (CIS) and seminoma samples. Confocal microscopy was used to assess the expression of markers...... of proliferation (PCNA and Ki67) and functional differentiation (androgen receptor). As additional markers of differentiation, the organization of Sertoli cell tight junction and associated proteins were assessed in specimens with carcinoma in situ. In normal men, Sertoli cells exhibited a differentiated phenotype...

  6. Application of graphene for preconcentration and highly sensitive stripping voltammetric analysis of organophosphate pesticide

    Energy Technology Data Exchange (ETDEWEB)

    Wu Shuo, E-mail: wushuo@dlut.edu.cn [School of Chemistry, Dalian University of Technology, Dalian 116023 (China); Lan Xiaoqin; Cui Lijun; Zhang Lihui; Tao Shengyang; Wang Hainan; Han Mei; Liu Zhiguang; Meng Changgong [School of Chemistry, Dalian University of Technology, Dalian 116023 (China)

    2011-08-12

    Highlights: {yields} An electrochemical sensor is fabricated based on {beta}-CD dispersed graphene. {yields} The sensor could selectively detect organophosphate pesticide with high sensitivity. {yields} The {beta}-CD dispersed graphene owns large adsorption capacity for MP and superconductivity. {yields} The {beta}-CD dispersed graphene is superior to most of the porous sorbents ever known. - Abstract: Electrochemical reduced {beta}-cyclodextrin dispersed graphene ({beta}-CD-graphene) was developed as a sorbent for the preconcentration and electrochemical sensing of methyl parathion (MP), a representative nitroaromatic organophosphate pesticide with good redox activity. Benefited from the ultra-large surface area, large delocalized {pi}-electron system and the superconductivity of {beta}-CD-graphene, large amount of MP could be extracted on {beta}-CD-graphene modified electrode via strong {pi}-{pi} interaction and exhibited fast accumulation and electron transfer rate. Combined with differential pulse voltammetric analysis, the sensor shows ultra-high sensitivity, good selectivity and fast response. The limit of detection of 0.05 ppb is more than 10 times lower than those obtained from other sorbent based sensors. The method may open up a new possibility for the widespread use of electrochemical sensors for monitoring of ultra-trace OPs.

  7. Protease-sensitive synthetic prions.

    Directory of Open Access Journals (Sweden)

    David W Colby

    2010-01-01

    Full Text Available Prions arise when the cellular prion protein (PrP(C undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc. Frequently, PrP(Sc is protease-resistant but protease-sensitive (s prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164, denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174 did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc. These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc.

  8. Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling.

    Science.gov (United States)

    Piao, Jinying; Tsuji, Kunikazu; Ochi, Hiroki; Iwata, Munetaka; Koga, Daisuke; Okawa, Atsushi; Morita, Sadao; Takeda, Shu; Asou, Yoshinori

    2013-10-23

    Sirtuin 6 (Sirt6) is a mammalian homologue of NAD⁺-dependent histone deacetylase Sir2. Although Sirt6⁻/⁻ mice exhibit growth retardation, the role of Sirt6 in cartilage metabolism is unclear. The aim of this study was to investigate the Sirt6 signaling pathway in cartilage metabolism. Immunohistological evaluation of the tibial growth plate in Sirt6⁻/⁻ mice exhibited impaired proliferation and differentiation of chondrocytes, reduced expression of Indian hedgehog (Ihh), and a senescent phenotype. When Sirt6 was knocked down in chondrocytes in vitro, expression of Ihh and its downstream genes were reduced. Impaired differentiation by Sirt6 silencing was completely rescued by administration of a Hh signal agonist. When sirtuins were activated, chondrocyte differentiation was enhanced together with activation of Ihh signal, and these effects were abrogated by Sirt6 silencing. ChIP assay revealed the affinity of ATF4 to the Ihh promoter was markedly decreased by Sirt6 knockdown. These data indicate Sirt6 directly controls proliferation and differentiation of chondrocytes.

  9. A genome-wide methylation study on obesity: differential variability and differential methylation.

    Science.gov (United States)

    Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Hidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling

    2013-05-01

    Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14-20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances.

  10. Paralogs hnRNP L and hnRNP LL exhibit overlapping but distinct RNA binding constraints.

    Directory of Open Access Journals (Sweden)

    Sarah A Smith

    Full Text Available HnRNP (heterogeneous nuclear ribonucleoprotein proteins are a large family of RNA-binding proteins that regulate numerous aspects of RNA processing. Interestingly, several paralogous pairs of hnRNPs exist that exhibit similar RNA-binding specificity to one another, yet have non-redundant functional targets in vivo. In this study we systematically investigate the possibility that the paralogs hnRNP L and hnRNP LL have distinct RNA binding determinants that may underlie their lack of functional redundancy. Using a combination of RNAcompete and native gel analysis we find that while both hnRNP L and hnRNP LL preferentially bind sequences that contain repeated CA dinucleotides, these proteins differ in their requirement for the spacing of the CAs. Specifically, hnRNP LL has a more stringent requirement for a two nucleotide space between CA repeats than does hnRNP L, resulting in hnRNP L binding more promiscuously than does hnRNP LL. Importantly, this differential requirement for the spacing of CA dinucleotides explains the previously observed differences in the sensitivity of hnRNP L and LL to mutations within the CD45 gene. We suggest that overlapping but divergent RNA-binding preferences, as we show here for hnRNP L and hnRNP LL, may be commonplace among other hnRNP paralogs.

  11. DIFFERENTIAL SENSITIVITY OF MALE GERM CELLS TO MAINSTREAM AND SIDESTREAM TOBACCO SMOKE IN THE MOUSE

    Energy Technology Data Exchange (ETDEWEB)

    Polyzos, Aris; Schmid, Thomas Ernst; Pina-Guzman, Belem; Quintanilla-Vega, Betzabet; Marchetti, Francesco

    2009-03-13

    Cigarette smoking in men has been associated with increased chromosomal abnormalities in sperm and with increased risks for spontaneous abortions, birth defects and neonatal death. Little is known, however, about the reproductive consequences of paternal exposure to second-hand smoke. We used a mouse model to investigate the effects of paternal exposure to sidestream (SS) smoke, the main constituent of second-hand smoke, on the genetic integrity and function of sperm, and to determine whether male germ cells were equally sensitive to mainstream (MS) and SS smoke. A series of sperm DNA quality and reproductive endpoints were investigated after exposing male mice for two weeks to MS or SS smoke. Our results indicated that: (i) only SS smoke significantly affected sperm motility; (ii) only MS smoke induced DNA strand breaks in sperm; (iii) both MS and SS smoke increased sperm chromatin structure abnormalities; and (iv) MS smoke affected both fertilization and the rate of early embryonic development, while SS smoke affected fertilization only. These results show that MS and SS smoke have differential effects on the genetic integrity and function of sperm and provide further evidence that male exposure to second-hand smoke, as well as direct cigarette smoke, may diminish a couple's chance for a successful pregnancy and the birth of a healthy baby.

  12. The role of parental personality traits in differential parenting.

    Science.gov (United States)

    Browne, Dillon T; Meunier, Jean Christophe; O'Connor, Thomas G; Jenkins, Jennifer M

    2012-08-01

    Significant relationships have been demonstrated between parental personality and parenting toward individual children, but there is little research exploring the relationship between parental personality and differential parenting (DP). The present study examined the relationship between the Big Five personality dimensions and differential positivity and negativity in parenting (observed and self-report measures). The analyses are based on a sample of 867 children nested within 381 families. Using multilevel modeling and controlling for child age, gender, birth order, behavior, and family socioeconomic status analyses revealed that maternal and paternal agreeableness were inversely related to reports of differential positivity. Agreeableness predicted observed differential negativity, and the relationship was curvilinear (at both high and low levels of agreeableness, differential negativity was higher). Finally, mothers with the most openness to experience exhibited the highest levels of reported differential negativity. The findings suggest that parental personality is a modest yet important influence to consider when conceptualizing the sources of DP. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  13. A yeast mutant specifically sensitive to bifunctional alkylation

    International Nuclear Information System (INIS)

    Ruhland, A.; Kircher, M.; Wilborn, F.; Brendel, M.

    1981-01-01

    A mutation that specifically confers sensitivity to bi- and tri-functional alkylating agents is presented. No or little cross-sensitivity to radiation or monofunctional agents could be detected. Sensitivity does not seem to be due to preferential alkylation of mutant DNA as parent and mutant strain exhibit the same amount of DNA alkylation and the same pattern of DNA lesions including interstrand crosslinks. The mutation is due to a defect in a nuclear gene which has been designated SNM1 (sensitive to nitrogen mustard); it may control an important step in the repair of DNA interstrand crosslinks (orig.(AJ)

  14. Differentiation of Students in the Early Danish Welfare State

    DEFF Research Database (Denmark)

    Ydesen, Christian; Andreasen, Karen Egedal; Hamre, Bjørn Frithiof

    2018-01-01

    Historically, differentiation of students has been influenced by to numerous contextual factors. Scholars and practitioners consider it a context-sensitive practice subject to negotiations and entanglements among various agents, groups, interests, ideas, and values. This article pursues the pract......Historically, differentiation of students has been influenced by to numerous contextual factors. Scholars and practitioners consider it a context-sensitive practice subject to negotiations and entanglements among various agents, groups, interests, ideas, and values. This article pursues...... of the education system. This entailed an increased division of labour among professional groups; debates reflecting different ideas about eugenics, heredity, and social equality; the schooling of psychologists and psychiatrists in Denmark; and the development of psychology and psychiatry as academic disciplines....

  15. A panchromatic anthracene-fused porphyrin sensitizer for dye-sensitized solar cells

    KAUST Repository

    Ball, James M.

    2012-01-01

    The development of ruthenium-free sensitizers which absorb light over a broad range of the solar spectrum is important for improving the power conversion efficiency of dye-sensitized solar cells. Here we study three chemically tailored porphyrin-based dyes. We show that by fusing the porphyrin core to an anthracene unit, we can extend the conjugation length and lower the optical gap, shifting the absorption spectrum into the near-infrared (NIR). All three dyes were tested in dye-sensitized solar cells, using both titanium dioxide and tin dioxide as the electron-transport material. Solar cells incorporating the anthracene-fused porphyrin dye exhibit photocurrent collection at wavelengths up to about 1100 nm, which is the longest reported for a porphyrin-based system. Despite extending the photon absorption bandwidth, device efficiency is found to be low, which is a common property of cells based on porphyrin dyes with NIR absorption. We show that in the present case the efficiency is reduced by inefficient electron injection into the oxide, as opposed to dye regeneration, and highlight some important design considerations for panchromatic sensitizers. © 2012 The Royal Society of Chemistry.

  16. The World of Virtual Exhibitions

    Directory of Open Access Journals (Sweden)

    Irena Eiselt

    2013-09-01

    Full Text Available EXTENDED ABSTRACTSpecial collections of the National and University Library (NUK hide a lot of items of precious value. The Slovenian cultural heritage is stored on paper or on other media as a part of the library’s Manuscripts, Incunabula and Rare Books Collection, Old Prints Collection, Maps and Pictorial Collection, Music Collection, Ephemera Collection, Serials Collection, and Slovenian Diaspora Publications Collection. Only a small part of the treasures is temporary revealed to the public on special exhibitions. The idea of virtual exhibitions of library treasures was born in 2005. The library aimed to exhibit precious items of special collections of high historical or artistic value. In 2008 the first two virtual exhibitions were created in-house offering access to the rich collections of old postcards of Ljubljana at the beginning of 20th century kept in the Maps and Pictorial Collection of NUK. They were soon followed by other virtual exhibitions. At the beginning they were organised in the same way as physical exhibitions, afterwards different programs were used for creation of special effects (for ex. 3D wall. About two years ago it was decided that the creation of virtual exhibitions will be simplified. Files of digitised and borndigital library materials in jpg format are imported to MS PowerPoint 2010. Each jpg file is now formatted by adding a frame, a description … to the slides which are saved as jpg files. The last step is the import of jpg files into Cooliris application used for NUK web exhibitions. In the paper the virtual exhibition design and creation, the technical point of view and criteria for the selection of exhibition content are explained following the example of the virtual exhibitions the Old Postcards of Ljubljana, Photo Ateliers in Slovenia, a collection of photographs Four Seasons by Fran Krašovec and photos of Post-Earthquake Ljubljana in 1895.

  17. Galectin-12 in Cellular Differentiation, Apoptosis and Polarization

    Directory of Open Access Journals (Sweden)

    Lei Wan

    2018-01-01

    Full Text Available Galectin-12 is a member of a family of mammalian lectins characterized by their affinity for β-galactosides and consensus amino acid sequences. The protein structure consists of a single polypeptide chain containing two carbohydrate-recognition domains joined by a linker region. Galectin-12 is predominantly expressed in adipose tissue, but is also detected in macrophages and other leukocytes. Downregulation of galectin-12 in mouse 3T3-L1 cells impairs their differentiation into adipocytes. Conversely, overexpression of galectin-12 in vitro induces cell cycle arrest in G1 and apoptosis. Upregulation of galectin-12 and initiation of G1 cell cycle arrest are associated with driving pre-adipocytes toward terminal differentiation. Galectin-12 deficiency increases insulin sensitivity and glucose tolerance in obese animals. Galectin-12 inhibits macrophage polarization to the M2 population, enhancing inflammation and decreasing insulin sensitivity in adipocytes. Galectin-12 also affects myeloid differentiation, which is associated with chemotherapy resistance. In addition to highlighting the above-mentioned aspects, this review also discusses the potential clinical applications of modulating the function of galectin-12.

  18. Chaotic Behavior of a Generalized Sprott E Differential System

    Science.gov (United States)

    Oliveira, Regilene; Valls, Claudia

    A chaotic system with only one equilibrium, a stable node-focus, was introduced by Wang and Chen [2012]. This system was found by adding a nonzero constant b to the Sprott E system [Sprott, 1994]. The coexistence of three types of attractors in this autonomous system was also considered by Braga and Mello [2013]. Adding a second parameter to the Sprott E differential system, we get the autonomous system ẋ = ayz + b,ẏ = x2 - y,ż = 1 - 4x, where a,b ∈ ℝ are parameters and a≠0. In this paper, we consider theoretically some global dynamical aspects of this system called here the generalized Sprott E differential system. This polynomial differential system is relevant because it is the first polynomial differential system in ℝ3 with two parameters exhibiting, besides the point attractor and chaotic attractor, coexisting stable limit cycles, demonstrating that this system is truly complicated and interesting. More precisely, we show that for b sufficiently small this system can exhibit two limit cycles emerging from the classical Hopf bifurcation at the equilibrium point p = (1/4, 1/16, 0). We also give a complete description of its dynamics on the Poincaré sphere at infinity by using the Poincaré compactification of a polynomial vector field in ℝ3, and we show that it has no first integrals in the class of Darboux functions.

  19. Differential consolidation and pattern reverberations within episodic cell assemblies in the mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Remus Oşan

    2011-02-01

    Full Text Available One hallmark feature of consolidation of episodic memory is that only a fraction of original information, which is usually in a more abstract form, is selected for long-term memory storage. How does the brain perform these differential memory consolidations? To investigate the neural network mechanism that governs this selective consolidation process, we use a set of distinct fearful events to study if and how hippocampal CA1 cells engage in selective memory encoding and consolidation. We show that these distinct episodes activate a unique assembly of CA1 episodic cells, or neural cliques, whose response-selectivity ranges from general-to-specific features. A series of parametric analyses further reveal that post-learning CA1 episodic pattern replays or reverberations are mostly mediated by cells exhibiting event intensity-invariant responses, not by the intensity-sensitive cells. More importantly, reactivation cross-correlations displayed by intensity-invariant cells encoding general episodic features during immediate post-learning period tend to be stronger than those displayed by invariant cells encoding specific features. These differential reactivations within the CA1 episodic cell populations can thus provide the hippocampus with a selection mechanism to consolidate preferentially more generalized knowledge for long-term memory storage.

  20. Differentiation of Spermatogonia Stem Cells into Functional Mature Neurons Characterized with Differential Gene Expression.

    Science.gov (United States)

    Bojnordi, Maryam Nazm; Azizi, Hossein; Skutella, Thomas; Movahedin, Mansoureh; Pourabdolhossein, Fereshteh; Shojaei, Amir; Hamidabadi, Hatef Ghasemi

    2017-09-01

    Transplantation of embryonic stem cells (ESCs) is a promising therapeutic approach for the treatment of neurodegenerative diseases. However, ESCs are not usable clinically due to immunological and ethical limitations. The identification of an alternative safe cell source opens novel options via autologous transplantation in neuro-regeneration circumventing these problems. Here, we examined the neurogenic capacity of embryonic stem-like cells (ES-like cells) derived from the testis using neural growth factor inducers and utilized them to generate functional mature neurons. The neuronal differentiation of ES-like cells is induced in three stages. Stage 1 is related to embryoid body (EB) formation. To induce neuroprogenitor cells, EBs were cultured in the presence of retinoic acid, N 2 supplement and fibroblast growth factor followed by culturing in a neurobasal medium containing B 27 , N 2 supplements for additional 10 days, to allow the maturation and development of neuronal progenitor cells. The neurogenic differentiation was confirmed by immunostaining for markers of mature neurons. The differentiated neurons were positive for Tuj1 and Tau1. Real-time PCR dates indicated the expression of Nestin and Neuro D (neuroprogenitor markers) in induced cells at the second stage of the differentiation protocol. The differentiated mature neurons exhibited the specific neuron markers Map2 and β-tubulin. The functional maturity of neurons was confirmed by an electrophysiological analysis of passive and active neural membrane properties. These findings indicated a differentiation capacity of ES-like cells derived from the testis to functionally mature neurons, which proposes them as a novel cell source for neuroregenerative medicine.

  1. Exhibition at the AAA library

    DEFF Research Database (Denmark)

    2013-01-01

    Sonnesgade 11 The exhibition at the AAA library presents selected work produced by students prior to the exhibition of installations in project and praxis constructing an archive at Sonnesgade 11. The exhibition at Sonnesgade 11 was the culmination of collaboration with SLETH architects and studio...

  2. Upcycling CERN Exhibitions

    CERN Multimedia

    Katarina Anthony

    2015-01-01

    Summer is coming - and with it, a new Microcosm exhibition showcasing CERN (see here). But while the new exhibit is preparing to enchant visitors, many have been asking about the site's former content. Will it simply be out with the old and in with the new? Not as such!   The plasma ball from Microcosm is now on display at the LHCb site. As Microcosm's new content is moving in, its old content is moving up. From LHCb to IdeaSquare, former Microcosm displays and objects are being installed across the CERN site. "Microcosm featured many elements that were well suited to life outside of the exhibition," says Emma Sanders, Microcosm project leader in the EDU group. "We didn't want this popular content to go to waste, and so set out to find them new homes across CERN." The LHCb experiment has received a number of Microcosm favourites, including the Rutherford experiment, the cosmic ray display and the Thomson experiment. "We&...

  3. Globe exhibit wins international acclaim

    CERN Multimedia

    Katarina Anthony

    2011-01-01

    The Globe’s “Universe of Particles” exhibition has recently received four prestigious awards for its avant-garde design. This external praise is great encouragement for the CERN exhibitions currently on the drawing board.   The Universe of Particles exhibition has won 4 awards for its avant-garde design. Back in 2008, the design company Atelier Brückner was presented with a challenge: to design the layout of a new permanent exhibition for CERN, one that would epitomize both the Organization and its research. The brief was concise but complex: the exhibit had to be symbolic of the Organization, use modern technology, engage and immerse visitors, and, preferably, use touch-screen technology. With the help of IArt, an interactive technology firm, and based on the content provided by CERN’s Education Group, Atelier Brückner developed the “Universe of Particles” exhibit as it is today. Its principal concept centred on the s...

  4. Genetic Variation for Lettuce Seed Thermoinhibition Is Associated with Temperature-Sensitive Expression of Abscisic Acid, Gibberellin, and Ethylene Biosynthesis, Metabolism, and Response Genes1[C][W][OA

    Science.gov (United States)

    Argyris, Jason; Dahal, Peetambar; Hayashi, Eiji; Still, David W.; Bradford, Kent J.

    2008-01-01

    Lettuce (Lactuca sativa ‘Salinas’) seeds fail to germinate when imbibed at temperatures above 25°C to 30°C (termed thermoinhibition). However, seeds of an accession of Lactuca serriola (UC96US23) do not exhibit thermoinhibition up to 37°C in the light. Comparative genetics, physiology, and gene expression were analyzed in these genotypes to determine the mechanisms governing the regulation of seed germination by temperature. Germination of the two genotypes was differentially sensitive to abscisic acid (ABA) and gibberellin (GA) at elevated temperatures. Quantitative trait loci associated with these phenotypes colocated with a major quantitative trait locus (Htg6.1) from UC96US23 conferring germination thermotolerance. ABA contents were elevated in Salinas seeds that exhibited thermoinhibition, consistent with the ability of fluridone (an ABA biosynthesis inhibitor) to improve germination at high temperatures. Expression of many genes involved in ABA, GA, and ethylene biosynthesis, metabolism, and response was differentially affected by high temperature and light in the two genotypes. In general, ABA-related genes were more highly expressed when germination was inhibited, and GA- and ethylene-related genes were more highly expressed when germination was permitted. In particular, LsNCED4, a gene encoding an enzyme in the ABA biosynthetic pathway, was up-regulated by high temperature only in Salinas seeds and also colocated with Htg6.1. The temperature sensitivity of expression of LsNCED4 may determine the upper temperature limit for lettuce seed germination and may indirectly influence other regulatory pathways via interconnected effects of increased ABA biosynthesis. PMID:18753282

  5. A potent trifluoromethyl ketone histone deacetylase inhibitor exhibits class-dependent mechanism of action

    DEFF Research Database (Denmark)

    Madsen, Andreas Stahl; Olsen, Christian Adam

    2016-01-01

    Histone deacetylase (HDAC) enzymes are validated targets for treatment of certain cancers and have potential as targets for pharmacological intervention in a number of other diseases. Thus, inhibitors of these enzymes have received considerable attention, but these are often evaluated by IC50 value......-on–fast-off mechanism was observed, but the trifluoromethyl ketone compound exhibited differential mechanisms depending on the enzyme isoform. The trifluoromethyl ketone compound displayed a fast-on–fast-off mechanism against class-IIa HDACs 4 and 7, but slow-binding mechanisms against class-I and class-IIb enzymes...

  6. Secondary Psychometric Examination of the Dimensional Obsessive-Compulsive Scale: Classical Testing, Item Response Theory, and Differential Item Functioning.

    Science.gov (United States)

    Thibodeau, Michel A; Leonard, Rachel C; Abramowitz, Jonathan S; Riemann, Bradley C

    2015-12-01

    The Dimensional Obsessive-Compulsive Scale (DOCS) is a promising measure of obsessive-compulsive disorder (OCD) symptoms but has received minimal psychometric attention. We evaluated the utility and reliability of DOCS scores. The study included 832 students and 300 patients with OCD. Confirmatory factor analysis supported the originally proposed four-factor structure. DOCS total and subscale scores exhibited good to excellent internal consistency in both samples (α = .82 to α = .96). Patient DOCS total scores reduced substantially during treatment (t = 16.01, d = 1.02). DOCS total scores discriminated between students and patients (sensitivity = 0.76, 1 - specificity = 0.23). The measure did not exhibit gender-based differential item functioning as tested by Mantel-Haenszel chi-square tests. Expected response options for each item were plotted as a function of item response theory and demonstrated that DOCS scores incrementally discriminate OCD symptoms ranging from low to extremely high severity. Incremental differences in DOCS scores appear to represent unbiased and reliable differences in true OCD symptom severity. © The Author(s) 2014.

  7. You're Just Like Your Dad: Intergenerational Patterns of Differential Treatment of Siblings.

    Science.gov (United States)

    Jensen, Alexander C; Whiteman, Shawn D; Rand, Joseph S; Fingerman, Karen L

    2017-10-01

    Past work highlights that parents' differential treatment has implications for offspring's mental and relational health across the life course. Although the current body of literature has examined offspring- and parent-level correlates of differential treatment, research has yet to consider whether and how patterns of differential treatment are transmitted across generations. As part of a two-wave longitudinal study of 157 families, both grandparents (M age = 76.50 years, SD = 6.20) and parents (M age = 51.10 years, SD = 4.41) reported on differential treatment of their own offspring at both phases. A series of residualized change models revealed support for both continuity and compensation hypotheses. Middle-aged parents tended to model the patterns of differential treatment exhibited by their fathers, but middle-aged men who experienced more differential treatment from their own parents in recent years tended to subsequently exhibit lower levels of differential treatment to their offspring. These findings suggest that patterns of differential treatment both continue and diverge across generations, and those patterns vary by gender. On a broader level, these results also suggest that siblings not only impact one another's development, but in adulthood, they may indirectly influence their nieces' and nephews' development by virtue of their influence on their siblings' parenting. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. The use of (125I) iodocyanopindolol as a specific probe for beta-adrenergic receptors in differentiating cultured rat skeletal muscle

    International Nuclear Information System (INIS)

    Schonberg, Michael; Morris, S.A.; Krichevsky, Alexander; Bilezikian, J.P.

    1983-01-01

    In order to examine more precisely the role of beta-adrenergic receptors in the process of differentiation the new radioligand iodocyanopindolol was used, and found to be a very useful probe to identify beta receptors. Binding charcteristics conformed to those expected for a physiologically relevant beta receptor. L 6 E 9 cells grown in horse serum, which allows differentiation exhibit increased beta receptor density in intact cells as a function of age. In contrast, cells grown in fetal calf serum, which does not allow differentiation, exhibit constant beta receptor density. In broken cells, however, both differentiating and non-differentiating cells show an increase in beta receptors. These results suggest that the process of differentiation is associated with an unmasking of beta receptors which are increasing but cryptic in undifferentiated cells. (author)

  9. Proteomic differences between tellurite-sensitive and tellurite-resistant E.coli.

    Directory of Open Access Journals (Sweden)

    Jana Aradská

    Full Text Available Tellurite containing compounds are in use for industrial processes and increasing delivery into the environment generates specific pollution that may well result in contamination and subsequent potential adverse effects on public health. It was the aim of the current study to reveal mechanism of toxicity in tellurite-sensitive and tellurite-resistant E. coli at the protein level. In this work an approach using gel-based mass spectrometrical analysis to identify a differential protein profile related to tellurite toxicity was used and the mechanism of ter operon-mediated tellurite resistance was addressed. E. coli BL21 was genetically manipulated for tellurite-resistance by the introduction of the resistance-conferring ter genes on the pLK18 plasmid. Potassium tellurite was added to cultures in order to obtain a final 3.9 micromolar concentration. Proteins from tellurite-sensitive and tellurite-resistant E. coli were run on 2-D gel electrophoresis, spots of interest were picked, in-gel digested and subsequently analysed by nano-LC-MS/MS (ion trap. In addition, Western blotting and measurement of enzymatic activity were performed to verify the expression of certain candidate proteins. Following exposure to tellurite, in contrast to tellurite-resistant bacteria, sensitive cells exhibited increased levels of antioxidant enzymes superoxide dismutases, catalase and oxidoreductase YqhD. Cysteine desulfurase, known to be related to tellurite toxicity as well as proteins involved in protein folding: GroEL, DnaK and EF-Tu were upregulated in sensitive cells. In resistant bacteria, several isoforms of four essential Ter proteins were observed and following tellurite treatment the abovementioned protein levels did not show any significant proteome changes as compared to the sensitive control. The absence of general defense mechanisms against tellurite toxicity in resistant bacteria thus provides further evidence that the four proteins of the ter operon

  10. Genetic basis of allochronic differentiation in the fall armyworm

    NARCIS (Netherlands)

    Hänniger, S.; Dumas, P.; Schöfl, G.; Gebauer-Jung, S.; Vogel, H.; Unbehend, M.; Heckel, D.G.; Groot, A.T.

    2017-01-01

    Background: Very little is known on how changes in circadian rhythms evolve. The noctuid moth Spodoptera frugiperda (Lepidoptera: Noctuidae) consists of two strains that exhibit allochronic differentiation in their mating time, which acts as a premating isolation barrier between the strains. We

  11. A delay differential equation model of follicle waves in women.

    Science.gov (United States)

    Panza, Nicole M; Wright, Andrew A; Selgrade, James F

    2016-01-01

    This article presents a mathematical model for hormonal regulation of the menstrual cycle which predicts the occurrence of follicle waves in normally cycling women. Several follicles of ovulatory size that develop sequentially during one menstrual cycle are referred to as follicle waves. The model consists of 13 nonlinear, delay differential equations with 51 parameters. Model simulations exhibit a unique stable periodic cycle and this menstrual cycle accurately approximates blood levels of ovarian and pituitary hormones found in the biological literature. Numerical experiments illustrate that the number of follicle waves corresponds to the number of rises in pituitary follicle stimulating hormone. Modifications of the model equations result in simulations which predict the possibility of two ovulations at different times during the same menstrual cycle and, hence, the occurrence of dizygotic twins via a phenomenon referred to as superfecundation. Sensitive parameters are identified and bifurcations in model behaviour with respect to parameter changes are discussed. Studying follicle waves may be helpful for improving female fertility and for understanding some aspects of female reproductive ageing.

  12. Dual exponential polynomials and linear differential equations

    Science.gov (United States)

    Wen, Zhi-Tao; Gundersen, Gary G.; Heittokangas, Janne

    2018-01-01

    We study linear differential equations with exponential polynomial coefficients, where exactly one coefficient is of order greater than all the others. The main result shows that a nontrivial exponential polynomial solution of such an equation has a certain dual relationship with the maximum order coefficient. Several examples illustrate our results and exhibit possibilities that can occur.

  13. Strain hardening rate sensitivity and strain rate sensitivity in TWIP steels

    Energy Technology Data Exchange (ETDEWEB)

    Bintu, Alexandra [TEMA, Department of Mechanical Engineering, University of Aveiro, Campus Universitário de Santiago, 3810-193 (Portugal); Vincze, Gabriela, E-mail: gvincze@ua.pt [TEMA, Department of Mechanical Engineering, University of Aveiro, Campus Universitário de Santiago, 3810-193 (Portugal); Picu, Catalin R. [Department of Mechanical, Aerospace and Nuclear Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180 (United States); Lopes, Augusto B. [CICECO, Department of Materials and Ceramic Engineering, University of Aveiro, Campus Universitário de Santiago, 3810-193 (Portugal); Grácio, Jose J. [TEMA, Department of Mechanical Engineering, University of Aveiro, Campus Universitário de Santiago, 3810-193 (Portugal); Barlat, Frederic [Materials Mechanics Laboratory, Graduate Institute of Ferrous Technology, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of)

    2015-04-01

    TWIP steels are materials with very high strength and exceptional strain hardening capability, parameters leading to large energy absorption before failure. However, TWIP steels also exhibit reduced (often negative) strain rate sensitivity (SRS) which limits the post-necking deformation. In this study we demonstrate for an austenitic TWIP steel with 18% Mn a strong dependence of the twinning rate on the strain rate, which results in negative strain hardening rate sensitivity (SHRS). The instantaneous component of SHRS is large and negative, while its transient is close to zero. The SRS is observed to decrease with strain, becoming negative for larger strains. Direct observations of the strain rate dependence of the twinning rate are made using electron microscopy and electron backscatter diffraction, which substantiate the proposed mechanism for the observed negative SHRS.

  14. Strain hardening rate sensitivity and strain rate sensitivity in TWIP steels

    International Nuclear Information System (INIS)

    Bintu, Alexandra; Vincze, Gabriela; Picu, Catalin R.; Lopes, Augusto B.; Grácio, Jose J.; Barlat, Frederic

    2015-01-01

    TWIP steels are materials with very high strength and exceptional strain hardening capability, parameters leading to large energy absorption before failure. However, TWIP steels also exhibit reduced (often negative) strain rate sensitivity (SRS) which limits the post-necking deformation. In this study we demonstrate for an austenitic TWIP steel with 18% Mn a strong dependence of the twinning rate on the strain rate, which results in negative strain hardening rate sensitivity (SHRS). The instantaneous component of SHRS is large and negative, while its transient is close to zero. The SRS is observed to decrease with strain, becoming negative for larger strains. Direct observations of the strain rate dependence of the twinning rate are made using electron microscopy and electron backscatter diffraction, which substantiate the proposed mechanism for the observed negative SHRS

  15. Differential pulse voltammetric determination of methyl parathion based on multiwalled carbon nanotubes–poly(acrylamide) nanocomposite film modified electrode

    International Nuclear Information System (INIS)

    Zeng, Yanbo; Yu, Dajun; Yu, Yanyan; Zhou, Tianshu; Shi, Guoyue

    2012-01-01

    Highlights: ► A sensitive electrochemical sensor for detecting methyl parathion in environmental samples. ► The preparation, characterization and application of this novel MWCNTs–PAAM nanocomposite. ► The MWCNTs–PAAM/GCE exhibited a high adsorption and strong affinity toward methyl parathion. ► Wide linear range and low detection limit of the proposed method for detecting methyl parathion. - Abstract: A sensitive electrochemical differential pulse voltammetry method was developed for detecting methyl parathion based on multiwalled carbon nanotubes–poly(acrylamide) (MWCNTs–PAAM) nanocomposite film modified glassy carbon electrode. The novel MWCNTs–PAAM nanocomposite, containing high content of amide groups, was synthesized by PAAM polymerizing at the vinyl group functionalized MWCNTs surface using free radical polymerization. The MWCNTs–PAAM nanocomposite was characterized by Fourier transform infrared spectroscopy, thermal gravimetric analysis and scanning electron microscopy. Electrochemical behavior and interference studies of MWCNTs–PAAM/GCE for methyl parathion were investigated. The experimental results demonstrated that the MWCNTs–PAAM/GCE exhibited a high adsorption and strong affinity toward methyl parathion compared with some metal ions and nitroaromatic compounds, which exist in environmental samples. The adsorbed amount of methyl parathion on the MWCNTs–PAAM/GCE approached the equilibrium value upon 5 min adsorption time. A linear calibration curve for methyl parathion was obtained in the concentration range from 5.0 × 10 −9 to 1.0 × 10 −5 mol L −1 , with a detection limit of 2.0 × 10 −9 mol L −1 . The MWCNTs–PAAM/GCE was proved to be a suitable sensing tool for the fast, sensitive and selective determination of methyl parathion in environmental water samples.

  16. Applications of advances in nonlinear sensitivity analysis

    Energy Technology Data Exchange (ETDEWEB)

    Werbos, P J

    1982-01-01

    The following paper summarizes the major properties and applications of a collection of algorithms involving differentiation and optimization at minimum cost. The areas of application include the sensitivity analysis of models, new work in statistical or econometric estimation, optimization, artificial intelligence and neuron modelling.

  17. Digital differential confocal microscopy based on spatial shift transformation.

    Science.gov (United States)

    Liu, J; Wang, Y; Liu, C; Wilson, T; Wang, H; Tan, J

    2014-11-01

    Differential confocal microscopy is a particularly powerful surface profilometry technique in industrial metrology due to its high axial sensitivity and insensitivity to noise. However, the practical implementation of the technique requires the accurate positioning of point detectors in three-dimensions. We describe a simple alternative based on spatial transformation of a through-focus series of images obtained from a homemade beam scanning confocal microscope. This digital differential confocal microscopy approach is described and compared with the traditional Differential confocal microscopy approach. The ease of use of the digital differential confocal microscopy system is illustrated by performing measurements on a 3D standard specimen. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

  18. Operator overloading as an enabling technology for automatic differentiation

    International Nuclear Information System (INIS)

    Corliss, G.F.; Griewank, A.

    1993-01-01

    We present an example of the science that is enabled by object-oriented programming techniques. Scientific computation often needs derivatives for solving nonlinear systems such as those arising in many PDE algorithms, optimization, parameter identification, stiff ordinary differential equations, or sensitivity analysis. Automatic differentiation computes derivatives accurately and efficiently by applying the chain rule to each arithmetic operation or elementary function. Operator overloading enables the techniques of either the forward or the reverse mode of automatic differentiation to be applied to real-world scientific problems. We illustrate automatic differentiation with an example drawn from a model of unsaturated flow in a porous medium. The problem arises from planning for the long-term storage of radioactive waste

  19. Sensitivity Filters In Topology Optimisation As A Solution To Helmholtz Type Differential Equation

    DEFF Research Database (Denmark)

    Lazarov, Boyan Stefanov; Sigmund, Ole

    2009-01-01

    The focus of the study in this article is on the use of a Helmholtz type differential equation as a filter for topology optimisation problems. Until now various filtering schemes have been utilised in order to impose mesh independence in this type of problems. The usual techniques require topology...... information about the neighbour sub-domains is an expensive operation. The proposed filtering technique requires only mesh information necessary for the finite element discretisation of the problem. The main idea is to define the filtered variable implicitly as a solution of a Helmholtz type differential...... equation with homogeneous Neumann boundary conditions. The properties of the filter are demonstrated for various 2D and 3D topology optimisation problems in linear elasticity, solved on sequential and parallel computers....

  20. Sibship size, sibling cognitive sensitivity, and children's receptive vocabulary.

    Science.gov (United States)

    Prime, Heather; Pauker, Sharon; Plamondon, André; Perlman, Michal; Jenkins, Jennifer

    2014-02-01

    The aim of the current study was to examine the relationship between sibship size and children's vocabulary as a function of quality of sibling interactions. It was hypothesized that coming from a larger sibship (ie, 3+ children) would be related to lower receptive vocabulary in children. However, we expected this association to be moderated by the level of cognitive sensitivity shown by children's next-in-age older siblings. Data on 385 children (mean age = 3.15 years) and their next-in-age older siblings (mean age = 5.57 years) were collected and included demographic questionnaires, direct testing of children's receptive vocabulary, and videos of mother-child and sibling interactions. Sibling dyads were taped engaging in a cooperative building task and tapes were coded for the amount of cognitive sensitivity the older sibling exhibited toward the younger sibling. Hierarchical regression analyses were conducted and showed an interaction between sibship size and sibling cognitive sensitivity in the prediction of children's receptive vocabulary; children exposed to large sibships whose next-in-age older sibling exhibited higher levels of cognitive sensitivity were less likely to show low vocabulary skills when compared with those children exposed to large sibships whose siblings showed lower levels of cognitive sensitivity. Children who show sensitivity to the cognitive needs of their younger siblings provide a rich environment for language development. The negative impact of large sibships on language development is moderated by the presence of an older sibling who shows high cognitive sensitivity.

  1. Religious beliefs are factual beliefs: Content does not correlate with context sensitivity.

    Science.gov (United States)

    Levy, Neil

    2017-04-01

    Neil Van Leeuwen argues that religious beliefs are not factual beliefs: typically, at least, they are attitudes of a different type. He argues that they exhibit much more sensitivity to context than factual beliefs: outside of contexts in which they are salient, they do not govern behaviour or inference, or provide background assumptions for cognition. This article surveys a large range of data to show that the kind of context sensitivity that Van Leeuwen thinks is the province of religious beliefs does not correlate with belief content. Beliefs about matters of fact beyond the theological realm exhibit this kind of sensitivity too. Conversely, theological and supernatural beliefs often guide behaviour across contexts. It is the intuitiveness of representations across contexts that predicts context (in)sensitivity, and intuitiveness is powerfully influenced by processing fluency. Fluency, in turn, is sensitive to cues that vary across contexts. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Absolute Position Sensing Based on a Robust Differential Capacitive Sensor with a Grounded Shield Window

    Directory of Open Access Journals (Sweden)

    Yang Bai

    2016-05-01

    Full Text Available A simple differential capacitive sensor is provided in this paper to measure the absolute positions of length measuring systems. By utilizing a shield window inside the differential capacitor, the measurement range and linearity range of the sensor can reach several millimeters. What is more interesting is that this differential capacitive sensor is only sensitive to one translational degree of freedom (DOF movement, and immune to the vibration along the other two translational DOFs. In the experiment, we used a novel circuit based on an AC capacitance bridge to directly measure the differential capacitance value. The experimental result shows that this differential capacitive sensor has a sensitivity of 2 × 10−4 pF/μm with 0.08 μm resolution. The measurement range of this differential capacitive sensor is 6 mm, and the linearity error are less than 0.01% over the whole absolute position measurement range.

  3. Binaural sensitivity changes between cortical on and off responses

    Science.gov (United States)

    Dahmen, Johannes C.; King, Andrew J.; Schnupp, Jan W. H.

    2011-01-01

    Neurons exhibiting on and off responses with different frequency tuning have previously been described in the primary auditory cortex (A1) of anesthetized and awake animals, but it is unknown whether other tuning properties, including sensitivity to binaural localization cues, also differ between on and off responses. We measured the sensitivity of A1 neurons in anesthetized ferrets to 1) interaural level differences (ILDs), using unmodulated broadband noise with varying ILDs and average binaural levels, and 2) interaural time delays (ITDs), using sinusoidally amplitude-modulated broadband noise with varying envelope ITDs. We also assessed fine-structure ITD sensitivity and frequency tuning, using pure-tone stimuli. Neurons most commonly responded to stimulus onset only, but purely off responses and on-off responses were also recorded. Of the units exhibiting significant binaural sensitivity nearly one-quarter showed binaural sensitivity in both on and off responses, but in almost all (∼97%) of these units the binaural tuning of the on responses differed significantly from that seen in the off responses. Moreover, averaged, normalized ILD and ITD tuning curves calculated from all units showing significant sensitivity to binaural cues indicated that on and off responses displayed different sensitivity patterns across the population. A principal component analysis of ITD response functions suggested a continuous cortical distribution of binaural sensitivity, rather than discrete response classes. Rather than reflecting a release from inhibition without any functional significance, we propose that binaural off responses may be important to cortical encoding of sound-source location. PMID:21562191

  4. Gene expression underlying enhanced, steroid-dependent auditory sensitivity of hair cell epithelium in a vocal fish.

    Science.gov (United States)

    Fergus, Daniel J; Feng, Ni Y; Bass, Andrew H

    2015-10-14

    Successful animal communication depends on a receiver's ability to detect a sender's signal. Exemplars of adaptive sender-receiver coupling include acoustic communication, often important in the context of seasonal reproduction. During the reproductive summer season, both male and female midshipman fish (Porichthys notatus) exhibit similar increases in the steroid-dependent frequency sensitivity of the saccule, the main auditory division of the inner ear. This form of auditory plasticity enhances detection of the higher frequency components of the multi-harmonic, long-duration advertisement calls produced repetitively by males during summer nights of peak vocal and spawning activity. The molecular basis of this seasonal auditory plasticity has not been fully resolved. Here, we utilize an unbiased transcriptomic RNA sequencing approach to identify differentially expressed transcripts within the saccule's hair cell epithelium of reproductive summer and non-reproductive winter fish. We assembled 74,027 unique transcripts from our saccular epithelial sequence reads. Of these, 6.4 % and 3.0 % were upregulated in the reproductive and non-reproductive saccular epithelium, respectively. Gene ontology (GO) term enrichment analyses of the differentially expressed transcripts showed that the reproductive saccular epithelium was transcriptionally, translationally, and metabolically more active than the non-reproductive epithelium. Furthermore, the expression of a specific suite of candidate genes, including ion channels and components of steroid-signaling pathways, was upregulated in the reproductive compared to the non-reproductive saccular epithelium. We found reported auditory functions for 14 candidate genes upregulated in the reproductive midshipman saccular epithelium, 8 of which are enriched in mouse hair cells, validating their hair cell-specific functions across vertebrates. We identified a suite of differentially expressed genes belonging to neurotransmission and

  5. Interfacing of differential-capacitive biomimetic hair flow-sensors for optimal sensitivity

    International Nuclear Information System (INIS)

    + Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" data-affiliation=" (Transducers Science and Technology Group, MESA+ Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" >Dagamseh, A M K; + Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" data-affiliation=" (Transducers Science and Technology Group, MESA+ Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" >Bruinink, C M; + Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" data-affiliation=" (Transducers Science and Technology Group, MESA+ Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" >Wiegerink, R J; + Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" data-affiliation=" (Transducers Science and Technology Group, MESA+ Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" >Lammerink, T S J; + Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" data-affiliation=" (Transducers Science and Technology Group, MESA+ Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" >Droogendijk, H; + Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" data-affiliation=" (Transducers Science and Technology Group, MESA+ Research Institute, University of Twente, PO Box 217, 7500 AE Enschede (Netherlands))" >Krijnen, G J M

    2013-01-01

    Biologically inspired sensor-designs are investigated as a possible path to surpass the performance of more traditionally engineered designs. Inspired by crickets, artificial hair sensors have shown the ability to detect minute flow signals. This paper addresses developments in the design, fabrication, interfacing and characterization of biomimetic hair flow-sensors towards sensitive high-density arrays. Improvement of the electrode design of the hair sensors has resulted in a reduction of the smallest hair movements that can be measured. In comparison to the arrayed hairs-sensor design, the detection-limit was arguably improved at least twelve-fold, down to 1 mm s –1 airflow amplitude at 250 Hz as measured in a bandwidth of 3 kHz. The directivity pattern closely resembles a figure-of-eight. These sensitive hair-sensors open possibilities for high-resolution spatio-temporal flow pattern observations. (paper)

  6. Adaptive Epigenetic Differentiation between Upland and Lowland Rice Ecotypes Revealed by Methylation-Sensitive Amplified Polymorphism

    OpenAIRE

    Xia, Hui; Huang, Weixia; Xiong, Jie; Tao, Tao; Zheng, Xiaoguo; Wei, Haibin; Yue, Yunxia; Chen, Liang; Luo, Lijun

    2016-01-01

    The stress-induced epimutations could be inherited over generations and play important roles in plant adaption to stressful environments. Upland rice has been domesticated in water-limited environments for thousands of years and accumulated drought-induced epimutations of DNA methylation, making it epigenetically differentiated from lowland rice. To study the epigenetic differentiation between upland and lowland rice ecotypes on their drought-resistances, the epigenetic variation was investig...

  7. Electrodermal responses during appetitive conditioning are sensitive to contingency instruction ambiguity.

    Science.gov (United States)

    van den Akker, Karolien; Nederkoorn, Chantal; Jansen, Anita

    2017-08-01

    Studies on human appetitive conditioning using food rewards can benefit from including psychophysiological outcome measures. The present study tested whether the skin conductance response can function as a measure of differential responding in an appetitive conditioning paradigm including an acquisition and extinction phase, and examined which time window during a trial is most sensitive to conditioning effects. As a secondary aim, the effects of ambiguous vs. non-ambiguous contingency instructions on conditioned responses (skin conductance responses, US expectancies, chocolate desires, and CS evaluations) were assessed. Results indicated differential skin conductance responses in an anticipatory time window and during unexpected omission of the US in early extinction. Interestingly however, anticipatory responses were only found for participants who received ambiguous contingency instructions - possibly indicating a call for additional processing resources in response to the ambiguous CS+. Further, ambiguous instructions slowed the extinction of US expectancies but did not influence chocolate desires and CS evaluations. It is concluded that skin conductance can function as a sensitive measure of differential responding in appetitive conditioning, though its sensitivity might depend on the specific task context. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Greenhouse Earth: A Traveling Exhibition

    International Nuclear Information System (INIS)

    Booth, W.H.; Caesar, S.

    1992-09-01

    The Franklin Institute Science Museum provided an exhibit entitled the Greenhouse Earth: A Traveling Exhibition. This 3500 square-foot exhibit on global climate change was developed in collaboration with the Association of Science-Technology Centers. The exhibit opened at The Franklin Institute on February 14, 1992, welcoming 291,000 visitors over its three-month stay. During its three-year tour, Greenhouse Earth will travel to ten US cities, reaching two million visitors. Greenhouse Earth aims to deepen public understanding of the scientific issues of global warming and the conservation measures that can be taken to slow its effects. The exhibit features hands-on exhibitry, interactive computer programs and videos, a theater production, a ''demonstration cart,'' guided tours, and lectures. supplemental educational programs at the Institute included a teachers preview, a symposium on climate change, and a ''satellite field trip.'' The development of Greenhouse Earth included front-end and formative evaluation procedures. Evaluation includes interviews with visitors, prototypes, and summative surveys for participating museums. During its stay in Philadelphia, Greenhouse Earth was covered by the local and national press, with reviews in print and broadcast media. Greenhouse Earth is the first large-scale museum exhibit to address global climate change

  9. Differential effects of Rhodiola rosea on regulatory T cell differentiation and interferon‑γ production in vitro and in vivo.

    Science.gov (United States)

    Xu, Xi; Li, Pingping; Zhang, Peng; Chu, Ming; Liu, Hongju; Chen, Xiaoping; Ge, Qing

    2016-07-01

    Rhodiola rosea (R. rosea), a type of adaptogen, has been previously reported to exhibit immunostimulating activity in rodents and in human peripheral blood mononuclear cells (PBMCs) in vitro. To examine the effect of R. rosea on T cells under simulated microgravity, spaceflight analogs of human head‑down bed rest (HDBR) at ‑6˚ and murine hind limb unloading (HU) were used. A decrease in the levels of interferon‑γ (IFN‑γ) and interleukin‑17 (IL‑17) and an increase in regulatory T (Treg) cells were observed in the placebo group following HDBR. The R. rosea treated HBDR group demonstrated further decreased IFN‑γ production, however, R. rosea exhibited no effect on the ratio of circulating Tregs or Treg cell differentiation. By contrast, the treatment of R. rosea on human T cells in vitro did not alter IFN‑γ secretion, however, Treg differentiation was significantly reduced. An R. rosea‑induced upregulation of hypoxia‑inducible factor 1α (HIF‑1α) contributed to the suppression of Treg differentiation in vitro. Differences in the effect of R. rosea in vitro and in vivo were also observed using a mouse model of microgravity. The results of the current study suggest that R. rosea has differential modulatory effects on T cells in vivo and in vitro and care should be taken when evaluating the effects of R. rosea on the immune system.

  10. Marker evaluation for differentiation of blood and menstrual fluid by methylation-sensitive SNaPshot analysis.

    Science.gov (United States)

    Holtkötter, Hannah; Schwender, Kristina; Wiegand, Peter; Pfeiffer, Heidi; Vennemann, Marielle

    2018-03-01

    The differentiation of blood and menstrual fluid is especially important in cases of alleged sexual assault. While the identification of blood is relatively straightforward, the identification of menstrual fluid in trace evidence has been shown to be more challenging. This may be due to the complex nature of menstrual fluid that leads to intra- and inter-individual differences in composition. Nevertheless, recent advances in DNA methylation profiling have revealed promising markers for the differentiation of the two body fluids and furthermore, markers to distinguish menstrual fluid from vaginal fluid. A literature study was performed and in total, 11 markers were evaluated in this study of which seven could be validated for menstrual fluid and blood identification purposes. Marker "BLU2" (chr16:29757334) was identified as most suitable for differentiation of blood and menstrual fluid.

  11. Perturbative methods applied for sensitive coefficients calculations in thermal-hydraulic systems

    International Nuclear Information System (INIS)

    Andrade Lima, F.R. de

    1993-01-01

    The differential formalism and the Generalized Perturbation Theory (GPT) are applied to sensitivity analysis of thermal-hydraulics problems related to pressurized water reactor cores. The equations describing the thermal-hydraulic behavior of these reactors cores, used in COBRA-IV-I code, are conveniently written. The importance function related to the response of interest and the sensitivity coefficient of this response with respect to various selected parameters are obtained by using Differential and Generalized Perturbation Theory. The comparison among the results obtained with the application of these perturbative methods and those obtained directly with the model developed in COBRA-IV-I code shows a very good agreement. (author)

  12. Cytological diagnostic clues in poorly differentiated squamous cell carcinomas of the breast: Streaming arrangement, necrotic background, nucleolar enlargement and cannibalism of cancer cells.

    Science.gov (United States)

    Kinoshita, M; Matsuda, Y; Arai, T; Soejima, Y; Sawabe, M; Honma, N

    2018-02-01

    Squamous cell carcinoma (SCC) is a rare histological type of breast cancer. The cytological diagnosis of non-keratinising, poorly differentiated SCC is often difficult, and distinguishing it from invasive ductal carcinoma or apocrine carcinoma (AC) is especially challenging. We aimed to define the diagnostic cytological features of poorly differentiated SCC of the breast. We studied the cytological findings of poorly differentiated SCC (n=10) and compared them to those of IDC (n=15) and AC (n=14). The following six cytological features were evaluated: streaming arrangement, nucleolar enlargement, dense nuclei, cannibalism, atypical keratinocytes and necrotic background. SCC exhibited significantly higher frequencies of streaming arrangement (70% vs 6.7%, P=.002), nucleolar enlargement (80% vs 27%, P=.02), and necrotic background (80% vs 36%, P=.002) than invasive ductal carcinoma. The detection of two or three of these features yielded a higher sensitivity (80%) and specificity (93%) for the diagnosis of SCC. Streaming arrangement (70% vs 0%, Pstreaming arrangement, a necrotic background, nucleolar enlargement and cannibalism are useful indicators for the diagnosis of SCC of the breast. As such, greater attention should be paid to these morphological features in daily clinical practice. © 2017 John Wiley & Sons Ltd.

  13. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    Encounters Hanne Blitz From February 1st to 12th 2016 CERN Meyrin, Main Building What is our reaction to a first encounter with a tourist attraction? Contemporary Dutch painter Hanne Blitz captures visitors' responses to art and architecture, sweeping vistas and symbolic memorials. Encounters, a series of oil paintings curated specially for this CERN exhibition, depicts tourists visiting cultural highlights around the world. A thought-provoking journey not to be missed, and a tip of the hat to CERN's large Hadron Collider.

  14. Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy

    Science.gov (United States)

    Miller-Delaney, Suzanne F.C.; Bryan, Kenneth; Das, Sudipto; McKiernan, Ross C.; Bray, Isabella M.; Reynolds, James P.; Gwinn, Ryder; Stallings, Raymond L.

    2015-01-01

    Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain. PMID

  15. Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.

    Science.gov (United States)

    Ding, Xiaofeng; Zhou, Xixi; Cooper, Karen L; Huestis, Juliana; Hudson, Laurie G; Liu, Ke Jian

    2017-09-15

    Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)-induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA). In this study, we investigated the difference in response to arsenite exposure between XPA and PARP-1, and the differential effectiveness of zinc supplementation in restoring protein DNA binding and DNA damage repair. Arsenite targeted both XPA and PARP-1 in human keratinocytes, resulting in zinc loss from each protein and a pronounced decrease in XPA and PARP-1 binding to chromatin as demonstrated by Chip-on-Western assays. Zinc effectively restored DNA binding of PARP-1 and XPA to chromatin when zinc concentrations were equal to those of arsenite. In contrast, zinc was more effective in rescuing arsenite-augmented direct UVR-induced DNA damage than oxidative DNA damage. Taken together, our findings indicate that arsenite interferes with PARP-1 and XPA binding to chromatin, and that zinc supplementation fully restores DNA binding activity to both proteins in the cellular context. Interestingly, rescue of arsenite-inhibited DNA damage repair by supplemental zinc was more sensitive for DNA damage repaired by the XPA-associated NER pathway than for the PARP-1-dependent BER pathway. This study expands our understanding of arsenite's role in DNA repair inhibition and co-carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Using Network-Based Language Analysis to Bridge Expertise and Cultivate Sensitivity to Differentiated Language Use in Interdisciplinary Geoscience Research

    Science.gov (United States)

    Hannah, M. A.; Simeone, M.

    2017-12-01

    sensitivity to subdisciplinary colleagues by making visible the nuanced ways they use language to organize and communicate their research. Ultimately, understanding the impact of differentiated language use is an unmet need in Earth science research, and our method offers a unique way to visualize and understand how such use impacts team communication.

  17. Sensory Processing Sensitivity as a Marker of Differential Susceptibility to Parenting

    Science.gov (United States)

    Slagt, Meike; Dubas, Judith Semon; van Aken, Marcel A. G.; Ellis, Bruce J.; Dekovic, Maja

    2018-01-01

    In this longitudinal multiinformant study negative emotionality and sensory processing sensitivity were compared as susceptibility markers among kindergartners. Participating children (N = 264, 52.9% boys) were Dutch kindergartners (M[subscript age] = 4.77, SD = 0.60), followed across three waves, spaced seven months apart. Results show that…

  18. Variational analysis and generalized differentiation I basic theory

    CERN Document Server

    Mordukhovich, Boris S

    2006-01-01

    Contains a study of the basic concepts and principles of variational analysis and generalized differentiation in both finite-dimensional and infinite-dimensional spaces. This title presents many applications to problems in optimization, equilibria, stability and sensitivity, control theory, economics, mechanics, and more.

  19. The MAPKK FgMkk1 of Fusarium graminearum regulates vegetative differentiation, multiple stress response, and virulence via the cell wall integrity and high-osmolarity glycerol signaling pathways.

    Science.gov (United States)

    Yun, Yingzi; Liu, Zunyong; Zhang, Jingze; Shim, Won-Bo; Chen, Yun; Ma, Zhonghua

    2014-07-01

    Mitogen-activated protein (MAP) kinases play crucial roles in regulating fungal development, growth and pathogenicity, and in responses to the environment. In this study, we characterized a MAP kinase kinase FgMkk1 in Fusarium graminearum, the causal agent of wheat head blight. Phenotypic analyses of the FgMKK1 mutant (ΔFgMKK1) showed that FgMkk1 is involved in the regulation of hyphal growth, pigmentation, conidiation, deoxynivalenol biosynthesis and virulence of F. graminearum. ΔFgMKK1 also showed increased sensitivity to cell wall-damaging agents, and to osmotic and oxidative stresses, but exhibited decreased sensitivity to the fungicides iprodione and fludioxonil. In addition, the mutant revealed increased sensitivity to a biocontrol agent, Trichoderma atroviride. Western blot assays revealed that FgMkk1 positively regulates phosphorylation of the MAP kinases Mgv1 and FgOs-2, the key component in the cell wall integrity (CWI) and high-osmolarity glycerol (HOG) signalling pathway respectively. Yeast two-hybrid assay indicated that Mgv1 interacts with a transcription factor FgRlm1. The FgRLM1 mutant (ΔFgRLM1) showed increased sensitivity to cell wall-damaging agents and exhibited decreased virulence. Taken together, our data indicated that FgMkk1 is an upstream component of Mgv1, and regulates vegetative differentiation, multiple stress response and virulence via the CWI and HOG signalling pathways. FgRlm1 may be a downstream component of Mgv1 in the CWI pathway in F. graminearum. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. Investigating Design Research Landscapes through Exhibition

    DEFF Research Database (Denmark)

    Jönsson, Li; Hansen, Flemming Tvede; Mäkelä, Maarit

    2013-01-01

    What characterizes a design research exhibition compared to a traditional design and art exhibition? How do you show the very materialities of the design experiments as a means for communicating knowledge of research and of practice? How do you present, review and utilize such an exhibition......? With those questions in mind, the intention and challenge for the Nordes 2013 Design Research Exhibition was to expand on current notions of staging research enquires in design research conference contexts. Artefacts, installations, performances, and other materialities that relate to the theme...... of the conference - Experiments in Design Research – were displayed as tools to express and communicate different design research enquires. Through this paper we will describe the Nordes exhibition as a specific case that renders questions visible in relation to how to utilize a design research exhibition...

  1. Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells.

    Science.gov (United States)

    Ma, Jiao; Lu, Pin; Guo, Ailin; Cheng, Shuhua; Zong, Hongliang; Martin, Peter; Coleman, Morton; Wang, Y Lynn

    2014-09-01

    Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one-third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach. © 2014 John Wiley & Sons Ltd.

  2. Technical and clinical performance of a new assay to detect squamous cell carcinoma antigen levels for the differential diagnosis of cervical, lung, and head and neck cancer.

    Science.gov (United States)

    Holdenrieder, Stefan; Molina, Rafael; Qiu, Ling; Zhi, Xiuyi; Rutz, Sandra; Engel, Christine; Kasper-Sauer, Pia; Dayyani, Farshid; Korse, Catharina M

    2018-04-01

    under the curve: 86.3%; 95% confidence interval: 81.2-91.3; sensitivity: 61.4%; specificity: 95.0%), and other cervical cancers (n = 157; area under the curve: 78.9%; 95% confidence interval: 70.8-87.1; sensitivity: 61.4%; specificity: 86.7%). Squamous cell carcinoma may also aid in the differential diagnosis of lung cancer. The Elecsys squamous cell carcinoma assay exhibited good technical performance and is suitable for differential diagnosis of cervical squamous cell carcinoma in clinical practice.

  3. Highly sensitive determination of atropine using cobalt oxide nanostructures: Influence of functional groups on the signal sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Soomro, Razium Ali, E-mail: raziumsoomro@gmail.com [Interface Analysis Centre, School of Physics, University of Bristol, Bristol, BS8 1TL (United Kingdom); National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080 (Pakistan); Nafady, Ayman [Department of Chemistry, College of Science, King Saud University, Riyadh (Saudi Arabia); Department of Chemistry, Faculty of Science, Sohag University, Sohag (Egypt); Hallam, Keith Richard [Interface Analysis Centre, School of Physics, University of Bristol, Bristol, BS8 1TL (United Kingdom); Jawaid, Sana [National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080 (Pakistan); Al Enizi, Abdullah [Department of Chemistry, College of Science, King Saud University, Riyadh (Saudi Arabia); Sherazi, Syed Tufail Hussain; Sirajuddin [National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080 (Pakistan); Ibupoto, Zafar Hussain [Dr M.A. Kazi Institute of Chemistry, University of Sindh, Jamshoro, 76080 (Pakistan); Willander, Magnus [Department of Science and Technology, Campus Norrkoping, Linkoping University, SE-60174, Norrkoping (Sweden)

    2016-12-15

    This study describes sensitive determination of atropine using glassy carbon electrodes (GCE) modified with Co{sub 3}O{sub 4} nanostructures. The as-synthesised nanostructures were grown using cysteine (CYS), glutathione (GSH) and histidine (HYS) as effective templates under hydrothermal action. The obtained morphologies revealed interesting structural features, including both cavity-based and flower-shaped structures. The as-synthesised morphologies were noted to actively participate in electro-catalysis of atropine (AT) drug where GSH-assisted structures exhibited the best signal response in terms of current density and over-potential value. The study also discusses the influence of functional groups on the signal sensitivity of atropine electro-oxidation. The functionalisation was carried with the amino acids originally used as effective templates for the growth of Co{sub 3}O{sub 4} nanostructures. The highest increment was obtained when GSH was used as the surface functionalising agent. The GSH-functionalised Co{sub 3}O{sub 4}-modified electrode was utilised for the electro-chemical sensing of AT in a concentration range of 0.01–0.46 μM. The developed sensor exhibited excellent working linearity (R{sup 2} = 0.999) and signal sensitivity up to 0.001 μM of AT. The noted high sensitivity of the sensor is associated with the synergy of superb surface architectures and favourable interaction facilitating the electron transfer kinetics for the electro-catalytic oxidation of AT. Significantly, the developed sensor demonstrated excellent working capability when used for AT detection in human urine samples with strong anti-interference potential against common co-existing species, such as glucose, fructose, cysteine, uric acid, dopamine and ascorbic acid. - Highlights: • Template-assisted growth of Co{sub 3}O{sub 4} nanostructures. • Shape-dependent electro-catalysis of atropine. • Effect of functionalisation of signal sensitivity.

  4. Sigmoid stenosis caused by diverticulitis vs. carcinoma: usefulness of sonographic features for their differentiation in the emergency setting.

    Science.gov (United States)

    Ripollés, Tomás; Martínez-Pérez, María Jesús; Gómez Valencia, Diana Patricia; Vizuete, José; Martín, Gregorio

    2015-10-01

    To retrospectively evaluate the accuracy of ultrasound as a diagnostic method for differentiating acute diverticulitis from colon cancer in patients with sigmoid colon stenosis. Ultrasound examinations of 91 consecutive patients with sigmoid stenosis (50 diverticulitis and 41 colon cancers) were reviewed by two trained radiologists. Sixty-five (71%) patients presented with acute abdominal symptoms. Thirteen sonographic criteria retrieved from the literature were evaluated to differentiate benign from malignant strictures. A score including all parameters which showed significant differences between benign vs. malignant was built. Sensitivity, specificity, accuracy, and positive or negative predictive values of each sonographic sign, the overall diagnosis, and sonographic score were calculated. Loss of the bowel wall stratification was the most reliable criteria for the diagnosis of malignancy (92% and 94% of sensitivity and specificity, respectively), and the best inter-radiologist agreement (κ = 0.848). Adjacent lymph nodes were the most specific feature (98%) for colon cancer, but its sensitivity was low. Global assessment could differentiate both diseases with high sensitivity (92-94.9%) and specificity (98-100%). Sonographic score >3 enabled differentiation of carcinoma from diverticulitis with 95% sensitivity and 92-94% specificity, with an area under the ROC curve of 0.98-0.987. There were no significant differences in the results between patients with acute and nonacute abdominal symptoms. The combination of several morphological sonographic findings using a score can differentiate most cases of diverticulitis from colon carcinoma in sigmoid strictures.

  5. Thyroid Ultrasonography in Differentiation between Graves' Disease and Hashimoto's Thyroiditis.

    Science.gov (United States)

    Pishdad, P; Pishdad, G R; Tavanaa, S; Pishdad, R; Jalli, R

    2017-03-01

    Graves' disease and Hashimoto's thyroiditis are the most common causes of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases, if the patient is euthyroid, may sometimes be extremely difficult on the basis of clinical and laboratory findings. The purpose of this study was to determine the sensitivity and specificity of gray scale sonography in differentiation of Graves' disease from Hashimoto's thyroiditis. This study included 149 patients divided into three groups, patients with Graves' disease (34 patients, mean age = 36.8 ± 10.17 years), Patients with Hashimoto's thyroiditis (62 patients, mean age = 33.4 ± 12.16 years) and control group (53 healthy people, mean age = 34.74 ± 16.87 years). Members of all groups were referred to a single radiologist for thyroid sonography for evaluation of thyroid echogenicity pattern. A total of 117 women and 32 men were examined by sonography. The most common sonographic pattern in Hashimoto and Graves' was homogenous hypo-echogenicity which was observed in 45.2% and 47.1% of cases, respectively. Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto's group with 100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was observed in 17.6% of Graves' group with 100% and 17.6% specificity and sensitivity, respectively. Our findings indicate that sonography has high specificity but low sensitivity in the diagnosis of either Graves' disease or Hashimoto's thyroiditis. It is therefore not possible to differentiate between these two diseases using sonography alone. Confirmation by laboratory data is also needed.

  6. A mini-exhibition with maximum content

    CERN Multimedia

    Laëtitia Pedroso

    2011-01-01

    The University of Budapest has been hosting a CERN mini-exhibition since 8 May. While smaller than the main travelling exhibition it has a number of major advantages: its compact design alleviates transport difficulties and makes it easier to find suitable venues in the Member States. Its content can be updated almost instantaneously and it will become even more interactive and high-tech as time goes by.   The exhibition on display in Budapest. The purpose of CERN's new mini-exhibition is to be more interactive and easier to install. Due to its size, the main travelling exhibition cannot be moved around quickly, which is why it stays in the same country for 4 to 6 months. But this means a long waiting list for the other Member States. To solve this problem, the Education Group has designed a new exhibition, which is smaller and thus easier to install. Smaller maybe, but no less rich in content, as the new exhibition conveys exactly the same messages as its larger counterpart. However, in the slimm...

  7. New computer-aided diagnosis of dementia using positron emission tomography: brain regional sensitivity-mapping method.

    Directory of Open Access Journals (Sweden)

    Akihiro Kakimoto

    Full Text Available PURPOSE: We devised a new computer-aided diagnosis method to segregate dementia using one estimated index (Total Z score derived from the Brodmann area (BA sensitivity map on the stereotaxic brain atlas. The purpose of this study is to investigate its accuracy to differentiate patients with Alzheimer's disease (AD or mild cognitive impairment (MCI from normal adults (NL. METHODS: We studied 101 adults (NL: 40, AD: 37, MCI: 24 who underwent (18FDG positron emission tomography (PET measurement. We divided NL and AD groups into two categories: a training group with (Category A and a test group without (Category B clinical information. In Category A, we estimated sensitivity by comparing the standard uptake value per BA (SUVR between NL and AD groups. Then, we calculated a summated index (Total Z score by utilizing the sensitivity-distribution maps and each BA z-score to segregate AD patterns. To confirm the validity of this method, we examined the accuracy in Category B. Finally, we applied this method to MCI patients. RESULTS: In Category A, we found that the sensitivity and specificity of differentiation between NL and AD were all 100%. In Category B, those were 100% and 95%, respectively. Furthermore, we found this method attained 88% to differentiate AD-converters from non-converters in MCI group. CONCLUSIONS: The present automated computer-aided evaluation method based on a single estimated index provided good accuracy for differential diagnosis of AD and MCI. This good differentiation power suggests its usefulness not only for dementia diagnosis but also in a longitudinal study.

  8. New Computer-Aided Diagnosis of Dementia Using Positron Emission Tomography: Brain Regional Sensitivity-Mapping Method

    Science.gov (United States)

    Kakimoto, Akihiro; Kamekawa, Yuichi; Ito, Shigeru; Yoshikawa, Etsuji; Okada, Hiroyuki; Nishizawa, Sadahiko; Minoshima, Satoshi; Ouchi, Yasuomi

    2011-01-01

    Purpose We devised a new computer-aided diagnosis method to segregate dementia using one estimated index (Total Z score) derived from the Brodmann area (BA) sensitivity map on the stereotaxic brain atlas. The purpose of this study is to investigate its accuracy to differentiate patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) from normal adults (NL). Methods We studied 101 adults (NL: 40, AD: 37, MCI: 24) who underwent 18FDG positron emission tomography (PET) measurement. We divided NL and AD groups into two categories: a training group with (Category A) and a test group without (Category B) clinical information. In Category A, we estimated sensitivity by comparing the standard uptake value per BA (SUVR) between NL and AD groups. Then, we calculated a summated index (Total Z score) by utilizing the sensitivity-distribution maps and each BA z-score to segregate AD patterns. To confirm the validity of this method, we examined the accuracy in Category B. Finally, we applied this method to MCI patients. Results In Category A, we found that the sensitivity and specificity of differentiation between NL and AD were all 100%. In Category B, those were 100% and 95%, respectively. Furthermore, we found this method attained 88% to differentiate AD-converters from non-converters in MCI group. Conclusions The present automated computer-aided evaluation method based on a single estimated index provided good accuracy for differential diagnosis of AD and MCI. This good differentiation power suggests its usefulness not only for dementia diagnosis but also in a longitudinal study. PMID:21966405

  9. Differential pulse voltammetric determination of methyl parathion based on multiwalled carbon nanotubes-poly(acrylamide) nanocomposite film modified electrode

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Yanbo [Department of Chemistry and Shanghai Key Laboratory of Green Chemistry and Chemical Process, East China Normal University, 3663 Zhongshan Road(N), Shanghai, 200062 (China); College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314001 (China); Yu, Dajun; Yu, Yanyan [Department of Chemistry and Shanghai Key Laboratory of Green Chemistry and Chemical Process, East China Normal University, 3663 Zhongshan Road(N), Shanghai, 200062 (China); Zhou, Tianshu [Department of Environmental Science, East China Normal University, 3663 Zhongshan Road(N), Shanghai, 200062 (China); Shi, Guoyue, E-mail: gyshi@chem.ecnu.edu.cn [Department of Chemistry and Shanghai Key Laboratory of Green Chemistry and Chemical Process, East China Normal University, 3663 Zhongshan Road(N), Shanghai, 200062 (China)

    2012-05-30

    Highlights: Black-Right-Pointing-Pointer A sensitive electrochemical sensor for detecting methyl parathion in environmental samples. Black-Right-Pointing-Pointer The preparation, characterization and application of this novel MWCNTs-PAAM nanocomposite. Black-Right-Pointing-Pointer The MWCNTs-PAAM/GCE exhibited a high adsorption and strong affinity toward methyl parathion. Black-Right-Pointing-Pointer Wide linear range and low detection limit of the proposed method for detecting methyl parathion. - Abstract: A sensitive electrochemical differential pulse voltammetry method was developed for detecting methyl parathion based on multiwalled carbon nanotubes-poly(acrylamide) (MWCNTs-PAAM) nanocomposite film modified glassy carbon electrode. The novel MWCNTs-PAAM nanocomposite, containing high content of amide groups, was synthesized by PAAM polymerizing at the vinyl group functionalized MWCNTs surface using free radical polymerization. The MWCNTs-PAAM nanocomposite was characterized by Fourier transform infrared spectroscopy, thermal gravimetric analysis and scanning electron microscopy. Electrochemical behavior and interference studies of MWCNTs-PAAM/GCE for methyl parathion were investigated. The experimental results demonstrated that the MWCNTs-PAAM/GCE exhibited a high adsorption and strong affinity toward methyl parathion compared with some metal ions and nitroaromatic compounds, which exist in environmental samples. The adsorbed amount of methyl parathion on the MWCNTs-PAAM/GCE approached the equilibrium value upon 5 min adsorption time. A linear calibration curve for methyl parathion was obtained in the concentration range from 5.0 Multiplication-Sign 10{sup -9} to 1.0 Multiplication-Sign 10{sup -5} mol L{sup -1}, with a detection limit of 2.0 Multiplication-Sign 10{sup -9} mol L{sup -1}. The MWCNTs-PAAM/GCE was proved to be a suitable sensing tool for the fast, sensitive and selective determination of methyl parathion in environmental water samples.

  10. Investigation on nickel ferrite nanowire device exhibiting negative differential resistance — a first-principles investigation

    Directory of Open Access Journals (Sweden)

    V. Nagarajan

    2017-06-01

    Full Text Available The electronic property of NiFe_2O_4 nanowire device is investigated through nonequilibrium Green’s functions (NEGF in combination with density functional theory (DFT. The electronic transport properties of NiFe_2O_4 nanowire are studied in terms of density of states, transmission spectrum and I–V characteristics. The density of states gets modified with the applied bias voltage across NiFe_2O_4 nanowire device, the density of charge is observed both in the valence band and in the conduction band on increasing the bias voltage. The transmission spectrum of NiFe_2O_4 nanowire device gives the insights on the transition of electrons at different energy intervals. The findings of the present work suggest that NiFe_2O_4 nanowire device can be used as negative differential resistance (NDR device and its NDR property can be tuned with the bias voltage, which may be used in microwave device, memory devices and in fast switching devices.

  11. Familial melanoma associated with dominant ultraviolet radiation sensitivity

    International Nuclear Information System (INIS)

    Ramsay, R.G.; Chen, P.; Imray, F.P.; Kidson, C.; Lavin, M.F.; Hockey, A.

    1982-01-01

    Sensitivity to ultraviolet radiation was studied in lymphoblastoid cell lines derived from 32 members of two families with histories of multiple primary melanomas in several generations. As assayed by colony formation in agar or by trypan blue exclusion following irradiation, cellular sensitivity showed a bimodal distribution. All persons with melanoma or multiple moles were in the sensitive group, while some family members exhibited responses similar to those of controls. Cells from four cases of sporadic melanoma showed normal levels of sensitivity. The data are consistent with a dominantly inherited ultraviolet light sensitivity associated with these examples of familial melanoma. Spontaneous and ultraviolet light-induced sister chromatid exchange frequencies were similar to those in control cell lines. No defect in excision repair was detected in any of the above cell lines, but the sensitive group showed postirradiation inhibition of DNA replication intermediate between controls and an excision-deficient xeroderma pigmentosum cell line

  12. Small-molecule compounds exhibiting target-mediated drug disposition - A case example of ABT-384.

    Science.gov (United States)

    An, Guohua; Liu, Wei; Dutta, Sandeep

    2015-10-01

    Nonlinearities are frequently encountered in pharmacokinetics, and they can occur when 1 or more processes of absorption, distribution, metabolism, and excretion are saturable. One special source of nonlinearity that has been noticed recently is the saturable binding of the drug to a high-affinity-low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Although TMDD can occur in both small-molecule compounds and large-molecule compounds, the latter has received much more attention because of its high prevalence. With the development of more potent small-molecule drugs acting on highly specific targets and the availability of increasingly sensitive analytical techniques, small-molecule compounds exhibiting TMDD have been increasingly reported in the past several years. ABT-384 is a small-molecule drug candidate that exhibited significant nonlinear pharmacokinetics, potentially imparted by TMDD, in a first-in-human clinical trial conducted in healthy volunteers. Compared with published small-molecule compounds exhibiting TMDD, ABT-384 pharmacokinetic characteristics are more consistent with TMDD. To expand current knowledge of TMDD of small-molecule compounds and increase awareness of this interesting and clinically important phenomenon, in this review the general features of small-molecule compounds exhibiting TMDD are highlighted, with ABT-384 provided as an example. © 2015, The American College of Clinical Pharmacology.

  13. Negative differential electrolyte resistance in a solid-state nanopore resulting from electroosmotic flow bistability.

    Science.gov (United States)

    Luo, Long; Holden, Deric A; White, Henry S

    2014-03-25

    A solid-state nanopore separating two aqueous solutions containing different concentrations of KCl is demonstrated to exhibit negative differential resistance (NDR) when a constant pressure is applied across the nanopore. NDR refers to a decrease in electrical current when the voltage applied across the nanopore is increased. NDR results from the interdependence of solution flow (electroosmotic and pressure-engendered) with the distributions of K+ and Cl- within the nanopore. A switch from a high-conductivity state to a low-conductivity state occurs over a very narrow voltage window (flow, yielding a true bistability in fluid flow and electrical current at a critical applied voltage, i.e., the NDR "switching potential". Solution pH and Ca2+ were separately employed as chemical stimuli to investigate the dependence of the NDR on the surface charge density. The NDR switching potential is remarkably sensitive to the surface charge density, and thus to pH and the presence of Ca2+, suggesting possible applications in chemical sensing.

  14. Sensitivity Enhancement of FBG-Based Strain Sensor.

    Science.gov (United States)

    Li, Ruiya; Chen, Yiyang; Tan, Yuegang; Zhou, Zude; Li, Tianliang; Mao, Jian

    2018-05-17

    A novel fiber Bragg grating (FBG)-based strain sensor with a high-sensitivity is presented in this paper. The proposed FBG-based strain sensor enhances sensitivity by pasting the FBG on a substrate with a lever structure. This typical mechanical configuration mechanically amplifies the strain of the FBG to enhance overall sensitivity. As this mechanical configuration has a high stiffness, the proposed sensor can achieve a high resonant frequency and a wide dynamic working range. The sensing principle is presented, and the corresponding theoretical model is derived and validated. Experimental results demonstrate that the developed FBG-based strain sensor achieves an enhanced strain sensitivity of 6.2 pm/με, which is consistent with the theoretical analysis result. The strain sensitivity of the developed sensor is 5.2 times of the strain sensitivity of a bare fiber Bragg grating strain sensor. The dynamic characteristics of this sensor are investigated through the finite element method (FEM) and experimental tests. The developed sensor exhibits an excellent strain-sensitivity-enhancing property in a wide frequency range. The proposed high-sensitivity FBG-based strain sensor can be used for small-amplitude micro-strain measurement in harsh industrial environments.

  15. Smokers exhibit biased neural processing of smoking and affective images.

    Science.gov (United States)

    Oliver, Jason A; Jentink, Kade G; Drobes, David J; Evans, David E

    2016-08-01

    There has been growing interest in the role that implicit processing of drug cues can play in motivating drug use behavior. However, the extent to which drug cue processing biases relate to the processing biases exhibited to other types of evocative stimuli is largely unknown. The goal of the present study was to determine how the implicit cognitive processing of smoking cues relates to the processing of affective cues using a novel paradigm. Smokers (n = 50) and nonsmokers (n = 38) completed a picture-viewing task, in which participants were presented with a series of smoking, pleasant, unpleasant, and neutral images while engaging in a distractor task designed to direct controlled resources away from conscious processing of image content. Electroencephalogram recordings were obtained throughout the task for extraction of event-related potentials (ERPs). Smokers exhibited differential processing of smoking cues across 3 different ERP indices compared with nonsmokers. Comparable effects were found for pleasant cues on 2 of these indices. Late cognitive processing of smoking and pleasant cues was associated with nicotine dependence and cigarette use. Results suggest that cognitive biases may extend across classes of stimuli among smokers. This raises important questions about the fundamental meaning of cognitive biases, and suggests the need to consider generalized cognitive biases in theories of drug use behavior and interventions based on cognitive bias modification. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  16. Myofilament Calcium Sensitivity: Mechanistic Insight into TnI Ser-23/24 and Ser-150 Phosphorylation Integration

    Directory of Open Access Journals (Sweden)

    Hussam E Salhi

    2016-12-01

    Full Text Available Troponin I (TnI is a major regulator of cardiac muscle contraction and relaxation. During physiological and pathological stress, TnI is differentially phosphorylated at multiple residues through different signaling pathways to match cardiac function to demand. The combination of these TnI phosphorylations can exhibit an expected or unexpected functional integration, whereby the function of two phosphorylations are different than that predicted from the combined function of each individual phosphorylation alone. We have shown that TnI Ser-23/24 and Ser-150 phosphorylation exhibit functional integration and are simultaneously increased in response to cardiac stress. In the current study, we investigated the functional integration of TnI Ser-23/24 and Ser-150 to alter cardiac contraction. We hypothesized that Ser-23/24 and Ser-150 phosphorylation each utilize distinct molecular mechanisms to alter the TnI binding affinity within the thin filament. Mathematical modeling predicts that Ser-23/24 and Ser-150 phosphorylation affect different TnI affinities within the thin filament to distinctly alter the Ca2+-binding properties of troponin. Protein binding experiments validate this assertion by demonstrating pseudo-phosphorylated Ser-150 decreases the affinity of isolated TnI for actin, whereas Ser-23/24 pseudo-phosphorylation is not different from unphosphorylated. Thus, our data supports that TnI Ser-23/24 affects TnI-TnC binding, while Ser-150 phosphorylation alters TnI-actin binding. By measuring force development in troponin-exchanged skinned myocytes, we demonstrate that the Ca2+ sensitivity of force is directly related to the amount of phosphate present on TnI. Furthermore, we demonstrate that Ser-150 pseudo-phosphorylation blunts Ser-23/24-mediated decreased Ca2+-sensitive force development whether on the same or different TnI molecule. Therefore, TnI phosphorylations can integrate across troponins along the myofilament. These data demonstrate

  17. Vantage sensitivity: individual differences in response to positive experiences.

    Science.gov (United States)

    Pluess, Michael; Belsky, Jay

    2013-07-01

    The notion that some people are more vulnerable to adversity as a function of inherent risk characteristics is widely embraced in most fields of psychology. This is reflected in the popularity of the diathesis-stress framework, which has received a vast amount of empirical support over the years. Much less effort has been directed toward the investigation of endogenous factors associated with variability in response to positive influences. One reason for the failure to investigate individual differences in response to positive experiences as a function of endogenous factors may be the absence of adequate theoretical frameworks. According to the differential-susceptibility hypothesis, individuals generally vary in their developmental plasticity regardless of whether they are exposed to negative or positive influences--a notion derived from evolutionary reasoning. On the basis of this now well-supported proposition, we advance herein the new concept of vantage sensitivity, reflecting variation in response to exclusively positive experiences as a function of individual endogenous characteristics. After distinguishing vantage sensitivity from theoretically related concepts of differential-susceptibility and resilience, we review some recent empirical evidence for vantage sensitivity featuring behavioral, physiological, and genetic factors as moderators of a wide range of positive experiences ranging from family environment and psychotherapy to educational intervention. Thereafter, we discuss genetic and environmental factors contributing to individual differences in vantage sensitivity, potential mechanisms underlying vantage sensitivity, and practical implications. 2013 APA, all rights reserved

  18. Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?

    Science.gov (United States)

    Lubbers, Ellen R; List, Edward O; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D; Kineman, Rhonda D; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J; Berryman, Darlene E

    2013-03-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying that the effects of GH on adiponectin are depot specific. Interestingly, rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity.

  19. Dynamics of partial differential equations

    CERN Document Server

    Wayne, C Eugene

    2015-01-01

    This book contains two review articles on the dynamics of partial differential equations that deal with closely related topics but can be read independently. Wayne reviews recent results on the global dynamics of the two-dimensional Navier-Stokes equations. This system exhibits stable vortex solutions: the topic of Wayne's contribution is how solutions that start from arbitrary initial conditions evolve towards stable vortices. Weinstein considers the dynamics of localized states in nonlinear Schrodinger and Gross-Pitaevskii equations that describe many optical and quantum systems. In this contribution, Weinstein reviews recent bifurcations results of solitary waves, their linear and nonlinear stability properties, and results about radiation damping where waves lose energy through radiation.   The articles, written independently, are combined into one volume to showcase the tools of dynamical systems theory at work in explaining qualitative phenomena associated with two classes of partial differential equ...

  20. Characterization of Chlamydia MurC-Ddl, a fusion protein exhibiting D-alanyl-D-alanine ligase activity involved in peptidoglycan synthesis and D-cycloserine sensitivity.

    Science.gov (United States)

    McCoy, Andrea J; Maurelli, Anthony T

    2005-07-01

    Recent characterization of chlamydial genes encoding functional peptidoglycan (PG)-synthesis proteins suggests that the Chlamydiaceae possess the ability to synthesize PG yet biochemical evidence for the synthesis of PG has yet to be demonstrated. The presence of D-amino acids in PG is a hallmark of bacteria. Chlamydiaceae do not appear to encode amino acid racemases however, a D-alanyl-D-alanine (D-Ala-D-Ala) ligase homologue (Ddl) is encoded in the genome. Thus, we undertook a genetics-based approach to demonstrate and characterize the D-Ala-D-Ala ligase activity of chlamydial Ddl, a protein encoded as a fusion with MurC. The full-length murC-ddl fusion gene from Chlamydia trachomatis serovar L2 was cloned and placed under the control of the arabinose-inducible ara promoter and transformed into a D-Ala-D-Ala ligase auxotroph of Escherichia coli possessing deletions of both the ddlA and ddlB genes. Viability of the E. coliDeltaddlADeltaddlB mutant in the absence of exogenous D-Ala-D-Ala dipeptide became dependent on the expression of the chlamydial murC-ddl thus demonstrating functional ligase activity. Domain mapping of the full-length fusion protein and site-directed mutagenesis of the MurC domain revealed that the structure of the full fusion protein but not MurC enzymatic activity was required for ligase activity in vivo. Recombinant MurC-Ddl exhibited substrate specificity for D-Ala. Chlamydia growth is inhibited by D-cycloserine (DCS) and in vitro analysis provided evidence for the chlamydial MurC-Ddl as the target for DCS sensitivity. In vivo sensitivity to DCS could be reversed by addition of exogenous D-Ala and D-Ala-D-Ala. Together, these findings further support our hypothesis that PG is synthesized by members of the Chlamydiaceae family and suggest that D-amino acids, specifically D-Ala, are present in chlamydial PG.

  1. Vantage Sensitivity: Environmental Sensitivity to Positive Experiences as a Function of Genetic Differences.

    Science.gov (United States)

    Pluess, Michael

    2017-02-01

    A large number of gene-environment interaction studies provide evidence that some people are more likely to be negatively affected by adverse experiences as a function of specific genetic variants. However, such "risk" variants are surprisingly frequent in the population. Evolutionary analysis suggests that genetic variants associated with increased risk for maladaptive development under adverse environmental conditions are maintained in the population because they are also associated with advantages in response to different contextual conditions. These advantages may include (a) coexisting genetic resilience pertaining to other adverse influences, (b) a general genetic susceptibility to both low and high environmental quality, and (c) a coexisting propensity to benefit disproportionately from positive and supportive exposures, as reflected in the recent framework of vantage sensitivity. After introducing the basic properties of vantage sensitivity and highlighting conceptual similarities and differences with diathesis-stress and differential susceptibility patterns of gene-environment interaction, selected and recent empirical evidence for the notion of vantage sensitivity as a function of genetic differences is reviewed. The unique contribution that the new perspective of vantage sensitivity may make to our understanding of social inequality will be discussed after suggesting neurocognitive and molecular mechanisms hypothesized to underlie the propensity to benefit disproportionately from benevolent experiences. © 2015 Wiley Periodicals, Inc.

  2. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction.

    Science.gov (United States)

    Kirk, Erik; Reeds, Dominic N; Finck, Brian N; Mayurranjan, S Mitra; Mayurranjan, Mitra S; Patterson, Bruce W; Klein, Samuel

    2009-05-01

    We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate (HC) diet or a low-carbohydrate (LC) diet on hepatic and skeletal muscle insulin sensitivity. Twenty-two obese subjects (body mass index, 36.5 +/- 0.8 kg/m2) were randomized to an HC (>180 g/day) or LC (vs 8.9% +/- 1.4%; P vs 7.2% +/- 1.4%; P vs 7.9% +/- 1.2%; P < .05). Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7% weight loss (48.4% +/- 14.3%; P < .05). In both groups, insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29% +/- 13% and phosphorylation of Akt and insulin receptor substrate 1 increased by 35% +/- 9% and 36% +/- 9%, respectively, after 7% weight loss (all P < .05). Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 hours of calorie restriction affects the liver (IHTG content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

  3. Sensitivity and uncertainty analyses for performance assessment modeling

    International Nuclear Information System (INIS)

    Doctor, P.G.

    1988-08-01

    Sensitivity and uncertainty analyses methods for computer models are being applied in performance assessment modeling in the geologic high level radioactive waste repository program. The models used in performance assessment tend to be complex physical/chemical models with large numbers of input variables. There are two basic approaches to sensitivity and uncertainty analyses: deterministic and statistical. The deterministic approach to sensitivity analysis involves numerical calculation or employs the adjoint form of a partial differential equation to compute partial derivatives; the uncertainty analysis is based on Taylor series expansions of the input variables propagated through the model to compute means and variances of the output variable. The statistical approach to sensitivity analysis involves a response surface approximation to the model with the sensitivity coefficients calculated from the response surface parameters; the uncertainty analysis is based on simulation. The methods each have strengths and weaknesses. 44 refs

  4. Am80 induces neuronal differentiation via increased tropomyosin-related kinase B expression in a human neuroblastoma SH-SY5Y cell line.

    Science.gov (United States)

    Shiohira, Hideo; Kitaoka, Akira; Enjoji, Munechika; Uno, Tsukasa; Nakashima, Manabu

    2012-01-01

    Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.

  5. On the existence of weak solutions of quantum stochastic differential ...

    African Journals Online (AJOL)

    We establish further results concerning the existence, uniqueness and stability of weak solutions of quantum stochastic differential equations (QSDEs). Our results are achieved by considering a more general Lipschit condition on the coefficients than our previous considerations in [1]. We exhibit a class of Lipschitzian ...

  6. Vendor Testing of Sensitive Compounds in Simulated Dry Sludge

    International Nuclear Information System (INIS)

    Dworjanyn, L.O.

    1999-01-01

    This assessment covers thermal screening, differential scanning calorimetry, and impact sensitivity testing on Mercury Fulminate, and mixtures of the fulminate in dry inorganic sludge, which is present in large quantities in a number of storage tanks at Westinghouse Savannah River

  7. Measurement of differential cross sections of isolated-photon plus heavy-flavour jet production in pp collisions at √{ s } = 8 TeV using the ATLAS detector

    Science.gov (United States)

    Aaboud, M.; Aad, G.; Abbott, B.; Abdinov, O.; Abeloos, B.; Abidi, S. H.; Abouzeid, O. S.; Abraham, N. L.; Abramowicz, H.; Abreu, H.; Abreu, R.; Abulaiti, Y.; Acharya, B. S.; Adachi, S.; Adamczyk, L.; Adelman, J.; Adersberger, M.; Adye, T.; Affolder, A. A.; Afik, Y.; Agheorghiesei, C.; Aguilar-Saavedra, J. A.; Ahlen, S. P.; Ahmadov, F.; Aielli, G.; Akatsuka, S.; Akerstedt, H.; Åkesson, T. P. A.; Akilli, E.; Akimov, A. V.; Alberghi, G. L.; Albert, J.; Albicocco, P.; Alconada Verzini, M. J.; Alderweireldt, S. C.; Aleksa, M.; Aleksandrov, I. N.; Alexa, C.; Alexander, G.; Alexopoulos, T.; Alhroob, M.; Ali, B.; Aliev, M.; Alimonti, G.; Alison, J.; Alkire, S. P.; Allbrooke, B. M. M.; Allen, B. W.; Allport, P. P.; Aloisio, A.; Alonso, A.; Alonso, F.; Alpigiani, C.; Alshehri, A. A.; Alstaty, M. I.; Alvarez Gonzalez, B.; Álvarez Piqueras, D.; Alviggi, M. G.; Amadio, B. T.; Amaral Coutinho, Y.; Amelung, C.; Amidei, D.; Amor Dos Santos, S. P.; Amoroso, S.; Anastopoulos, C.; Ancu, L. S.; Andari, N.; Andeen, T.; Anders, C. F.; Anders, J. K.; Anderson, K. J.; Andreazza, A.; Andrei, V.; Angelidakis, S.; Angelozzi, I.; Angerami, A.; Anisenkov, A. V.; Anjos, N.; Annovi, A.; Antel, C.; Antonelli, M.; Antonov, A.; Antrim, D. J.; Anulli, F.; Aoki, M.; Aperio Bella, L.; Arabidze, G.; Arai, Y.; Araque, J. P.; Araujo Ferraz, V.; Arce, A. T. H.; Ardell, R. E.; Arduh, F. A.; Arguin, J.-F.; Argyropoulos, S.; Arik, M.; Armbruster, A. J.; Armitage, L. J.; Arnaez, O.; Arnold, H.; Arratia, M.; Arslan, O.; Artamonov, A.; Artoni, G.; Artz, S.; Asai, S.; Asbah, N.; Ashkenazi, A.; Asquith, L.; Assamagan, K.; Astalos, R.; Atkinson, M.; Atlay, N. B.; Augsten, K.; Avolio, G.; Axen, B.; Ayoub, M. K.; Azuelos, G.; Baas, A. E.; Baca, M. J.; Bachacou, H.; Bachas, K.; Backes, M.; Bagnaia, P.; Bahmani, M.; Bahrasemani, H.; Baines, J. T.; Bajic, M.; Baker, O. K.; Bakker, P. J.; Baldin, E. M.; Balek, P.; Balli, F.; Balunas, W. K.; Banas, E.; Bandyopadhyay, A.; Banerjee, Sw.; Bannoura, A. A. E.; Barak, L.; Barberio, E. L.; Barberis, D.; Barbero, M.; Barillari, T.; Barisits, M.-S.; Barkeloo, J. T.; Barklow, T.; Barlow, N.; Barnes, S. L.; Barnett, B. M.; Barnett, R. M.; Barnovska-Blenessy, Z.; Baroncelli, A.; Barone, G.; Barr, A. J.; Barranco Navarro, L.; Barreiro, F.; Barreiro Guimarães da Costa, J.; Bartoldus, R.; Barton, A. E.; Bartos, P.; Basalaev, A.; Bassalat, A.; Bates, R. L.; Batista, S. J.; Batley, J. R.; Battaglia, M.; Bauce, M.; Bauer, F.; Bauer, K. T.; Bawa, H. S.; Beacham, J. B.; Beattie, M. D.; Beau, T.; Beauchemin, P. H.; Bechtle, P.; Beck, H. P.; Beck, H. C.; Becker, K.; Becker, M.; Becot, C.; Beddall, A. J.; Beddall, A.; Bednyakov, V. A.; Bedognetti, M.; Bee, C. P.; Beermann, T. A.; Begalli, M.; Begel, M.; Behr, J. K.; Bell, A. S.; Bella, G.; Bellagamba, L.; Bellerive, A.; Bellomo, M.; Belotskiy, K.; Beltramello, O.; Belyaev, N. L.; Benary, O.; Benchekroun, D.; Bender, M.; Benekos, N.; Benhammou, Y.; Benhar Noccioli, E.; Benitez, J.; Benjamin, D. P.; Benoit, M.; Bensinger, J. R.; Bentvelsen, S.; Beresford, L.; Beretta, M.; Berge, D.; Bergeaas Kuutmann, E.; Berger, N.; Bergsten, L. J.; Beringer, J.; Berlendis, S.; Bernard, N. R.; Bernardi, G.; Bernius, C.; Bernlochner, F. U.; Berry, T.; Berta, P.; Bertella, C.; Bertoli, G.; Bertram, I. A.; Bertsche, C.; Besjes, G. J.; Bessidskaia Bylund, O.; Bessner, M.; Besson, N.; Bethani, A.; Bethke, S.; Betti, A.; Bevan, A. J.; Beyer, J.; Bianchi, R. M.; Biebel, O.; Biedermann, D.; Bielski, R.; Bierwagen, K.; Biesuz, N. V.; Biglietti, M.; Billoud, T. R. V.; Bilokon, H.; Bindi, M.; Bingul, A.; Bini, C.; Biondi, S.; Bisanz, T.; Bittrich, C.; Bjergaard, D. M.; Black, J. E.; Black, K. M.; Blair, R. E.; Blazek, T.; Bloch, I.; Blocker, C.; Blue, A.; Blumenschein, U.; Blunier, S.; Bobbink, G. J.; Bobrovnikov, V. S.; Bocchetta, S. S.; Bocci, A.; Bock, C.; Boehler, M.; Boerner, D.; Bogavac, D.; Bogdanchikov, A. G.; Bohm, C.; Boisvert, V.; Bokan, P.; Bold, T.; Boldyrev, A. S.; Bolz, A. E.; Bomben, M.; Bona, M.; Boonekamp, M.; Borisov, A.; Borissov, G.; Bortfeldt, J.; Bortoletto, D.; Bortolotto, V.; Boscherini, D.; Bosman, M.; Bossio Sola, J. D.; Boudreau, J.; Bouhova-Thacker, E. V.; Boumediene, D.; Bourdarios, C.; Boutle, S. K.; Boveia, A.; Boyd, J.; Boyko, I. R.; Bozson, A. J.; Bracinik, J.; Brandt, A.; Brandt, G.; Brandt, O.; Braren, F.; Bratzler, U.; Brau, B.; Brau, J. E.; Breaden Madden, W. D.; Brendlinger, K.; Brennan, A. J.; Brenner, L.; Brenner, R.; Bressler, S.; Briglin, D. L.; Bristow, T. M.; Britton, D.; Britzger, D.; Brochu, F. M.; Brock, I.; Brock, R.; Brooijmans, G.; Brooks, T.; Brooks, W. K.; Brost, E.; Broughton, J. H.; Bruckman de Renstrom, P. A.; Bruncko, D.; Bruni, A.; Bruni, G.; Bruni, L. S.; Bruno, S.; Brunt, Bh; Bruschi, M.; Bruscino, N.; Bryant, P.; Bryngemark, L.; Buanes, T.; Buat, Q.; Buchholz, P.; Buckley, A. G.; Budagov, I. A.; Buehrer, F.; Bugge, M. K.; Bulekov, O.; Bullock, D.; Burch, T. J.; Burdin, S.; Burgard, C. D.; Burger, A. M.; Burghgrave, B.; Burka, K.; Burke, S.; Burmeister, I.; Burr, J. T. P.; Büscher, D.; Büscher, V.; Bussey, P.; Butler, J. M.; Buttar, C. M.; Butterworth, J. M.; Butti, P.; Buttinger, W.; Buzatu, A.; Buzykaev, A. R.; Changqiao, C.-Q.; Cabrera Urbán, S.; Caforio, D.; Cai, H.; Cairo, V. M.; Cakir, O.; Calace, N.; Calafiura, P.; Calandri, A.; Calderini, G.; Calfayan, P.; Callea, G.; Caloba, L. P.; Calvente Lopez, S.; Calvet, D.; Calvet, S.; Calvet, T. P.; Camacho Toro, R.; Camarda, S.; Camarri, P.; Cameron, D.; Caminal Armadans, R.; Camincher, C.; Campana, S.; Campanelli, M.; Camplani, A.; Campoverde, A.; Canale, V.; Cano Bret, M.; Cantero, J.; Cao, T.; Capeans Garrido, M. D. M.; Caprini, I.; Caprini, M.; Capua, M.; Carbone, R. M.; Cardarelli, R.; Cardillo, F.; Carli, I.; Carli, T.; Carlino, G.; Carlson, B. T.; Carminati, L.; Carney, R. M. D.; Caron, S.; Carquin, E.; Carrá, S.; Carrillo-Montoya, G. D.; Casadei, D.; Casado, M. P.; Casha, A. F.; Casolino, M.; Casper, D. W.; Castelijn, R.; Castillo Gimenez, V.; Castro, N. F.; Catinaccio, A.; Catmore, J. R.; Cattai, A.; Caudron, J.; Cavaliere, V.; Cavallaro, E.; Cavalli, D.; Cavalli-Sforza, M.; Cavasinni, V.; Celebi, E.; Ceradini, F.; Cerda Alberich, L.; Cerqueira, A. S.; Cerri, A.; Cerrito, L.; Cerutti, F.; Cervelli, A.; Cetin, S. A.; Chafaq, A.; Chakraborty, D.; Chan, S. K.; Chan, W. S.; Chan, Y. L.; Chang, P.; Chapman, J. D.; Charlton, D. G.; Chau, C. C.; Chavez Barajas, C. A.; Che, S.; Cheatham, S.; Chegwidden, A.; Chekanov, S.; Chekulaev, S. V.; Chelkov, G. A.; Chelstowska, M. A.; Chen, C.; Chen, C.; Chen, H.; Chen, J.; Chen, S.; Chen, S.; Chen, X.; Chen, Y.; Cheng, H. C.; Cheng, H. J.; Cheplakov, A.; Cheremushkina, E.; Cherkaoui El Moursli, R.; Cheu, E.; Cheung, K.; Chevalier, L.; Chiarella, V.; Chiarelli, G.; Chiodini, G.; Chisholm, A. S.; Chitan, A.; Chiu, Y. H.; Chizhov, M. V.; Choi, K.; Chomont, A. R.; Chouridou, S.; Chow, Y. S.; Christodoulou, V.; Chu, M. C.; Chudoba, J.; Chuinard, A. J.; Chwastowski, J. J.; Chytka, L.; Ciftci, A. K.; Cinca, D.; Cindro, V.; Cioara, I. A.; Ciocio, A.; Cirotto, F.; Citron, Z. H.; Citterio, M.; Ciubancan, M.; Clark, A.; Clark, M. R.; Clark, P. J.; Clarke, R. N.; Clement, C.; Coadou, Y.; Cobal, M.; Coccaro, A.; Cochran, J.; Colasurdo, L.; Cole, B.; Colijn, A. P.; Collot, J.; Colombo, T.; Conde Muiño, P.; Coniavitis, E.; Connell, S. H.; Connelly, I. A.; Constantinescu, S.; Conti, G.; Conventi, F.; Cooke, M.; Cooper-Sarkar, A. M.; Cormier, F.; Cormier, K. J. R.; Corradi, M.; Corrigan, E. E.; Corriveau, F.; Cortes-Gonzalez, A.; Costa, G.; Costa, M. J.; Costanzo, D.; Cottin, G.; Cowan, G.; Cox, B. E.; Cranmer, K.; Crawley, S. J.; Creager, R. A.; Cree, G.; Crépé-Renaudin, S.; Crescioli, F.; Cribbs, W. A.; Cristinziani, M.; Croft, V.; Crosetti, G.; Cueto, A.; Cuhadar Donszelmann, T.; Cukierman, A. R.; Cummings, J.; Curatolo, M.; Cúth, J.; Czekierda, S.; Czodrowski, P.; D'Amen, G.; D'Auria, S.; D'Eramo, L.; D'Onofrio, M.; da Cunha Sargedas de Sousa, M. J.; da Via, C.; Dabrowski, W.; Dado, T.; Dai, T.; Dale, O.; Dallaire, F.; Dallapiccola, C.; Dam, M.; Dandoy, J. R.; Daneri, M. F.; Dang, N. P.; Daniells, A. C.; Dann, N. S.; Danninger, M.; Dano Hoffmann, M.; Dao, V.; Darbo, G.; Darmora, S.; Dassoulas, J.; Dattagupta, A.; Daubney, T.; Davey, W.; David, C.; Davidek, T.; Davis, D. R.; Davison, P.; Dawe, E.; Dawson, I.; de, K.; de Asmundis, R.; de Benedetti, A.; de Castro, S.; de Cecco, S.; de Groot, N.; de Jong, P.; de la Torre, H.; de Lorenzi, F.; de Maria, A.; de Pedis, D.; de Salvo, A.; de Sanctis, U.; de Santo, A.; de Vasconcelos Corga, K.; de Vivie de Regie, J. B.; Debbe, R.; Debenedetti, C.; Dedovich, D. V.; Dehghanian, N.; Deigaard, I.; Del Gaudio, M.; Del Peso, J.; Delgove, D.; Deliot, F.; Delitzsch, C. M.; Dell'Acqua, A.; Dell'Asta, L.; Dell'Orso, M.; Della Pietra, M.; Della Volpe, D.; Delmastro, M.; Delporte, C.; Delsart, P. A.; Demarco, D. A.; Demers, S.; Demichev, M.; Demilly, A.; Denisov, S. P.; Denysiuk, D.; Derendarz, D.; Derkaoui, J. E.; Derue, F.; Dervan, P.; Desch, K.; Deterre, C.; Dette, K.; Devesa, M. R.; Deviveiros, P. O.; Dewhurst, A.; Dhaliwal, S.; di Bello, F. A.; di Ciaccio, A.; di Ciaccio, L.; di Clemente, W. K.; di Donato, C.; di Girolamo, A.; di Girolamo, B.; di Micco, B.; di Nardo, R.; di Petrillo, K. F.; di Simone, A.; di Sipio, R.; di Valentino, D.; Diaconu, C.; Diamond, M.; Dias, F. A.; Diaz, M. A.; Dickinson, J.; Diehl, E. B.; Dietrich, J.; Díez Cornell, S.; Dimitrievska, A.; Dingfelder, J.; Dita, P.; Dita, S.; Dittus, F.; Djama, F.; Djobava, T.; Djuvsland, J. I.; Do Vale, M. A. B.; Dobre, M.; Dodsworth, D.; Doglioni, C.; Dolejsi, J.; Dolezal, Z.; Donadelli, M.; Donati, S.; Donini, J.; Dopke, J.; Doria, A.; Dova, M. T.; Doyle, A. T.; Drechsler, E.; Dris, M.; Du, Y.; Duarte-Campderros, J.; Dubinin, F.; Dubreuil, A.; Duchovni, E.; Duckeck, G.; Ducourthial, A.; Ducu, O. A.; Duda, D.; Dudarev, A.; Chr. Dudder, A.; Duffield, E. M.; Duflot, L.; Dührssen, M.; Dulsen, C.; Dumancic, M.; Dumitriu, A. E.; Duncan, A. K.; Dunford, M.; Duperrin, A.; Duran Yildiz, H.; Düren, M.; Durglishvili, A.; Duschinger, D.; Dutta, B.; Duvnjak, D.; Dyndal, M.; Dziedzic, B. S.; Eckardt, C.; Ecker, K. M.; Edgar, R. C.; Eifert, T.; Eigen, G.; Einsweiler, K.; Ekelof, T.; El Kacimi, M.; El Kosseifi, R.; Ellajosyula, V.; Ellert, M.; Elles, S.; Ellinghaus, F.; Elliot, A. A.; Ellis, N.; Elmsheuser, J.; Elsing, M.; Emeliyanov, D.; Enari, Y.; Ennis, J. S.; Epland, M. B.; Erdmann, J.; Ereditato, A.; Ernst, M.; Errede, S.; Escalier, M.; Escobar, C.; Esposito, B.; Estrada Pastor, O.; Etienvre, A. I.; Etzion, E.; Evans, H.; Ezhilov, A.; Ezzi, M.; Fabbri, F.; Fabbri, L.; Fabiani, V.; Facini, G.; Fakhrutdinov, R. M.; Falciano, S.; Falla, R. J.; Faltova, J.; Fang, Y.; Fanti, M.; Farbin, A.; Farilla, A.; Farina, E. M.; Farooque, T.; Farrell, S.; Farrington, S. M.; Farthouat, P.; Fassi, F.; Fassnacht, P.; Fassouliotis, D.; Faucci Giannelli, M.; Favareto, A.; Fawcett, W. J.; Fayard, L.; Fedin, O. L.; Fedorko, W.; Feigl, S.; Feligioni, L.; Feng, C.; Feng, E. J.; Feng, M.; Fenton, M. J.; Fenyuk, A. B.; Feremenga, L.; Fernandez Martinez, P.; Ferrando, J.; Ferrari, A.; Ferrari, P.; Ferrari, R.; Ferreira de Lima, D. E.; Ferrer, A.; Ferrere, D.; Ferretti, C.; Fiedler, F.; Filipčič, A.; Filipuzzi, M.; Filthaut, F.; Fincke-Keeler, M.; Finelli, K. D.; Fiolhais, M. C. N.; Fiorini, L.; Fischer, A.; Fischer, C.; Fischer, J.; Fisher, W. C.; Flaschel, N.; Fleck, I.; Fleischmann, P.; Fletcher, R. R. M.; Flick, T.; Flierl, B. M.; Flores Castillo, L. R.; Flowerdew, M. J.; Forcolin, G. T.; Formica, A.; Förster, F. A.; Forti, A.; Foster, A. G.; Fournier, D.; Fox, H.; Fracchia, S.; Francavilla, P.; Franchini, M.; Franchino, S.; Francis, D.; Franconi, L.; Franklin, M.; Frate, M.; Fraternali, M.; Freeborn, D.; Fressard-Batraneanu, S. M.; Freund, B.; Froidevaux, D.; Frost, J. A.; Fukunaga, C.; Fusayasu, T.; Fuster, J.; Gabizon, O.; Gabrielli, A.; Gabrielli, A.; Gach, G. P.; Gadatsch, S.; Gadomski, S.; Gagliardi, G.; Gagnon, L. G.; Galea, C.; Galhardo, B.; Gallas, E. J.; Gallop, B. J.; Gallus, P.; Galster, G.; Gan, K. K.; Ganguly, S.; Gao, Y.; Gao, Y. S.; Garay Walls, F. M.; García, C.; García Navarro, J. E.; García Pascual, J. A.; Garcia-Sciveres, M.; Gardner, R. W.; Garelli, N.; Garonne, V.; Gascon Bravo, A.; Gasnikova, K.; Gatti, C.; Gaudiello, A.; Gaudio, G.; Gavrilenko, I. L.; Gay, C.; Gaycken, G.; Gazis, E. N.; Gee, C. N. P.; Geisen, J.; Geisen, M.; Geisler, M. P.; Gellerstedt, K.; Gemme, C.; Genest, M. H.; Geng, C.; Gentile, S.; Gentsos, C.; George, S.; Gerbaudo, D.; Geßner, G.; Ghasemi, S.; Ghneimat, M.; Giacobbe, B.; Giagu, S.; Giangiacomi, N.; Giannetti, P.; Gibson, S. M.; Gignac, M.; Gilchriese, M.; Gillberg, D.; Gilles, G.; Gingrich, D. M.; Giordani, M. P.; Giorgi, F. M.; Giraud, P. F.; Giromini, P.; Giugliarelli, G.; Giugni, D.; Giuli, F.; Giuliani, C.; Giulini, M.; Gjelsten, B. K.; Gkaitatzis, S.; Gkialas, I.; Gkougkousis, E. L.; Gkountoumis, P.; Gladilin, L. K.; Glasman, C.; Glatzer, J.; Glaysher, P. C. F.; Glazov, A.; Goblirsch-Kolb, M.; Godlewski, J.; Goldfarb, S.; Golling, T.; Golubkov, D.; Gomes, A.; Gonçalo, R.; Goncalves Gama, R.; Goncalves Pinto Firmino da Costa, J.; Gonella, G.; Gonella, L.; Gongadze, A.; Gonnella, F.; Gonski, J. L.; González de La Hoz, S.; Gonzalez-Sevilla, S.; Goossens, L.; Gorbounov, P. A.; Gordon, H. A.; Gorini, B.; Gorini, E.; Gorišek, A.; Goshaw, A. T.; Gössling, C.; Gostkin, M. I.; Gottardo, C. A.; Goudet, C. R.; Goujdami, D.; Goussiou, A. G.; Govender, N.; Gozani, E.; Grabowska-Bold, I.; Gradin, P. O. J.; Graham, E. C.; Gramling, J.; Gramstad, E.; Grancagnolo, S.; Gratchev, V.; Gravila, P. M.; Gray, C.; Gray, H. M.; Greenwood, Z. D.; Grefe, C.; Gregersen, K.; Gregor, I. M.; Grenier, P.; Grevtsov, K.; Griffiths, J.; Grillo, A. A.; Grimm, K.; Grinstein, S.; Gris, Ph.; Grivaz, J.-F.; Groh, S.; Gross, E.; Grosse-Knetter, J.; Grossi, G. C.; Grout, Z. J.; Grummer, A.; Guan, L.; Guan, W.; Guenther, J.; Guescini, F.; Guest, D.; Gueta, O.; Gui, B.; Guido, E.; Guillemin, T.; Guindon, S.; Gul, U.; Gumpert, C.; Guo, J.; Guo, W.; Guo, Y.; Gupta, R.; Gurbuz, S.; Gustavino, G.; Gutelman, B. J.; Gutierrez, P.; Gutierrez Ortiz, N. G.; Gutschow, C.; Guyot, C.; Guzik, M. P.; Gwenlan, C.; Gwilliam, C. B.; Haas, A.; Haber, C.; Hadavand, H. K.; Haddad, N.; Hadef, A.; Hageböck, S.; Hagihara, M.; Hakobyan, H.; Haleem, M.; Haley, J.; Halladjian, G.; Hallewell, G. D.; Hamacher, K.; Hamal, P.; Hamano, K.; Hamilton, A.; Hamity, G. N.; Hamnett, P. G.; Han, K.; Han, L.; Han, S.; Hanagaki, K.; Hanawa, K.; Hance, M.; Handl, D. M.; Haney, B.; Hanke, P.; Hansen, J. B.; Hansen, J. D.; Hansen, M. C.; Hansen, P. H.; Hara, K.; Hard, A. S.; Harenberg, T.; Hariri, F.; Harkusha, S.; Harrison, P. F.; Hartmann, N. M.; Hasegawa, Y.; Hasib, A.; Hassani, S.; Haug, S.; Hauser, R.; Hauswald, L.; Havener, L. B.; Havranek, M.; Hawkes, C. M.; Hawkings, R. J.; Hayden, D.; Hays, C. P.; Hays, J. M.; Hayward, H. S.; Haywood, S. J.; Heck, T.; Hedberg, V.; Heelan, L.; Heer, S.; Heidegger, K. K.; Heim, S.; Heim, T.; Heinemann, B.; Heinrich, J. J.; Heinrich, L.; Heinz, C.; Hejbal, J.; Helary, L.; Held, A.; Hellman, S.; Helsens, C.; Henderson, R. C. W.; Heng, Y.; Henkelmann, S.; Henriques Correia, A. M.; Henrot-Versille, S.; Herbert, G. H.; Herde, H.; Herget, V.; Hernández Jiménez, Y.; Herr, H.; Herten, G.; Hertenberger, R.; Hervas, L.; Herwig, T. C.; Hesketh, G. G.; Hessey, N. P.; Hetherly, J. W.; Higashino, S.; Higón-Rodriguez, E.; Hildebrand, K.; Hill, E.; Hill, J. C.; Hiller, K. H.; Hillier, S. J.; Hils, M.; Hinchliffe, I.; Hirose, M.; Hirschbuehl, D.; Hiti, B.; Hladik, O.; Hlaluku, D. R.; Hoad, X.; Hobbs, J.; Hod, N.; Hodgkinson, M. C.; Hodgson, P.; Hoecker, A.; Hoeferkamp, M. R.; Hoenig, F.; Hohn, D.; Holmes, T. R.; Holzbock, M.; Homann, M.; Honda, S.; Honda, T.; Hong, T. M.; Hooberman, B. H.; Hopkins, W. H.; Horii, Y.; Horton, A. J.; Hostachy, J.-Y.; Hostiuc, A.; Hou, S.; Hoummada, A.; Howarth, J.; Hoya, J.; Hrabovsky, M.; Hrdinka, J.; Hristova, I.; Hrivnac, J.; Hryn'ova, T.; Hrynevich, A.; Hsu, P. J.; Hsu, S.-C.; Hu, Q.; Hu, S.; Huang, Y.; Hubacek, Z.; Hubaut, F.; Huegging, F.; Huffman, T. B.; Hughes, E. W.; Huhtinen, M.; Hunter, R. F. H.; Huo, P.; Huseynov, N.; Huston, J.; Huth, J.; Hyneman, R.; Iacobucci, G.; Iakovidis, G.; Ibragimov, I.; Iconomidou-Fayard, L.; Idrissi, Z.; Iengo, P.; Igonkina, O.; Iizawa, T.; Ikegami, Y.; Ikeno, M.; Ilchenko, Y.; Iliadis, D.; Ilic, N.; Iltzsche, F.; Introzzi, G.; Ioannou, P.; Iodice, M.; Iordanidou, K.; Ippolito, V.; Isacson, M. F.; Ishijima, N.; Ishino, M.; Ishitsuka, M.; Issever, C.; Istin, S.; Ito, F.; Iturbe Ponce, J. M.; Iuppa, R.; Iwasaki, H.; Izen, J. M.; Izzo, V.; Jabbar, S.; Jackson, P.; Jacobs, R. M.; Jain, V.; Jakobi, K. B.; Jakobs, K.; Jakobsen, S.; Jakoubek, T.; Jamin, D. O.; Jana, D. K.; Jansky, R.; Janssen, J.; Janus, M.; Janus, P. A.; Jarlskog, G.; Javadov, N.; Javůrek, T.; Javurkova, M.; Jeanneau, F.; Jeanty, L.; Jejelava, J.; Jelinskas, A.; Jenni, P.; Jeske, C.; Jézéquel, S.; Ji, H.; Jia, J.; Jiang, H.; Jiang, Y.; Jiang, Z.; Jiggins, S.; Jimenez Pena, J.; Jin, S.; Jinaru, A.; Jinnouchi, O.; Jivan, H.; Johansson, P.; Johns, K. A.; Johnson, C. A.; Johnson, W. J.; Jon-And, K.; Jones, R. W. L.; Jones, S. D.; Jones, S.; Jones, T. J.; Jongmanns, J.; Jorge, P. M.; Jovicevic, J.; Ju, X.; Juste Rozas, A.; Köhler, M. K.; Kaczmarska, A.; Kado, M.; Kagan, H.; Kagan, M.; Kahn, S. J.; Kaji, T.; Kajomovitz, E.; Kalderon, C. W.; Kaluza, A.; Kama, S.; Kamenshchikov, A.; Kanaya, N.; Kanjir, L.; Kantserov, V. A.; Kanzaki, J.; Kaplan, B.; Kaplan, L. S.; Kar, D.; Karakostas, K.; Karastathis, N.; Kareem, M. J.; Karentzos, E.; Karpov, S. N.; Karpova, Z. M.; Kartvelishvili, V.; Karyukhin, A. N.; Kasahara, K.; Kashif, L.; Kass, R. D.; Kastanas, A.; Kataoka, Y.; Kato, C.; Katre, A.; Katzy, J.; Kawade, K.; Kawagoe, K.; Kawamoto, T.; Kawamura, G.; Kay, E. F.; Kazanin, V. F.; Keeler, R.; Kehoe, R.; Keller, J. S.; Kellermann, E.; Kempster, J. J.; Kendrick, J.; Keoshkerian, H.; Kepka, O.; Kerševan, B. P.; Kersten, S.; Keyes, R. A.; Khader, M.; Khalil-Zada, F.; Khanov, A.; Kharlamov, A. G.; Kharlamova, T.; Khodinov, A.; Khoo, T. J.; Khovanskiy, V.; Khramov, E.; Khubua, J.; Kido, S.; Kilby, C. R.; Kim, H. Y.; Kim, S. H.; Kim, Y. K.; Kimura, N.; Kind, O. M.; King, B. T.; Kirchmeier, D.; Kirk, J.; Kiryunin, A. E.; Kishimoto, T.; Kisielewska, D.; Kitali, V.; Kivernyk, O.; Kladiva, E.; Klapdor-Kleingrothaus, T.; Klein, M. H.; Klein, M.; Klein, U.; Kleinknecht, K.; Klimek, P.; Klimentov, A.; Klingenberg, R.; Klingl, T.; Klioutchnikova, T.; Klitzner, F. F.; Kluge, E.-E.; Kluit, P.; Kluth, S.; Kneringer, E.; Knoops, E. B. F. G.; Knue, A.; Kobayashi, A.; Kobayashi, D.; Kobayashi, T.; Kobel, M.; Kocian, M.; Kodys, P.; Koffas, T.; Koffeman, E.; Köhler, N. M.; Koi, T.; Kolb, M.; Koletsou, I.; Kondo, T.; Kondrashova, N.; Köneke, K.; König, A. C.; Kono, T.; Konoplich, R.; Konstantinidis, N.; Konya, B.; Kopeliansky, R.; Koperny, S.; Korcyl, K.; Kordas, K.; Korn, A.; Korolkov, I.; Korolkova, E. V.; Kortner, O.; Kortner, S.; Kosek, T.; Kostyukhin, V. V.; Kotwal, A.; Koulouris, A.; Kourkoumeli-Charalampidi, A.; Kourkoumelis, C.; Kourlitis, E.; Kouskoura, V.; Kowalewska, A. B.; Kowalewski, R.; Kowalski, T. Z.; Kozakai, C.; Kozanecki, W.; Kozhin, A. S.; Kramarenko, V. A.; Kramberger, G.; Krasnopevtsev, D.; Krasny, M. W.; Krasznahorkay, A.; Krauss, D.; Kremer, J. A.; Kretzschmar, J.; Kreutzfeldt, K.; Krieger, P.; Krizka, K.; Kroeninger, K.; Kroha, H.; Kroll, J.; Kroll, J.; Kroseberg, J.; Krstic, J.; Kruchonak, U.; Krüger, H.; Krumnack, N.; Kruse, M. C.; Kubota, T.; Kucuk, H.; Kuday, S.; Kuechler, J. T.; Kuehn, S.; Kugel, A.; Kuger, F.; Kuhl, T.; Kukhtin, V.; Kukla, R.; Kulchitsky, Y.; Kuleshov, S.; Kulinich, Y. P.; Kuna, M.; Kunigo, T.; Kupco, A.; Kupfer, T.; Kuprash, O.; Kurashige, H.; Kurchaninov, L. L.; Kurochkin, Y. A.; Kurth, M. G.; Kuwertz, E. S.; Kuze, M.; Kvita, J.; Kwan, T.; Kyriazopoulos, D.; La Rosa, A.; La Rosa Navarro, J. L.; La Rotonda, L.; La Ruffa, F.; Lacasta, C.; Lacava, F.; Lacey, J.; Lack, D. P. J.; Lacker, H.; Lacour, D.; Ladygin, E.; Lafaye, R.; Laforge, B.; Lai, S.; Lammers, S.; Lampl, W.; Lançon, E.; Landgraf, U.; Landon, M. P. J.; Lanfermann, M. C.; Lang, V. S.; Lange, J. C.; Langenberg, R. J.; Lankford, A. J.; Lanni, F.; Lantzsch, K.; Lanza, A.; Lapertosa, A.; Laplace, S.; Laporte, J. F.; Lari, T.; Lasagni Manghi, F.; Lassnig, M.; Lau, T. S.; Laurelli, P.; Lavrijsen, W.; Law, A. T.; Laycock, P.; Lazovich, T.; Lazzaroni, M.; Le, B.; Le Dortz, O.; Le Guirriec, E.; Le Quilleuc, E. P.; Leblanc, M.; Lecompte, T.; Ledroit-Guillon, F.; Lee, C. A.; Lee, G. R.; Lee, S. C.; Lee, L.; Lefebvre, B.; Lefebvre, G.; Lefebvre, M.; Legger, F.; Leggett, C.; Lehmann Miotto, G.; Lei, X.; Leight, W. A.; Leite, M. A. L.; Leitner, R.; Lellouch, D.; Lemmer, B.; Leney, K. J. C.; Lenz, T.; Lenzi, B.; Leone, R.; Leone, S.; Leonidopoulos, C.; Lerner, G.; Leroy, C.; Les, R.; Lesage, A. A. J.; Lester, C. G.; Levchenko, M.; Levêque, J.; Levin, D.; Levinson, L. J.; Levy, M.; Lewis, D.; Li, B.; Li, H.; Li, L.; Li, Q.; Li, Q.; Li, S.; Li, X.; Li, Y.; Liang, Z.; Liberti, B.; Liblong, A.; Lie, K.; Liebig, W.; Limosani, A.; Lin, C. Y.; Lin, K.; Lin, S. C.; Lin, T. H.; Linck, R. A.; Lindquist, B. E.; Lionti, A. E.; Lipeles, E.; Lipniacka, A.; Lisovyi, M.; Liss, T. M.; Lister, A.; Litke, A. M.; Liu, B.; Liu, H.; Liu, H.; Liu, J. K. K.; Liu, J.; Liu, J. B.; Liu, K.; Liu, L.; Liu, M.; Liu, Y. L.; Liu, Y.; Livan, M.; Lleres, A.; Llorente Merino, J.; Lloyd, S. L.; Lo, C. Y.; Lo Sterzo, F.; Lobodzinska, E. M.; Loch, P.; Loebinger, F. K.; Loesle, A.; Loew, K. M.; Lohse, T.; Lohwasser, K.; Lokajicek, M.; Long, B. A.; Long, J. D.; Long, R. E.; Longo, L.; Looper, K. A.; Lopez, J. A.; Lopez Paz, I.; Lopez Solis, A.; Lorenz, J.; Lorenzo Martinez, N.; Losada, M.; Lösel, P. J.; Lou, X.; Lounis, A.; Love, J.; Love, P. A.; Lu, H.; Lu, N.; Lu, Y. J.; Lubatti, H. J.; Luci, C.; Lucotte, A.; Luedtke, C.; Luehring, F.; Lukas, W.; Luminari, L.; Lund-Jensen, B.; Lutz, M. S.; Luzi, P. M.; Lynn, D.; Lysak, R.; Lytken, E.; Lyu, F.; Lyubushkin, V.; Ma, H.; Ma, L. L.; Ma, Y.; Maccarrone, G.; Macchiolo, A.; MacDonald, C. M.; Maček, B.; Machado Miguens, J.; Madaffari, D.; Madar, R.; Mader, W. F.; Madsen, A.; Madysa, N.; Maeda, J.; Maeland, S.; Maeno, T.; Maevskiy, A. S.; Magerl, V.; Maiani, C.; Maidantchik, C.; Maier, T.; Maio, A.; Majersky, O.; Majewski, S.; Makida, Y.; Makovec, N.; Malaescu, B.; Malecki, Pa.; Maleev, V. P.; Malek, F.; Mallik, U.; Malon, D.; Malone, C.; Maltezos, S.; Malyukov, S.; Mamuzic, J.; Mancini, G.; Mandić, I.; Maneira, J.; Manhaes de Andrade Filho, L.; Manjarres Ramos, J.; Mankinen, K. H.; Mann, A.; Manousos, A.; Mansoulie, B.; Mansour, J. D.; Mantifel, R.; Mantoani, M.; Manzoni, S.; Mapelli, L.; Marceca, G.; March, L.; Marchese, L.; Marchiori, G.; Marcisovsky, M.; Marin Tobon, C. A.; Marjanovic, M.; Marley, D. E.; Marroquim, F.; Marsden, S. P.; Marshall, Z.; Martensson, M. U. F.; Marti-Garcia, S.; Martin, C. B.; Martin, T. A.; Martin, V. J.; Martin Dit Latour, B.; Martinez, M.; Martinez Outschoorn, V. I.; Martin-Haugh, S.; Martoiu, V. S.; Martyniuk, A. C.; Marzin, A.; Masetti, L.; Mashimo, T.; Mashinistov, R.; Masik, J.; Maslennikov, A. L.; Mason, L. H.; Massa, L.; Mastrandrea, P.; Mastroberardino, A.; Masubuchi, T.; Mättig, P.; Maurer, J.; Maxfield, S. J.; Maximov, D. A.; Mazini, R.; Maznas, I.; Mazza, S. M.; Mc Fadden, N. C.; Mc Goldrick, G.; Mc Kee, S. P.; McCarn, A.; McCarthy, R. L.; McCarthy, T. G.; McClymont, L. I.; McDonald, E. F.; McFayden, J. A.; McHedlidze, G.; McMahon, S. J.; McNamara, P. C.; McNicol, C. J.; McPherson, R. A.; Meehan, S.; Megy, T. J.; Mehlhase, S.; Mehta, A.; Meideck, T.; Meier, K.; Meirose, B.; Melini, D.; Mellado Garcia, B. R.; Mellenthin, J. D.; Melo, M.; Meloni, F.; Melzer, A.; Menary, S. B.; Meng, L.; Meng, X. T.; Mengarelli, A.; Menke, S.; Meoni, E.; Mergelmeyer, S.; Merlassino, C.; Mermod, P.; Merola, L.; Meroni, C.; Merritt, F. S.; Messina, A.; Metcalfe, J.; Mete, A. S.; Meyer, C.; Meyer, J.-P.; Meyer, J.; Meyer Zu Theenhausen, H.; Miano, F.; Middleton, R. P.; Miglioranzi, S.; Mijović, L.; Mikenberg, G.; Mikestikova, M.; Mikuž, M.; Milesi, M.; Milic, A.; Millar, D. A.; Miller, D. W.; Mills, C.; Milov, A.; Milstead, D. A.; Minaenko, A. A.; Minami, Y.; Minashvili, I. A.; Mincer, A. I.; Mindur, B.; Mineev, M.; Minegishi, Y.; Ming, Y.; Mir, L. M.; Mirto, A.; Mistry, K. P.; Mitani, T.; Mitrevski, J.; Mitsou, V. A.; Miucci, A.; Miyagawa, P. S.; Mizukami, A.; Mjörnmark, J. U.; Mkrtchyan, T.; Mlynarikova, M.; Moa, T.; Mochizuki, K.; Mogg, P.; Mohapatra, S.; Molander, S.; Moles-Valls, R.; Mondragon, M. C.; Mönig, K.; Monk, J.; Monnier, E.; Montalbano, A.; Montejo Berlingen, J.; Monticelli, F.; Monzani, S.; Moore, R. W.; Morange, N.; Moreno, D.; Moreno Llácer, M.; Morettini, P.; Morgenstern, M.; Morgenstern, S.; Mori, D.; Mori, T.; Morii, M.; Morinaga, M.; Morisbak, V.; Morley, A. K.; Mornacchi, G.; Morris, J. D.; Morvaj, L.; Moschovakos, P.; Mosidze, M.; Moss, H. J.; Moss, J.; Motohashi, K.; Mount, R.; Mountricha, E.; Moyse, E. J. W.; Muanza, S.; Mueller, F.; Mueller, J.; Mueller, R. S. P.; Muenstermann, D.; Mullen, P.; Mullier, G. A.; Munoz Sanchez, F. J.; Murray, W. J.; Musheghyan, H.; Muškinja, M.; Mwewa, C.; Myagkov, A. G.; Myska, M.; Nachman, B. P.; Nackenhorst, O.; Nagai, K.; Nagai, R.; Nagano, K.; Nagasaka, Y.; Nagata, K.; Nagel, M.; Nagy, E.; Nairz, A. M.; Nakahama, Y.; Nakamura, K.; Nakamura, T.; Nakano, I.; Naranjo Garcia, R. F.; Narayan, R.; Narrias Villar, D. I.; Naryshkin, I.; Naumann, T.; Navarro, G.; Nayyar, R.; Neal, H. A.; Nechaeva, P. Yu.; Neep, T. J.; Negri, A.; Negrini, M.; Nektarijevic, S.; Nellist, C.; Nelson, A.; Nelson, M. E.; Nemecek, S.; Nemethy, P.; Nessi, M.; Neubauer, M. S.; Neumann, M.; Newman, P. R.; Ng, T. Y.; Ng, Y. S.; Nguyen Manh, T.; Nickerson, R. B.; Nicolaidou, R.; Nielsen, J.; Nikiforou, N.; Nikolaenko, V.; Nikolic-Audit, I.; Nikolopoulos, K.; Nilsson, P.; Ninomiya, Y.; Nisati, A.; Nishu, N.; Nisius, R.; Nitsche, I.; Nitta, T.; Nobe, T.; Noguchi, Y.; Nomachi, M.; Nomidis, I.; Nomura, M. A.; Nooney, T.; Nordberg, M.; Norjoharuddeen, N.; Novgorodova, O.; Nozaki, M.; Nozka, L.; Ntekas, K.; Nurse, E.; Nuti, F.; O'Connor, K.; O'Neil, D. C.; O'Rourke, A. A.; O'Shea, V.; Oakham, F. G.; Oberlack, H.; Obermann, T.; Ocariz, J.; Ochi, A.; Ochoa, I.; Ochoa-Ricoux, J. P.; Oda, S.; Odaka, S.; Oh, A.; Oh, S. H.; Ohm, C. C.; Ohman, H.; Oide, H.; Okawa, H.; Okumura, Y.; Okuyama, T.; Olariu, A.; Oleiro Seabra, L. F.; Olivares Pino, S. A.; Oliveira Damazio, D.; Olsson, M. J. R.; Olszewski, A.; Olszowska, J.; Onofre, A.; Onogi, K.; Onyisi, P. U. E.; Oppen, H.; Oreglia, M. J.; Oren, Y.; Orestano, D.; Orlando, N.; Orr, R. S.; Osculati, B.; Ospanov, R.; Otero Y Garzon, G.; Otono, H.; Ouchrif, M.; Ould-Saada, F.; Ouraou, A.; Oussoren, K. P.; Ouyang, Q.; Owen, M.; Owen, R. E.; Ozcan, V. E.; Ozturk, N.; Pachal, K.; Pacheco Pages, A.; Pacheco Rodriguez, L.; Padilla Aranda, C.; Pagan Griso, S.; Paganini, M.; Paige, F.; Palacino, G.; Palazzo, S.; Palestini, S.; Palka, M.; Pallin, D.; St. Panagiotopoulou, E.; Panagoulias, I.; Pandini, C. E.; Panduro Vazquez, J. G.; Pani, P.; Panitkin, S.; Pantea, D.; Paolozzi, L.; Papadopoulou, Th. D.; Papageorgiou, K.; Paramonov, A.; Paredes Hernandez, D.; Parker, A. J.; Parker, M. A.; Parker, K. A.; Parodi, F.; Parsons, J. A.; Parzefall, U.; Pascuzzi, V. R.; Pasner, J. M.; Pasqualucci, E.; Passaggio, S.; Pastore, Fr.; Pataraia, S.; Pater, J. R.; Pauly, T.; Pearson, B.; Pedraza Lopez, S.; Pedro, R.; Peleganchuk, S. V.; Penc, O.; Peng, C.; Peng, H.; Penwell, J.; Peralva, B. S.; Perego, M. M.; Perepelitsa, D. V.; Peri, F.; Perini, L.; Pernegger, H.; Perrella, S.; Peschke, R.; Peshekhonov, V. D.; Peters, K.; Peters, R. F. Y.; Petersen, B. A.; Petersen, T. C.; Petit, E.; Petridis, A.; Petridou, C.; Petroff, P.; Petrolo, E.; Petrov, M.; Petrucci, F.; Pettersson, N. E.; Peyaud, A.; Pezoa, R.; Phillips, F. H.; Phillips, P. W.; Piacquadio, G.; Pianori, E.; Picazio, A.; Pickering, M. A.; Piegaia, R.; Pilcher, J. E.; Pilkington, A. D.; Pinamonti, M.; Pinfold, J. L.; Pirumov, H.; Pitt, M.; Plazak, L.; Pleier, M.-A.; Pleskot, V.; Plotnikova, E.; Pluth, D.; Podberezko, P.; Poettgen, R.; Poggi, R.; Poggioli, L.; Pogrebnyak, I.; Pohl, D.; Pokharel, I.; Polesello, G.; Poley, A.; Policicchio, A.; Polifka, R.; Polini, A.; Pollard, C. S.; Polychronakos, V.; Pommès, K.; Ponomarenko, D.; Pontecorvo, L.; Popeneciu, G. A.; Portillo Quintero, D. M.; Pospisil, S.; Potamianos, K.; Potrap, I. N.; Potter, C. J.; Potti, H.; Poulsen, T.; Poveda, J.; Pozo Astigarraga, M. E.; Pralavorio, P.; Pranko, A.; Prell, S.; Price, D.; Primavera, M.; Prince, S.; Proklova, N.; Prokofiev, K.; Prokoshin, F.; Protopopescu, S.; Proudfoot, J.; Przybycien, M.; Puri, A.; Puzo, P.; Qian, J.; Qin, Y.; Quadt, A.; Queitsch-Maitland, M.; Quilty, D.; Raddum, S.; Radeka, V.; Radescu, V.; Radhakrishnan, S. K.; Radloff, P.; Rados, P.; Ragusa, F.; Rahal, G.; Raine, J. A.; Rajagopalan, S.; Rangel-Smith, C.; Rashid, T.; Raspopov, S.; Ratti, M. G.; Rauch, D. M.; Rauscher, F.; Rave, S.; Ravinovich, I.; Rawling, J. H.; Raymond, M.; Read, A. L.; Readioff, N. P.; Reale, M.; Rebuzzi, D. M.; Redelbach, A.; Redlinger, G.; Reece, R.; Reed, R. G.; Reeves, K.; Rehnisch, L.; Reichert, J.; Reiss, A.; Rembser, C.; Ren, H.; Rescigno, M.; Resconi, S.; Resseguie, E. D.; Rettie, S.; Reynolds, E.; Rezanova, O. L.; Reznicek, P.; Rezvani, R.; Richter, R.; Richter, S.; Richter-Was, E.; Ricken, O.; Ridel, M.; Rieck, P.; Riegel, C. J.; Rieger, J.; Rifki, O.; Rijssenbeek, M.; Rimoldi, A.; Rimoldi, M.; Rinaldi, L.; Ripellino, G.; Ristić, B.; Ritsch, E.; Riu, I.; Rizatdinova, F.; Rizvi, E.; Rizzi, C.; Roberts, R. T.; Robertson, S. H.; Robichaud-Veronneau, A.; Robinson, D.; Robinson, J. E. M.; Robson, A.; Rocco, E.; Roda, C.; Rodina, Y.; Rodriguez Bosca, S.; Rodriguez Perez, A.; Rodriguez Rodriguez, D.; Roe, S.; Rogan, C. S.; Røhne, O.; Roloff, J.; Romaniouk, A.; Romano, M.; Romano Saez, S. M.; Romero Adam, E.; Rompotis, N.; Ronzani, M.; Roos, L.; Rosati, S.; Rosbach, K.; Rose, P.; Rosien, N.-A.; Rossi, E.; Rossi, L. P.; Rosten, J. H. N.; Rosten, R.; Rotaru, M.; Rothberg, J.; Rousseau, D.; Roy, D.; Rozanov, A.; Rozen, Y.; Ruan, X.; Rubbo, F.; Rühr, F.; Ruiz-Martinez, A.; Rurikova, Z.; Rusakovich, N. A.; Russell, H. L.; Rutherfoord, J. P.; Ruthmann, N.; Rüttinger, E. M.; Ryabov, Y. F.; Rybar, M.; Rybkin, G.; Ryu, S.; Ryzhov, A.; Rzehorz, G. F.; Saavedra, A. F.; Sabato, G.; Sacerdoti, S.; Sadrozinski, H. F.-W.; Sadykov, R.; Safai Tehrani, F.; Saha, P.; Sahinsoy, M.; Saimpert, M.; Saito, M.; Saito, T.; Sakamoto, H.; Sakurai, Y.; Salamanna, G.; Salazar Loyola, J. E.; Salek, D.; Sales de Bruin, P. H.; Salihagic, D.; Salnikov, A.; Salt, J.; Salvatore, D.; Salvatore, F.; Salvucci, A.; Salzburger, A.; Sammel, D.; Sampsonidis, D.; Sampsonidou, D.; Sánchez, J.; Sanchez Pineda, A.; Sandaker, H.; Sandbach, R. L.; Sander, C. O.; Sandhoff, M.; Sandoval, C.; Sankey, D. P. C.; Sannino, M.; Sano, Y.; Sansoni, A.; Santoni, C.; Santos, H.; Santoyo Castillo, I.; Sapronov, A.; Saraiva, J. G.; Sasaki, O.; Sato, K.; Sauvan, E.; Savage, G.; Savard, P.; Savic, N.; Sawyer, C.; Sawyer, L.; Sbarra, C.; Sbrizzi, A.; Scanlon, T.; Scannicchio, D. A.; Schaarschmidt, J.; Schacht, P.; Schachtner, B. M.; Schaefer, D.; Schaefer, L.; Schaeffer, J.; Schaepe, S.; Schaetzel, S.; Schäfer, U.; Schaffer, A. C.; Schaile, D.; Schamberger, R. D.; Schegelsky, V. A.; Scheirich, D.; Schenck, F.; Schernau, M.; Schiavi, C.; Schier, S.; Schildgen, L. K.; Schillo, C.; Schioppa, M.; Schlenker, S.; Schmidt-Sommerfeld, K. R.; Schmieden, K.; Schmitt, C.; Schmitt, S.; Schmitz, S.; Schnoor, U.; Schoeffel, L.; Schoening, A.; Schoenrock, B. D.; Schopf, E.; Schott, M.; Schouwenberg, J. F. P.; Schovancova, J.; Schramm, S.; Schuh, N.; Schulte, A.; Schultens, M. J.; Schultz-Coulon, H.-C.; Schumacher, M.; Schumm, B. A.; Schune, Ph.; Schwartzman, A.; Schwarz, T. A.; Schweiger, H.; Schwemling, Ph.; Schwienhorst, R.; Schwindling, J.; Sciandra, A.; Sciolla, G.; Scornajenghi, M.; Scuri, F.; Scutti, F.; Searcy, J.; Seema, P.; Seidel, S. C.; Seiden, A.; Seixas, J. M.; Sekhniaidze, G.; Sekhon, K.; Sekula, S. J.; Semprini-Cesari, N.; Senkin, S.; Serfon, C.; Serin, L.; Serkin, L.; Sessa, M.; Seuster, R.; Severini, H.; Šfiligoj, T.; Sforza, F.; Sfyrla, A.; Shabalina, E.; Shaikh, N. W.; Shan, L. Y.; Shang, R.; Shank, J. T.; Shapiro, M.; Shatalov, P. B.; Shaw, K.; Shaw, S. M.; Shcherbakova, A.; Shehu, C. Y.; Shen, Y.; Sherafati, N.; Sherman, A. D.; Sherwood, P.; Shi, L.; Shimizu, S.; Shimmin, C. O.; Shimojima, M.; Shipsey, I. P. J.; Shirabe, S.; Shiyakova, M.; Shlomi, J.; Shmeleva, A.; Shoaleh Saadi, D.; Shochet, M. J.; Shojaii, S.; Shope, D. R.; Shrestha, S.; Shulga, E.; Shupe, M. A.; Sicho, P.; Sickles, A. M.; Sidebo, P. E.; Sideras Haddad, E.; Sidiropoulou, O.; Sidoti, A.; Siegert, F.; Sijacki, Dj.; Silva, J.; Silverstein, S. B.; Simak, V.; Simic, L.; Simion, S.; Simioni, E.; Simmons, B.; Simon, M.; Sinervo, P.; Sinev, N. B.; Sioli, M.; Siragusa, G.; Siral, I.; Sivoklokov, S. Yu.; Sjölin, J.; Skinner, M. B.; Skubic, P.; Slater, M.; Slavicek, T.; Slawinska, M.; Sliwa, K.; Slovak, R.; Smakhtin, V.; Smart, B. H.; Smiesko, J.; Smirnov, N.; Smirnov, S. Yu.; Smirnov, Y.; Smirnova, L. N.; Smirnova, O.; Smith, J. W.; Smith, M. N. K.; Smith, R. W.; Smizanska, M.; Smolek, K.; Snesarev, A. A.; Snyder, I. M.; Snyder, S.; Sobie, R.; Socher, F.; Soffer, A.; Søgaard, A.; Soh, D. A.; Sokhrannyi, G.; Solans Sanchez, C. A.; Solar, M.; Soldatov, E. Yu.; Soldevila, U.; Solodkov, A. A.; Soloshenko, A.; Solovyanov, O. V.; Solovyev, V.; Sommer, P.; Son, H.; Sopczak, A.; Sosa, D.; Sotiropoulou, C. L.; Sottocornola, S.; Soualah, R.; Soukharev, A. M.; South, D.; Sowden, B. C.; Spagnolo, S.; Spalla, M.; Spangenberg, M.; Spanò, F.; Sperlich, D.; Spettel, F.; Spieker, T. M.; Spighi, R.; Spigo, G.; Spiller, L. A.; Spousta, M.; St. Denis, R. D.; Stabile, A.; Stamen, R.; Stamm, S.; Stanecka, E.; Stanek, R. W.; Stanescu, C.; Stanitzki, M. M.; Stapf, B. S.; Stapnes, S.; Starchenko, E. A.; Stark, G. H.; Stark, J.; Stark, S. H.; Staroba, P.; Starovoitov, P.; Stärz, S.; Staszewski, R.; Stegler, M.; Steinberg, P.; Stelzer, B.; Stelzer, H. J.; Stelzer-Chilton, O.; Stenzel, H.; Stevenson, T. J.; Stewart, G. A.; Stockton, M. C.; Stoebe, M.; Stoicea, G.; Stolte, P.; Stonjek, S.; Stradling, A. R.; Straessner, A.; Stramaglia, M. E.; Strandberg, J.; Strandberg, S.; Strauss, M.; Strizenec, P.; Ströhmer, R.; Strom, D. M.; Stroynowski, R.; Strubig, A.; Stucci, S. A.; Stugu, B.; Styles, N. A.; Su, D.; Su, J.; Suchek, S.; Sugaya, Y.; Suk, M.; Sulin, V. V.; Sultan, Dms; Sultansoy, S.; Sumida, T.; Sun, S.; Sun, X.; Suruliz, K.; Suster, C. J. E.; Sutton, M. R.; Suzuki, S.; Svatos, M.; Swiatlowski, M.; Swift, S. P.; Sykora, I.; Sykora, T.; Ta, D.; Tackmann, K.; Taenzer, J.; Taffard, A.; Tafirout, R.; Tahirovic, E.; Taiblum, N.; Takai, H.; Takashima, R.; Takasugi, E. H.; Takeda, K.; Takeshita, T.; Takubo, Y.; Talby, M.; Talyshev, A. A.; Tanaka, J.; Tanaka, M.; Tanaka, R.; Tanioka, R.; Tannenwald, B. B.; Tapia Araya, S.; Tapprogge, S.; Tarem, S.; Tartarelli, G. F.; Tas, P.; Tasevsky, M.; Tashiro, T.; Tassi, E.; Tavares Delgado, A.; Tayalati, Y.; Taylor, A. C.; Taylor, A. J.; Taylor, G. N.; Taylor, P. T. E.; Taylor, W.; Teixeira-Dias, P.; Temple, D.; Ten Kate, H.; Teng, P. K.; Teoh, J. J.; Tepel, F.; Terada, S.; Terashi, K.; Terron, J.; Terzo, S.; Testa, M.; Teuscher, R. J.; Thais, S. J.; Theveneaux-Pelzer, T.; Thiele, F.; Thomas, J. P.; Thomas-Wilsker, J.; Thompson, P. D.; Thompson, A. S.; Thomsen, L. A.; Thomson, E.; Tian, Y.; Tibbetts, M. J.; Ticse Torres, R. E.; Tikhomirov, V. O.; Tikhonov, Yu. A.; Timoshenko, S.; Tipton, P.; Tisserant, S.; Todome, K.; Todorova-Nova, S.; Todt, S.; Tojo, J.; Tokár, S.; Tokushuku, K.; Tolley, E.; Tomlinson, L.; Tomoto, M.; Tompkins, L.; Toms, K.; Tong, B.; Tornambe, P.; Torrence, E.; Torres, H.; Torró Pastor, E.; Toth, J.; Touchard, F.; Tovey, D. R.; Treado, C. J.; Trefzger, T.; Tresoldi, F.; Tricoli, A.; Trigger, I. M.; Trincaz-Duvoid, S.; Tripiana, M. F.; Trischuk, W.; Trocmé, B.; Trofymov, A.; Troncon, C.; Trovatelli, M.; Truong, L.; Trzebinski, M.; Trzupek, A.; Tsang, K. W.; Tseng, J. C.-L.; Tsiareshka, P. V.; Tsirintanis, N.; Tsiskaridze, S.; Tsiskaridze, V.; Tskhadadze, E. G.; Tsukerman, I. I.; Tsulaia, V.; Tsuno, S.; Tsybychev, D.; Tu, Y.; Tudorache, A.; Tudorache, V.; Tulbure, T. T.; Tuna, A. N.; Turchikhin, S.; Turgeman, D.; Turk Cakir, I.; Turra, R.; Tuts, P. M.; Ucchielli, G.; Ueda, I.; Ughetto, M.; Ukegawa, F.; Unal, G.; Undrus, A.; Unel, G.; Ungaro, F. C.; Unno, Y.; Uno, K.; Urban, J.; Urquijo, P.; Urrejola, P.; Usai, G.; Usui, J.; Vacavant, L.; Vacek, V.; Vachon, B.; Vadla, K. O. H.; Vaidya, A.; Valderanis, C.; Valdes Santurio, E.; Valente, M.; Valentinetti, S.; Valero, A.; Valéry, L.; Vallier, A.; Valls Ferrer, J. A.; van den Wollenberg, W.; van der Graaf, H.; van Gemmeren, P.; van Nieuwkoop, J.; van Vulpen, I.; van Woerden, M. C.; Vanadia, M.; Vandelli, W.; Vaniachine, A.; Vankov, P.; Vardanyan, G.; Vari, R.; Varnes, E. W.; Varni, C.; Varol, T.; Varouchas, D.; Vartapetian, A.; Varvell, K. E.; Vasquez, J. G.; Vasquez, G. A.; Vazeille, F.; Vazquez Furelos, D.; Vazquez Schroeder, T.; Veatch, J.; Veeraraghavan, V.; Veloce, L. M.; Veloso, F.; Veneziano, S.; Ventura, A.; Venturi, M.; Venturi, N.; Vercesi, V.; Verducci, M.; Verkerke, W.; Vermeulen, A. T.; Vermeulen, J. C.; Vetterli, M. C.; Viaux Maira, N.; Viazlo, O.; Vichou, I.; Vickey, T.; Vickey Boeriu, O. E.; Viehhauser, G. H. A.; Viel, S.; Vigani, L.; Villa, M.; Villaplana Perez, M.; Vilucchi, E.; Vincter, M. G.; Vinogradov, V. B.; Vishwakarma, A.; Vittori, C.; Vivarelli, I.; Vlachos, S.; Vogel, M.; Vokac, P.; Volpi, G.; von Buddenbrock, S. E.; von der Schmitt, H.; von Toerne, E.; Vorobel, V.; Vorobev, K.; Vos, M.; Voss, R.; Vossebeld, J. H.; Vranjes, N.; Vranjes Milosavljevic, M.; Vrba, V.; Vreeswijk, M.; Vuillermet, R.; Vukotic, I.; Wagner, P.; Wagner, W.; Wagner-Kuhr, J.; Wahlberg, H.; Wahrmund, S.; Wakamiya, K.; Walder, J.; Walker, R.; Walkowiak, W.; Wallangen, V.; Wang, C.; Wang, C.; Wang, F.; Wang, H.; Wang, H.; Wang, J.; Wang, J.; Wang, Q.; Wang, R.-J.; Wang, R.; Wang, S. M.; Wang, T.; Wang, W.; Wang, W.; Wang, Z.; Wanotayaroj, C.; Warburton, A.; Ward, C. P.; Wardrope, D. R.; Washbrook, A.; Watkins, P. M.; Watson, A. T.; Watson, M. F.; Watts, G.; Watts, S.; Waugh, B. M.; Webb, A. F.; Webb, S.; Weber, M. S.; Weber, S. M.; Weber, S. W.; Weber, S. A.; Webster, J. S.; Weidberg, A. R.; Weinert, B.; Weingarten, J.; Weirich, M.; Weiser, C.; Wells, P. S.; Wenaus, T.; Wengler, T.; Wenig, S.; Wermes, N.; Werner, M. D.; Werner, P.; Wessels, M.; Weston, T. D.; Whalen, K.; Whallon, N. L.; Wharton, A. M.; White, A. S.; White, A.; White, M. J.; White, R.; Whiteson, D.; Whitmore, B. W.; Wickens, F. J.; Wiedenmann, W.; Wielers, M.; Wiglesworth, C.; Wiik-Fuchs, L. A. M.; Wildauer, A.; Wilk, F.; Wilkens, H. G.; Williams, H. H.; Williams, S.; Willis, C.; Willocq, S.; Wilson, J. A.; Wingerter-Seez, I.; Winkels, E.; Winklmeier, F.; Winston, O. J.; Winter, B. T.; Wittgen, M.; Wobisch, M.; Wolf, A.; Wolf, T. M. H.; Wolff, R.; Wolter, M. W.; Wolters, H.; Wong, V. W. S.; Woods, N. L.; Worm, S. D.; Wosiek, B. K.; Wotschack, J.; Wozniak, K. W.; Wu, M.; Wu, S. L.; Wu, X.; Wu, Y.; Wyatt, T. R.; Wynne, B. M.; Xella, S.; Xi, Z.; Xia, L.; Xu, D.; Xu, L.; Xu, T.; Xu, W.; Yabsley, B.; Yacoob, S.; Yamaguchi, D.; Yamaguchi, Y.; Yamamoto, A.; Yamamoto, S.; Yamanaka, T.; Yamane, F.; Yamatani, M.; Yamazaki, T.; Yamazaki, Y.; Yan, Z.; Yang, H.; Yang, H.; Yang, Y.; Yang, Z.; Yao, W.-M.; Yap, Y. C.; Yasu, Y.; Yatsenko, E.; Yau Wong, K. H.; Ye, J.; Ye, S.; Yeletskikh, I.; Yigitbasi, E.; Yildirim, E.; Yorita, K.; Yoshihara, K.; Young, C.; Young, C. J. S.; Yu, J.; Yu, J.; Yuen, S. P. Y.; Yusuff, I.; Zabinski, B.; Zacharis, G.; Zaidan, R.; Zaitsev, A. M.; Zakharchuk, N.; Zalieckas, J.; Zaman, A.; Zambito, S.; Zanzi, D.; Zeitnitz, C.; Zemaityte, G.; Zemla, A.; Zeng, J. C.; Zeng, Q.; Zenin, O.; Ženiš, T.; Zerwas, D.; Zhang, D.; Zhang, D.; Zhang, F.; Zhang, G.; Zhang, H.; Zhang, J.; Zhang, L.; Zhang, L.; Zhang, M.; Zhang, P.; Zhang, R.; Zhang, R.; Zhang, X.; Zhang, Y.; Zhang, Z.; Zhao, X.; Zhao, Y.; Zhao, Z.; Zhemchugov, A.; Zhou, B.; Zhou, C.; Zhou, L.; Zhou, M.; Zhou, M.; Zhou, N.; Zhou, Y.; Zhu, C. G.; Zhu, H.; Zhu, J.; Zhu, Y.; Zhuang, X.; Zhukov, K.; Zibell, A.; Zieminska, D.; Zimine, N. I.; Zimmermann, C.; Zimmermann, S.; Zinonos, Z.; Zinser, M.; Ziolkowski, M.; Živković, L.; Zobernig, G.; Zoccoli, A.; Zou, R.; Zur Nedden, M.; Zwalinski, L.; Atlas Collaboration

    2018-01-01

    This Letter presents the measurement of differential cross sections of isolated prompt photons produced in association with a b-jet or a c-jet. These final states provide sensitivity to the heavy-flavour content of the proton and aspects related to the modelling of heavy-flavour quarks in perturbative QCD. The measurement uses proton-proton collision data at a centre-of-mass energy of 8 TeV recorded by the ATLAS detector at the LHC in 2012 corresponding to an integrated luminosity of up to 20.2 fb-1. The differential cross sections are measured for each jet flavour with respect to the transverse energy of the leading photon in two photon pseudorapidity regions: |ηγ | high photon transverse energies. The total uncertainty in the measurement ranges between 13% and 66%, while the central γ + b measurement exhibits the smallest uncertainty, ranging from 13% to 27%, which is comparable to the precision of the theoretical predictions.

  8. Differential sensitivity of p53+ and p53- cells to caffeine-induced radiosensitization and override of G2 delay

    International Nuclear Information System (INIS)

    Powell, S.N.; DeFrank, J.S.; Connell, P.; Eogan, M.; Preffer, F.; Dombkowski, D.; Tang, W.; Friend, S.H.

    1995-01-01

    Purpose: Most drug discovery efforts have focused on finding new DNA damaging agents to kill tumor cells preferentially. An alternative approach is to find ways to increase tumor specific killing by modifying tumor specific responses to that damage. We asked whether cells lacking the G1/S arrest in response to X-rays are more sensitive to X-ray damage when treated with agents that override G2/M arrest. Materials and Methods: Mouse embryonic fibroblasts genetically matched to be (+/+) or (-/-) p53 and rat embryonic fibroblasts (REF) made (+) or (-) for wild-type p53 function by transfection were irradiated with and without caffeine, a known checkpoint inhibitor. Caffeine treatment was maintained for 24 hours from 1 hour prior to irradiation. Cell survival following ionizing radiation was measured by clonogenic assay. For cell-cycle analysis, cells were in exponential asynchronous growth at the time of irradiation. The proportion of cells in G1, S and G2/M phases of the cell cycle were recorded immediately before and following irradiation and subsequently at 3,6,9,12,24 and 48 hours following irradiation. Results: Caffeine was found to cause radiosensitzation at low dose (0.5mM) in (-/-) cells but not in (+/+) cells. The sensitization enhancement ratio (SER) was 1.45 at 0.1 survival and 1.56 at 0.01 survival. At this dose of caffeine, this SER reflected therapeutic gain as there was no detectable effect on (+/+) cells. At 1mM caffeine, sensitization of (-/-) cells was 1.77, but (+/+) cells now also showed sensitization (SER=1.25). In (-/-) cells at 0.1mM caffeine the SER was 1.5 at 0.01 survival. The transfected REF cells (functionally null for p53) also exhibited caffeine-induced radiosensitization at both 0.5 and 2mM caffeine with a SER 1.45 for 2mM at 0.1 survival. No significant sensitization could be demonstrated for REF cells at the same doses of caffeine. The REF cells, with wild-type p53, transfected with pCMVneo alone showed no change in radiosensitivity or

  9. Sensitivity technologies for large scale simulation

    International Nuclear Information System (INIS)

    Collis, Samuel Scott; Bartlett, Roscoe Ainsworth; Smith, Thomas Michael; Heinkenschloss, Matthias; Wilcox, Lucas C.; Hill, Judith C.; Ghattas, Omar; Berggren, Martin Olof; Akcelik, Volkan; Ober, Curtis Curry; van Bloemen Waanders, Bart Gustaaf; Keiter, Eric Richard

    2005-01-01

    Sensitivity analysis is critically important to numerous analysis algorithms, including large scale optimization, uncertainty quantification,reduced order modeling, and error estimation. Our research focused on developing tools, algorithms and standard interfaces to facilitate the implementation of sensitivity type analysis into existing code and equally important, the work was focused on ways to increase the visibility of sensitivity analysis. We attempt to accomplish the first objective through the development of hybrid automatic differentiation tools, standard linear algebra interfaces for numerical algorithms, time domain decomposition algorithms and two level Newton methods. We attempt to accomplish the second goal by presenting the results of several case studies in which direct sensitivities and adjoint methods have been effectively applied, in addition to an investigation of h-p adaptivity using adjoint based a posteriori error estimation. A mathematical overview is provided of direct sensitivities and adjoint methods for both steady state and transient simulations. Two case studies are presented to demonstrate the utility of these methods. A direct sensitivity method is implemented to solve a source inversion problem for steady state internal flows subject to convection diffusion. Real time performance is achieved using novel decomposition into offline and online calculations. Adjoint methods are used to reconstruct initial conditions of a contamination event in an external flow. We demonstrate an adjoint based transient solution. In addition, we investigated time domain decomposition algorithms in an attempt to improve the efficiency of transient simulations. Because derivative calculations are at the root of sensitivity calculations, we have developed hybrid automatic differentiation methods and implemented this approach for shape optimization for gas dynamics using the Euler equations. The hybrid automatic differentiation method was applied to a first

  10. Parallel development of contour integration and visual contrast sensitivity at low spatial frequencies

    DEFF Research Database (Denmark)

    Benedek, Krisztina; Janáky, Márta; Braunitzer, Gábor

    2010-01-01

    It has been suggested that visual contrast sensitivity and contour integration functions exhibit a late maturation during adolescence. However, the relationship between these functions has not been investigated. The aim of this study was to assess the development of visual contrast sensitivity...

  11. Science Fiction Exhibits as STEM Gateways

    Science.gov (United States)

    Robie, Samantha

    Women continue to hold less than a quarter of all STEM jobs in the United States, prompting many museums to develop programs and exhibits with the express goal of interesting young girls in scientific fields. At the same time, a number of recent museum exhibits have harnessed the popularity of pop culture and science fiction in order to interest general audiences in STEM subject matter, as well as using the exhibits as springboards to expand or shift mission goals and focus. Because science fiction appears to be successful at raising interest in STEM fields, it may be an effective way to garner the interest of young girls in STEM in particular. This research seeks to describe the ways in which museums are currently using science fiction exhibits to interest young girls in STEM fields and careers. Research focused on four institutions across the country hosting three separate exhibits, and included staff interviews and content analysis of exhibit descriptions, promotional materials, a summative evaluation and supplementary exhibit productions. In some ways, science fiction exhibits do serve young girls, primarily through the inclusion of female role models, staff awareness, and prototype testing to ensure interactives are attractive to girls as well as to boys. However, STEM appears to be underutilized, which may be partly due to a concern within the field that the outcome of targeting a specific gender could be construed as "stereotyping".

  12. ANTIBODIES TO LEUKEMIA DIFFERENTIATION FACTOR (HLDF IN PATIENTS WITH GASTROINTESTINAL CANCER

    Directory of Open Access Journals (Sweden)

    A. I. Autenshlus

    2010-01-01

    Full Text Available Antibodies to leukemia differentiation factor (HLDF in patients with gastrointestinal cancer Abstract. Patients with gastric cancer exhibit higher levels of IgG4-antibodies to human leukemia differentiation factor (HLDF, as compared with healthy individuals, whereas, in patients with colorectal cancer, one may detect high levels of IgA anti-HDLF antibodies, along with lower levels of IgG1 class antibodies against HLDF than in control group. Among patients with gastrointestinal cancer, a positive correlation is revealed between contents of highly differentiated cells in the tumor, and IgM antibodies to HDLF. Meanwhile, a reverse relationship is noted between low differentiation of tumor cells and levels of IgG2 antibodies to HDLF in gastric cancer patients, or IgG3 antibodies to HDLF in patients with colorectal cancer.

  13. In vitro differentiation of rat spermatogonia into round spermatids in tissue culture.

    Science.gov (United States)

    Reda, A; Hou, M; Winton, T R; Chapin, R E; Söder, O; Stukenborg, J-B

    2016-09-01

    Do the organ culture conditions, previously defined for in vitro murine male germ cell differentiation, also result in differentiation of rat spermatogonia into post-meiotic germ cells exhibiting specific markers for haploid germ cells? We demonstrated the differentiation of rat spermatogonia into post-meiotic cells in vitro, with emphasis on exhibiting, protein markers described for round spermatids. Full spermatogenesis in vitro from immature germ cells using an organ culture technique in mice was first reported 5 years ago. However, no studies reporting the differentiation of rat spermatogonia into post-meiotic germ cells exhibiting the characteristic protein expression profile or into functional sperm have been reported. Organ culture of testicular fragments of 5 days postpartum (dpp) neonatal rats was performed for up to 52 days. Evaluation of microscopic morphology, testosterone levels, mRNA and protein expression as measured by RT-qPCR and immunostaining were conducted to monitor germ cell differentiation in vitro. Potential effects of melatonin, Glutamax® medium, retinoic acid and the presence of epidydimal fat tissue on the spermatogenic process were evaluated. A minimum of three biological replicates were performed for all experiments presented in this study. One-way ANOVA, ANOVA on ranks and student's t-test were applied to perform the statistical analysis. Male germ cells, present in testicular tissue pieces grown from 5 dpp rats, exhibited positive protein expression for Acrosin and Crem (cAMP (cyclic adenosine mono phosphate) response element modulator) after 52 days of culture in vitro. Intra-testicular testosterone production could be observed after 3 days of culture, while when epididymal fat tissue was added, spontaneous contractility of cultured seminiferous tubules could be observed after 21 days. However, no supportive effect of the supplementation with any factor or the co-culturing with epididymal fat tissue on germ cell differentiation in

  14. A mouse model of the schizophrenia-associated 1q21.1 microdeletion syndrome exhibits altered mesolimbic dopamine transmission

    DEFF Research Database (Denmark)

    Nielsen, Jacob; Fejgin, Kim; Sotty, Florence

    2017-01-01

    on schizophrenia-related assays. Df(h1q21)/+ mice displayed increased hyperactivity in response to amphetamine challenge and increased sensitivity to the disruptive effects of amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition. Probing of the direct dopamine (DA) pathway using the DA D1...... and basic functions such as reflexes, ASR, thermal pain sensitivity, and motor performance were unaltered. Similarly, anxiety related measures, baseline prepulse inhibition, and seizure threshold were unaltered. In addition to the central nervous system-related phenotypes, Df(h1q21)/+ mice exhibited reduced...

  15. Differential mobility in plasm

    International Nuclear Information System (INIS)

    Jewur, S.S.

    1983-01-01

    Theoretical considerations about the technique based on differential plasma mobility are made for the analysis of trace amounts of chemical products. The mechanisms for the formation of reagent-ion, reaction between ion and molecule, separation of ions and molecules and production of plasmogram, are explained. Despite being a very modern technique and the equipment has not yet been put in the market, it is already confirmed that the structural sensitivity of the fluctuation time in DPM is greater than the retention time in chromatographic techniques. (CLB) [pt

  16. Proteomic analysis reveals contrasting stress response to uranium in two nitrogen-fixing Anabaena strains, differentially tolerant to uranium

    Energy Technology Data Exchange (ETDEWEB)

    Panda, Bandita; Basu, Bhakti; Acharya, Celin; Rajaram, Hema; Apte, Shree Kumar, E-mail: aptesk@barc.gov.in

    2017-01-15

    Highlights: • Response of two native cyanobacterial strains to uranium exposure was studied. • Anabaena L-31 exhibited higher tolerance to uranium as compared to Anabaena 7120. • Uranium exposure differentially affected the proteome profiles of the two strains. • Anabaena L-31 showed better sustenance of photosynthesis and carbon metabolism. • Anabaena L-31 displayed superior oxidative stress defense than Anabaena 7120. - Abstract: Two strains of the nitrogen-fixing cyanobacterium Anabaena, native to Indian paddy fields, displayed differential sensitivity to exposure to uranyl carbonate at neutral pH. Anabaena sp. strain PCC 7120 and Anabaena sp. strain L-31 displayed 50% reduction in survival (LD{sub 50} dose), following 3 h exposure to 75 μM and 200 μM uranyl carbonate, respectively. Uranium responsive proteome alterations were visualized by 2D gel electrophoresis, followed by protein identification by MALDI-ToF mass spectrometry. The two strains displayed significant differences in levels of proteins associated with photosynthesis, carbon metabolism, and oxidative stress alleviation, commensurate with their uranium tolerance. Higher uranium tolerance of Anabaena sp. strain L-31 could be attributed to sustained photosynthesis and carbon metabolism and superior oxidative stress defense, as compared to the uranium sensitive Anabaena sp. strain PCC 7120. Significance: Uranium responsive proteome modulations in two nitrogen-fixing strains of Anabaena, native to Indian paddy fields, revealed that rapid adaptation to better oxidative stress management, and maintenance of metabolic and energy homeostasis underlies superior uranium tolerance of Anabaena sp. strain L-31 compared to Anabaena sp. strain PCC 7120.

  17. Approximating chaotic saddles for delay differential equations.

    Science.gov (United States)

    Taylor, S Richard; Campbell, Sue Ann

    2007-04-01

    Chaotic saddles are unstable invariant sets in the phase space of dynamical systems that exhibit transient chaos. They play a key role in mediating transport processes involving scattering and chaotic transients. Here we present evidence (long chaotic transients and fractal basins of attraction) of transient chaos in a "logistic" delay differential equation. We adapt an existing method (stagger-and-step) to numerically construct the chaotic saddle for this system. This is the first such analysis of transient chaos in an infinite-dimensional dynamical system, and in delay differential equations in particular. Using Poincaré section techniques we illustrate approaches to visualizing the saddle set, and confirm that the saddle has the Cantor-like fractal structure consistent with a chaotic saddle generated by horseshoe-type dynamics.

  18. Approximating chaotic saddles for delay differential equations

    Science.gov (United States)

    Taylor, S. Richard; Campbell, Sue Ann

    2007-04-01

    Chaotic saddles are unstable invariant sets in the phase space of dynamical systems that exhibit transient chaos. They play a key role in mediating transport processes involving scattering and chaotic transients. Here we present evidence (long chaotic transients and fractal basins of attraction) of transient chaos in a “logistic” delay differential equation. We adapt an existing method (stagger-and-step) to numerically construct the chaotic saddle for this system. This is the first such analysis of transient chaos in an infinite-dimensional dynamical system, and in delay differential equations in particular. Using Poincaré section techniques we illustrate approaches to visualizing the saddle set, and confirm that the saddle has the Cantor-like fractal structure consistent with a chaotic saddle generated by horseshoe-type dynamics.

  19. Trait anxiety and attenuated negative affect differentiation: a vulnerability factor to consider?

    Science.gov (United States)

    Matt, Lindsey M; Fresco, David M; Coifman, Karin G

    2016-11-01

    Describing emotional experiences using distinct terms, or affect differentiation, has been associated with emotion regulation and adaptive behavior under stress. There is little data, however, examining the association between differentiation and dispositional factors underlying psychopathology. The current study examines the association between differentiation and trait anxiety (TA) given prior evidence of cognitive biases in TA relevant to higher order processing of emotional experiences. We examined cross-sectionally, via lab-based repeated assessment, the association between differentiation of negative and positive experiences and TA. Two hundred twenty-two adults completed an emotion reactivity task including repeated assessments of affect. We hypothesized that individuals higher in trait anxiety (HTA) would have greater difficulty differentiating their experiences. HTA individuals exhibited lower levels of negative affect (NA) differentiation even when controlling for depression. Although negative emotion intensity was consistently associated with lower differentiation, this did not account for the influence of HTA on differentiation. These data suggest that HTA individuals have greater difficulty differentiating negative emotions, regardless of negative emotion intensity and depression. As HTA is common to many emotional disorders; this evidence suggests that poor differentiation may also be an important transdiagnostic consideration in models of risk and of affective disease.

  20. Theoretical Analysis of Fas Ligand-Induced Apoptosis with an Ordinary Differential Equation Model.

    Science.gov (United States)

    Shi, Zhimin; Li, Yan; Liu, Zhihai; Mi, Jun; Wang, Renxiao

    2012-12-01

    Upon the treatment of Fas ligand, different types of cells exhibit different apoptotic mechanisms, which are determined by a complex network of biological pathways. In order to derive a quantitative interpretation of the cell sensitivity and apoptosis pathways, we have developed an ordinary differential equation model. Our model is intended to include all of the known major components in apoptosis pathways mediated by Fas receptor. It is composed of 29 equations using a total of 49 rate constants and 13 protein concentrations. All parameters used in our model were derived through nonlinear fitting to experimentally measured concentrations of four selected proteins in Jurkat T-cells, including caspase-3, caspase-8, caspase-9, and Bid. Our model is able to correctly interpret the role of kinetic parameters and protein concentrations in cell sensitivity to FasL. It reveals the possible reasons for the transition between type-I and type-II pathways and also provides some interesting predictions, such as the more decisive role of Fas over Bax in apoptosis pathway and a possible feedback mechanism between type-I and type-II pathways. But our model failed in predicting FasL-induced apoptotic mechanism of NCI-60 cells from their gene-expression levels. Limitations in our model are also discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. In vitro sensitivity of normal and hereditary retinoblastoma fibroblasts to DNA-damaging agents

    International Nuclear Information System (INIS)

    Woods, W.G.; Byrne, T.D.

    1986-01-01

    We investigated the ability of nine fibroblast cell strains from patients with the hereditary form of retinoblastoma (RB) to handle various types of DNA-damaging agents and compared the results with those obtained in nine normal strains. Cell strains were exposed to gamma-radiation, which causes DNA scission; actinomycin D, a DNA-intercalating agent; and mitomycin C, a bifunctional alkylating agent leading to DNA-DNA cross-linking. Cell strains were studied for their ability to survive in a cytotoxicity assay. Nine normal strains exhibited a mean D0 (inverse of the slope of the straight line portion of the survival curve) of 134-178 cGy after radiation exposure, compared to a range of 119-186 cGy in the nine RB strains (P = 0.33). Similarly, exposure to actinomycin D led to D0 values of 0.024-0.069 microgram/ml in the nine normal strains and D0 values of 0.016-0.067 microgram/ml in the RB strains (P = 0.64). The nine RB strains did exhibit a small overall increase in sensitivity after exposure to mitomycin C, with D0 values ranging from 0.14-0.32 microgram/ml versus 0.19-0.66 microgram/ml in the nine normal strains (P = 0.002); however, when the two most resistant normal strains were excluded from analysis, results were similar. Three RB cell strains derived from individuals who had either developed second cancers or who had a family history of additional sarcomas consistently exhibited increases in sensitivity to all three DNA-damaging agents studied compared with other hereditary RB cell strains as well as normal strains. The results suggest that normal human fibroblast cell strains exhibit a wide response to DNA-damaging agents, especially chemical agents. Most hereditary RB strains exhibit sensitivity well within the normal range; however, strains from RB patients predisposed to second cancers exhibit increases in sensitivity to DNA-damaging agents

  2. Photowalk Exhibition opens at Microcosm

    CERN Document Server

    Katarina Anthony

    2011-01-01

    The winning photographs from the 2010 Global Particle Physics Photowalk competition will go on display at Microcosm from 11 February to 2 April. The exhibition is part of a global photography event taking place over three continents, with Photowalk exhibitions opening simultaneously at Fermilab in the US, KEK in Japan and here at CERN.   DESY wire chamber - First place people's choice; second place global jury competition. Photographer: Hans-Peter Hildebrandt  If you were one of the 1,300 photography lovers who voted in last year’s Photowalk competition, this exhibition is your chance to see the winning entries in print. The exhibition will take place in the downstairs gallery of Microcosm, overlooking the garden. 15 photographs will be on display, with each of the laboratories that participated in Photowalk represented by their 3 winning entries. Among them will be the “people’s choice” sunburst photo of a particle detector at DESY (Photo 1), and...

  3. Creating National Narrative: The Red Guard Art Exhibitions and the National Exhibitions in the Chinese Cultural Revolution 1966 - 1976

    Directory of Open Access Journals (Sweden)

    Winnie Tsang

    2014-06-01

    Full Text Available The artistic development in China experienced drastic changes during the Cultural Revolution from 1966 to 1976. Traditional Chinese art was denounced, whereas propaganda art became predominant in shaping the public’s loyalty towards the Communist Party and the country. Two major groups of art exhibitions emerged during the Revolution—the unofficial Red Guard art exhibitions organized by student activists in collaboration with local communes and art schools between 1966 and 1968, and the state-run national exhibitions from 1972 to 1975. These exhibitions were significant to this period because they were held frequently in the capital city Beijing and occasionally elsewhere, and through art they presented unique revolutionary beliefs to the Chinese people in a public setting. While the Red Guard art exhibitions and the national exhibitions certainly created different national narratives, I argue that the national exhibitions were in fact an attempt to revise the national narrative created by the Red Guard art exhibitions in order to re-establish a more utopian, consistent, and official national narrative. This paper unravels the intricate relationship between the two groups of exhibitions by comparing their exhibition venues, ideological focuses, work selection and quality editing. 

  4. Digital position sensitive discrimination for 2-dimensional scintillation detectors

    International Nuclear Information System (INIS)

    Engels, R.; Reinartz, R.; Reinhart, P.

    1996-01-01

    The energy sensitivity of a two-dimensional scintillation gamma detector based on position sensitive photomultipliers has been minimized by a digital differential discrimination unit. Since the photomultiplier gain is position-dependent by 50%, a discrimination unit has been developed where digital upper and lower discrimination levels are set due to the position-dependent photomultiplier gain obtained from calibration measurements. Depending on the spatial resolution there can be up to 65.536 position-sensitive discriminator levels defining energy windows. By this method, narrow discriminator windows can be used for reducing the low and high energy quanta without effecting the sensitivity of the detector. The new discrimination method, its performance and test measurements with gamma rays will be described. Furthermore experimental results are presented

  5. P(MMA-EMA Random Copolymer Electrolytes Incorporating Sodium Iodide for Potential Application in a Dye-Sensitized Solar Cell

    Directory of Open Access Journals (Sweden)

    Nurul Akmaliah Dzulkurnain

    2015-02-01

    Full Text Available Polymer electrolytes based on 90 wt% of methyl methacrylate and 10 wt% of ethyl methacrylate (90MMA-co-10EMA incorporating different weight ratios of sodium iodide were prepared using the solution casting method. The complexation between salt and copolymer host has been investigated using Fourier transform infrared spectroscopy. The ionic conductivity and thermal stability of the electrolytes were measured using impedance spectroscopy and differential scanning calorimetry, respectively. Scanning electron microscopy was used to study the morphology of the polymer electrolytes. The ionic conductivity and glass transition temperature increased up to 20 wt% of sodium iodide (5.19 × 10−6 S·cm−1 and decreased with the further addition of salt concentration, because of the crosslinked effect. The morphology behavior of the highest conducting sample also showed smaller pores compared to the other concentration. The total ionic transference number proved that this system was mainly due to ions, and the electrochemical stability window was up to 2.5 V, which is suitable for a dye-sensitized solar cell application. This sample was then tested in a dye-sensitized solar cell and exhibited an efficiency of 0.62%.

  6. Sensitivity of Mantel Haenszel Model and Rasch Model as Viewed From Sample Size

    OpenAIRE

    ALWI, IDRUS

    2011-01-01

    The aims of this research is to study the sensitivity comparison of Mantel Haenszel and Rasch Model for detection differential item functioning, observed from the sample size. These two differential item functioning (DIF) methods were compared using simulate binary item respon data sets of varying sample size,  200 and 400 examinees were used in the analyses, a detection method of differential item functioning (DIF) based on gender difference. These test conditions were replication 4 tim...

  7. Methanol leaves extract Hibiscus micranthus Linn exhibited antibacterial and wound healing activities.

    Science.gov (United States)

    Begashaw, Berhan; Mishra, Bharat; Tsegaw, Asegedech; Shewamene, Zewdneh

    2017-06-26

    Infectious diseases are the most common causes of morbidity and mortality in developing countries. Wound and wound infections are also major health problem. Nowadays, medicinal plants play a major role in treatment of infectious diseases and wound healing and they are easily available and more affordable as compared to synthetic compounds. The aim of this study is therefore, to investigate the antibacterial and wound healing activities of 80% methanol extract of Hibiscus micranthus leaves using disc diffusion methods and rat excision model respectively. In vitro antibacterial screening was carried out against S. aureus, S.pneumoniae, S. pyogenes, E. coli, P. aeruginosa, K. pneumoniae and P. mirabilis bacterial strains using disc-well diffusion assay. Would healing activity was done in rats divided into four groups each consisting of six animals. Group I was served as a negative control (ointment base), Group II served as a positive control Nitrofurazone (NFZ 0.2% ointment), Groups III and IV was treated 5 and 10% extracts respectively. The acute oral toxicity test and skin sensitivity test were also performed before conducting the actual study. The extract was analyzed for secondary metabolites using standard methods. Preliminary phytochemical screening have revealed the presence of alkaloids, flavonoids, saponins, tannins, steroids, phenols, diterpines, anthraquinones and the absence of glycosides, terpinoides and triterpines. Based on acute oral toxicity test the extract was found to be safe up to a dose of 2 g/kg. In addition, acute dermal toxicity test indicated no sign of skin irritation. The leaves extract exhibited varying degrees of sensitivity with zones of inhibition ranging from 14.00 ± 0.333 (S.pyogenes) to 22.67 ± 1.202 mm (S.aureus). It was found that S. aureus and S. pneumonia (p < 0.05) were the most sensitive to the extracts of the leaves at concentrations of 800 μg/ml and 400 μg/ml respectively followed by P. aeuruginosa [(18.33

  8. CD44+CD24+ subset of PANC-1 cells exhibits radiation resistance via decreased levels of reactive oxygen species.

    Science.gov (United States)

    Wang, Lei; Li, Pengping; Hu, Wei; Xia, Youyou; Hu, Chenxi; Liu, Liang; Jiang, Xiaodong

    2017-08-01

    Emerging evidence has suggested that pancreatic adenocarcinoma is sustained by pancreatic cancer stem cells. The present study aimed to investigate the expression patterns of the pancreatic cancer stem cell surface markers cluster of differentiation CD44 and CD24 in a pancreatic adenocarcinoma cell line, and to investigate the possible mechanisms for their radiation resistance. Flow cytometry was used to analyze the expression patterns of CD44 and CD24 in the pancreatic adenocarcinoma PANC-1 cell line. In addition, a multi-target click model was used to fit cell survival curves and determine the sensitizer enhancement ratio. The apoptosis and cycle distribution of the four cell subsets was determined using flow cytometry, and the level of reactive oxygen species (ROS) was determined using the 2',7'-dichlorofluorescin diacetate probe. The present results identified that the ratios of CD44 + and CD24 + in the sorted PANC-1 cell line were 92.0 and 4.7%, respectively. Prior to radiation, no statistically significant differences were observed among the four groups. Following treatment with 6 MV of X-rays, the rate of apoptosis was decreased in the CD44 + CD24 + group compared with other subsets. The percentage of G0/G1 cells was highest in the CD44 + CD24 + group compared with the three other groups, which exhibited increased radiosensitivity. In addition, the level of ROS in the CD44 + CD24 + group was reduced compared with the other groups. In summary, the results of the present study indicated that CD44 + CD24 + exhibited stem cell properties. The lower level of ROS and apoptosis in CD44 + CD24 + cells may contribute to their resistance to radiation in pancreatic adenocarcinoma.

  9. Thyroid Ultrasonography in Differentiation between Graves’ Disease and Hashimoto’s Thyroiditis

    Science.gov (United States)

    Pishdad, P.; Pishdad, G.R.; Tavanaa, S.; Pishdad, R.; Jalli, R.

    2017-01-01

    Objective: Graves’ disease and Hashimoto’s thyroiditis are the most common causes of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases, if the patient is euthyroid, may sometimes be extremely difficult on the basis of clinical and laboratory findings. The purpose of this study was to determine the sensitivity and specificity of gray scale sonography in differentiation of Graves’ disease from Hashimoto’s thyroiditis. Methods: This study included 149 patients divided into three groups, patients with Graves’ disease (34 patients, mean age = 36.8 ± 10.17 years), Patients with Hashimoto’s thyroiditis (62 patients, mean age = 33.4 ± 12.16 years) and control group (53 healthy people, mean age = 34.74 ± 16.87 years). Members of all groups were referred to a single radiologist for thyroid sonography for evaluation of thyroid echogenicity pattern. Results: A total of 117 women and 32 men were examined by sonography. The most common sonographic pattern in Hashimoto and Graves’ was homogenous hypo-echogenicity which was observed in 45.2% and 47.1% of cases, respectively. Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto’s group with 100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was observed in 17.6% of Graves’ group with 100% and 17.6% specificity and sensitivity, respectively. Conclusion: Our findings indicate that sonography has high specificity but low sensitivity in the diagnosis of either Graves’ disease or Hashimoto’s thyroiditis. It is therefore not possible to differentiate between these two diseases using sonography alone. Confirmation by laboratory data is also needed. PMID:28451576

  10. Designing immersion exhibits as border-crossing environments

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    2010-01-01

    be applied to achieve an understanding of the immersion exhibit form. The argument proceeds by demonstrating how the characteristics of immersion exhibits, and visitors to them, classify them as microcultures, and examining the implications of this for exhibit design using a hypothetical immersion exhibit...

  11. Cadmium stimulates myofibroblast differentiation and mouse lung fibrosis

    International Nuclear Information System (INIS)

    Hu, Xin; Fernandes, Jolyn; Jones, Dean P.; Go, Young-Mi

    2017-01-01

    Highlights: • Low-dose Cd stimulates differentiation of human lung fibroblast to myofibroblast. • Cd-stimulated fibrosis signaling involves activation of SMAD transcription factor. • Low-dose Cd intake in mice activates myofibroblast differentiation. - Abstract: Increasing evidence suggests that Cd at levels found in the human diet can cause oxidative stress and activate redox-sensitive transcription factors in inflammatory signaling. Following inflammation, tissue repair often involves activation of redox-sensitive transcription factors in fibroblasts. In lungs, epithelial barrier remodeling is required to restore gas exchange and barrier function, and aberrant myofibroblast differentiation leads to pulmonary fibrosis. Contributions of exogenous exposures, such as dietary Cd, to pulmonary fibrosis remain inCompletely defined. In the current study, we tested whether Cd activates fibrotic signaling in human fetal lung fibroblasts (HFLF) at micromolar and submicromolar Cd concentrations that do not cause cell death. Exposure of HFLF to low-dose Cd (≤1.0 μM) caused an increase in stress fibers and increased protein levels of myofibroblast differentiation markers, including α-smooth muscle actin (α-SMA) and extra-domain-A-containing fibronectin (ED-A-FN). Assay of transcription factor (TF) activity using a 45-TF array showed that Cd increased activity of 12 TF, including SMAD2/3/4 (mothers against decapentaplegic homolog) signaling differentiation and fibrosis. Results were confirmed by real-time PCR and supported by increased expression of target genes of SMAD2/3/4. Immunocytochemistry of lungs of mice exposed to low-dose Cd (0.3 and 1.0 mg/L in drinking water) showed increased α-SMA protein level with lung Cd accumulation similar to lung Cd in non-smoking humans. Together, the results show that relatively low Cd exposures stimulate pulmonary fibrotic signaling and myofibroblast differentiation by activating SMAD2/3/4-dependent signaling. The results

  12. Serotonin-related gene expression in female monkeys with individual sensitivity to stress.

    Science.gov (United States)

    Bethea, C L; Streicher, J M; Mirkes, S J; Sanchez, R L; Reddy, A P; Cameron, J L

    2005-01-01

    Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. In this study, the expression of four genes pivotal to serotonin neural function was assessed in monkeys previously categorized as highly stress resistant (n=3; normal menstrual cyclicity through two stress cycles), medium stress resistant (n=5; ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e. stress-sensitive; n=4; anovulatory as soon as stress is initiated). In situ hybridization and quantitative image analysis was used to measure mRNAs coding for SERT (serotonin transporter), 5HT1A autoreceptor, MAO-A and MAO-B (monoamine oxidases) at six levels of the dorsal raphe nucleus (DRN). Optical density (OD) and positive pixel area were measured with NIH Image software. In addition, serotonin neurons were immunostained and counted at three levels of the DRN. Finally, each animal was genotyped for the serotonin transporter long polymorphic region (5HTTLPR). Stress sensitive animals had lower expression of SERT mRNA in the caudal region of the DRN (PMAO-A mRNA signal in the stress-sensitive group (PMAO-A OD was positively correlated with progesterone from a pre-stress control cycle (PMAO-B mRNA exhibited a similar downward trend in the stress-sensitive group. MAO-B OD also correlated with control cycle progesterone (PMAO-A) or exhibited a lower trend (5HT1A, MAO-B) in the stress sensitive animals, which probably reflects the lower number of serotonin neurons present.

  13. Highly sensitive and selective determination of methylergometrine maleate using carbon nanofibers/silver nanoparticles composite modified carbon paste electrode.

    Science.gov (United States)

    Kalambate, Pramod K; Rawool, Chaitali R; Karna, Shashi P; Srivastava, Ashwini K

    2016-12-01

    A highly sensitive and selective voltammetric method for determination of Methylergometrine maleate (MM) in pharmaceutical formulations, urine and blood serum samples has been developed based on enhanced electrochemical response of MM at carbon nanofibers and silver nanoparticles modified carbon paste electrode (CNF-AgNP-CPE). The electrode material was characterized by various techniques viz., X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy. The electrocatalytic response of MM at CNF-AgNP-CPE was studied by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Under optimized conditions, the proposed sensor exhibits excellent electrochemical response towards MM. The DPV study shows greatly enhanced electrochemical signal for MM at CNF-AgNP-CPE lending high sensitivity to the proposed sensor for MM detection. The peak (Ip) current for MM is found to be rectilinear in the range 4.0×10(-8)-2.0×10(-5)M with a detection limit of 7.1×10(-9)M using DPV. The feasibility of the proposed sensor in analytical applications was investigated by conducting experiments on commercial pharmaceutical formulations, human urine and blood serum samples, which yielded satisfactory recoveries of MM. The proposed electrochemical sensor offers high sensitivity, selectivity, reproducibility and practical utility. We recommend it as an authentic and productive electrochemical sensor for successful determination of MM. Copyright © 2016. Published by Elsevier B.V.

  14. Augmented GNSS Differential Corrections Minimum Mean Square Error Estimation Sensitivity to Spatial Correlation Modeling Errors

    Directory of Open Access Journals (Sweden)

    Nazelie Kassabian

    2014-06-01

    Full Text Available Railway signaling is a safety system that has evolved over the last couple of centuries towards autonomous functionality. Recently, great effort is being devoted in this field, towards the use and exploitation of Global Navigation Satellite System (GNSS signals and GNSS augmentation systems in view of lower railway track equipments and maintenance costs, that is a priority to sustain the investments for modernizing the local and regional lines most of which lack automatic train protection systems and are still manually operated. The objective of this paper is to assess the sensitivity of the Linear Minimum Mean Square Error (LMMSE algorithm to modeling errors in the spatial correlation function that characterizes true pseudorange Differential Corrections (DCs. This study is inspired by the railway application; however, it applies to all transportation systems, including the road sector, that need to be complemented by an augmentation system in order to deliver accurate and reliable positioning with integrity specifications. A vector of noisy pseudorange DC measurements are simulated, assuming a Gauss-Markov model with a decay rate parameter inversely proportional to the correlation distance that exists between two points of a certain environment. The LMMSE algorithm is applied on this vector to estimate the true DC, and the estimation error is compared to the noise added during simulation. The results show that for large enough correlation distance to Reference Stations (RSs distance separation ratio values, the LMMSE brings considerable advantage in terms of estimation error accuracy and precision. Conversely, the LMMSE algorithm may deteriorate the quality of the DC measurements whenever the ratio falls below a certain threshold.

  15. Effects of extra virgin olive oil phenols on HL60 cell lines sensitive and resistant to anthracyclines

    Directory of Open Access Journals (Sweden)

    M. Crescimanno

    2009-01-01

    Full Text Available The aim of our study was to evaluate the capability of a crude extract of phenols from extra virgin olive oil of Moraiolo cultivar to induce apoptosis and/or differentiation in sensitive and resistant HL60 cell lines to anticancer drugs (Typical Multidrug Resistance. Our data highlight that the crude extract is able to induce apoptosis on both sensitive and resistant cells, whereas the exposure to a number of anticancer drugs does not induce apoptosis in resistant cells. In differentiation experiments we investigated the capability of crude extract of phenols to induce the expression of CD11 granulocytic or CD14 monocytic cell surface antigen in sensitive and resistant HL60 cell lines. At IC50 dose level (17 ug/ml and 32 ug/ml respectively for sensitive and resistant cell lines, the crude extract induced differentiation associated with the expression of CD14 monocytic cell lines but not that of CD11 granulocityc cell surface antigen. Further investigations are in progress to better clarify the mechanism by which olive oil phenols induce diffentiation on this cell line.

  16. Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

    Science.gov (United States)

    Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

    2017-12-01

    Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

  17. Surface Crack Detection for Carbon Fiber Reinforced Plastic Materials Using Pulsed Eddy Current Based on Rectangular Differential Probe

    Directory of Open Access Journals (Sweden)

    Jialong Wu

    2014-01-01

    Full Text Available Aiming at the surface defect inspection of carbon fiber reinforced composite, the differential and the direct measurement finite element simulation models of pulsed eddy current flaw detection were built. The principle of differential pulsed eddy current detection was analyzed and the sensitivity of defect detection was compared through two kinds of measurements. The validity of simulation results was demonstrated by experiments. The simulation and experimental results show that the pulsed eddy current detection method based on rectangular differential probe can effectively improve the sensitivity of surface defect detection of carbon fiber reinforced composite material.

  18. Risk-sensitive mean-field games

    KAUST Repository

    Tembine, Hamidou

    2014-04-01

    In this paper, we study a class of risk-sensitive mean-field stochastic differential games. We show that under appropriate regularity conditions, the mean-field value of the stochastic differential game with exponentiated integral cost functional coincides with the value function satisfying a Hamilton -Jacobi- Bellman (HJB) equation with an additional quadratic term. We provide an explicit solution of the mean-field best response when the instantaneous cost functions are log-quadratic and the state dynamics are affine in the control. An equivalent mean-field risk-neutral problem is formulated and the corresponding mean-field equilibria are characterized in terms of backward-forward macroscopic McKean-Vlasov equations, Fokker-Planck-Kolmogorov equations, and HJB equations. We provide numerical examples on the mean field behavior to illustrate both linear and McKean-Vlasov dynamics. © 1963-2012 IEEE.

  19. Risk-sensitive mean-field games

    KAUST Repository

    Tembine, Hamidou; Zhu, Quanyan; Başar, Tamer

    2014-01-01

    In this paper, we study a class of risk-sensitive mean-field stochastic differential games. We show that under appropriate regularity conditions, the mean-field value of the stochastic differential game with exponentiated integral cost functional coincides with the value function satisfying a Hamilton -Jacobi- Bellman (HJB) equation with an additional quadratic term. We provide an explicit solution of the mean-field best response when the instantaneous cost functions are log-quadratic and the state dynamics are affine in the control. An equivalent mean-field risk-neutral problem is formulated and the corresponding mean-field equilibria are characterized in terms of backward-forward macroscopic McKean-Vlasov equations, Fokker-Planck-Kolmogorov equations, and HJB equations. We provide numerical examples on the mean field behavior to illustrate both linear and McKean-Vlasov dynamics. © 1963-2012 IEEE.

  20. Low swing differential logic for mixed signal applications

    International Nuclear Information System (INIS)

    Fischer, P.; Kraft, E.

    2004-01-01

    Low swing differential logic operated at a constant bias current is a promising approach to reduce the switching noise in sensitive mixed mode circuits. Most differential logic families do not allow a significant change in bias current between cells so that it is difficult to optimize the power consumption for a required speed. A nonlinear load circuit for differential current-steering logic consisting of a current source in parallel with a diode connected FET is therefore proposed. The logic levels can be easily adjusted with an external supply voltage so that the circuit design is significantly simplified. As an example application a counter for the use in pixel readout chips is presented. The layout area using radiation hard design rules is not significantly larger than CMOS. The logic can be operated at very low power

  1. Adiponectin in mice with altered growth hormone action: links to insulin sensitivity and longevity?

    Science.gov (United States)

    Lubbers, Ellen R.; List, Edward O.; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D.; Kineman, Rhonda D.; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J.; Berryman, Darlene E.

    2013-01-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH versus IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying the effects of GH on adiponectin are depot-specific. Interestingly rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity. PMID:23261955

  2. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Sintropie Flavio Pellegrini From 13 to 24 March 2017 CERN Meyrin, Main Building Energia imprigionata - Flavio Pellegrini. The exhibition is composed by eleven wood artworks with the expression of movement as theme. The artworks are the result of harmonics math applied to sculpture. The powerful black colour is dominated by the light source, generating reflexes and modulations. The result is a continuous variation of perspective visions. The works generate, at a first approach, an emotion of mystery and incomprehension, only a deeper contemplation lets one discover entangling and mutative details, evidencing the elegance of the lines and letting the meaning emerge. For more information : staff.association@cern.ch | Tél: 022 766 37 38

  3. The Culture of Exhibitions and Conservation

    Directory of Open Access Journals (Sweden)

    Dimitrios Doumas

    2013-11-01

    Full Text Available The article reflects on temporary exhibitions from a theoretical as well as practical perspective. Regarded as a particularly effective mass-communication medium, exhibitions have a dual nature: they are scholarly undertakings, bringing off a curator’s vision and, simultaneously, they are projects with economic implications that need to be well managed and administered. The role of conservation in the making of temporary exhibitions, either in-house or touring, is here discussed in relation to how work is planned and prioritized as well as how time is managed and staff is allocated. Reference to weaknesses that lessen the crucial input of conservation in the decision-making process is also made. Much of the debate, which focuses on art exhibitions, concerns practicalities encountered in a private museum that extend from the very early stages of selecting objects for display to the mounting of an exhibition.

  4. Differential Susceptibility to the Environment: Are Developmental Models Compatible with the Evidence from Twin Studies?

    Science.gov (United States)

    Del Giudice, Marco

    2016-01-01

    According to models of differential susceptibility, the same neurobiological and temperamental traits that determine increased sensitivity to stress and adversity also confer enhanced responsivity to the positive aspects of the environment. Differential susceptibility models have expanded to include complex developmental processes in which genetic…

  5. From the hypergeometric differential equation to a non-linear Schrödinger one

    International Nuclear Information System (INIS)

    Plastino, A.; Rocca, M.C.

    2015-01-01

    We show that the q-exponential function is a hypergeometric function. Accordingly, it obeys the hypergeometric differential equation. We demonstrate that this differential equation can be transformed into a non-linear Schrödinger equation (NLSE). This NLSE exhibits both similarities and differences vis-a-vis the Nobre–Rego-Monteiro–Tsallis one. - Highlights: • We show that the q-exponential is a hypergeometric function. • It thus obeys the hypergeometric differential equation (HDE). • We show that the HDE can be cast as a non-linear Schrödinger equation. • This is different from the Nobre, Rego-Monteiro, Tsallis one.

  6. Downregulation of HIF-1a sensitizes U251 glioma cells to the temozolomide (TMZ) treatment

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jun-Hai [Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Ma, Zhi-Xiong [National Institute of Biological Sciences, Beijing 102206 (China); Huang, Guo-Hao; Xu, Qing-Fu; Xiang, Yan [Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China); Li, Ningning; Sidlauskas, Kastytis [Division of Neuropathology and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG (United Kingdom); Zhang, Eric Erquan [National Institute of Biological Sciences, Beijing 102206 (China); Lv, Sheng-Qing, E-mail: lvsq0518@hotmail.com [Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 (China)

    2016-05-01

    Purpose: The aim of this study was to investigate the effect of downregulation of HIF-1α gene on human U251 glioma cells and examine the consequent changes of TMZ induced effects and explore the molecular mechanisms. Methods: U251 cell line stably expressing HIF-1α shRNA was acquired via lentiviral vector transfection. The mRNA and protein expression alterations of genes involved in our study were determined respectively by qRT-PCR and Western blot. Cell proliferation was measured by MTT assay and colony formation assay, cell invasion/migration capacity was determined by transwell invasion assay/wound healing assay, and cell apoptosis was detected by flow cytometry. Results: We successfully established a U251 cell line with highly efficient HIF-1α knockdown. HIF-1a downregulation sensitized U251 cells to TMZ treatment and enhanced the proliferation-inhibiting, invasion/migration-suppressing, apoptosis-inducing and differentiation-promoting effects exerted by TMZ. The related molecular mechanisms demonstrated that expression of O{sup 6}-methylguanine DNA methyltransferase gene (MGMT) and genes of Notch1 pathway were significantly upregulated by TMZ treatment. However, this upregulation was abrogated by HIF-1α knockdown. We further confirmed important regulatory roles of HIF-1α in the expression of MGMT and activation of Notch1 pathways. Conclusion: HIF-1α downregulation sensitizes U251 glioma cells to the temozolomide treatment via inhibiting MGMT expression and Notch1 pathway activation. - Highlights: • TMZ caused more significant proliferation inhibition and apoptosis in U251 cells after downregulating HIF-1α. • Under TMZ treatment, HIF-1 downregulated U251 cells exhibited weaker mobility and more differentiated state. • TMZ caused MGMT over-expression and Notch1 pathway activation, which could be abrogated by HIF-1α downregulation.

  7. Covariant differential calculus on the quantum exterior vector space

    International Nuclear Information System (INIS)

    Parashar, P.; Soni, S.K.

    1992-01-01

    We formulate a differential calculus on the quantum exterior vector space spanned by the generators of a non-anticommutative algebra satisfying r ij = θ i θ j +B kl ij θ k θ l =0 i, j=1, 2, ..., n. and (θ i ) 2 =(θ j ) 2 =...=(θ n ) 2 =0, where B kl ij is the most general matrix defined in terms of complex deformation parameters. Following considerations analogous to those of Wess and Zumino, we are able to exhibit covariance of our calculus under ( 2 n )+1 parameter deformation of GL(n) and explicitly check that the non-anticommutative differential calculus satisfies the general constraints given by them, such as the 'linear' conditions dr ij ≅0 and the 'quadratic' condition r ij x n ≅0 where x n =dθ n are the differentials of the variables. (orig.)

  8. Enhancement of power conversion efficiency of dye-sensitized solar cells by co-sensitization of Phloxine B and Bromophenol blue dyes on ZnO photoanode

    Energy Technology Data Exchange (ETDEWEB)

    Kushwaha, Suman; Bahadur, Lal, E-mail: lbahadur@bhu.ac.in

    2015-05-15

    A single dye usually absorbs light only in a limited range of solar spectrum. In order to widen the absorption range, a combination of dyes, namely, Phloxine B and Bromophenol blue have been used as sensitizers in ZnO based dye sensitized solar cell (DSSC). It has been found that the DSSC sensitized by mixed dyes exhibited better photovoltaic performance than those observed with the DSSCs using test dyes individually. It has been ascribed to the enhanced absorption of light particularly in higher energy region (λ=400–550 nm) when both dyes were used together as was evident from the absorption spectra of dyes adsorbed onto ZnO electrode. The DSSC using ZnO electrode sensitized by mixed dyes provided J{sub SC}=5.6 mA cm{sup −2}, V{sub OC}=0.606 V, FF=0.53 and maximum energy conversion efficiency (η) of 1.35% on illuminating the cell with visible light of 150 mW cm{sup −2} intensity. - Highlights: • Phloxine B and Bromophenol blue have been used as sensitizers in ZnO based DSSC. • DSSC sensitized by mixed dyes exhibited better photovoltaic performance than those observed with the DSSCs using test dyes individually. • Enhanced absorption of light particularly in higher energy region (λ=400–550 nm) have been observed when both dyes were used together. • The DSSC using ZnO electrode sensitized by mixed dyes provided J{sub sc}=5.6 mA cm{sup −2}, V{sub oc}=0.606 V, FF=0.53. • Efficiency of 1.35% is achieved at visible light intensity of 150 mW cm{sup −2}.

  9. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions

    International Nuclear Information System (INIS)

    Ren Hongying; Cao Ying; Zhao, Qinjun; Li Jing; Zhou Cixiang; Liao Lianming; Jia Mingyue; Zhao Qian; Cai Huiguo; Han Zhongchao; Yang Renchi; Chen Guoqiang; Zhao, R.C.

    2006-01-01

    Low oxygen tension is a potent differentiation inducer of numerous cell types and an effective stimulus of many gene expressions. Here, we described that under 8% O 2 , bone marrow stromal cells (MSCs) exhibited proliferative and morphologic changes. The level of differentiated antigen H-2Dd and the number of G 2 /S/M phase cells increased evidently under 8% O 2 condition. Also, the proportion of wide, flattened, and epithelial-like cells (which were alkaline phosphatase staining positive) in MSCs increased significantly. When cultured in adipogenic medium, there was a 5- to 6-fold increase in the number of lipid droplets under hypoxic conditions compared with that in normoxic culture. We also demonstrated the existence of MSC differentiation under hypoxic conditions by electron microscopy. Expression of Oct4 was inhibited under 8% O 2 condition, but after adipocyte differentiation in normoxic culture and hypoxia-mimicking agents cobalt chloride (CoCl 2 ) and deferoxamine mesylate (DFX) treatments, Oct4 was still expressed in MSCs. These results indicate hypoxia accelerates MSC differentiation and hypoxia and hypoxia-mimicking agents exert different effects on MSC differentiation

  10. Detection and differentiation of the six Brucella species by polymerase chain reaction.

    Science.gov (United States)

    Sifuentes-Rincón, A M; Revol, A; Barrera-Saldaña, H A

    1997-11-01

    Brucelosis is a severe acute febrile disease caused by bacteria of the genus Brucella. Its current diagnosis is based on clinical observations that may be complemented by serology and microbiological culture tests; however, the former is limited in sensitivity and specificity, the latter is time consuming. To improve brucelosis diagnosis we developed a test which is specific and sensitive and is capable of differentiating the six species of Brucella. Four primers were designed from B. abortus sequences at the well-conserved Omp2 locus that are able to amplify the DNAs of all six species of Brucella. Our test detected all six species of Brucella. Their differentiation resulted directly from differences in the amplification patterns or was achieved indirectly using a RFLP present in one of the PCR products. The sensitivity and specificity of the new test were then determined; it was applied successfully in confirming the diagnosis of a patient whose clinical history and serology indicated infection with Brucella. The results make possible the use of a PCR test for Brucella detection and differentiation without relying on the measurement of the antibodies or microorganism culture. Our first results showed that the PCR test can confirm the presence of Brucella in blood samples of infected patients.

  11. Differential proteomics reveals novel insights into Nosema-honey bee interactions.

    Science.gov (United States)

    Kurze, Christoph; Dosselli, Ryan; Grassl, Julia; Le Conte, Yves; Kryger, Per; Baer, Boris; Moritz, Robin F A

    2016-12-01

    Host manipulation is a common strategy by parasites to reduce host defense responses, enhance development, host exploitation, reproduction and, ultimately, transmission success. As these parasitic modifications can reduce host fitness, increased selection pressure may result in reciprocal adaptations of the host. Whereas the majority of studies on host manipulation have explored resistance against parasites (i.e. ability to prevent or limit an infection), data describing tolerance mechanisms (i.e. ability to limit harm of an infection) are scarce. By comparing differential protein abundance, we provide evidence of host-parasite interactions in the midgut proteomes of N. ceranae-infected and uninfected honey bees from both Nosema-tolerant and Nosema-sensitive lineages. We identified 16 proteins out of 661 protein spots that were differentially abundant between experimental groups. In general, infections of Nosema resulted in an up-regulation of the bee's energy metabolism. Additionally, we identified 8 proteins that were differentially abundant between tolerant and sensitive honey bees regardless of the Nosema infection. Those proteins were linked to metabolism, response to oxidative stress and apoptosis. In addition to bee proteins, we also identified 3 Nosema ceranae proteins. Interestingly, abundance of two of these Nosema proteins were significantly higher in infected Nosema-sensitive honeybees relative to the infected Nosema-tolerant lineage. This may provide a novel candidate for studying the molecular interplay between N. ceranae and its honey bee host in more detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Online Exhibits & Concept Maps

    Science.gov (United States)

    Douma, M.

    2009-12-01

    Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors

  13. Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells

    Science.gov (United States)

    Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

    2015-01-01

    Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased γ-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity.Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively

  14. Affordances and distributed cognition in museum exhibitions

    DEFF Research Database (Denmark)

    Achiam, Marianne; May, Michael; Marandino, Martha

    2014-01-01

    consistent framework. Here, we invoke the notions of affordance and distributed cognition to explain in a coherent way how visitors interact with exhibits and exhibit spaces and make meaning from those interactions, and we exemplify our points using observations of twelve visitors to exhibits at a natural...... history museum. We show how differences in exhibit characteristics give rise to differences in the interpretive strategies used by visitors in their meaning-making process, and conclude by discussing how the notions of affordance and distributed cognition can be used in an exhibit design perspective....

  15. Sensitive determination of bisphenol A base on arginine functionalized nanocomposite graphene film

    International Nuclear Information System (INIS)

    Zhang Yan; Wang Letao; Lu Daban; Shi Xuezhao; Wang Chunming; Duan Xiaojuan

    2012-01-01

    Highlights: ► The water-soluble arginine functionalized graphene was produced successfully by an environment-friendly method. ► Electrochemical behaviors and some kinetic parameters of bisphenol A on the Arg-G/GCE were investigated. ► The proposed sensor showed more outstanding sensitivity properties toward the bisphenol A than the reported sensors. ► The proposed method opened a new simply way to detection of bisphenol A in the environmental protection. - Abstract: Arginine (Arg) functionalized graphene (Arg-G) nanocomposite was produced successfully by an environment-friendly method, and the morphology of the nanocomposite was characterized by transmission electron microscopy (TEM), Raman spectra, etc. Based on Arg-G nanocomposite, an electrochemical sensor was fabricated for sensitive detection of bisphenol A (BPA). The electrochemical behaviors of BPA on Arg-G modified glassy carbon electrode (GCE) were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Experimental parameters, such as the accumulation potential and time, scan rate, and the pH value of buffer solution were optimized. Under the optimized conditions, the oxidation peak current was proportional to BPA concentration in the range between 5.0 nmol/L and 40.0 μmol/L with the correlation coefficient of 0.9986 and the limit of detection of 1.1 nmol/L (S/N = 3). Moreover, the fabricated electrode also exhibited good reproducibility and stability. The proposed sensor was successfully employed to determine BPA in real plastic products and the recoveries were satisfactory.

  16. Holland at CERN – Industrial exhibition

    CERN Multimedia

    GS Department

    2010-01-01

    Sponsored by EVD, an agency of the Dutch Ministry of the Economy From 8 to 11 November 2010 Industrial Exhibition Administration Building Bldg. 61 9-00 - 17-30 Twenty seven companies will present their latest technology at the industrial exhibition "Holland at CERN". Dutch industry will exhibit products and technologies which are related to the field of particle physics. Individual interviews will take place directly at the stands in the Main Building. The firms will contact relevant users/technicians but any user wishing to make contact with a particular firm is welcome to use the contact details which are available from each departmental secretariat or at the following URL: http://gs-dep.web.cern.ch/gs-dep/groups/sem/ls/Industrial_Exhibitions.htm#Industrial_exhibitions You will find the list of exhibitors below. LIST OF EXHIBITORS: Schelde Exotech Vernooy BV Triumph Group INCAA Computers DeMaCo Holland bv TNO Science & Industry Janssen Precision Engi...

  17. Transposon mutagenesis reveals differential pathogenesis of Ralstonia solanacearum on tomato and Arabidopsis.

    Science.gov (United States)

    Lin, Yu-Mei; Chou, I-Chun; Wang, Jaw-Fen; Ho, Fang-I; Chu, Yu-Ju; Huang, Pei-Cheng; Lu, Der-Kang; Shen, Hwei-Ling; Elbaz, Mounira; Huang, Shu-Mei; Cheng, Chiu-Ping

    2008-09-01

    Ralstonia solanacearum causes a deadly wilting disease on a wide range of crops. To elucidate pathogenesis of this bacterium in different host plants, we set out to identify R. solanacearum genes involved in pathogenesis by screening random transposon insertion mutants of a highly virulent strain, Pss190, on tomato and Arabidopsis thaliana. Mutants exhibiting various decreased virulence levels on these two hosts were identified. Sequence analysis showed that most, but not all, of the identified pathogenesis genes are conserved among distinct R. solanacearum strains. A few of the disrupted loci were not reported previously as being involved in R. solanacearum pathogenesis. Notably, a group of mutants exhibited differential pathogenesis on tomato and Arabidopsis. These results were confirmed by characterizing allelic mutants in one other R. solanacearum strain of the same phylotype. The significantly decreased mutants' colonization in Arabidopsis was found to be correlated with differential pathogenesis on these two plants. Differential requirement of virulence genes suggests adaptation of this bacterium in different host environments. Together, this study reveals commonalities and differences of R. solanacearum pathogenesis on single solanaceous and nonsolanaceous hosts, and provides important new insights into interactions between R. solanacearum and different host plants.

  18. Cytogenetic analysis of a case of myxoid liposarcoma with cartilaginous differentiation

    NARCIS (Netherlands)

    Dijkhuizen, T; Molenaar, WM; Hoekstra, HJ; Wiersema, J; vandenBerg, E

    1996-01-01

    The cytogenetic analysis of a patient with a myxoid liposarcoma exhibiting cartilaginous differentiation is presented. A complex translocation involving chromosome 12, 16, and 19 was found, instead of the t(12;16), specific for myxoid liposarcoma. The involvement of 19q13 in a tumor with

  19. Plasmonic light-sensitive skins of nanocrystal monolayers

    Science.gov (United States)

    Akhavan, Shahab; Gungor, Kivanc; Mutlugun, Evren; Demir, Hilmi Volkan

    2013-04-01

    We report plasmonically coupled light-sensitive skins of nanocrystal monolayers that exhibit sensitivity enhancement and spectral range extension with plasmonic nanostructures embedded in their photosensitive nanocrystal platforms. The deposited plasmonic silver nanoparticles of the device increase the optical absorption of a CdTe nanocrystal monolayer incorporated in the device. Controlled separation of these metallic nanoparticles in the vicinity of semiconductor nanocrystals enables optimization of the photovoltage buildup in the proposed nanostructure platform. The enhancement factor was found to depend on the excitation wavelength. We observed broadband sensitivity improvement (across 400-650 nm), with a 2.6-fold enhancement factor around the localized plasmon resonance peak. The simulation results were found to agree well with the experimental data. Such plasmonically enhanced nanocrystal skins hold great promise for large-area UV/visible sensing applications.

  20. Michler’s Hydrol Blue: A Sensitive Probe for Amyloid Fibril Detection

    KAUST Repository

    Kitts, Catherine C.

    2011-05-03

    Michler\\'s hydrol blue (MHB) is investigated with respect to photophysical properties in varied solvent environment and when bound to insulin and lysozyme fibrils. The MHB chromophore is shown to act like a molecular rotor and bind well to amyloid fibrils, where it exhibits a characteristic red-shift in its excitation spectrum and an increase in the emission quantum yield upon binding. MHB is more sensitive to environmental changes than Thioflavin T (ThT) and furthermore, in contrast to the latter amyloid probe, can differentiate between insulin and lysozyme fibrils by a more red-shifted excitation spectrum for insulin fibrils. To support the experimental observations, time-dependent density functional theory (TDDFT) calculations were performed on MHB at several levels of theory. The predicted changes of spectral properties as a function of the environment are in good agreement with the experimental results. Linear dichroism (LD) is used to determine the orientation of the MHB within the fibrils. It was shown through LD and molecular modeling that MHB aligns itself preferentially parallel with the amyloid fiber at an angle of 14°-22° to the fibril axis and along the grooves of the β-sheet. © 2011 American Chemical Society.

  1. Ability of the rhTSH stimulation test to predict relapse in patients with differentiated thyroid carcinoma, after long-term follow-up

    Science.gov (United States)

    MARCELINO, MAFALDA; LOPES, ANA FILIPA; MADUREIRA, DEOLINDA; FERREIRA, TERESA C.; LIMBERT, EDWARD; LEITE, VALERIANO

    2015-01-01

    The analysis of serum thyroglobulin (Tg) following thyroid-stimulating hormone (TSH) stimulation (sTg) has been recommended in the follow-up of differentiated thyroid carcinoma (DTC) patients, however, its routine use remains controversial. The aim of the current study was to evaluate the accuracy of sTg testing following recombinant human (rh) TSH stimulation in DTC patients, with a follow-up of 12.4 years. Retrospective studies were conducted of 125 DTC patients, who underwent rhTSH stimulation testing between 1999 and 2002. The exclusion criteria were: Patients with anti-Tg antibodies, Tg levels >1 ng/ml under TSH suppression and the absence of radioactive iodine (RAI) ablation therapy following surgery. In total, 49 patients were included in the study and all had been previously treated with total or near total thyroidectomy (with or without central neck dissection) and RAI, postoperatively. The Tg functional sensitivity was 1.0 ng/ml. The follow-up for patients was performed annually. During the median follow-up of 12.4 years after the rhTSH stimulation test, nine patients exhibited recurrence (18.4%). Of the nine patients, six exhibited sTg levels >2 ng/ml (positive result) and three exhibited levels <2 ng/ml (negative result). Relapse occurred at a mean of 5.9 years following the rhTSH stimulation test. The positive predictive value and negative predictive value (NPV) of positive sTg were 50 and 91.9%, respectively, with a sensitivity of 66.6% and a specificity of 85.0%. The rhTSH-stimulated Tg levels have a high NPV, allowing the identification of the patients who are free of the tumour. These results are consistent with the previously published data; however, to the best of our knowledge, this is the study with the longest follow-up duration after rhTSH stimulation. PMID:25663898

  2. Multivariate sensitivity to voice during auditory categorization.

    Science.gov (United States)

    Lee, Yune Sang; Peelle, Jonathan E; Kraemer, David; Lloyd, Samuel; Granger, Richard

    2015-09-01

    Past neuroimaging studies have documented discrete regions of human temporal cortex that are more strongly activated by conspecific voice sounds than by nonvoice sounds. However, the mechanisms underlying this voice sensitivity remain unclear. In the present functional MRI study, we took a novel approach to examining voice sensitivity, in which we applied a signal detection paradigm to the assessment of multivariate pattern classification among several living and nonliving categories of auditory stimuli. Within this framework, voice sensitivity can be interpreted as a distinct neural representation of brain activity that correctly distinguishes human vocalizations from other auditory object categories. Across a series of auditory categorization tests, we found that bilateral superior and middle temporal cortex consistently exhibited robust sensitivity to human vocal sounds. Although the strongest categorization was in distinguishing human voice from other categories, subsets of these regions were also able to distinguish reliably between nonhuman categories, suggesting a general role in auditory object categorization. Our findings complement the current evidence of cortical sensitivity to human vocal sounds by revealing that the greatest sensitivity during categorization tasks is devoted to distinguishing voice from nonvoice categories within human temporal cortex. Copyright © 2015 the American Physiological Society.

  3. Histologic differentiation of desmoplastic melanoma from cicatrices.

    Science.gov (United States)

    Kaneishi, N K; Cockerell, C J

    1998-04-01

    Desmoplastic malignant melanoma (DMM) is a rare variant of melanoma that can be very difficult to diagnose correctly both clinically and histologically. The problem is compounded by the fact that many lesions persist at previous biopsy or excision sites so that scar tissue is often present admixed with or adjacent to the spindle cell neoplasm which may exhibit fibroblastic differentiation itself. In order to assess this problem, we compared and contrasted the histologic features of six DMM with 15 examples of cicatrices from various sources. Mature scars were readily differentiated from DMM by light microscopy. In contrast, immature scar and DMM had many features in common including hypercellularity, nodular lymphoid infiltrates, myxoid stroma, and atypical nuclei. The presence of a melanocytic proliferation within the epidermis above the dermal component, neurotropism, and S-100 and/or HMB-45 positivity of neoplastic cells were the only features that permitted reliable differentiation between the two. Clinical correlation and review of previous biopsy specimens are crucial in preventing a delayed diagnosis of DMM. Re-excision is advised in all questionable cases.

  4. Coupling between the differential and perturbation theory methods for calculating sensitivity coefficients in nuclear transmutation problems

    International Nuclear Information System (INIS)

    Rossi, Lubianka Ferrari Russo

    2014-01-01

    The main target of this study is to introduce a new method for calculating the coefficients of sensibility through the union of differential method and generalized perturbation theory, which are the two methods generally used in reactor physics to obtain such variables. These two methods, separated, have some issues turning the sensibility coefficients calculation slower or computationally exhaustive. However, putting them together, it is possible to repair these issues and build a new equation for the coefficient of sensibility. The method introduced in this study was applied in a PWR reactor, where it was performed the sensibility analysis for the production and 239 Pu conversion rate during 120 days (1 cycle) of burnup. The computational code used for both burnup and sensibility analysis, the CINEW, was developed in this study and all the results were compared with codes widely used in reactor physics, such as CINDER and SERPENT. The new mathematical method for calculating the sensibility coefficients and the code CINEW provide good numerical agility and also good efficiency and security, once the new method, when compared with traditional ones, provide satisfactory results, even when the other methods use different mathematical approaches. The burnup analysis, performed using the code CINEW, was compared with the code CINDER, showing an acceptable variation, though CINDER presents some computational issues due to the period it was built. The originality of this study is the application of such method in problems involving temporal dependence and, not least, the elaboration of the first national code for burnup and sensitivity analysis. (author)

  5. Role of glutathione in determining the differential sensitivity between the cortical and cerebellar regions towards mercury-induced oxidative stress

    International Nuclear Information System (INIS)

    Kaur, Parvinder; Aschner, Michael; Syversen, Tore

    2007-01-01

    Certain discrete areas of the CNS exhibit enhanced sensitivity towards MeHg. To determine whether GSH is responsible for this particular sensitivity, we investigated its role in MeHg-induced oxidative insult in primary neuronal and astroglial cell cultures of both cerebellar and cortical origins. For this purpose, ROS and GSH were measured with the fluorescent indicators, CMH 2 DCFDA and MCB. Cell associated-MeHg was measured with 14 C-radiolabeled MeHg. The intracellular GSH content was modified by pretreatment with NAC or DEM. For each of the dependent variables (ROS, GSH, and MTT), there was an overall significant effect of cellular origin, MeHg and pretreatment in all the cell cultures. A trend towards significant interaction between origin x MeHg x pretreatment was observed only for the dependent variable, ROS (astrocytes p = 0.056; neurons p = 0.000). For GSH, a significant interaction between origin x MeHg was observed only in astrocytes (p = 0.030). The cerebellar cell cultures were more vulnerable (astrocytes mean = 223.77; neurons mean = 138.06) to ROS than the cortical cell cultures (astrocytes mean = 125.18; neurons mean 107.91) for each of the tested treatments. The cell associated-MeHg increased when treated with DEM, and the cerebellar cultures varied significantly from the cortical cultures. Non-significant interactions between origin x MeHg x pretreatment for GSH did not explain the significant interactions responsible for the increased amount of ROS produced in these cultures. In summary, although GSH modulation influences MeHg-induced toxicity, the difference in the content of GSH in cortical and cerebellar cultures fails to account for the increased ROS production in cerebellar cultures. Hence, different approaches for the future studies regarding the mechanisms behind selectivity of MeHg have been discussed

  6. Identification of Subgroups of Women with Carpal Tunnel Syndrome with Central Sensitization.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Fernández-Muñoz, Juan J; Navarro-Pardo, Esperanza; da-Silva-Pocinho, Ricardo F; Ambite-Quesada, Silvia; Pareja, Juan A

    2016-09-01

    Identification of subjects with different sensitization mechanisms can help to identify better therapeutic strategies for carpal tunnel syndrome (CTS). The aim of the current study was to identify subgroups of women with CTS with different levels of sensitization. A total of 223 women with CTS were recruited. Self-reported variables included pain intensity, function, disability, and depression. Pressure pain thresholds (PPT) were assessed bilaterally over median, ulnar, and radial nerves, C5-C6 joint, carpal tunnel, and tibialis anterior to assess widespread pressure pain hyperalgesia. Heat (HPT) and cold (CPT) pain thresholds were also bilaterally assessed over the carpal tunnel and the thenar eminence to determine thermal pain hyperalgesia. Pinch grip force between the thumb and the remaining fingers was calculated to determine motor assessment. Subgroups were determined according to the status on a previous clinical prediction rule: PPT over the affected C5-C6 joint 66 points. The ANOVA showed that women within group 1 (positive rule, n = 60) exhibited bilateral widespread pressure hyperalgesia (P < 0.001) and bilateral thermal thresholds (P < 0.001) than those within group 2 (negative rule, n = 162). Women in group 1 also exhibited higher depression than those in group 2 (P = 0.023). No differences in self-reported variables were observed. This study showed that a clinical prediction rule originally developed for identifying women with CTS who are likely to respond favorably to manual physical therapy was able to identify women exhibiting higher widespread pressure hyper-sensitivity and thermal hyperalgesia. This subgroup of women with CTS exhibiting higher sensitization may need specific therapeutic programs. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence.

    Science.gov (United States)

    Nikitopoulos, Jörg; Zohsel, Katrin; Blomeyer, Dorothea; Buchmann, Arlette F; Schmid, Brigitte; Jennen-Steinmetz, Christine; Becker, Katja; Schmidt, Martin H; Esser, Günter; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred

    2014-12-01

    Insensitive and unresponsive caregiving during infancy has been linked to externalizing behavior problems during childhood and adolescence. The 7-repeat (7r) allele of the dopamine D4 receptor (DRD4) gene has meta-analytically been associated with a heightened susceptibility to adverse as well as supportive environments. In the present study, we examined long-term effects of early maternal care, DRD4 genotype and the interaction thereof on externalizing and internalizing psychopathology during adolescence. As part of an ongoing epidemiological cohort study, early maternal care was assessed at child's age 3 months during a nursing and playing situation. In a sample of 296 offspring, externalizing and internalizing symptoms were assessed using a psychiatric interview conducted at age 15 years. Parents additionally filled out a questionnaire on their children's psychopathic behaviors. Results indicated that adolescents with the DRD4 7r allele who experienced less responsive and stimulating early maternal care exhibited more symptoms of ADHD and CD/ODD as well as higher levels of psychopathic behavior. In accordance with the hypothesis of differential susceptibility, 7r allele carriers showed fewer ADHD symptoms and lower levels of psychopathic behavior when exposed to especially beneficial early caregiving. In contrast, individuals without the DRD4 7r allele proved to be insensitive to the effects of early maternal care. This study replicates earlier findings with regard to an interaction between DRD4 genotype and early caregiving on externalizing behavior problems in preschoolers. It is the first one to imply continuity of this effect until adolescence. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    Directory of Open Access Journals (Sweden)

    Li Chen

    2018-05-01

    Full Text Available Human stromal stem cells (hMSCs differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs: Cofilin 1 (CFL1 and Destrin (DSTN or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4. In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1 which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation. Keywords: Actin cytoskeleton, Actin depolymerizing factors, Adipocyte differentiation, Human stromal stem cells

  9. Electromyographic Study of Differential Sensitivity to Succinylcholine of the Diaphragm, Laryngeal and Somatic Muscles: A Swine Model

    Directory of Open Access Journals (Sweden)

    I-Cheng Lu

    2010-12-01

    Full Text Available Neuromuscular blocking agents (NMBAs might diminish the electromyography signal of the vocalis muscles during intraoperative neuromonitoring of the recurrent laryngeal nerve. The aim of this study was to compare differential sensitivity of different muscles to succinylcholine in a swine model, and to realize the influence of NMBAs on neuromonitoring. Six male Duroc-Landrace piglets were anesthetized with thiamylal and underwent tracheal intubation without the use of an NMBA. The left recurrent laryngeal nerve, the spinal accessory nerve, the right phrenic nerve and the brachial plexus were stimulated. Evoked potentials (electromyography signal of four muscle groups were elicited from needle electrodes before and after intravenous succinylcholine bolus (1.0 mg/kg. Recorded muscles included the vocalis muscles, trapezius muscle, diaphragm and triceps brachii muscles. The onset time and 80% recovery of control response were recorded and analyzed. The testing was repeated after 30 minutes. The onset time of neuromuscular blocking for the vocalis muscles, trapezius muscle, diaphragm and triceps brachii muscle was 36.3 ± 6.3 seconds, 38.8 ± 14.9 seconds, 52.5 ± 9.7 seconds and 45.0 ± 8.2 seconds during the first test; and 49.3 ± 10.8 seconds, 40.0 ± 12.2 seconds, 47.5 ± 11.9 seconds and 41.3 ± 10.1 seconds during the second test. The 80% recovery of the control response for each muscle was 18.3 ± 2.7 minutes, 16.5±6.9 minutes, 8.1±2.5 minutes and 14.8±2.9 minutes during the first test; and 21.5±3.8 minutes, 12.5 ± 4.3 minutes, 10.5 ± 3.1 minutes and 16.4 ± 4.2 minutes during the second test. The sensitivity of the muscles to succinylcholine, ranked in order, was: the vocalis muscles, the triceps brachii muscle, the trapezius muscle and the diaphragm. We demonstrated a useful and reliable animal model to investigate the effects of NMBAs on intraoperative neuromonitoring. Extrapolation of these data to humans should be done with caution.

  10. Differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension.

    Science.gov (United States)

    Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2012-01-01

    Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

  11. Differentiation of human umbilical cord mesenchymal stromal cells into low immunogenic hepatocyte-like cells.

    Science.gov (United States)

    Zhao, Qinjun; Ren, Hongying; Li, Xiyuan; Chen, Zhong; Zhang, Xiangyu; Gong, Wei; Liu, Yongjun; Pang, Tianxiang; Han, Zhong Chao

    2009-01-01

    Mesenchymal stromal cells (MSC) isolated from several human tissues have been known to differentiate into the hepatic lineage in vitro, but the immunogenicity of the differentiated hepatocyte-like cells (DHC) has not been reported. Umbilical cord (UC) MSC are thought to be an attractive cell source for cell therapy because of their young age and low infection rate compared with adult tissue MSC. Hepatic differentiation of UC-MSC was induced with a 2-step protocol. The expressions of hepatic markers were detected by RT-PCR and immunofluorescence staining. Albumin production and urea secretion were measured by ELISA and colorimetric assay respectively. The immunosuppressive properties of DHC was detected by mixed lymphocyte culture. After incubation with specific growth factors, including hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF), UC MSC exhibited a high hepatic differentiation ability in an adherent culture condition. The differentiated UC MSC showed hepatocyte-like morphology and expressed several liver-specific markers at gene and protein levels. Furthermore, the DHC exhibited hepatocyte-specific functions, including albumin secretion, low-density lipoprotein uptake and urea production. More importantly, DHC did not express major histocompatibility complex (MHC) II antigen and were not able to induce lymphocyte proliferation in mixed lymphocyte culture, as undifferentiated UC MSC did. Our results indicate that UC MSC are able to differentiate into functional hepatocyte-like cells that still retain their low immunogenicity in vitro. More importantly, DHC incorporated into the parenchyma of liver when transplanted into mice with CCl(4)-induced liver injury. Therefore, DHC may be an ideal source for cell therapy of liver diseases.

  12. Apomorphine conditioning and sensitization: the paired/unpaired treatment order as a new major determinant of drug conditioned and sensitization effects.

    Science.gov (United States)

    de Matos, Liana Wermelinger; Carey, Robert J; Carrera, Marinete Pinheiro

    2010-09-01

    Repeated treatments with psychostimulant drugs generate behavioral sensitization. In the present study we employed a paired/unpaired protocol to assess the effects of repeated apomorphine (2.0 mg/kg) treatments upon locomotion behavior. In the first experiment we assessed the effects of conditioning upon apomorphine sensitization. Neither the extinction of the conditioned response nor a counter-conditioning procedure in which we paired an inhibitory treatment (apomorphine 0.05 mg/kg) with the previously established conditioned stimulus modified the sensitization response. In the second experiment, we administered the paired/unpaired protocol in two phases. In the second phase, we reversed the paired/unpaired protocol. Following the first phase, the paired group alone exhibited conditioned locomotion in the vehicle test and a sensitization response. In the second phase, the initial unpaired group which received 5 paired apomorphine trials during the reversal phase did not develop a conditioned response but developed a potentiated sensitization response. This disassociation of the conditioned response from the sensitization response is attributed to an apomorphine anti-habituation effect that can generate a false positive Pavlovian conditioned response effect. The potentiated sensitization response induced by the treatment reversal protocol points to an important role for the sequential experience of the paired/unpaired protocol in behavioral sensitization. 2010 Elsevier Inc. All rights reserved.

  13. "Detecting Differential Item Functioning and Differential Step Functioning due to Differences that ""Should"" Matter"

    Directory of Open Access Journals (Sweden)

    Tess Miller

    2010-07-01

    Full Text Available This study illustrates the use of differential item functioning (DIF and differential step functioning (DSF analyses to detect differences in item difficulty that are related to experiences of examinees, such as their teachers' instructional practices, that are relevant to the knowledge, skill, or ability the test is intended to measure. This analysis is in contrast to the typical use of DIF or DSF to detect differences related to characteristics of examinees, such as gender, language, or cultural knowledge, that should be irrelevant. Using data from two forms of Ontario's Grade 9 Assessment of Mathematics, analyses were performed comparing groups of students defined by their teachers' instructional practices. All constructed-response items were tested for DIF using the Mantel Chi-Square, standardized Liu Agresti cumulative common log-odds ratio, and standardized Cox's noncentrality parameter. Items exhibiting moderate to large DIF were subsequently tested for DSF. In contrast to typical DIF or DSF analyses, which inform item development, these analyses have the potential to inform instructional practice.

  14. Tailoring force sensitivity and selectivity by microstructure engineering of multidirectional electronic skins

    Science.gov (United States)

    Park, Jonghwa; Kim, Jinyoung; Hong, Jaehyung; Lee, Hochan; Lee, Youngoh; Cho, Seungse; Kim, Sung-Woo; Kim, Jae Joon; Kim, Sung Youb; Ko, Hyunhyub

    2018-04-01

    Electronic skins (e-skins) with high sensitivity to multidirectional mechanical stimuli are crucial for healthcare monitoring devices, robotics, and wearable sensors. In this study, we present piezoresistive e-skins with tunable force sensitivity and selectivity to multidirectional forces through the engineered microstructure geometries (i.e., dome, pyramid, and pillar). Depending on the microstructure geometry, distinct variations in contact area and localized stress distribution are observed under different mechanical forces (i.e., normal, shear, stretching, and bending), which critically affect the force sensitivity, selectivity, response/relaxation time, and mechanical stability of e-skins. Microdome structures present the best force sensitivities for normal, tensile, and bending stresses. In particular, microdome structures exhibit extremely high pressure sensitivities over broad pressure ranges (47,062 kPa-1 in the range of <1 kPa, 90,657 kPa-1 in the range of 1-10 kPa, and 30,214 kPa-1 in the range of 10-26 kPa). On the other hand, for shear stress, micropillar structures exhibit the highest sensitivity. As proof-of-concept applications in healthcare monitoring devices, we show that our e-skins can precisely monitor acoustic waves, breathing, and human artery/carotid pulse pressures. Unveiling the relationship between the microstructure geometry of e-skins and their sensing capability would provide a platform for future development of high-performance microstructured e-skins.

  15. Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

    Science.gov (United States)

    Rao, Sambasiva P.; Sancho, Jose; Campos-Rivera, Juanita; Boutin, Paula M.; Severy, Peter B.; Weeden, Timothy; Shankara, Srinivas; Roberts, Bruce L.; Kaplan, Johanne M.

    2012-01-01

    Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact. PMID:22761788

  16. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis.

    Directory of Open Access Journals (Sweden)

    Sambasiva P Rao

    Full Text Available Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs display the highest number while natural killer (NK cells, plasmacytoid dendritic cells (pDCs and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact.

  17. Filters in topology optimization based on Helmholtz‐type differential equations

    DEFF Research Database (Denmark)

    Lazarov, Boyan Stefanov; Sigmund, Ole

    2011-01-01

    The aim of this paper is to apply a Helmholtz‐type partial differential equation as an alternative to standard density filtering in topology optimization problems. Previously, this approach has been successfully applied as a sensitivity filter. The usual filtering techniques in topology...... from the neighbor subdomains is an expensive operation. The proposed filter technique requires only mesh information necessary for the finite element discretization of the problem. The main idea is to define the filtered variable implicitly as a solution of a Helmholtz‐type differential equation...

  18. High-sensitivity C-reactive protein does not improve the differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes: A grey zone analysis.

    Science.gov (United States)

    Bellanné-Chantelot, C; Coste, J; Ciangura, C; Fonfrède, M; Saint-Martin, C; Bouché, C; Sonnet, E; Valéro, R; Lévy, D-J; Dubois-Laforgue, D; Timsit, J

    2016-02-01

    Low plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been suggested to differentiate hepatocyte nuclear factor 1 alpha-maturity-onset diabetes of the young (HNF1A-MODY) from type 2 diabetes (T2D). Yet, differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes (F-YT2D) remains a difficult challenge. Thus, this study assessed the added value of hs-CRP to distinguish between the two conditions. This prospective multicentre study included 143 HNF1A-MODY patients, 310 patients with a clinical history suggestive of HNF1A-MODY, but not confirmed genetically (F-YT2D), and 215 patients with T2D. The ability of models, including clinical characteristics and hs-CRP to predict HNF1A-MODY was analyzed, using the area of the receiver operating characteristic (AUROC) curve, and a grey zone approach was used to evaluate these models in clinical practice. Median hs-CRP values were lower in HNF1A-MODY (0.25mg/L) than in F-YT2D (1.14mg/L) and T2D (1.70mg/L) patients. Clinical parameters were sufficient to differentiate HNF1A-MODY from classical T2D (AUROC: 0.99). AUROC analyses to distinguish HNF1A-MODY from F-YT2D were 0.82 for clinical features and 0.87 after including hs-CRP. For the grey zone analysis, the lower boundary was set to missMODY with F-YT2D, 65% of patients were classified in between these categories - in the zone of diagnostic uncertainty - even after adding hs-CRP to clinical parameters. hs-CRP does not improve the differential diagnosis of HNF1A-MODY and F-YT2D. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Students-exhibits interaction at a science center

    Science.gov (United States)

    Botelho, Agostinho; Morais, Ana M.

    2006-12-01

    In this study we investigate students' learning during their interaction with two exhibits at a science center. Specifically, we analyze both students' procedures when interacting with exhibits and their understanding of the scientific concepts presented therein. Bernstein's theory of pedagogic discourse (1990, 2000) provided the sociological foundation to assess the exhibit-student interaction and allowed analysis of the influence of the characteristics of students, exhibits, and interactions on students' learning. Eight students (ages 12ndash;13 years of age) with distinct sociological characteristics participated in the study. Several findings emerged from the results. First, the characteristics of the students, exhibits, and interactions appeared to influence student learning. Second, to most students, what they did interactively (procedures) seems not to have had any direct consequence on what they learned (concept understanding). Third, the data analysis suggest an important role for designers and teachers in overcoming the limitations of exhibit-student interaction.

  20. A nitrate sensitive planar optode; performance and interferences

    DEFF Research Database (Denmark)

    Pedersen, Lasse; Dechesne, Arnaud; Smets, Barth F.

    2015-01-01

    We present a newly developed nitrate sensitive planar optode. It exhibits a linear response to nitrate from 1 to 50 mM at pH 8.0, a fast response time below 10 s and a good lifetime, allowing for fast two dimensional nitrate measurements over long periods of time. Interference from nitrite...

  1. Ligase-deficient yeast cells exhibit defective DNA rejoining and enhanced gamma ray sensitivity

    International Nuclear Information System (INIS)

    Moore, C.W.

    1982-01-01

    Yeast cells deficient in DNA ligase were also deficient in their capacity to rejoin single-strand scissions in prelabeled nuclear DNA. After high-dose-rate gamma irradiation (10 and 25 krads), cdc9-9 mutant cells failed to rejoin single-strand scissions at the restrictive temperature of 37 0 C. In contrast, parental (CDC9) cells (incubated with mutant cells both during and after irradiation) exhibited rapid medium-independent DNA rejoining after 10 min of post-irradiation incubation and slower rates of rejoining after longer incubation. Parental cells were also more resistant than mutant cells to killing by gamma irradiation. Approximately 2.5 +- 0.07 and 5.7 +- 0.6 single-strand breaks per 10 8 daltons were detected in DNAs from either CDC9 or cdc9-9 cells converted to spheroplasts immediately after 10 and 25 krads of irradiation, respectively. At the permissive temperature of 23 0 C, the cdc9-9 cells contained 2 to 3 times the number of DNA single-strand breaks as parental cells after 10 min to 4 h of incubation after 10 krads of irradiation, and two- to eightfold more breaks after 10 min to 2.5 h of incubation after 25 krads of irradiation. Rejoining of single-strand scissions was faster in medium. After only 10 min in buffered growth medium after 10 krads of irradiation, the number of DNA single-strand breaks was reduced to 0.32 +- 0.3 (at 23 0 C) or 0.21 +- 0.05 (at 37 0 C) per 10 8 daltons in parental cells, but remained at 2.1 +- 0.06 (at 23 0 C) or 2.3 +- 0.07 (at 37 0 C) per 10 8 daltons in mutant cells. After 10 or 25 krads of irradiation plus 1 h of incubation in medium at 37 0 C, only DNA from CDC9 cells was rejoined to the size of DNA from unirradiated cells, whereas at 23 0 C, DNAs in both strains were completely rejoined

  2. Differential antibiotic sensitivity determined by the large ribosomal subunit in thermophilic archaea.

    OpenAIRE

    Ruggero, D; Londei, P

    1996-01-01

    Hybrid ribosomes obtained by mixing the ribosomal subunits of the extremely thermophilic archaea Sulfolobus solfataricus and Desulfurococcus mobilis were tested for their sensitivity to selected antibiotics. It is shown that structural differences in the large ribosomal subunits determine qualitatively and quantitatively the patterns of response to alpha-sarcin and paromomycin in these species.

  3. Ontogeny of pulmonary alveolar epithelial markers of differentiation.

    Science.gov (United States)

    Joyce-Brady, M F; Brody, J S

    1990-02-01

    We studied differentiation of the pulmonary epithelium in the periphery of fetal rat lung in vivo and in vitro by comparing the ontogeny of cell-surface glycoconjugates with that of surfactant phospholipids. Apical surface binding of the lectin Maclura pomifera agglutinin (MPA) and expression of a 200-kDa MPA-binding glycoprotein (MPA-gp200) was evident at 20 days gestation in type 2 cells, but did not correlate with ultrastructural features of type 2 cell differentiation. Epithelial cells isolated from peripheral lung of 18-day gestation fetal rats displayed hormone-sensitive surfactant synthesis prior to the hormone-insensitive expression of MPA-gp200. Expression of MPA-gp200 occurred in association with the appearance of many new apical surface proteins suggesting a hormone-independent process of polar membrane differentiation. Thus membrane and secretory differentiation are discordant and can be dissociated. In vivo binding of Ricinus communis 1 agglutinin (RCA1), an apical marker of the differentiated alveolar type 1 cell occurred in undifferentiated peripheral lung epithelial cells as early as 18 days gestation, disappeared from differentiating type 2 cells and appeared in differentiated type 1 cells. Both undifferentiated fetal epithelial cells at 18 days gestation and fully differentiated type 1 cells express multiple glycoproteins with terminal beta-linked galactose residues which bind RCA1. Some of these RCA1-binding glycoproteins appear to be similar. These observations suggest that alveolar epithelial type 1 cells may derive directly from undifferentiated peripheral lung epithelial cells as well as from fully differentiated type 2 cells. In addition, terminal differentiation of fetal lung peripheral epithelium into type 1 and type 2 cells may involve repression as well as induction of differentiation-related genes.

  4. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells.

    Science.gov (United States)

    Chen, Li; Hu, Huimin; Qiu, Weimin; Shi, Kaikai; Kassem, Moustapha

    2018-05-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Diffuse reflectance spectroscopy for optical soft tissue differentiation as remote feedback control for tissue-specific laser surgery.

    Science.gov (United States)

    Stelzle, Florian; Tangermann-Gerk, Katja; Adler, Werner; Zam, Azhar; Schmidt, Michael; Douplik, Alexandre; Nkenke, Emeka

    2010-04-01

    Laser surgery does not provide haptic feedback for operating layer-by-layer and thereby preserving vulnerable anatomical structures like nerve tissue or blood vessels. Diffuse reflectance spectra can facilitate remote optical tissue differentiation. It is the aim of the study to use this technique on soft tissue samples, to set a technological basis for a remote optical feedback system for tissue-specific laser surgery. Diffuse reflectance spectra (wavelength range: 350-650 nm) of ex vivo types of soft tissue (a total of 10,800 spectra) of the midfacial region of domestic pigs were remotely measured under reduced environmental light conditions and analyzed in order to differentiate between skin, mucosa, muscle, subcutaneous fat, and nerve tissue. We performed a principal components (PC) analysis (PCA) to reduce the number of variables. Linear discriminant analysis (LDA) was utilized for classification. For the tissue differentiation, we calculated the specificity and sensitivity by receiver operating characteristic (ROC) analysis and the area under curve (AUC). Six PCs were found to be adequate for tissue differentiation with diffuse reflectance spectra using LDA. All of the types of soft tissue could be differentiated with high specificity and sensitivity. Only the tissue pairs nervous tissue/fatty tissue and nervous tissue/mucosa showed a decline of differentiation due to bio-structural similarity. However, both of these tissue pairs could still be differentiated with a specificity and sensitivity of more than 90%. Analyzing diffuse reflectance spectroscopy with PCA and LDA allows for remote differentiation of biological tissue. Considering the limitations of the ex vivo conditions, the obtained results are promising and set a basis for the further development of a feedback system for tissue-specific laser surgery. (c) 2010 Wiley-Liss, Inc.

  6. Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

    International Nuclear Information System (INIS)

    Chen, P.-Y.; Huang, Lynn L.H.; Hsieh, H.-J.

    2007-01-01

    For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs

  7. Hypermutability of a UV-sensitive aphidicolin-resistant mutant of Chinese hamster fibroblasts

    International Nuclear Information System (INIS)

    Liu, P.K.; Chang, C.; Trosko, J.E.

    1982-01-01

    An ultraviolet light (UV)-sensitive thymidine auxotroph of Chinese hamster V79 cells that exhibits pleiotropic effects such as a high level of deoxycytidine triphosphate, slow growth, sensitivity to cytidine, and high frequencies of site-specific bromodeoxyuridine-dependent chromosomal aberrations was selected by its resistance to aphidicolin. The UV-induced mutability of this mutant and one of its revertants, which retains some of the phenotypes listed above, was studied in 3 mutation assay systems. The results showed that the mutant was hypermutable for ouabain and diphtheria-toxin-resistant mutations compared to wild-type V79 cells at the same UV dose or the same survival level. The mutant exhibits a delayed expression of maximal frequency of induced 6-thioguanine-resistant mutants. When maximal frequencies are compared at the same UV dose, the mutant also has higher mutation frequencies at the hypoxanthine-guanine phosphoribosyl transferase locus. The revertant was similar to the wild-type in UV sensitivity and mutability. (orig./AJ)

  8. Differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension.

    Directory of Open Access Journals (Sweden)

    Victoria L M Herrera

    Full Text Available Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs affecting blood pressure (BP in 16-month old post-menopausal F2 (Dahl S×R-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001 and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001 F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50 and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65, four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5 were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

  9. Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

    Directory of Open Access Journals (Sweden)

    Xiaoke Ma

    2015-06-01

    Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

  10. Effect of Fluticasone and Salmeterol on Tracheal Responsiveness to Ovalbumin and Lung Inflammation, Administrated during and after Sensitization

    Directory of Open Access Journals (Sweden)

    Zahra Gholamnezhad

    2014-01-01

    Full Text Available The effect of duration of administration of fluticasone propionate and salmeterol on tracheal responsiveness to ovalbumin and total and differential white blood cell in sensitized guinea pig was examined. Six groups of guinea pigs (n=7 were sensitized to ovalbumin. Three groups of them were subjected to inhaled fluticasone propionate and salmeterol, one group during sensitization (A, one group after that (for 18 days, B, and the other one during sensitization but with 18 days delay before measurements (C. Three other groups were treated with placebo in the same manner. The tracheal responsiveness to ovalbumin and total and differential white blood cells of three placebo groups were significantly higher than those of control group (P<0.001 for all cases. Tracheal responsiveness to ovalbumin and total and differential white blood cell in treated groups with fluticasone propionate and salmeterol were significantly decreased compared to those of placebo groups (nonsignificant to P<0.001. The improvement in all variables in treatment groups A and C were more pronounced than group B. The results showed that fluticasone propionate and salmeterol had a prevention effect on tracheal hyperresponsiveness to ovalbumin and lung inflammation which was more pronounced when administered during than after sensitization.

  11. Exhibition - Mathematics, A Beautiful Elsewhere

    CERN Multimedia

    2011-01-01

    From 21 October 2011 to 18 March 2012, the Fondation Cartier pour l’art contemporain will present the exhibition Mathematics: A Beautiful Elsewhere, an exhibition developed in association with the Institut des Hautes Études Scientifiques (IHÉS) and under the patronage of UNESCO. For this unprecedented event, the foundation invited mathematicians to work with artists with whom it has previously worked to create an exhibition that allows visitors to see, hear, do, interpret and think about mathematics. By bringing mathematics into its premises, the Fondation Cartier is itself undergoing the “sudden change of scenery” described by mathematician Alexandre Grothendieck. More information is available here. Fondation Cartier pour l’art contemporain 261, boulevard Raspail 75014 Paris http://fondation.cartier.com Private Visit For professors, researchers and all the staff of Mathematics departments...

  12. Reactive oxygen species dynamics in roots of salt sensitive and salt tolerant cultivars of rice.

    Science.gov (United States)

    Saini, Shivani; Kaur, Navdeep; Pati, Pratap Kumar

    2018-06-01

    Salinity stress is one of the major constraints for growth and survival of plants that affects rice productivity worldwide. Hence, in the present study, roots of two contrasting salinity sensitive cultivars, IR64 (IR64, salt sensitive) and Luna Suvarna (LS, salt tolerant) were compared with regard to the levels of reactive oxygen species (ROS) to derive clues for their differential salt stress adaptation mechanisms. In our investigation, the tolerant cultivar exhibited longer primary roots, more lateral roots, higher root number leading to increased root biomass, with respect to IR64. It was observed that LS roots maintained higher level of H 2 O 2 in comparison to IR64. The activities of various enzymes involved in enzymatic antioxidant defense mechanism (SOD, CAT, GPX, DHAR and MDHAR) were found to be greater in LS roots. Further, the higher transcript level accumulation of genes encoding ROS generating (RbohA, RbohD and RbohE) and scavenging enzymes (Fe-SOD, Chloroplastic Cu/Zn-SOD, CAT and DHAR) were noticed in the roots of tolerant cultivar, LS. Moreover, the content of other stress markers such as total protein and proline were also elevated in LS roots. While, the expression of proline biosynthesis gene (P5CS) and proline catabolism gene (PDH) was observed to be lower in LS. Copyright © 2018. Published by Elsevier Inc.

  13. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Hongying, Ren; Huiguo, Cai; Zhongchao, Han; Renchi, Yang; Zhao, Qinjun [State Key Lab of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin (China); Ying, Cao; Jing, Li [Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Cixiang, Zhou [Health Science Center, Shanghai Institutes of Biological Sciences, Chinese Academy of Science-SSMU, Shanghai (China); Lianming, Liao; Mingyue, Jia [Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Qian, Zhao [Health Science Center, Shanghai Institutes of Biological Sciences, Chinese Academy of Science-SSMU, Shanghai (China); Guoqiang, Chen [Health Science Center, Shanghai Institutes of Biological Sciences, Chinese Academy of Science-SSMU, Shanghai (China); Zhao, R C [State Key Lab of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin (China); [Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)]. E-mail: chunhuaz@public.tpt.tj.cn

    2006-08-18

    Low oxygen tension is a potent differentiation inducer of numerous cell types and an effective stimulus of many gene expressions. Here, we described that under 8% O{sub 2}, bone marrow stromal cells (MSCs) exhibited proliferative and morphologic changes. The level of differentiated antigen H-2Dd and the number of G{sub 2}/S/M phase cells increased evidently under 8% O{sub 2} condition. Also, the proportion of wide, flattened, and epithelial-like cells (which were alkaline phosphatase staining positive) in MSCs increased significantly. When cultured in adipogenic medium, there was a 5- to 6-fold increase in the number of lipid droplets under hypoxic conditions compared with that in normoxic culture. We also demonstrated the existence of MSC differentiation under hypoxic conditions by electron microscopy. Expression of Oct4 was inhibited under 8% O{sub 2} condition, but after adipocyte differentiation in normoxic culture and hypoxia-mimicking agents cobalt chloride (CoCl{sub 2}) and deferoxamine mesylate (DFX) treatments, Oct4 was still expressed in MSCs. These results indicate hypoxia accelerates MSC differentiation and hypoxia and hypoxia-mimicking agents exert different effects on MSC differentiation.

  14. Review of Signaling Pathways Governing MSC Osteogenic and Adipogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Aaron W. James

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSC are multipotent cells, functioning as precursors to a variety of cell types including adipocytes, osteoblasts, and chondrocytes. Between osteogenic and adipogenic lineage commitment and differentiation, a theoretical inverse relationship exists, such that differentiation towards an osteoblast phenotype occurs at the expense of an adipocytic phenotype. This balance is regulated by numerous, intersecting signaling pathways that converge on the regulation of two main transcription factors: peroxisome proliferator-activated receptor-γ (PPARγ and Runt-related transcription factor 2 (Runx2. These two transcription factors, PPARγ and Runx2, are generally regarded as the master regulators of adipogenesis and osteogenesis. This review will summarize signaling pathways that govern MSC fate towards osteogenic or adipocytic differentiation. A number of signaling pathways follow the inverse balance between osteogenic and adipogenic differentiation and are generally proosteogenic/antiadipogenic stimuli. These include β-catenin dependent Wnt signaling, Hedgehog signaling, and NELL-1 signaling. However, other signaling pathways exhibit more context-dependent effects on adipogenic and osteogenic differentiation. These include bone morphogenic protein (BMP signaling and insulin growth factor (IGF signaling, which display both proosteogenic and proadipogenic effects. In summary, understanding those factors that govern osteogenic versus adipogenic MSC differentiation has significant implications in diverse areas of human health, from obesity to osteoporosis to regenerative medicine.

  15. Characterization of Catalase from Psychrotolerant Psychrobacter piscatorii T-3 Exhibiting High Catalase Activity

    Science.gov (United States)

    Kimoto, Hideyuki; Yoshimune, Kazuaki; Matsuyma, Hidetoshi; Yumoto, Isao

    2012-01-01

    A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii), that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H2O2 as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein−1) that was higher than that of Micrococcus luteus used for industrial catalase production. Catalase was approximately 10% of the total proteins in the cell extract of the strain. The catalase (PktA) was purified homogeneously by only two purification steps, anion exchange and hydrophobic chromatographies. The purified catalase exhibited higher catalytic efficiency and higher sensitivity of activity at high temperatures than M. luteus catalase. The deduced amino acid sequence showed the highest homology with catalase of Psycrobacter cryohalolentis, a psychrotolelant bacterium obtained from Siberian permafrost. These findings suggest that the characteristics of the PktA molecule reflected the taxonomic relationship of the isolate as well as the environmental conditions (low temperatures and high concentrations of H2O2) under which the bacterium survives. Strain T-3 efficiently produces a catalase (PktA) at a higher rate than Exiguobacterium oxidotolerans, which produces a very strong activity of catalase (EktA) at a moderate rate, in order to adapt to high concentration of H2O2. PMID:22408420

  16. Sensitivity analysis in the WWTP modelling community – new opportunities and applications

    DEFF Research Database (Denmark)

    Sin, Gürkan; Ruano, M.V.; Neumann, Marc B.

    2010-01-01

    design (BSM1 plant layout) using Standardized Regression Coefficients (SRC) and (ii) Applying sensitivity analysis to help fine-tuning a fuzzy controller for a BNPR plant using Morris Screening. The results obtained from each case study are then critically discussed in view of practical applications......A mainstream viewpoint on sensitivity analysis in the wastewater modelling community is that it is a first-order differential analysis of outputs with respect to the parameters – typically obtained by perturbing one parameter at a time with a small factor. An alternative viewpoint on sensitivity...

  17. LIF inhibits osteoblast differentiation at least in part by regulation of HAS2 and its product hyaluronan.

    Science.gov (United States)

    Falconi, Dominic; Aubin, Jane E

    2007-08-01

    LIF arrests osteogenesis in fetal rat calvaria cells in a differentiation stage-specific manner. Differential display identified HAS2 as a LIF-induced gene and its product, HA, modulated osteoblast differentiation similarly to LIF. Our data suggest that LIF arrests osteoblast differentiation by altering HA content of the extracellular matrix. Leukemia inhibitory factor (LIF) elicits both anabolic and catabolic effects on bone. We previously showed in the fetal rat calvaria (RC) cell system that LIF inhibits osteoblast differentiation at the late osteoprogenitor/early osteoblast stage. To uncover potential molecular mediators of this inhibitory activity, we used a positive-negative genome-wide differential display screen to identify LIF-induced changes in the developing osteoblast transcriptome. Although LIF signaling is active throughout the RC cell proliferation-differentiation sequence, only a relatively small number of genes, in several different functional clusters, are modulated by LIF specifically during the LIF-sensitive inhibitory time window. Based on their known and predicted functions, most of the LIF-regulated genes identified are plausible candidates to be involved in the LIF-induced arrest of osteoprogenitor differentiation. To test this hypothesis, we further analyzed the function of one of the genes identified, hyaluronan synthase 2 (HAS2), in the LIF-induced inhibition. Synthesis of hyaluronan (HA), the product of HAS enzymatic activity, was stimulated by LIF and mimicked the HAS2 expression profile, with highest expression in early/proliferative and late/maturing cultures and lowest levels in intermediate/late osteoprogenitor-early osteoblast cultures. Exogenously added high molecular weight HA, the product of HAS2, dose-dependently inhibited osteoblast differentiation, with pulse-treatment effective in the same differentiation stage-specific inhibitory window as seen with LIF. In addition, however, pulse treatment with HA in early cultures

  18. Korean Addenbrooke's Cognitive Examination Revised (K-ACER) for differential diagnosis of Alzheimer's disease and subcortical ischemic vascular dementia.

    Science.gov (United States)

    Kwak, Yong Tae; Yang, Youngsoon; Kim, Gyung Whan

    2010-10-01

    Sensitive, specific neuropsychological screening tests, such as the Addenbrooke's Cognitive Examination Revised (ACE-R), are essential for dementia diagnosis. We aimed to validate the use of the Korean version of ACE-R (K-ACER) to differentiate Alzheimer's disease (AD) from subcortical ischemic vascular dementia (SIVD). Standard tests for dementia screening were applied to 156 subjects (84 controls, 30 AD, 42 SIVD), and total and sub-domain scores on the K-ACER, as well as the sub-domain ratio (VLOM), were compared. The reliability of the K-ACER was very good (α-coefficient 0.84), and cut-off score for dementia was determined (cut-off value 78, sensitivity 0.93, specificity 0.95). The likelihood ratio for dementia was calculated as between 78 and 82. At a cut-off of 78, the likelihood of dementia was 18.6:1. Although a comparison of K-ACER scores between AD and SIVD patients revealed significant differences in verbal fluency, language domain and VLOM ratio, sensitivity and specificity for differential diagnosis between AD and SVID proved less accurate. The K-ACER is a rapid, sensitive and specific dementia screening test. Though sub-domains of items may be useful for differentiating between AD and SIVD, sensitivity and specificity is less accurate than dementia screening itself. © 2010 Japan Geriatrics Society.

  19. TEMPERA-V2. A computer program for sensitivity analysis in a cooling channel of nuclear reactors-V.1

    International Nuclear Information System (INIS)

    Andrade Lima, F.R. de; Alvim, A.C.M.

    1986-09-01

    The sensitivity of linear responses associated with physical quantities governed by non linear differential systems is studied, using perturbation theory. The equivalence and formal differences of differential and GPT formalisms are shown. Both of them and also the matricial formalism are used for sensitivity calculations of transient problems in a typical PWR coolant channel. The results obtained are encouraging with respect to the potentiality of the method for thermal-hydraulic calculations normally performed for reactor design and safety analysis. (Author) [pt

  20. Risk-sensitive control of stochastic hybrid systems on infinite time horizon

    Directory of Open Access Journals (Sweden)

    Runolfsson Thordur

    1999-01-01

    Full Text Available A risk-sensitive optimal control problem is considered for a hybrid system that consists of continuous time diffusion process that depends on a discrete valued mode variable that is modeled as a Markov chain. Optimality conditions are presented and conditions for the existence of optimal controls are derived. It is shown that the optimal risk-sensitive control problem is equivalent to the upper value of an associated stochastic differential game, and insight into the contributions of the noise input and mode variable to the risk sensitivity of the cost functional is given. Furthermore, it is shown that due to the mode variable risk sensitivity, the equivalence relationship that has been observed between risk-sensitive and H ∞ control in the nonhybrid case does not hold for stochastic hybrid systems.

  1. Highly sensitive determination of TSH in the follow-up of TSH-suppressive therapy of patients with differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Mann, K.; Saller, B.; Mehl, U.; Hoermann, R.; Moser, E.

    1988-01-01

    Basal and TRH-stimulated TSH levels were determined in 72 patients with differentiated thyroid cancer on hormonal treatment, using a highly sensitive immunoradiometric assay (IRMAclon, Henning). 43 patients were under treatment with levothyroxine (T 4 ), 29 patients with triiodothyronine (T 3 ). In 33/43 patients (77%) under T 4 - and in 18/29 patients (62%) under T 3 -treatment basal TSH levels were below 0.1 mU/l. 3 patients showed a significant response (to above 0.5 mU/l) in the TRH test despite basal values of less than 0.1 mU/l. In 2 patients with elevated basal TSH levels (0.23 and 0.60 mU/l, resp.) in the IRMAclon, total suppression of TSH secretion was suggested by a failure of TSH to rise after TRH. By retesting these samples in an own TSH IRMA, basal and stimulated TSH values were below 0.1 mU/l. In conclusion, basal and TRH-stimulated TSH levels are well correlated in most patients with thyroid cancer under hormonal treatment. However, in some cases (5/72) determination of basal TSH could not clearly define the degree of thyrotropic suppression. Thus, TRH testing is still necessary to establish definitely complete TSH suppression in patients with thyroid carcinoma under suppressive treatment. (orig.) [de

  2. Thallium 201 thyroid scan: differential diagnosis of benign and malignant nodules

    International Nuclear Information System (INIS)

    Oh, Jong Sub; Kim, Byong Geun; Park, Byung Ran; Kim, Se Jong; Ko, Kang Seok; Kim, Min Joong; Ji, Joo Yun

    1995-01-01

    To evaluate useful findings and diagnostic value of TI-201 thyroid scan in differentiating benign from malignant nodules. We studied 77 cold thyroid nodules proven histologically(27 malignant and 50 benign). Early (5-15 min) and delayed images(3-5 hours) were obtained after intravenous injection of thallium 201. In these nodules, we retrospectively analyzed the degree of TI-201 uptake in early and delayed images, histopathologic type, size, and presence or absence of cystic change in the sonograms of 22 malignant nodules. Useful finding for diagnosis of malignant nodules was strong uptake of TI-201 in early and delayed images(specificity: 98%, sensitivity: 63%, positive predictive value: 94.4%). Useful finding for benign nodules was no uptake of TI-201 in delayed image(specificity: 88.9%, sensitivity: 68%, positive predictive value: 91.9%). The accuracy of TI-201 thyroid scan in differentiating benign from malignant nodules was 66.2%. The nodules with strong TI-201 uptake in early image and low TI-201 uptake in delayed image were malignant in 29.4%. Cystic changes were found in 40% of malignant nodules with atypical TI-201 uptake. TI-201 thyroid scan showed high specificity in follicular neoplasm and adenomatous goiter in which differentiation of benignancy and malignancy is difficult with only cytologic examination. We consider that TI-201 thyroid scan is valuable in differentiating benign from malignant nodules and when combined with fine needle aspiration and ultrasound examination, it will enable more accurate differential diagnosis between benign and malignant thyroid nodules

  3. Human Exhibitions

    DEFF Research Database (Denmark)

    Andreassen, Rikke

    light on the staging of exhibitions, the daily life of the exhibitees, the wider connections between shows across Europe and the thinking of the time on matters of race, science, gender and sexuality. A window onto contemporary racial understandings, the book presents interviews with the descendants...... of displayed people, connecting the attitudes and science of the past with both our (continued) modern fascination with ‘the exotic’, and contemporary language and popular culture. As such, it will be of interest to scholars of sociology, anthropology and history working in the areas of gender and sexuality...

  4. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    Energy Technology Data Exchange (ETDEWEB)

    Li, Luchuan; Lv, Bin; Chen, Bo [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Guan, Ming [Department of General Surgery, Qihe People' s Hospital, Qihe, Shandong 251100 (China); Sun, Yongfeng [Department of General Surgery, Licheng District People' s Hospital, Jinan, Shandong 250115 (China); Li, Haipeng [Department of General Surgery, Caoxian People' s Hospital, Caoxian, Shandong 274400 (China); Zhang, Binbin; Ding, Changyuan; He, Shan [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Zeng, Qingdong, E-mail: qingdz0201@163.com [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China)

    2015-07-10

    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  5. Microsphere Suspension Array Assays for Detection and Differentiation of Hendra and Nipah Viruses

    Directory of Open Access Journals (Sweden)

    Adam J. Foord

    2013-01-01

    Full Text Available Microsphere suspension array systems enable the simultaneous fluorescent identification of multiple separate nucleotide targets in a single reaction. We have utilized commercially available oligo-tagged microspheres (Luminex MagPlex-TAG to construct and evaluate multiplexed assays for the detection and differentiation of Hendra virus (HeV and Nipah virus (NiV. Both these agents are bat-borne zoonotic paramyxoviruses of increasing concern for veterinary and human health. Assays were developed targeting multiple sites within the nucleoprotein (N and phosphoprotein (P encoding genes. The relative specificities and sensitivities of the assays were determined using reference isolates of each virus type, samples from experimentally infected horses, and archival veterinary diagnostic submissions. Results were assessed in direct comparison with an established qPCR. The microsphere array assays achieved unequivocal differentiation of HeV and NiV and the sensitivity of HeV detection was comparable to qPCR, indicating high analytical and diagnostic specificity and sensitivity.

  6. Anniversary Exhibition. Nechvolodov.

    Directory of Open Access Journals (Sweden)

    - -

    2006-03-01

    Full Text Available On the 10th of August, 2005 in Tartu (the second biggest educational and cultural city in Estonia Stanislav Nechvolodov's exhibition was opened to show the 5-year cycle of his work, traditional for the author and his admirers. At the opening ceremony Nechvolodov said that the exhibition was the last one and appointed on his 70th anniversary.The architectural and building society in Irkutsk remembers Stanislav Nechvolodov as an architect working on dwelling and civil buildings in 1960-70s. Below are some extracts from the Estonian press.«Postimees» newspaper, December 1993. The interview «Expressionistic naturalist, conservative Nechvolodov» by journalist Eric Linnumyagi. He asks about all the details and describes the troubles experienced by Nechvolodov during the perestroika period in Estonia, for example: the Tartu University refused to install the sculpture of Socrat, the art school refused to engage him as an instructor, the sculpture of Socrat moved to Vrotzlav, Poland, and Nechvolodov moved to Poland to read lectures there.«Tartu» newspaper, November 2000. Mats Oun, artist, says in the article «Nechvolodov: a man of Renaissance»: «Nechvolodov works in Estonia, his works are placed in many local and foreign museums. Regardless some insignificant faults, he deserves a high estimation, and his manysided open exhibition can be an example for other artists. He is a man of Renaissance».

  7. Radiation sensitivity of T-lymphocytes from immunodeficient wasted mice

    International Nuclear Information System (INIS)

    Padilla, M.; Libertin, C.; Krco, C.; Woloschak, G.E.

    1990-01-01

    Mice with the autosomal recessive gene wasted (wst/wst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of gamma-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease in the percentage of Thyl + cells in wasted mice, in contrast to cultures from control mice in which significant increases in Thyl + cells were observed. Furthermore, when cells were treated with gamma-rays in combination with Con A, Thyl + cells were decreased in control spleen and thymus, but were elevated in similarly treated wasted cultures. These changes were accompanied by an increase in cell volume in T-cells from wasted but not from control mice. These results describe the sensitivity of T-cells from wasted mice to ionizing radiation; in addition, they suggest that the wst/wst abnormality may be associated with cell cycle aberrancies

  8. Creating Virtual Exhibitions for Educational and Cultural Development

    Directory of Open Access Journals (Sweden)

    Gabriela DUMITRESCU

    2014-01-01

    Full Text Available The paper presents different tools and mechanisms to implement a virtual exhibition in different cultural areas, such as museums and libraries. Quality characteristics of virtual exhibitions are identified and described. The possibility to create native mobile applications for virtual exhibitions presentation is analyzed. The functional flow of creating a virtual exhibition is presented and discussed. The Seals - History Treasure exhibition is presented and significant historical documents are revealed.

  9. Accuracy of apparent diffusion coefficient in differentiating pancreatic neuroendocrine tumour from intrapancreatic accessory spleen

    International Nuclear Information System (INIS)

    Pandey, Ankur; Pandey, Pallavi; Ghasabeh, Mounes Aliyari; Varzaneh, Farnaz Najmi; Khoshpouri, Pegah; Shao, Nannan; Pour, Manijeh Zargham; Fouladi, Daniel Fadaei; Kamel, Ihab R.; Hruban, Ralph H.; O'Broin-Lennon, Anne Marie

    2018-01-01

    To evaluate and compare the accuracy of absolute apparent diffusion coefficient (ADC) and normalised ADC (lesion-to-spleen ADC ratio) in differentiating pancreatic neuroendocrine tumour (NET) from intrapancreatic accessory spleen (IPAS). Study included 62 patients with the diagnosis of pancreatic NET (n=51) or IPAS (n=11). Two independent reviewers measured ADC on all lesions and spleen. Receiver operating characteristics (ROC) analysis to differentiate NET from IPAS was performed and compared for absolute and normalised ADC. Inter-reader reliability for the two methods was assessed. Pancreatic NET had significantly higher absolute ADC (1.431 x 10 -3 vs 0.967 x 10 -3 mm 2 /s; P<0.0001) and normalised ADC (1.59 vs 1.09; P<0.0001) compared to IPAS. An ADC value of ≥1.206 x 10 -3 mm 2 /s was 70.6% sensitive and 90.9% specific for the diagnosis of NET vs. IPAS. Lesion to spleen ADC ratio of ≥1.25 was 80.4% sensitive, and 81.8% specific while ratio of ≥1.29 was 74.5% sensitive and 100% specific in the differentiation. The area under the curve (AUCs) for two methods were similar (88.2% vs. 88.8%; P=0.899). Both methods demonstrated excellent inter-reader reliability with ICCs for absolute ADC and ADC ratio being 0.957 and 0.927, respectively. Both absolute and normalised ADC allow clinically relevant differentiation of pancreatic NET and IPAS. (orig.)

  10. Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening.

    Science.gov (United States)

    Tong, Zhi-Bin; Hogberg, Helena; Kuo, David; Sakamuru, Srilatha; Xia, Menghang; Smirnova, Lena; Hartung, Thomas; Gerhold, David

    2017-02-01

    More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Autoerythrocyte Sensitization Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Pinar Ozuguz

    2014-04-01

    Full Text Available Autoerythrocyte sensitization syndrome or Gardner-Diamond syndrome is a rare syndrome, characterized by recurrent, spontaneous, painful ecchymosis. The lesions occur particularly after emotional stress or mild trauma. Psychiatric problems are commonly observed in these patients. The lower limbs and the trunk are the most often localizations; however, lesions can appear on any other skin area. It is thought to be a sensitivity to intradermally injected autoerythrocyte. The diagnosis is usually based on typical anamnesis, clinical presentation, absence of specific laboratory changes and positive intradermal test. This syndrome should be considered in the differential diagnosis of purpura, especially in patients with psychiatric problems and without any coagulopathy. Herein, a case of 38 year-old-female who has recurrent ecchymoses on her legs, fatigue, headache and sleeping problems is presented.

  12. The multiparametric deformation of GL(n) and the covariant differential calculus on the quantum vector space

    International Nuclear Information System (INIS)

    Schirrmacher, A.

    1991-01-01

    A n(n-1)/2+1 parameter solution of the Yang Baxter equation is presented giving rise to the quantum Group GL x;qij (n). Determinant and inverse are constructed. The group acts covariantly on a quantum vector space of non-commutative coordinates. The associated exterior space can be identified with the differentials exhibiting a multiparameter deformed differential calculus following the construction of Wess and Zumino. (orig.)

  13. The exploration of the exhibition informatization

    Science.gov (United States)

    Zhang, Jiankang

    2017-06-01

    The construction and management of exhibition informatization is the main task and choke point during the process of Chinese exhibition industry’s transformation and promotion. There are three key points expected to realize a breakthrough during the construction of Chinese exhibition informatization, and the three aspects respectively are adopting service outsourcing to construct and maintain the database, adopting advanced chest card technology to collect various kinds of information, developing statistics analysis to maintain good cutomer relations. The success of Chinese exhibition informatization mainly calls for mature suppliers who can provide construction and maintenance of database, the proven technology, a sense of data security, advanced chest card technology, the ability of data mining and analysis and the ability to improve the exhibition service basing on the commercial information got from the data analysis. Several data security measures are expected to apply during the process of system developing, including the measures of the terminal data security, the internet data security, the media data security, the storage data security and the application data security. The informatization of this process is based on the chest card designing. At present, there are several types of chest card technology: bar code chest card; two-dimension code card; magnetic stripe chest card; smart-chip chest card. The information got from the exhibition data will help the organizers to make relevant service strategies, quantify the accumulated indexes of the customers, and improve the level of the customer’s satisfaction and loyalty, what’s more, the information can also provide more additional services like the commercial trips, VIP ceremonial reception.

  14. Method for HEPA filter leak scanning with differentiating aerosol detector

    Energy Technology Data Exchange (ETDEWEB)

    Kovach, B.J.; Banks, E.M.; Wikoff, W.O. [NUCON International, Inc., Columbus, OH (United States)

    1997-08-01

    While scanning HEPA filters for leaks with {open_quotes}Off the Shelf{close_quote} aerosol detection equipment, the operator`s scanning speed is limited by the time constant and threshold sensitivity of the detector. This is based on detection of the aerosol density, where the maximum signal is achieved when the scanning probe resides over the pinhole longer than several detector time-constants. Since the differential value of the changing signal can be determined by observing only the first small fraction of the rising signal, using a differentiating amplifier will speed up the locating process. The other advantage of differentiation is that slow signal drift or zero offset will not interfere with the process of locating the leak, since they are not detected. A scanning hand-probe attachable to any NUCON{reg_sign} Aerosol Detector displaying the combination of both aerosol density and differentiated signal was designed. 3 refs., 1 fig.

  15. Xanthogranulomatous cholecystitis: Diagnostic performance of CT to differentiate from gallbladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goshima, Satoshi, E-mail: gossy@par.odn.ne.j [Department of Radiology, University of Pittsburgh Medical Center, Lothrop St., Pittsburgh, PA 15213 (United States); Department of Radiology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Chang, Samuel; Wang, Jin Hong [Department of Radiology, University of Pittsburgh School of Medicine, 3362 Fifth Ave., Pittsburgh, PA15213 (United States); Kanematsu, Masayuki [Department of Radiology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Department of Radiology Services, Gifu University School of Medicine, 1-1- Yanagido, Gifu 501-1194 (Japan); Bae, Kyongtae T. [Department of Radiology, University of Pittsburgh School of Medicine, 3362 Fifth Ave., Pittsburgh, PA15213 (United States); Federle, Michael P. [Department of Radiology, University of Pittsburgh Medical Center, Lothrop St., Pittsburgh, PA 15213 (United States); Department of Radiology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305-5105 (United States)

    2010-06-15

    Purpose: To retrospectively evaluate CT findings of xanthogranulomatous cholecystitis (XGC) and to measure diagnostic performance for distinguishing it from gallbladder (GB) cancer. Methods and materials: Our institutional review board approved this retrospective study. Three blinded radiologists, first independently and then in consensus, retrospectively evaluated postcontrast CT images of 35 patients with histopathologically proved XGC and GB cancer, all of whom subsequently had cholecystectomy. These included 18 patients with XGC (13 male, 5 female; age range, 35-84, mean 63 years) and 17 with GB cancer (6 male, 11 female; age range, 45-95, mean 69). Differences in CT findings between XGC and GB cancer and diagnostic performances for each CT finding were calculated. Sensitivity, specificity, and accuracy were calculated for each radiologist and observer performance was also determined by receiver-operating-characteristic curve analysis. Results: Five CT findings showed significant differences between XGC and GB cancer. Sensitivity, specificity, and accuracy of each finding for the differentiation of XGC were 89%, 65%, 77% with diffuse GB wall thickening, 67%, 82%, 74% with a continuous mucosal line, 61%, 71%, 66% with intra-mural hypo-attenuated nodules, 72%, 77%, 74% with absence of macroscopic hepatic invasion, and 67%, 71%, 69% with absence of intra-hepatic bile duct dilatation, respectively. When at least three of these five CT findings were observed in combination, sensitivity, specificity, and accuracy were 83%, 100% and 91%, respectively. Sensitivities, specificities and Az values for the differentiation of XGC from GB cancer were 83%, 88%, 0.94 for reader 1, 78%, 88%, 0.93 for reader 2, and 78%, 82%, 0.84 for reader 3. Conclusions: The combination of three of the five CT findings that are common with XGC can provide excellent accuracy for the differentiation of XGC and GB cancer.

  16. Better differential diagnosis of iron deficiency anemia from beta-thalassemia trait

    Directory of Open Access Journals (Sweden)

    Fakher Rahim

    2009-09-01

    Full Text Available Objective: Iron deficiency anemia (IDA and beta-thalassemia trait (ß-TT are the most common forms of microcytic anemia. This study was conducted to compare the validity of various discrimination indices in differentiating β-TT from IDA by calculating their sensitivity, specificity and Youden's index.Methods: Totally 323 subjects (173 children and 150 adults with microcytic anemia were involved in this study. We calculated 10 discrimination indices in all patients with IDA and β-TT. We divided the patients into two different groups as younger or older than 10 years. Results: None of the indices showed sensitivity and specificity of 100% in the patients older than 10 years, and in the patients younger than 10 years, only Shine & Lal index showed sensitivity close to 90% and specificity of 100%. The most accurate discriminative index for patients younger than 10 years was Shine & Lal and for those older than 10 years it was RDW index. According to Youden's index, Shine & Lal and RBC count showed the greatest diagnostic value in patients younger than 10 years and RDW and RBC count indices in those older than 10 years. Conclusion: None of the indices was completely sensitive and specific in differentiation between β-TT and IDA. Mean and median mean cell Hb density (MCHD were very close to normal values in both IDA and β-TT patients, but in the case of mean density of Hb/liter (MDHL, we found that the mean and median were significantly higher than normal values in β-TT and lower than normal values in IDA patients. In our study, Youden's index of RBC and Shine & Lal were the highest and most reliable indices in differentiating β-TT from IDA in the patients younger than 10 years. For patients older than 10 years, the most reliable discrimination indices were RBC and RDW.

  17. Can magnetic resonance imaging differentiate undifferentiated arthritis?

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Duer, Anne; Hørslev-Petersen, K

    2005-01-01

    A high sensitivity for the detection of inflammatory and destructive changes in inflammatory joint diseases makes magnetic resonance imaging potentially useful for assigning specific diagnoses, such as rheumatoid arthritis and psoriatic arthritis in arthritides, that remain undifferentiated after...... conventional clinical, biochemical and radiographic examinations. With recent data as the starting point, the present paper describes the current knowledge on magnetic resonance imaging in the differential diagnosis of undifferentiated arthritis....

  18. Digital Natives: Creating Emergent Exhibitions through Digital Technologies

    DEFF Research Database (Denmark)

    Smith, Rachel Charlotte; Iversen, Ole Sejer; Dindler, Christian

    2011-01-01

    . In this way, digital technology can contribute to the creation of emergent exhibitions in which the exhibition is created in dialogue between audiences and the museum. We present experiences from a current research project, the Digital Natives exhibition, in which digital technology was designed......Digital Technology can support the creation of dialogical spaces in the museum, both playful and reflective, that allow audiences to engage in the ongoing construction and reproduction of cultural heritage creating novel connections between self and others and between past, present and future...... as an integral part of the exhibition to encourage dialogue between audiences and the exhibition materials and thereby investigate how the exhibition emerge as a result of this dialogic co-construction inside the exhibition space. In short, the opportunities offered by digital technologies prompts us to consider...

  19. A simple method to measure critical angles for high-sensitivity differential refractometry.

    Science.gov (United States)

    Zilio, S C

    2012-01-16

    A total internal reflection-based differencial refractometer, capable of measuring the real and imaginary parts of the complex refractive index in real time, is presented. The device takes advantage of the phase difference acquired by s- and p-polarized light to generate an easily detectable minimum at the reflected profile. The method allows to sensitively measuring transparent and turbid liquid samples.

  20. Artefacts and the performance of an exhibition

    DEFF Research Database (Denmark)

    Svabo, Connie

    2008-01-01

    The article explores the role of mediating artefacts in children's encounters with a museum of natural history. Using actor network theory it explores how a specific artefact shapes the way users relate to exhibited objects and how the artefact guides users' movements in the exhibition....... The mediated performance of an exhibition is explored through an empirical case....

  1. PI3 kinase is involved in cocaine behavioral sensitization and its reversal with brain area specificity

    International Nuclear Information System (INIS)

    Zhang Xiuwu; Mi Jing; Wetsel, William C.; Davidson, Colin; Xiong Xieying; Chen Qiang; Ellinwood, Everett H.; Lee, Tong H.

    2006-01-01

    Phosphatidylinositol 3-kinase (PI3K) is an important signaling molecule involved in cell differentiation, proliferation, survival, and phagocytosis, and may participate in various brain functions. To determine whether it is also involved in cocaine sensitization, we measured the p85α/p110 PI3K activity in the nuclear accumbens (NAc) shell, NAc core, and prefrontal cortex (PFC) following establishment of cocaine sensitization and its subsequent reversal. Naive rats were rank-ordered and split into either daily cocaine or saline pretreatment group based on their locomotor responses to an acute cocaine injection (7.5 mg/kg, i.p.). These two groups were then injected with cocaine (40 mg/kg, s.c.) or saline for 4 consecutive days followed by 9-day withdrawal. Cocaine sensitization was subsequently reversed by 5 daily injections of the D 1 /D 2 agonist pergolide (0.1 mg/kg, s.c.) in combination with the 5-HT 3 antagonist ondansetron (0.2 mg/kg, s.c., 3.5 h after pergolide injection). After another 9-day withdrawal, behavioral cocaine sensitization and its reversal were confirmed with an acute cocaine challenge (7.5 mg/kg, i.p.), and animals were sacrificed the next day for measurement of p85α/p110 PI3K activity. Cocaine-sensitized animals exhibited increased PI3K activity in the NAc shell, and this increase was reversed by combined pergolide/ondansetron treatment, which also reversed behavioral sensitization. In the NAc core and PFC, cocaine sensitization decreased and increased the PI3K activity, respectively. These changes, in contrast to that in the NAc shell, were not normalized following the reversal of cocaine-sensitization. Interestingly, daily injections of pergolide alone in saline-pretreated animals induced PI3K changes that were similar to the cocaine sensitization-associated changes in the NAc core and PFC but not the NAc shell; furthermore, these changes in saline-pretreated animals were prevented by ondansetron given 3.5 h after pergolide. The present

  2. A high sensitivity nanomaterial based SAW humidity sensor

    Energy Technology Data Exchange (ETDEWEB)

    Wu, T-T; Chou, T-H [Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan (China); Chen, Y-Y [Department of Mechanical Engineering, Tatung University, Taipei 104, Taiwan (China)], E-mail: wutt@ndt.iam.ntu.edu.tw

    2008-04-21

    In this paper, a highly sensitive humidity sensor is reported. The humidity sensor is configured by a 128{sup 0}YX-LiNbO{sub 3} based surface acoustic wave (SAW) resonator whose operating frequency is at 145 MHz. A dual delay line configuration is realized to eliminate external temperature fluctuations. Moreover, for nanostructured materials possessing high surface-to-volume ratio, large penetration depth and fast charge diffusion rate, camphor sulfonic acid doped polyaniline (PANI) nanofibres are synthesized by the interfacial polymerization method and further deposited on the SAW resonator as selective coating to enhance sensitivity. The humidity sensor is used to measure various relative humidities in the range 5-90% at room temperature. Results show that the PANI nanofibre based SAW humidity sensor exhibits excellent sensitivity and short-term repeatability.

  3. A content-oriented model for science exhibit engineering

    DEFF Research Database (Denmark)

    Achiam, Marianne

    2013-01-01

    Recently, science museums have begun to review their educational purposes and redesign their pedagogies. At the most basic level, this entails accounting for the performance of individual exhibits, and indeed, in some cases, research indicates shortcomings in exhibit design: While often successful......: as a means to operationalize the link between exhibit features and visitor activities; and as a template to transform scientists’ practices in the research context into visitors’ activities in the exhibit context. The resulting model of science exhibit engineering is presented and exemplified, and its...... implications for science exhibit design are discussed at three levels: the design product, the design process, and the design methodology....

  4. Study on Temperature and Synthetic Compensation of Piezo-Resistive Differential Pressure Sensors by Coupled Simulated Annealing and Simplex Optimized Kernel Extreme Learning Machine.

    Science.gov (United States)

    Li, Ji; Hu, Guoqing; Zhou, Yonghong; Zou, Chong; Peng, Wei; Alam Sm, Jahangir

    2017-04-19

    As a high performance-cost ratio solution for differential pressure measurement, piezo-resistive differential pressure sensors are widely used in engineering processes. However, their performance is severely affected by the environmental temperature and the static pressure applied to them. In order to modify the non-linear measuring characteristics of the piezo-resistive differential pressure sensor, compensation actions should synthetically consider these two aspects. Advantages such as nonlinear approximation capability, highly desirable generalization ability and computational efficiency make the kernel extreme learning machine (KELM) a practical approach for this critical task. Since the KELM model is intrinsically sensitive to the regularization parameter and the kernel parameter, a searching scheme combining the coupled simulated annealing (CSA) algorithm and the Nelder-Mead simplex algorithm is adopted to find an optimal KLEM parameter set. A calibration experiment at different working pressure levels was conducted within the temperature range to assess the proposed method. In comparison with other compensation models such as the back-propagation neural network (BP), radius basis neural network (RBF), particle swarm optimization optimized support vector machine (PSO-SVM), particle swarm optimization optimized least squares support vector machine (PSO-LSSVM) and extreme learning machine (ELM), the compensation results show that the presented compensation algorithm exhibits a more satisfactory performance with respect to temperature compensation and synthetic compensation problems.

  5. Application of perturbation methods and sensitivity analysis to water hammer problems in hydraulic networks

    International Nuclear Information System (INIS)

    Balino, Jorge L.; Larreteguy, Axel E.; Andrade Lima, Fernando R.

    1995-01-01

    The differential method was applied to the sensitivity analysis for water hammer problems in hydraulic networks. Starting from the classical water hammer equations in a single-phase liquid with friction, the state vector comprising the piezometric head and the velocity was defined. Applying the differential method the adjoint operator, the adjoint equations with the general form of their boundary conditions, and the general form of the bilinear concomitant were calculated. The discretized adjoint equations and the corresponding boundary conditions were programmed and solved by using the so called method of characteristics. As an example, a constant-level tank connected through a pipe to a valve discharging to atmosphere was considered. The bilinear concomitant was calculated for this particular case. The corresponding sensitivity coefficients due to the variation of different parameters by using both the differential method and the response surface generated by the computer code WHAT were also calculated. The results obtained with these methods show excellent agreement. (author). 11 refs, 2 figs, 2 tabs

  6. A non-human primate model for gluten sensitivity.

    Directory of Open Access Journals (Sweden)

    Michael T Bethune

    2008-02-01

    Full Text Available Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity.Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity.When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse.Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease.

  7. France at CERN – Industrial exhibition

    CERN Multimedia

    FP Department

    2012-01-01

    Industrial Exhibition Administration Building Bldg 61 – 1st Floor Tuesday 27 March: 9 a.m. – 5.30 p.m. Wednesday 28 March: 9 a.m. – 2 p.m.   About thirty French companies are presenting their latest technological advances during the industrial exhibition "France at CERN", featuring products and technologies specifically related to CERN activities. Individual B2B meetings can be organized with the sales and technical representatives of participating firms and will take place at either the companies’ exhibition stands or in conference rooms in the Main Building. Individuals wishing to make contact with one or more companies must use the contact details available from each secretariat of department or by using this link. B2B meetings will be coordinated by UBIFRANCE. You will also find the list of exhibiting and participating companies online here. This event is sponsored by the French subsidiary of RS Components, the most important distri...

  8. Modulation of taste sensitivity by GLP-1 signaling in taste buds.

    Science.gov (United States)

    Martin, Bronwen; Dotson, Cedrick D; Shin, Yu-Kyong; Ji, Sunggoan; Drucker, Daniel J; Maudsley, Stuart; Munger, Steven D

    2009-07-01

    Modulation of sensory function can help animals adjust to a changing external and internal environment. Even so, mechanisms for modulating taste sensitivity are poorly understood. Using immunohistochemical, biochemical, and behavioral approaches, we found that the peptide hormone glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are expressed in mammalian taste buds. Furthermore, we found that GLP-1 signaling plays an important role in the modulation of taste sensitivity: GLP-1R knockout mice exhibit a dramatic reduction in sweet taste sensitivity as well as an enhanced sensitivity to umami-tasting stimuli. Together, these findings suggest a novel paracrine mechanism for the hormonal modulation of taste function in mammals.

  9. Identification of transcript regulatory patterns in cell differentiation.

    Science.gov (United States)

    Gusnanto, Arief; Gosling, John Paul; Pope, Christopher

    2017-10-15

    Studying transcript regulatory patterns in cell differentiation is critical in understanding its complex nature of the formation and function of different cell types. This is done usually by measuring gene expression at different stages of the cell differentiation. However, if the gene expression data available are only from the mature cells, we have some challenges in identifying transcript regulatory patterns that govern the cell differentiation. We propose to exploit the information of the lineage of cell differentiation in terms of correlation structure between cell types. We assume that two different cell types that are close in the lineage will exhibit many common genes that are co-expressed relative to those that are far in the lineage. Current analysis methods tend to ignore this correlation by testing for differential expression assuming some sort of independence between cell types. We employ a Bayesian approach to estimate the posterior distribution of the mean of expression in each cell type, by taking into account the cell formation path in the lineage. This enables us to infer genes that are specific in each cell type, indicating the genes are involved in directing the cell differentiation to that particular cell type. We illustrate the method using gene expression data from a study of haematopoiesis. R codes to perform the analysis are available in http://www1.maths.leeds.ac.uk/∼arief/R/CellDiff/. a.gusnanto@leeds.ac.uk. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. Temporary and Travelling Exhibitions. Museums and Monuments, X.

    Science.gov (United States)

    Daifuku, Hiroshi; And Others

    The permanent exhibition, the most typical form of museum exhibition, has failed to attract repeated visitation, since visitors quickly become familiar with the objects shown. The temporary exhibition evolved as a result for the need of repeated visitation. The temporary exhibition, set up for a period of one to six months, introduces fresh…

  11. Neural computations underlying social risk sensitivity

    Directory of Open Access Journals (Sweden)

    Nina eLauharatanahirun

    2012-08-01

    Full Text Available Under standard models of expected utility, preferences over stochastic events are assumed to be independent of the source of uncertainty. Thus, in decision-making, an agent should exhibit consistent preferences, regardless of whether the uncertainty derives from the unpredictability of a random process or the unpredictability of a social partner. However, when a social partner is the source of uncertainty, social preferences can influence decisions over and above pure risk attitudes. Here, we compared risk-related hemodynamic activity and individual preferences for two sets of options that differ only in the social or non-social nature of the risk. Risk preferences in social and non-social contexts were systematically related to neural activity during decision and outcome phases of each choice. Individuals who were more risk averse in the social context exhibited decreased risk-related activity in the amygdala during non-social decisions, while individuals who were more risk averse in the non-social context exhibited the opposite pattern. Differential risk preferences were similarly associated with hemodynamic activity in ventral striatum at the outcome of these decisions. These findings suggest that social preferences, including aversion to betrayal or exploitation by social partners, may be associated with variability in the response of these subcortical regions to social risk.

  12. The Role of Numerical Methods in the Sensitivity Analysis of a ...

    African Journals Online (AJOL)

    The mathematical modelling of physiochemical interaction in the framework of industrial and environmental physics which relies on an initial value problem is defined by a first order ordinary differential equation. Two numerical methods of studying sensitivity analysis of physiochemical interaction data are developed.

  13. Monte Carlo Calculation of Sensitivities to Secondaries' Angular Distributions

    International Nuclear Information System (INIS)

    Perel, R.L.

    2003-01-01

    An algorithm for Monte Carlo calculation of sensitivities of responses to secondaries' angular distributions (SAD) is developed, based on the differential operator approach. The algorithm was formulated for the sensitivity to Legendre coefficients of the SAD and is valid even in cases where the actual representation of SAD is not in the form of a Legendre series. The algorithm was implemented, for point- or ring-detectors, in a local version of the code MCNP. Numerical tests were performed to validate the algorithm and its implementation. In addition, an algorithm specific for the Kalbach-Mann representation of SAD is presented

  14. Dosage sensitivity shapes the evolution of copy-number varied regions.

    Directory of Open Access Journals (Sweden)

    Benjamin Schuster-Böckler

    2010-03-01

    Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

  15. Establishment of reverse transcription loop-mediated isothermal amplification for rapid detection and differentiation of canine distemper virus infected and vaccinated animals.

    Science.gov (United States)

    Liu, Da-Fei; Liu, Chun-Guo; Tian, Jin; Jiang, Yi-Tong; Zhang, Xiao-Zhan; Chai, Hong-Liang; Yang, Tian-Kuo; Yin, Xiu-Chen; Zhang, Hong-Ying; Liu, Ming; Hua, Yu-Ping; Qu, Lian-Dong

    2015-06-01

    Although widespread vaccination against canine distemper virus (CDV) has been conducted for many decades, several canine distemper outbreaks in vaccinated animals have been reported frequently. In order to detect and differentiate the wild-type and vaccine strains of the CDV from the vaccinated animals, a novel reverse transcription loop-mediated isothermal amplification (RT-LAMP) method was developed. A set of four primers-two internal and two external-were designed to target the H gene for the specific detection of wild-type CDV variants. The CDV-H RT-LAMP assay rapidly amplified the target gene, within 60 min, using a water bath held at a constant temperature of 65°C. The assay was 100-fold more sensitive than conventional RT-PCR, with a detection limit of 10(-1)TCID50ml(-1). The system showed a preference for wild-type CDV, and exhibited less sensitivity to canine parvovirus, canine adenovirus type 1 and type 2, canine coronavirus, and canine parainfluenza virus. The assay was validated using 102 clinical samples obtained from vaccinated dog farms, and the results were comparable to a multiplex nested RT-PCR assay. The specific CDV-H RT-LAMP assay provides a simple, rapid, and sensitive tool for the detection of canines infected with wild-type CDV from canines vaccinated with attenuated vaccine. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Stimulatory effect of undecylenic acid on mouse osteoblast differentiation.

    Science.gov (United States)

    Kim, Myung Hee; Shim, Ki Shuk; Lee, Su-Ui; Kim, Young Sup; Min, Yong Ki; Kim, Seong Hwan

    2010-04-01

    Natural compounds with bone-forming (or anabolic) activity have been recently focused on in bone research. The present study investigated the effect of undecylenic acid (UA) on osteoblast differentiation in mouse osteoblastic MC3T3-E1 subclone 4 cells and primary mouse calvarial cells. Low concentrations of UA (up to 5 microM) exhibited no cytotoxicity and significantly increased the expression and activity of alkaline phosphatase (early differentiation marker of osteoblast) and calcium deposition with the induction of expression of the osteocalcin gene in both cells. Interestingly, at low concentration of UA, the induction of NF-kappaB p65 translocation into nucleus and the up-regulation of AP-1 and NFATc1 transcript levels were also observed, suggesting that the stimulatory effect of UA on osteoblast differentiation could be mediated through the activation of transcription factors. Additionally, although the patterns of UA-induced activation of MAP kinases (JNK and p38) were not completely consistent with the increase of both ALP activity and calcium deposition by UA, MAP kinases might be partially involved in the biological function of UA during the early and late stages of osteoblast differentiation. Copyright (c) 2009 John Wiley & Sons, Ltd.

  17. CERN Industrials Exhibitions - Over 30 Years of Tradition

    CERN Multimedia

    2001-01-01

    Industrial exhibitions have been part of the CERN landscape for 33 years. At least once each year several companies from the same country come to CERN to present their products and services. Now, a new scheme of one-day visits is giving potential exhibitors at CERN a lighter option. The United Kingdom inaugurated the Industrial Exhibitions in 1968, and it wasn't till 1971 that other countries staged exhibitions at CERN. This photo was taken in 1969, at the second British exhibition, where 16 companies were present. Four years after joining CERN, Poland inaugurated its first exhibition at CERN in 1995 in the presence of the former Director-General Chris Llewellyn-Smith. Almost all the Member States have held industrial exhibitions at the Organization. May '68 wasn't only revolutionary in Paris. For the very first time, an industrial exhibition took place at CERN. Great Britain was first to come with eight companies and remains until this day the most devoted country to the programme with 17 exhibitions and ...

  18. German and Korean mothers' sensitivity and related parenting beliefs

    Science.gov (United States)

    Ziehm, Jeanette; Trommsdorff, Gisela; Heikamp, Tobias; Park, Seong-Yeon

    2013-01-01

    This study contributes to a differentiated understanding of maternal sensitivity in cultural and situational context. We investigated differences and similarities in German and Korean mothers' maternal sensitivity. We interviewed 92 German and 100 Korean mothers of first graders about their preference for proactive (anticipating children's needs) or reactive sensitivity (responding to children's direct cues) in different scenarios. Related parenting beliefs were assessed by asking the mothers to explain the reasons why they would prefer specific parenting behaviors. Results revealed significant cultural differences in reactive vs. proactive sensitivity preferences. Overall, German mothers were more likely to indicate that a mother should respond reactively and less likely to report that a mother should act proactively than were Korean mothers. Korean mothers gave preference to both reactive and proactive sensitivity depending on the scenario. With regard to parenting beliefs, analyses revealed that German and Korean mothers who preferred reactive sensitivity mainly explained their choices as attempts to encourage children's development of independence. In contrast, Korean and German mothers with a preference for proactive sensitivity were more likely to report that mothers would assist their children due to their immaturity in dealing with emotional distress. Results are discussed in the framework of the different meanings and functions of maternal sensitivity for socialization in different cultural contexts. PMID:23986740

  19. Sensitive Electrochemical Determination of Gallic Acid: Application in Estimation of Total Polyphenols in Plant Samples

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Sheikh-Mohseni

    2016-12-01

    Full Text Available A modified electrode was prepared by modification of the carbon paste electrode (CPE with graphene nano-sheets. The fabricated modified electrode exhibited an electrocatalytic activity toward gallic acid (GA oxidation because of good conductivity, low electron transfer resistance and catalytic effect. The graphene modified CPE had a lower overvoltage and enhanced electrical current respect to the bare CPE for the oxidation of GA. The oxidation potential of GA decreased more than 210 mV by the modified electrode. The modified electrode responded to the GA in the concentration range of 3.0 × 10-5-1.5 × 10-4 M with high sensitivity by the technique of differential pulse voltammetry. Also, detection limit of 1.1 × 10-7 M was obtained by this modified electrode for GA. This electrode was used for the successful determination of GA in plant samples. Therefore, the content of total polyphenols in plant samples can be determined by the proposed modified electrode based on the concentration of GA in the sample.

  20. Memory and Mourning: An Exhibit History

    Science.gov (United States)

    Eberle, Scott G.

    2005-01-01

    Mounted by the Strong Museum in Rochester, New York, in 1993, and traveling nationally thereafter, the exhibit Memory and Mourning provided historical and contemporary perspectives to help museum guests explore their own reactions to loss and grief. In the process the exhibit's development team encountered a range of philosophical, historical,…

  1. Hybrid organic/inorganic position-sensitive detectors based on PEDOT:PSS/n-Si

    Science.gov (United States)

    Javadi, Mohammad; Gholami, Mahdiyeh; Torbatiyan, Hadis; Abdi, Yaser

    2018-03-01

    Various configurations like p-n junctions, metal-semiconductor Schottky barriers, and metal-oxide-semiconductor structures have been widely used in position-sensitive detectors. In this report, we propose a PEDOT:PSS/n-Si heterojunction as a hybrid organic/inorganic configuration for position-sensitive detectors. The influence of the thickness of the PEDOT:PSS layer, the wavelength of incident light, and the intensity of illumination on the device performance are investigated. The hybrid PSD exhibits very high sensitivity (>100 mV/mm), excellent nonlinearity (0.995) with a response time of heterojunction are very promising for developing a new class of position-sensitive detectors based on the hybrid organic/inorganic junctions.

  2. RuO2 pH Sensor with Super-Glue-Inspired Reference Electrode

    OpenAIRE

    Lonsdale, Wade; Wajrak, Magdalena; Alameh, Kamal

    2017-01-01

    A pH-sensitive RuO2 electrode coated in a commercial cyanoacrylate adhesive typically exhibits very low pH sensitivity, and could be paired with a RuO2 working electrode as a differential type pH sensor. However, such sensors display poor performance in real sample matrices. A pH sensor employing a RuO2 pH-sensitive working electrode and a SiO2-PVB junction-modified RuO2 reference electrode is developed as an alternative high-performance solution. This sensor exhibits a performance similar to...

  3. Legacies from extreme drought increase ecosystem sensitivity to future extremes

    Science.gov (United States)

    Smith, M. D.; Knapp, A.; Hoover, D. L.; Avolio, M. L.; Felton, A. J.; Wilcox, K. R.

    2016-12-01

    Climate extremes, such as drought, are increasing in frequency and intensity, and the ecological consequences of these extreme events can be substantial and widespread. Although there is still much to be learned about how ecosystems will respond to an intensification of drought, even less is known about the factors that determine post-drought recovery of ecosystem function. Such knowledge is particularly important because post-drought recovery periods can be protracted depending on the extent to which key plant populations, community structure and biogeochemical processes are affected. These drought legacies may alter ecosystem function for many years post-drought and may impact future sensitivity to climate extremes. We experimentally imposed two extreme growing season droughts in a central US grassland to assess the impacts of repeated droughts on ecosystem resistance (response) and resilience (recovery). We found that this grassland was not resistant to the first extreme drought due to reduced productivity and differential sensitivity of the co-dominant C4 grass (Andropogon gerardii) and C3 forb (Solidago canadensis) species. This differential sensitivity led to a reordering of species abundances within the plant community. Yet, despite this large shift in plant community composition, which persisted post-drought, the grassland was highly resilient post-drought, due to increased abundance of the dominant C4 grass. Because of this shift to increased C4 grass dominance, we expected that previously-droughted grassland would be more resistant to a second extreme drought. However, contrary to these expectations, previously droughted grassland was more sensitive to drought than grassland that had not experienced drought. Thus, our result suggest that legacies of drought (shift in community composition) may increase ecosystem sensitivity to future extreme events.

  4. High-energy coordination polymers (CPs) exhibiting good catalytic effect on the thermal decomposition of ammonium dinitramide

    Science.gov (United States)

    Li, Xin; Han, Jing; Zhang, Sheng; Zhai, Lianjie; Wang, Bozhou; Yang, Qi; Wei, Qing; Xie, Gang; Chen, Sanping; Gao, Shengli

    2017-09-01

    High-energy coordination polymers (CPs) not only exhibit good energetic performances but also have a good catalytic effect on the thermal decomposition of energetic materials. In this contribution, two high-energy CPs Cu2(DNBT)2(CH3OH)(H2O)3·3H2O (1) and [Cu3(DDT)2(H2O)2]n (2) (H2DNBT = 3,3‧-dinitro-5,5‧-bis(1H-1,2,4-triazole and H3DDT = 4,5-bis(1H-tetrazol-5-yl)-2H-1,2,3-triazole) were synthesized and structurally characterized. Furthermore, 1 was thermos-dehydrated to produce Cu2(DNBT)2(CH3OH)(H2O)3 (1a). The thermal decomposition kinetics of 1, 1a and 2 were studied by Kissinger's method and Ozawa's method. Thermal analyses and sensitivity tests show that all compounds exhibit high thermal stability and low sensitivity for external stimuli. Meanwhile, all compounds have large positive enthalpy of formation, which are calculated as being (1067.67 ± 2.62) kJ mol-1 (1), (1464.12 ± 3.12) kJ mol-1 (1a) and (3877.82 ± 2.75) kJ mol-1 (2), respectively. The catalytic effects of 1a and 2 on the thermal decomposition of ammonium dinitramide (ADN) were also investigated.

  5. Sex Differences in Medium Spiny Neuron Excitability and Glutamatergic Synaptic Input: Heterogeneity Across Striatal Regions and Evidence for Estradiol-Dependent Sexual Differentiation

    Directory of Open Access Journals (Sweden)

    Jinyan Cao

    2018-04-01

    Full Text Available Steroid sex hormones and biological sex influence how the brain regulates motivated behavior, reward, and sensorimotor function in both normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the caudate–putamen, nucleus accumbens core (AcbC, and shell. These brain regions are of particular interest to neuroendocrinologists given that they express membrane-associated but not nuclear estrogen receptors, and also the well-established role of the sex steroid hormone 17β-estradiol (estradiol in modulating striatal dopamine systems. Indeed, output neurons of the striatum, the medium spiny neurons (MSNs, exhibit estradiol sensitivity and sex differences in electrophysiological properties. Here, we review sex differences in rat MSN glutamatergic synaptic input and intrinsic excitability across striatal regions, including evidence for estradiol-mediated sexual differentiation in the nucleus AcbC. In prepubertal animals, female MSNs in the caudate–putamen exhibit a greater intrinsic excitability relative to male MSNs, but no sex differences are detected in excitatory synaptic input. Alternatively, female MSNs in the nucleus AcbC exhibit increased excitatory synaptic input relative to male MSNs, but no sex differences in intrinsic excitability were detected. Increased excitatory synaptic input onto female MSNs in the nucleus AcbC is abolished after masculinizing estradiol or testosterone exposure during the neonatal critical period. No sex differences are detected in MSNs in prepubertal nucleus accumbens shell. Thus, despite possessing the same neuron type, striatal regions exhibit heterogeneity in sex differences in MSN electrophysiological properties, which likely contribute to the sex differences observed in striatal function.

  6. Reduced Baroreflex Sensitivity in Cluster Headache Patients

    DEFF Research Database (Denmark)

    Barloese, Mads C J; Mehlsen, Jesper; Brinth, Louise

    2015-01-01

    by baroreflex sensitivity (BRS) in CH patients. METHODS: Twenty-six active CH patients and an equal number of age-, sex-, and BMI-matched controls underwent head-up tilt table test and BRS was determined by the sequence method. RESULTS: Compared with controls, patients exhibited a blunted reactivity of RR...... patients who had not (n = 13, 16.0 ms/mmHg, P = .1523). In the tilted position, the drop in SBP at the carotid sinuses was higher in patients who had recently suffered an attack. Despite this, they exhibited a less marked shortening of RR intervals when compared with patients who had been attack free...... of the autonomic nervous system or in the central relay of impulses from the baroreceptors....

  7. 18{beta}-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Myung-Hee; Jeong, Jae-Kyo; Lee, You-Jin; Seol, Jae-Won; Ahn, Dong-Choon; Kim, In-Shik [Center for Healthcare Technology Development, Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Park, Sang-Youel, E-mail: sypark@chonbuk.ac.kr [Center for Healthcare Technology Development, Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer 18{beta}-GA inhibits adipogenic differentiation in 3T3-L1 preadipocytes and stimulates lipolysis in differentiated adipocytes. Black-Right-Pointing-Pointer Anti-adipogenic effect of 18{beta}-GA is caused by down-regulation of PPAR{gamma} and inactivation of Akt signalling. Black-Right-Pointing-Pointer Lipolytic effect of 18{beta}-GA is mediated by up-regulation of HSL, ATGL and perilipin and activation of HSL. -- Abstract: 18{beta}-Glycyrrhetinic acid (18{beta}-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18{beta}-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18{beta}-GA dose-dependently (1-40 {mu}M) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 {mu}M of 18{beta}-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor {gamma}, CCAAT/enhancer-binding protein {alpha} and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18{beta}-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18{beta

  8. Decreased value-sensitivity in schizophrenia.

    Science.gov (United States)

    Martinelli, Cristina; Rigoli, Francesco; Dolan, Ray J; Shergill, Sukhwinder S

    2018-01-01

    Pathophysiology in schizophrenia has been linked to aberrant incentive salience, namely the dysfunctional processing of value linked to abnormal dopaminergic activity. In line with this, recent studies showed impaired learning of value in schizophrenia. However, how value is used to guide behaviour independently from learning, as in risky choice, has rarely been examined in this disorder. We studied value-guided choice under risk in patients with schizophrenia and in controls using a task requiring a choice between a certain monetary reward, varying trial-by-trial, and a gamble offering an equal probability of getting double this certain amount or nothing. We observed that patients compared to controls exhibited reduced sensitivity to values, implying that their choices failed to flexibly adapt to the specific values on offer. Moreover, the degree of this value sensitivity inversely correlated with aberrant salience experience, suggesting that the inability to tune choice to value may be a key element of aberrant salience in the illness. Our results help clarify the cognitive mechanisms underlying improper attribution of value in schizophrenia and may thus inform cognitive interventions aimed at reinstating value sensitivity in patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Unique B cell differentiation profile in tolerant kidney transplant patients.

    Science.gov (United States)

    Chesneau, M; Pallier, A; Braza, F; Lacombe, G; Le Gallou, S; Baron, D; Giral, M; Danger, R; Guerif, P; Aubert-Wastiaux, H; Néel, A; Michel, L; Laplaud, D-A; Degauque, N; Soulillou, J-P; Tarte, K; Brouard, S

    2014-01-01

    Operationally tolerant patients (TOL) display a higher number of blood B cells and transcriptional B cell signature. As they rarely develop an allo-immune response, they could display an abnormal B cell differentiation. We used an in vitro culture system to explore T-dependent differentiation of B cells into plasma cells. B cell phenotype, apoptosis, proliferation, cytokine, immunoglobulin production and markers of differentiation were followed in blood of these patients. Tolerant recipients show a higher frequency of CD20(+) CD24(hi) CD38(hi) transitional and CD20(+) CD38(lo) CD24(lo) naïve B cells compared to patients with stable graft function, correlating with a decreased frequency of CD20(-) CD38(+) CD138(+) differentiated plasma cells, suggestive of abnormal B cell differentiation. B cells from TOL proliferate normally but produce more IL-10. In addition, B cells from tolerant recipients exhibit a defective expression of factors of the end step of differentiation into plasma cells and show a higher propensity for cell death apoptosis compared to patients with stable graft function. This in vitro profile is consistent with down-regulation of B cell differentiation genes and anti-apoptotic B cell genes in these patients in vivo. These data suggest that a balance between B cells producing IL-10 and a deficiency in plasma cells may encourage an environment favorable to the tolerance maintenance. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Anxiety sensitivity and marijuana use: an analysis from ecological momentary assessment

    NARCIS (Netherlands)

    Buckner, J.D.; Zvolensky, M.J.; Smits, J.A.J.; Norton, P.J.; Crosby, R.D.; Wonderlich, S.A.; Schmidt, N.B.

    2011-01-01

    Background: The cognitive factor of Anxiety Sensitivity (AS; the fear of anxiety and related bodily sensations) is theorized to play a role in cannabis use and its disorders. Lower-order facets of AS (physical concerns, mental incapacitation concerns, and social concerns) may be differentially

  11. CERN exhibition a big hit in Bulgaria

    CERN Multimedia

    2005-01-01

    The first CERN exhibition in Bulgaria attracted many visitors. In the first ever CERN exhibition to be held in Bulgaria, over 1,400 visitors, many of them students and young physicists, visited the 10-day event in Sofia. The CERN mini-exhibition took place at the National Earth and Mankind Museum between 8 and 17 November. Permanently staffed by young physicists from Sofia University, there were exhibits on display about research activities at CERN, as well as four additional posters describing Bulgaria's participation. The inauguration took place on the morning of 8 November in the presence of the Vice-Minister for Science and Education, Mrs. Vanya Dobreva, and some 200 guests. A series of short speeches were followed by a visit to the exhibition. CERN's representative at the event, Ray Lewis, was then asked by Professor Matey Mateev, President of the Union of Physicists in Bulgaria, to say a few words on behalf of the Organization. Numerous journalists were also present at the inauguration. A painting enti...

  12. CERN’s travelling exhibition goes to Austria

    CERN Multimedia

    Mélissa Lanaro

    2011-01-01

    Since April 2009 CERN’s travelling exhibition has been touring through some of the Organization's Member States. After Italy and Denmark it has been on show since February at Austria’s Hartberg Ökopark, a very popular science museum situated some one hundred kilometres from Vienna. To coincide with the CERN exhibition, Austria’s scientific community has organised a series of events for the general public which have had marked success. The exhibition's next destination will be Portugal and preparations are already underway to ensure that it is another resounding success   The travelling exhibition was designed in collaboration with the University of Geneva, as part of the celebrations for its 450th anniversary, and has already notched up a good number of kilometres as it travels from country to country. “In 2010 the exhibition already had around 55,000 visitors,” explains Rolf Landua, who heads the Education Group. Since its inauguration ...

  13. “Accelerating Science” exhibition zooms to Turkey

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    'Accelerating Science', CERN’s travelling science outreach exhibition, has just arrived at the Middle East Technical University (METU) in Ankara, Turkey for a four-month stay there. This is the first time it has moved outside the circle of the Member States. The Turkish venue will inaugurate some new exhibits that have recently been developed by CERN’s software developers.   “It’s been a very busy day,” says Bilge Demirkoz, an associate professor of physics at METU and a member of AMS-02, who had been overseeing the unloading of the lorries when we spoke to her. “As the University doesn’t have a specific exhibition space, the CERN exhibits are going to be housed in the covered tennis courts just behind the cultural and congress centre. It’s a beautiful venue, and there are plenty of parking spaces.” The University has sent invitations to the exhibition to high schools and to about 100 ...

  14. Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Fenming Zhang

    Full Text Available To explore the diagnostic models of Crohn's disease (CD, Intestinal tuberculosis (ITB and the differential diagnostic model between CD and ITB by analyzing serum proteome profiles.Serum proteome profiles from 30 CD patients, 21 ITB patients and 30 healthy controls (HCs were analyzed by using weak cationic magnetic beads combined with MALDI-TOF-MS technique to detect the differentially expressed proteins of serum samples. Three groups were made and compared accordingly: group of CD patients and HCs, group of ITB patients and HCs, group of CD patients and ITB patients. Wilcoxon rank sum test was used to screen the ten most differentiated protein peaks (P < 0.05. Genetic algorithm combining with support vector machine (SVM was utilized to establish the optimal diagnostic models for CD, ITB and the optimal differential diagnostic model between CD and ITB. The predictive effects of these models were evaluated by Leave one out (LOO cross validation method.There were 236 protein peaks differently expressed between group of CD patients and HCs, 305 protein peaks differently expressed between group of ITB patients and HCs, 332 protein peaks differently expressed between group of CD patients and ITB patients. Ten most differentially expressed peaks were screened out between three groups respectively (P < 0.05 to establish diagnostic models and differential diagnostic model. A diagnostic model comprising of four protein peaks (M/Z 4964, 3029, 2833, 2900 can well distinguish CD patients and HCs, with a specificity and sensitivity of 96.7% and 96.7% respectively. A diagnostic model comprising four protein peaks (M/Z 3030, 2105, 2545, 4210 can well distinguish ITB patients and HCs, with a specificity and sensitivity of 93.3% and 95.2% respectively. A differential diagnostic model comprising three potential biomarkers protein peaks (M/Z 4267, 4223, 1541 can well distinguish CD patients and ITB patients, with a specificity and sensitivity of 76.2% and 80

  15. Field-based optimal-design of an electric motor: a new sensitivity formulation

    Science.gov (United States)

    Barba, Paolo Di; Mognaschi, Maria Evelina; Lowther, David Alister; Wiak, Sławomir

    2017-12-01

    In this paper, a new approach to robust optimal design is proposed. The idea is to consider the sensitivity by means of two auxiliary criteria A and D, related to the magnitude and isotropy of the sensitivity, respectively. The optimal design of a switched-reluctance motor is considered as a case study: since the case study exhibits two design criteria, the relevant Pareto front is approximated by means of evolutionary computing.

  16. UV laser radiation alters the embryonic protein profile of adrenal-kidney-gonadal complex and gonadal differentiation in the lizard, Calotes Versicolor.

    Science.gov (United States)

    Khodnapur, Bharati S; Inamdar, Laxmi S; Nindi, Robertraj S; Math, Shivkumar A; Mulimani, B G; Inamdar, Sanjeev R

    2015-02-01

    To examine the impact of ultraviolet (UV) laser radiation on the embryos of Calotes versicolor in terms of its effects on the protein profile of the adrenal-kidney-gonadal complex (AKG), sex determination and differentiation, embryonic development and hatching synchrony. The eggs of C. versicolor, during thermo-sensitive period (TSP), were exposed to third harmonic laser pulses at 355 nm from a Q-switched Nd:YAG laser for 180 sec. Subsequent to the exposure they were incubated at the male-producing temperature (MPT) of 25.5 ± 0.5°C. The AKG of hatchlings was subjected to protein analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and to histology. The UV laser radiation altered the expression of the protein banding pattern in the AKG complex of hatchlings and it also affected the gonadal sex differentiation. SDS-PAGE of AKG of one-day-old hatchlings revealed a total of nine protein bands in the control group whereas UV laser irradiated hatchlings expressed a total of seven protein bands only one of which had the same Rf as a control band. The UV laser treated hatchlings have an ovotestes kind of gonad exhibiting a tendency towards femaleness instead of the typical testes. It is inferred that 355 nm UV laser radiation during TSP induces changes in the expression of proteins as well as their secretions. UV laser radiation had an impact on the gonadal differentiation pathway but no morphological anomalies were noticed.

  17. VMAT2 identified as a regulator of late-stage β-cell differentiation.

    Science.gov (United States)

    Sakano, Daisuke; Shiraki, Nobuaki; Kikawa, Kazuhide; Yamazoe, Taiji; Kataoka, Masateru; Umeda, Kahoko; Araki, Kimi; Mao, Di; Matsumoto, Shirou; Nakagata, Naomi; Andersson, Olov; Stainier, Didier; Endo, Fumio; Kume, Kazuhiko; Uesugi, Motonari; Kume, Shoen

    2014-02-01

    Cell replacement therapy for diabetes mellitus requires cost-effective generation of high-quality, insulin-producing, pancreatic β cells from pluripotent stem cells. Development of this technique has been hampered by a lack of knowledge of the molecular mechanisms underlying β-cell differentiation. The present study identified reserpine and tetrabenazine (TBZ), both vesicular monoamine transporter 2 (VMAT2) inhibitors, as promoters of late-stage differentiation of Pdx1-positive pancreatic progenitor cells into Neurog3 (referred to henceforth as Ngn3)-positive endocrine precursors. VMAT2-controlled monoamines, such as dopamine, histamine and serotonin, negatively regulated β-cell differentiation. Reserpine or TBZ acted additively with dibutyryl adenosine 3',5'-cyclic AMP, a cell-permeable cAMP analog, to potentiate differentiation of embryonic stem (ES) cells into β cells that exhibited glucose-stimulated insulin secretion. When ES cell-derived β cells were transplanted into AKITA diabetic mice, the cells reversed hyperglycemia. Our protocol provides a basis for the understanding of β-cell differentiation and its application to a cost-effective production of functional β cells for cell therapy.

  18. A Lateral Differential Resonant Pressure Microsensor Based on SOI-Glass Wafer-Level Vacuum Packaging

    Directory of Open Access Journals (Sweden)

    Bo Xie

    2015-09-01

    Full Text Available This paper presents the fabrication and characterization of a resonant pressure microsensor based on SOI-glass wafer-level vacuum packaging. The SOI-based pressure microsensor consists of a pressure-sensitive diaphragm at the handle layer and two lateral resonators (electrostatic excitation and capacitive detection on the device layer as a differential setup. The resonators were vacuum packaged with a glass cap using anodic bonding and the wire interconnection was realized using a mask-free electrochemical etching approach by selectively patterning an Au film on highly topographic surfaces. The fabricated resonant pressure microsensor with dual resonators was characterized in a systematic manner, producing a quality factor higher than 10,000 (~6 months, a sensitivity of about 166 Hz/kPa and a reduced nonlinear error of 0.033% F.S. Based on the differential output, the sensitivity was increased to two times and the temperature-caused frequency drift was decreased to 25%.

  19. PDF constraints from top-quark pair differential measurements

    CERN Document Server

    García Navarro, José Enrique; The ATLAS collaboration

    2018-01-01

    Constraints on parton distribution functions are presented that are based on differential cross-section measurements of single lepton and dilepton kinematic distributions in dileptonic top quark pair events. The measurements utilize 20.2 fb-1 of sqrt(s) = 8 TeV pp collisions recorded by the ATLAS experiment at the LHC. The sensitivity of the cross-sections to the gluon parton distribution function is explored.

  20. Cellular network entropy as the energy potential in Waddington's differentiation landscape

    Science.gov (United States)

    Banerji, Christopher R. S.; Miranda-Saavedra, Diego; Severini, Simone; Widschwendter, Martin; Enver, Tariq; Zhou, Joseph X.; Teschendorff, Andrew E.

    2013-01-01

    Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape. PMID:24154593

  1. Mast Cells Density in Fibrotic Capsule of Enchondroma and Well-Differentiated Chondrosarcoma: A Method for Histopathologic Differentiation

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Kharazi Fard

    2012-02-01

    Full Text Available Background: An enchondroma is a benign and a well-differentiated chondrosarcoma is an invasive chondroid tumor with high recurrence potential. In spite of biologic differences, these two tumors have very similar histopathologic appearance. It has been shown that the biologic nature of the connective tissue around benign and malignant tumors varies in the number of mast cells. The aim of this study was to study the histopathologic distinction of enchondroma and well-differentiated chondrosarcoma using the density of the mast cells in fibrotic capsule. Methods: Twelve enchondroma and 15 well-differentiated chondrosarcoma were collected from Pathology department of Cancer Institute and Central Pathology department of Imam Khomeini Hospital in Tehran. 3 micron paraffin embedded tissue sections were stained by toluidine blue for mast cells counting. Mast cells were counted in fibrous capsule of all cases. Mast cells counts were accomplished in 10 high power fields .The average number of mast cells in 10HPF was determined as an index for each lesion. Mann-Whitney U test was used for statistical analysis. Results: Mean index in enchondroma and well-differentiated chondrosarcoma groups were 0.1±0.12 and 0.31±0.33 respectively, showing a significant difference between number of mast cells in the fibrotic capsule in these two lesions (p=0.028. Comparison of the corresponding points in ROC curve, showed a cut-off point = 0.15, with positive predictive value of 61%, negative predictive value 71%, specificity of 33.3% and sensitivity of 66.7%, (p=0.025. Conclusion: Average density of the mast cells in the surrounding fibrotic capsules of enchondroma and well-differentiated chondrosarcoma along with other criterions, could be a beneficial factor for histologically differentiation between these two lesions.

  2. Cell cycle sensitivity of HL-60 cells to the differentiation-inducing effects of 1-alpha,25-dihydroxyvitamin D3

    International Nuclear Information System (INIS)

    Studzinski, G.P.; Bhandal, A.K.; Brelvi, Z.S.

    1985-01-01

    A recently described system for monocyte-like differentiation of HL-60 cells was utilized to determine if the initiation of this pathway can be linked to a set of replicative cellular events. The standard induction system consisted of a 4-h exposure to 100 nM 1-alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] followed by determination of nonspecific esterase and phagocytic activity 24 h later. The cell cycle status was ascertained by the incorporation of [ 3 H]thymidine and autoradiography. Studies in which cell cycle block in the G1/S phase boundary region was produced by a partial inhibition of DNA synthesis with thymidine, or sodium butyrate, showed that the exposure of such semisynchronous cultures to 1,25(OH)2D3 resulted in an increased proportion of differentiated cells. Conversely, blocking the cell cycle with vinblastine (G2/M block) or theobromine (mid-G1 block) inhibited the initiation of differentiation by 1,25(OH)2D3. Experiments in which the differentiated cells were examined for the cell cycle position at the time of the exposure to 1,25(OH)2D3 by [ 3 H]thymidine labeling and autoradiography confirmed that the late G1 and early S phase cells are those which predominate in the differentiated fraction of 1,25(OH)2D3-treated HL-60 cultures. These results link pre- and early replicative cellular events to the induction of monocytic differentiation by 1,25(OH)2D3

  3. Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation

    DEFF Research Database (Denmark)

    Pérez-Galán, Patricia; Mora-Jensen, Helena; Weniger, Marc A

    2011-01-01

    bortezomib-resistant MCL cell lines and primary tumor cells from MCL patients with inferior clinical response to bortezomib also expressed plasmacytic features. Knockdown of IRF4 was toxic for the subset of MCL cells with plasmacytic differentiation, but only slightly sensitized cells to bortezomib. We...

  4. Visual Contrast Sensitivity in Early-Stage Parkinson's Disease.

    Science.gov (United States)

    Ming, Wendy; Palidis, Dimitrios J; Spering, Miriam; McKeown, Martin J

    2016-10-01

    Visual impairments are frequent in Parkinson's disease (PD) and impact normal functioning in daily activities. Visual contrast sensitivity is a powerful nonmotor sign for discriminating PD patients from controls. However, it is usually assessed with static visual stimuli. Here we examined the interaction between perception and eye movements in static and dynamic contrast sensitivity tasks in a cohort of mildly impaired, early-stage PD patients. Patients (n = 13) and healthy age-matched controls (n = 12) viewed stimuli of various spatial frequencies (0-8 cyc/deg) and speeds (0°/s, 10°/s, 30°/s) on a computer monitor. Detection thresholds were determined by asking participants to adjust luminance contrast until they could just barely see the stimulus. Eye position was recorded with a video-based eye tracker. Patients' static contrast sensitivity was impaired in the intermediate spatial-frequency range and this impairment correlated with fixational instability. However, dynamic contrast sensitivity and patients' smooth pursuit were relatively normal. An independent component analysis revealed contrast sensitivity profiles differentiating patients and controls. Our study simultaneously assesses perceptual contrast sensitivity and eye movements in PD, revealing a possible link between fixational instability and perceptual deficits. Spatiotemporal contrast sensitivity profiles may represent an easily measurable metric as a component of a broader combined biometric for nonmotor features observed in PD.

  5. Ordinary differential equations with applications in molecular biology.

    Science.gov (United States)

    Ilea, M; Turnea, M; Rotariu, M

    2012-01-01

    Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances

  6. Low-threshold potassium currents stabilize IID-sensitivity in the inferior colliculus.

    Directory of Open Access Journals (Sweden)

    Anita eKarcz

    2012-08-01

    Full Text Available The inferior colliculus (IC is a midbrain nucleus that exhibits sensitivity to differences in interaural time and intensity (ITDs and IIDs and integrates information from the auditory brainstem to provide an unambiguous representation of sound location across the azimuth. Further upstream, in the lateral superior olive (LSO, absence of low-threshold potassium currents in Kcna1-/- mice interfered with response onset timing and restricted IID-sensitivity to the hemifield of the excitatory ear. Assuming the IID-sensitivity in the IC to be at least partly inherited from LSO neurons, the IC IID-encoding was compared between wild-type (Kcna1+/+ and Kcna1-/- mice. We asked whether the effect observed in the Kcna1-/- LSO was (I simply propagated into the IC, (II is enhanced and amplified or, (III alternatively, was compensated and so no longer detectable. Our results show that general IC response properties as well as the distribution of IID-functions were comparable in Kcna1-/- and Kcna1+/+ mice. In agreement with the literature IC neurons exhibited a higher level-invariance of IID-sensitivity compared to LSO neurons. However, manipulating the timing between the inputs of the two ears caused significantly larger shifts of IID-sensitivity in Kcna1-/- mice, whereas in the wild-type IC the IID functions were stable and less sensitive to changes of the temporal relationship between the binaural inputs. We conclude that the IC not only inherits IID-sensitivity from the LSO, but that the convergence with other, non-olivary inputs in the wild-type IC acts to quality-control, consolidate and stabilize IID representation; this necessary integration of inputs is impaired in the absence of the low-threshold potassium currents mediated by Kv1.1.

  7. Synthetic (+)-antroquinonol exhibits dual actions against insulin resistance by triggering AMP kinase and inhibiting dipeptidyl peptidase IV activities.

    Science.gov (United States)

    Hsu, C Y; Sulake, R S; Huang, P-K; Shih, H-Y; Sie, H-W; Lai, Y-K; Chen, C; Weng, C F

    2015-01-01

    The fungal product (+)-antroquinonol activates AMP kinase (AMPK) activity in cancer cell lines. The present study was conducted to examine whether chemically synthesized (+)-antroquinonol exhibited beneficial metabolic effects in insulin-resistant states by activating AMPK and inhibiting dipeptidyl peptidase IV (DPP IV) activity. Effects of (+)-antroquinonol on DPP IV activity were measured with a DPPIV Assay Kit and effects on GLP-1-induced PKA were measured in AR42J cells. Translocation of the glucose transporter 4, GLUT4, induced either by insulin-dependent PI3K/AKT signalling or by insulin-independent AMPK activation, was assayed in differentiated myotubes. Glucose uptake and GLUT4 translocation were assayed in L6 myocytes. Mice with diet-induced obesity were used to assess effects of acute and chronic treatment with (+)-antroquinonol on glycaemic control in vivo. The results showed that of (+)-antroquinonol (100 μM ) inhibited the DPP IV activity as effectively as the clinically used inhibitor, sitagliptin. The phosphorylation of AMPK Thr(172) in differentiated myotubes was significantly increased by (+)-antroquinonol. In cells simultaneously treated with S961 (insulin receptor antagonist), insulin and (+)-antroquinonol, the combination of (+)-antroquinonol plus insulin still increased both GLUT4 translocation and glucose uptake. Further, (+)-antroquinonol and sitagliptin reduced blood glucose, when given acutely or chronically to DIO mice. Chemically synthesized (+)-antroquinonol exhibits dual effects to ameliorate insulin resistance, by increasing AMPK activity and GLUT4 translocation, along with inhibiting DPP IV activity. © 2014 The British Pharmacological Society.

  8. The Inability to Screen Exhibition Swine for Influenza A Virus Using Body Temperature.

    Science.gov (United States)

    Bowman, A S; Nolting, J M; Workman, J D; Cooper, M; Fisher, A E; Marsh, B; Forshey, T

    2016-02-01

    Agricultural fairs create an unconventional animal-human interface that has been associated with swine-to-human transmission of influenza A virus (IAV) in recent years. Early detection of IAV-infected pigs at agricultural fairs would allow veterinarians to better protect swine and human health during these swine exhibitions. This study assessed the use of swine body temperature measurement, recorded by infrared and rectal thermometers, as a practical method to detect IAV-infected swine at agricultural fairs. In our first objective, infrared thermometers were used to record the body surface temperature of 1,092 pigs at the time of IAV nasal swab collection at the end of the exhibition period of 55 agricultural fairs. IAV was recovered from 212 (19.4%) pigs, and the difference in mean infrared body temperature measurement of IAV-positive and IAV-negative pigs was 0.83°C. In a second objective, snout wipes were collected from 1,948 pigs immediately prior to the unloading of the animals at a single large swine exhibition. Concurrent to the snout wipe collection, owners took the rectal temperatures of his/her pigs. In this case, 47 (2.4%) pigs tested positive for IAV before they entered the swine barn. The mean rectal temperatures differed by only 0.19°C between IAV-positive and IAV-negative pigs. The low prevalence of IAV among the pigs upon entry to the fair in the second objective provides evidence that limiting intraspecies spread of IAV during the fairs will likely have significant impacts on the zoonotic transmission. However, in both objectives, the high degree of similarity in the body temperature measurements between the IAV-positive and IAV-negative pigs made it impossible to set a diagnostically meaningful cut point to differentiate IAV status of the individual animals. Unfortunately, body temperature measurement cannot be used to accurately screen exhibition swine for IAV. © 2015 Blackwell Verlag GmbH.

  9. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Marianne van; Murphy, Eoin [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); Morrell, Ruth [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Knapper, Steven [Department of Haematology, School of Medicine, Cardiff University, Heath Park, CF14 4XN Cardiff (United Kingdom); O' Dwyer, Michael [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Samali, Afshin; Szegezdi, Eva, E-mail: eva.szegezdi@nuigalway.ie [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)

    2011-03-15

    Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  10. "Big Science" exhibition at Balexert

    CERN Multimedia

    2008-01-01

    CERN is going out to meet those members of the general public who were unable to attend the recent Open Day. The Laboratory will be taking its "Big Science" exhibition from the Globe of Science and Innovation to the Balexert shopping centre from 19 to 31 May 2008. The exhibition, which shows the LHC and its experiments through the eyes of a photographer, features around thirty spectacular photographs measuring 4.5 metres high and 2.5 metres wide. Welcomed and guided around the exhibition by CERN volunteers, shoppers at Balexert will also have the opportunity to discover LHC components on display and watch films. "Fun with Physics" workshops will be held at certain times of the day. Main hall of the Balexert shopping centre, ground floor, from 9.00 a.m. to 7.00 p.m. Monday to Friday and from 10 a.m. to 6 p.m. on the two Saturdays. Call for volunteers All members of the CERN personnel are invited to enrol as volunteers to help welcom...

  11. Modeling endocrine regulation of the menstrual cycle using delay differential equations.

    Science.gov (United States)

    Harris, Leona A; Selgrade, James F

    2014-11-01

    This article reviews an effective mathematical procedure for modeling hormonal regulation of the menstrual cycle of adult women. The procedure captures the effects of hormones secreted by several glands over multiple time scales. The specific model described here consists of 13 nonlinear, delay, differential equations with 44 parameters and correctly predicts blood levels of ovarian and pituitary hormones found in the biological literature for normally cycling women. In addition to this normal cycle, the model exhibits another stable cycle which may describe a biologically feasible "abnormal" condition such as polycystic ovarian syndrome. Model simulations illustrate how one cycle can be perturbed to the other cycle. Perturbations due to the exogenous administration of each ovarian hormone are examined. This model may be used to test the effects of hormone therapies on abnormally cycling women as well as the effects of exogenous compounds on normally cycling women. Sensitive parameters are identified and bifurcations in model behavior with respect to parameter changes are discussed. Modeling various aspects of menstrual cycle regulation should be helpful in predicting successful hormone therapies, in studying the phenomenon of cycle synchronization and in understanding many factors affecting the aging of the female reproductive endocrine system. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Sarah Straud

    2010-07-01

    Full Text Available Many cell lines derived from tumors as well as transformed cell lines are far more sensitive to V-ATPase inhibitors than normal counterparts. The molecular mechanisms underlying these differences in sensitivity are not known. Using global gene expression data, we show that the most sensitive responses to HeLa cells to low doses of V-ATPase inhibitors involve genes responsive to decreasing intracellular iron or decreasing cholesterol and that sensitivity to iron uptake is an important determinant of V-ATPase sensitivity in several cancer cell lines. One of the most sensitive cell lines, melanoma derived SK-Mel-5, over-expresses the iron efflux transporter ferroportin and has decreased expression of proteins involved in iron uptake, suggesting that it actively suppresses cytoplasmic iron. SK-Mel-5 cells have increased production of reactive oxygen species and may be seeking to limit additional production of ROS by iron.

  13. The impact of laser ablation on optical soft tissue differentiation for tissue specific laser surgery-an experimental ex vivo study

    Directory of Open Access Journals (Sweden)

    Stelzle Florian

    2012-06-01

    Full Text Available Abstract Background Optical diffuse reflectance can remotely differentiate various bio tissues. To implement this technique in an optical feedback system to guide laser surgery in a tissue-specific way, the alteration of optical tissue properties by laser ablation has to be taken into account. It was the aim of this study to evaluate the general feasibility of optical soft tissue differentiation by diffuse reflectance spectroscopy under the influence of laser ablation, comparing the tissue differentiation results before and after laser intervention. Methods A total of 70 ex vivo tissue samples (5 tissue types were taken from 14 bisected pig heads. Diffuse reflectance spectra were recorded before and after Er:YAG-laser ablation. The spectra were analyzed and differentiated using principal component analysis (PCA, followed by linear discriminant analysis (LDA. To assess the potential of tissue differentiation, area under the curve (AUC, sensitivity and specificity was computed for each pair of tissue types before and after laser ablation, and compared to each other. Results Optical tissue differentiation showed good results before laser exposure (total classification error 13.51%. However, the tissue pair nerve and fat yielded lower AUC results of only 0.75. After laser ablation slightly reduced differentiation results were found with a total classification error of 16.83%. The tissue pair nerve and fat showed enhanced differentiation (AUC: 0.85. Laser ablation reduced the sensitivity in 50% and specificity in 80% of the cases of tissue pair comparison. The sensitivity of nerve–fat differentiation was enhanced by 35%. Conclusions The observed results show the general feasibility of tissue differentiation by diffuse reflectance spectroscopy even under conditions of tissue alteration by laser ablation. The contrast enhancement for the differentiation between nerve and fat tissue after ablation is assumed to be due to laser removal of the

  14. CONSTRUCTION AND ADAPTATION OF GENETIC SEXING STRAIN OF THE MEDFLY CERATITIS CAPITATA (WIED.)BASED ON TEMPERATURE SENSITIVE MUTATION IN THE EGYPTIAN FRUITFLY LABORATORIES

    International Nuclear Information System (INIS)

    SHOMAN, A.A.

    2007-01-01

    Special strains that produce only males are used now for the control of the medfly Ceratitis capitata using the sterile insect technique. The use of these strains has a major impact on the overall efficiency of SIT, by increasing significantly the amount of sterility induced in field population comparing by using bisexual strains. Genetic sexing strains (GSS) are based on the use of male-linked chromosomal translocations which enable selectable marker genes to be linked to the male sex. Two basic components are required in the medfly to construct and adapt a laboratory strain which exhibits genetic sexing properties. The first is Y-auto some translocation strain, which enables male and female pupae to be differentiated on the basis of colour and the second is temperature sensitive lethal (tsl) mutation strain, which enables females to be killed by an increase in ambient temperature

  15. Label-free signal-on aptasensor for sensitive electrochemical detection of arsenite.

    Science.gov (United States)

    Cui, Lin; Wu, Jie; Ju, Huangxian

    2016-05-15

    A signal-on aptasensor was fabricated for highly sensitive and selective electrochemical detection of arsenite with a label-free Ars-3 aptamer self-assembled on a screen-printed carbon electrode (SPCE) via Au-S bond. The Ars-3 aptamer could adsorb cationic polydiallyldimethylammonium (PDDA) via electrostatic interaction to repel other cationic species. In the presence of arsenite, the change of Ars-3 conformation due to the formation of Ars-3/arsenite complex led to less adsorption of PDDA, and the complex could adsorb more positively charged [Ru(NH3)6](3+) as an electrochemically active indicator on the aptasensor surface, which produced a sensitive "turn-on" response. The target-induced structure switching could be used for sensitive detection of arsenite with a linear range from 0.2 nM to 100 nM and a detection limit down to 0.15 nM. Benefiting from Ars-3 aptamer, the proposed system exhibited excellent specificity against other heavy metal ions. The SPCE-based aptasensor exhibited the advantages of low cost and simple fabrication, providing potential application of arsenite detection in environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Knockdown of Indian hedgehog protein induces an inhibition of cell growth and differentiation in osteoblast MC3T3-E1 cells

    OpenAIRE

    Deng, Ang; Zhang, Hongqi; Hu, Minyu; Liu, Shaohua; Gao, Qile; Wang, Yuxiang; Guo, Chaofeng

    2017-01-01

    Indian hedgehog protein (Ihh) is evolutionarily conserved and serves important roles in controlling the differentiation of progenitor cells into osteoblasts. Ihh null mutant mice exhibit a failure of osteoblast development in endochondral bone. Although studies have demonstrated that Ihh signaling is a potent local factor that regulates osteoblast differentiation, the specific transcription factors that determine osteoblast differentiation remain unclear. Further studies are required to deter...

  17. Systematic Review and Meta-Analysis of CT Features for Differentiating Complicated and Uncomplicated Appendicitis.

    Science.gov (United States)

    Kim, Hae Young; Park, Ji Hoon; Lee, Yoon Jin; Lee, Sung Soo; Jeon, Jong-June; Lee, Kyoung Ho

    2018-04-01

    Purpose To perform a systematic review and meta-analysis to identify computed tomographic (CT) features for differentiating complicated appendicitis in patients suspected of having appendicitis and to summarize their diagnostic accuracy. Materials and Methods Studies on diagnostic accuracy of CT features for differentiating complicated appendicitis (perforated or gangrenous appendicitis) in patients suspected of having appendicitis were searched in Ovid-MEDLINE, EMBASE, and the Cochrane Library. Overlapping descriptors used in different studies to denote the same image finding were subsumed under a single CT feature. Pooled diagnostic accuracy of the CT features was calculated by using a bivariate random effects model. CT features with pooled diagnostic odds ratios with 95% confidence intervals not including 1 were considered as informative. Results Twenty-three studies were included, and 184 overlapping descriptors for various CT findings were subsumed under 14 features. Of these, 10 features were informative for complicated appendicitis. There was a general tendency for these features to show relatively high specificity but low sensitivity. Extraluminal appendicolith, abscess, appendiceal wall enhancement defect, extraluminal air, ileus, periappendiceal fluid collection, ascites, intraluminal air, and intraluminal appendicolith showed pooled specificity greater than 70% (range, 74%-100%), but sensitivity was limited (range, 14%-59%). Periappendiceal fat stranding was the only feature that showed high sensitivity (94%; 95% confidence interval: 86%, 98%) but low specificity (40%; 95% confidence interval, 23%, 60%). Conclusion Ten informative CT features for differentiating complicated appendicitis were identified in this study, nine of which showed high specificity, but low sensitivity. © RSNA, 2017 Online supplemental material is available for this article.

  18. The mere exposure effect is differentially sensitive to different judgment tasks.

    Science.gov (United States)

    Seamon, J G; McKenna, P A; Binder, N

    1998-03-01

    The mere exposure effect is the increase in positive affect that results from the repeated exposure to previously novel stimuli. We sought to determine if judgments other than affective preference could reliably produce a mere exposure effect for two-dimensional random shapes. In two experiments, we found that brighter and darker judgments did not differentiate target from distracter shapes, liking judgments led to target selection greater than chance, and disliking judgments led to distracter selection greater than chance. These results for brighter, darker, and liking judgments were obtained regardless of whether shape recognition was greater (Experiment 1) or not greater (Experiment 2) than chance. Effects of prior exposure to novel shapes were reliably observed only for affective judgment tasks. These results are inconsistent with general predictions made by the nonspecific activation hypothesis, but not the affective primacy or perceptual fluency hypotheses which were discussed in terms of cognitive neuroscience research. Copyright 1998 Academic Press.

  19. Directed Differentiation of Zebrafish Pluripotent Embryonic Cells to Functional Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Yao Xiao

    2016-09-01

    Full Text Available A cardiomyocyte differentiation in vitro system from zebrafish embryos remains to be established. Here, we have determined pluripotency window of zebrafish embryos by analyzing their gene-expression patterns of pluripotency factors together with markers of three germ layers, and have found that zebrafish undergoes a very narrow period of pluripotency maintenance from zygotic genome activation to a brief moment after oblong stage. Based on the pluripotency and a combination of appropriate conditions, we established a rapid and efficient method for cardiomyocyte generation in vitro from primary embryonic cells. The induced cardiomyocytes differentiated into functional and specific cardiomyocyte subtypes. Notably, these in vitro generated cardiomyocytes exhibited typical contractile kinetics and electrophysiological features. The system provides a new paradigm of cardiomyocyte differentiation from primary embryonic cells in zebrafish. The technology provides a new platform for the study of heart development and regeneration, in addition to drug discovery, disease modeling, and assessment of cardiotoxic agents.

  20. Alendronate-Eluting Biphasic Calcium Phosphate (BCP Scaffolds Stimulate Osteogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Sung Eun Kim

    2015-01-01

    Full Text Available Biphasic calcium phosphate (BCP scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN- eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM, energy-dispersive X-ray spectroscopy (EDS, and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR. An in vitro release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation.