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Sample records for vivo direct correlation

  1. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control.

    Directory of Open Access Journals (Sweden)

    Adam R Hersperger

    2010-05-01

    Full Text Available Many immune correlates of CD8(+ T-cell-mediated control of HIV replication, including polyfunctionality, proliferative ability, and inhibitory receptor expression, have been discovered. However, no functional correlates using ex vivo cells have been identified with the known ability to cause the direct elimination of HIV-infected cells. We have recently discovered the ability of human CD8(+ T-cells to rapidly upregulate perforin--an essential molecule for cell-mediated cytotoxicity--following antigen-specific stimulation. Here, we examined perforin expression capability in a large cross-sectional cohort of chronically HIV-infected individuals with varying levels of viral load: elite controllers (n = 35, viremic controllers (n = 29, chronic progressors (n = 27, and viremic nonprogressors (n = 6. Using polychromatic flow cytometry and standard intracellular cytokine staining assays, we measured perforin upregulation, cytokine production, and degranulation following stimulation with overlapping peptide pools encompassing all proteins of HIV. We observed that HIV-specific CD8(+ T-cells from elite controllers consistently display an enhanced ability to express perforin directly ex vivo compared to all other groups. This ability is not restricted to protective HLA-B haplotypes, does not require proliferation or the addition of exogenous factors, is not restored by HAART, and primarily originates from effector CD8(+ T-cells with otherwise limited functional capability. Notably, we found an inverse relationship between HIV-specific perforin expression and viral load. Thus, the capability of HIV-specific CD8(+ T-cells to rapidly express perforin defines a novel correlate of control in HIV infection.

  2. Temporal correlation coefficient for directed networks.

    Science.gov (United States)

    Büttner, Kathrin; Salau, Jennifer; Krieter, Joachim

    2016-01-01

    Previous studies dealing with network theory focused mainly on the static aggregation of edges over specific time window lengths. Thus, most of the dynamic information gets lost. To assess the quality of such a static aggregation the temporal correlation coefficient can be calculated. It measures the overall possibility for an edge to persist between two consecutive snapshots. Up to now, this measure is only defined for undirected networks. Therefore, we introduce the adaption of the temporal correlation coefficient to directed networks. This new methodology enables the distinction between ingoing and outgoing edges. Besides a small example network presenting the single calculation steps, we also calculated the proposed measurements for a real pig trade network to emphasize the importance of considering the edge direction. The farm types at the beginning of the pork supply chain showed clearly higher values for the outgoing temporal correlation coefficient compared to the farm types at the end of the pork supply chain. These farm types showed higher values for the ingoing temporal correlation coefficient. The temporal correlation coefficient is a valuable tool to understand the structural dynamics of these systems, as it assesses the consistency of the edge configuration. The adaption of this measure for directed networks may help to preserve meaningful additional information about the investigated network that might get lost if the edge directions are ignored.

  3. In vitro-in vivo correlation in skin permeation.

    Science.gov (United States)

    Mohammed, D; Matts, P J; Hadgraft, J; Lane, M E

    2014-02-01

    In vitro skin permeation studies have been used extensively in the development and optimisation of delivery of actives in vivo. However, there are few reported correlations of such in vitro studies with in vivo data. The aim of this study was to investigate the skin permeation of a model active, niacinamide, both in vitro and in vivo. Conventional diffusion cell studies were conducted in human skin to determine niacinamide permeation from a range of vehicles which included dimethyl isosorbide (DMI), propylene glycol (PG), propylene glycol monolaurate (PGML), N-methyl 2-pyrrolidone (NMP), Miglyol 812N® (MG), and mineral oil (MO). Single, binary or ternary systems were examined. The same vehicles were subsequently examined to investigate niacinamide delivery in vivo. For this proof-of-concept study one donor was used for the in vitro studies and one volunteer for the in vivo investigations to minimise biovariability. Analysis of in vitro samples was conducted using HPLC and in vivo uptake of niacinamide was evaluated using Confocal Raman spectroscopy (CRS). The amount of niacinamide permeated through skin in vitro was linearly proportional to the intensity of the niacinamide signal determined in the stratum corneum in vivo. A good correlation was observed between the signal intensities of selected vehicles and niacinamide signal intensity. The findings provide further support for the use of CRS to monitor drug delivery into and across the skin. In addition, the results highlight the critical role of the vehicle and its disposition in skin for effective dermal delivery.

  4. Correlated responses in tissue weights measured in vivo by ...

    African Journals Online (AJOL)

    The aim of this study was to estimate correlated responses in lean, fat and bone weights in vivo in Dorset Down sheep selected for lean tissue growth. Over the period 1986-1992 inclusive, the lean tissue growth line had been selected using two economic indices for an increased aggregate breeding value incorporating ...

  5. In vivo percutaneous microwave ablation in kidneys: Correlation with ex vivo data and ablation work.

    Science.gov (United States)

    Marcelin, C; Leiner, J; Nasri, S; Petitpierre, F; Le Bras, Y; Yacoub, M; Grenier, N; Bernhard, J C; Cornelis, F

    2017-10-21

    To compare diameters of in vivo microwave ablation (MWA) performed in swine kidneys with ex vivo diameters, and to correlate with ablation work (AW), a new metric reflecting total energy delivered. Eighteen in vivo MWA were performed in 6 swine kidneys successively using one or two antennas (MicroThermX®). Ablation consisted in delivering power (45-120W) for 5-15minutes. Ex vivo diameters were provided by the vendors and obtained on bovine liver tissue. AW was defined as the sum of (power)*(time)*(number of antennas) for all phases of an ablation (in kJoules). Kidneys were removed laparoscopically immediately after ablation. After sacrifice, ablations zones were evaluated macroscopically, and maximum diameters of the zones were recorded. Wilcoxon sum rank test and Pearson's correlation were used for comparisons. For a single antenna (n=12), the in vivo diameters ranged from 12 to 35mm, and 15-49mm for 2 antennas (n=6). The in vivo diameters remained shorter than ex vivo diameters by 8.6%±30.1 on 1 antenna and 11.7%±26.5 on 2 antennas (P=0.31 and 0.44, respectively). AW ranged from 13.5 to 108kJ. Diameters increased linearly with AW both with 1 and 2 antennas, but only moderate correlations were observed (r=0.43 [95% confidence interval: -0.19; 0.81], P=0.16; and 0.57 [-0.44; 0.95], P=0.24, respectively). Although diameters after in vivo renal MWA increased linearly with AW, the moderate correlation and wide standard deviations observed may justify a careful imaging monitoring during treatment delivery and settings adaptation, if needed, for optimal ablation. Copyright © 2017 Editions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  6. Electron-gamma directional correlations; Correlations directionnelles electron-gamma

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    Gerholm, T.R. [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France)

    1966-10-01

    The theory of the angular correlation between conversion electrons and gamma rays is briefly outlined. The experimental methods used for the study of the electron-gamma correlation are described. The effects of the formation of a hole and the hyperfine structure magnetic coupling dependent on time are then considered. The experimental results showed that the attenuations found for different metallic media plainly conform to a simple quadrupolar interaction mechanism. For a source surrounded by an insulator, however, the results show that a rapidly disappearing coupling occurs as a supplement to the quadrupolar interaction mechanism. This coupling attenuates the angular correlation by about 75% of the non-perturbed value. It was concluded that for an intermediate half life of the level of the order of the nanosecond, the attenuations produced by the secondary effects of the hole formation can not be completely neglected. The metallic media considered were Ag, Au, Al, and Ga. In the study of E2 conversion processes, the radical matrix elements governing the E2 conversion process in the 412-KeV transition of {sup 198}Hg were determined. The results exclude the presence of dynamic contributions within the limits of experimental error. The values b{sub 2} (E2) and {alpha}-k (E2) obtained indirectly from the experimentally determined b{sub 4} particle parameter are in complete agreement with the theoretical values obtained by applying the corrections due to the shielding effect and to the finite dimension of the nucleus and excluding the dynamic contributions. The value for the internal conversion coefficient was also in good agreement. Experimental results from the intensity ratios between the peak and the continuum, however, seem to show significant deviations with respect to other experimental and theoretical values. There is good agreement between experimental and theoretical results on the internal conversion of {sup 203}Tl, {sup 201}Tl, and {sup 181}Ta. The theory

  7. In vitro - in vivo correlation: from theory to applications.

    Science.gov (United States)

    Emami, Jaber

    2006-01-01

    A key goal in pharmaceutical development of dosage forms is a good understanding of the in vitro and in vivo performance of the dosage forms. One of the challenges of biopharmaceutics research is correlating in vitro drug release information of various drug formulations to the in vivo drug profiles (IVIVC). Thus the need for a tool to reliably correlate in vitro and in vivo drug release data has exceedingly increased. Such a tool shortens the drug development period, economizes the resources and leads to improved product quality. Increased activity in developing IVIVCs indicates the value of IVIVCs to the pharmaceutical industry. IVIVC can be used in the development of new pharmaceuticals to reduce the number of human studies during the formulation development as the main objective of an IVIVC is to serve as a surrogate for in vivo bioavailability and to support biowaivers. It supports and/or validates the use of dissolution methods and specification settings. This is because the IVIVC includes in vivo relevance to in vitro dissolution specifications. It can also assist in quality control for certain scale-up and post-approval changes (SUPAC). With the proliferation of modified-release products, it becomes necessary to examine the concept of IVIVC in greater depth. Investigations of IVIVC are increasingly becoming an integral part of extended release drug development. There must be some in vitro means of assuring that each batch of the same product will perform identically in vivo. This review article represents the FDA guidance, development, evaluation, and validation of an IVIVC to grant biowaivers, and to set dissolution specifications for oral dosage forms, biopharmaceutics classification systems (BCS), BCS biowaivers, application of BCS in IVIVC development and concept of mapping. The importance of dissolution media and methodology and pharmacokinetic studies in the context of IVIVC has been highlighted. The review also covers the literature examples of IVIVCs

  8. Correlation of In Vivo and Ex Vivo ADC and T2 of In Situ and Invasive Murine Mammary Cancers

    Science.gov (United States)

    Fan, Xiaobing; Macleod, Kay; Mustafi, Devkumar; Conzen, Suzanne D.; Markiewicz, Erica; Zamora, Marta; Vosicky, James; Mueller, Jeffrey; Karczmar, Gregory S.

    2015-01-01

    Ex vivo MRI may aid in the evaluation of surgical specimens, and provide valuable information regarding the micro-anatomy of mammary/breast cancer. The use of ex vivo MRI to study mouse mammary cancer would be enhanced if there is a strong correlation between parameters derived from in vivo and ex vivo scans. Here, we report the correlation between apparent diffusion coefficient (ADC) and T2 values measured in vivo and ex vivo in mouse mammary glands with in situ cancers (mammary intraepithelial neoplasia (MIN)) and invasive cancers (those which spread outside the ducts into surrounding tissue). MRI experiments were performed on the Polyoma middle T oncoprotein breast cancer mouse model (n = 15) in a 9.4T scanner. For in vivo experiments, T2-weighted (T2W) images were acquired to identify abnormal regions, then ADC and T2 values were measured for nine selected slices. For ex vivo experiments, a midline incision was made along the spine, and then skin, glands, and tumors were gently peeled from the body. Tissue was fixed in formalin, placed around a mouse-sized sponge, and sutured together mimicking the geometry of the gland when attached to the mouse. The same pulse sequences used for in vivo experiments were repeated for ex vivo scans at room temperature. Regions of interest were manually traced on T2W images defining features that could be identified on in vivo and ex vivo images. The results demonstrate a strong positive correlations between in vivo and ex vivo invasive cancers for ADC (r = 0.89, p vivo and ex vivo in situ cancers for ADC (r = 0.61, p vivo ADC value was about 54% of the in vivo value; and the average ex vivo T2 was similar to the in vivo value for cancers. Although motion, fixation, and temperature differences affect ADC and T2, these results show a reliable relationship between ADC and T2 in vivo and ex vivo. As a result ex vivo images can provide valuable information with clinical and research applications. PMID:26208092

  9. In Vivo Vector Flow Imaging Using Improved Directional Beamforming

    DEFF Research Database (Denmark)

    Henze, Lasse; Holfort, Iben Kraglund; Kortbek, Jacob

    2007-01-01

    Directional beamforming has shown promising results for creating vector flow images. The method measures both the flow angle and the magnitude of the velocity. The flow angle is estimated by focusing lines in a range of angles from 0 to 180 degrees. The true angle is identified as the angle...... determination fails, the correct velocity can no longer be found. The purpose of this work is to improve the robustness of the directional beamforming method, making precise in vivo measurement possible. A more robust angle estimator is proposed. Spatial averaging in the axial direction is applied over a depth...... on all human volunteers as a gold standard. For the phantom measurement 76.30 % of the angle estimates are within +- 5 degrees of the actual angle, when using the traditional setup. Using our new approach 98.32 % of the angle estimates are within +-5 degrees from the true angle. The comparison between...

  10. Hepatic colon cancer metastases in mice: dynamic in vivo correlation with hypoechoic rims visible at US.

    Science.gov (United States)

    Kruskal, J B; Thomas, P; Nasser, I; Cay, O; Kane, R A

    2000-06-01

    To use videomicroscopy of tumor-bearing livers of live mice to depict tumors directly to determine the exact nature of rims seen on corresponding ultrasonographic (US) scans. Seventy-six hepatic colorectal cancer metastases were studied in exteriorized livers of 18 mice by using intravital microscopy, US, and histologic examination of the same tumors. Hypoechoic rims correlated with distended sinusoidal spaces in vivo. These spaces surrounded only locally invasive tumors (mean diameter, 0.85 mm) that had obstructed the supplying terminal portal venules. These spaces, containing adherent leukocytes and tumor cells, gave rise to new tumor vasculature. Results of histologic examination of rims (portal inflammation, congested or compressed sinusoids, cell atrophy) correlated with leukocyte endothelial adherence, occluded sinusoids, and new vessel formation in vivo. Unlike results from previous studies, dynamic in vivo observations of peritumoral rims demonstrated distended sinusoidal spaces giving rise to new tumor-penetrating vessels. These sinusoids arose around locally invasive tumors and were associated with more advanced intrahepatic disease. These dynamic observations provide a pathophysiologic explanation for previous histologic correlates of peritumoral rims.

  11. Activity-dependent increases in local oxygen consumption correlate with postsynaptic currents in the mouse cerebellum in vivo

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Caesar, Kirsten; Thomsen, Kirsten Engelund

    2011-01-01

    and current source density analysis to study real-time Ca(2+) dynamics and transmembrane ionic currents in relation to CMRO(2) in the mouse cerebellar cortex in vivo. We report a direct correlation between CMRO(2) and summed (i.e., the sum of excitatory, negative currents during the whole stimulation period...

  12. Fiducial markers for MR histological correlation in ex vivo or short-term in vivo animal experiments: a screening study.

    Science.gov (United States)

    Rouvière, Olivier; Reynolds, Carol; Le, Yuan; Lai, Jinping; Roberts, Lewis R; Felmlee, Joel P; Ehman, Richard L

    2006-01-01

    To test injectable fiducial markers for magnetic resonance (MR) histological correlation in ex vivo or in vivo animal experiments. A total of 35 potential markers were tested ex vivo in pork muscle. The end-points were: 1) visibility, size, and shape on MR images and at macroscopic examination; 2) 24-hour stability; and 3) microscopic appearance. Selected markers were injected in vivo (rabbit's muscle and breast tumor tissue) to test their three-hour in vivo stability and their potential toxicity. Finally, different dilutions of the two best markers were assessed again through the same screening tests to determine whether their size on MR images could be customized by dilution. Two fluid acrylic paints containing inorganic pigments were found to be potentially interesting markers. On MR images, they created well-defined susceptibility artifacts. The markers made with iridescent bronze paint (iron oxide coated mica particles) were readily visible on microscopy and their size on MR images could be customized by dilution. The iridescent stainless steel paint (iron, chromium, nickel) created ex vivo the smallest markers in tissue but needed colloidal iron staining to be visible on microscopy and could not be easily diluted. Fluid acrylic paints are potentially interesting markers for MR histological correlation. Further studies are needed to assess their long-term properties.

  13. Heavy-quark correlations in direct photon-photon collisions

    CERN Document Server

    Krämer, M; Kramer, Michael; Laenen, Eric

    1996-01-01

    In two-photon collisions at LEP2 and a future e^+e^- linear collider heavy quarks (mainly charm) will be pair-produced rather copiously. The production via direct and resolved photons can be distinguished experimentally via a remnant-jet tag. We study correlations of the heavy quarks at next-to-leading order in QCD in the direct channel, which is free from phenomenological parton densities in the photon. These correlations are therefore directly calculable in perturbative QCD and provide a stringent test of the production mechanism.

  14. [Relationship between Golgi apparatus and cell migration direction in vivo and in vitro].

    Science.gov (United States)

    Liu, Bin; Liu, Zhi-feng; Ren, Bing-cheng; Chen, Cong; Ming, Hao-lang; Wang, Lei-lei; Zhao, Kai; Yang, Xue-jun

    2013-07-02

    To explore the relationship between Golgi apparatus and the direction of tumor cell migration in vivo and in vitro. Cell migration assays were conducted with rat C6 glioma cells, human U251 and SNB19 glioma cells respectively. Then immunofluorescence was used to detect the position of Golgi apparatus in migrating cells. The percentage of cells with Golgi apparatus facing towards wound edge was calculated. Cell pseudopodium was stained with TRITC-phalloidin and the relationship between Golgi apparatus and pseudopodium detected. Immunohistochemistry was used to reveal the Golgi apparatus in tumor tissue samples. And the percentage of cells with Golgi apparatus facing opposite to the necrotic zones was calculated. In cells located at wound edge, the Golgi apparatus was found facing towards the wound in the vast majority of cells (C6 83% ± 6%, U251 80% ± 7%, SNB19 82% ± 6%). In U251 and SNB19 cells, the golgi apparatus was located in the same direction with cellular pseudopodium. Immunohistochemical staining showed that in cells located around the necrotic zone, the Golgi apparatus faced opposite to the necrotic zones in most cells (rat tissue samples 80% ± 7%, human tissue samples 82% ± 6%). The Golgi apparatus is closely correlated with cell migration and it may be considered as a direction indicator of cell migration. And it provides an important index for the study of tumor cell invasion both in vivo and in vitro.

  15. Blue-green spectral minimum correlates with oxyhemoglobin saturation in vivo.

    Science.gov (United States)

    Denninghoff, Kurt R; Salyer, David A; Basavanthappa, Sreenivasa; Park, Robert I; Chipman, Russell A

    2008-01-01

    An imaging multi-spectral retinal oximeter with intravitrial illumination is used to perform the first in vivo test of the blue-green minima shift oximetry method (BGO) in swine eyes [K. R. Dennighoff, R. A. Chipman, and L. W. Hillman, Opt. Lett. 31, 924-926 (2006); J. Biomed. Opt. 12, 034020 (2007).] A fiber optic intravitreal illuminator inserted through the pars plana was coupled to a monochromator and used to illuminate the retina from an angle. A camera viewing through the cornea recorded a series of images at each wavelength. This intravitreal light source moves the specular vessel glint away from the center of the vessel and directly illuminates the fundus behind most blood vessels. These two conditions combine to provide accurate measurements of vessel and perivascular reflectance. Equations describing these different light paths are solved, and BGO is used to evaluate large retinal vessels. In order to test BGO calibration in vivo, data were acquired from swine with varied retinal arterial oxyhemoglobin saturations (60-100% saturation.). The arterial saturations determined using BGO to analyze the multispectral image sets showed excellent correlation with co-oximeter data (r2=0.98, and residual error +/-3.4% saturation) and are similar to results when hemoglobin and blood were analyzed using this technique.

  16. Formulation and In Vitro-In Vivo Correlation of Timolol Maleate Ocular Insert

    Directory of Open Access Journals (Sweden)

    Sunil Thakral

    2015-12-01

    Full Text Available The concept of in-vitro and in-vivo correlation studies was used in pharmaceutical research because a simple in-vitro release study on a drug product will be insufficient to predict its therapeutic efficiency. Therefore, correlation between in-vitro release behavior of a drug and its in-vivo absorption in rabbits must be demonstrated experimentally to reproduce therapeutic response. Aim of the study was to study the in vitro and in vivo evaluation and correlation of timolol maleate ocular insert. Timolol maleate ocular inserts were prepared by solvent casting method using guar gum in different proportions (0.25% w/v, 0.50% w/v, 0.75 % w/v, and 1.0% w/v. In vitro transcorneal permeation study was performed on goat cornea using modified Franz diffusion cell. The in vivo study was done using New Zeland albino rabbits and the in vitro invivo correlation (IVIVC was determined by plotting a graph of in vivo drug release was plotted against in vitro release to determine the correlation. The cumulative % drug releases from the formulation ranged from 50.22±1.41 to 97.72±0.67over a period of 24 h. In vivo release of the timolol maleate from the optimized ocular inserts F2, through conjunctival cul-de-sac of rabbits was 76.03±1.43 at the end of 24 h. A high value of correlation coefficient (r2=0.9965 suggested good correlation between the in vitro-in vivo data of the timolol maleate ocular insert.

  17. Directionality and Resultativity: The Cross-linguistic Correlation Revisited

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    Minjeong Son

    2007-12-01

    Full Text Available Recent approaches to the cross-linguistic variation in the expressions of directed motion assume a tight correlation between adjectival resultative and directed motion constructions (e.g., Beck and Snyder 2001, Mateu and Rigau 2001; 2002, McIntyre 2004, Beavers et al. 2004. Beck and Snyder (2001, in particular, argue that languages that allow adjectival resultatives also allow directed motion with goal PP (or telic Path PP based on the compounding parameter proposed by Snyder (1995; 2001. This paper, however, shows that such ‘macro’-parametric approaches to the cross-linguistic variation (in directed motion fail when individual languages are investigated in detail. Based on Korean, Japanese, Hebrew, Czech, and Indonesian, I show that there is no necessary correlation between directed motion (i.e., goal PP constructions and the availability of resultative phrases, and that the previous parameter approaches face challenges in explaining the facts drawn from these languages. I further show that the variation in directed motion is better explained by careful examination of individual adpositions that differ from one language (e.g., English to another (e.g., Korean.

  18. In-vivo/in-vitro correlation of four extended release formulations of pseudoephedrine sulfate.

    Science.gov (United States)

    Mojaverian, P; Rosen, J; Vadino, W A; Liebowitz, S; Radwanski, E

    1997-01-01

    An in-vivo/in-vitro correlation was established for four formulations of pseudoephedrine sulfate modified release tablets exhibiting different in-vivo and in-vitro release rate and absorption characteristics. In-vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2 paddle stirrer at 50 rev min-1 in 1000 ml 0.1 N hydrochloric acid for the first hour followed by 0.1 M phosphate buffer at pH 7.5 for hours 2-16. Inspection of the individual and mean release rate data indicated that the in-vitro release rate of pseudoephedrine sulfate was consistent with the intended design of the four extended release formulations. The in-vivo bioavailability and pharmacokinetics of these formulations were evaluated in 20 healthy volunteers under fasted conditions. Wagner-Nelson analyses of the in-vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in-vitro release resulted in statistically significant correlations (r2 > 0.99, p < 0.0001) for each formulation. Qualitative rank order correlations were observed among all combinations of in-vivo and in-vitro parameters. These data support a Level A correlation between in-vivo absorption profiles and in-vitro release rates of four pseudoephedrine sulfate extended release formulations determined in fasted healthy volunteers.

  19. Direct detection and quantification of abasic sites for in vivo studies of DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yanming [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States)], E-mail: yanming.wang@case.edu; Liu Lili [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States); Wu Chunying [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States); Bulgar, Alina [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States); Somoza, Eduardo; Zhu Wenxia [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States); Gerson, Stanton L. [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States)

    2009-11-15

    Use of chemotherapeutic agents to induce cytotoxic DNA damage and programmed cell death is a key strategy in cancer treatments. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway resulted in formation of abasic or apurinic/apyrimidinic (AP) sites, and blockage of AP sites led to a significant enhancement of drug sensitivity due to reduction of DNA base excision repair. Since a number of chemotherapeutic agents also induce formation of AP sites, monitoring of these sites as a clinical correlate of drug effect will provide a useful tool in the development of DNA-targeted chemotherapies aimed at blocking abasic sites from repair. Here we report an imaging technique based on positron emission tomography (PET) that allows for direct quantification of AP sites in vivo. For this purpose, positron-emitting carbon-11 has been incorporated into methoxyamine ([{sup 11}C]MX) that binds covalently to AP sites with high specificity. The binding specificity of [{sup 11}C]MX for AP sites was demonstrated by in vivo blocking experiments. Using [{sup 11}C]MX as a radiotracer, animal PET studies have been conducted in melanoma and glioma xenografts for quantification of AP sites. Following induction of AP sites by temozolomide, both tumor models showed significant increase of [{sup 11}C]MX uptake in tumor regions in terms of radioactivity concentration as a function of time, which correlates well with conventional aldehyde reactive probe (ARP)-based bioassays for AP sites.

  20. In Vitro and In Vivo Correlation of Colon-Targeted Compression-Coated Tablets

    Directory of Open Access Journals (Sweden)

    Siddhartha Maity

    2016-01-01

    Full Text Available This study was performed to assess and correlate in vitro drug release with in vivo absorption of prednisolone (PDL from a colon-targeted tablet prepared by compression coating of core tablet. In vivo drug absorption study was conducted using a high performance liquid chromatographic (HPLC method, which was developed and validated for the estimation of PDL in rabbit plasma. The calibration curve showed linearity in the concentration range of 0.05 to 50 μg/mL with the correlation coefficient (r of 0.999. The method was specific and sensitive with the limit of detection (LOD and lower limit of quantification (LLOQ of 31.89±1.10 ng/mL and 96.63±3.32 ng/mL, respectively. The extraction recovery (ER of PDL from three different levels of quality control (QC samples ranged from 98.18% to 103.54%. In vitro drug release study revealed that less than 10% drug was released in 6.34 h and almost complete (98.64% drug release was achieved in the following 6 h. In vivo drug absorption study demonstrated lower values of Cmax, AUCtotal, and protracted Tmax from compression-coated tablet. The results confirmed the maximum release of drug in the colon while minimizing release in the upper gastrointestinal tract (GIT. An excellent in vitro and in vivo correlation (IVIVC was also achieved after considering the lag time.

  1. Direct comparison of in vivo versus postmortem second-order motion-compensated cardiac diffusion tensor imaging.

    Science.gov (United States)

    Stoeck, Christian T; von Deuster, Constantin; Fleischmann, Thea; Lipiski, Miriam; Cesarovic, Nikola; Kozerke, Sebastian

    2017-08-22

    To directly compare in vivo versus postmortem second-order motion-compensated spin-echo diffusion tensor imaging of the porcine heart. Second-order motion-compensated spin-echo cardiac diffusion tensor imaging was performed during systolic contraction in vivo and repeated upon cardiac arrest by bariumchloride without repositioning of the study animal or replaning of imaging slices. In vivo and postmortem reproducibility was assessed by repeat measurements. Comparison of helix, transverse, and sheet (E2A) angulation as well as mean diffusivity and fractional anisotropy was performed. Intraclass correlation coefficients for repeated measurements (postmortem/in vivo) were 0.95/0.96 for helix, 0.70/0.66 for transverse, and 0.79/0.72 for E2A angulation; 0.83/0.72 for mean diffusivity; and 0.78/0.76 for fractional anisotropy. The corresponding 95% levels of agreement across the left ventricle were: helix 14 to 18°/12 to 15°, transverse 9 to 10°/10 to 11°, E2A 15 to 20°/16 to 18°. The 95% levels of agreement across the left ventricle for the comparison of postmortem versus in vivo were 20 to 22° for helix, 13 to 19° for transverse, and 24 to 31° for E2A angulation. Parameters derived from in vivo second-order motion-compensated spin-echo diffusion tensor imaging agreed well with postmortem imaging, indicating sufficient suppression of motion-induced signal distortions of in vivo cardiac diffusion tensor imaging. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  2. Correlation of total, diffuse, and direct solar radiation

    Science.gov (United States)

    Buyco, E. H.; Namkoong, D.

    1977-01-01

    Present requirements for realistic solar energy system evaluations necessitate a comprehensive body of solar-radition data. The data should include both diffuse and direct solar radiation as well as their total on an hourly (or shorter) basis. In general, however, only the total solar radiation values were recorded. This report presents a correlation that relates the diffuse component of an hourly total solar radiation value to the total radiation ratio of the maximum value attainable. The data used were taken at the Blue Hill Observatory in Milton, Massachusetts, for the period 1952. The relation - in the form of the data plots - can be used in situations in which only the hourly total radiation data are available but the diffuse component is desired.

  3. Direct correlation functions in two-dimensional anisotropic fluids

    Science.gov (United States)

    Chamoux, Antoine; Perera, Aurelien

    1998-08-01

    A geometrical approximation for the direct correlation of two-dimensional multicomponent fluids is introduced herein. This approximation is semianalytical and involves the knowledge of elementary geometrical properties of a single particle. The formalism is applied to anisotropic two-dimensional fluids of various particle shapes such as hard ellipses, diskorectangles, and cut disks of various size ratios. The particular case of the hard needles fluid is also investigated. The accuracy of the approximation is tested by comparing the equation of state and the correlation functions to those obtained by integral equation techniques and Monte Carlo simulations. In almost all cases these comparisons are found to be quite satisfactory and even excellent in the case of moderate size ratios. Both the isotropic and orientationally ordered phases are investigated and particular attention is paid to the orientational stability of the isotropic phase. The cut disk fluid has a particularly interesting long-range order for thicknesses around 0.3, which is very much reminiscent of the cubatic order observed in the corresponding three-dimensional case of cut spheres. This feature observable by both the simulations and the hypernetted chain integral equation is also predicted by the present geometrical theory, but at larger thicknesses.

  4. Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Brian C. Wilson

    2015-01-01

    Full Text Available Excited-state singlet oxygen (1O2, generated during photodynamic therapy (PDT, is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers. Its relative concentration in cells or tissues can be measured directly through its near-infrared (NIR luminescence emission, which has correlated well with in vitro cell and in vivo normal skin treatment responses. Here, its correlation with the response of tumor tissue in vivo is examined, using the photosensitizer meso-tetrahydroxyphenylchlorin (mTHPC in an animal model comprising luciferase- and green fluorescent protein (GFP-transduced gliosarcoma grown in a dorsal window chamber. The change in the bioluminescence signal, imaged pretreatment and at 2, 5 and 9 d post treatment, was used as a quantitative measure of the tumor response, which was classified in individual tumors as "non", "moderate" and "strong" in order to reduce the variance in the data. Plotting the bioluminescence-based response vs the 1O2 counts demonstrated clear correlation, indicating that 1O2 luminescence provides a valid dosimetric technique for PDT in tumor tissue.

  5. In vivo imaging and quantitative analysis of leukocyte directional migration and polarization in inflamed tissue.

    Directory of Open Access Journals (Sweden)

    Alexander Georg Khandoga

    Full Text Available Directional migration of transmigrated leukocytes to the site of injury is a central event in the inflammatory response. Here, we present an in vivo chemotaxis assay enabling the visualization and quantitative analysis of subtype-specific directional motility and polarization of leukocytes in their natural 3D microenvironment. Our technique comprises the combination of i semi-automated in situ microinjection of chemoattractants or bacteria as local chemotactic stimulus, ii in vivo near-infrared reflected-light oblique transillumination (RLOT microscopy for the visualization of leukocyte motility and morphology, and iii in vivo fluorescence microscopy for the visualization of different leukocyte subpopulations or fluorescence-labeled bacteria. Leukocyte motility parameters are quantified off-line in digitized video sequences using computer-assisted single cell tracking. Here, we show that perivenular microinjection of chemoattractants [macrophage inflammatory protein-1alpha (MIP-1alpha/Ccl3, platelet-activating factor (PAF] or E. coli into the murine cremaster muscle induces target-oriented intravascular adhesion and transmigration as well as polarization and directional interstitial migration of leukocytes towards the locally administered stimuli. Moreover, we describe a crucial role of Rho kinase for the regulation of directional motility and polarization of transmigrated leukocytes in vivo. Finally, combining in vivo RLOT and fluorescence microscopy in Cx3CR1(gfp/gfp mice (mice exhibiting green fluorescent protein-labeled monocytes, we are able to demonstrate differences in the migratory behavior of monocytes and neutrophils.Taken together, we propose a novel approach for investigating the mechanisms and spatiotemporal dynamics of subtype-specific motility and polarization of leukocytes during their directional interstitial migration in vivo.

  6. Approximations for the direct correlation function in multicomponent molecular fluids

    Science.gov (United States)

    Chamoux, A.; Perera, A.

    1996-01-01

    Analytical approximations for the pair direct correlation function (DCF) of molecular fluids and their mixtures are derived within the frame of a new formalism based on weighted density functional methods which represents a generalization of Rosenfeld theory for hard spheres mixtures [J. Chem. Phys. 89, 4271 (1988)]. These approximations rest upon the geometrical properties of individual molecules such as the volume, the surface, and the mean radius. They are Percus-Yevick (PY) like in nature and reduce to the analytical PY solution for DCF in the hard sphere case. By construction the approximations incorporate several interesting features: They yield the Mayer function in the low density limit as expected, and they are anisotropic at zero separation as well as at contact. In addition they predict an orientational instability of the isotropic phase with respect to the nematic phase, a feature that is absent from the Percus-Yevick theory. Comparisons are made with the Percus-Yevick numerical results for the DCF for various convex hard bodies such as hard ellipsoids of revolutions (prolate and oblate), prolate spherocylinders, cutspheres, and generally the agreement is very good for a large range of liquid densities. Analytical expressions for the virial and compressibility routes for the pressures are also given. The results obtained for a large varieties of convex bodies are in very good agreement with corresponding numerical Percus-Yevick results. These approximations can be generalized to inhomogeneous systems in a straightforward manner.

  7. Correlations between in vivo (1)H MRS and ex vivo (1)H HRMAS metabolite measurements in adult human gliomas.

    NARCIS (Netherlands)

    Opstad, K.S.; Wright, A.J.; Bell, B.A.; Griffiths, J.R.; Howe, F.A.

    2010-01-01

    PURPOSE: To assess how accurately ex vivo high-resolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy ((1)H MRS) from small biopsy tissues relate to in vivo (1)H MRS (from larger tumor volumes) in human astrocytomas. MATERIALS AND METHODS: In vivo (PRESS, TE = 30 msec) and ex

  8. 7.0 tesla MRI brain atlas. In-vivo atlas with cryomacrotome correlation. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Zang-Hee (ed.) [Gachon Univ., Incheon (Korea, Republic of). Neuroscience Research Institute

    2015-04-01

    Revised edition with updated in vivo images. Features a coordination matrix in each image, facilitating identification of brain structures and anatomy. User-friendly format and size. The inaugural publication of the 7.0 Tesla MRI Brain Atlas: In-vivo Atlas with Cryomacrotome Correlation in 2010 provided readers with a spectacular source of ultra-high resolution images revealing a wealth of details of the brainstem and midbrain structures. This second edition contributes additional knowledge gained as a result of technologic advances and recent research. To facilitate identification and comparison of brain structures and anatomy, a detailed coordination matrix is featured in each image. Updated axial, sagittal, and coronal images are also included. This state-of-the-art and user-friendly reference will provide researchers and clinicians with important new perspectives.

  9. In vitro-in vivo correlation of parenteral risperidone polymeric microspheres.

    Science.gov (United States)

    Shen, Jie; Choi, Stephanie; Qu, Wen; Wang, Yan; Burgess, Diane J

    2015-11-28

    The objective of the present study was to determine whether an in vitro-in vivo correlation (IVIVC) can be established for polymeric microspheres that are equivalent in formulation composition but prepared with different manufacturing processes. Risperidone was chosen as a model therapeutic and poly(lactic-co-glycolic acid) (PLGA) with similar molecular weight as that used in the commercial product Risperdal® Consta® was used to prepare risperidone microspheres. Various manufacturing processes were investigated to produce the risperidone microspheres with similar drug loading (approx. 37%) but distinctly different physicochemical properties (e.g. porosity, particle size and particle size distribution). In vitro release of the risperidone microspheres was investigated using different release testing methods (such as sample-and-separate and USP apparatus 4). In vivo pharmacokinetic profiles of the risperidone microsphere formulations following intramuscular administration were determined using a rabbit model. Furthermore, the obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method and the calculated in vivo release was compared with the in vitro release of these microspheres. Level A IVIVCs were established and validated for the compositionally equivalent risperidone microspheres based on the in vitro release data obtained using USP apparatus 4. The developed IVIVCs demonstrated good predictability and were robust. These results showed that the developed USP apparatus 4 method was capable of discriminating PLGA microspheres that are equivalent in formulation composition but with manufacturing differences and predicting their in vivo performance in the investigated animal model. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Monodispersity of recombinant Cre recombinase correlates with its effectiveness in vivo

    Directory of Open Access Journals (Sweden)

    Edenhofer Frank

    2009-09-01

    Full Text Available Abstract Background Cre recombinase is a common reagent used for the in vivo on/off switching of the expression of target genes flanked by loxP sites. In particular, recombinant TAT-Cre fusion constructs purified from bacteria have been used to promote the cell uptake of the enzyme. However, the recovery of active TAT-Cre remains a demanding process and its specific activity varies significantly among batches, making difficult data comparison. Results We noticed a strong correlation between recombinase activity and enzyme monodispersity. The existence of such correlation enabled us to indirectly monitor the TAT-Cre recombinase activity during the multi-step purification process by measuring its monodispersity, a parameter detectable by means of a spectrofluorimetric assay that allows the calculation of the Aggregation Index (AI in an easy and rapid way. AI values were recorded after each purification passage to identify the critical steps and to choose optimal alternatives for chromatographic conditions, desalting procedures, and protocols for bacterial endotoxin removal. Furthermore, the effect of metal ions and temperature on TAT-Cre aggregation and inactivation was characterized in vitro. Finally, we optimized the enzyme delivery protocol in vivo by following the accumulation tuning of the reporter protein β-catenin. Conclusion A rational purification protocol for TAT-Cre has been developed by choosing the options that minimize the enzyme aggregation. Our data suggest that AI measurement should support the optimization of any protocol aiming at the recovery of monodispersed protein.

  11. Internalized Heterosexism: Measurement, Psychosocial Correlates, and Research Directions

    Science.gov (United States)

    Szymanski, Dawn M.; Kashubeck-West, Susan; Meyer, Jill

    2008-01-01

    This article provides an integrated critical review of the literature on internalized heterosexism/internalized homophobia (IH), its measurement, and its psychosocial correlates. It describes the psychometric properties of six published measures used to operationalize the construct of IH. It also critically reviews empirical studies on correlates…

  12. Generic sustained release tablets of trimetazidine hydrochloride: Preparation and in vitro–in vivo correlation studies

    Directory of Open Access Journals (Sweden)

    Longmei Wang

    2016-06-01

    Full Text Available The aim of the current work was to develop generic sustained-release tablets containing 35 mg trimetazidine dihydrochloride and to establish an in vitro–in vivo correlation that could predict the bioavailability. The marketed sustained release tablet (Vastarel MR used as reference, a sustained-release matrix tablet was prepared using hydroxypropyl methylcellulose (HPMC as matrix by wet granulation and the in vitro dissolution profiles of the self-made tablets were determined in four different dissolution media (0.1 M HCl, pH 4.5 PBS, pH 6.8 PBS and water. A higher similarity between prepared tablets and Vastarel MR was established, with similarity factor (f2 ranging from 60 to 75 in the four media. The in vivo pharmacokinetics was studied in six healthy beagles. Compared with Vastarel MR, the Cmax of self-made tablets was slightly decreased, while the Tmax and MRT0–t were slightly prolonged, but with no significant difference (P > 0.05. The average of relative bioavailability (F was 102.52% based on AUC0–t. For log-transformed AUC0–t and Cmax, the upper confidence limit on the appropriate criterion is <0, indicating these two formulations were population bioequivalent. The in vivo–in vitro correlation coefficient obtained from point-to-point analysis of self-made tablets was 0.9720. In conclusion, the prepared tablets were bioequivalent to the marketed tablets, according to both the in vitro release rate and extent of absorption, and a good in vivo–in vitro correlation was established for the self-made tablets that indicated in vitro dissolution tests could be used as a surrogate for bioavailability studies.

  13. Factors affecting SPF in vitro measurement and correlation with in vivo results.

    Science.gov (United States)

    Dimitrovska Cvetkovska, A; Manfredini, S; Ziosi, P; Molesini, S; Dissette, V; Magri, I; Scapoli, C; Carrieri, A; Durini, E; Vertuani, S

    2017-06-01

    The in vitro evaluation of SPF is still a problem due to the lack of repeatability and correlation between the in vitro and in vivo data, and many authors are currently working to develop an internationally harmonized method. Very recently, the use of several "adjuvant" ingredients such as boosters, antioxidants, immunomodulators, solvents and film-forming ingredients have further complicated the pattern for product developers that should frequently run in vivo test. The aim of this study was to understand whether a simple and cheap in vitro method could be optimized in order to provide both statistically repeatable and predictive SPF measurement. In vitro SPF assessments were carried out on 75 commercial products. The SPF was measured according to two laboratory methods (A and B), using different substrates (PMMA and surgical tape Transpore™), quantity of product and spectrophotometers. In order to evaluate whether a standard technique of spreading could lead to a statistically reliable result, we applied different spreading pressure (100 g and 200 g). Furthermore, we investigate whether other parameters characterizing the product (SPF category, filter and texture) might represent statically significant variables affecting the measures. We then compared the results obtained from in vitro SPF measure of 11 products to in vivo SPF, in order to assess the predictability of in vitro methods. Several problems were encountered in confirming the weakness of the in vitro procedures. Pressure, SPF category, filter and texture did not affect significantly the results. Overall best results were obtained with the B2 method that in terms of repeatability and predictivity provided statistically better results. Method A with Transpore™ tape showed better in vitro-in vivo correlation than Method B with PMMA plates. In our investigation, we demonstrated that it is possible for a single laboratory to optimize internal methods and protocols to achieve repeatable and predictive

  14. Correlated response in longevity from direct selection for production ...

    African Journals Online (AJOL)

    The objective of the current study was to investigate whether direct selection for production resulted in an undesirable genetic response in longevity in the South African Jersey breed. Longevity was defined as survival in the first three lactations from first calving to culling or death, adjusted for the effect of milk yield.

  15. [Imaging of corneal dystrophies: Correlations between en face anterior segment OCT and in vivo confocal microscopy].

    Science.gov (United States)

    Ghouali, W; Tahiri Joutei Hassani, R; Liang, H; Dupont-Monod, S; Auclin, F; Baudouin, C; Labbé, A

    2015-05-01

    To evaluate the usefulness of en face Optical Coherence Tomography (OCT) for evaluation of corneal dystrophies and to describe correlations with in vivo confocal microscopy (IVCM). Thirty-two eyes of 16 patients with 4 types of corneal dystrophies (epithelial basement membrane dystrophy, Fuchs dystrophy, Reis-Bücklers corneal dystrophy and Crocodile Shagreen dystrophy) were enrolled in this study. Axial and reconstructed en face scans were acquired using OCT. Images were then correlated to IVCM findings. En face OCT provided new insights into the structure, size and depth of corneal tissue alterations in various corneal dystrophies. OCT en face images were well correlated with IVCM features. Despite lower resolution than IVCM, en face OCT offers the advantages of being non-invasive and allowing the analysis of larger corneal areas. En face OCT provides useful new information in corneal dystrophies. This imaging technique will probably increase in popularity in the near future for the assessment of various anterior segment diseases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. In-vivo imaging of the photoreceptor mosaic in retinal dystrophies and correlations with visual function

    Energy Technology Data Exchange (ETDEWEB)

    Choi, S; Doble, N; Hardy, J; Jones, S; Keltner, J; Olivier, S; Werner, J S

    2005-10-26

    To relate in-vivo microscopic retinal changes to visual function assessed with clinical tests in patients with various forms of retinal dystrophies. The UC Davis Adaptive Optics (AO) Fundus Camera was used to acquire in-vivo retinal images at the cellular level. Visual function tests, consisting of visual field analysis, multifocal electroretinography (mfERG), contrast sensitivity and color vision measures, were performed on all subjects. Five patients with different forms of retinal dystrophies and three control subjects were recruited. Cone densities were quantified for all retinal images. In all images of diseased retinas, there were extensive areas of dark space between groups of photoreceptors, where no cone photoreceptors were evident. These irregular features were not seen in healthy retinas, but were characteristic features in fundi with retinal dystrophies. There was a correlation between functional vision loss and the extent to which the irregularities occurred in retinal images. Cone densities were found to decrease with an associated decrease in retinal function. AO fundus photography is a reliable technique for assessing and quantifying the changes in the photoreceptor layer as disease progresses. Furthermore, this technique can be useful in cases where visual function tests give borderline or ambiguous results, as it allows visualization of individual photoreceptors.

  17. Cell cycle-dependent mobility of Cdc45 determined in vivo by fluorescence correlation spectroscopy.

    Directory of Open Access Journals (Sweden)

    Ronan Broderick

    Full Text Available Eukaryotic DNA replication is a dynamic process requiring the co-operation of specific replication proteins. We measured the mobility of eGFP-Cdc45 by Fluorescence Correlation Spectroscopy (FCS in vivo in asynchronous cells and in cells synchronized at the G1/S transition and during S phase. Our data show that eGFP-Cdc45 mobility is faster in G1/S transition compared to S phase suggesting that Cdc45 is part of larger protein complex formed in S phase. Furthermore, the size of complexes containing Cdc45 was estimated in asynchronous, G1/S and S phase-synchronized cells using gel filtration chromatography; these findings complemented the in vivo FCS data. Analysis of the mobility of eGFP-Cdc45 and the size of complexes containing Cdc45 and eGFP-Cdc45 after UVC-mediated DNA damage revealed no significant changes in diffusion rates and complex sizes using FCS and gel filtration chromatography analyses. This suggests that after UV-damage, Cdc45 is still present in a large multi-protein complex and that its mobility within living cells is consistently similar following UVC-mediated DNA damage.

  18. Bioequivalence study of paracetamol tablets: in vitro-in vivo correlation.

    Science.gov (United States)

    Domínguez, A; Medina, R; Hurtado, M

    2000-08-01

    The bioequivalence of three chemically equivalent paracetamol generic Mexican products (500 mg tablets) was evaluated in 12 healthy volunteers using the American innovator product (Tylenol, McNeil, Fort Washington, PA), as the reference. Single oral doses of each product were administered at 1-week intervals using a 4 x 4 Latin square design balanced for the first residual effect. The total amount of paracetamol excreted in urine in 24 hr was taken as a measure of bioavailability. In addition, moment analysis was used to estimate in vitro mean dissolution time (MDT) from dissolution profiles obtained following the USP 23 dissolution test specified for paracetamol tablets and to estimate in vivo mean residence time (MRT) from urinary excretion data. Significant differences in the dissolution performance and in the cumulative amount of paracetamol excreted in urine up to 24 hr were observed when the data were analyzed by analysis of variance (ANOVA) (p paracetamol products studied can be considered equivalent to the reference product Tylenol. A linear correlation between in vitro MDT and in vivo MRT was found.

  19. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss

    DEFF Research Database (Denmark)

    Archibald, Sarah L.; Masliah, Eliezer; Fennema-Notestine, Christine

    2004-01-01

    previous studies have linked brain viral levels to these alterations, other neuropathological mechanisms might also contribute to them. OBJECTIVE: To examine the relationship between findings on premortem magnetic resonance images and postmortem neuropathologic evidence of human immunodeficiency virus (HIV......) encephalitis and neurodegeneration. DESIGN: Morphometric analysis of magnetic resonance imaging in seropositive cases with matched seronegative controls, and the correlation of these volumes to neuropathological measures in autopsied seropositive cases. SETTING: University of California, San Diego, HIV...... Neurobehavioral Research Center. SUBJECTS: Twenty-one seropositive subjects studied at autopsy and 19 seronegative cases. MAIN OUTCOME MEASURES: In vivo structural magnetic resonance imaging data analyzed by quantitative methods, with comparison of volumes from magnetic resonance imaging and neuropathological...

  20. Ex Vivo Correlation of the Permeability of Metoprolol Across Human and Porcine Buccal Mucosa

    DEFF Research Database (Denmark)

    Meng-Lund, Emil; Marxen, Eva; Pedersen, Anne Marie Lynge

    2014-01-01

    The pH partition theory proposes a correlation between fraction of unionized drug substance and permeability. The aim of this study was to compare the permeability of metoprolol and mannitol in ex vivo human and porcine buccal mucosa models at varying pH to validate whether the porcine permeability...... model is predictive for human buccal absorption. Human (n = 9-10) and porcine (n = 6-7) buccal mucosa were mounted in a modified Ussing chamber, and the kinetics of metoprolol and mannitol transport was assessed for a period of 5.5 h with the pH values of donor medium set at 7.4, 8.5, and 9...

  1. Correlation of in vivo and ex vivo 1H-MRI with histology in two severities of mouse spinal cord injury

    Directory of Open Access Journals (Sweden)

    Harun Najib NORISTANI

    2015-03-01

    Full Text Available Spinal cord injury (SCI is a debilitating neuropathology with no effective treatment. Magnetic resonance imaging (MRI technology is the only method used to assess the impact of an injury on the structure and function of the human spinal cord. Moreover, in pre-clinical SCI research, MRI is a non-invasive method with great translational potential since it provides relevant longitudinal assessment of anatomical and structural alterations induced by an injury. It is only recently that MRI techniques have been effectively used for the follow-up of SCI in rodents. However, the vast majority of these studies have been carried out on rats and when conducted in mice, the contusion injury model was predominantly chosen. Due to the remarkable potential of transgenic mice for studying the pathophysiology of SCI, we examined the use of both in and ex vivo 1H-MRI (9.4 T in two severities of the mouse spinal cord injury (hemisection and over-hemisection and documented their correlation with histological assessments. We demonstrated that a clear distinction between the two injury severities is possible using in and ex vivo 1H-MRI and that ex vivo MR images closely correlate with histology. Moreover, tissue modifications at a remote location from the lesion epicentre were identified by conventional ex vivo MRI analysis. Therefore, in vivo MRI has the potential to accurately identify in mice the progression of tissue alterations induced by SCI and is successfully implemented by ex vivo MRI examination. This combination of in and ex vivo MRI follow-up associated with histopathological assessment provides a valuable approach for further studies intended to evaluate therapeutic strategies on SCI.

  2. Development of in vitro-in vivo correlation of parenteral naltrexone loaded polymeric microspheres.

    Science.gov (United States)

    Andhariya, Janki V; Shen, Jie; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J

    2017-06-10

    Establishment of in vitro-in vivo correlations (IVIVCs) for parenteral polymeric microspheres has been very challenging, due to their complex multiphase release characteristics (which is affected by the nature of the drug) as well as the lack of compendial in vitro release testing methods. Previously, a Level A correlation has been established and validated for polymeric microspheres containing risperidone (a practically water insoluble small molecule drug). The objectives of the present study were: 1) to investigate whether a Level A IVIVC can be established for polymeric microspheres containing another small molecule drug with different solubility profiles compared to risperidone; and 2) to determine whether release characteristic differences (bi-phasic vs tri-phasic) between microspheres can affect the development and predictability of IVIVCs. Naltrexone was chosen as the model drug. Three compositionally equivalent formulations of naltrexone microspheres with different release characteristics were prepared using different manufacturing processes. The critical physicochemical properties (such as drug loading, particle size, porosity, and morphology) as well as the in vitro release characteristics of the prepared naltrexone microspheres and the reference-listed drug (Vivitrol®) were determined. The pharmacokinetics of the naltrexone microspheres were investigated using a rabbit model. The obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method, and compared with the in vitro release profiles of the naltrexone microspheres obtained using USP apparatus 4. Level A IVIVCs were established and validated for predictability. The results demonstrated that the developed USP 4 method was capable of detecting manufacturing process related performance changes, and most importantly, predicting the in vivo performance of naltrexone microspheres in the investigated animal model. A critical difference between naltrexone and risperidone loaded

  3. In vivo analysis of trapeziometacarpal joint arthrokinematics during multi-directional thumb motions.

    Science.gov (United States)

    Su, Fong-Chin; Lin, Chien-Ju; Wang, Chien-Kuo; Chen, Guan-Po; Sun, Yung-Nien; Chuang, Alan K; Kuo, Li-Chieh

    2014-11-01

    The investigation of the joint arthrokinematics of the trapeziometacarpal joint is critical to comprehend the causative mechanism underlying this common form of osteoarthritis. Therefore, the purpose of this study is to evaluate the arthrokinematics of the trapeziometacarpal joint during thumb postures in vivo. Fifteen healthy participants were enrolled in this study. Static computed tomography images of the 1st metacarpal bone and trapezium were taken at specific thumb postures during thumb flexion-extension, abduction-adduction, and circumduction motions. Images were analyzed to examine the joint gliding, expressed as displacement of the centroid of the articular surface of the 1st metacarpal bone, relative to the trapezium. The gliding ratio, defined as joint gliding in each direction normalized to the dimension of the trapezium joint surface in the given direction, was computed and compared between different thumb motions. The results indicate that thumb motions influenced joint gliding. The centroids of the articular surface of the 1st metacarpal bone were primarily located at the central and dorsal-radial regions while executing these motions. The maximum joint gliding of the 1st metacarpal bone occurred in the radial-ulnar direction when performing abduction-adduction, and in the dorsal-volar direction while performing flexion-extension and circumduction, with the gliding ratio values of 42.35%, 51.65%, and 51.85%, respectively. Activities that involved abduction-adduction in the trapeziometacarpal joint caused greater joint gliding in the ulnar-radial direction, while flexion-extension resulted in greater joint gliding in the dorsal-volar and distal-proximal directions. Understanding normal joint kinematics in vivo may provide insights into the possible mechanism leading to osteoarthritis of the trapeziometacarpal joint, and help to improve the design of implants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Direct Observation of Correlated Interdomain Motion in Alcohol Dehydrogenase

    Science.gov (United States)

    Biehl, Ralf; Hoffmann, Bernd; Monkenbusch, Michael; Falus, Peter; Préost, Sylvain; Merkel, Rudolf; Richter, Dieter

    2008-09-01

    Interdomain motions in proteins are essential to enable or promote biochemical function. Neutron spin-echo spectroscopy is used to directly observe the domain dynamics of the protein alcohol dehydrogenase. The collective motion of domains as revealed by their coherent form factor relates to the cleft opening dynamics between the binding and the catalytic domains enabling binding and release of the functional important cofactor. The cleft opening mode hardens as a result of an overall stiffening of the domain complex due to the binding of the cofactor.

  5. Ex Vivo Produced Oral Mucosa Equivalent by Using the Direct Explant Cell Culture Technique

    Directory of Open Access Journals (Sweden)

    Kamile Öztürk

    2012-09-01

    Full Text Available Objective: The aim of this study is the histological and immunohistochemical evaluation of ex vivo produced oral mucosal equivalents using keratinocytes cultured by direct explant technique.Material and Methods: Oral mucosa tissue samples were obtained from the keratinized gingival tissues of 14 healthy human subjects. Human oral mucosa keratinocytes from an oral mucosa biopsy specimen were dissociated by the explant technique. Once a sufficient population of keratinocytes was reached, they were seeded onto the type IV collagen coated “AlloDerm” and taken for histological and immunohistochemical examinations at 11 days postseeding of the keratinocytes on the cadaveric human dermal matrix.Results: Histopathologically and immunohistochemically, 12 out of 14 successful ex vivo produced oral mucosa equivalents (EVPOME that consisted of a stratified epidermis on a dermal matrix have been developed with keratinocytes cultured by the explant technique.Conclusion: The technical handling involved in the direct explant method at the beginning of the process has fewer steps than the enzymatic method and use of the direct explant technique protocol for culturing of human oral mucosa keratinocyte may be more adequate for EVPOME production.

  6. Direct determination of the redox status of cysteine residues in proteins in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Satoshi [Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta 4259-R1-8, Midori-ku, Yokohama 226-8503 (Japan); Tatenaka, Yuki; Ohuchi, Yuya [Dojindo Laboratories, 2025-5 Tabaru, Mashiki-machi, Kumamoto 861-2202 (Japan); Hisabori, Toru, E-mail: thisabor@res.titech.ac.jp [Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta 4259-R1-8, Midori-ku, Yokohama 226-8503 (Japan); Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 102-0075 (Japan)

    2015-01-02

    Highlights: • A new DNA-maleimide which is cleaved by UV irradiation, DNA-PCMal, was developed. • DNA-PCMal can be used like DNA-Mal to analyze the redox state of cysteine residues. • It is useful for detecting the thiol redox status of a protein in vivo by Western blotting method. • Thus, DNA-PCMal can be a powerful tool for redox proteomics analysis. - Abstract: The redox states of proteins in cells are key factors in many cellular processes. To determine the redox status of cysteinyl thiol groups in proteins in vivo, we developed a new maleimide reagent, a photocleavable maleimide-conjugated single stranded DNA (DNA-PCMal). The DNA moiety of DNA-PCMal is easily removed by UV-irradiation, allowing DNA-PCMal to be used in Western blotting applications. Thereby the state of thiol groups in intracellular proteins can be directly evaluated. This new maleimide compound can provide information concerning redox proteins in vivo, which is important for our understanding of redox networks in the cell.

  7. In vivo reprogramming for heart regeneration: A glance at efficiency, environmental impacts, challenges and future directions.

    Science.gov (United States)

    Ebrahimi, Behnam

    2017-07-01

    Replacing dying or diseased cells of a tissue with new ones that are converted from patient's own cells is an attractive strategy in regenerative medicine. In vivo reprogramming is a novel strategy that can circumvent the hurdles of autologous/allogeneic cell injection therapies. Interestingly, studies have demonstrated that direct injection of cardiac transcription factors or specific miRNAs into the infarct border zone of murine hearts following myocardial infarction converts resident cardiac fibroblasts into functional cardiomyocytes. Moreover, in vivo cardiac reprogramming not only drives cardiac tissue regeneration, but also improves cardiac function and survival rate after myocardial infarction. Thanks to the influence of cardiac microenvironment and the same developmental origin, cardiac fibroblasts seem to be more amenable to reprogramming toward cardiomyocyte fate than other cell sources (e.g. skin fibroblasts). Thus, reprogramming of cardiac fibroblasts to functional induced cardiomyocytes in the cardiac environment holds great promises for induced regeneration and potential clinical purposes. Application of small molecules in future studies may represent a major advancement in this arena and pharmacological reprogramming would convey reprogramming technology to the translational medicine paradigm. This study reviews accomplishments in the field of in vitro and in vivo mouse cardiac reprogramming and then deals with strategies for the enhancement of the efficiency and quality of the process. Furthermore, it discusses challenges ahead and provides suggestions for future research. Human cardiac reprogramming is also addressed as a foundation for possible application of in vivo cardiac reprogramming for human heart regeneration in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy.

    Directory of Open Access Journals (Sweden)

    Leonidas Apostolidis

    Full Text Available To investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP by magnetic resonance neurography (MRN.Twenty patients (7 female, 13 male, 58.9±10.0 years with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG, sciatic nerve normalized T2 (nT2 signal and caliber, and fractional anisotropy (FA, mean diffusivity (MD, axial (AD and radial diffusivity (RD. Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions.DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001 was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80 and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16. AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged.OXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.

  9. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of (111)In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin).

    Science.gov (United States)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle; Reilly, Raymond M

    2008-08-01

    Our objective was to define the relationships between tumor uptake of [(111)In]-IGF-1 and [(111)In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. The tumor and normal tissue uptake of [(111)In]-IGF-1 and [(111)In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10(4), 1.4x10(4), 4.0x10(4) and 1.0x10(5) IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 microg) or IGFBP-3 (2 or 25 microg) was studied. The relationship between tumor uptake of [(111)In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [(111)In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 mug/ml) in the absence/presence of IGFBP-3 (1 microg/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 microg/ml), was determined. [(111)In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9+/-0.1 vs. 1.0+/-0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [(111)In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r(2)=0.99) between the tumor uptake of (111)In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4+/-0.05 %ID/g for H2N to 2.5+/-0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC cells to trastuzumab was directly associated with IGF-1R expression, despite co-expression of

  10. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of {sup 111}In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin)

    Energy Technology Data Exchange (ETDEWEB)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Reilly, Raymond M. [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network Toronto, Toronto, ON, M5S 3M2 (Canada)], E-mail: raymond.reilly@utoronto.ca

    2008-08-15

    Introduction: Our objective was to define the relationships between tumor uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. Methods: The tumor and normal tissue uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10{sup 4}, 1.4x10{sup 4}, 4.0x10{sup 4} and 1.0x10{sup 5} IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 {mu}g) or IGFBP-3 (2 or 25 {mu}g) was studied. The relationship between tumor uptake of [{sup 111}In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [{sup 111}In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 {mu}g/ml) in the absence/presence of IGFBP-3 (1 {mu}g/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 {mu}g/ml), was determined. Results: [{sup 111}In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9{+-}0.1 vs. 1.0{+-}0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [{sup 111}In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r{sup 2}=0.99) between the tumor uptake of {sup 111}In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4{+-}0.05 %ID/g for H2N to 2.5{+-}0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC

  11. An attempt to establish an in vitro-in vivo correlation: case of paracetamol immediate-release tablets.

    Science.gov (United States)

    Radovanović, J; Durić, Z; Jovanović, M; Ibrić, S; Petrović, M

    1998-01-01

    The purpose of this study was to investigate the possibility of developing different levels of in vitro-in vivo correlation for immediate-release paracetamol tablets using in vitro dissolution data obtained under various experimental conditions. The influence of agitation intensity and pH value of the dissolution media was investigated. The level B approach, using statistical moment analysis led to poor correlation results. The results obtained by numerical deconvolution in order to study level A correlation indicated that good correlation should be sought with moderate levels of agitation (beyond 50 rpm in rotating basket apparatus). Results obtained by numerical convolution showed the highest level of correlation, level A, with one-to-one relationship between observed and predicted in vivo profiles.

  12. Establishing in vitro-in vivo correlation for antibody drug conjugate efficacy: a PK/PD modeling approach.

    Science.gov (United States)

    Shah, Dhaval K; Loganzo, Frank; Haddish-Berhane, Nahor; Musto, Sylvia; Wald, Hallie S; Barletta, Frank; Lucas, Judy; Clark, Tracey; Hansel, Steve; Betts, Alison

    2018-02-08

    The objective of this manuscript was to establish in vitro-in vivo correlation (IVIVC) between the in vitro efficacy and in vivo efficacy of antibody drug conjugates (ADCs), using a PK/PD modeling approach. Nineteen different ADCs were used to develop IVIVC. In vitro efficacy of ADCs was evaluated using a kinetic cell cytotoxicity assay. The cytotoxicity data obtained from in vitro studies was characterized using a novel mathematical model, parameter estimates from which were used to derive an in vitro efficacy matrix for each ADC, termed as 'in vitro tumor static concentration' (TSCin vitro). TSCin vitro is a theoretical concentration at continuous exposure of which the number of cells will neither increase nor decrease, compared to the initial cell number in the experiment. The in vivo efficacy of ADCs was evaluated using tumor growth inhibition (TGI) studies performed on human tumor xenograft bearing mice. The TGI data obtained from in vivo studies was characterized using a PK/PD model, parameter estimates from which were used to derive an in vivo efficacy matrix for each ADC, termed as 'in vivo tumor static concentration' (TSCin vivo). TSCin vivo is a theoretical concentration if one were to maintain in the plasma of a tumor bearing mouse, the tumor volume will neither increase nor decrease compared to the initial tumor volume. Comparison of the TSCin vitro and TSCin vivo values from 19 ADCs provided a linear and positive IVIVC. The Spearman's rank correlation coefficient for TSCin vitro and TSCin vivo was found to be 0.82. On average TSCin vivo was found to be ~ 27 times higher than TSCin vitro. The reasonable IVIVC for ADCs suggests that in vitro efficacy data was correctly able to differentiate ADCs for their in vivo efficacy. Thus, IVIVC can be used as a tool to triage ADC molecules in the discovery stage, thereby preventing unnecessary scaling-up of ADCs and waste of time and resources. An ability to predict the concentration of ADC that is efficacious

  13. Directed evolution relieves product inhibition and confers in vivo function to a rationally designed tyrosine aminotransferase.

    Science.gov (United States)

    Rothman, Steven C; Voorhies, Mark; Kirsch, Jack F

    2004-03-01

    The Escherichia coli aspartate (AATase) and tyrosine (TATase) aminotransferases share 43% sequence identity and 72% similarity, but AATase has only 0.08% and 0.01% of the TATase activities (k(cat)/K(m)) for tyrosine and phenylalanine, respectively. Approximately 5% of TATase activity was introduced into the AATase framework earlier both by rational design (six mutations, termed HEX) and by directed evolution (9-17 mutations). The enzymes realized from the latter procedure complement tyrosine auxotrophy in TATase deficient E. coli. HEX complements even more poorly than does wild-type AATase, even though the (k(cat)/K(m)) value for tyrosine exhibited by HEX is similar to those of the enzymes found from directed evolution. HEX, however, is characterized by very low values of K(m) and K(D) for dicarboxylic ligands, and by a particularly slow release for oxaloacetate, the product of the reaction with aspartate and a TCA cycle intermediate. These observations suggest that HEX exists largely as an enzyme-product complex in vivo. HEX was therefore subjected to a single round of directed evolution with selection for complementation of tyrosine auxotrophy. A variant with a single amino acid substitution, A293D, exhibited substantially improved TATase function in vivo. The A293D mutation alleviates the tight binding to dicarboxylic ligands as K(m)s for aspartate and alpha-ketoglutarate are >20-fold higher in the HEX + A293D construct compared to HEX. This mutation also increased k(cat)/K(m)(Tyr) threefold. A second mutation, I73V, elicited smaller but similar effects. Both residues are in close proximity to Arg292 and the mutations may function to modulate the arginine switch mechanism responsible for dual substrate recognition in TATases and HEX.

  14. Determination of velocity vector angles using the directional cross-correlation method

    DEFF Research Database (Denmark)

    Kortbek, Jacob; Jensen, Jørgen Arendt

    2005-01-01

    and then select the angle with the highest normalized correlation between directional signals. The approach is investigated using Field II simulations and data from the experimental ultrasound scanner RASMUS and with a parabolic flow having a peak velocity of 0.3 m/s. A 7 MHz linear array transducer is used......A method for determining both velocity magnitude and angle in any direction is suggested. The method uses focusing along the velocity direction and cross-correlation for finding the correct velocity magnitude. The angle is found from beamforming directional signals in a number of directions...

  15. Direct parametric reconstruction in dynamic PET myocardial perfusion imaging: in vivo studies

    Science.gov (United States)

    Petibon, Yoann; Rakvongthai, Yothin; El Fakhri, Georges; Ouyang, Jinsong

    2017-05-01

    Dynamic PET myocardial perfusion imaging (MPI) used in conjunction with tracer kinetic modeling enables the quantification of absolute myocardial blood flow (MBF). However, MBF maps computed using the traditional indirect method (i.e. post-reconstruction voxel-wise fitting of kinetic model to PET time-activity-curves-TACs) suffer from poor signal-to-noise ratio (SNR). Direct reconstruction of kinetic parameters from raw PET projection data has been shown to offer parametric images with higher SNR compared to the indirect method. The aim of this study was to extend and evaluate the performance of a direct parametric reconstruction method using in vivo dynamic PET MPI data for the purpose of quantifying MBF. Dynamic PET MPI studies were performed on two healthy pigs using a Siemens Biograph mMR scanner. List-mode PET data for each animal were acquired following a bolus injection of ~7-8 mCi of 18F-flurpiridaz, a myocardial perfusion agent. Fully-3D dynamic PET sinograms were obtained by sorting the coincidence events into 16 temporal frames covering ~5 min after radiotracer administration. Additionally, eight independent noise realizations of both scans—each containing 1/8th of the total number of events—were generated from the original list-mode data. Dynamic sinograms were then used to compute parametric maps using the conventional indirect method and the proposed direct method. For both methods, a one-tissue compartment model accounting for spillover from the left and right ventricle blood-pools was used to describe the kinetics of 18F-flurpiridaz. An image-derived arterial input function obtained from a TAC taken in the left ventricle cavity was used for tracer kinetic analysis. For the indirect method, frame-by-frame images were estimated using two fully-3D reconstruction techniques: the standard ordered subset expectation maximization (OSEM) reconstruction algorithm on one side, and the one-step late maximum a posteriori (OSL-MAP) algorithm on the other

  16. Direct parametric reconstruction in dynamic PET myocardial perfusion imaging: in vivo studies.

    Science.gov (United States)

    Petibon, Yoann; Rakvongthai, Yothin; El Fakhri, Georges; Ouyang, Jinsong

    2017-05-07

    Dynamic PET myocardial perfusion imaging (MPI) used in conjunction with tracer kinetic modeling enables the quantification of absolute myocardial blood flow (MBF). However, MBF maps computed using the traditional indirect method (i.e. post-reconstruction voxel-wise fitting of kinetic model to PET time-activity-curves-TACs) suffer from poor signal-to-noise ratio (SNR). Direct reconstruction of kinetic parameters from raw PET projection data has been shown to offer parametric images with higher SNR compared to the indirect method. The aim of this study was to extend and evaluate the performance of a direct parametric reconstruction method using in vivo dynamic PET MPI data for the purpose of quantifying MBF. Dynamic PET MPI studies were performed on two healthy pigs using a Siemens Biograph mMR scanner. List-mode PET data for each animal were acquired following a bolus injection of ~7-8 mCi of 18 F-flurpiridaz, a myocardial perfusion agent. Fully-3D dynamic PET sinograms were obtained by sorting the coincidence events into 16 temporal frames covering ~5 min after radiotracer administration. Additionally, eight independent noise realizations of both scans-each containing 1/8th of the total number of events-were generated from the original list-mode data. Dynamic sinograms were then used to compute parametric maps using the conventional indirect method and the proposed direct method. For both methods, a one-tissue compartment model accounting for spillover from the left and right ventricle blood-pools was used to describe the kinetics of 18 F-flurpiridaz. An image-derived arterial input function obtained from a TAC taken in the left ventricle cavity was used for tracer kinetic analysis. For the indirect method, frame-by-frame images were estimated using two fully-3D reconstruction techniques: the standard ordered subset expectation maximization (OSEM) reconstruction algorithm on one side, and the one-step late maximum a posteriori (OSL-MAP) algorithm on the other

  17. In vivo quantitative magnetization transfer imaging correlates with histology during de- and remyelination in cuprizone-treated mice.

    Science.gov (United States)

    Turati, Laura; Moscatelli, Marco; Mastropietro, Alfonso; Dowell, Nicholas G; Zucca, Ileana; Erbetta, Alessandra; Cordiglieri, Chiara; Brenna, Greta; Bianchi, Beatrice; Mantegazza, Renato; Cercignani, Mara; Baggi, Fulvio; Minati, Ludovico

    2015-03-01

    The pool size ratio measured by quantitative magnetization transfer MRI is hypothesized to closely reflect myelin density, but their relationship has so far been confirmed mostly in ex vivo conditions. We investigate the correspondence between this parameter measured in vivo at 7.0 T, with Black Gold II staining for myelin fibres, and with myelin basic protein and beta-tubulin immunofluorescence in a hybrid longitudinal study of C57BL/6 and SJL/J mice treated with cuprizone, a neurotoxicant causing relatively selective myelin loss followed by spontaneous remyelination upon treatment suspension. Our results confirm that pool size ratio measurements correlate with myelin content, with the correlation coefficient depending on strain and staining method, and demonstrate the in vivo applicability of this MRI technique to experimental mouse models of multiple sclerosis. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived from the PK-Eye.

    Science.gov (United States)

    Awwad, Sahar; Day, Richard M; Khaw, Peng T; Brocchini, Steve; Fadda, Hala M

    2017-04-30

    Corticosteroids have long been used to treat intraocular inflammation by intravitreal injection. We describe dexamethasone loaded poly-DL-lactide-co-glycolide (PLGA) microparticles that were fabricated by thermally induced phase separation (TIPS). The dexamethasone loaded microparticles were evaluated using a two-compartment, in vitro aqueous outflow model of the eye (PK-Eye) that estimates drug clearance time from the back of the eye via aqueous outflow by the anterior route. A dexamethasone dose of 0.20±0.02mg in a 50μL volume of TIPS microparticles resulted in a clearance t1/2 of 9.6±0.3days using simulated vitreous in the PK-Eye. Since corticosteroids can also clear through the retina, it is necessary to account for clearance through the back of the eye. Retinal permeability data, published human ocular pharmacokinetics (PK) and the PK-Eye clearance times were then used to establish in vitro in vivo correlations (IVIVCs) for intraocular clearance times of corticosteroid formulations. A t1/2 of 48h was estimated for the dexamethasone-TIPS microparticles, which is almost 9 times longer than that reported for dexamethasone suspension in humans. The prediction of human clearance times of permeable molecules from the vitreous compartment can be determined by accounting for drug retinal permeation and determining the experimental clearance via the anterior aqueous outflow pathway using the PK-Eye. Copyright © 2017. Published by Elsevier B.V.

  19. The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts.

    Directory of Open Access Journals (Sweden)

    Lucia Pagani

    Full Text Available BACKGROUND: Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls", clock properties measured in human fibroblasts correlated with extreme diurnal behavior. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have measured circadian period in human primary fibroblasts taken from normal individuals and, for the first time, compared it directly with physiological period measured in vivo in the same subjects. Human physiological period length was estimated via the secretion pattern of the hormone melatonin in two different groups of sighted subjects and one group of totally blind subjects, each using different methods. Fibroblast period length was measured via cyclical expression of a lentivirally delivered circadian reporter. Within each group, a positive linear correlation was observed between circadian period length in physiology and in fibroblast gene expression. Interestingly, although blind individuals showed on average the same fibroblast clock properties as sighted ones, their physiological periods were significantly longer. CONCLUSIONS/SIGNIFICANCE: We conclude that the period of human circadian behaviour is mostly driven by cellular clock properties in normal individuals and can be approximated by measurement in peripheral cells such as fibroblasts. Based upon differences among sighted and blind subjects, we also speculate that period can be modified by prolonged unusual conditions such as the total light deprivation of blindness.

  20. In vivo measurement of the shape of the tissue-refractive-index correlation function and its application to detection of colorectal field carcinogenesis.

    Science.gov (United States)

    Gomes, Andrew J; Ruderman, Sarah; DelaCruz, Mart; Wali, Ramesh K; Roy, Hemant K; Backman, Vadim

    2012-04-01

    Polarization-gated spectroscopy is an established method to depth-selectively interrogate the structural properties of biological tissue. We employ this method in vivo in the azoxymethane (AOM)-treated rat model to monitor the morphological changes that occur in the field of a tumor during early carcinogenesis. The results demonstrate a statistically significant change in the shape of the refractive-index correlation function for AOM-treated rats versus saline-treated controls. Since refractive index is linearly proportional to mass density, these refractive-index changes can be directly linked to alterations in the spatial distribution patterns of macromolecular density. Furthermore, we found that alterations in the shape of the refractive-index correlation function shape were an indicator of both present and future risk of tumor development. These results suggest that noninvasive measurement of the shape of the refractive-index correlation function could be a promising marker of early cancer development.

  1. Effects of marathon running on platelet activation markers : direct evidence for in vivo platelet activation.

    Science.gov (United States)

    Kratz, Alexander; Wood, Malissa J; Siegel, Arthur J; Hiers, Jennifer R; Van Cott, Elizabeth M

    2006-02-01

    We used the ADVIA 2120 Hematology System (Bayer HealthCare, Diagnostics Division, Tarrytown, NY) to study the effects of vigorous exercise on CBC count, WBC differential, RBC fragmentation, and platelet activation parameters in 32 healthy participants in a 26.2-mile (42.2-km) marathon. The runners demonstrated increases in hematocrit and platelet count consistent with dehydration and leukocytosis indicative of demargination of neutrophils or inflammation secondary to tissue destruction (eg, rhabdomyolysis). The number of RBC fragments was increased after the race (P = .008), consistent with exercise-induced hemolysis. The mean platelet component, a measure of platelet granularity, was decreased (P marathon. By using direct measurement of platelet granularity, our study confirms the in vivo activation of platelets by vigorous exercise and establishes the usefulness of automated cell counters for the assessment of platelet activation and of RBC fragmentation in this setting.

  2. Human hair growth ex vivo is correlated with in vivo hair growth: selective categorization of hair follicles for more reliable hair follicle organ culture.

    Science.gov (United States)

    Kwon, Oh Sang; Oh, Jun Kyu; Kim, Mi Hyang; Park, So Hyun; Pyo, Hyun Keol; Kim, Kyu Han; Cho, Kwang Hyun; Eun, Hee Chul

    2006-02-01

    Of the numerous assays used to assess hair growth, hair follicle organ culture model is one of the most popular and powerful in vitro systems. Changes in hair growth are commonly employed as a measurement of follicular activity. Hair cycle stage of mouse vibrissa follicles in vivo is known to determine subsequent hair growth and follicle behavior in vitro and it is recommended that follicles be taken at precisely the same cyclic stage. This study was performed to evaluate whether categorization of human hair follicles by the growth in vivo could be used to select follicles of the defined anagen stage for more consistent culture. Occipital scalp samples were obtained from three subjects, 2 weeks later after hair bleaching. Hair growth and follicle length of isolated anagen VI follicles were measured under a videomicroscope. Follicles were categorized into four groups according to hair growth and some were cultured ex vivo for 6 days. Follicles showed considerable variations with respect to hair growth and follicle length; however, these two variables were relatively well correlated. Hair growth in culture was closely related with hair growth rate in vivo. Moreover, minoxidil uniquely demonstrated a significant increase of hair growth in categorized hair follicles assumed at a similar early anagen VI stage of hair cycle. Selection of follicles at a defined stage based on hair-growth rate would permit a more reliable outcome in human hair follicle organ culture.

  3. Direct Determination of Ascorbic Acid in a Grapefruit: Paving the Way for In Vivo Spectroelectrochemistry.

    Science.gov (United States)

    Garoz-Ruiz, Jesus; Heras, Aranzazu; Colina, Alvaro

    2017-02-07

    The study of real samples is more complicated than the study of other systems. However, the inherent advantages of UV-vis absorption spectroelectrochemistry should overcome some difficulties related to direct measurements in complex matrices. For this reason, a singular spectroelectrochemistry device has been fabricated and validated. The novel cell is based on single-walled carbon nanotubes, which are filtered and subsequently press-transferred on a polyethylene terephthalate support using a stencil with a custom design. With this new methodology, working, counter, and reference electrodes are completely flat on the surface, where two optical fibers are fixed in a long optical path length configuration. To demonstrate the usefulness of this device and the power of spectroelectrochemistry techniques to solve problems of the current world, this device is used to quantitatively detect the concentration of ascorbic acid in a complex matrix such as a fruit, directly, without any previous sample pretreatment. The ease to fabricate the device, the advantages related to its use, and the excellent results obtained not only with univariate but also with multivariate analysis, shed more light on the analysis of samples as they occur in nature. According to the particular features of this cell, to the best of our knowledge this is the first spectroelectrochemical sensor that can be inserted directly in a biological matrix, laying the groundwork to perform in vivo measurements in a near future.

  4. Automatic frequency and phase alignment of in vivo J-difference-edited MR spectra by frequency domain correlation.

    Science.gov (United States)

    Wiegers, Evita C; Philips, Bart W J; Heerschap, Arend; van der Graaf, Marinette

    2017-06-01

    J-difference editing is often used to select resonances of compounds with coupled spins in (1)H-MR spectra. Accurate phase and frequency alignment prior to subtracting J-difference-edited MR spectra is important to avoid artefactual contributions to the edited resonance. In-vivo J-difference-edited MR spectra were aligned by maximizing the normalized scalar product between two spectra (i.e., the correlation over a spectral region). The performance of our correlation method was compared with alignment by spectral registration and by alignment of the highest point in two spectra. The correlation method was tested at different SNR levels and for a broad range of phase and frequency shifts. In-vivo application of the proposed correlation method showed reduced subtraction errors and increased fit reliability in difference spectra as compared with conventional peak alignment. The correlation method and the spectral registration method generally performed equally well. However, better alignment using the correlation method was obtained for spectra with a low SNR (down to ~2) and for relatively large frequency shifts. Our correlation method for simultaneously phase and frequency alignment is able to correct both small and large phase and frequency drifts and also performs well at low SNR levels.

  5. Influence of drug property and product design on in vitro-in vivo correlation of complex modified-release dosage forms.

    Science.gov (United States)

    Qiu, Yihong; Li, Xia; Duan, John Z

    2014-02-01

    The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of tmax and maximum observed plasma concentration (Cmax) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to Cmax, or (3) be meaningless because of the insensitivity of Cmax to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. The evolution of trade-offs under directional and correlational selection.

    Science.gov (United States)

    Roff, Derek A; Fairbairn, Daphne J

    2012-08-01

    Using quantitative genetic theory, we develop predictions for the evolution of trade-offs in response to directional and correlational selection. We predict that directional selection favoring an increase in one trait in a trade-off will result in change in the intercept but not the slope of the trade-off function, with the mean value of the selected trait increasing and that of the correlated trait decreasing. Natural selection will generally favor an increase in some combination of trait values, which can be represented as directional selection on an index value. Such selection induces both directional and correlational selection on the component traits. Theory predicts that selection on an index value will also change the intercept but not the slope of the trade-off function but because of correlational selection, the direction of change in component traits may be in the same or opposite directions. We test these predictions using artificial selection on the well-established trade-off between fecundity and flight capability in the cricket, Gryllus firmus and compare the empirical results with a priori predictions made using genetic parameters from a separate half-sibling experiment. Our results support the predictions and illustrate the complexity of trade-off evolution when component traits are subject to both directional and correlational selection. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  7. Estimation of velocity vector angles using the directional cross-correlation method

    DEFF Research Database (Denmark)

    Kortbek, Jacob; Jensen, Jørgen Arendt

    2006-01-01

    and then select the angle with the highest normalized correlation between directional signals. The approach is investigated using Field II simulations and data from the experimental ultrasound scanner RASMUS and a circulating flow rig with a parabolic flow having a peak velocity of 0.3 m/s. A 7 MHz linear array......A method for determining both velocity magnitude and angle in any direction is suggested. The method uses focusing along the velocity direction and cross-correlation for finding the correct velocity magnitude. The angle is found from beamforming directional signals in a number of directions...... transducer is used with a normal transmission of a focused ultrasound field. In the simulations the relative standard deviation of the velocity magnitude is between 0.7% and 7.7% for flow angles between 45 deg and 90 deg. The study showed that angle estimation by directional beamforming can be estimated...

  8. A new rapidly absorbed paracetamol tablet containing sodium bicarbonate. II. Dissolution studies and in vitro/in vivo correlation.

    Science.gov (United States)

    Rostami-Hodjegan, A; Shiran, M R; Tucker, G T; Conway, B R; Irwin, W J; Shaw, L R; Grattan, T J

    2002-05-01

    The objective of this study was to compare the in vitro dissolution profile of a new rapidly absorbed paracetamol tablet containing sodium bicarbonate (PS) with that of a conventional paracetamol tablet (P), and to relate these by deconvolution and mapping to in vivo release. The dissolution methods used include the standard procedure described in the USP monograph for paracetamol tablets, employing buffer at pH 5.8 or 0.05 M HCl at stirrer speeds between 10 and 50 rpm. The mapping process was developed and implemented in Microsoft Excel worksheets that iteratively calculated the optimal values of scale and shape factors which linked in vivo time to in vitro time. The in vitro-in vivo correlation (IVIVC) was carried out simultaneously for both formulations to produce common mapping factors. The USP method, using buffer at pH 5.8, demonstrated no difference between the two products. However, using an acidic medium the rate of dissolution of P but not of PS decreased with decreasing stirrer speed. A significant correlation (r = 0.773; p dissolution using the profiles obtained with 0.05 M HCl and a stirrer speed of 30 rpm. The scale factor for optimal simultaneous IVIVC in the fasting state was 2.54 and the shape factor was 0.16; corresponding values for mapping in the fed state were 3.37 and 0.13 (implying a larger in vitro-in vivo time difference but reduced shape difference in the fed state). The current IVIVC explains, in part, the observed in vivo variability of the two products. The approach to mapping may also be extended to different batches of these products, to predict the impact of any changes of in vitro dissolution on in vivo release and plasma drug concentration-time profiles.

  9. Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Rita S Santos

    2015-01-01

    Full Text Available Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA/2’-OMethyl RNA (2'OMe have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers—the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria.

  10. Direct tissue oxygen monitoring by in vivo photoacoustic lifetime imaging (PALI)

    Science.gov (United States)

    Shao, Qi; Morgounova, Ekaterina; Ashkenazi, Shai

    2014-03-01

    Tissue oxygen plays a critical role in maintaining tissue viability and in various diseases, including response to therapy. Images of oxygen distribution provide the history of tissue hypoxia and evidence of oxygen availability in the circulatory system. Currently available methods of direct measuring or imaging tissue oxygen all have significant limitations. Previously, we have reported a non-invasive in vivo imaging modality based on photoacoustic lifetime. The technique maps the excited triplet state of oxygen-sensitive dye, thus reflects the spatial and temporal distribution of tissue oxygen. We have applied PALI on tumor hypoxia in small animals, and the hypoxic region imaged by PALI is consistent with the site of the tumor imaged by ultrasound. Here, we present two studies of applying PALI to monitor changes of tissue oxygen by modulations. The first study involves an acute ischemia model using a thin thread tied around the hind limb of a normal mouse to reduce the blood flow. PALI images were acquired before, during, and after the restriction. The drop of muscle pO2 and recovery from hypoxia due to reperfusion were observed by PALI tracking the same region. The second study modulates tissue oxygen by controlling the percentage of oxygen the mouse inhales. We demonstrate that PALI is able to reflect the change of oxygen level with respect to both hyperbaric and hypobaric conditions. We expect this technique to be very attractive for a range of clinical applications in which tissue oxygen mapping would improve therapy decision making and treatment planning.

  11. Spatial Vertical Directionality and Correlation of Low-Frequency Ambient Noise in Deep Ocean Direct-Arrival Zones.

    Science.gov (United States)

    Yang, Qiulong; Yang, Kunde; Cao, Ran; Duan, Shunli

    2018-01-23

    Wind-driven and distant shipping noise sources contribute to the total noise field in the deep ocean direct-arrival zones. Wind-driven and distant shipping noise sources may significantly and simultaneously affect the spatial characteristics of the total noise field to some extent. In this work, a ray approach and parabolic equation solution method were jointly utilized to model the low-frequency ambient noise field in a range-dependent deep ocean environment by considering their calculation accuracy and efficiency in near-field wind-driven and far-field distant shipping noise fields. The reanalysis databases of National Center of Environment Prediction (NCEP) and Volunteer Observation System (VOS) were used to model the ambient noise source intensity and distribution. Spatial vertical directionality and correlation were analyzed in three scenarios that correspond to three wind speed conditions. The noise field was dominated by distant shipping noise sources when the wind speed was less than 3 m/s, and then the spatial vertical directionality and vertical correlation of the total noise field were nearly consistent with those of distant shipping noise field. The total noise field was completely dominated by near field wind generated noise sources when the wind speed was greater than 12 m/s at 150 Hz, and then the spatial vertical correlation coefficient and directionality pattern of the total noise field was approximately consistent with that of the wind-driven noise field. The spatial characteristics of the total noise field for wind speeds between 3 m/s and 12 m/s were the weighted results of wind-driven and distant shipping noise fields. Furthermore, the spatial characteristics of low-frequency ambient noise field were compared with the classical Cron/Sherman deep water noise field coherence function. Simulation results with the described modeling method showed good agreement with the experimental measurement results based on the vertical line array deployed near

  12. Ex vivo fracture resistance of direct resin composite complete crowns with and without posts on maxillary premolars.

    NARCIS (Netherlands)

    Fokkinga, W.A.; Bell, A.M. Le; Kreulen, C.M.; Lassila, L.V.; Vallittu, P.K.; Creugers, N.H.J.

    2005-01-01

    AIM: To investigate ex vivo the fracture resistance and failure mode of direct resin composite complete crowns with and without various root canal posts made on maxillary premolars. METHODOLOGY: The clinical crowns of 40 human extracted single-rooted maxillary premolars were sectioned at the

  13. Establishing in vitro in vivo correlations to screen monoclonal antibodies for physicochemical properties related to favorable human pharmacokinetics.

    Science.gov (United States)

    Avery, Lindsay B; Wade, Jason; Wang, Mengmeng; Tam, Amy; King, Amy; Piche-Nicholas, Nicole; Kavosi, Mania S; Penn, Steve; Cirelli, David; Kurz, Jeffrey C; Zhang, Minlei; Cunningham, Orla; Jones, Rhys; Fennell, Brian J; McDonnell, Barry; Sakorafas, Paul; Apgar, James; Finlay, William J; Lin, Laura; Bloom, Laird; O'Hara, Denise M

    2017-12-22

    Implementation of in vitro assays that correlate with in vivo human pharmacokinetics (PK) would provide desirable preclinical tools for the early selection of therapeutic monoclonal antibody (mAb) candidates with minimal non-target-related PK risk. Use of these tools minimizes the likelihood that mAbs with unfavorable PK would be advanced into costly preclinical and clinical development. In total, 42 mAbs varying in isotype and soluble versus membrane targets were tested in in vitro and in vivo studies. MAb physicochemical properties were assessed by measuring non-specific interactions (DNA- and insulin-binding ELISA), self-association (affinity-capture self-interaction nanoparticle spectroscopy) and binding to matrix-immobilized human FcRn (surface plasmon resonance and column chromatography). The range of scores obtained from each in vitro assay trended well with in vivo clearance (CL) using both human FcRn transgenic (Tg32) mouse allometrically projected human CL and observed human CL, where mAbs with high in vitro scores resulted in rapid CL in vivo. Establishing a threshold value for mAb CL in human of 0.32 mL/hr/kg enabled refinement of thresholds for each in vitro assay parameter, and using a combinatorial triage approach enabled the successful differentiation of mAbs at high risk for rapid CL (unfavorable PK) from those with low risk (favorable PK), which allowed mAbs requiring further characterization to be identified. Correlating in vitro parameters with in vivo human CL resulted in a set of in vitro tools for use in early testing that would enable selection of mAbs with the greatest likelihood of success in the clinic, allowing costly late-stage failures related to an inadequate exposure profile, toxicity or lack of efficacy to be avoided.

  14. Cortical microinfarcts detected in vivo on 3 Tesla MRI: clinical and radiological correlates

    NARCIS (Netherlands)

    Dalen, J.W. van; Scuric, E.E.; Veluw, S.J. van; Caan, M.W.; Nederveen, A.J.; Biessels, G.J.; Gool, W.A. van; Richard, E.

    2015-01-01

    BACKGROUND AND PURPOSE: Cortical microinfarcts (CMIs) are a common postmortem finding associated with vascular risk factors, cognitive decline, and dementia. Recently, CMIs identified in vivo on 7 Tesla MRI also proved retraceable on 3 Tesla MRI. METHODS: We evaluated CMIs on 3 Tesla MRI in a

  15. Cortical microinfarcts detected in vivo on 3 tesla MRI : Clinical and radiological correlates

    NARCIS (Netherlands)

    Van Dalen, Jan Willem; Scuric, Eva E M; Van Veluw, Susanne J.; Caan, Matthan W A; Nederveen, Aart J.; Biessels, Geert Jan; Van Gool, Willem A.; Richard, Edo

    2015-01-01

    Background and Purpose-Cortical microinfarcts (CMIs) are a common postmortem finding associated with vascular risk factors, cognitive decline, and dementia. Recently, CMIs identified in vivo on 7 Tesla MRI also proved retraceable on 3 Tesla MRI. Methods-We evaluated CMIs on 3 Tesla MRI in a

  16. Jet properties from direct $\\gamma$ - hadron correlation in PHENIX at RHIC

    CERN Document Server

    Kim, D J; Rak, Jan

    2010-01-01

    Two-particle correlations of direct photon triggers with associated hadrons are obtained by isolation method in p+p collisions at \\sqrt{s} = 200 GeV in PHENIX at RHIC. The initial momentum of the away-side parton is tightly constrained, because the parton-photon pair is balanced in momentum at the leading order in perturbative quantum chromodynamics (pQCD). Therefore making such correlations can be used as a tool to measure the away-side parton fragmentation function. The direct photon associated yields in p+p collisions are compared with PYTHIA and the effect of the $k_{T}$ smearing in the spectra is discussed.

  17. In vitro - in vivo correlations for endocrine activity of a mixture of currently used pesticides

    Energy Technology Data Exchange (ETDEWEB)

    Taxvig, Camilla, E-mail: camta@food.dtu.dk [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark); Hadrup, Niels; Boberg, Julie; Axelstad, Marta [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark); Bossi, Rossana [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark); Bonefeld-Jørgensen, Eva Cecilie [Department of Public Health, University of Aarhus, DK-8000 Aarhus C (Denmark); Vinggaard, Anne Marie [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark)

    2013-11-01

    Two pesticide mixtures were investigated for potential endocrine activity. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin, and Mix 5 included malathion and terbuthylazine in addition to the three pesticides in Mix 3. All five single pesticides and the two mixtures were investigated for their ability to affect steroidogenesis in vitro in H295R cells. The pesticides alone and both mixtures affected steroidogenesis with both mixtures causing increase in progesterone and decrease in testosterone. For Mix 5 an increase in estradiol was seen as well, indicating increased aromatase activity. The two mixtures were also investigated in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. Decreased estradiol and reduced placental testosterone were seen in dams exposed to Mix 5. Also a significant increase in aromatase mRNA-levels in female adrenal glands was found for Mix5. However, either of the two mixtures showed any effects on fetal hormone levels in plasma or testis, or on anogenital distance. Overall, potential aromatase induction was found for Mix 5 both in vitro and in vivo, but not for Mix 3, an effect likely owed to terbuthylazine in Mix 5. However, the hormonal responses in vitro were only partly reflected in vivo, probably due to some toxicokinetic issues, as the pesticide levels in the amniotic fluid also were found to be negatively affected by the number of compounds present in the mixtures. Nonetheless, the H295R assay gives hints on conceivable interference with steroidogenesis, thus generating hypotheses on in vivo effects. - Highlights: • The study examines the endocrine disrupting potential of mixtures of pesticides. • All single pesticides and both mixtures affected steroidogenesis in vitro. • Potential aromatase induction was found for Mix 5 both in vitro and in vivo. • The hormonal responses in vitro were only partly reflected in vivo.

  18. Directed evolution of human heavy chain variable domain (VH using in vivo protein fitness filter.

    Directory of Open Access Journals (Sweden)

    Dong-Sik Kim

    Full Text Available Human immunoglobulin heavy chain variable domains (VH are promising scaffolds for antigen binding. However, VH is an unstable and aggregation-prone protein, hindering its use for therapeutic purposes. To evolve the VH domain, we performed in vivo protein solubility selection that linked antibiotic resistance to the protein folding quality control mechanism of the twin-arginine translocation pathway of E. coli. After screening a human germ-line VH library, 95% of the VH proteins obtained were identified as VH3 family members; one VH protein, MG2x1, stood out among separate clones expressing individual VH variants. With further screening of combinatorial framework mutation library of MG2x1, we found a consistent bias toward substitution with tryptophan at the position of 50 and 58 in VH. Comparison of the crystal structures of the VH variants revealed that those substitutions with bulky side chain amino acids filled the cavity in the VH interface between heavy and light chains of the Fab arrangement along with the increased number of hydrogen bonds, decreased solvation energy, and increased negative charge. Accordingly, the engineered VH acquires an increased level of thermodynamic stability, reversible folding, and soluble expression. The library built with the VH variant as a scaffold was qualified as most of VH clones selected randomly were expressed as soluble form in E. coli regardless length of the combinatorial CDR. Furthermore, a non-aggregation feature of the selected VH conferred a free of humoral response in mice, even when administered together with adjuvant. As a result, this selection provides an alternative directed evolution pathway for unstable proteins, which are distinct from conventional methods based on the phage display.

  19. Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson's disease therapy

    Science.gov (United States)

    Yoo, Junsang; Lee, Euiyeon; Kim, Hee Young; Youn, Dong-Ho; Jung, Junghyun; Kim, Hongwon; Chang, Yujung; Lee, Wonwoong; Shin, Jaein; Baek, Soonbong; Jang, Wonhee; Jun, Won; Kim, Soochan; Hong, Jongki; Park, Hi-Joon; Lengner, Christopher J.; Moh, Sang Hyun; Kwon, Youngeun; Kim, Jongpil

    2017-10-01

    Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes. In vivo dopaminergic neuron reprogramming by EMF stimulation of AuNPs efficiently and non-invasively alleviated symptoms in mouse Parkinson's disease models. This study provides a proof of principle for EMF-based in vivo lineage conversion as a potentially viable and safe therapeutic strategy for the treatment of neurodegenerative disorders.

  20. Pharmacokinetics and correlation between in vitro release and in vivo absorption of bio-adhesive pellets of panax notoginseng saponins.

    Science.gov (United States)

    Li, Ying; Zhang, Yun; Zhu, Chun-Yan

    2017-02-01

    The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins (PNS) with hydroxy propyl methyl cellulose (HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release (IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in pH 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased Cmax, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  1. Field and action potential recordings in heart slices: correlation with established in vitro and in vivo models

    Science.gov (United States)

    Himmel, Herbert M; Bussek, Alexandra; Hoffmann, Michael; Beckmann, Rolf; Lohmann, Horst; Schmidt, Matthias; Wettwer, Erich

    2012-01-01

    BACKGROUND AND PURPOSE Action potential (AP) recordings in ex vivo heart preparations constitute an important component of the preclinical cardiac safety assessment according to the ICH S7B guideline. Most AP measurement models are sensitive, predictive and informative but suffer from a low throughput. Here, effects of selected anti-arrhythmics (flecainide, quinidine, atenolol, sotalol, dofetilide, nifedipine, verapamil) on field/action potentials (FP/AP) of guinea pig and rabbit ventricular slices are presented and compared with data from established in vitro and in vivo models. EXPERIMENTAL APPROACH Data from measurements of membrane currents (hERG, INa), AP/FP (guinea pig and rabbit ventricular slices), AP (rabbit Purkinje fibre), haemodynamic/ECG parameters (conscious, telemetered dog) were collected, compared and correlated to complementary published data (focused literature search). KEY RESULTS The selected anti-arrhythmics, flecainide, quinidine, atenolol, sotalol, dofetilide, nifedipine and verapamil, influenced the shape of AP/FP of guinea pig and rabbit ventricular slices in a manner similar to that observed for rabbit PF. The findings obtained from slice preparations are in line with measurements of membrane currents in vitro, papillary muscle AP in vitro and haemodynamic/ECG parameters from conscious dogs in vivo, and were also corroborated by published data. CONCLUSION AND IMPLICATIONS FP and AP recordings from heart slices correlated well with established in vitro and in vivo models in terms of pharmacology and predictability. Heart slice preparations yield similar results as papillary muscle but offer enhanced throughput for mechanistic investigations and may substantially reduce the use of laboratory animals. PMID:22074238

  2. Direct correlation between strengthening mechanisms and electrical noise in strained copper wires

    OpenAIRE

    Bellido, Natalia; Pautrat, Alain; Keller, Clement; Hug, Eric

    2011-01-01

    We have measured the resistance noise of copper metallic wires during a tensile stress. The time variation of the main resistance is continuous up to the wire breakdown, but its fluctuations reveal the intermittent and heterogeneous character of plastic flow. We show in particular direct correlations between strengthening mechanisms and noise spectra characteristics.

  3. Perturbed γ-γ directional correlations and the complex chemistry of hafnium and tantalum

    NARCIS (Netherlands)

    Hollander, R.W.; Plicht, J. van der

    1976-01-01

    In the experiments described in this paper, the γ-γ directional correlation in the decay of 181Hf was measured in dilute aqueous solutions containing varying amounts of fluoride. The observed variations in the anisotropy are explained from complex formation and precipitation, possibly preceeded by

  4. Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems.

    Science.gov (United States)

    Yang, Yang; Manda, Prashanth; Pavurala, Naresh; Khan, Mansoor A; Krishnaiah, Yellela S R

    2015-07-28

    The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermal drug delivery systems (TDDS). In vitro drug permeation studies across human skin were carried out to obtain the percent of estradiol permeation from marketed products. The in vivo time versus plasma concentration data of three estradiol TDDS at drug loadings of 2.0, 3.8 and 7.6mg (delivery rates of 25, 50 and 100μg/day, respectively) was deconvoluted using Wagner-Nelson method to obtain percent of in vivo drug absorption in postmenopausal women. The IVIVC between the in vitro percent of drug permeation (X) and in vivo percent of drug absorption (Y) for these three estradiol TDDS was constructed using GastroPlus® software. There was a high correlation (R(2)=1.0) with a polynomial regression of Y=-0.227X(2)+0.331X-0.001. These three estradiol TDDS were used for internal validation whereas another two products of the same formulation design (with delivery rates of 60 and 100μg/day) were used for external validation. The predicted estradiol serum concentrations (convoluted from in vitro skin permeation data) were compared with the observed serum concentrations for the respective products. The developed IVIVC model passed both the internal and external validations as the prediction errors (%PE) for Cmax and AUC were less than 15%. When another marketed estradiol TDDS with a delivery rate of 100μg/day but with a slight variation in formulation design was chosen, it did not pass external validation indicating the product-specific nature of IVIVC model. Results suggest that the IVIVC model developed in this study can be used to successfully predict the in vivo performance of the same estradiol TDDS with in vivo delivery rates ranging from 25 to 100μg/day. Published by Elsevier B.V.

  5. Direct correlation of radiologic and cadaveric structures in a gross anatomy course.

    Science.gov (United States)

    Phillips, Andrew W; Smith, Sandy G; Ross, Callum F; Straus, Christopher M

    2012-01-01

    Radiologic imaging is increasingly utilized as supplemental material in preclinical gross anatomy courses, but few studies have investigated its utility as a fully integrated instructional tool. Establish the benefit of a teaching method that simultaneously correlates cadaveric and radiologic structures for learning human anatomy. We performed a mixed-methods randomized controlled trial and one-way cross-over study comparing exam grades and subjective student perception in a gross anatomy course. The intervention consisted of daily direct correlation small group sessions in which students simultaneously identified and correlated radiologic and cadaveric structures. The control method utilized identical laboratory and teaching conditions but students did not simultaneously correlate structures. Spatial relationships of structures within each respective media (gross or radiologic) were emphasized in both groups. No significant differences in radiology, gross, or written exam scores were observed between the intervention and control groups. The cross-over group preferred the intervention and control methods equally. The correlation teaching sessions ranked equally with active dissection as the most important instructional components of the course. Direct, simultaneous correlation of radiologic and cadaveric structures did not affect exam scores or student preference but helped students understand anatomical concepts in comparison with other course components.

  6. In vivo preclinical verification of a multimodal diffuse reflectance and correlation spectroscopy system for sensing tissue perfusion

    Science.gov (United States)

    Pakela, Julia M.; Lee, Seung Yup; Hedrick, Taylor L.; Vishwanath, Karthik; Helton, Michael C.; Chung, Yooree G.; Kolodziejski, Noah J.; Staples, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Christian, James F.; O'Reilly, Jameson; Farkas, Dana; Ward, Brent B.; Feinberg, Stephen E.; Mycek, Mary-Ann

    2017-02-01

    In reconstructive surgery, impeded blood flow in microvascular free flaps due to a compromise in arterial or venous patency secondary to blood clots or vessel spasms can rapidly result in flap failures. Thus, the ability to detect changes in microvascular free flaps is critical. In this paper, we report progress on in vivo pre-clinical testing of a compact, multimodal, fiber-based diffuse correlation and reflectance spectroscopy system designed to quantitatively monitor tissue perfusion in a porcine model's surgically-grafted free flap. We also describe the device's sensitivity to incremental blood flow changes and discuss the prospects for continuous perfusion monitoring in future clinical translational studies.

  7. Correlation between in vitro and in vivo parameters of commercial paracetamol tablets.

    Science.gov (United States)

    Babalola, C P; Oladimeji, F A; Femi-Oyewo, M N

    2001-12-01

    Three leading and competitive commercial products of paracetamol tablets coded as brands A, B and C (A, being the innovator product) in the country were evaluated for their in vitro properties and in vivo comparative bioavailability. The studies included chemical equivalence, hardness, disintegration time, dissolution rate and systemic availability among eight healthy volunteers. The disintegration times were 2.1 min for brand A, 5.7 min for brand B and 36.2 min for brand C. The dissolution rate (T70) were 33.0 min, 74.5 min and 56.5 min for brands A, B and C, respectively. While brand A passed all the in vitro tests as specified in the official monograph, brand B failed only the dissolution rate test and brand C failed both the disintegration and dissolution tests. These significant differences observed among the products after in vitro tests were not reflected in the in vivo availability. While the absorption rate (indicated by tmax) of brand C was significantly faster (i.e. shorter) than those of Brands A and B, the extent of absorption (indicated by AUC) was comparable among the three brands. The relative bioavailabilities (with respect to brand A) were 92 and 91% for brands B and C, respectively indicating that the products were bioequivalent. Comparison of the in vitro and in vivo data suggest that the systemic absorption of paracetamol may not be dissolution--rate limited and that using in vitro dissolution rate studies alone to establish bioequivalency of paracetamol tablets should be done with caution.

  8. In vivo neural stem cell imaging: current modalities and future directions.

    Science.gov (United States)

    Gera, Atul; Steinberg, Gary K; Guzman, Raphael

    2010-01-01

    Neural stem cells have been proposed as a promising therapy for treating a wide variety of neuropathologies. While several studies have demonstrated the therapeutic benefits of neural stem cells, the exact mechanism remains elusive. In order to facilitate research efforts to understand these mechanisms, and before neural stem cell-based therapies can be utilized in a clinical context, we must develop means of monitoring these cells in vivo. However, because of tissue depth and the blood-brain barrier, in vivo imaging of neural stem cells in the brain has unique challenges that do not apply to stem cells for other purposes. In this paper, we review contemporary methods for in vivo neural stem cell imaging, including MRI, PET and optical imaging techniques.

  9. Multi-factorial in vivo stable isotope fractionation: causes, correlations, consequences and applications.

    Science.gov (United States)

    Schmidt, Hanns-Ludwig; Robins, Richard J; Werner, Roland A

    2015-01-01

    Many physical and chemical processes in living systems are accompanied by isotope fractionation on H, C, N, O and S. Although kinetic or thermodynamic isotope effects are always the basis, their in vivo manifestation is often modulated by secondary influences. These include metabolic branching events or metabolite channeling, metabolite pool sizes, reaction mechanisms, anatomical properties and compartmentation of plants and animals, and climatological or environmental conditions. In the present contribution, the fundamentals of isotope effects and their manifestation under in vivo conditions are outlined. The knowledge about and the understanding of these interferences provide a potent tool for the reconstruction of physiological events in plants and animals, their geographical origin, the history of bulk biomass and the biosynthesis of defined representatives. It allows the use of isotope characteristics of biomass for the elucidation of biochemical pathways and reaction mechanisms and for the reconstruction of climatic, physiological, ecological and environmental conditions during biosynthesis. Thus, it can be used for the origin and authenticity control of food, the study of ecosystems and animal physiology, the reconstruction of present and prehistoric nutrition chains and paleaoclimatological conditions. This is demonstrated by the outline of fundamental and application-orientated examples for all bio-elements. The aim of the review is to inform (advanced) students from various disciplines about the whole potential and the scope of stable isotope characteristics and fractionations and to provide them with a comprehensive introduction to the literature on fundamental aspects and applications.

  10. Microcoil-based MR phase imaging and manganese enhanced microscopy of glial tumor neurospheres with direct optical correlation.

    Science.gov (United States)

    Baxan, Nicoleta; Kahlert, Ulf; Maciaczyk, Jaroslaw; Nikkhah, Guido; Hennig, Jürgen; von Elverfeldt, Dominik

    2012-07-01

    Susceptibility differences among tissues were recently used for highlighting complementary contrast in MRI different from the conventional T(1), T(2), or spin density contrasts. This method, based on the signal phase, previously showed improved image contrast of human or rodent neuroarchitecture in vivo, although direct MR phase imaging of cellular architecture was not available until recently. In this study, we present for the first time the ability of microcoil-based phase MRI to resolve the structure of human glioma neurospheres at significantly improved resolutions (10 × 10 μm(2)) with direct optical image correlation. The manganese chloride property to function as a T(1) contrast agent enabled a closer examination of cell physiology with MRI. Specifically the temporal changes of manganese chloride uptake, retention and release time within and from individual clusters were assessed. The optimal manganese chloride concentration for improved MR signal enhancement was determined while keeping the cellular viability unaffected. The presented results demonstrate the possibilities to reveal structural and functional observation of living glioblastoma human-derived cells. This was achieved through the combination of highly sensitive microcoils, high magnetic field, and methods designed to maximize contrast to noise ratio. The presented approach may provide a powerful multimodal tool that merges structural and functional information of submilimeter biological samples. Copyright © 2011 Wiley Periodicals, Inc.

  11. Total and Direct Correlation Function Integrals from Molecular Simulation of Binary Systems

    DEFF Research Database (Denmark)

    Wedberg, Nils Hejle Rasmus Ingemar; O’Connell, John P.; Peters, Günther H.J.

    2011-01-01

    The possibility for obtaining derivative properties for mixtures from integrals of spatial total and direct correlation functions obtained from molecular dynamics simulations is explored. Theoretically well-supported methods are examined to extend simulation radial distribution functions to long...... are consistent with an excess Helmholtz energy model fitted to available simulations. In addition, simulations of water/methanol and water/t-butanol mixtures have been carried out. The method yields results for partial molar volumes, activity coefficient derivatives, and individual correlation function integrals...

  12. Search for small-scale angular correlations of neutrino arrival directions in IceCube

    Energy Technology Data Exchange (ETDEWEB)

    Schimp, Michael; Glagla, Martin; Haack, Christian; Leuermann, Martin; Raedel, Leif; Reimann, Rene; Schoenen, Sebastian; Wiebusch, Christopher [III. Physikalisches Institut, RWTH Aachen University, 52056 Aachen (Germany); Collaboration: IceCube-Collaboration

    2015-07-01

    Recently, the IceCube Neutrino Observatory discovered a diffuse flux of extra-terrestrial high-energy neutrinos. The identification of their astrophysical sources is one of the goals of current investigations. This analysis is based on the expansion of muon neutrino arrival directions in spherical harmonics, which is sensitive to angular correlations. A large number of point sources distributed over the sky would leave an imprint on the spectrum of observed expansion coefficients, even if the sources are too weak to be detected individually. We present the analysis method and discuss possible astrophysical interpretations for the observation or non-observation of such a correlation.

  13. Mapping soil deformation around plant roots using in vivo 4D X-ray Computed Tomography and Digital Volume Correlation.

    Science.gov (United States)

    Keyes, S D; Gillard, F; Soper, N; Mavrogordato, M N; Sinclair, I; Roose, T

    2016-06-14

    The mechanical impedance of soils inhibits the growth of plant roots, often being the most significant physical limitation to root system development. Non-invasive imaging techniques have recently been used to investigate the development of root system architecture over time, but the relationship with soil deformation is usually neglected. Correlative mapping approaches parameterised using 2D and 3D image data have recently gained prominence for quantifying physical deformation in composite materials including fibre-reinforced polymers and trabecular bone. Digital Image Correlation (DIC) and Digital Volume Correlation (DVC) are computational techniques which use the inherent material texture of surfaces and volumes, captured using imaging techniques, to map full-field deformation components in samples during physical loading. Here we develop an experimental assay and methodology for four-dimensional, in vivo X-ray Computed Tomography (XCT) and apply a Digital Volume Correlation (DVC) approach to the data to quantify deformation. The method is validated for a field-derived soil under conditions of uniaxial compression, and a calibration study is used to quantify thresholds of displacement and strain measurement. The validated and calibrated approach is then demonstrated for an in vivo test case in which an extending maize root in field-derived soil was imaged hourly using XCT over a growth period of 19h. This allowed full-field soil deformation data and 3D root tip dynamics to be quantified in parallel for the first time. This fusion of methods paves the way for comparative studies of contrasting soils and plant genotypes, improving our understanding of the fundamental mechanical processes which influence root system development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Three-dimensional optical micro-angiography maps directional blood perfusion deep within microcirculation tissue beds in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruikang K [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97237 (United States)

    2007-12-07

    Optical micro-angiography (OMAG) is a recently developed method of imaging localized blood perfusion at capillary level resolution within microcirculatory beds. This paper reports that the OMAG is capable of directional blood perfusion mapping in vivo. This is achieved simply by translating the mirror located in the reference arm back and forth while 3D imaging is performed. The mirror which moves toward the incident beam gives the blood perfusion that flows away from the beam direction and vice versa. The approach is experimentally demonstrated by imaging of a flow phantom and then cerebro-vascular perfusion of a live mouse with cranium intact.

  15. Macrophage solubilization and cytotoxicity of indium-containing particles as in vitro correlates to pulmonary toxicity in vivo.

    Science.gov (United States)

    Gwinn, William M; Qu, Wei; Bousquet, Ronald W; Price, Herman; Shines, Cassandra J; Taylor, Genie J; Waalkes, Michael P; Morgan, Daniel L

    2015-03-01

    Macrophage-solubilized indium-containing particles (ICPs) were previously shown in vitro to be cytotoxic. In this study, we compared macrophage solubilization and cytotoxicity of indium phosphide (InP) and indium-tin oxide (ITO) with similar particle diameters (∼ 1.5 µm) and then determined if relative differences in these in vitro parameters correlated with pulmonary toxicity in vivo. RAW 264.7 macrophages were treated with InP or ITO particles and cytotoxicity was assayed at 24 h. Ionic indium was measured in 24 h culture supernatants. Macrophage cytotoxicity and particle solubilization in vitro were much greater for InP compared with ITO. To correlate changes in vivo, B6C3F1 mice were treated with InP or ITO by oropharyngeal aspiration. On Days 14 and 28, bronchoalveolar lavage (BAL) and pleural lavage (PL) fluids were collected and assayed for total leukocytes. Cell differentials, lactate dehydrogenase activity, and protein levels were also measured in BAL. All lavage parameters were greatly increased in mice treated with InP compared with ITO. These data suggest that macrophage solubilization and cytotoxicity of some ICPs in vitro are capable of predicting pulmonary toxicity in vivo. In addition, these differences in toxicity were observed despite the two particulate compounds containing similar amounts of indium suggesting that solubilization, not total indium content, better reflects the toxic potential of some ICPs. Soluble InCl3 was shown to be more cytotoxic than InP to macrophages and lung epithelial cells in vitro further suggesting that ionic indium is the primary cytotoxic component of InP. Published by Oxford University Press on behalf of the Society of Toxicology 2014. This work is written by US Government employees and is in the public domain in the US.

  16. Correlating In Vitro Splice Switching Activity With Systemic In Vivo Delivery Using Novel ZEN-modified Oligonucleotides

    Directory of Open Access Journals (Sweden)

    Suzan M Hammond

    2014-01-01

    Full Text Available Splice switching oligonucleotides (SSOs induce alternative splicing of pre-mRNA and typically employ chemical modifications to increase nuclease resistance and binding affinity to target pre-mRNA. Here we describe a new SSO non-base modifier (a naphthyl-azo group, “ZEN™” to direct exon exclusion in mutant dystrophin pre-mRNA to generate functional dystrophin protein. The ZEN modifier is placed near the ends of a 2′-O-methyl (2′OMe oligonucleotide, increasing melting temperature and potency over unmodified 2′OMe oligonucleotides. In cultured H2K cells, a ZEN-modified 2′OMe phosphorothioate (PS oligonucleotide delivered by lipid transfection greatly enhanced dystrophin exon skipping over the same 2′OMePS SSO lacking ZEN. However, when tested using free gymnotic uptake in vitro and following systemic delivery in vivo in dystrophin deficient mdx mice, the same ZEN-modified SSO failed to enhance potency. Importantly, we show for the first time that in vivo activity of anionic SSOs is modelled in vitro only when using gymnotic delivery. ZEN is thus a novel modifier that enhances activity of SSOs in vitro but will require improved delivery methods before its in vivo clinical potential can be realized.

  17. Cytotoxic activity of metformin in vitro does not correlate with its antitumor action in vivo.

    Science.gov (United States)

    Pyaskovskaya, O N; Kolesnik, D L; Fedorchuk, A G; Gorbik, G V; Solyanik, G I

    2017-12-01

    It is known that metformin is a hypoglycemic drug used to treat type II diabetes mellitus. Recently active studies of its antitumor activity in relation to different types of malignant cells are conducted. To determine the relationship between cytotoxic activity of metformin in vitro and its antitumor activity in vivo. The rat C6 glioma cell line and mouse Lewis lung carcinoma cells (LLC) were used in this work. The number of living cells in the cytotoxic test was evaluated using sulforhodamine B. Parameters of tumor cell susceptibility to metformin activity in vitro were calculated using nonlinear and linear regression of experimental data. The antitumor action of metformin in vivo was evaluated routinely by the extension of survival time (ST) (in rats with intracerebral C6 glioma) and its effect on the volume of the primary tumor, the number and volume of metastases (in mice with LLC). In cultured LLC cells in vitro, the proportions of metformin-resistant (A1, %) and metformin-sensitive (A2, %) subpopulations were 10.0 ± 2.2% and 92.0 ± 3.5%, respectively, in terms of the total number of living cells. Parameter t, which characterizes the sensitivity of cancer cells to metformin action (the lower is the value of this parameter the higher is sensitivity of cells to metformin cytotoxicity), for metformin-resistant and metformin-sensitive subpopulations was: t1(mM) = ∞ and t2(mM) = 2.9 ± 0.3, correspondingly. For metformin-sensitive subpopulation of LLC cells IC50 (mM) = 2.42 ± 0.34. The volume of the primary tumor, the amount and volume of metastases in mice receiving metformin at a dose of Dmin (0.15 g/kg) and Dmax (0.3 g/kg) values did not significantly differ from those in the control. However, in the case of Dmin, there was a tendency to increased volume of the primary tumor, in the case of Dmax, there was a tendency to increased volume of metastases. The analogical parameters (A1, A2, b1, b2, IC50 (1), IC50 (2)) characterizing cell sensitivity

  18. In vivo dentate nucleus MRI relaxometry correlates with previous administration of Gadolinium-based contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Tedeschi, Enrico; Canna, Antonietta; Cocozza, Sirio; Russo, Carmela; Angelini, Valentina; Brunetti, Arturo [University ' ' Federico II' ' , Neuroradiology, Department of Advanced Biomedical Sciences, Naples (Italy); Palma, Giuseppe; Quarantelli, Mario [National Research Council, Institute of Biostructure and Bioimaging, Naples (Italy); Borrelli, Pasquale; Salvatore, Marco [IRCCS SDN, Naples (Italy); Lanzillo, Roberta; Postiglione, Emanuela; Morra, Vincenzo Brescia [University ' ' Federico II' ' , Department of Neurosciences, Reproductive and Odontostomatological Sciences, Naples (Italy)

    2016-12-15

    To evaluate changes in T1 and T2* relaxometry of dentate nuclei (DN) with respect to the number of previous administrations of Gadolinium-based contrast agents (GBCA). In 74 relapsing-remitting multiple sclerosis (RR-MS) patients with variable disease duration (9.8±6.8 years) and severity (Expanded Disability Status Scale scores:3.1±0.9), the DN R1 (1/T1) and R2* (1/T2*) relaxation rates were measured using two unenhanced 3D Dual-Echo spoiled Gradient-Echo sequences with different flip angles. Correlations of the number of previous GBCA administrations with DN R1 and R2* relaxation rates were tested, including gender and age effect, in a multivariate regression analysis. The DN R1 (normalized by brainstem) significantly correlated with the number of GBCA administrations (p<0.001), maintaining the same significance even when including MS-related factors. Instead, the DN R2* values correlated only with age (p=0.003), and not with GBCA administrations (p=0.67). In a subgroup of 35 patients for whom the administered GBCA subtype was known, the effect of GBCA on DN R1 appeared mainly related to linear GBCA. In RR-MS patients, the number of previous GBCA administrations correlates with R1 relaxation rates of DN, while R2* values remain unaffected, suggesting that T1-shortening in these patients is related to the amount of Gadolinium given. (orig.)

  19. Direct and correlated responses to selection for total weight of lamb ...

    African Journals Online (AJOL)

    Unknown

    South African Society of Animal Science. The South African Journal of Animal Science is available online at http://www.sasas.co.za/Sajas.html. 115. Direct and correlated responses to selection for total weight of lamb weaned in. Merino sheep. W.J. Olivier# 1, M.A. Snyman1, J.J. Olivier2, J.B. van Wyk3 and G.J. Erasmus3.

  20. Prediction of direct and indirect genetic gains and genotypic correlations in rubber tree progenies

    Directory of Open Access Journals (Sweden)

    Cecília Khusala Verardi

    2011-09-01

    Full Text Available The objective of this work was to estimate the genetic parameters, genotypic and phenotypic correlations, and direct and indirect genetic gains among and within rubber tree (Hevea brasiliensis progenies. The experiment was set up at the Municipality of Jaú, SP, Brazil. A randomized complete block design was used, with 22 treatments (progenies, 6 replicates, and 10 plants per plot at a spacing of 3x3 m. Three‑year‑old progenies were assessed for girth, rubber yield, and bark thickness by direct and indirect gains and genotypic correlations. The number of latex vessel rings showed the best correlations, correlating positively and significantly with girth and bark thickness. Selection gains among progenies were greater than within progeny for all the variables analyzed. Total gains obtained were high, especially for girth increase and rubber yield, which were 93.38 and 105.95%, respectively. Young progeny selection can maximize the expected genetic gains, reducing the rubber tree selection cycle.

  1. Electrical resistivity and spatial variation in agriculture terraces: statistical correlation between ert and flow direction algorithms

    Directory of Open Access Journals (Sweden)

    Fernandes J.

    2017-02-01

    Full Text Available The construction of earthen embankment terraces in the Douro Region raises a set of problems related to hydrological processes. The main objective of this study is the evaluation of the spatial variation of electrical resistivity in agriculture terraces at Douro valley (Portugal. To achieve this objective, two variables are analysed, the soil electrical resistivity and the flow direction algorithm. In a field survey we recorded 13 electrical resistivity profiles. The contributing area was calculated with the algorithms D∞ (Deterministic Infinity Flow and MFD (Multiple Flow Direction and the results are the base of the internal runoff modelling, both supported by the digital elevation model with a spatial resolution of 1m2. A correlation between the spatial variation of the soil electrical resistivity represented by the standard deviation of the electrical resistivity for each profile and the average value of the contributing area coincident with each profile was established. The electrical resistivity standard deviation seems to be moderately well correlated according to the D∞ algorithm at about 1m of depth, and it has a good correlation at 1,5m to 2m of depth with the MFD algorithm. Taken together, the results show a significant positive statistical correlation between the electrical resistivity standard deviation and the contributing areas (MFD and D∞ depending on the soil depth.

  2. In vivo optical molecular imaging of matrix metalloproteinase activity in abdominal aortic aneurysms correlates with treatment effects on growth rate.

    Science.gov (United States)

    Sheth, Rahul A; Maricevich, Marco; Mahmood, Umar

    2010-09-01

    We present a method to quantify the inflammatory processes that drive abdominal aortic aneurysm (AAA) development that may help predict the rate of growth and thus guide medical and surgical management. We use an in vivo optical molecular imaging approach to quantify protease activity within the walls of AAAs in a rodent model. AAAs were generated in mice by topical application of calcium chloride, followed by the administration of the MMP inhibitor doxycycline for 3 months. After this time period, an enzyme-activatable optical molecular imaging agent sensitive to MMP activity was administered, and MMP proteolytic activity was measured in vivo. Histology and in situ zymography were performed for validation. AAAs were also generated in rats, and MMP activity within the walls of the AAAs was also quantified endovascularly. A dose-dependent response of AAA growth rate to doxycycline administration was demonstrated, with high doses of the drug resulting in nearly complete suppression of aneurysm formation. There was a direct relationship between the rate of aneurysmal growth and measured MMP activity, with a linear best-fit well approximating the relationship. We additionally performed endovascular imaging of AAAs in rats and demonstrated a similar suppression of intramural MMP activity following doxycycline administration. We present an in vivo evaluation of MMP activity within the walls of AAAs in rodents and show a direct, linear relationship between proteolytic activity and aneurysmal growth. We also illustrate that this functional imaging method can be performed endovascularly, demonstrating potential pre-clinical and clinical applications. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Chronological changes of radiofrequency ablation zone in rabbit liver: an in vivo correlation between gross pathology and histopathology.

    Science.gov (United States)

    Song, Kyoung D; Lee, Min Woo; Rhim, Hyunchul; Kang, Tae Wook; Cha, Dong Ik; Yang, Jehoon

    2017-03-01

    To examine the gross pathology and histopathology of ablation zones created from radiofrequency (RF) ablation and to correlate their chronological changes. A total of 48 in vivo ablation zones (16 rabbit livers) were obtained immediately after and also 30 min, 1 h and 2 h after RF ablation and were subjected to haematoxylin and eosin (H&E) staining, nicotinamide adenine dinucleotide (NADH) diaphorase staining, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining. Chronological changes in gross pathology and histopathology were evaluated and correlated with each other. Peripheral red zones on gross pathology correlated with peripheral zones on H&E staining, lightly stained peripheral zones on NADH staining and peripheral positive zones on TUNEL staining. Central white zones on gross pathology correlated with combined central and border zones on H&E staining, central negative zones on NADH staining and combined central-positive and middle-negative zones on TUNEL staining. Boundary visibility between central white and peripheral red zones on gross pathology was significantly higher at 1 and 2 h than immediately after RF ablation. As time increased after RF ablation, visibility of the border zone on H&E staining and the grade of positively stained hepatocytes in the peripheral zone on TUNEL staining increased. Chronological changes in gross pathology of RF ablation zones correlated well with histopathology. The boundary between the central white and peripheral red zones tended to become clear at 1 h after RF ablation. Advances in knowledge: (1) RF ablation zones show chronological changes on gross pathology and histopathology. (2) Gross pathology and histopathology correlate well with each other.

  4. Histological correlation of 7 T multi-parametric MRI performed in ex-vivo Achilles tendon

    Energy Technology Data Exchange (ETDEWEB)

    Juras, Vladimir [Center of Excellence for High Field MR, Department of Radiology, Medical University of Vienna Waehringer Guertel 18-20, A-1090, Vienna (Austria); Institute of Measurement Science, Department of Imaging Methods, Dubravska cesta 9, 84104, Bratislava (Slovakia); Apprich, Sebastian; Pressl, Christina; Zbyn, Stefan [Center of Excellence for High Field MR, Department of Radiology, Medical University of Vienna Waehringer Guertel 18-20, A-1090, Vienna (Austria); Szomolanyi, Pavol [Center of Excellence for High Field MR, Department of Radiology, Medical University of Vienna Waehringer Guertel 18-20, A-1090, Vienna (Austria); Institute of Measurement Science, Department of Imaging Methods, Dubravska cesta 9, 84104, Bratislava (Slovakia); Domayer, Stephan; Hofstaetter, Jochen G. [Department of Orthopedic Surgery, Vienna General Hospital, Medical University of Vienna, A-1090 Vienna (Austria); Trattnig, Siegfried, E-mail: siegfried.trattnig@meduniwien.ac.at [Center of Excellence for High Field MR, Department of Radiology, Medical University of Vienna Waehringer Guertel 18-20, A-1090, Vienna (Austria)

    2013-05-15

    Introduction: The goal of this in vitro validation study was to investigate the feasibility of biochemical MRI techniques, such as sodium imaging, T{sub 2} mapping, fast imaging with steady state precession (FISP), and reversed FISP (PSIF), as potential markers for collagen, glycosaminoglycan and water content in the Achilles tendon. Materials and methods: Five fresh cadaver ankles acquired from a local anatomy department were used in the study. To acquire a sodium signal from the Achilles tendon, a 3D-gradient-echo sequence, optimized for sodium imaging, was used with TE = 7.71 ms and TR = 17 ms. The T{sub 2} relaxation times were obtained using a multi-echo, spin-echo technique with a repetition time (TR) of 1200 ms and six echo times. A 3D, partially balanced, steady-state gradient echo pulse sequence was used to acquire FISP and PSIF images, with TR/TE = 6.96/2.46 ms. MRI parameters were correlated with each other, as well as with histologically assessed glycosaminoglycan and water content in cadaver Achilles tendons. Results: The highest relevant Pearson correlation coefficient was found between sodium SNR and glycosaminoglycan content (r = 0.71, p = 0.007). Relatively high correlation was found between the PSIF signal and T{sub 2} values (r = 0.51, p = 0.036), and between the FISP signal and T{sub 2} values (r = 0.56, p = 0.047). Other correlations were found to be below the moderate level. Conclusion: This study demonstrated the feasibility of progressive biochemical MRI methods for the imaging of the AT. A GAG-specific, contrast-free method (sodium imaging), as well as collagen- and water-sensitive methods (T{sub 2} mapping, FISP, PSIF), may be used in fast-relaxing tissues, such as tendons, in reasonable scan times.

  5. Cortical microinfarcts detected in vivo on 3 Tesla MRI: clinical and radiological correlates.

    Science.gov (United States)

    van Dalen, Jan Willem; Scuric, Eva E M; van Veluw, Susanne J; Caan, Matthan W A; Nederveen, Aart J; Biessels, Geert Jan; van Gool, Willem A; Richard, Edo

    2015-01-01

    Cortical microinfarcts (CMIs) are a common postmortem finding associated with vascular risk factors, cognitive decline, and dementia. Recently, CMIs identified in vivo on 7 Tesla MRI also proved retraceable on 3 Tesla MRI. We evaluated CMIs on 3 Tesla MRI in a population-based cohort of 194 nondemented older people (72-80 years) with systolic hypertension. Using a case-control design, participants with and without CMIs were compared on age, sex, cardiovascular risk factors, and white matter hyperintensity volume. We identified 23 CMIs in 12 participants (6%). CMIs were associated with older age, higher diastolic blood pressure, and a history of recent stroke. There was a trend for a higher white matter hyperintensity volume in participants with CMIs. We found an association of CMIs with clinical parameters, including age and cardiovascular risk factors. Although the prevalence of CMIs is relatively low, our results suggest that the study of CMIs in larger clinical studies is possible using 3 Tesla MRI. This opens the possibility of large-scale prospective investigation of the clinical relevance of CMIs in older people. © 2014 American Heart Association, Inc.

  6. In vitro selection criteria for probiotic bacteria of human origin: correlation with in vivo findings.

    Science.gov (United States)

    Dunne, C; O'Mahony, L; Murphy, L; Thornton, G; Morrissey, D; O'Halloran, S; Feeney, M; Flynn, S; Fitzgerald, G; Daly, C; Kiely, B; O'Sullivan, G C; Shanahan, F; Collins, J K

    2001-02-01

    The enteric flora comprises approximately 95% of the total number of cells in the human body and can elicit immune responses while protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract may also be implicated in the pathogenesis of diseases such as inflammatory bowel disease (ulcerative colitis and Crohn disease). The objectives of the Probiotic Research Group based at University College Cork were to isolate and identify lactic acid bacteria exhibiting beneficial probiotic traits, such as bile tolerance in the absence of deconjugation activity, acid resistance, adherence to host epithelial tissue, and in vitro antagonism of pathogenic microorganisms or those suspected of promoting inflammation. To isolate potentially effective probiotic bacteria, we screened the microbial population adhering to surgically resected segments of the gastrointestinal tract (the environment in which they may subsequently be reintroduced and required to function). In total, 1500 bacterial strains from resected human terminal ilea were assessed. From among these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was selected for further study. In mouse feeding trials, milk-borne L. salivarius strain UCC118 could successfully colonize the murine gastrointestinal tract. A human feeding study conducted in 80 healthy volunteers showed that yogurt can be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. In summary, we developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host such as modulation of gastrointestinal tract microflora.

  7. In vivo features of melanocytic lesions: multimode hyperspectral dermoscopy, reflectance confocal microscopy, and histopathologic correlates (Conference Presentation)

    Science.gov (United States)

    Vasefi, Fartash; MacKinnon, Nicholas B.; Jain, Manu; Cordova, Miguel A.; Kose, Kivanc; Rajadhyaksha, Milind; Halpern, Allan C.; Farkas, Daniel L.

    2017-02-01

    Motivation and background: Melanoma, the fastest growing cancer worldwide, kills more than one person every hour in the United States. Determining the depth and distribution of dermal melanin and hemoglobin adds physio-morphologic information to the current diagnostic standard, cellular morphology, to further develop noninvasive methods to discriminate between melanoma and benign skin conditions. Purpose: To compare the performance of a multimode dermoscopy system (SkinSpect), which is designed to quantify and map in three dimensions, in vivo melanin and hemoglobin in skin, and to validate this with histopathology and three dimensional reflectance confocal microscopy (RCM) imaging. Methods: Sequentially capture SkinSpect and RCM images of suspect lesions and nearby normal skin and compare this with histopathology reports, RCM imaging allows noninvasive observation of nuclear, cellular and structural detail in 1-5 μm-thin optical sections in skin, and detection of pigmented skin lesions with sensitivity of 90-95% and specificity of 70-80%. The multimode imaging dermoscope combines polarization (cross and parallel), autofluorescence and hyperspectral imaging to noninvasively map the distribution of melanin, collagen and hemoglobin oxygenation in pigmented skin lesions. Results: We compared in vivo features of ten melanocytic lesions extracted by SkinSpect and RCM imaging, and correlated them to histopathologic results. We present results of two melanoma cases (in situ and invasive), and compare with in vivo features from eight benign lesions. Melanin distribution at different depths and hemodynamics, including abnormal vascularity, detected by both SkinSpect and RCM will be discussed. Conclusion: Diagnostic features such as dermal melanin and hemoglobin concentration provided in SkinSpect skin analysis for melanoma and normal pigmented lesions can be compared and validated using results from RCM and histopathology.

  8. A study of the dynamics of PTEN proteins in living cells using in vivo fluorescence correlation spectroscopy

    Science.gov (United States)

    Du, Zhixue; Dong, Chaoqing; Ren, Jicun

    2017-06-01

    PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most important tumor-suppressor proteins, which plays a key role in negative regulation of the PI3K/AKT pathway, and governs many cellular processes including growth, proliferation, survival and migration. The dynamics of PTEN proteins in single living cells is as yet unclear owing to a shortage of suitable in vivo approaches. Here, we report a single-molecule method for in vivo study of the dynamics of PTEN proteins in living cells using fluorescence correlation spectroscopy (FCS). First, we established a monoclonal H1299 stable cell line expressing enhanced green fluorescent protein (EGFP) and PTEN (EGFP-PTEN) fusion proteins; we then developed an in vivo FCS method to study the dynamics of EGFP-PTEN both in the nucleus and the cytoplasm. We investigated the diffusion behaviors of EGFP and EGFP-PTEN in solution, nucleus and cytosol, and observed that the motion of PTEN in living cells was restricted compared with EGFP. Finally, we investigated the protein dynamics in living cells under oxidative stress stimulation and a cellular ATP depletion treatment. Under oxidative stress stimulation, the EGFP-PTEN concentration increased in the nucleus, but slightly decreased in the cytoplasm. The diffusion coefficient and alpha value of EGFP-PTEN reduced significantly both in the nucleus and cytoplasm; the significantly decreased alpha parameter indicates a more restricted Brownian diffusion behavior. Under the cellular ATP depletion treatment, the concentration of EGFP-PTEN remained unchanged in the nucleus and decreased significantly in cytosol. The diffusion coefficient of EGFP-PTEN decreased significantly in cytosol, but showed no significant change in the nucleus; the alpha value decreased significantly in both the nucleus and cytoplasm. These results suggest that the concentration and mobility of PTEN in the nucleus and cytoplasm can be regulated by stimulation methods. Our approach provides a unique

  9. Disease quantification in dermatology: in vivo near-infrared spectroscopy measures correlate strongly with the clinical assessment of psoriasis severity

    Science.gov (United States)

    Greve, Tanja Maria; Kamp, Søren; Jemec, Gregor B. E.

    2013-03-01

    Accurate documentation of disease severity is a prerequisite for clinical research and the practice of evidence-based medicine. The quantification of skin diseases such as psoriasis currently relies heavily on clinical scores. Although these clinical scoring methods are well established and very useful in quantifying disease severity, they require an extensive clinical experience and carry a risk of subjectivity. We explore the opportunity to use in vivo near-infrared (NIR) spectra as an objective and noninvasive method for local disease severity assessment in 31 psoriasis patients in whom selected plaques were scored clinically. A partial least squares (PLS) regression model was used to analyze and predict the severity scores on the NIR spectra of psoriatic and uninvolved skin. The correlation between predicted and clinically assigned scores was R=0.94 (RMSE=0.96), suggesting that in vivo NIR provides accurate clinical quantification of psoriatic plaques. Hence, NIR may be a practical solution to clinical severity assessment of psoriasis, providing a continuous, linear, numerical value of severity.

  10. Correlation between In Vitro and In Vivo Antifungal Activities in Experimental Fluconazole-Resistant Oropharyngeal and Esophageal Candidiasis

    Science.gov (United States)

    Walsh, Thomas J.; Gonzalez, Corina E.; Piscitelli, Steven; Bacher, John D.; Peter, Joanne; Torres, Richard; Shetti, Daiva; Katsov, Victoria; Kligys, Kristina; Lyman, Caron A.

    2000-01-01

    Oropharyngeal and esophageal candidiasis (OPEC) is a frequent opportunistic mycosis in immunocompromised patients. Azole-resistant OPEC is a refractory form of this infection occurring particularly in human immunodeficiency virus (HIV)-infected patients. The procedures developed by the Antifungal Subcommittee of the National Committee for Clinical Laboratory Standards (NCCLS) are an important advance in standardization of in vitro antifungal susceptibility methodology. In order to further understand the relationship between NCCLS methodology and antifungal therapeutic response, we studied the potential correlation between in vitro susceptibility to fluconazole and in vivo response in a rabbit model of fluconazole-resistant OPEC. MICs of fluconazole were determined by NCCLS methods. Three fluconazole-susceptible (FS) (MIC, ≤0.125 μg/ml) and three fluconazole-resistant (FR) (MIC, ≥64 μg/ml) isolates of Candida albicans from prospectively monitored HIV-infected children with OPEC were studied. FR isolates were recovered from children with severe OPEC refractory to fluconazole, and FS isolates were recovered from those with mucosal candidiasis responsive to fluconazole. Fluconazole at 2 mg/kg of body weight/day was administered to infected animals for 7 days. The concentrations of fluconazole in plasma were maintained above the MICs for FS isolates throughout the dosing interval. Fluconazole concentrations in the esophagus were greater than or equal to those in plasma. Rabbits infected with FS isolates and treated with fluconazole had significant reductions in oral mucosal quantitative cultures (P < 0.001) and tissue burden of C. albicans in tongue, soft palate, and esophagus (P < 0.001). In comparison, rabbits infected with FR isolates were unresponsive to fluconazole and had no reduction in oral mucosal quantitative cultures or tissue burden of C. albicans versus untreated controls. We conclude that there is a strong correlation between in vitro fluconazole

  11. Direct Generation and Detection of Quantum Correlated Photons with 3.2 um Wavelength Spacing.

    Science.gov (United States)

    Sua, Yong Meng; Fan, Heng; Shahverdi, Amin; Chen, Jia-Yang; Huang, Yu-Ping

    2017-12-13

    Quantum correlated, highly non-degenerate photons can be used to synthesize disparate quantum nodes and link quantum processing over incompatible wavelengths, thereby constructing heterogeneous quantum systems for otherwise unattainable superior performance. Existing techniques for correlated photons have been concentrated in the visible and near-IR domains, with the photon pairs residing within one micron. Here, we demonstrate direct generation and detection of high-purity photon pairs at room temperature with 3.2 um wavelength spacing, one at 780 nm to match the rubidium D2 line, and the other at 3950 nm that falls in a transparent, low-scattering optical window for free space applications. The pairs are created via spontaneous parametric downconversion in a lithium niobate waveguide with specially designed geometry and periodic poling. The 780 nm photons are measured with a silicon avalanche photodiode, and the 3950 nm photons are measured with an upconversion photon detector using a similar waveguide, which attains 34% internal conversion efficiency. Quantum correlation measurement yields a high coincidence-to-accidental ratio of 54, which indicates the strong correlation with the extremely non-degenerate photon pairs. Our system bridges existing quantum technology to the challenging mid-IR regime, where unprecedented applications are expected in quantum metrology and sensing, quantum communications, medical diagnostics, and so on.

  12. Directed percolation process in the presence of velocity fluctuations: Effect of compressibility and finite correlation time

    Science.gov (United States)

    Antonov, N. V.; Hnatič, M.; Kapustin, A. S.; Lučivjanský, T.; Mižišin, L.

    2016-01-01

    The direct bond percolation process (Gribov process) is studied in the presence of random velocity fluctuations generated by the Gaussian self-similar ensemble with finite correlation time. We employ the renormalization group in order to analyze a combined effect of the compressibility and finite correlation time on the long-time behavior of the phase transition between an active and an absorbing state. The renormalization procedure is performed to the one-loop order. Stable fixed points of the renormalization group and their regions of stability are calculated in the one-loop approximation within the three-parameter (ɛ ,y ,η ) expansion. Different regimes corresponding to the rapid-change limit and frozen velocity field are discussed, and their fixed points' structure is determined in numerical fashion.

  13. Metformin Accumulation Correlates with Organic Cation Transporter 2 Protein Expression and Predicts Mammary Tumor Regression In Vivo.

    Science.gov (United States)

    Checkley, L Allyson; Rudolph, Michael C; Wellberg, Elizabeth A; Giles, Erin D; Wahdan-Alaswad, Reema S; Houck, Julie A; Edgerton, Susan M; Thor, Ann D; Schedin, Pepper; Anderson, Steven M; MacLean, Paul S

    2017-03-01

    Several epidemiologic studies have associated metformin treatment with a reduction in breast cancer incidence in prediabetic and type II diabetic populations. Uncertainty exists regarding which patient populations and/or tumor subtypes will benefit from metformin treatment, and most preclinical in vivo studies have given little attention to the cellular pharmacology of intratumoral metformin uptake. Epidemiologic reports consistently link western-style high fat diets (HFD), which drive overweight and obesity, with increased risk of breast cancer. We used a rat model of HFD-induced overweight and mammary carcinogenesis to define intratumoral factors that confer metformin sensitivity. Mammary tumors were initiated with 1-methyl-1-nitrosourea, and rats were randomized into metformin-treated (2 mg/mL drinking water) or control groups (water only) for 8 weeks. Two-thirds of existing mammary tumors responded to metformin treatment with decreased tumor volumes (P 0.11 cm3 reduction in tumor volume. Metformin treatment also decreased proinflammatory arachidonic acid >1.5-fold in responsive tumors (P = 0.023). Collectively, these preclinical data provide evidence for a direct effect of metformin in vivo and suggest that OCT2 expression may predict metformin uptake and tumor response. Cancer Prev Res; 10(3); 198-207. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Loss of pluripotency in human embryonic stem cells directly correlates with an increase in nuclear zinc.

    Directory of Open Access Journals (Sweden)

    Janet L Wolford

    Full Text Available The pluripotency of human embryonic stem cells (hESCs is important to investigations of early development and to cell replacement therapy, but the mechanism behind pluripotency is incompletely understood. Zinc has been shown to play a key role in differentiation of non-pluripotent cell types, but here its role in hESCs is directly examined. By mapping the distribution of metals in hESCs at high resolution by x-ray fluorescence microprobe (XFM and by analyzing subcellular metal content, we have found evidence that loss of pluripotency is directly correlated with an increase in nuclear zinc. Zinc elevation not only redefines our understanding of the mechanisms that support pluripotency, but also may act as a biomarker and an intervention point for stem cell differentiation.

  15. Direct identification of base-paired RNA nucleotides by correlated chemical probing.

    Science.gov (United States)

    Krokhotin, Andrey; Mustoe, Anthony M; Weeks, Kevin M; Dokholyan, Nikolay V

    2017-01-01

    Many RNA molecules fold into complex secondary and tertiary structures that play critical roles in biological function. Among the best-established methods for examining RNA structure are chemical probing experiments, which can report on local nucleotide structure in a concise and extensible manner. While probing data are highly useful for inferring overall RNA secondary structure, these data do not directly measure through-space base-pairing interactions. We recently introduced an approach for single-molecule correlated chemical probing with dimethyl sulfate (DMS) that measures RNA interaction groups by mutational profiling (RING-MaP). RING-MaP experiments reveal diverse through-space interactions corresponding to both secondary and tertiary structure. Here we develop a framework for using RING-MaP data to directly and robustly identify canonical base pairs in RNA. When applied to three representative RNAs, this framework identified 20%-50% of accepted base pairs with a RNA Society.

  16. Loss of pluripotency in human embryonic stem cells directly correlates with an increase in nuclear zinc.

    Energy Technology Data Exchange (ETDEWEB)

    Finney, L.; Vogt, S.; Wolford, J. L.; Chishti, Y.; Jin, Q.; Ward, J.; Chen, L. (Biosciences Division); ( XSD)

    2010-01-01

    The pluripotency of human embryonic stem cells (hESCs) is important to investigations of early development and to cell replacement therapy, but the mechanism behind pluripotency is incompletely understood. Zinc has been shown to play a key role in differentiation of non-pluripotent cell types, but here its role in hESCs is directly examined. By mapping the distribution of metals in hESCs at high resolution by x-ray fluorescence microprobe (XFM) and by analyzing subcellular metal content, we have found evidence that loss of pluripotency is directly correlated with an increase in nuclear zinc. Zinc elevation not only redefines our understanding of the mechanisms that support pluripotency, but also may act as a biomarker and an intervention point for stem cell differentiation.

  17. Correlation Between Sonographic and In Vivo Measurement of A1 Pulleys in Trigger Fingers.

    Science.gov (United States)

    Spirig, Andres; Juon, Bettina; Banz, Yara; Rieben, Robert; Vögelin, Esther

    2016-07-01

    The thickness of 210 A1 pulleys of 21 male and female healthy volunteers in two different age groups (20-35 y and 50-70 y) were measured by ultrasound. In a second group, the thickness of 15 diseased A1 pulleys and 15 A1 pulleys of the corresponding other hand of 10 patients with the clinical diagnosis of trigger finger were measured by ultrasound. During open trigger finger release, a strip of A1 pulley was excised and immediately measured using an electronic caliper. The average pulley thickness of healthy volunteers was 0.43-0.47 mm, compared to 0.77-0.79 mm in patients with trigger finger. Based on the receiver operating characteristic (ROC) curve, a diagnostic cut-off value of the pulley thickness at 0.62 mm was defined in order to differ a trigger finger from a healthy finger (sensitivity and specificity of 85%). The correlation between sonographic and effective intra-operative measurements of pulley thickness was linear and very strong (Pearson coefficient 0.86-0.90). In order to distinguish between healthy and diseased A1 pulleys, 0.62 mm is a simple value to use, which can be applied regardless of age, sex, body mass index (BMI) and height in adults. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  18. Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori

    DEFF Research Database (Denmark)

    Santos, Rita S; Dakwar, George R; Xiong, Ranhua

    2015-01-01

    Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid...... mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical...... barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without...

  19. Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo.

    Science.gov (United States)

    Bruno, Robert D; Fleming, Jodie M; George, Andrea L; Boulanger, Corinne A; Schedin, Pepper; Smith, Gilbert H

    2017-01-10

    Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo.

  20. Direct Quantification of Solute Diffusivity in Agarose and Articular Cartilage Using Correlation Spectroscopy.

    Science.gov (United States)

    Shoga, Janty S; Graham, Brian T; Wang, Liyun; Price, Christopher

    2017-10-01

    Articular cartilage is an avascular tissue; diffusive transport is critical for its homeostasis. While numerous techniques have been used to quantify diffusivity within porous, hydrated tissues and tissue engineered constructs, these techniques have suffered from issues regarding invasiveness and spatial resolution. In the present study, we implemented and compared two separate correlation spectroscopy techniques, fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), for the direct, and minimally-invasive quantification of fluorescent solute diffusion in agarose and articular cartilage. Specifically, we quantified the diffusional properties of fluorescein and Alexa Fluor 488-conjugated dextrans (3k and 10k) in aqueous solutions, agarose gels of varying concentration (i.e. 1, 3, 5%), and in different zones of juvenile bovine articular cartilage explants (i.e. superficial, middle, and deep). In agarose, properties of solute diffusion obtained via FCS and RICS were inversely related to molecule size, gel concentration, and applied strain. In cartilage, the diffusional properties of solutes were similarly dependent upon solute size, cartilage zone, and compressive strain; findings that agree with work utilizing other quantification techniques. In conclusion, this study established the utility of FCS and RICS as simple and minimally invasive techniques for quantifying microscale solute diffusivity within agarose constructs and articular cartilage explants.

  1. Ex vivo tissue imaging of human glioblastoma using a small bore 7T MRI and correlation with digital pathology and proteomics profiling

    Science.gov (United States)

    Matsuda, Kant M.; Lopes-Calcas, Ana; Magyar, Thalia; O'Brien-Moran, Zoe; Buist, Richard; Martin, Melanie

    2017-03-01

    Recent advancement in MRI established multi-parametric imaging for in vivo characterization of pathologic changes in brain cancer, which is expected to play a role in imaging biomarker development. Diffusion Tensor Imaging (DTI) is a prime example, which has been deployed for assessment of therapeutic response via analysis of apparent diffusion coefficient (ADC) / mean diffusivity (MD) values. They have been speculated to reflect apoptosis/necrosis. As newer medical imaging emerges, it is essential to verify that apparent abnormal features in imaging correlate with histopathology. Furthermore, the feasibility of imaging correlation with molecular profile should be explored in order to enhance the potential of biomedical imaging as a reliable biomarker. We focus on glioblastoma, which is an aggressive brain cancer. Despite the increased number of studies involving DTI in glioblastoma; however, little has been explored to bridge the gap between the molecular biomarkers and DTI data. Due to spatial heterogeneity in, MRI signals, pathologic change and protein expression, precise correlation is required between DTI, pathology and proteomics data in a histoanatomically identical manner. The challenge is obtaining an identical plane from in vivo imaging data that exactly matches with histopathology section. Thus, we propose to incorporate ex vivo tissue imaging to bridge between in vivo imaging data and histopathology. With ex vivo scan of removed tissue, it is feasible to use high-field 7T MRI scanner, which can achieve microscopic resolution. Once histology section showing the identical plane, it is feasible to correlate protein expression by a unique technology, "multiplex tissue immunoblotting".

  2. In vitro-in vivo correlations for nicotine transdermal delivery systems evaluated by both in vitro skin permeation (IVPT) and in vivo serum pharmacokinetics under the influence of transient heat application.

    Science.gov (United States)

    Shin, Soo Hyeon; Thomas, Sherin; Raney, Sam G; Ghosh, Priyanka; Hammell, Dana C; El-Kamary, Samer S; Chen, Wilbur H; Billington, M Melissa; Hassan, Hazem E; Stinchcomb, Audra L

    2018-01-28

    The in vitro permeation test (IVPT) has been widely used to characterize the bioavailability (BA) of compounds applied on the skin. In this study, we performed IVPT studies using excised human skin (in vitro) and harmonized in vivo human serum pharmacokinetic (PK) studies to evaluate the potential in vitro-in vivo correlation (IVIVC) of nicotine BA from two, matrix-type, nicotine transdermal delivery systems (TDS). The study designs used for both in vitro and in vivo studies included 1h of transient heat (42±2°C) application during early or late time periods post-dosing. The goal was to evaluate whether any IVIVC observed would be evident even under conditions of heat exposure, in order to investigate further whether IVPT may have the potential to serve as a possible surrogate method to evaluate the in vivo effects of heat on the bioavailability of a drug delivered from a TDS. The study results have demonstrated that the BA of nicotine characterized by the IVPT studies correlated with and was predictive of the in vivo BA of nicotine from the respective TDS, evaluated under the matched study designs and conditions. The comparisons of single parameters such as steady-state concentration, heat-induced increase in partial AUCs and post-treatment residual content of nicotine in TDS from the in vitro and in vivo data sets showed no significant differences (p≥0.05). In addition, a good point-to-point IVIVC (Level A correlation) for the entire study duration was achieved by predicting in vivo concentrations of nicotine using two approaches: Approach I requiring only an in vitro data set and Approach II involving deconvolution and convolution steps. The results of our work suggest that a well designed IVPT study with adequate controls can be a useful tool to evaluate the relative effects of heat on the BA of nicotine from TDS with different formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Inter-neuronal correlation distinguishes mechanisms of direction selectivity in cortical circuit models

    Science.gov (United States)

    Baker, Pamela M.; Bair, Wyeth

    2012-01-01

    Direction selectivity is a fundamental physiological property that arises from V1 circuitry, yet basic questions of how direction selective (DS) receptive fields are constructed remain unanswered. We built a set of simple, plausible neuronal circuits that produce DS cells via different mechanisms and tested these circuits to determine how they can be distinguished experimentally. Our models consisted of populations of spiking units representing physiological cell classes ranging from LGN cells to V1 complex DS cells. They differed in network architecture and DS mechanism: including linear summation of non-DS simple cell inputs or nonlinear pairwise combinations of non-DS inputs. The circuits also varied in the location of the DS time delay and whether the DS interaction was facilitatory or suppressive. We tested the models with visual stimuli often employed experimentally, including sinusoidal gratings and flashed bars, and computed shuffle-corrected cross-correlograms (CCGs) of spike trains from pairs of units that would be accessible to extracellular recording. We found that CCGs revealed fundamental features of the DS models, including the location of signal delays in the DS circuit and the sign (facilitatory or suppressive) of DS interactions. We also found that correlation was strongly stimulus-dependent, changing with direction and temporal frequency in a manner that generalized across model architectures. Our models make specific predictions for designing, optimizing and interpreting electrophysiology experiments aimed at resolving DS circuitry and provide new insights into mechanisms that could underlie stimulus-dependent correlation. The models are available and easy to explore at www.iModel.org. PMID:22745482

  4. Directly patching high-level exchange-correlation potential based on fully determined optimized effective potentials.

    Science.gov (United States)

    Huang, Chen; Chi, Yu-Chieh

    2017-12-28

    The key element in Kohn-Sham (KS) density functional theory is the exchange-correlation (XC) potential. We recently proposed the exchange-correlation potential patching (XCPP) method with the aim of directly constructing high-level XC potential in a large system by patching the locally computed, high-level XC potentials throughout the system. In this work, we investigate the patching of the exact exchange (EXX) and the random phase approximation (RPA) correlation potentials. A major challenge of XCPP is that a cluster's XC potential, obtained by solving the optimized effective potential equation, is only determined up to an unknown constant. Without fully determining the clusters' XC potentials, the patched system's XC potential is "uneven" in the real space and may cause non-physical results. Here, we developed a simple method to determine this unknown constant. The performance of XCPP-RPA is investigated on three one-dimensional systems: H20, H10Li8, and the stretching of the H19-H bond. We investigated two definitions of EXX: (i) the definition based on the adiabatic connection and fluctuation dissipation theorem (ACFDT) and (ii) the Hartree-Fock (HF) definition. With ACFDT-type EXX, effective error cancellations were observed between the patched EXX and the patched RPA correlation potentials. Such error cancellations were absent for the HF-type EXX, which was attributed to the fact that for systems with fractional occupation numbers, the integral of the HF-type EXX hole is not -1. The KS spectra and band gaps from XCPP agree reasonably well with the benchmarks as we make the clusters large.

  5. Directly patching high-level exchange-correlation potential based on fully determined optimized effective potentials

    Science.gov (United States)

    Huang, Chen; Chi, Yu-Chieh

    2017-12-01

    The key element in Kohn-Sham (KS) density functional theory is the exchange-correlation (XC) potential. We recently proposed the exchange-correlation potential patching (XCPP) method with the aim of directly constructing high-level XC potential in a large system by patching the locally computed, high-level XC potentials throughout the system. In this work, we investigate the patching of the exact exchange (EXX) and the random phase approximation (RPA) correlation potentials. A major challenge of XCPP is that a cluster's XC potential, obtained by solving the optimized effective potential equation, is only determined up to an unknown constant. Without fully determining the clusters' XC potentials, the patched system's XC potential is "uneven" in the real space and may cause non-physical results. Here, we developed a simple method to determine this unknown constant. The performance of XCPP-RPA is investigated on three one-dimensional systems: H20, H10Li8, and the stretching of the H19-H bond. We investigated two definitions of EXX: (i) the definition based on the adiabatic connection and fluctuation dissipation theorem (ACFDT) and (ii) the Hartree-Fock (HF) definition. With ACFDT-type EXX, effective error cancellations were observed between the patched EXX and the patched RPA correlation potentials. Such error cancellations were absent for the HF-type EXX, which was attributed to the fact that for systems with fractional occupation numbers, the integral of the HF-type EXX hole is not -1. The KS spectra and band gaps from XCPP agree reasonably well with the benchmarks as we make the clusters large.

  6. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation.

    Science.gov (United States)

    Chassaing, Benoit; Van de Wiele, Tom; De Bodt, Jana; Marzorati, Massimo; Gewirtz, Andrew T

    2017-08-01

    The intestinal microbiota plays a central role in the development of many chronic inflammatory diseases including IBD and metabolic syndrome. Administration of substances that alter microbiota composition, including the synthetic dietary emulsifiers polysorbate 80 (P80) and carboxymethylcellulose (CMC), can promote such inflammatory disorders. However, that inflammation itself impacts microbiota composition has obfuscated defining the extent to which these compounds or other substances act directly upon the microbiota versus acting on host parameters that promote inflammation, which subsequently reshapes the microbiota. We examined the direct impact of CMC and P80 on the microbiota using the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME) model that maintains a complex stable human microbiota in the absence of a live host. This approach revealed that both P80 and CMC acted directly upon human microbiota to increase its proinflammatory potential, as revealed by increased levels of bioactive flagellin. The CMC-induced increase in flagellin was rapid (1 day) and driven by altered microbiota gene expression. In contrast, the P80-induced flagellin increase occurred more slowly and was closely associated with altered species composition. Transfer of both emulsifier-treated M-SHIME microbiotas to germ-free recipient mice recapitulated many of the host and microbial alterations observed in mice directly treated with emulsifiers. These results demonstrate a novel paradigm of deconstructing host-microbiota interactions and indicate that the microbiota can be directly impacted by these commonly used food additives, in a manner that subsequently drives intestinal inflammation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. The correlation between dendritic microstructure and mechanical properties of directionally solidified hypoeutectic Al-Ni alloys

    Science.gov (United States)

    Canté, Manuel V.; Spinelli, José E.; Cheung, Noé; Garcia, Amauri

    2010-02-01

    Al-Ni hypoeutectic alloys were directionally solidified under upward transient heat flow conditions. The aim of the present study is to set up correlations between the as-cast microstructure and the resulting mechanical properties of these alloys. The dependence of primary and secondary dendrite arm spacing on the alloy solute content and on solidification thermal parameters is also analyzed. The results include transient metal/mold heat transfer coefficient, tip growth rate, cooling rate, dendrite arm spacing, ultimate tensile strength, yield tensile strength and elongation. Expressions relating dendrite spacing to solidification thermal parameters and mechanical properties to the scale of the dendritic microstructure have been determined. It was found that the ultimate tensile strength and the yield tensile strength increase with increasing alloy solute content and with decreasing primary and secondary dendrite arm spacing. In contrast, the elongation was found to be independent of both alloy composition and dendritic arrangement.

  8. Direct correlation functions of binary mixtures of hard Gaussian overlap molecules

    Science.gov (United States)

    Moradi, M.; Khordad, R.

    2006-12-01

    We study the direct correlation function (DCF) of a classical fluid mixture of nonspherical molecules. The components of the mixture are two types of hard ellipsoidal molecules with different elongations, interacting through the hard Gaussian overlap (HGO) model. Two different approaches are used to calculate the DCFs of this fluid, and the results are compared. Here, the Pynn approximation [J. Chem. Phys. 60, 4579 (1974)] is extended to calculate the DCF of the binary mixtures of HGO molecules, then we use a formalism based on the weighted density functional theory introduced by Chamoux and Perera [J. Chem. Phys. 104, 1493 (1996)]. These results are fairly in agreement with each other. The pressure of this system is also calculated using the Fourier zero components of the DCF. The results are in agreement with the Monte Carlo molecular simulation.

  9. Direct measurement of the oceanic carbon monoxide flux by eddy correlation

    Directory of Open Access Journals (Sweden)

    B. W. Blomquist

    2012-12-01

    Full Text Available This report presents results from a field trial of ship-based air–sea flux measurements of carbon monoxide (CO by direct eddy correlation with an infrared-laser trace gas analyzer. The analyzer utilizes Off-Axis Integrated-Cavity-Output Spectroscopy (OA-ICOS to achieve high selectivity for CO, rapid response (~2 Hz and low noise. Over a two-day sea trial, peak daytime seawater CO concentrations were ~1.5 nM and wind speeds were consistently 10–12 m s−1. A clear diel cycle in CO flux with an early afternoon maximum was observed. An analysis of flux error suggests the effects of non-stationarity are important, and air–sea CO flux measurements are best performed in regions remote from continental pollution sources.

  10. Targeted in vitro and in vivo gene transfer into T Lymphocytes: potential of direct inhibition of allo-immune activation

    Directory of Open Access Journals (Sweden)

    Mehra Mandeep R

    2006-11-01

    Full Text Available Abstract Background Successful inhibition of alloimmune activation in organ transplantation remains one of the key events in achieving a long-term graft survival. Since T lymphocytes are largely responsible for alloimmune activation, targeted gene transfer of gene of cyclin kinase inhibitor p21 into T cells might inhibit their aberrant proliferation. A number of strategies using either adenoviral or lentiviral vectors linked to mono or bispecific antibodies directed against T cell surface markers/cytokines did not yield the desired results. Therefore, this study was designed to test if a CD3promoter-p21 chimeric construct would in vitro and in vivo transfer p21 gene to T lymphocytes and result in inhibition of proliferation. CD3 promoter-p21 chimeric constructs were prepared with p21 in the sense and antisense orientation. For in vitro studies EL4-IL-2 thyoma cells were used and for in vivo studies CD3p21 sense and antisense plasmid DNA was injected intramuscularly in mice. Lymphocyte proliferation was quantified by 3H-thymidine uptake assay; IL-2 mRNA expression was studied by RT-PCR and using Real Time PCR assay, we monitored the CD3, p21, TNF-α and IFN-γ mRNA expression. Results Transfection of CD3p21 sense and antisense in mouse thyoma cell line (EL4-IL-2 resulted in modulation of mitogen-induced proliferation. The intramuscular injection of CD3p21 sense and antisense plasmid DNA into mice also modulated lymphocyte proliferation and mRNA expression of pro-inflammatory cytokines. Conclusion These results demonstrate a novel strategy of in vitro and in vivo transfer of p21 gene to T cells using CD3-promoter to achieve targeted inhibition of lymphocyte proliferation and immune activation.

  11. Transcranial direct current stimulation transiently increases the blood-brain barrier solute permeability in vivo

    Science.gov (United States)

    Shin, Da Wi; Khadka, Niranjan; Fan, Jie; Bikson, Marom; Fu, Bingmei M.

    2016-03-01

    Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Whereas prior studies have focused exclusively on direct neuron polarization, our hypothesis is that tDCS directly modulates endothelial cells leading to transient changes in blood-brain-barrier (BBB) permeability (P) that are highly meaningful for neuronal activity. For this, we developed state-of-the-art imaging and animal models to quantify P to various sized solutes after tDCS treatment. tDCS was administered using a constant current stimulator to deliver a 1mA current to the right frontal cortex of rat (approximately 2 mm posterior to bregma and 2 mm right to sagittal suture) to obtain similar physiological outcome as that in the human tDCS application studies. Sodium fluorescein (MW=376), or FITC-dextrans (20K and 70K), in 1% BSA mammalian Ringer was injected into the rat (SD, 250-300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. To determine P, multiphoton microscopy with 800-850 nm wavelength laser was applied to take the images from the region of interest (ROI) with proper microvessels, which are 100-200 micron below the pia mater. It shows that the relative increase in P is about 8-fold for small solute, sodium fluorescein, ~35-fold for both intermediate sized (Dex-20k) and large (Dex-70k) solutes, 10 min after 20 min tDCS pretreatment. All of the increased permeability returns to the control after 20 min post treatment. The results confirmed our hypothesis.

  12. In Vivo High Frame Rate Vector Flow Imaging Using Plane Waves and Directional Beamforming

    DEFF Research Database (Denmark)

    Jensen, Jonas; Villagómez Hoyos, Carlos Armando; Stuart, Matthias Bo

    2016-01-01

    oscillation (TO) estimators and only 3 directional beamformed lines. The suggested DB vector flow estimator is employed with steered plane wave transmissions for high frame rate imaging.Two distinct plane wave sequences are used: a short sequence(3 angles) for fast flow and an interleaved long sequence (21....... The long sequence has a higher sensitivity, and when used forestimation of slow flow with a peak velocity of 0.04 m/s, the SDis 2.5 % and bias is 0.1 %. This is a factor of 4 better than ifthe short sequence is used. The carotid bifurcation was scanned on a healthy volunteer, and the short sequence...

  13. On the Direct Correlation between Gamma-Rays and PeV Neutrinos from Blazars

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Shan; Pohl, Martin; Winter, Walter, E-mail: shan.gao@desy.de [Deutsches Elektronen-Synchrotron (DESY), Platanenallee 6, D-15738 Zeuthen (Germany)

    2017-07-10

    We study the frequently used assumption in multi-messenger astrophysics that the gamma-ray and neutrino fluxes are directly connected because they are assumed to be produced by the same photohadronic production chain. An interesting candidate source for this test is the flat-spectrum radio quasar PKS B1424-418, which recently called attention to a potential correlation between an IceCube PeV neutrino event and its burst phase. We simulate both the multi-waveband photon and the neutrino emission from this source using a self-consistent radiation model. We demonstrate that a simple hadronic model cannot adequately describe the spectral energy distribution for this source, but a lepto-hadronic model with a subdominant hadronic component can reproduce the multi-waveband photon spectrum observed during various activity phases of the blazar. As a conclusion, up to about 0.3 neutrino events may coincide with the burst, which implies that the leptonic contribution dominates in the relevant energy band. We also demonstrate that the time-wise correlation between the neutrino event and burst phase is weak.

  14. Control of directed cell migration in vivo by membrane-to-cortex attachment.

    Directory of Open Access Journals (Sweden)

    Alba Diz-Muñoz

    2010-11-01

    Full Text Available Cell shape and motility are primarily controlled by cellular mechanics. The attachment of the plasma membrane to the underlying actomyosin cortex has been proposed to be important for cellular processes involving membrane deformation. However, little is known about the actual function of membrane-to-cortex attachment (MCA in cell protrusion formation and migration, in particular in the context of the developing embryo. Here, we use a multidisciplinary approach to study MCA in zebrafish mesoderm and endoderm (mesendoderm germ layer progenitor cells, which migrate using a combination of different protrusion types, namely, lamellipodia, filopodia, and blebs, during zebrafish gastrulation. By interfering with the activity of molecules linking the cortex to the membrane and measuring resulting changes in MCA by atomic force microscopy, we show that reducing MCA in mesendoderm progenitors increases the proportion of cellular blebs and reduces the directionality of cell migration. We propose that MCA is a key parameter controlling the relative proportions of different cell protrusion types in mesendoderm progenitors, and thus is key in controlling directed migration during gastrulation.

  15. In Vivo CT Direct Volume Rendering: A Three-Dimensional Anatomical Description of the Heart.

    Science.gov (United States)

    Cutroneo, Giuseppina; Bruschetta, Daniele; Trimarchi, Fabio; Cacciola, Alberto; Cinquegrani, Maria; Duca, Antonio; Rizzo, Giuseppina; Alati, Emanuela; Gaeta, Michele; Milardi, Demetrio

    2016-01-01

    Since cardiac anatomy continues to play an important role in the practice of medicine and in the development of medical devices, the study of the heart in three dimensions is particularly useful to understand its real structure, function and proper location in the body. This study demonstrates a fine use of direct volume rendering, processing the data set images obtained by Computed Tomography (CT) of the heart of 5 subjects with age range between 18 and 42 years (2 male, 3 female), with no history of any overt cardiac disease. The cardiac structure in CT images was first extracted from the thorax by marking manually the regions of interest on the computer, and then it was stacked to create new volumetric data. The use of a specific algorithm allowed us to observe with a good perception of depth the heart and the skeleton of the thorax at the same time. Besides, in all examined subjects, it was possible to depict its structure and its position within the body and to study the integrity of papillary muscles, the fibrous tissue of cardiac valve and chordae tendineae and the course of coronary arteries. Our results demonstrated that one of the greatest advantages of algorithmic modifications of direct volume rendering parameters is that this method provides much necessary information in a single radiologic study. It implies a better accuracy in the study of the heart, being complementary to other diagnostic methods and facilitating the therapeutic plans.

  16. In vivo morphology of the limbal palisades of vogt correlates with progressive stem cell deficiency in aniridia-related keratopathy.

    Science.gov (United States)

    Lagali, Neil; Edén, Ulla; Utheim, Tor Paaske; Chen, Xiangjun; Riise, Ruth; Dellby, Anette; Fagerholm, Per

    2013-08-07

    To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell-deficient patients.

  17. In vivo evaluation of rabbit sciatic nerve regeneration with diffusion tensor imaging (DTI): correlations with histology and behavior.

    Science.gov (United States)

    Yamasaki, Tetsuro; Fujiwara, Hiroyoshi; Oda, Ryo; Mikami, Yasuo; Ikeda, Takumi; Nagae, Masateru; Shirai, Toshiharu; Morisaki, Shinsuke; Ikoma, Kazuya; Masugi-Tokita, Miwako; Yamada, Kei; Kawata, Mitsuhiro; Kubo, Toshikazu

    2015-01-01

    Diffusion tensor imaging (DTI) is widely used in the study of the central nervous system. DTI represents a potential diagnostic tool for the peripheral nerve. However, more detailed information is needed for application of DTI in the clinical setting. In this study, peripheral degeneration and regeneration were evaluated using DTI-based analyses in a rabbit model. The changes in DTI parameters were compared to histological and functional changes after nerve injury. We used a high magnetic field (7.04T) MRI system. Japanese white male rabbits were used as the model of sciatic nerve crush injury. MR images were obtained before injury and at 2, 4, 6 and 8 weeks post-injury. The DTI parameters of fractional anisotropy (FA), axial diffusivity (λ||), and radial diffusivity (λ⊥) were calculated. Our results showed decreased FA and increased λ⊥ during the degenerative phase after sciatic nerve injury. In contrast, increased FA and decreased λ⊥ were observed during the regenerative phase. FA changes were correlated with axon number and with motor function recovery, assessed with the toe-spreading index. This study clearly demonstrates the validity of applying DTI parameters to the in vivo evaluation of peripheral nerve regeneration. Furthermore, results suggest that DTI can be a potent tool for predicting the extent of functional recovery after peripheral nerve injury. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Weikop, Pia; Mikkelsen, Maria D

    2017-01-01

    Central Kv7 (KCNQ) channels are voltage-dependent potassium channels composed of different combinations of four Kv7 subunits, being differently expressed in the brain. Notably, striatal dopaminergic neurotransmission is strongly suppressed by systemic administration of the pan-Kv7 channel opener...... retigabine. The effect of retigabine likely involves the inhibition of the activity in mesencephalic dopaminergic neurons projecting to the striatum, but whether Kv7 channels expressed in the striatum may also play a role is not resolved. We therefore assessed the effect of intrastriatal retigabine...... by acute systemic haloperidol administration in the rat. The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo....

  19. Antibody-directed double suicide gene therapy targeting of MUC1- positive leukemia cells in vitro and in vivo.

    Science.gov (United States)

    Dong, Xiao-Ya; Wang, Wen-Qian; Zhao, Yu; Li, Xu-Dong; Fang, Zhi-Gang; Lin, Dong-Jun; Xiao, Ruo-Zhi; Huang, Ren-Wei; Pan, Guang-Jin; Liu, Jia-Jun

    2013-10-01

    Our aim was to specifically transfer the cytosine deaminase (CD) and thymidine kinase (TK) genes into mucin 1 (MUC1)-positive leukemia cells by anti-MUC1 antibody directed infection of replication-defective lentivirus and to evaluate the targeted cytotoxicity of double suicide genes to leukemia. The target gene vector (containing CD and TK) and envelope (containing GFP and anti-MUC1) and packaging plasmids were cotransfected into 293T cells to produce the recombinant lentivirus. Suicide genes in virus-infected leukemia cells (U937, Jurkat, and K562) were detected by western blot. The cytotoxicity and bystander effect in vitro and the therapeutic effect in vivo were detected after treatment with the prodrugs. The results revealed that combined treatment with prodrug 5-fluorocytosine (5-FC) and ganciclovir (GCV) inhibited leukemia cell growth and caused significant bystander effect than treatment with either prodrug alone. TK/GCV treatment alone induced degeneration and cell death while the effect of CD/5-FC alone mainly caused vacuolar degeneration and necrosis. The addictive effects of combinatorial use of GCV and 5-FC mainly induced swelling of the mitochondria followed by necrosis of the leukemia cells. In vivo experiments revealed that both single and combinatorial prodrug treatments could prolong the survival time of leukemic mice. In summary, anti-MUC1 antibody directed lentiviral vector successfully transduced dual suicide genes and exerted targeted cytotoxicity against MUC1 positive leukemia cells. This targeted lentiviral dual suicide gene delivering system provides a promising approach for clinical treatment of leukemia in future.

  20. A BMP7 Variant Inhibits Tumor Angiogenesis In Vitro and In Vivo through Direct Modulation of Endothelial Cell Biology.

    Directory of Open Access Journals (Sweden)

    Courtney M Tate

    Full Text Available Bone morphogenetic proteins (BMPs, members of the TGF-β superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Using an in vitro co-culture endothelial cord formation assay, we investigated the role of a BMP7 variant (BMP7v in VEGF, bFGF, and tumor-driven angiogenesis. BMP7v treatment led to disruption of neo-endothelial cord formation and regression of existing VEGF and bFGF cords in vitro. Using a series of tumor cell models capable of driving angiogenesis in vitro, BMP7v treatment completely blocked cord formation. Pre-treatment of endothelial cells with BMP7v significantly reduced their cord forming ability, indicating a direct effect on endothelial cell function. BMP7v activated the canonical SMAD signaling pathway in endothelial cells but targeted gene knockdown using shRNA directed against SMAD4 suggests this pathway is not required to mediate the anti-angiogenic effect. In contrast to SMAD activation, BMP7v selectively decreased ERK and AKT activation, significantly decreased endothelial cell migration and down-regulated expression of critical RTKs involved in VEGF and FGF angiogenic signaling, VEGFR2 and FGFR1 respectively. Importantly, in an in vivo angiogenic plug assay that serves as a measurement of angiogenesis, BMP7v significantly decreased hemoglobin content indicating inhibition of neoangiogenesis. In addition, BMP7v significantly decreased angiogenesis in glioblastoma stem-like cell (GSLC Matrigel plugs and significantly impaired in vivo growth of a GSLC xenograft with a concomitant reduction in microvessel density. These data support BMP7v as a potent anti-angiogenic molecule that is effective in the context of tumor angiogenesis.

  1. Acute pressure changes in the brain are correlated with MR elastography stiffness measurements: initial feasibility in an in vivo large animal model.

    Science.gov (United States)

    Arani, Arvin; Min, Hoon-Ki; Fattahi, Nikoo; Wetjen, Nicholas M; Trzasko, Joshua D; Manduca, Armando; Jack, Clifford R; Lee, Kendall H; Ehman, Richard L; Huston, John

    2018-02-01

    The homeostasis of intracranial pressure (ICP) is of paramount importance for maintaining normal brain function. A noninvasive technique capable of making direct measurements of ICP currently does not exist. MR elastography (MRE) is capable of noninvasively measuring brain tissue stiffness in vivo, and may act as a surrogate to measure ICP. The objective of this study was to investigate the impact of changing ICP on brain stiffness using MRE in a swine model. Baseline MRE measurements were obtained, and then catheters were surgically placed into the left and right lateral ventricles of three animals. ICP was systematically increased over the range of 0 to 55 millimeters mercury (mmHg), and stiffness measurements were made using brain MRE at vibration frequencies of 60 hertz (Hz), 90 Hz, 120 Hz, and 150 Hz. A significant linear correlation between stiffness and ICP in the cross-subject comparison was observed for all tested vibrational frequencies (P ≤ 0.01). The 120 Hz (0.030 ± 0.004 kilopascal (kPa)/mmHg, P Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  2. Direct In Vivo Electrochemical Detection of Haemoglobin in Red Blood Cells

    Science.gov (United States)

    Toh, Rou Jun; Peng, Weng Kung; Han, Jongyoon; Pumera, Martin

    2014-08-01

    The electrochemical behavior of iron ion in haemoglobin provides insight to the chemical activity in the red blood cell which is important in the field of hematology. Herein, the detection of haemoglobin in human red blood cells on glassy carbon electrode (GC) was demonstrated. Red blood cells or raw blood cells was immobilized on a glassy carbon electrode surface with Nafion films employed to sandwich the layer of biological sample firmly on the electrode surface. Cyclic voltammetry (CV) analyses revealed a well-defined reduction peak for haemoglobin at about -0.30 V (vs. Ag/AgCl) at the red blood cell (GC-Nf-RBC-3Nf) and blood (GC-Nf-B-3Nf) film modified GCE in a pH 3.5 phosphate buffer solution. We further demonstrated that the complex biological conditions of a human red blood cell displayed no interference with the detection of haemoglobin. Such findings shall have an implication on the possibilities of studying the electrochemical behaviour of haemoglobin directly from human blood, for various scientific and clinical purposes.

  3. Direct current combined with bipolar radiofrequency ablation: an ex vivo feasibility study.

    Science.gov (United States)

    Tanaka, Toshihiro; Penzkofer, Tobias; Isfort, Peter; Bruners, Philipp; Disselhorst-Klug, Catherine; Junker, Elmar; Kichikawa, Kimihiko; Schmitz-Rode, Thomas; Mahnken, Andreas H

    2011-06-01

    The combination of radiofrequency ablation (RFA) with direct current (DC) is a promising strategy to improve the efficiency of RFA. However, DC-enhanced monopolar RFA is limited by electrolytic injury at the positive-electrode site. The aim of this study was to investigate the feasibility of the DC-enhanced bipolar RFA. To obviate the need for the subcutaneous positive electrode, the DC circuit was combined with a commercially available bipolar RFA system, in which both poles of the DC circuit are connected to a single RF probe. DC was applied for 15 min and followed by RFA in bovine livers using the following various DC currents: (1) no DC (control), (2) 3V continued until the end of RFA, (3) 5V continued until the end of RFA, (4) 10V continued until the end of RFA, (5) 5V continued in the circuit with reversed pole, (6) 3V stopped after initiation of RFA, and (7) 5V stopped. Coagulation volume, temperatures at a distance of 5, 10, and 15 mm from the RF probe, mean amperage, ablation duration, applied energy, minimum impedance, and degree of tissue charring were assessed and compared (analysis of variance, Student-Newman-Keuls test). All combined DC and RFA groups did increase coagulation volume. The 10V continued group showed significantly lower applied energy, shortest ablation duration, highest minimum impedance, and highest degree of charring with the lowest coagulation volume (p<0.05). DC-enhanced bipolar RFA with both poles of the DC circuit on a single probe appears to be ineffective.

  4. Quantitative Correlation of in Vivo Properties with in Vitro Assay Results: The in Vitro Binding of a Biotin–DNA Analogue Modifier with Streptavidin Predicts the in Vivo Avidin-Induced Clearability of the Analogue-Modified Antibody

    Science.gov (United States)

    Dou, Shuping; Virostko, John; Greiner, Dale L.; Powers, Alvin C.; Liu, Guozheng

    2016-01-01

    Quantitative prediction of in vivo behavior using an in vitro assay would dramatically accelerate pharmaceutical development. However, studies quantitatively correlating in vivo properties with in vitro assay results are rare because of the difficulty in quantitatively understanding the in vivo behavior of an agent. We now demonstrate such a correlation as a case study based on our quantitative understanding of the in vivo chemistry. In an ongoing pretargeting project, we designed a trifunctional antibody (Ab) that concomitantly carried a biotin and a DNA analogue (hereafter termed MORF). The biotin and the MORF were fused into one structure prior to conjugation to the Ab for the concomitant attachment. Because it was known that avidin-bound Ab molecules leave the circulation rapidly, this design would theoretically allow complete clearance by avidin. The clearability of the trifunctional Ab was determined by calculating the blood MORF concentration ratio of avidin-treated Ab to non-avidin-treated Ab using mice injected with these compounds. In theory, any compromised clearability should be due to the presence of impurities. In vitro, we measured the biotinylated percentage of the Ab-reacting (MORF-biotin)⊃-NH2 modifier, by addition of streptavidin to the radiolabeled (MORF-biotin)⊃-NH2 samples and subsequent high-performance liquid chromatography (HPLC) analysis. On the basis of our previous quantitative understanding, we predicted that the clearability of the Ab would be equal to the biotinylation percentage measured via HPLC. We validated this prediction within a 3% difference. In addition to the high avidin-induced clearability of the trifunctional Ab (up to ~95%) achieved by the design, we were able to predict the required quality of the (MORF-biotin)⊃-NH2 modifier for any given in vivo clearability. This approach may greatly reduce the steps and time currently required in pharmaceutical development in the process of synthesis, chemical analysis, in

  5. Quantitative Correlation of in Vivo Properties with in Vitro Assay Results: The in Vitro Binding of a Biotin-DNA Analogue Modifier with Streptavidin Predicts the in Vivo Avidin-Induced Clearability of the Analogue-Modified Antibody.

    Science.gov (United States)

    Dou, Shuping; Virostko, John; Greiner, Dale L; Powers, Alvin C; Liu, Guozheng

    2015-08-03

    Quantitative prediction of in vivo behavior using an in vitro assay would dramatically accelerate pharmaceutical development. However, studies quantitatively correlating in vivo properties with in vitro assay results are rare because of the difficulty in quantitatively understanding the in vivo behavior of an agent. We now demonstrate such a correlation as a case study based on our quantitative understanding of the in vivo chemistry. In an ongoing pretargeting project, we designed a trifunctional antibody (Ab) that concomitantly carried a biotin and a DNA analogue (hereafter termed MORF). The biotin and the MORF were fused into one structure prior to conjugation to the Ab for the concomitant attachment. Because it was known that avidin-bound Ab molecules leave the circulation rapidly, this design would theoretically allow complete clearance by avidin. The clearability of the trifunctional Ab was determined by calculating the blood MORF concentration ratio of avidin-treated Ab to non-avidin-treated Ab using mice injected with these compounds. In theory, any compromised clearability should be due to the presence of impurities. In vitro, we measured the biotinylated percentage of the Ab-reacting (MORF-biotin)⊃-NH2 modifier, by addition of streptavidin to the radiolabeled (MORF-biotin)⊃-NH2 samples and subsequent high-performance liquid chromatography (HPLC) analysis. On the basis of our previous quantitative understanding, we predicted that the clearability of the Ab would be equal to the biotinylation percentage measured via HPLC. We validated this prediction within a 3% difference. In addition to the high avidin-induced clearability of the trifunctional Ab (up to ∼95%) achieved by the design, we were able to predict the required quality of the (MORF-biotin)⊃-NH2 modifier for any given in vivo clearability. This approach may greatly reduce the steps and time currently required in pharmaceutical development in the process of synthesis, chemical analysis, in

  6. A time scaling approach to develop an in vitro-in vivo correlation (IVIVC) model using a convolution-based technique.

    Science.gov (United States)

    Costello, Cian; Rossenu, Stefaan; Vermeulen, An; Cleton, Adriaan; Dunne, Adrian

    2011-10-01

    In vitro-in vivo correlation (IVIVC) models prove very useful during drug formulation development, the setting of dissolution specifications and bio-waiver applications following post approval changes. A convolution-based population approach for developing an IVIVC has recently been proposed as an alternative to traditional deconvolution based methods, which pose some statistical concerns. Our aim in this study was to use a time-scaling approach using a convolution-based technique to successfully develop an IVIVC model for a drug with quite different in vitro and in vivo time scales. The in vitro and the in vivo data were longitudinal in nature with considerable between subject variation in the in vivo data. The model was successfully developed and fitted to the data using the NONMEM package. Model utility was assessed by comparing model-predicted plasma concentration-time profiles with the observed in vivo profiles. This comparison met validation criteria for both internal and external predictability as set out by the regulatory authorities. This study demonstrates that a time-scaling approach may prove useful when attempting to develop an IVIVC for data with the aforementioned properties. It also demonstrates that the convolution-based population approach is quite versatile and that it is capable of producing an IVIVC model with a big difference between the in vitro and in vivo time scales.

  7. Three-dimensional histological imaging of primate brain and correlation with in vivo medical device images Imagerie histologique tri-dimensionnelle du cerveau de primate et corrélation avec l'imagerie médicale in vivo

    Directory of Open Access Journals (Sweden)

    Julien Dauguet

    2011-02-01

    Full Text Available The 3D reconstruction of series of histological slices is an imaging technique that appeared about 25 years ago but that is only starting now to become recognized as an imaging modality per se. Thanks to this technique, it becomes possible to restore the spatial consistency of the brain and to match accurately histological slices with an in vivo medical device image such as an MRI or a PET scan. This is of high interest since it allows direct comparison between the histology, often considered as the gold standard in terms of information, and the same medical devices used in clinical routine to image human patients. Thanks to the similarity of their brain with humans and the disease models widely developed for them, non-human primates are privileged species to benefit from this possibility of 3D analysis and in vivo - post mortem correlation. We present in this article a state of the art review of the main techniques proposed to achieve this original imaging technique, followed by a set of some particularly promising neuroimaging applications.La reconstruction 3D de séries de coupes histologiques est une technique d'imagerie qui est apparue il y a 25 ans environ mais qui commence seulement à être reconnue comme une modalité d'imagerie à part entière. Grâce à cette technique, la cohérence 3D du cerveau est rétablie et il devient notamment possible de mettre en correspondance précisément des coupes histologiques avec un examen issu d'un imageur médical comme une IRM ou une TEP. C'est d'un intérêt majeur car cela permet une comparaison directe entre l'histologie, souvent considérée comme la référence étalon en termes d'information fournie, et les mêmes imageurs médicaux que ceux utilisés en routine clinique pour suivre les patients humains. Grâce à leur similarité avec les humains et aux nombreux modèles animaux de maladies développés pour eux, les primates non-humains sont une espèce privilégiée pour bénéficier de

  8. Study of cold and hot nuclear matter effects on jets with direct photon triggered correlations from PHENIX

    OpenAIRE

    Osborn, J. D.; Collaboration, for the PHENIX

    2017-01-01

    Direct photons, being colorless objects, provide an unmodified control particle that can be used in conjunction with jets to probe the quark-gluon plasma. To leading order the direct photon momentum balances the momentum of opposing jets and can therefore provide a clean handle on the jet energy. Therefore, angular correlations with direct photons provide a mechanism to study the fragmentation of the opposing jet without performing jet reconstruction. Jet fragmentation modification has been m...

  9. Direct in vivo inflammatory cell-induced corrosion of CoCrMo alloy orthopedic implant surfaces.

    Science.gov (United States)

    Gilbert, Jeremy L; Sivan, Shiril; Liu, Yangping; Kocagöz, Sevi B; Arnholt, Christina M; Kurtz, Steven M

    2015-01-01

    Cobalt-chromium-molybdenum (CoCrMo) alloy, used for over five decades in orthopedic implants, may corrode and release wear debris into the body during use. These degradation products may stimulate immune and inflammatory responses in vivo. We report here on evidence of direct inflammatory cell-induced corrosion of human implanted and retrieved CoCrMo implant surfaces. Corrosion morphology on CoCrMo implant surfaces, in unique and characteristic patterns, and the presence of cellular remnants and biological materials intimately entwined with the corrosion indicates direct cellular attack under the cell membrane region of adhered and/or migrating inflammatory cells. Evidence supports a Fenton-like reaction mechanism driving corrosion in which reactive oxygen species are the major driver of corrosion. Using in vitro tests, large increases in corrosion susceptibility of CoCrMo were seen (40-100 fold) when immersed in phosphate buffered saline solutions modified with hydrogen peroxide and hydrochloric acid to represent the chemistry under inflammatory cells. This discovery raises significant new questions about the clinical consequences of such corrosion interactions, the role of patient inflammatory reactions, and the detailed mechanisms at play. © 2014 Wiley Periodicals, Inc.

  10. Correlating the structure and in vitro digestion viscosities of different pectin fibers to in vivo human satiety.

    Science.gov (United States)

    Logan, Kirstyn; Wright, Amanda J; Goff, H Douglas

    2015-01-01

    The effects of a simulated in vitro digestion on the viscosity of orange juice with added high methoxyl (HM), low methoxyl (LM), and low methoxyl amidated (LMA) pectins were examined in conjunction with a human satiety study with healthy men (n=10) and women (n=15). Orange juice solutions were formulated to be either low (0.039±0.007 Pa s) or high viscosity (0.14±0.035 Pa s). The apparent viscosities after an in vitro digestion simulating the gastric and small intestinal phases in the presence of hydrolytic enzymes and bile salts were recorded at 10 and 50 s⁻¹. The viscosity induced by LM pectin increased considerably after the gastric phase whereas samples with all pectin types showed considerable reductions in viscosity, compared to initial apparent viscosity, after the small intestinal phase. For satiety testing, the orange juice solutions were consumed with a standardized breakfast meal after a 12 h overnight fast. Self-reported visual analogue scale (VAS) measurements of Hunger, Fullness, Satisfaction and Prospective Food Intake were obtained at fasting, after consumption of the breakfast and for the subsequent 3 h. The LM low and high viscosity pectin beverages were associated with the greatest effects on subjective ratings of satiety. The HM low and high viscosity pectin beverages had lower but significant effects on satiety, while LMA pectin had no effect. There was not a strong correlation between apparent viscosity of in vitro digested beverages and in vivo satiety scores. Thus, in this study, fiber-induced satiety could not be fully explained by digestate viscosity alone although gastric-phase viscosity may have played a significant role.

  11. Directed Functional Connectivity in Fronto-Centroparietal Circuit Correlates With Motor Adaptation in Gait Training.

    Science.gov (United States)

    Youssofzadeh, Vahab; Zanotto, Damiano; Wong-Lin, KongFatt; Agrawal, Sunil K; Prasad, Girijesh

    2016-11-01

    Lower-extremity robotic exoskeletons are used in gait rehabilitation to achieve functional motor recovery. To date, little is known about how gait training and post-training are characterized in brain signals and their causal connectivity. In this work, we used time-domain partial Granger causality (PGC) analysis to elucidate the directed functional connectivity of electroencephalogram (EEG) signals of healthy adults in robot-assisted gait training (RAGT). Our results confirm the presence of EEG rhythms and corticomuscular relationships during standing and walking using spectral and coherence analyses. The PGC analysis revealed enhanced connectivity close to sensorimotor areas ( C3 and CP3 ) during standing, whereas additional connectivities involve the centroparietal ( CP z) and frontal ( F z ) areas during walking with respect to standing. In addition, significant fronto-centroparietal causal effects were found during both training and post-training. Strong correlations were also found between kinematic errors and fronto-centroparietal connectivity during training and post-training. This study suggests fronto-centroparietal connectivity as a potential neuromarker for motor learning and adaptation in RAGT.

  12. Foreign Direct Investment and Energy Supply in the Middle East and North Africa: A Correlational Study

    Science.gov (United States)

    Elghali, Siddig

    Middle East and North Africa countries have been criticized for failing to utilize foreign direct investment energy resources efficiently. The changing of energy resources environment of the past decades with its growing emphasis on the importance of imminent energy supply challenges require strategists to consider different types of energy resources investment to improve energy supply. One type of energy investment will show effectiveness and efficiency in utilizing foreign direct investment in exposing RE, fossil fuels, natural gas, and reducing CO2 emissions. The purpose of this quantitative correlational study was to utilize foreign direct investment to predict total primary energy supply in the Middle East and North Africa region between 1971 and 2013. The study was conducted using a sample size of 43 years of energy supply resources and foreign direct investment from 1971 to 2013, which includes all of the years for which FDI is available. RE potential may equip Middle East and North Africa countries with sustainable and clean electricity for centuries to come, as non-renewable energy resources may not meet the demands globally and domestically or environmentally. As demands for fossil fuels grow, carbon emissions will increase. RE may be a better option of CO 2 emissions sequestration and will increase electricity to rural areas without government subsidies and complex decision-making policies. RE infrastructure will reduce water desalinization costs, cooling systems, and be useful in heating. Establishing concentrated solar power may be useful for the region cooperation, negotiations, and integration to share this energy. The alternative sought to fossil fuels was nuclear power. However, nuclear power depends on depleting, non-renewable uranium resources. The cost of uranium will increase if widely used and the presence of a nuclear plant in an unstable region is unsafe. Thus, renewable energy as a long-term option is efficient. A nonlinear regression

  13. Neural Correlates of Direct Access Trading in a Real Stock Market: An fMRI Investigation.

    Science.gov (United States)

    Raggetti, GianMario; Ceravolo, Maria G; Fattobene, Lucrezia; Di Dio, Cinzia

    2017-01-01

    Background: While financial decision making has been barely explored, no study has previously investigated the neural correlates of individual decisions made by professional traders involved in real stock market negotiations, using their own financial resources. Aim: We sought to detect how different brain areas are modulated by factors like age, expertise, psychological profile (speculative risk seeking or aversion) and, eventually, size and type (Buy/Sell) of stock negotiations, made through Direct Access Trading (DAT) platforms. Subjects and methods: Twenty male traders underwent fMRI while negotiating in the Italian stock market using their own preferred trading platform. Results: At least 20 decision events were collected during each fMRI session. Risk averse traders performed a lower number of financial transactions with respect to risk seekers, with a lower average economic value, but with a higher rate of filled proposals. Activations were observed in cortical and subcortical areas traditionally involved in decision processes, including the ventrolateral and dorsolateral prefrontal cortex (vlPFC, dlPFC), the posterior parietal cortex (PPC), the nucleus accumbens (NAcc), and dorsal striatum. Regression analysis indicated an important role of age in modulating activation of left NAcc, while traders' expertise was negatively related to activation of vlPFC. High value transactions were associated with a stronger activation of the right PPC when subjects' buy rather than sell. The success of the trading activity, based on a large number of filled transactions, was related with higher activation of vlPFC and dlPFC. Independent of chronological and professional age, traders differed in their attitude to DAT, with distinct brain activity profiles being detectable during fMRI sessions. Those subjects who described themselves as very self-confident, showed a lower or absent activation of both the caudate nucleus and the dlPFC, while more reflexive traders showed

  14. MicroRNA-494 inhibits cell proliferation and invasion of chondrosarcoma cells in vivo and in vitro by directly targeting SOX9.

    Science.gov (United States)

    Li, Jingyuan; Wang, Lijuan; Liu, Zongzhi; Zu, Chao; Xing, Fanfan; Yang, Pei; Yang, Yongkang; Dang, Xiaoqian; Wang, Kunzheng

    2015-09-22

    Accumulating evidence indicates that dysregulation of miRNAs could contribute to tumor growth and metastasis of chondrosarcoma by infuencing cell proliferation and invasion. In the current study, we are interested to examine the role of miRNAs in the carcinogenesis and progression of chondrosarcoma. Here, using comparative miRNA profiling of tissues and cells of chondrosarcoma and cartilage, we identified miR-494 as a commonly downregulated miRNA in the tissues of patients with chondrosarcoma and chondrosarcoma cancer cell line, and upregulation of miR-494 could inhibit proliferation and invasion of chondrosarcoma cancer cells in vivo and in vitro. Moreover, our data demonstrated that SOX9, the essential regulator of the process of cartilage differentiation, was the direct target and functional mediator of miR-494 in chondrosarcoma cells. And downregulation of SOX9 could also inhibit migration and invasion of chondrosarcoma cells. In the last, we identified low expression of miR-494 was significantly correlated with poor overall survival and prognosis of chondrosarcoma patients. Thus, miR-494 may be a new common therapeutic target and prognosis biomarker for chondrosarcoma.

  15. Continuous noninvasive in vivo monitoring of intravascular plasma volume and hematocrit changes during hemodialysis in humans: direct comparison with the CRIT-LINE

    Science.gov (United States)

    Deng, Bin; Kastner, Evan; Narsipur, Sriram S.; Goodisman, Jerry; Chaiken, J.

    2014-02-01

    We report a new device and algorithm that allows simultaneous monitoring of the hematocrit and plasma volume fraction of blood within the intravascular space of an optically probed volume of skin. Skin is probed with a near infrared (NIR) laser and simultaneously collecting the Rayleigh and Mie scattered light as one raw signal and the undifferentiated Raman and fluorescence emission as the second raw signal. These signals are combined using six parameters that can be obtained by either direct calculation or empirical calibration to permit monitoring of the blood in human skin (e.g. fingertips). We tested a device based on the algorithm that might be useful in allowing the early detection of blood loss for people who have no external injury but may be hemorrhaging internally. IRB allowed experiments monitoring blood in human fingertip skin in vivo during routine hemodialysis demonstrated good agreement between the experimental device and the CRIT-LINE®, an FDA approved device that is built into the dialysis machine and applies the Twersky algorithm to blood in the dialysis machine (i.e. in vitro). Based on observation of 9 different test subjects, as dialysis removes fluid from the intravascular space causing an increase in hematocrit and a decrease in plasma volume, the CRIT-LINE response is closely emulated (typical per session linear correlation r2=0.78, N=87, pfactors will also be discussed.

  16. Bone mineral density directly correlates with duodenal Marsh stage in newly diagnosed adult celiac patients.

    Science.gov (United States)

    García-Manzanares, Alvaro; Tenias, José M; Lucendo, Alfredo J

    2012-09-01

    To estimate the prevalence of low bone mineral density (BMD) in a prospective series of adult celiac patients and to identify nutritional and metabolic factors associated with osteoporosis and osteopenia. Patients over 18 years of age who were consecutively and newly diagnosed with celiac disease (CD) were recruited. A bone density scan with dual-energy X-ray absorptiometry was carried out on the left hip and lumbar spine; nutritional parameters were analyzed and a hormone study conducted in order to exclude secondary low BMD. 40 patients (36 females/4 males) between the ages of 18 and 68 (mean 44.25 years) were recruited. Overall, at the moment of diagnosis 45% of patients exhibited low BMD at both demarcations. Risk of hip fracture was generally low, but ascended to mild in patients with villous atrophy (p = 0.011). Differences in major fracture risk were also observed depending on Marsh stage (p = 0.015). Significant differences were observed in nutritional status between patients with and without duodenal villous atrophy, with body mass index and blood levels of prealbumin, iron, vitamin D and folic acid significantly lower in Marsh III stage patients. No differences were found in blood hormone levels between Marsh stages or BMDs. The degree of bone mass loss in the lumbar spine directly correlated to Marsh stage. In the hip, a parallel association between BMD and Marsh stage was also observed, but did not reach statistical significance. Duodenal villous atrophy, through malabsorption, was the main determinant factor for low BMD in adult-onset CD patients.

  17. No direct correlation between rotavirus diarrhea and breast feeding: A meta-analysis.

    Science.gov (United States)

    Shen, Jian; Zhang, Bi-Meng; Zhu, Sheng-Guo; Chen, Jian-Jie

    2017-08-26

    Some studies indicated that children with exclusive breast feeding had a reduction in the prevalence of rotavirus diarrhea, while some others held the opposite views. In this study, we aimed to systematically find the associations between rotavirus diarrhea and breast feeding. A literature search up to June 2016 in electronic literature databases, including PubMed and Embase, was performed. The Newcastle-Ottawa Scale was used to conduct the quality assessment of all the selected studies. Statistical analyses were performed using the R package version 3.12 (R Foundation for Statistical Computing, Beijing1, China, meta package), and odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. The heterogeneity was assessed by Cochran's Q-statistic and I 2 test, and the sensitivity analysis was performed by trimming one study at a time. A total of 17 articles, which included 10,841 participants, were investigated in the present meta-analysis. There was no significant difference between the case group and control group (OR, 0.59 95% CI 0.33-1.07) in the meta-analysis of exclusive breast feeding, and no significant difference was found between the case group and the control group (OR, 0.86; 95% CI 0.63-1.16) in the meta-analysis of breast feeding. No significant difference was found between the case group and control group (OR, 0.78 95% CI 0.59-1.04) for all quantitative data. There may be no direct correlation between rotavirus diarrhea and breast feeding. Copyright © 2017. Published by Elsevier B.V.

  18. Influence of dissolution media composition on drug release and in-vitro/in-vivo correlation for paracetamol matrix tablets prepared with novel carbomer polymers.

    Science.gov (United States)

    Parojcić, J; Ethurić, Z; Jovanović, M; Ibrić, S; Jovanović, D

    2004-06-01

    The influence of dissolution media composition on drug release kinetics and in-vitro/in-vivo correlation (IVIVC) for hydrophilic matrix tablets based on Carbopol 971P and Carbopol 71G was investigated. A number of buffered and unbuffered media differing with respect to their pH value, ionic strength and ionic species was evaluated. The observed in-vitro drug release profiles were compared with the hypothetical drug release profiles in-vivo calculated by numerical deconvolution from the results of an in-vivo study. The obtained IVIVC plots were examined using linear and non-linear (proportional odds, proportional hazards and proportional reversed hazards) mathematical models. Although the studied sustained release agents were chemically identical, they exhibited pronounced differences in drug product behaviour both in-vitro and in-vivo. The use of non-linear modelling resulted in an improved level of correlation, especially in the case of Carbopol 71G matrices. The obtained results indicated the susceptibility of drug release kinetics and hence IVIVC in the case of anionic polymer matrices to media composition, and emphasized the need for thorough evaluation of applied media during the development of biorelevant dissolution methodology. Although the use of non-linear modelling could be advantageous, the need for a simple and meaningful non-linear relationship is pointed out. Copyright 2004 The Authors

  19. Quantitative In Vivo Fluorescence Cross-Correlation Analyses Highlight the Importance of Competitive Effects in the Regulation of Protein-Protein Interactions

    Science.gov (United States)

    Sadaie, Wakako; Harada, Yoshie; Matsuda, Michiyuki

    2014-01-01

    Computer-assisted simulation is a promising approach for clarifying complicated signaling networks. However, this approach is currently limited by a deficiency of kinetic parameters determined in living cells. To overcome this problem, we applied fluorescence cross-correlation spectrometry (FCCS) to measure dissociation constant (Kd) values of signaling molecule complexes in living cells (in vivo Kd). Among the pairs of fluorescent molecules tested, that of monomerized enhanced green fluorescent protein (mEGFP) and HaloTag-tetramethylrhodamine was most suitable for the measurement of in vivo Kd by FCCS. Using this pair, we determined 22 in vivo Kd values of signaling molecule complexes comprising the epidermal growth factor receptor (EGFR)–Ras–extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. With these parameters, we developed a kinetic simulation model of the EGFR-Ras-ERK MAP kinase pathway and uncovered a potential role played by stoichiometry in Shc binding to EGFR during the peak activations of Ras, MEK, and ERK. Intriguingly, most of the in vivo Kd values determined in this study were higher than the in vitro Kd values reported previously, suggesting the significance of competitive bindings inside cells. These in vivo Kd values will provide a sound basis for the quantitative understanding of signal transduction. PMID:24958104

  20. Direct visualization of Parkinson's disease by in vivo human brain imaging using 7.0T magnetic resonance imaging.

    Science.gov (United States)

    Cho, Zang-Hee; Oh, Se-Hong; Kim, Jong-Min; Park, Sung-Yeon; Kwon, Dae-Hyuk; Jeong, Hye-Jin; Kim, Young-Bo; Chi, Je-Geun; Park, Chan-Woong; Huston, John; Lee, Kendall H; Jeon, Beom S

    2011-03-01

    Parkinson's disease (PD) is a neurodegenerative disorder resulting from progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. Therefore, imaging of the SN has been regarded to hold greatest potential for use in the diagnosis of PD. At the 7.0T magnetic resonance imaging (MRI), it is now possible to delineate clearly the shapes and boundaries of the SN. We scanned eight early and two advanced PD patients, along with nine age-matched control subjects, using a 7.0T MRI in an attempt to directly visualize the SN and quantify the differences in shape and boundaries of SN between PD subjects in comparison with the normal control subjects. In the normal controls, the boundaries between the SN and crus cerebri appear smooth, and clean "arch" shapes that stretch ventrally from posterior to anterior. In contrast, these smooth and clean arch-like boundaries were lost in PD subjects. The measured correlation analyses show that, in PD patients, there is age-dependent correlation and substantially stronger UPDRS motor score-dependent correlation. These results suggest that, by using 7.0T MRI, it appears possible to use these visible and distinctive changes in morphology as a diagnostic marker of PD. Copyright © 2011 Movement Disorder Society.

  1. Development of a discriminative biphasic in vitro dissolution test and correlation with in vivo pharmacokinetic studies for differently formulated racecadotril granules.

    Science.gov (United States)

    Deng, Jia; Staufenbiel, Sven; Hao, Shilei; Wang, Bochu; Dashevskiy, Andriy; Bodmeier, Roland

    2017-06-10

    The purpose of this study was to discriminate the release behavior from three differently formulated racecadotril (BCS II) granules and to establish an in vitro-in vivo correlation. Three granule formulations of the lipophilic drug were prepared with equivalent composition but prepared with different manufacturing processes (dry granulation, wet granulation with or without binder). In vitro release of the three granules was investigated using a biphasic dissolution system (phosphate buffer pH6.8 and octanol) and compared to the conventional single phase USP II dissolution test performed under sink and non-sink conditions. In vivo studies with each granule formulation were performed in rats. Interestingly, the granule formulations exhibited pronouncedly different behavior in the different dissolution systems depending on different wetting and dissolution conditions. Single phase USP II dissolution tests lacked discrimination. In contrast, remarkable discrimination between the granule formulations was observed in the octanol phase of biphasic dissolution system with a rank order of release from granules prepared by wet granulation with binder>wet granulation without binder>dry granulation. This release order correlated well with the wettability of these granules. An excellent correlation was also established between in vitro release in the octanol phase of the biphasic test and in vivo data (R(2)=0.999). Compared to conventional dissolution methods, the biphasic method provides great potential to discriminate between only minor formulation and process changes within the same dosage form for poorly soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Enzyme-Directed Assembly of Nanoparticles in Tumors Monitored by In Vivo Whole Animal and Ex Vivo Super-Resolution Fluorescence Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Miao-Ping; Carlini, Andrea S.; Hu, Dehong; Barback, Christopher V.; Rush, Anthony M.; Hall, David J.; Orr, Galya; Gianneschi, Nathan C.

    2013-12-18

    Matrix metalloproteinase enzymes, overexpressed in HT-1080 human fibrocarcinoma tumors, were used to guide the accumulation and retention of an enzyme-responsive nanoparticle in a xenograft mouse model. The nanoparticles were prepared as micelles from amphiphilic block copolymers bearing a simple hydrophobic block, and a hydrophilic peptide brush. The polymers were end-labeled with Alexa Fluor 647 dyes leading to the formation of labeled micelles upon dialysis of the polymers from DMSO to aqueous buffer. This dye-labeling strategy allowed the presence of the retained material to be visualized via whole animal imaging in vivo, and in ex vivo organ analysis following intratumoral injection into HT-1080 xenograft tumors. We propose that the material is retained by virtue of an enzyme-induced accumulation process whereby particles change morphology from 20 nm spherical micelles to micron-scale aggregates, kinetically trapping them within the tumor. This hypothesis is tested here via an unprecedented super resolution fluorescence analysis of ex vivo tissue slices confirming a particle size increase occurs concomitantly with extended retention of responsive particles compared to unresponsive controls.

  3. Correlation of intrinsic in vitro and in vivo clearance for drugs metabolized by hepatic UDP-glucuronosyltransferases in rats.

    Science.gov (United States)

    Nakamori, Fumihiro; Naritomi, Yoichi; Furutani, Masako; Takamura, Fujiko; Miura, Hiroya; Murai, Hidetsugu; Terashita, Shigeyuki; Teramura, Toshio

    2011-01-01

    A method for quantitatively predicting the hepatic clearance of drugs by UDP-glucuronosyltransferases (UGTs) from in vitro data has not yet been established. We examined the relationship between in vitro and in vivo intrinsic clearance by rat hepatic UGTs using 10 drugs. For these 10 drugs, the in vitro intrinsic clearance by UGTs (CL(int, in vitro)) measured using alamethicin-activated rat liver microsomes was in the range 0.10-4500 ml/min/kg. Microsomal binding (f(u, mic)) was determined to be in the range 0.29-0.95 and the unbound intrinsic clearance (CL(uint, in vitro)) to be in the range 0.11-9600 ml/min/kg. The contribution of rat hepatic glucuronidation to drug elimination was 12.0%-76.6% and in vivo intrinsic clearance by UGTs was 5.7-9000 ml/min/kg. To evaluate the discrepancy between the in vitro and in vivo values, a scaling factor was calculated (CL(int, in vivo)/CL(int, in vitro)); the values were found to be in the range 0.89-110. The average fold error of the scaling factor values incorporating f(u, mic) was closer to unity than that without f(u, mic). The scaling factor values incorporating f(u, mic) were drugs and drugs, indicating a small discrepancy between in vitro and in vivo values. Thus, using alamethicin-activated liver microsomes, incorporating f(u, mic) into CL(int, in vitro), and considering the contribution of glucuronidation may enable us to quantitatively predict in vivo hepatic glucuronidation from in vitro data.

  4. In vivo comparison of Kodak E-speed film and direct digital imaging system for assessment of interproximal bone loss

    Directory of Open Access Journals (Sweden)

    Mellekatte C Neetha

    2014-01-01

    Full Text Available Aims: To evaluate the diagnostic accuracy of direct digital radiography as compared to a conventional radiographic film for the assessment of interproximal bone loss with intrasurgical measurements as the gold standard. Materials and Methods: A total of 100 patients, with untreated moderate-to-advanced periodontal disease, were included in the study. The presurgical radiographs were made using a Kodak E-speed film and a Dexis digital sensor simultaneously, for sites with interproximal bone loss. At the time of surgery, the distance from the cementoenamel junction to the bone defect (CEJ-BD was measured for 331 interproximal defects. The radiographs were randomized and then linear measurements were taken for the same sites in both conventional and digital radiographs. Stastistical Analysis: Comparison between the conventional, digital, and intrasurgical measurements was done statistically using the Student′s t-test. The agreement and correlation among the methods was assessed using the weighted Kappa measure of agreement and Pearson′s correlation, respectively. Results: The results showed that the conventional (5.15 ± 2.19 mm and digital analyzing techniques (5.13 ± 2.19 mm underestimated the interproximal bone loss, as compared to the intrasurgical measurements (6.07 ± 2.05 mm (p < 0.001. The difference between conventional and digital radiographic methods was found to be statistically insignificant (p = 0.92. Conclusion: Under normal clinical use, the alveolar bone levels revealed on intraoral direct digital radiographs and Kodak E speed film were almost same. Therefore, the digital radiographic system can be routinely used in clinical practice as an alternative to conventional film.

  5. MRI morphologic alterations after liver SBRT. Direct dose correlation with intermodal matching

    Energy Technology Data Exchange (ETDEWEB)

    Boda-Heggemann, Judit; Jahnke, Anika; Jahnke, Lennart; Vogel, Lena; Simeonova-Chergou, Anna O.; Herskind, Carsten; Wenz, Frederik; Lohr, Frank [University of Heidelberg, Department of Radiation Oncology, University Medical Center Mannheim, Mannheim (Germany); Attenberger, Ulrike; Budjan, Johannes [University of Heidelberg, Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Mannheim (Germany)

    2016-09-15

    CT morphologic and histopathologic alterations have been reported after SBRT. We analyzed the correlation of MRI morphologic alterations with radiation doses to assess the potential for MRI-based dose-effect correlation in healthy liver tissue. MRI data of 24 patients with liver metastases 7±3 weeks after image-guided SBRT in deep-inspiration breath-hold were retrospectively analyzed. MRI images were intermodally matched to the planning CT and corresponding dose distribution. Absolute doses were converted to EQD{sub 2,α/β=x} with α/β values of 2, 3 for healthy liver tissue, 8 Gy for modelled predamaged liver tissue and 10 Gy for tumor tissue. A central nonenhancing area was observed within the isodose lines of nominally 48.2 ± 15.2 Gy, EQD{sub 2Gy/α/β=10} 92.5 ± 27.7 Gy. Contrast-enhancement around the central nonenhancing area was observed within the isodose lines of nominally 46.9 ± 15.3 Gy, EQD{sub 2Gy/α/β=10} 90.5 ± 28.3 Gy. Outside the high-dose volume, in the beam path, characteristic sharply defined, nonblurred MRI morphologic alterations were observed that corresponded with the following isodose lines: T1-intensity changes occurred at isodose lines of nominally 21.9 ± 6.7 Gy (EQD{sub 2,α/β=2} 42.5 ± 8.7 Gy, EQD{sub 2,α/β=3} 38.5 ± 7.6 Gy, EQD{sub 2,α/β=8} 30.2 ±6.3 Gy). T2-hyper/hypointensity was observed within isodose lines of nominally 22.4 ± 6.6 Gy (EQD{sub 2,α/β=2} 42.7 ± 8.1 Gy, EQD{sub 2,α/β=3} 38.7 ± 7 Gy; EQD{sub 2,α/β=8} 30.5 ± 5.9 Gy). Using deformable matching, direct spatial/dosimetric correlation of SBRT-induced changes in liver tissue was possible. In the PTV high-dose region, a central nonenhancing area and peripheral contrast medium accumulation was observed. Beam path doses of 38-42 Gy (EQD{sub 2,α/β=2-3}) induce characteristic MRI morphologic alterations. (orig.) [German] CT-morphologische Veraenderungen nach SBRT sind beschrieben und korrelieren mit histopathologischen Veraenderungen. Ziel war es, MRT

  6. Direct and correlated responses to selection for yearling weight on reproductive performance of Nelore cows1

    National Research Council Canada - National Science Library

    M E Z Mercadante; I U Packer; A G Razook; J N S G Cyrillo; L A Figueiredo

    2003-01-01

    ...) and the correlated responses on the size and reproduction traits of cows. The experiment was started in 1976, and in 1980 three lines of Nelore cattle were established: selection (NeS), traditional (NeT...

  7. Development of a Physiologically Relevant Population Pharmacokinetic in Vitro-in Vivo Correlation Approach for Designing Extended-Release Oral Dosage Formulation.

    Science.gov (United States)

    Kim, Tae Hwan; Shin, Soyoung; Bulitta, Jürgen B; Youn, Yu Seok; Yoo, Sun Dong; Shin, Beom Soo

    2017-01-03

    Establishing a level A in vitro-in vivo correlation (IVIVC) for a drug with complex absorption kinetics is challenging. The objective of the present study was to develop an IVIVC approach based on population pharmacokinetic (POP-PK) modeling that incorporated physiologically relevant absorption kinetics. To prepare three extended release (ER) tablets of loxoprofen, three types of hydroxypropyl methylcellulose (HPMC 100, 4000, and 15000 cps) were used as drug release modifiers, while lactose and magnesium stearate were used as the diluent and lubricant, respectively. An in vitro dissolution test in various pH conditions showed that loxoprofen dissolution was faster at higher pH. The in vivo pharmacokinetics of loxoprofen was assessed following oral administration of the different loxoprofen formulations to Beagle dogs (n = 22 in total). Secondary peaks or shoulders were observed in many of the individual plasma concentration vs time profiles after ER tablet administration, which may result from secondary absorption in the intestine due to a dissolution rate increase under intestinal pH compared to that observed at stomach pH. In addition, in vivo oral bioavailability was found to decrease with prolonged drug dissolution, indicating site-specific absorption. Based on the in vitro dissolution and in vivo absorption data, a POP-PK IVIVC model was developed using S-ADAPT software. pH-dependent biphasic dissolution kinetics, described using modified Michaelis-Menten kinetics with varying Vmax, and site-specific absorption, modeled using a changeable absorbed fraction parameter, were applied to the POP-PK IVIVC model. To experimentally determine the biphasic dissolution profiles of the ER tablets, another in vitro dissolution test was conducted by switching dissolution medium pH based on an in vivo estimate of gastric emptying time. The model estimated, using linear regression, that in vivo initial maximum dissolution rate (Vmax(0)in vivo) was highly correlated (r2 > 0

  8. In vivo characterization of protein-protein interactions in the AP1 system with fluorescence correlation spectroscopy (FCS).

    NARCIS (Netherlands)

    N. Baudendistel (Nina); T.A. Knoch (Tobias); G. Müller (Gabriele); M. Wachsmuth (Malte); T. Weidemann (Thomas); W. Waldeck (Waldemar); J. Langowski (Jörg)

    2002-01-01

    textabstractThe aim of these studies is the quantitative investigation of protein-protein interactions in the AP1 system in vivo. First results of FCS measurements show an exchange in the nucleus of the proteins Fos-CFP and Jun-YFP in the stably mono-transfected HeLa-Cells. This is also shown by

  9. Resveratrol-Loaded Lipid Nanocarriers: Correlation between In Vitro Occlusion Factor and In Vivo Skin Hydrating Effect

    Directory of Open Access Journals (Sweden)

    Lucia Montenegro

    2017-12-01

    Full Text Available Lipid nanocarriers show occlusive properties that may be related to their ability to improve skin hydration. The aim of this work was to evaluate the relationship between in vitro occlusion factor and in vivo skin hydration for three types of lipid nanocarriers: nanoemulsions (NEs, solid lipid nanoparticles (SLNs and nanostructured lipid carriers (NLCs. These lipid nanocarriers were loaded with trans-resveratrol (RSV and incorporated in gel vehicles. In vitro occlusion factor was in the order SLNs > NLCs > NEs. Gels containing unloaded or RSV loaded lipid nanocarriers were applied on the back of a hand of 12 healthy volunteers twice a day for one week, recording skin hydration changes using the instrument Soft Plus. An increase of skin hydration was observed for all lipid nanocarriers (SLNs > NLCs > NEs. RSV loading into these nanocarriers did not affect in vitro and in vivo lipid nanocarriers effects. A linear relationship (r2 = 0.969 was observed between occlusion factor and in vivo increase of skin hydration. Therefore, the results of this study showed the feasibility of using the occlusion factor to predict in vivo skin hydration resulting from topical application of different lipid nanocarriers loading an active ingredient with no inherent hydrating activity.

  10. Correlates of direct care staffs'attitutdes towards agression of persons with intellectual disabilities

    NARCIS (Netherlands)

    Knotter, M.H.; Stams, G.J.J.M.; Moonen, X.M.H.; Wissink, I.B.

    2016-01-01

    Background and aim To explain direct care staff's attitudes (responsive or rejecting) towards aggression of clients with intellectual disability (ID), data were collected about client characteristics as well as individual and team characteristics of 475 direct care staff members, working in 71

  11. Correlating in Vitro Solubilization and Supersaturation Profiles with in Vivo Exposure for Lipid Based Formulations of the CETP Inhibitor CP-532,623.

    Science.gov (United States)

    McEvoy, Claire L; Trevaskis, Natalie L; Feeney, Orlagh M; Edwards, Glenn A; Perlman, Michael E; Ambler, Catherine M; Porter, Christopher J H

    2017-12-04

    Lipid based formulations (LBFs) are a promising formulation strategy for many poorly water-soluble drugs and have been shown previously to enhance the oral exposure of CP-532,623, an oral cholesteryl ester transfer protein inhibitor. In the current study, an in vitro lipid digestion model was used to probe the relationship between drug solubilization and supersaturation on in vitro dispersion and digestion of LBF containing long chain (LC) lipids and drug absorption in vivo. After in vitro digestion of LBF based on LC lipids, the proportion of CP-532,623 maintained in the solubilized state in the aqueous phase of the digest was highest in formulations containing Kolliphor RH 40, and in most cases outperformed equivalent formulations based on MC lipids. Subsequent administration of the LC-LBFs to beagle dogs resulted in reasonable correlation between concentrations of CP-532,623 measured in the aqueous phase of the in vitro digest after 30 min digestion and in vivo exposure (AUC); however, the LC-LBFs required greater in vitro drug solubilization to elicit similar in vivo exposure when compared to previous studies with MC-LBF. Although post digestion solubilization was enhanced in LC-LBF compared to MC-LBF, equilibrium solubility studies of CP-532,623 in the aqueous phase isolated from blank lipid digestion experiments revealed that equilibrium solubility was also higher, and therefore supersaturation lower. A revised correlation based on supersaturation in the digest aqueous phase and drug absorption was therefore generated. A single, linear correlation was evident for both LC- and MC-LBF containing Kolliphor RH 40, but this did not extend to formulations based on other surfactants. The data suggest that solubilization and supersaturation are significant drivers of drug absorption in vivo, and that across formulations with similar formulation composition good correlation is evident between in vitro and in vivo measures. However, across dissimilar formulations

  12. Ex vivo

    Science.gov (United States)

    Matsuda, Kant M; Lopes-Calcas, Ana; Honke, Michael L; O'Brien-Moran, Zoe; Buist, Richard; West, Michael; Martin, Melanie

    2017-07-01

    To advance magnetic resonance imaging (MRI) technologies further for in vivo tissue characterization with histopathologic validation, we investigated the feasibility of ex vivo tissue imaging of a surgically removed human brain tumor as a comprehensive approach for radiology-pathology correlation in histoanatomically identical fashion in a rare case of pigmented ganglioglioma with complex paramagnetic properties. Pieces of surgically removed ganglioglioma, containing melanin and hemosiderin pigments, were imaged with a small bore 7-T MRI scanner to obtain T1-, T2-, and T2*-weighted image and diffusion tensor imaging (DTI). Corresponding histopathological slides were prepared for routine hematoxylin and eosin stain and special stains for melanin and iron/hemosiderin to correlate with MRI signal characteristics. Furthermore, mean diffusivity (MD) maps were generated from DTI data and correlated with cellularity using image analysis. While the presence of melanin was difficult to interpret in in vivo MRI with certainty due to concomitant hemosiderin pigments and calcium depositions, ex vivo tissue imaging clearly demonstrated pieces of tissue exhibiting the characteristic MR signal pattern for melanin with pathologic confirmation in a histoanatomically identical location. There was also concordant correlation between MD and cellularity. Although it is still in an initial phase of development, ex vivo tissue imaging is a promising approach, which offers radiology-pathology correlation in a straightforward and comprehensive manner.

  13. A Direct Correlation between Viscosity and Liquid Structure in Cu-Sn Alloys

    Directory of Open Access Journals (Sweden)

    Yan Zhao

    2017-01-01

    Full Text Available The viscosity and liquid structure of Cu100-xSnx (x=10, 20, 30, 40, at.% melts were investigated. Temperature dependence of viscosity η and correlation length D all shows an exponential decay function (Arrhenius-type equation, which is similar to our former studied Cu-Ag alloys. The correlation between viscosity and liquid structure had been studied. A simple relation between viscosity and correlation length D was found. The ratio of D and η shows a linear relationship with temperature, which is different from our former studied results in Cu-Ag alloys. Among the four Cu-Sn alloys, Cu80Sn20 and Cu70Sn30 alloys have higher activation energy for viscous flow (Ea,V, activation energy for structural evolution (Ea,D, and the slope (γ of the linear relationship of D/η with temperature due to the Cu3Sn clusters formation.

  14. Correlation between sperm characteristics and testosterone in bovine seminal plasma by direct radioimmunoassay

    Directory of Open Access Journals (Sweden)

    Luiz Waldemar de Oliveira Souza

    2011-12-01

    Full Text Available The objectives of this study were to validate a non-extractive RIA for seminal testosterone and quantify the hormone using a solid-phase commercial kit, and study the correlation between testosterone in seminal plasma and sperm characteristics. Parallelism showed a correlation index r = 0.992 (Y = -5.47 + 1.073X; R² = 0.985, indicating that the non-extractive method presented is indicated particularly for assessment of testosterone when establishing comparisons between samples. Overall mean (±SD of testosterone level was 0.60±0.65 ng/mL. Correlation was only found between the seminal concentrations of testosterone and pH of the semen.

  15. Correlation between in vitro mucus adhesion and the in vivo colonization ability of lactic acid bacteria: screening of new candidate carp probiotics.

    Science.gov (United States)

    Sugimura, Yuya; Hagi, Tatsuro; Hoshino, Takayuki

    2011-01-01

    We measured the adhesion of candidate probiotic lactic acid bacteria (LAB) to carp intestinal mucus. The percentage of adherent bacteria varied among strains. Four strains, two with high adhesion and two with low adhesion in vitro, were tested for in vivo colonization ability. Carp were fed LAB-containing feed for 12 d, and then unsupplemented feed until day 33, and the numbers and compositions of intestinal LAB were analyzed during the entire period. LAB with lower in vitro adhesion disappeared quickly from the intestine after LAB feeding stopped. LAB with higher in vitro adhesion remained in the intestine 3 weeks after LAB feeding stopped, indicating a strong correlation between mucus adhesion in vitro and colonization ability in vivo. Next we isolated nine candidate probiotic LAB with high in vitro mucus-binding ability. Three of them were fed to carp, and all three were stably maintained in the intestine.

  16. In vivo fitness correlates with host-specific virulence of Infectious hematopoietic necrosis virus (IHNV) in sockeye salmon and rainbow trout

    Science.gov (United States)

    Penaranda, M.M.D.; Wargo, A.R.; Kurath, G.

    2011-01-01

    The relationship between virulence and overall within-host fitness of the fish rhabdovirus Infectious hematopoietic necrosis virus (IHNV) was empirically investigated in vivo for two virus isolates belonging to different IHNV genogroups that exhibit opposing host-specific virulence. U group isolates are more virulent in sockeye salmon and M group isolates are more virulent in rainbow trout. In both single and mixed infections in the two fish hosts, the more virulent IHNV type exhibited higher prevalence and higher viral load than the less virulent type. Thus, a positive correlation was observed between higher in vivo fitness and higher host-specific virulence in sockeye salmon and rainbow trout. Comparisons of mean viral loads in single and mixed infections revealed no evidence for limitation due to competition effects between U and M viruses in either rainbow trout or sockeye salmon co-infections.

  17. Virulence correlates with fitness in vivo for two M group genotypes of Infectious hematopoietic necrosis virus (IHNV).

    Science.gov (United States)

    Wargo, Andrew R.; Garver, Kyle A.; Kurath, Gael

    2010-01-01

    The nature of the association between viral fitness and virulence remains elusive in vertebrate virus systems, partly due to a lack of in vivo experiments using statistically sufficient numbers of replicate hosts. We examined the relationship between virulence and fitness in Infectious hematopoietic necrosis virus (IHNV), in vivo, in intact living rainbow trout. Trout were infected with a high or low virulence genotype of M genogroup IHNV, or a mixture of the two genotypes, so as to calculate relative fitness and the effect of a competition environment on fitness. Fitness was measured as total viral load in the host at time of peak viral density, quantified by genotype-specific quantitative RT-PCR (qRT-PCR). The more virulent IHNV genotype reached higher densities in both single and mixed infections. There was no effect of competition on the performance of either genotype. Our results suggest a positive link between IHNV genotype fitness and virulence.

  18. Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion

    DEFF Research Database (Denmark)

    Poulsen, Marie Sønnegaard; Rytting, Erik; Mose, Tina

    2009-01-01

    . Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984-991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport......The placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008...... across the BeWo cells was observed in the rank order of caffeine>antipyrine>benzoic acid>glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare...

  19. Advance Care Planning in Nursing Homes: Correlates of Capacity and Possession of Advance Directives

    Science.gov (United States)

    Allen, Rebecca S.; DeLaine, Shermetra R.; Chaplin, William F.; Marson, Daniel C.; Bourgeois, Michelle S.; Dijkstra, Katinka; Burgio, Louis D.

    2003-01-01

    Purpose: The identification of nursing home residents who can continue to participate in advance care planning about end-of-life care is a critical clinical and bioethical issue. This study uses high quality observational research to identify correlates of advance care planning in nursing homes, including objective measurement of capacity. Design…

  20. Maternal Directiveness in Interactions with Developmentally Delayed Children: A Correlational Analysis.

    Science.gov (United States)

    Marfo, Kofi

    Interactions between 25 mothers and their developmentally delayed children (ages 2-5) during 15 minutes of semi-structured free play were coded independently with a global rating scale and a behavior count coding scheme. Correlational analyses were performed around three central themes: (1) the nature of the relationship between maternal…

  1. Correlations between the in vitro and in vivo bioactivity of the Ti/HA composites fabricated by a powder metallurgy method.

    Science.gov (United States)

    Ning, Congqin; Zhou, Yu

    2008-11-01

    Ti/HA composites were successfully prepared by a powder metallurgy method and the effect of phase composition on the in vitro and in vivo bioactivity of the Ti/HA composites was investigated in the present study. The correlations between the in vitro and in vivo biological behaviors were highlighted. The results showed that the in vitro and in vivo bioactivity of the Ti/HA composites was dependent on their phase composition. The in vitro bioactivity of the Ti/HA composites was evaluated in simulated body fluid with ion concentrations similar to those of human plasma. After immersion in the simulated body fluid for a certain time, apatite precipitations formed on the surface of the composites with an initial titanium content of 50 and 70 wt.%, and no apatite was found on the surface of the composite with 30% titanium. Ti(2)O was responsible for the apatite formation on the surfaces of the composites. For in vivo analysis, Ti/HA cylinders were implanted in the metaphases of the rabbit femur. At the early stage of implantation, the new bone formed on the surface of the composite with 30% titanium was much less than that on the surfaces of the composites with 50% and 70% titanium. All the Ti/HA composites formed a chemical bone-bonding interface with the host bone by 6 months after implantation. The Ti/HA composites formed the bone-bonding interface with the surrounding bone through an apatite layer. The results in the present study suggested that the in vivo results agreed well with the in vitro results.

  2. Correlates of direct care staffs' attitudes towards aggression of persons with intellectual disabilities.

    Science.gov (United States)

    Knotter, M H; Stams, G J J M; Moonen, X M H; Wissink, I B

    2016-12-01

    To explain direct care staff's attitudes (responsive or rejecting) towards aggression of clients with intellectual disability (ID), data were collected about client characteristics as well as individual and team characteristics of 475 direct care staff members, working in 71 teams. Multilevel analyses revealed that a positive team climate was positively associated with both a rejecting and responsive attitude towards aggression. Senior staff members and females showed a less responsive attitude towards aggression, whereas a relatively high percentage of females in a team and a positive attitude towards external professionals were associated with a more responsive attitude towards aggression. Unexpectedly, staff who experienced less verbal and/or physical aggressive incidents of their clients with ID showed a more rejecting attitude towards aggression. Finally, characteristics of the clients with ID accounted for the largest part of the variance in the attitude towards aggression of direct care staff, in particular psychiatric diagnoses. Further research is necessary in order to understand how team processes affect the attitude towards aggression of direct care staff. Further it is recommended to provide direct care staff with knowledge about mental disorders in clients with ID. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Direct and correlated responses to selection for total weight of lamb ...

    African Journals Online (AJOL)

    Unknown

    For this calculation, weaning weights were adjusted to 120 d for both flocks, followed by least-squares adjustments for sex of lamb. No adjustments were made for birth status. The total weight of ... root of the heritability of X, hY is the square-root of the heritability of Y, rA is the genetic correlation between X and. Y and äPY is ...

  4. Vector velocity estimation using directional beam forming and cross-correlation

    DEFF Research Database (Denmark)

    2000-01-01

    The two-dimensional velocity vector using a pulsed ultrasound field can be determined with the invention. The method uses a focused ultrasound field along the velocity direction for probing the moving medium under investigation. Several pulses are emitted and the focused received fields along...

  5. Direct and correlated responses to selection for total weight of lamb ...

    African Journals Online (AJOL)

    The estimated selection responses indicate that direct selection for TWW would be the most suitable selection criterion for improving reproductive performance in flocks with a high reproduction rate where an increase in the number of lambs would be undesirable. (South African Journal of Animal Science, 2001, 31(2): ...

  6. In Vivo Direct Molecular Imaging of Early Tumorigenesis and Malignant Progression Induced by Transgenic Expression of GFP-Met

    Directory of Open Access Journals (Sweden)

    Sharon Moshitch-Moshkovitz

    2006-05-01

    Full Text Available The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor/scatter factor (HGF/SF, play an important role in normal developmental processes, as well as in tumorigenicity and metastasis. We constructed a green fluorescent protein (GFP Met chimeric molecule that functions similarly to the wild-type Met receptor and generated GFP-Met transgenic mice. These mice ubiquitously expressed GFP-Met in specific epithelial and endothelial cells and displayed enhanced GFP-Met fluorescence in sebaceous glands. Thirty-two percent of males spontaneously developed adenomas, adenocarcinomas, and angiosarcomas in their lower abdominal sebaceous glands. Approximately 70% of adenocarcinoma tumors metastasized to the kidneys, lungs, or liver. Quantitative subcellularresolution intravital imaging revealed very high levels of GFP-Met in tumor lesions and in single isolated cells surrounding them, relative to normal sebaceous glands. These single cells preceded the formation of local and distal metastases. Higher GFP-Met levels correlated with earlier tumor onset and aggressiveness, further demonstrating the role of Met-HGF/SF signaling in cellular transformation and acquisition of invasive and metastatic phenotypes. Our novel mouse model and high-resolution intravital molecular imaging create a powerful tool that enables direct realtime molecular imaging of receptor expression and localization during primary events of tumorigenicity and metastasis at single-cell resolution.

  7. The diffusion dynamics of PEGylated liposomes in the intact vitreous of the ex vivo porcine eye: A fluorescence correlation spectroscopy and biodistribution study

    DEFF Research Database (Denmark)

    Eriksen, Anne Zebitz; Brewer, Jonathan; Andresen, Thomas Lars

    2017-01-01

    The diffusion dynamics of nanocarriers in the vitreous and the influence of nanocarrier physicochemical properties on these dynamics is an important aspect of the efficacy of intravitreal administered nanomedicines for the treatment of posterior segment eye diseases. Here we use fluorescence...... correlation spectroscopy (FCS) to determine liposome diffusion coefficients in the intact vitreous (DVit) of ex vivo porcine eyes using a modified Miyake-Apple technique to minimize the disruption of the vitreous fine structure. We chose to investigate whether the zeta potential of polyethylene glycol...

  8. Modulating the bioluminescence emission of photoproteins by in vivo site-directed incorporation of non-natural amino acids.

    Science.gov (United States)

    Rowe, Laura; Ensor, Mark; Mehl, Ryan; Daunert, Sylvia

    2010-05-21

    The in vivo incorporation of non-natural amino acids into specific sites within proteins has become an extremely powerful tool for bio- and protein chemists in recent years. One avenue that has yet to be explored, however, is whether or not the incorporation of non-natural amino acids can tune the color of light emitted by bioluminescent proteins, whose light emission mechanisms are more complex and less well understood than their fluorescent counterparts. Bioluminescent proteins are becoming increasingly important in a variety of research fields, such as in situ imaging and the study of protein-protein interactions in vivo, and an increased spectral variety of bioluminescent reporters is needed for further progress. Thus, herein we report the first successful spectral shifting (44 nm) of a bioluminescent protein, aequorin, via the site-specific incorporation of several non-natural amino acids into an integral amino acid position within the aequorin structure in vivo.

  9. Calibration of a prompt gamma in vivo neutron activation facility for direct measurement of total body protein in intensive care patients

    Energy Technology Data Exchange (ETDEWEB)

    Mitra, S.; Plank, L.D.; Hill, G.L. (Auckland Univ. Hospital (New Zealand). Dept. of Surgery)

    1993-12-01

    The Auckland in vivo prompt gamma neutron activation analysis facility has been calibrated for direct measurement of protein and chlorine in intensive care patients without reliance on hydrogen as an internal standard. These patients often present with massive fluid overload and the technique using hydrogen as an internal standard may be invalidated. Eight variable anthropomorphic phantoms containing physiological amounts of the major body elements were constructed from commercially available flexible polythene tubes and used for calibration. (author).

  10. The Correlation between Managers’ Delegation of Authority with the Manner of Employee Direction in Hospitals of Qom Province

    Directory of Open Access Journals (Sweden)

    Maleki M.R

    2011-08-01

    Full Text Available Background and Objectives: The destructive effect of centralized management can be found throughout each organization, which is a barrier for delegation of authority and productivity leading to administrative violence increase and compression and frigidity of affairs. With attention to the importance of delegation of authority this research aimed at determining the correlation between the manager's delegation of authority with the manner of employee direction in Qom hospitals, designed for contributing to improvement of managers’ performance in hospitals.Methods: This correlational and cross-sectional research, was carried out on all the employees under the control of managers and chiefs of Qom province hospitals (N=2167. Sampling was done by cluster sampling method through the use of Cokran sampling based on Morgan and kerjsi chart. 998 samples with the confidence level of %95 and permitted errors of 0.05 were randomly selected. Data were collected via questionnaires which were answered by self-report method. The data were then analyzed by the Pearson correlation coefficient, variance's test F analyses, multiple variant regression and T-test.Results: The mean score of the manager's non-delegation of authority was (32.4. Among the indicators of the direction, there was a significant relationship between the motivation (mean= 61.44 and organizational communication (49.39, also there was a significant relationship between the managers’ delegation of authority and the manner of their employees direction (non-delegation of authority R=-0.13. Conclusion: Due to the meaningful and direct relationship between most of direction variables with the managers’ delegation of authority, increasing the delegation of authority and deconcentration can lead to an increase in employee motivation and (vertical and formal communication and improved performance of affairs.

  11. Neuronal firing rate, inter-neuron correlation and synchrony in area MT are correlated with directional choices during stimulus and reward expectation.

    Science.gov (United States)

    Thiele, A; Hoffmann, K-P

    2008-07-01

    Sensation, memories, and predictions contribute to choices in everyday life, and their relative impact should change with task constraints. To investigate how the impact from sensory cortex on decision making varies with task constraints we trained macaque monkeys in a direction discrimination task where they could maximize reward by waiting for sensory visual information early in a trial, while focusing on memory and reward prediction as a trial progressed. The task constraints caused animals to indicate decisions in complete absence of visual motion stimuli (stimulus independent decisions), as 25% of the trials were 'no stimulus' trials. On 'no stimulus' trials reward delivery depended on the current decision in relation to the decision history. Stimulus independent decisions occurred during an epoch when a stimulus could in principle have been presented, or afterwards when stimuli could not occur anymore. Stimulus independent decisions were significantly different during these two periods. Reward exploitation was more efficient late in the trial, but it was not associated with systematic activity changes in directionally selective neurons in area MT. Conversely, systematic changes of neuronal activity and firing rate correlation in directionally selective middle temporal area (MT) neurons were restricted to a short time period before early decisions. Changing task constraints in the course of a single trial thus determines how neurons in sensory areas contribute to decision making.

  12. Catheter-based intraluminal optical coherence tomography (OCT) of the ureter: ex-vivo correlation with histology in porcine specimens

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Lisse, Ulrike L.; Stief, Christian G. [University of Munich, Department of Urology, Munich (Germany); Meissner, Oliver A.; Bauer, Margit; Eibel, Roger; Reiser, Maximilian F.; Mueller-Lisse, Ullrich G. [University of Munich, Department of Radiology, Munich (Germany); Babaryka, Gregor [University of Munich, Department Pathology, Munich (Germany)

    2006-10-15

    Intraluminal optical coherence tomography (OCT) applies coherent light to provide cross-sectional images with a spatial resolution of 10-25 {mu}m. We compared OCT and matching whole-mount histology microscopy sections of porcine upper ureters ex vivo for visualization and delineation of different tissue layers of the ureteral wall. Porcine ureters (six specimens, 24 quadrants) were flushed with normal saline solution prior to insertion of the OCT catheter (diameter, 0.014 inch, OCT wavelength, 1,300{+-}20 nm). Cross-sectional OCT images were obtained in marked locations before specimens were fixed in 4% formalin, cut at marked locations, whole-mounted, and stained with hematoxilin and eosin. Visualization and delineation of different tissue layers of the ureteral wall by OCT was compared with matching histology by two independent observers (O1,O2). OCT distinguished tissue layers of the ureteral wall in all quadrants. In OCT images, O1/O2 delineated urothelium and lamina propria in 23/24 quadrants, lamina propria and muscle layer in 19/16 quadrants, inner and outer muscle layer in 13/0 quadrants, and urothelial cell layers in 13/2 quadrants, respectively. Intraluminal OCT provides histology-like images of the ureter in porcine specimens ex vivo and reliably distinguishes between urothelium and deeper tissue layers of the ureteral wall. (orig.)

  13. Correlation between the magic wavelengths and the polarization direction of the linearly polarized laser in the Ca+ optical clock

    Science.gov (United States)

    Liu, Pei-Liang; Huang, Yao; Bian, Wu; Shao, Hu; Qian, Yuan; Guan, Hua; Tang, Li-Yan; Gao, Ke-Lin

    2015-03-01

    The magic wavelengths for different Zeeman components are measured based on the 40Ca+ optical clock. The dynamic dipole polarizability of a non-zero angular moment level has correlation with the polarization direction of the linearly polarized laser beam, and we show that the four hyperfine structure levels of 4s1/2,m=±1/2 and 3d5/2,m=±1/2 for 40Ca+ have the same dynamic dipole polarizability at the magic wavelength and a certain polarization direction. In addition, the existence of a specific direction of polarization may provide a new idea for improving the precision of magic wavelength measurement in experiment. Project supported by the National Basic Research Program of China (Grant No. 2012CB821301), the National Natural Science Foundation of China (Grant Nos. 11474318, 91336211, and 11034009), and the Chinese Academy of Sciences.

  14. Co-localized or randomly distributed? Pair cross correlation of in vivo grown subgingival biofilm bacteria quantified by digital image analysis.

    Directory of Open Access Journals (Sweden)

    Claudia Schillinger

    Full Text Available The polymicrobial nature of periodontal diseases is reflected by the diversity of phylotypes detected in subgingival plaque and the finding that consortia of suspected pathogens rather than single species are associated with disease development. A number of these microorganisms have been demonstrated in vitro to interact and enhance biofilm integration, survival or even pathogenic features. To examine the in vivo relevance of these proposed interactions, we extended the spatial arrangement analysis tool of the software daime (digital image analysis in microbial ecology. This modification enabled the quantitative analysis of microbial co-localization in images of subgingival biofilm species, where the biomass was confined to fractions of the whole-image area, a situation common for medical samples. Selected representatives of the disease-associated red and orange complexes that were previously suggested to interact with each other in vitro (Tannerella forsythia with Fusobacterium nucleatum and Porphyromonas gingivalis with Prevotella intermedia were chosen for analysis and labeled with specific fluorescent probes via fluorescence in situ hybridization. Pair cross-correlation analysis of in vivo grown biofilms revealed tight clustering of F. nucleatum/periodonticum and T. forsythia at short distances (up to 6 µm with a pronounced peak at 1.5 µm. While these results confirmed previous in vitro observations for F. nucleatum and T. forsythia, random spatial distribution was detected between P. gingivalis and P. intermedia in the in vivo samples. In conclusion, we successfully employed spatial arrangement analysis on the single cell level in clinically relevant medical samples and demonstrated the utility of this approach for the in vivo validation of in vitro observations by analyzing statistically relevant numbers of different patients. More importantly, the culture-independent nature of this approach enables similar quantitative analyses for "as

  15. Co-localized or randomly distributed? Pair cross correlation of in vivo grown subgingival biofilm bacteria quantified by digital image analysis.

    Science.gov (United States)

    Schillinger, Claudia; Petrich, Annett; Lux, Renate; Riep, Birgit; Kikhney, Judith; Friedmann, Anton; Wolinsky, Lawrence E; Göbel, Ulf B; Daims, Holger; Moter, Annette

    2012-01-01

    The polymicrobial nature of periodontal diseases is reflected by the diversity of phylotypes detected in subgingival plaque and the finding that consortia of suspected pathogens rather than single species are associated with disease development. A number of these microorganisms have been demonstrated in vitro to interact and enhance biofilm integration, survival or even pathogenic features. To examine the in vivo relevance of these proposed interactions, we extended the spatial arrangement analysis tool of the software daime (digital image analysis in microbial ecology). This modification enabled the quantitative analysis of microbial co-localization in images of subgingival biofilm species, where the biomass was confined to fractions of the whole-image area, a situation common for medical samples. Selected representatives of the disease-associated red and orange complexes that were previously suggested to interact with each other in vitro (Tannerella forsythia with Fusobacterium nucleatum and Porphyromonas gingivalis with Prevotella intermedia) were chosen for analysis and labeled with specific fluorescent probes via fluorescence in situ hybridization. Pair cross-correlation analysis of in vivo grown biofilms revealed tight clustering of F. nucleatum/periodonticum and T. forsythia at short distances (up to 6 µm) with a pronounced peak at 1.5 µm. While these results confirmed previous in vitro observations for F. nucleatum and T. forsythia, random spatial distribution was detected between P. gingivalis and P. intermedia in the in vivo samples. In conclusion, we successfully employed spatial arrangement analysis on the single cell level in clinically relevant medical samples and demonstrated the utility of this approach for the in vivo validation of in vitro observations by analyzing statistically relevant numbers of different patients. More importantly, the culture-independent nature of this approach enables similar quantitative analyses for "as

  16. Direct terrestrial–marine correlation demonstrates surprisingly late onset of the last interglacial in central Europe

    Science.gov (United States)

    Sier, Mark J.; Roebroeks, Wil; Bakels, Corrie C.; Dekkers, Mark J.; Brühl, Enrico; De Loecker, Dimitri; Gaudzinski-Windheuser, Sabine; Hesse, Norbert; Jagich, Adam; Kindler, Lutz; Kuijper, Wim J.; Laurat, Thomas; Mücher, Herman J.; Penkman, Kirsty E.H.; Richter, Daniel; van Hinsbergen, Douwe J.J.

    2011-01-01

    An interdisciplinary study of a small sedimentary basin at Neumark Nord 2 (NN2), Germany, has yielded a high-resolution record of the palaeomagnetic Blake Event, which we are able to place at the early part of the last interglacial pollen sequence documented from the same section. We use this data to calculate the duration of this stratigraphically important event at 3400 ± 350 yr. More importantly, the Neumark Nord 2 data enables precise terrestrial–marine correlation for the Eemian stage in central Europe. This shows a remarkably large time lag of ca. 5000 yr between the MIS 5e ‘peak’ in the marine record and the start of the last interglacial in this region. PMID:26523075

  17. Blood pressure directly correlates with blood viscosity in diabetes type 1 children but not in normals.

    Science.gov (United States)

    Vázquez, Beatriz Y Salazar; Vázquez, Miguel A Salazar; Jáquez, Manuel Guajardo; Huemoeller, Antonio H Bracho; Intaglietta, Marcos; Cabrales, Pedro

    2010-01-01

    To determine the relationship between mean arterial blood pressure (MAP) and blood viscosity in diabetic type 1 children and healthy controls to investigate whether MAP is independent of blood viscosity in healthy children, and vice versa. Children with diabetes type 1 treated by insulin injection were studied. Controls were healthy children of both sexes. MAP was calculated from systolic and diastolic pressure measurements. Blood viscosity was determined indirectly by measuring blood hemoglobin (Hb) content. The relationship between Hb, hematocrit (Hct) and blood viscosity was determined in a subgroup of controls and diabetics selected at random. 21 (10.6+/-2.5 years) type 1 diabetic children treated with insulin and 25 healthy controls age 9.6+/-1.7 years were studied. Hb was 13.8+/-0.8 g/dl in normal children vs. 14.3+/-0.9 g/dl in the diabetic group (p<0.05). MAP was 71.4+/-8.2 in the normal vs. 82.9+/-7.2 mmHg in the diabetic group (p<0.001). Glucose was 89.3+/-10.6 vs. 202.4+/-87.4 mg/dl respectively. Diabetics had a positive MAP/Hb correlation (p=0.007), while normals showed a non significant (p=0.2) negative correlation. The blood viscosity/Hb relationship was studied in a subgroup of 8 healthy controls and 8 diabetic type 1 children. There was no significant difference in Hb and Hct between groups. Diabetics showed a trend of increasing blood viscosity (+7%, p=0.15). Normal children compensate for the increase in vascular resistance due to increased blood viscosity (increased Hb and Hct) while diabetic children do not, probably due to endothelial dysfunction.

  18. Visualizing the Acute Effects of Vascular-Targeted Therapy In Vivo Using Intravital Microscopy and Magnetic Resonance Imaging: Correlation with Endothelial Apoptosis, Cytokine Induction, and Treatment Outcome

    Directory of Open Access Journals (Sweden)

    Mukund Seshadri

    2007-02-01

    Full Text Available The acute effects of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA were investigated in vivo using intravital microscopy (IVM and magnetic resonance imaging (MRI. Changes in vascular permeability and blood flow of syngeneic CT-26 murine colon adenocarcinomas were assessed at 4 and 24 hours after DMXAA treatment (30 mg/kg, i.p. and correlated with induction of tumor necrosis factor-α (TNF-α, endothelial damage [CD31/terminal deoxynucleotidyl transferase (TdT], and treatment outcome. Intravital imaging revealed a marked increase in vascular permeability 4 hours after treatment, consistent with increases in intratumoral mRNA and protein levels of TNF-α. Parallel contrast-enhanced MRI studies showed a ~ 4-fold increase in longitudinal relaxation rates (ΔR1, indicative of increased contrast agent accumulation within the tumor. Dualimmunostained tumor sections (CD31/TdT revealed evidence of endothelial apoptosis at this time point. Twenty-four hours after treatment, extensive hemorrhage and complete disruption of vascular architecture were observed with IVM, along with a significant reduction in ΔR1 and virtual absence of CD31 immunostaining. DMXAA-induced tumor vascular damage resulted in significant long-term (60-day cures compared to untreated controls. Multimodality imaging approaches are useful in visualizing the effects of antivascular therapy in vivo. Such approaches allow cross validation and correlation of findings with underlying molecular changes contributing to treatment outcome.

  19. Direct fitness correlates and thermal consequences of facultative aggregation in a desert lizard.

    Directory of Open Access Journals (Sweden)

    Alison R Davis Rabosky

    Full Text Available Social aggregation is a common behavioral phenomenon thought to evolve through adaptive benefits to group living. Comparing fitness differences between aggregated and solitary individuals in nature--necessary to infer an evolutionary benefit to living in groups--has proven difficult because communally-living species tend to be obligately social and behaviorally complex. However, these differences and the mechanisms driving them are critical to understanding how solitary individuals transition to group living, as well as how and why nascent social systems change over time. Here we demonstrate that facultative aggregation in a reptile (the Desert Night Lizard, Xantusia vigilis confers direct reproductive success and survival advantages and that thermal benefits of winter huddling disproportionately benefit small juveniles, which can favor delayed dispersal of offspring and the formation of kin groups. Using climate projection models, however, we estimate that future aggregation in night lizards could decline more than 50% due to warmer temperatures. Our results support the theory that transitions to group living arise from direct benefits to social individuals and offer a clear mechanism for the origin of kin groups through juvenile philopatry. The temperature dependence of aggregation in this and other taxa suggests that environmental variation may be a powerful but underappreciated force in the rapid transition between social and solitary behavior.

  20. In vitro–in vivo correlations for endocrine activity of a mixture of 5 currently used pesticides

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Hadrup, Niels; Boberg, Julie

    2013-01-01

    Two pesticide mixtures consisting of three and five currently used pesticides, respectively, were investigated for potential endocrine disrupting effects. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin and Mix 5 contained the same 3 pesticides plus malathion and terbuthylazine. All...... five single pesticides and the two mixtures were tested in vitro in H295R cells for effects on steroidogenesis. All five pesticides individually and both mixtures affected steroidogenesis. The mixtures caused an increase in progesterone and a decrease in testosterone, and Mix 5 also increased estradiol......, indicating increased aromatase activity. The pesticide-mixtures were also investigated in vivo in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. All 5 pesticides could be detected in the amniotic fluid, demonstrating exposure of the fetuses. Decreased estradiol...

  1. Use of Bayesian Inference to Correlate In Vitro Embryo Production and In Vivo Fertility in Zebu Bulls

    Directory of Open Access Journals (Sweden)

    Mateus José Sudano

    2011-01-01

    Full Text Available The objective of this experiment was to test in vitro embryo production (IVP as a tool to estimate fertility performance in zebu bulls using Bayesian inference statistics. Oocytes were matured and fertilized in vitro using sperm cells from three different Zebu bulls (V, T, and G. The three bulls presented similar results with regard to pronuclear formation and blastocyst formation rates. However, the cleavage rates were different between bulls. The estimated conception rates based on combined data of cleavage and blastocyst formation were very similar to the true conception rates observed for the same bulls after a fixed-time artificial insemination program. Moreover, even when we used cleavage rate data only or blastocyst formation data only, the estimated conception rates were still close to the true conception rates. We conclude that Bayesian inference is an effective statistical procedure to estimate in vivo bull fertility using data from IVP.

  2. Activity-dependent increases in local oxygen consumption correlate with postsynaptic currents in the mouse cerebellum in vivo

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Caesar, Kirsten; Thomsen, Kirsten Engelund

    2011-01-01

    Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF). Activity-dependent rises in CMRO(2) fluctuate with ATP turnover due to ion pumping. In vitro studies suggest that increases in cytosolic Ca(2+) stimulate oxidative m...

  3. UNMASKING MASKED HYPERTENSION: PREVALENCE, CLINICAL IMPLICATIONS, DIAGNOSIS, CORRELATES, AND FUTURE DIRECTIONS

    Science.gov (United States)

    Peacock, James; Diaz, Keith M.; Viera, Anthony J.; Schwartz, Joseph E.; Shimbo, Daichi

    2014-01-01

    ‘Masked hypertension’ is defined as having non-elevated clinic blood pressure (BP) with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring. Approximately 15–30% of adults with non-elevated clinic BP have masked hypertension. Masked hypertension is associated with increased risks of cardiovascular morbidity and mortality compared to sustained normotension (non-elevated clinic and ambulatory BP), which is similar to or approaching the risk associated with sustained hypertension (elevated clinic and ambulatory BP). The confluence of increased cardiovascular risk and a failure to be diagnosed by the conventional approach of clinic BP measurement makes masked hypertension a significant public health concern. However, many important questions remain. First, the definition of masked hypertension varies across studies. Further, the best approach in the clinical setting to exclude masked hypertension also remains unknown. It is unclear whether home BP monitoring is an adequate substitute for ambulatory BP monitoring in identifying masked hypertension. Few studies have examined the mechanistic pathways that may explain masked hypertension. Finally, scarce data are available on the best approach to treating individuals with masked hypertension. Herein, we review the current literature on masked hypertension including definition, prevalence, clinical implications, special patient populations, correlates, issues related to diagnosis, treatment, and areas for future research. PMID:24573133

  4. Direct correlation between potentiometric and impedance biosensing of antibody-antigen interactions using an integrated system

    Science.gov (United States)

    Tsai, Meng-Yen; Creedon, Niamh; Brightbill, Eleanor; Pavlidis, Spyridon; Brown, Billyde; Gray, Darren W.; Shields, Niall; Sayers, Ríona; Mooney, Mark H.; O'Riordan, Alan; Vogel, Eric M.

    2017-08-01

    A fully integrated system that combines extended gate field-effect transistor (EGFET)-based potentiometric biosensors and electrochemical impedance spectroscopy (EIS)-based biosensors has been demonstrated. This integrated configuration enables the sequential measurement of the same immunological binding event on the same sensing surface and consequently sheds light on the fundamental origins of sensing signals produced by FET and EIS biosensors, as well as the correlation between the two. Detection of both the bovine serum albumin (BSA)/anti-BSA model system in buffer solution and bovine parainfluenza antibodies in complex blood plasma samples was demonstrated using the integrated biosensors. Comparison of the EGFET and EIS sensor responses reveals similar dynamic ranges, while equivalent circuit modeling of the EIS response shows that the commonly reported total impedance change (ΔZtotal) is dominated by the change in charge transfer resistance (Rct) rather than surface capacitance (Csurface). Using electrochemical kinetics and the Butler-Volmer equation, we unveil that the surface potential and charge transfer resistance, measured by potentiometric and impedance biosensors, respectively, are, in fact, intrinsically linked. This observation suggests that there is no significant gain in using the FET/EIS integrated system and leads to the demonstration that low-cost EGFET biosensors are sufficient as a detection tool to resolve the charge information of biomolecules for practical sensing applications.

  5. PilB localization correlates with the direction of twitching motility in the cyanobacterium Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Schuergers, Nils; Nürnberg, Dennis J; Wallner, Thomas; Mullineaux, Conrad W; Wilde, Annegret

    2015-05-01

    Twitching motility depends on the adhesion of type IV pili (T4P) to a substrate, with cell movement driven by extension and retraction of the pili. The mechanism of twitching motility, and the events that lead to a reversal of direction, are best understood in rod-shaped bacteria such as Myxococcus xanthus. In M. xanthus, the direction of movement depends on the unipolar localization of the pilus extension and retraction motors PilB and PilT to opposite cell poles. Reversal of direction results from relocalization of PilB and PilT. Some cyanobacteria utilize twitching motility for phototaxis. Here, we examine twitching motility in the cyanobacterium Synechocystis sp. PCC 6803, which has a spherical cell shape without obvious polarity. We use a motile Synechocystis sp. PCC 6803 strain expressing a functional GFP-tagged PilB1 protein to show that PilB1 tends to localize in 'crescents' adjacent to a specific region of the cytoplasmic membrane. Crescents are more prevalent under the low-light conditions that favour phototactic motility, and the direction of motility strongly correlates with the orientation of the crescent. We conclude that the direction of twitching motility in Synechocystis sp. PCC 6803 is controlled by the localization of the T4P apparatus, as it is in M. xanthus. The PilB1 crescents in the spherical cells of Synechocystis can be regarded as being equivalent to the leading pole in the rod-shaped cells. © 2015 The Authors.

  6. Modulating the bioluminescence emission of photoproteins by in vivo site-directed incorporation of non-natural amino acids

    OpenAIRE

    Rowe, Laura; Ensor, Mark; Mehl, Ryan; Daunert, Sylvia

    2010-01-01

    The in vivo incorporation of non-natural amino acids into specific sites within proteins has become an extremely powerful tool for bio- and protein chemists in recent years. One avenue that has yet to be explored however, is whether or not the incorporation of non-natural amino acids can tune the color of light emitted by bioluminescent proteins, whose light emission mechanisms are more complex and less well understood than their fluorescent counterparts. Bioluminescent proteins are becoming ...

  7. Prediction of in vivo potential for metabolic activation of drugs into chemically reactive intermediate: correlation of in vitro and in vivo generation of reactive intermediates and in vitro glutathione conjugate formation in rats and humans.

    Science.gov (United States)

    Masubuchi, Noriko; Makino, Chie; Murayama, Nobuyuki

    2007-03-01

    The covalent binding of reactive intermediates to macromolecules might have potential involvement in severe adverse drug reactions. Thus, quantification of reactive metabolites is necessary during the early stage of drug discovery to avoid serious toxicity. In this study, the relationship between covalent binding and glutathione (GSH) conjugate formation in rat and human liver microsomes were investigated using 10 representative radioactive compounds that have been reported as hepatotoxic or having other toxicity derived from their reactive intermediates: acetaminophen, amodiaquine, carbamazepine, clozapine, diclofenac, furosemide, imipramine, indomethacin, isoniazid, and tienilic acid, all at a concentration of 10 microM. The GSH conjugate formation rate correlates well with the covalent binding of radioactivity (both rat and human, r2 = 0.93), which suggests that quantification of the GSH conjugate can be used to estimate covalent binding. To quantify the GSH-conjugation rate with non-radiolabeled compounds in vitro, the validation study for the determination of GSH conjugate formation using 35S-GSH by radio-HPLC was useful to predict metabolic activation. Following oral administration of 20 mg/kg of the radiolabeled compounds to rats, radioactivity that covalently bound to plasma and liver proteins was determined. The in vivo maximum covalent binding level in liver based on the free fraction of plasma area under the concentration curve (AUC) and in vitro covalent binding rate was found to correlate well (r2 = 0.79). Therefore, this model for in vitro covalent binding studies in human and rat and in vivo rat studies might be useful in predicting human metabolic activation of compounds.

  8. Fast evaluation of 69 basal cell carcinomas with ex vivo fluorescence confocal microscopy: criteria description, histopathological correlation, and interobserver agreement.

    Science.gov (United States)

    Bennàssar, Antoni; Carrera, Cristina; Puig, Susana; Vilalta, Antoni; Malvehy, Josep

    2013-07-01

    Fluorescence confocal microscopy (FCM) represents a first step toward a rapid "bedside pathology" in the Mohs surgery setting and in other fields of general pathology. To describe and validate FCM criteria for the main basal cell carcinoma (BCC) subtypes and to demonstrate the overall agreement with classic pathologic analysis of hematoxylin-eosin-stained samples. DESIGN A total of 69 BCCs from 66 patients were prospectively imaged using ex vivo FCM. Confocal mosaics were evaluated in real time and compared with classic pathologic analysis. Department of Dermatology, Hospital Clínic of Barcelona, Barcelona, Spain, between November 2010 and July 2011. Patients with BCC attending the Mohs Surgery Unit. Presence or absence of BCC and histological subtype (superficial, nodular, and infiltrating) in the confocal mosaics. Eight criteria for BCC were described, evaluated, and validated. Although there were minor differences among BCC subtypes, the most BCC-defining criteria were peripheral palisading, clefting, nuclear pleomorphism, and presence of stroma. These criteria were validated with independent observers (κ values >0.7 [corrected] for most criteria). We herein propose, describe, and validate FCM criteria for BCC diagnosis. Fluorescence confocal microscopy is an attractive alternative to histopathologic analysis of frozen sections during Mohs surgery because large areas of freshly excised tissue can be assessed in real time without the need for tissue processing while minimizing labor and costs.

  9. Transient axonal glycoprotein-1 (TAG-1 and laminin-α1 regulate dynamic growth cone behaviors and initial axon direction in vivo

    Directory of Open Access Journals (Sweden)

    Yost H Joseph

    2008-02-01

    Full Text Available Abstract Background How axon guidance signals regulate growth cone behavior and guidance decisions in the complex in vivo environment of the central nervous system is not well understood. We have taken advantage of the unique features of the zebrafish embryo to visualize dynamic growth cone behaviors and analyze guidance mechanisms of axons emerging from a central brain nucleus in vivo. Results We investigated axons of the nucleus of the medial longitudinal fascicle (nucMLF, which are the first axons to extend in the zebrafish midbrain. Using in vivo time-lapse imaging, we show that both positive axon-axon interactions and guidance by surrounding tissue control initial nucMLF axon guidance. We further show that two guidance molecules, transient axonal glycoprotein-1 (TAG-1 and laminin-α1, are essential for the initial directional extension of nucMLF axons and their subsequent convergence into a tight fascicle. Fixed tissue analysis shows that TAG-1 knockdown causes errors in nucMLF axon pathfinding similar to those seen in a laminin-α1 mutant. However, in vivo time-lapse imaging reveals that while some defects in dynamic growth cone behavior are similar, there are also defects unique to the loss of each gene. Loss of either TAG-1 or laminin-α1 causes nucMLF axons to extend into surrounding tissue in incorrect directions and reduces axonal growth rate, resulting in stunted nucMLF axons that fail to extend beyond the hindbrain. However, defects in axon-axon interactions were found only after TAG-1 knockdown, while defects in initial nucMLF axon polarity and excessive branching of nucMLF axons occurred only in laminin-α1 mutants. Conclusion These results demonstrate how two guidance cues, TAG-1 and laminin-α1, influence the behavior of growth cones during axon pathfinding in vivo. Our data suggest that TAG-1 functions to allow growth cones to sense environmental cues and mediates positive axon-axon interactions. Laminin-α1 does not regulate

  10. The Correlation between Managers’ Delegation of Authority with the Manner of Employee Direction in Hospitals of Qom Province

    Directory of Open Access Journals (Sweden)

    M.R Maleki

    2012-05-01

    Full Text Available

    Background and Objectives: The destructive effect of centralized management can be found throughout each organization, which is a barrier for delegation of authority and productivity leading to administrative violence increase and compression and frigidity of affairs. With attention to the importance of delegation of authority this research aimed at determining the correlation between the manager's delegation of authority with the manner of employee direction in Qom hospitals, designed for contributing to improvement of managers’ performance in hospitals.

     

    Methods: This correlational and cross-sectional research, was carried out on all the employees under the control of managers and chiefs of Qom province hospitals (N=2167. Sampling was done by cluster sampling method through the use of Cokran sampling based on Morgan and kerjsi chart. 998 samples with the confidence level of 95% and permitted errors of 0.05 were randomly selected. Data were collected via questionnaires which were answered by self-report method. The data were then analyzed by the Pearson correlation coefficient, variance's test F analyses, multiple variant regression and T-test.

     

    Results: The mean score of the manager's non-delegation of authority was (32.4. Among the indicators of the direction, there was a significant relationship between the motivation (mean= 61.44 and organizational communication (49.39, also there was a significant relationship between the managers’ delegation of authority and the manner of their employees direction (non-delegation of authority R=-0.13.

     

    Conclusion: Due to the meaningful and direct relationship between most of direction variables with the managers’ delegation of authority, increasing the delegation of authority and deconcentration can lead to an increase

  11. Child and family-level correlates of direct and indirect peer victimization among children ages 6-9.

    Science.gov (United States)

    Boel-Studt, Shamra; Renner, Lynette M

    2014-06-01

    The purpose of this study was to examine the prevalence and child and family-level correlates of direct and indirect victimization by peers among children ages 6-9. Four hundred and twenty-five children were included in the final sample. Data for this study were drawn from the first wave of the Developmental Victimization Survey. Logistic regression models were used to examine associations between children's demographics, anxiety, depression, anger, parent-child relationship, and exposure to family violence and children's experience of direct or indirect victimization by peers. The results showed that increased depression scores and exposure to family violence were associated with increased risk for direct and indirect victimization by peers. Black children were more likely to experience direct victimization and less likely to experience indirect victimization compared to White children. Child's race significantly moderated the association between parental criticism and indirect victimization. Child's gender did not significantly moderate these associations. Implications for developmentally specific prevention and intervention approaches that are grounded in a social-ecological framework are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Direct in vivo evidence for increased proliferation of CLL cells in lymph nodes compared to bone marrow and peripheral blood

    DEFF Research Database (Denmark)

    Herndon, Thomas M; Chen, Shih-Ann; Saba, Nakhle S

    2017-01-01

    of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of 'newly born' cells would be highest in the LNs. Using a deuterium oxide ((2)H) in vivo labeling...... method in which patients consumed deuterated (heavy) water ((2)H2O), we determined CLL cell kinetics in concurrently obtained samples from LN, PB and BM. The LN was identified as the anatomical site harboring the largest fraction of newly born cells, compared to PB and BM. In fact, the calculated birth...

  13. In Vivo Noninvasive Imaging of Healthy Lower Lip Mucosa: A Correlation Study between High-Definition Optical Coherence Tomography, Reflectance Confocal Microscopy, and Histology

    Directory of Open Access Journals (Sweden)

    Alejandra García-Hernández

    2013-01-01

    Full Text Available In recent years, technology has allowed the development of new diagnostic techniques which allow real-time, in vivo, noninvasive evaluation of morphological changes in tissue. This study compares and correlates the images and findings obtained by high-definition optical coherence tomography (HD-OCT and reflectance confocal microscopy (RCM with histology in normal healthy oral mucosa. The healthy lip mucosa of ten adult volunteers was imaged with HD-OCT and RCM. Each volunteer was systematically evaluated by RCM starting in the uppermost part of the epithelium down to the lamina propia. Afterwards, volunteers were examined with a commercially available full-field HD-OCT system using both the “slice” and the “en-face” mode. A “punch” biopsy of the lower lip mucosa was obtained and prepared for conventional histology. The architectural overview offered by “slice” mode HD-OCT correlates with histologic findings at low magnification. In the superficial uppermost layers of the epithelium, RCM imaging provided greater cellular detail than histology. As we deepened into the suprabasal layers, the findings are in accordance with physiological cellular differentiation and correlate with the images obtained from conventional histology. The combined use of these two novel non-invasive imaging techniques provides morphological imaging with sufficient resolution and penetration depth, resulting in quasihistological images.

  14. Direct comparison of the histidine-rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR green I fluorescence (MSF) drug sensitivity tests in Plasmodium falciparum reference clones and fresh ex vivo field isolates from Cambodia.

    Science.gov (United States)

    Chaorattanakawee, Suwanna; Tyner, Stuart D; Lon, Chanthap; Yingyuen, Kritsanai; Ruttvisutinunt, Wiriya; Sundrakes, Siratchana; Sai-gnam, Piyaporn; Johnson, Jacob D; Walsh, Douglas S; Saunders, David L; Lanteri, Charlotte A

    2013-07-12

    Performance of the histidine-rich protein-2 enzyme-linked immunosorbent assay (HRP-2 ELISA) and malaria SYBR Green I fluorescence (MSF) drug sensitivity tests were directly compared using Plasmodium falciparum reference strains and fresh ex vivo isolates from Cambodia against a panel of standard anti-malarials. The objective was to determine which of these two common assays is more appropriate for studying drug susceptibility of "immediate ex vivo" (IEV) isolates, analysed without culture adaption, in a region of relatively low malaria transmission. Using the HRP-2 and MSF methods, the 50% inhibitory concentration (IC50) values against a panel of malaria drugs were determined for P. falciparum reference clones (W2, D6, 3D7 and K1) and 41 IEV clinical isolates from an area of multidrug resistance in Cambodia. Comparison of the IC50 values from the two methods was made using Wilcoxon matched pair tests and Pearson's correlation. The lower limit of parasitaemia detection for both methods was determined for reference clones and IEV isolates. Since human white blood cell (WBC) DNA in clinical samples is known to reduce MSF assay sensitivity, SYBR Green I fluorescence linearity of P. falciparum samples spiked with WBCs was evaluated to assess the relative degree to which MSF sensitivity is reduced in clinical samples. IC50 values correlated well between the HRP-2 and MSF methods when testing either P. falciparum reference clones or IEV isolates against 4-aminoquinolines (chloroquine, piperaquine and quinine) and the quinoline methanol mefloquine (Pearson r = 0.85-0.99 for reference clones and 0.56-0.84 for IEV isolates), whereas a weaker IC50 value correlation between methods was noted when testing artemisinins against reference clones and lack of correlation when testing IEV isolates. The HRP-2 ELISA produced a higher overall success rate (90% for producing IC50 best-fit sigmoidal curves), relative to only a 40% success rate for the MSF assay, when evaluating ex

  15. Digital image correlation and finite element modelling as a method to determine mechanical properties of human soft tissue in vivo

    CERN Document Server

    Moerman, Kevin M; Evans, Sam L; Simms, Ciaran K

    2016-01-01

    The mechanical properties of human soft tissue are crucial for impact biomechanics, rehabilitation engineering and surgical simulation. Validation of these constitutive models using human data remains challenging and often requires the use of non-invasive imaging and inverse finite element (FE) analysis. Post processing data from imaging methods such as tagged magnetic resonance imaging (MRI) can be challenging. Digital Image Correlation (DIC) however is a relatively straightforward imaging method and thus the goal of this study was to assess the use of DIC in combination with FE modelling to determine the bulk material properties of human soft tissue. Indentation experiments were performed on a silicone gel soft tissue phantom. A two camera DIC setup was then used to record the 3D surface deformation. The experiment was then simulated using a FE model.

  16. Using integrated correlative cryo-light and electron microscopy to directly observe syntaphilin-immobilized neuronal mitochondria in situ.

    Science.gov (United States)

    Wang, Shengliu; Li, Shuoguo; Ji, Gang; Huang, Xiaojun; Sun, Fei

    2017-01-01

    Correlative cryo-fluorescence and cryo-electron microscopy (cryo-CLEM) system has been fast becoming a powerful technique with the advantage to allow the fluorescent labeling and direct visualization of the close-to-physiologic ultrastructure in cells at the same time, offering unique insights into the ultrastructure with specific cellular function. There have been various engineered ways to achieve cryo-CLEM including the commercial FEI iCorr system that integrates fluorescence microscope into the column of transmission electron microscope. In this study, we applied the approach of the cryo-CLEM-based iCorr to image the syntaphilin-immobilized neuronal mitochondria in situ to test the performance of the FEI iCorr system and determine its correlation accuracy. Our study revealed the various morphologies of syntaphilin-immobilized neuronal mitochondria that interact with microtubules and suggested that the cryo-CLEM procedure by the FEI iCorr system is suitable with a half micron-meter correlation accuracy to study the cellular organelles that have a discrete distribution and large size, e.g. mitochondrion, Golgi complex, lysosome, etc.

  17. Clinical performance and marginal adaptation of class II direct and semidirect composite restorations over 3.5 years in vivo.

    Science.gov (United States)

    Spreafico, Roberto C; Krejci, Ivo; Dietschi, Didier

    2005-07-01

    The study evaluated the clinical performance and marginal adaptation of direct and semi-direct class II composite restorations in a split-mouth design over 3.5 years. 44 upper posterior teeth in 11 adults with primary carious lesions were treated with 22 direct and 22 semi-direct restorations. Conventional cavities were prepared for both types of restorations. A fine fine hybrid composite (APH) and a multifunctional adhesive system (Prisma universal bond 3) were used for all restorations. The incremental "3-sited light curing" technique was applied to direct restorations. Semi-direct inlays were prefabricated on silicone casts and post-cured using light and heat. Clinical performance was evaluated using modified USPHS parameters, while marginal adaptation was judged on replicas, using SEM and a standardized evaluation technique. Clinical results after 3.5 years revealed a 100% retention rate with no fractures, sensitivity or recurrent caries for both types of restorations. SEM-evaluation of the occlusal margins showed at the tooth-restoration interface relatively low rates of marginal openings over the observation period (4-8%). Marginal restoration fractures ranged between 1 and 2%, marginal tooth fractures between 3 and 9%. Differences between the restorative techniques and after the different time observation periods were not statistically significant. Proportions of marginal fractures and openings at the restoration-luting composite interface were less than 10% after 3.5 years. The results indicated no significant differences for direct and semi-direct fine hybrid composite restorations in medium size cavities in posterior teeth with respect to clinical performance and marginal adaptation over 3.5 years.

  18. Non-uniformly weighted sampling for faster localized two-dimensional correlated spectroscopy of the brain in vivo

    Science.gov (United States)

    Verma, Gaurav; Chawla, Sanjeev; Nagarajan, Rajakumar; Iqbal, Zohaib; Albert Thomas, M.; Poptani, Harish

    2017-04-01

    Two-dimensional localized correlated spectroscopy (2D L-COSY) offers greater spectral dispersion than conventional one-dimensional (1D) MRS techniques, yet long acquisition times and limited post-processing support have slowed its clinical adoption. Improving acquisition efficiency and developing versatile post-processing techniques can bolster the clinical viability of 2D MRS. The purpose of this study was to implement a non-uniformly weighted sampling (NUWS) scheme for faster acquisition of 2D-MRS. A NUWS 2D L-COSY sequence was developed for 7T whole-body MRI. A phantom containing metabolites commonly observed in the brain at physiological concentrations was scanned ten times with both the NUWS scheme of 12:48 duration and a 17:04 constant eight-average sequence using a 32-channel head coil. 2D L-COSY spectra were also acquired from the occipital lobe of four healthy volunteers using both the proposed NUWS and the conventional uniformly-averaged L-COSY sequence. The NUWS 2D L-COSY sequence facilitated 25% shorter acquisition time while maintaining comparable SNR in humans (+0.3%) and phantom studies (+6.0%) compared to uniform averaging. NUWS schemes successfully demonstrated improved efficiency of L-COSY, by facilitating a reduction in scan time without affecting signal quality.

  19. In vivo Stability of Ester- and Ether-Linked Phospholipid-Containing Liposomes as Measured by Perturbed Angular Correlation Spectroscopy

    Science.gov (United States)

    Derksen, Johannes T.; Baldeschwieler, John D.; Scherphof, Gerrit L.

    1988-12-01

    To evaluate liposome formulations for use as intracellular sustained-release drug depots, we have compared the uptake and degradation in rat liver and spleen of liposomes of various compositions, containing as their bulk phospholipid an ether-linked phospholipid or one of several ester-linked phospholipids, by perturbed angular correlation spectroscopy. Multilamellar and small unilamellar vesicles (MLVs and SUVs), composed of egg phosphatidylcholine, sphingomyelin, distearoyl phosphatidylcholine (DSPC), dipalmitoyl phosphatidylcholine (DPPC) or its analog dihexadecylglycerophosphorylcholine (DHPC), and cholesterol plus phosphatidylserine, and containing 111In complexed to nitrilotriacetic acid, were injected intravenously in rats. Recovery of 111In-labeled liposomes in blood, liver, and spleen was assessed at specific time points after injection and the percentage of liposomes still intact in liver and spleen was determined by measurement of the time-integrated angular perturbation factor 111In of the [G22(∞ )] label. We found that MLVs but not SUVs, having DHPC as their bulk phospholipid, showed an increased resistance against lysosomal degradation as compared to other phospholipid-containing liposomes. The use of diacyl phospholipids with a high gel/liquid-crystalline phase-transition temperature, such as DPPC and DSPC, also retarded degradation of MLV, but not of SUV in the dose range tested, while the rate of uptake of these liposomes by the liver was lower.

  20. Shear stress affects the intracellular distribution of eNOS: Direct demonstration by a novel in vivo technique

    NARCIS (Netherlands)

    C. Cheng (Caroline (Ka Lai)); M.J. van Haperen (Rien); M.C. de Waard (Monique); L.C.A. van Damme (Luc); D. Tempel (Dennie); R. Hanemaaijer (Roeland); W.A. van Cappellen (Gert); J.A. Bos (Joop); C.J. Slager (Cornelis); D.J.G.M. Duncker (Dirk); A.F.W. van der Steen (Ton); M.P.G. de Crom (Rini); R. Krams (Rob)

    2005-01-01

    textabstractThe focal location of atherosclerosis in the vascular tree is correlated with local variations in shear stress. We developed a method to induce defined variations in shear stress in a straight vessel segment of a mouse. To this end, a cylinder with a tapered lumen was placed around the

  1. Correlation of Friedewald's calculated low-density lipoprotein cholesterol levels with direct low-density lipoprotein cholesterol levels in a tertiary care hospital

    Science.gov (United States)

    Nanda, Sunil Kumar; Bharathy, M; Dinakaran, Asha; Ray, Lopamudra; Ravichandran, K

    2017-01-01

    Background: One of the risk factors for the development of coronary heart disease is high low-density lipoprotein (LDL) cholesterol levels. National Cholesterol Education Program ATP III guidelines suggest drug therapy to be considered at LDL-cholesterol levels >130 mg/dl. This makes accurate reporting of LDL cholesterol crucial in the management of Coronary heart disease. Estimation of LDL cholesterol by direct LDL method is accurate, but it is expensive. Hence, We compared Friedewald's calculated LDL values with direct LDL values. Aim: To evaluate the correlation of Friedewalds calculated LDL with direct LDL method. Materials and Methods: We compared LDL cholesterol measured by Friedewald's formula with direct LDL method in 248 samples between the age group of 20–70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald's formula. The level of significance was taken as P < 0.05. Pearsons correlation formula was used to test the correlation between direct LDL values with Friedewald's formula. Results: There was no significant difference between the direct LDL values when compared to calculated LDL by Friedewalds formula (P = 0.140). Pearson correlation showed there exists good correlation between direct LDL versus Friedewalds formula (correlation coefficient = 0.98). The correlation between direct LDL versus Friedewalds calculated LDL was best at triglycerides values between 101 and 200 mg/dl. Conclusion: This study indicates calculated LDL by Friedewalds equation can be used instead of direct LDL in patients who cannot afford direct LDL method. PMID:28251110

  2. The growth of glioblastoma orthotopic xenografts in nude mice is directly correlated with impaired object recognition memory.

    Science.gov (United States)

    Wasilewska-Sampaio, Ana Paula; Santos, Tiago G; Lopes, Marilene Hohmuth; Cammarota, Martin; Martins, Vilma Regina

    2014-01-17

    Cognitive dysfunction is found in patients with brain tumors and there is a need to determine whether it can be replicated in an experimental model. In the present study, the object recognition (OR) paradigm was used to investigate cognitive performance in nude mice, which represent one of the most important animal models available to study human tumors in vivo. Mice with orthotopic xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and 18days (D9, D14, and D18, respectively) after implantation of 5×10(5) cells. At D9, the mice showed normal behavior when tested 90min or 24h after training and compared to control nude mice. Animals at D14 were still able to discriminate between familiar and novel objects, but exhibited a lower performance than animals at D9. Total impairment in the OR memory was observed when animals were evaluated on D18. These alterations were detected earlier than any other clinical symptoms, which were observed only 22-24days after tumor implantation. There was a significant correlation between the discrimination index (d2) and time after tumor implantation as well as between d2 and tumor volume. These data indicate that the OR task is a robust test to identify early behavior alterations caused by glioblastoma in nude mice. In addition, these results suggest that OR task can be a reliable tool to test the efficacy of new therapies against these tumors. © 2013 Elsevier Inc. All rights reserved.

  3. Point correlation dimension can reveal functional changes caused by gap junction blockers in the 4-aminopyridine in vivo rat epilepsy model

    Energy Technology Data Exchange (ETDEWEB)

    Jardanhazy, Anett [Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725 (Hungary); Molnar, Mark [Department of Psychophysiology, Institute for Psychology of the Hungarian Academy of Sciences, P.O. Box 398, Budapest H-1394 (Hungary)], E-mail: molnar@cogpsyphy.hu; Jardanhazy, Tamas [Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725 (Hungary)], E-mail: jt@nepsy.szote.u-szeged.hu

    2009-04-15

    The contribution of gap junction (GJ) blockers to seizure initiation was reexamined by means of an analysis on nonlinear dynamics with point correlation dimension (PD2i) at as well as around the primary focus, and mirror focus in an already active 4-aminopyridine-induced in vivo epilepsy model. From the data base of the ECoGs of anesthetized adult rats treated with quinine, a selective blocker of Cx36, and in combination with an additional broad-spectrum GJ blocker, carbenoxolone, 14 cases of each condition were reexamined with a stationarity insensitive nonlinear PD2i method. The blockade of the Cx36 channels decreased the usual drop of the point correlation dimension at the beginning of the seizures, and this was enhanced by the additional use of the global blocker carbenoxolone. The so-called characteristic DC shift just prior to seizure onset denotes a low dimensional seizure event and the recognizable seizures display very variable, rapidly changing dynamics, as revealed by the PD2i analysis. This nonlinear PD2i analysis demonstrated that the different GJ blockers in the already active epileptic model helped seizure initiation, but exerted inhibitory effects on the seizure onset itself, acting differently on the local components of the network organization generating seizure discharges, possibly changing the coupling strengths and time delays in the GJ-s.

  4. Direct and correlated responses to long-term selection for increased body weight and egg production in turkeys.

    Science.gov (United States)

    Nestor, K E; Noble, D O; Zhu, N J; Moritsu, Y

    1996-10-01

    Lines of turkeys were selected long-term for increased egg production (E line; 34 generations) or increased 16-wk BW (F line; 28 generations). The E and F lines were started from randombred control populations (RBC1 and RBC2, respectively) that were also maintained to remove environmental variation among generations. Realized heritabilities (h2) +/- SE in the E line, based on regressions of response on cumulated actual selection differentials (selection differentials weighted for the number of offspring produced), for 180-d and 250-d egg production were 0.34 +/- 0.02 (17 generations) and 0.26 +/- 0.13 (8 generations), respectively. The realized h2 of 16-wk BW in the F line was 0.26 +/- 0.01. There was no consistent evidence of selection response reaching a plateau in either line. The genetic association of BW and egg production changed with selection in the E and F lines. The genetic correlation varied from near zero to strongly negative and fluctuated between these extremes in both lines even though they started from different base populations and selection criteria differed. Other correlated responses to selection for increased egg production were increased average clutch length (intensity of lay), and decreased broodiness (total days lost), egg weight, shell coloration, and rate of response to stimulatory lighting. Other correlated responses to selection for increased 16-wk BW in the F line included: increased egg weight (due to increased albumen), longer eating bouts, and decreased average clutch length, semen production, walking ability, and resistance to Pasteurella multocida and Newcastle disease virus. Selection within the E and F lines also changed the frequency of MHC haplotypes and the changes appeared to be in opposite directions in the two lines.

  5. Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation.

    Science.gov (United States)

    Valle, Andrea; Barbagiovanni, Giulia; Jofra, Tatiana; Stabilini, Angela; Perol, Louis; Baeyens, Audrey; Anand, Santosh; Cagnard, Nicolas; Gagliani, Nicola; Piaggio, Eliane; Battaglia, Manuela

    2015-03-01

    The tolerogenic anti-CD3ε monoclonal Abs (anti-CD3) are promising compounds for the treatment of type 1 diabetes. Anti-CD3 administration induces transient T cell depletion both in preclinical and in clinical studies. Notably, the said depletion mainly affects CD4(+) but not CD8(+) T cells. Moreover, type 1 diabetes reversal in preclinical models is accompanied by the selective expansion of CD4(+)Foxp3(+) T regulatory (Treg) cells, which are fundamental for the long-term maintenance of anti-CD3-mediated tolerance. The mechanisms that lead to this immune-shaping by affecting mainly CD4(+) T effector cells while sparing CD4(+)Foxp3(+) Treg cells have still to be fully elucidated. This study shows that CD3 expression levels differ from one T cell subset to another. CD4(+)Foxp3(-) T cells contain higher amounts of CD3 molecules than do CD4(+)Foxp3(+) and CD8(+) T cells in both mice and humans. The said differences correlate with the anti-CD3-mediated immune resetting that occurs in vivo after anti-CD3 administration in diabetic NOD mice. Additionally, transcriptome analysis demonstrates that CD4(+)Foxp3(+) Treg cells are significantly less responsive than are CD4(+)Foxp3(-) T cells to anti-CD3 treatment at a molecular level. Thus, heterogeneity in CD3 expression seems to confer to the various T cell subsets differing susceptibility to the in vivo tolerogenic anti-CD3-mediated modulation. These data shed new light on the molecular mechanism that underlies anti-CD3-mediated immune resetting and thus may open new opportunities to improve this promising treatment. Copyright © 2015 by The American Association of Immunologists, Inc.

  6. Multipolar radiofrequency ablation using internally cooled electrodes in ex vivo bovine liver: correlation between volume of coagulation and amount of applied energy.

    Science.gov (United States)

    Clasen, Stephan; Rempp, Hansjörg; Schmidt, Diethard; Schraml, Christina; Hoffmann, Rüdiger; Claussen, Claus D; Pereira, Philippe L

    2012-01-01

    To evaluate the relationship between applied energy and volume of coagulation induced by multipolar radiofrequency (RF) ablation. Multipolar RF ablations (n=80) were performed in ex vivo bovine liver. Three bipolar applicators with two electrodes located on each applicator shaft were placed in a triangular array. The power-output (75-225 W) and the distance between the different applicators (2, 3, 4, 5 cm) were systematically varied. The volume of confluent white coagulation and the amount of applied energy were assessed. Based on our experimental data the relationship between the volume of coagulation and applied energy was assessed by nonlinear regression analysis. The variability explained by the model was determined by the parameter r(2). The volume of coagulation increases with higher amounts of applied energy. The maximum amount of energy was applied at a power-output of 75 W and an applicator distance of 5 cm. The corresponding maximum volume of coagulation was 324 cm(3) and required an application of 453 kJ. The relationship between amount of applied energy (E) and volume (V) of coagulation can be described by the function, V=4.39E(0.7) (r(2)=0.88). By approximation the volume of coagulation can be calculated by the linear function V=0.61E+40.7 (r(2)=0.87). Ex vivo the relationship between volume of coagulation and amount of applied energy can be described by mathematical modeling. The amount of applied energy correlates to the volume of coagulation and may be a useful parameter to monitor multipolar RF ablation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Spectral shapes and a beta-gamma directional correlation in the beta decay of 172Tm (Jpi = 2-)

    DEFF Research Database (Denmark)

    Gregers Hansen, P.; Loft Nielsen, H.; Wilsky, K.

    1966-01-01

    +(gamma)0+ cascade has been measured at six energies from 1010 to 1550 keV and these results too are consistent with the assumption that the 2- rarr 2+ beta transition is purely of tensor rank 2. The data for the 2- rarr 2+ transition are analysed on the basis of the modified Bij approximation, which......The isotope 172Tm populates the 0+, 2+ and 4+ states of the 172Yb ground-state rotational band directly in beta decay. The shapes and intensities of the three beta groups have been measured by means of a six-gap magnetic spectrometer operated in coincidence with a Nal(Tl) crystal. The experimental...... shape factor plots are taken relative to the 90Y shape factor measured in the same circumstances, and it is concluded that on this basis the shapes of all three 172Tm beta groups agree with the theoretical shape for a first-forbidden unique transition. The directional correlation for the 2-(beta)2...

  8. Preliminary in vivo positional analysis of a posterior chamber phakic intraocular lens by optical coherence tomography and its correlation with clinical outcomes

    Science.gov (United States)

    Pérez-Cambrodí, Rafael J.; Piñero, David P.; Blanes-Mompó, Francisco J.; Ferrer-Blasco, Teresa; Cerviño, Alejandro

    2012-01-01

    Purpose To analyze by spectral-domain optical coherence tomography the anatomical relationship of a specific type of posterior chamber phakic intraocular lens (pIOL) implanted in cases of high to moderate myopia with the adjacent intraocular structures and to correlate it with clinical outcomes. Methods Prospective observational case series including 18 eyes with high to moderate myopia (spherical equivalent between −5.88 and −15.75 D) of 9 patients (age range, 29–49 years) undergoing bilateral Phakic Refractive Lens (PRL, Zeiss) implantation. Postoperative visual acuity, refraction, contrast sensitivity (CS), and ocular higher order aberrations (HOA) were evaluated. Furthermore, the in vivo position of the PRL was analyzed by means of spectral domain optical coherence tomography (3D OCT-1000, Topcon). Central (CENV), temporal (TEMV) and nasal vault (NASV) were measured. Correlation of these anatomical parameters with clinical data was also investigated. Mean follow-up was 47 ± 25 months. Results A statistically significant visual and refractive improvement (p < 0.01) was found postoperatively. Mean postoperative CENV, NASV, and TEMV were 157.88 ± 69.93 μm, 168.29 ± 65.02 μm, and 188.59 ± 55.99 μm, respectively. Significant difference was found between NASV and TEMV (p = 0.01). No significant correlations were found between ocular aberrometric and anatomical parameters (p ≥ 0.12). CENV, NASV and TEMV correlated significantly with 6-cycles per degree (cpd) photopic CS as well as with 18-cpd low mesopic CS (r ≥ 0.57, p ≤ 0.04). Furthermore, NASV also correlated significantly with preoperative anterior chamber depth (r = −0.65, p = 0.01). Conclusions This posterior chamber pIOL shows a trend to nasal position, with potential impact on refractive and visual outcomes, particularly in eyes with deep anterior chambers.

  9. In vivo requirement for RecJ, ExoVII, ExoI, and ExoX in methyl-directed mismatch repair

    Science.gov (United States)

    Burdett, Vickers; Baitinger, Celia; Viswanathan, Mohan; Lovett, Susan T.; Modrich, Paul

    2001-01-01

    Biochemical studies with model DNA heteroduplexes have implicated RecJ exonuclease, exonuclease VII, exonuclease I, and exonuclease X in Escherichia coli methyl-directed mismatch correction. However, strains deficient in the four exonucleases display only a modest increase in mutation rate, raising questions concerning involvement of these activities in mismatch repair in vivo. The quadruple mutant deficient in the four exonucleases, as well as the triple mutant deficient in RecJ exonuclease, exonuclease VII, and exonuclease I, grow poorly in the presence of the base analogue 2-aminopurine, and exposure to the base analogue results in filament formation, indicative of induction of SOS DNA damage response. The growth defect and filamentation phenotypes associated with 2-aminopurine exposure are effectively suppressed by null mutations in mutH, mutL, mutS, or uvrD/mutU, which encode activities that act upstream of the four exonucleases in the mechanism for the methyl-directed reaction that has been proposed based on in vitro studies. The quadruple exonuclease mutant is also cold-sensitive, having a severe growth defect at 30°C. This phenotype is suppressed by a uvrD/mutU defect, and partially suppressed by mutH, mutL, or mutS mutations. These observations confirm involvement of the four exonucleases in methyl-directed mismatch repair in vivo and suggest that the low mutability of exonuclease-deficient strains is a consequence of under recovery of mutants due to a reduction in viability and/or chromosome loss associated with activation of the mismatch repair system in the absence of RecJ exonuclease, exonuclease VII, exonuclease I, and exonuclease X. PMID:11381137

  10. Direct evidence of iNOS-mediated in vivo free radical production and protein oxidation in acetone-induced ketosis

    Science.gov (United States)

    Stadler, Krisztian; Bonini, Marcelo G.; Dallas, Shannon; Duma, Danielle; Mason, Ronald P.; Kadiiska, Maria B.

    2008-01-01

    Diabetic patients frequently encounter ketosis that is characterized by the breakdown of lipids with the consequent accumulation of ketone bodies. Several studies have demonstrated that reactive species are likely to induce tissue damage in diabetes, but the role of the ketone bodies in the process has not been fully investigated. In this study, electron paramagnetic resonance (EPR) spectroscopy combined with novel spin-trapping and immunological techniques has been used to investigate in vivo free radical formation in a murine model of acetone-induced ketosis. A six-line EPR spectrum consistent with the α-(4-pyridyl-1-oxide)-N-t-butylnitrone radical adduct of a carbon-centered lipid-derived radical was detected in the liver extracts. To investigate the possible enzymatic source of these radicals, inducible nitric oxide synthase (iNOS) and NADPH oxidase knockout mice were used. Free radical production was unchanged in the NADPH oxidase knockout but much decreased in the iNOS knockout mice, suggesting a role for iNOS in free radical production. Longer-term exposure to acetone revealed iNOS overexpression in the liver together with protein radical formation, which was detected by confocal microscopy and a novel immunospin-trapping method. Immunohistochemical analysis revealed enhanced lipid peroxidation and protein oxidation as a consequence of persistent free radical generation after 21 days of acetone treatment in control and NADPH oxidase knockout but not in iNOS knockout mice. Taken together, our data demonstrate that acetone administration, a model of ketosis, can lead to protein oxidation and lipid peroxidation through a free radical-dependent mechanism driven mainly by iNOS overexpression. PMID:18559982

  11. The in vivo dissection of direct RFX-target gene promoters in C. elegans reveals a novel cis-regulatory element, the C-box.

    Science.gov (United States)

    Burghoorn, Jan; Piasecki, Brian P; Crona, Filip; Phirke, Prasad; Jeppsson, Kristian E; Swoboda, Peter

    2012-08-15

    At the core of the primary transcriptional network regulating ciliary gene expression in Caenorhabditis elegans sensory neurons is the RFX/DAF-19 transcription factor, which binds and thereby positively regulates 13-15 bp X-box promoter motifs found in the cis-regulatory regions of many ciliary genes. However, the variable expression of direct RFX-target genes in various sets of ciliated sensory neurons (CSNs) occurs through as of yet uncharacterized mechanisms. In this study the cis-regulatory regions of 41 direct RFX-target genes are compared using in vivo genetic analyses and computational comparisons of orthologous nematode sequences. We find that neither the proximity to the translational start site nor the exact sequence composition of the X-box promoter motif of the respective ciliary gene can explain the variation in expression patterns observed among different direct RFX-target genes. Instead, a novel enhancer element appears to co-regulate ciliary genes in a DAF-19 dependent manner. This cytosine- and thymidine-rich sequence, the C-box, was found in the cis-regulatory regions in close proximity to the respective X-box motif for 84% of the most broadly expressed direct RFX-target genes sampled in this study. Molecular characterization confirmed that these 8-11 bp C-box sequences act as strong enhancer elements for direct RFX-target genes. An artificial promoter containing only an X-box promoter motif and two of the C-box enhancer elements was able to drive strong expression of a GFP reporter construct in many C. elegans CSNs. These data provide a much-improved understanding of how direct RFX-target genes are differentially regulated in C. elegans and will provide a molecular model for uncovering the transcriptional network mediating ciliary gene expression in animals. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.

    Science.gov (United States)

    Faisal, Amir; Mak, Grace W Y; Gurden, Mark D; Xavier, Cristina P R; Anderhub, Simon J; Innocenti, Paolo; Westwood, Isaac M; Naud, Sébastien; Hayes, Angela; Box, Gary; Valenti, Melanie R; De Haven Brandon, Alexis K; O'Fee, Lisa; Schmitt, Jessica; Woodward, Hannah L; Burke, Rosemary; vanMontfort, Rob L M; Blagg, Julian; Raynaud, Florence I; Eccles, Suzanne A; Hoelder, Swen; Linardopoulos, Spiros

    2017-04-25

    The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy. Therefore, MPS1 inhibition represents an attractive strategy to target cancers. To evaluate CCT271850 cellular potency, two specific antibodies that recognise the activation sites of MPS1 were used and its antiproliferative activity was determined in 91 human cancer cell lines. DLD1 cells with induced GFP-MPS1 and HCT116 cells were used in in vivo studies to directly measure MPS1 inhibition and efficacy of CCT271850 treatment. CCT271850 selectively and potently inhibits MPS1 kinase activity in biochemical and cellular assays and in in vivo models. Mechanistically, tumour cells treated with CCT271850 acquire aberrant numbers of chromosomes and the majority of cells divide their chromosomes without proper alignment because of abrogation of the mitotic checkpoint, leading to cell death. We demonstrated a moderate level of efficacy of CCT271850 as a single agent in a human colorectal carcinoma xenograft model. CCT271850 is a potent, selective and orally bioavailable MPS1 kinase inhibitor. On the basis of in vivo pharmacodynamic vs efficacy relationships, we predict that more than 80% inhibition of MPS1 activity for at least 24 h is required to achieve tumour stasis or regression by CCT271850.

  13. Direct visualization of peptide/MHC complexes at the surface and in the intracellular compartments of cells infected in vivo by Leishmania major.

    Directory of Open Access Journals (Sweden)

    Eric Muraille

    Full Text Available Protozoa and bacteria infect various types of phagocytic cells including macrophages, monocytes, dendritic cells and eosinophils. However, it is not clear which of these cells process and present microbial antigens in vivo and in which cellular compartments parasite peptides are loaded onto Major Histocompatibility Complex molecules. To address these issues, we have infected susceptible BALB/c (H-2d mice with a recombinant Leishmania major parasite expressing a fluorescent tracer. To directly visualize the antigen presenting cells that present parasite-derived peptides to CD4+ T cells, we have generated a monoclonal antibody that reacts to an antigenic peptide derived from the parasite LACK antigen bound to I-Ad Major Histocompatibility Complex class II molecule. Immunogold electron microscopic analysis of in vivo infected cells showed that intracellular I-Ad/LACK complexes were present in the membrane of amastigote-containing phagosomes in dendritic cells, eosinophils and macrophages/monocytes. In both dendritic cells and macrophages, these complexes were also present in smaller vesicles that did not contain amastigote. The presence of I-Ad/LACK complexes at the surface of dendritic cells, but neither on the plasma membrane of macrophages nor eosinophils was independently confirmed by flow cytometry and by incubating sorted phagocytes with highly sensitive LACK-specific hybridomas. Altogether, our results suggest that peptides derived from Leishmania proteins are loaded onto Major Histocompatibility Complex class II molecules in the phagosomes of infected phagocytes. Although these complexes are transported to the cell surface in dendritic cells, therefore allowing the stimulation of parasite-specific CD4+ T cells, this does not occur in other phagocytic cells. To our knowledge, this is the first study in which Major Histocompatibility Complex class II molecules bound to peptides derived from a parasite protein have been visualized within and

  14. In vitro analysis suggests that difference in cell movement during direct interaction can generate various pigment patterns in vivo.

    Science.gov (United States)

    Yamanaka, Hiroaki; Kondo, Shigeru

    2014-02-04

    Pigment patterns of organisms have invoked strong interest from not only biologists but also, scientists in many other fields. Zebrafish is a useful model animal for studying the mechanism of pigment pattern formation. The zebrafish stripe pattern is primarily two types of pigment cells: melanophores and xanthophores. Previous studies have reported that interactions among these pigment cells are important for pattern formation. In the recent report, we found that the direct contact by xanthophores induces the membrane depolarization of melanophores. From analysis of jaguar mutants, it is suggested that the depolarization affects the movements of melanophores. To analyze the cell movement in detail, we established a unique in vitro system. It allowed us to find that WT xanthophores induced repulsive movement of melanophores through direct contact. The xanthophores also chased the melanophores. As a result, they showed run-and-chase movements. We also analyzed the cell movement of pigment cells from jaguar and leopard mutants, which have fuzzy stripes and spot patterns, respectively. jaguar cells showed inhibited run-and-chase movements, and leopard melanophores scarcely showed repulsive response. Furthermore, we paired mutant and WT cells and showed which of the melanophores and xanthophores have responsibility for the altered cell movements. These results suggested that there is a correspondence relationship between the cell movements and pigment patterns. The correspondence relationship highlighted the importance of the cell movements in the pattern formation and showed that our system is a quite useful system for future study in this field.

  15. Direct restoration modalities of fractured central maxillary incisors: A multi-levels validated finite elements analysis with in vivo strain measurements.

    Science.gov (United States)

    Davide, Apicella; Raffaella, Aversa; Marco, Tatullo; Michele, Simeone; Syed, Jamaluddin; Massimo, Marrelli; Marco, Ferrari; Antonio, Apicella

    2015-12-01

    To quantify the influence of fracture geometry and restorative materials rigidity on the stress intensity and distribution of restored fractured central maxillary incisors (CMI) with particular investigation of the adhesive interfaces. Ancillary objectives are to present an innovative technology to measure the in vivo strain state of sound maxillary incisors and to present the collected data. A validation experimental biomechanics approach has been associated to finite element analysis. FEA models consisted of CMI, periodontal ligament and the corresponding alveolar bone process. Three models were created representing different orientation of the fracture planes. Three different angulations of the fracture plane in buccal-palatal direction were modeled: the fracture plane perpendicular to the long axis in the buccal-palatal direction (0°); the fracture plane inclined bucco-palatally in apical-coronal direction (-30°); the fracture plane inclined palatal-buccally in apical-coronal direction (+30°). First set of computing runs was performed for in vivo FE-model validation purposes. In the second part, a 50N force was applied on the buccal aspect of the CMI models. Ten patients were selected and subjected to the strain measurement of CMI under controlled loading conditions. The main differences were noticed in the middle and incisal thirds of incisors crowns, due to the presence of the incisal portion restoration. The stress intensity in -30° models is increased in the enamel structure close to the restoration, due to a thinning of the remaining natural tissues. The rigidity of the restoring material slightly reduces such phenomenon. -30° model exhibits the higher interfacial stress in the adhesive layer with respect to +30° and 0° models. The lower stress intensity was noticed in the 0° models, restoration material rigidity did not influenced the interfacial stress state in 0° models. On the contrary, material rigidity influenced the interfacial stress state

  16. An in vitro and in vivo analysis of the correlation between susceptibility-weighted imaging phase values and R2* in cirrhotic livers.

    Directory of Open Access Journals (Sweden)

    Ran Tao

    Full Text Available OBJECTIVE: To establish a baseline of susceptibility-weighted imaging (SWI phase value as a means of detecting iron abnormalities in cirrhotic liver and to analyze its relationship with R2*. MATERIALS AND METHODS: Sixteen MnCl(2 phantoms, thirty-seven healthy individuals and 87 cirrhotic patients were performed SWI and multi-echo T2*-weighted imaging, and the signal processing in NMR (SPIN software was used to measure the radian on SWI phase images and the R2* on T2* maps. The mean minus two times standard deviation (SD of Siemens Phase Unit (SPU in healthy individuals was designated as a threshold to separate the regions of interest (ROIs into high- and low-iron areas in healthy participants and cirrhotic patients. The SWI phase values of high-iron areas were calculated. The R2* values was measured in the same ROI in both healthy participants and patients. RESULTS: SWI phase values correlated linearly with R2* values in cases of MnCl(2 concentrations lower than 2.3 mM in vitro (r = -0.996, P<0.001. The mean value and SD of 37 healthy participants were 2003 and 15 (SPU, respectively. A threshold of 1973 SPU (-0.115 radians was determined. The SWI phase value and R2* values had a negative correlation in the cirrhotic patients (r = -0.742, P<0.001. However, no similar relationship was found in the healthy individuals (r = 0.096, P = 0.576. Both SWI phase values and R2* values were found to have significant correlations with serum ferritin concentrations in 42 patients with blood samples (r = -0.512, P = 0.001 and r = 0.641, P<0.001, respectively. CONCLUSION: SWI phase values had significant correlations with R2* after the establishment of a baseline on the phase image. SWI phase images may be used for non-invasive quantitative measurement of mild and moderate iron deposition in hepatic cirrhosis in vivo.

  17. Do the results of respirable dust samples obtained from direct-on-filter X-ray diffraction, direct-on-filter infrared and indirect infrared (KBr pellet) methods correlate?

    CSIR Research Space (South Africa)

    Pretorius, C

    2010-11-01

    Full Text Available The objective of this study was to determine whether a correlation exists between the quartz results obtained from direct-on-filter X-ray Diffraction analysis, direct-on-filter Fourier-Transform Infrared analysis and indirect analysis (Potassium...

  18. Prevalence and Correlates of Direct Self-Injurious Behavior among Chinese Adolescents: Findings from a Multicenter and Multistage Survey.

    Science.gov (United States)

    Xin, Xiuhong; Wang, Yuping; Fang, Jianqun; Ming, Qingsen; Yao, Shuqiao

    2017-05-01

    Direct self-injurious behavior (DSIB) has become an important focus due to its perniciousness and perplexity. Little is known about its prevalence and correlative factors in Chinese adolescents, including how data may differ according to gender. A multicenter, multistage stratified cluster random sampling was used to examine the previous 12-month prevalence of DSIB, as well as the possible correlates of demographics, risky behaviors, suicidality, and psychosocial factors associated with DSIB in a school-based sample of 11,880 students (49.5 % boys and 50.5 % girls). Approximately 30 % of the adolescents in the sample reported at least one incident of DSIB in the past 12-month period. After controlling for demographic variables, analyses of the independent relationships of DSIB with risky behaviors, suicidality, and psychosocial factors were conducted for each gender. Smoking, binge drinking, running away from home, suicide ideation, suicide plans, positive affect, and physical symptoms were identified as common factors associated with DSIB for both genders in the final model. In addition, truancy, fighting, physical inactivity, motor impulsiveness, and depressed affect were found to be related to DSIB in boys, whereas suicide attempts and somatic complaints were found to be related to DSIB in girls. Separation anxiety and social anxiety associated negatively with DSIB in boys and girls, respectively. DSIB was not found to independently relate to attention impulsiveness, non-planned impulsiveness, self-esteem, or harm avoidance in either genders. DSIB was prevalent in Chinese adolescents. Programs intended to promote physical and mental health in adolescents should take into account gender differences in DSIB-associated factors, including risky behaviors, suicidality, and psychosocial factors.

  19. Site-specific cross-linking of TBP in vivo and in vitro reveals a direct functional interaction with the SAGA subunit Spt3.

    Science.gov (United States)

    Mohibullah, Neeman; Hahn, Steven

    2008-11-01

    The TATA-binding protein (TBP) is critical for transcription by all three nuclear RNA polymerases. In order to identify factors that interact with TBP, the nonnatural photoreactive amino acid rho-benzoyl-phenylalanine (BPA) was substituted onto the surface of Saccharomyces cerevisiae TBP in vivo. Cross-linking of these TBP derivatives in isolated transcription preinitiation complexes or in living cells reveals physical interactions of TBP with transcriptional coregulator subunits and with the general transcription factor TFIIA. Importantly, the results show a direct interaction between TBP and the SAGA coactivator subunits Spt3 and Spt8. Mutations on the Spt3-interacting surface of TBP significantly reduce the interaction of TBP with SAGA, show a corresponding decrease in transcription activation, and fail to recruit TBP to a SAGA-dependent promoter, demonstrating that the direct interaction of these factors is important for activated transcription. These results prove a key prediction of the model for stimulation of transcription at SAGA-dependent genes via Spt3. Our cross-linking data also significantly extend the known surfaces of TBP that directly interact with the transcriptional regulator Mot1 and the general transcription factor TFIIA.

  20. Direct profiling of phytochemicals in tulip tissues and in vivo monitoring of the change of carbohydrate content in tulip bulbs by probe electrospray ionization mass spectrometry.

    Science.gov (United States)

    Yu, Zhan; Chen, Lee Chuin; Suzuki, Hiroaki; Ariyada, Osamu; Erra-Balsells, Rosa; Nonami, Hiroshi; Hiraoka, Kenzo

    2009-12-01

    Probe electrospray ionization (PESI) is a recently developed ESI-based ionization technique which generates electrospray from the tip of a solid needle. In this study, we have applied PESI interfaced with a time of flight mass spectrometer (TOF-MS) for direct profiling of phytochemicals in a section of a tulip bulb in different regions, including basal plate, outer and inner rims of scale, flower bud and foliage leaves. Different parts of tulip petals and leaves have also been investigated. Carbohydrates, amino acids and other phytochemicals were detected. A series of in vivo PESI-MS experiments were carried out on the second outermost scales of four living tulip bulbs to monitoring the change of carbohydrate content during the first week of initial growth. The breakdown of carbohydrates was observed which was in accordance with previous reports achieved by other techniques. This study has indicated that PESI-MS can be used for rapid and direct analysis of phytochemicals in living biological systems with advantages of low sample consumption and little sample preparation. Therefore, PESI-MS can be a new choice for direct analysis/profiling of bioactive compounds or monitoring metabolic changes in living biological systems.

  1. The diffusion dynamics of PEGylated liposomes in the intact vitreous of the ex vivo porcine eye: A fluorescence correlation spectroscopy and biodistribution study.

    Science.gov (United States)

    Eriksen, Anne Z; Brewer, Jonathan; Andresen, Thomas L; Urquhart, Andrew J

    2017-04-30

    The diffusion dynamics of nanocarriers in the vitreous and the influence of nanocarrier physicochemical properties on these dynamics is an important aspect of the efficacy of intravitreal administered nanomedicines for the treatment of posterior segment eye diseases. Here we use fluorescence correlation spectroscopy (FCS) to determine liposome diffusion coefficients in the intact vitreous (DVit) of ex vivo porcine eyes using a modified Miyake-Apple technique to minimize the disruption of the vitreous fine structure. We chose to investigate whether the zeta potential of polyethylene glycol functionalized (i.e. PEGylated) liposomes altered liposome in situ diffusion dynamics in the vitreous. Non-PEGylated cationic nanocarriers have previously shown little to no diffusion in the vitreous, whilst neutral and anionic have shown diffusion. The liposomes investigated had diameters below 150nm and zeta potentials ranging from -20 to +12mV. We observed that PEGylated cationic liposomes had significantly lower DVit values (1.14μm2s-1) than PEGylated neutral and anionic liposomes (2.78 and 2.87μm2s-1). However, PEGylated cationic liposomes had a similar biodistribution profile across the vitreous to the other systems. These results show that PEGylated cationic liposomes with limited cationic charge can diffuse across the vitreous and indicate that the vitreous as a barrier to nanocarriers (Ø<500nm) is more complicated than simply an electrostatic barrier as previously suggested. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

    Science.gov (United States)

    Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

    2014-11-01

    Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. Drug in adhesive patch of palonosetron: Effect of pressure sensitive adhesive on drug skin permeation and in vitro-in vivo correlation.

    Science.gov (United States)

    Liu, Chao; Hui, Mei; Quan, Peng; Fang, Liang

    2016-09-25

    Palonosetron (PAL) is recommended for the prevention of chemotherapy-induced nausea and vomiting. The aim of this study was to develop a long-acting PAL transdermal patch to improve patient compliance. We were particularly concerned about the effect of pressure sensitive adhesives (PSAs) on PAL skin permeability. Formulation factors including PSAs, backing films and drug loadings were investigated in the in vitro skin permeation study using rabbit skin. Fourier transform infrared spectrometer study and thermal analysis were conducted to investigate the drug-PSA interaction and thermodynamic activity of PSAs, respectively. The results indicated that high drug skin permeation amount was obtained in PSA DURO-TAK(®)87-2516, which had low interaction potential with PAL and high thermodynamic activity. The optimized patch was composed of PAL of 8 %, DURO-TAK(®)87-2516 as PSA, CoTran™ 9700 as backing film and Scotchpak™ 9744 as release liner. The in vitro skin permeation amount of the optimized patch was 734.0±55.8μg/cm(2) during 3-day administration. The absolute bioavailability of the optimized patch was 43 % in rabbit and a good in vitro-in vivo correlation coefficient was obtained (R(2)=0.989). These results indicated the feasibility of PAL transdermal patch in the prevention of chemotherapy-induced nausea and vomiting. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Electrophysiological correlates of refreshing: Event-related potentials associated with directing reflective attention to face, scene, or word representations

    Science.gov (United States)

    Johnson, Matthew R.; McCarthy, Gregory; Muller, Kathleen A.; Brudner, Samuel N.; Johnson, Marcia K.

    2016-01-01

    Refreshing is the component cognitive process of directing reflective attention to one of several active mental representations. Previous studies using functional magnetic resonance imaging (fMRI) suggested that refresh tasks involve a component process of initiating refreshing as well as the top-down modulation of representational regions central to refreshing. However, those studies were limited by fMRI’s low temporal resolution. In the present study, we used electroencephalography (EEG) to examine the timecourse of refreshing on the scale of milliseconds rather than seconds. Event-related potential (ERP) analyses showed that a typical refresh task does have a distinct electrophysiological response as compared to a control condition, and includes at least two main temporal components: an earlier (~400ms) positive peak reminiscent of a P3 response, and a later (~800ms–1400ms) sustained positivity over several sites reminiscent of the late directing attention positivity (LDAP). Overall, the evoked potentials for refreshing representations from three different visual categories (faces, scenes, words) were similar, but multivariate pattern analysis (MVPA) showed that some category information was nonetheless present in the EEG signal. When related to previous fMRI studies, these results are consistent with a two-phase model, with the first phase dominated by frontal control signals involved in initiating refreshing and the second by the top-down modulation of posterior perceptual cortical areas that constitutes refreshing a representation. This study also lays the foundation for future studies of the neural correlates of reflective attention at a finer temporal resolution than is possible using fMRI. PMID:25961640

  5. AR-13, a Celecoxib Derivative, Directly Kills Francisella In Vitro and Aids Clearance and Mouse Survival In Vivo

    Directory of Open Access Journals (Sweden)

    Ky V. Hoang

    2017-09-01

    Full Text Available Francisella tularensis (F. tularensis is the causative agent of tularemia and is classified as a Tier 1 select agent. No licensed vaccine is currently available in the United States and treatment of tularemia is confined to few antibiotics. In this study, we demonstrate that AR-13, a derivative of the cyclooxygenase-2 inhibitor celecoxib, exhibits direct in vitro bactericidal killing activity against Francisella including a type A strain of F. tularensis (SchuS4 and the live vaccine strain (LVS, as well as toward the intracellular proliferation of LVS in macrophages, without causing significant host cell toxicity. Identification of an AR-13-resistant isolate indicates that this compound has an intracellular target(s and that efflux pumps can mediate AR-13 resistance. In the mouse model of tularemia, AR-13 treatment protected 50% of the mice from lethal LVS infection and prolonged survival time from a lethal dose of F. tularensis SchuS4. Combination of AR-13 with a sub-optimal dose of gentamicin protected 60% of F. tularensis SchuS4-infected mice from death. Taken together, these data support the translational potential of AR-13 as a lead compound for the further development of new anti-Francisella agents.

  6. Adrenocorticotropic hormone and cortisol plasma levels directly correlate with childhood neglect and depression measures in addicted patients.

    Science.gov (United States)

    Gerra, Gilberto; Leonardi, Claudio; Cortese, Elena; Zaimovic, Amir; Dell'Agnello, Grazia; Manfredini, Matteo; Somaini, Lorenzo; Petracca, Francesca; Caretti, Vincenzo; Baroni, Cristina; Donnini, Claudio

    2008-03-01

    Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been reported to be involved in vulnerability to alcohol and drug dependence in humans, possibly underlying both addictive behaviour and depression susceptibility. The aim of the present study was to investigate the possible interactions between childhood adverse experiences, depressive symptoms and HPA axis function in addicted patients, in comparison with healthy control. Eighty-two abstinent heroin or cocaine dependent patients and 44 normal controls, matched for age and sex, completed the symptoms Check List-90 (SCL-90), measuring depressive symptoms, and the Childhood Experience of Care and Abuse Questionnaire. Blood samples were collected to determine adrenocorticotropic hormone (ACTH) and cortisol basal plasma levels at 8:00 and 8:30 a.m. Addicted individuals showed significantly higher neglect and depression scores and ACTH-cortisol plasma levels respect to control subjects. Depression scores at SCL-90 in addicted patients positively correlated with plasma ACTH and cortisol values. In turn, plasma ACTH levels were directly associated with childhood neglect measures, reaching statistical significance with 'mother-neglect' scores. Plasma cortisol levels were related to 'father antipathy' among cocaine addicts. These findings suggest the possibility that childhood experience of neglect and poor parent-child attachment may have a persistent effect on HPA axis function as an adult, partially contributing, together with genetic factors and other environmental conditions, to both depressive traits and substance abuse neurobiological vulnerability.

  7. Increasing Public Awareness of Direct-to-Consumer Genetic Tests: Health Care Access, Internet Use, and Population Density Correlates

    Directory of Open Access Journals (Sweden)

    Lila J. Finney Rutten

    2012-01-01

    Full Text Available Uncertainty around the value of and appropriate regulatory models for direct-to-consumer (DTC genetic testing underscores the importance of tracking public awareness of these services. We analyzed nationally representative, cross-sectional data from the Health Information National Trends Survey in 2008 (n=7,674 and 2011 (n=3,959 to assess population-level changes in awareness of DTC genetic testing in the U.S. and to explore sociodemographic, health care, Internet use, and population density correlates. Overall, awareness increased significantly from 29% in 2008 to 37% in 2011. The observed increase in awareness from 2008 to 2011 remained significant (OR=1.39 even when adjusted for sociodemographic variables, health care access, Internet use, and population density. Independent of survey year, the odds of awareness of DTC genetic tests were significantly higher for those aged 50–64 (OR=1.64, and 65–74 (OR=1.60; college graduates (OR=2.02; those with a regular source of health care (OR=1.27; those with a prior cancer diagnosis (OR=1.24; those who use the Internet (OR=1.27; and those living in urban areas (OR=1.25. Surveillance of awareness—along with empirical data on use of and response to genetic risk information—can inform public health and policy efforts to maximize benefits and minimize risks of DTC genetic testing.

  8. Genetic Code Optimization for Cotranslational Protein Folding: Codon Directional Asymmetry Correlates with Antiparallel Betasheets, tRNA Synthetase Classes

    Directory of Open Access Journals (Sweden)

    Hervé Seligmann

    2017-01-01

    Full Text Available A new codon property, codon directional asymmetry in nucleotide content (CDA, reveals a biologically meaningful genetic code dimension: palindromic codons (first and last nucleotides identical, codon structure XZX are symmetric (CDA = 0, codons with structures ZXX/XXZ are 5′/3′ asymmetric (CDA = −1/1; CDA = −0.5/0.5 if Z and X are both purines or both pyrimidines, assigning negative/positive (−/+ signs is an arbitrary convention. Negative/positive CDAs associate with (a Fujimoto's tetrahedral codon stereo-table; (b tRNA synthetase class I/II (aminoacylate the 2′/3′ hydroxyl group of the tRNA's last ribose, respectively; and (c high/low antiparallel (not parallel betasheet conformation parameters. Preliminary results suggest CDA-whole organism associations (body temperature, developmental stability, lifespan. Presumably, CDA impacts spatial kinetics of codon-anticodon interactions, affecting cotranslational protein folding. Some synonymous codons have opposite CDA sign (alanine, leucine, serine, and valine, putatively explaining how synonymous mutations sometimes affect protein function. Correlations between CDA and tRNA synthetase classes are weaker than between CDA and antiparallel betasheet conformation parameters. This effect is stronger for mitochondrial genetic codes, and potentially drives mitochondrial codon-amino acid reassignments. CDA reveals information ruling nucleotide-protein relations embedded in reversed (not reverse-complement sequences (5′-ZXX-3′/5′-XXZ-3′.

  9. Direct Comparison of the Histidine-rich Protein-2 Enzyme-linked Immunosorbent Assay (HRP-2 ELISA) and Malaria SYBR Green I Fluorescence (MSF) Drug Sensitivity Tests in Plasmodium falciparum Reference Clones and Fresh ex vivo Field Isolates from Cambodia

    Science.gov (United States)

    2013-07-12

    fluorescence (MSF) drug sensitivity tests in Plasmodium falciparum reference clones and fresh ex vivo field isolates from Cambodia Suwanna...assay (HRP-2 ELISA) and malaria SYBR Green I fluorescence (MSF) drug sensitivity tests were directly compared using Plasmodium falciparum reference... Plasmodium falciparum reference clones and fresh ex vivo field isolates from Cambodia Suwanna Chaorattanakawee 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

  10. Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study.

    Science.gov (United States)

    Molinet-Dronda, Francisco; Gago, Belén; Quiroga-Varela, Ana; Juri, Carlos; Collantes, María; Delgado, Mercedes; Prieto, Elena; Ecay, Margarita; Iglesias, Elena; Marín, Concepció; Peñuelas, Iván; Obeso, José A

    2015-05-01

    Carbon-11 labeled dihydrotetrabenazine ((11)C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied (11)C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague-Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. (11)C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new (11)C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). (11)C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between (11)C-DTBZ PET SB and striatal DAT immunostaining values (r=0.95, p<0.001). The data presented here indicate

  11. Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo.

    Science.gov (United States)

    Zeng, Xingruo; Xu, Zhou; Gu, Jiayan; Huang, Haishan; Gao, Guangxun; Zhang, Xiaoru; Li, Jingxia; Jin, Honglei; Jiang, Guosong; Sun, Hong; Huang, Chuanshu

    2016-03-01

    Our recent studies found that isorhapontigenin (ISO) showed a significant inhibitory effect on human bladder cancer cell growth, accompanied with cell-cycle G0-G1 arrest as well as downregulation of Cyclin D1 expression at transcriptional level via inhibition of Sp1 transactivation in bladder cancer cells. In the current study, the potential ISO inhibition of bladder tumor formation has been explored in a xenograft nude mouse model, and the molecular mechanisms underlying ISO inhibition of Sp1 expression and anticancer activities have been elucidated both in vitro and in vivo. Moreover, the studies demonstrated that ISO treatment induced the expression of miR-137, which in turn suppressed Sp1 protein translation by directly targeting Sp1 mRNA 3'-untranslated region (UTR). Similar to ISO treatment, ectopic expression of miR-137 alone led to G0-G1 cell growth arrest and inhibition of anchorage-independent growth in human bladder cancer cells, which could be completely reversed by overexpression of GFP-Sp1. The inhibition of miR-137 expression attenuated ISO-induced inhibition of Sp1/Cyclin D1 expression, induction of G0-G1 cell growth arrest, and suppression of cell anchorage-independent growth. Taken together, our studies have demonstrated that miR-137 induction by ISO targets Sp1 mRNA 3'-UTR and inhibits Sp1 protein translation, which consequently results in reduction of Cyclin D1 expression, induction of G0-G1 growth arrest, and inhibition of anchorage-independent growth in vitro and in vivo. Our results have provided novel insights into understanding the anticancer activity of ISO in the therapy of human bladder cancer. ©2016 American Association for Cancer Research.

  12. Direct Vpr-Vpr Interaction in Cells monitored by two Photon Fluorescence Correlation Spectroscopy and Fluorescence Lifetime Imaging

    Directory of Open Access Journals (Sweden)

    Mély Yves

    2008-09-01

    Full Text Available Abstract Background The human immunodeficiency virus type 1 (HIV-1 encodes several regulatory proteins, notably Vpr which influences the survival of the infected cells by causing a G2/M arrest and apoptosis. Such an important role of Vpr in HIV-1 disease progression has fuelled a large number of studies, from its 3D structure to the characterization of specific cellular partners. However, no direct imaging and quantification of Vpr-Vpr interaction in living cells has yet been reported. To address this issue, eGFP- and mCherry proteins were tagged by Vpr, expressed in HeLa cells and their interaction was studied by two photon fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy. Results Results show that Vpr forms homo-oligomers at or close to the nuclear envelope. Moreover, Vpr dimers and trimers were found in the cytoplasm and in the nucleus. Point mutations in the three α helices of Vpr drastically impaired Vpr oligomerization and localization at the nuclear envelope while point mutations outside the helical regions had no effect. Theoretical structures of Vpr mutants reveal that mutations within the α-helices could perturb the leucine zipper like motifs. The ΔQ44 mutation has the most drastic effect since it likely disrupts the second helix. Finally, all Vpr point mutants caused cell apoptosis suggesting that Vpr-mediated apoptosis functions independently from Vpr oligomerization. Conclusion We report that Vpr oligomerization in HeLa cells relies on the hydrophobic core formed by the three α helices. This oligomerization is required for Vpr localization at the nuclear envelope but not for Vpr-mediated apoptosis.

  13. Innate responses induced by whole inactivated virus or subunit influenza vaccines in cultured dendritic cells correlate with immune responses in vivo.

    Directory of Open Access Journals (Sweden)

    Maaike Stoel

    Full Text Available Vaccine development involves time-consuming and expensive evaluation of candidate vaccines in animal models. As mediators of both innate and adaptive immune responses dendritic cells (DCs are considered to be highly important for vaccine performance. Here we evaluated how far the response of DCs to a vaccine in vitro is in line with the immune response the vaccine evokes in vivo. To this end, we investigated the response of murine bone marrow-derived DCs to whole inactivated virus (WIV and subunit (SU influenza vaccine preparations. These vaccine preparations were chosen because they differ in the immune response they evoke in mice with WIV being superior to SU vaccine through induction of higher virus-neutralizing antibody titers and a more favorable Th1-skewed response phenotype. Stimulation of DCs with WIV, but not SU vaccine, resulted in a cytokine response that was comparable to that of DCs stimulated with live virus. Similarly, the gene expression profiles of DCs treated with WIV or live virus were similar and differed from that of SU vaccine-treated DCs. More specifically, exposure of DCs to WIV resulted in differential expression of genes in known antiviral pathways, whereas SU vaccine did not. The stronger antiviral and more Th1-related response of DCs to WIV as compared to SU vaccine correlates well with the superior immune response found in mice. These results indicate that in vitro stimulation of DCs with novel vaccine candidates combined with the assessment of multiple parameters, including gene signatures, may be a valuable tool for the selection of vaccine candidates.

  14. Bad to the Bone: On In Vitro and Ex Vivo Microbial Biofilm Ability to Directly Destroy Colonized Bone Surfaces without Participation of Host Immunity or Osteoclastogenesis.

    Science.gov (United States)

    Junka, Adam; Szymczyk, Patrycja; Ziółkowski, Grzegorz; Karuga-Kuzniewska, Ewa; Smutnicka, Danuta; Bil-Lula, Iwona; Bartoszewicz, Marzenna; Mahabady, Susan; Sedghizadeh, Parish Paymon

    2017-01-01

    Bone infections are a significant public health burden associated with morbidity and mortality in patients. Microbial biofilm pathogens are the causative agents in chronic osteomyelitis. Research on the pathogenesis of osteomyelitis has focused on indirect bone destruction by host immune cells and cytokines secondary to microbial insult. Direct bone resorption by biofilm pathogens has not yet been seriously considered. In this study, common osteomyelitis pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Streptococcus mutans) were grown as biofilms in multiple in vitro and ex vivo experiments to analyze quantitative and qualitative aspects of bone destruction during infection. Pathogens were grown as single or mixed species biofilms on the following substrates: hydroxyapatite, rat jawbone, or polystyrene wells, and in various media. Biofilm growth was evaluated by scanning electron microscopy and pH levels were monitored over time. Histomorphologic and quantitative effects of biofilms on tested substrates were analyzed by microcomputed tomography and quantitative cultures. All tested biofilms demonstrated significant damage to bone. Scanning electron microscopy indicated that all strains formed mature biofilms within 7 days on all substrate surfaces regardless of media. Experimental conditions impacted pH levels, although this had no impact on biofilm growth or bone destruction. Presence of biofilm led to bone dissolution with a decrease of total volume by 20.17±2.93% upon microcomputed tomography analysis, which was statistically significant as compared to controls (p biofilm formation (Kruskall-Wallis test, post-hoc Dunne's test; p biofilms associated with osteomyelitis have the ability to directly resorb bone. These findings should lead to a more complete understanding of the etiopathogenesis of osteomyelitis, where direct bone resorption by biofilm is considered in addition to the well-known osteoclastic and host cell destruction

  15. Bad to the Bone: On In Vitro and Ex Vivo Microbial Biofilm Ability to Directly Destroy Colonized Bone Surfaces without Participation of Host Immunity or Osteoclastogenesis

    Science.gov (United States)

    Junka, Adam; Szymczyk, Patrycja; Ziółkowski, Grzegorz; Karuga-Kuzniewska, Ewa; Smutnicka, Danuta; Bil-Lula, Iwona; Bartoszewicz, Marzenna; Mahabady, Susan; Sedghizadeh, Parish Paymon

    2017-01-01

    Bone infections are a significant public health burden associated with morbidity and mortality in patients. Microbial biofilm pathogens are the causative agents in chronic osteomyelitis. Research on the pathogenesis of osteomyelitis has focused on indirect bone destruction by host immune cells and cytokines secondary to microbial insult. Direct bone resorption by biofilm pathogens has not yet been seriously considered. In this study, common osteomyelitis pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Streptococcus mutans) were grown as biofilms in multiple in vitro and ex vivo experiments to analyze quantitative and qualitative aspects of bone destruction during infection. Pathogens were grown as single or mixed species biofilms on the following substrates: hydroxyapatite, rat jawbone, or polystyrene wells, and in various media. Biofilm growth was evaluated by scanning electron microscopy and pH levels were monitored over time. Histomorphologic and quantitative effects of biofilms on tested substrates were analyzed by microcomputed tomography and quantitative cultures. All tested biofilms demonstrated significant damage to bone. Scanning electron microscopy indicated that all strains formed mature biofilms within 7 days on all substrate surfaces regardless of media. Experimental conditions impacted pH levels, although this had no impact on biofilm growth or bone destruction. Presence of biofilm led to bone dissolution with a decrease of total volume by 20.17±2.93% upon microcomputed tomography analysis, which was statistically significant as compared to controls (p <0.05, ANOVA). Quantitative cultures indicated that media and substrate did not impact biofilm formation (Kruskall-Wallis test, post-hoc Dunne’s test; p <0.05). Overall, these results indicate that biofilms associated with osteomyelitis have the ability to directly resorb bone. These findings should lead to a more complete understanding of the etiopathogenesis of

  16. In vitro/in vivo correlation and modeling of emitted dose and lung deposition of inhaled salbutamol from metered dose inhalers with different types of spacers in noninvasively ventilated patients.

    Science.gov (United States)

    Hussein, Raghda R S; M A Ali, Ahmed; Salem, Heba F; Abdelrahman, Maha M; Said, Amira S A; Abdelrahim, Mohamed E A

    2017-11-01

    Substituting spacer by another in noninvasive ventilation (NIV) involves many variables, e.g. total emitted dose (TED), mass median aerodynamic diameter (MMAD), type of spacer, total lung deposition and total systemic absorption, which must be adjusted to ensure patient optimum therapy. Data mining based on artificial neural networks and genetic algorithms were used to model in vitro inhalation process, predict and optimize bioavailability from inhaled doses delivered by metered dose inhaler (MDI) using different spacers in NIV. Modeling of data indicated that in vitro performance of MDI-spacer systems was dependent mainly on fine particle dose (FPD), fine particle fraction (FPF), MMAD and to lesser extent on spacer type. Ex vivo model indicated that amount of salbutamol collected on facemask filter was directly affected by FPF. In vivo model (24hQ) depended directly on spacer type, FPF and TED. Female patients showed higher 0.5hQ and 24hQ values than males. AeroChamber VC spacer demonstrated higher TED and 24hQ in vivo values. Results indicated suitability of MDI-spacer systems in achieving appropriate in vitro inhalation performance. The possibility of modeling and predicting both ex vivo and in vivo capabilities of MDI-spacer systems from knowledge of in vitro attributes enabled detailed focus on important variables required to deliver safe and accurate doses of salbutamol to ventilated patients.

  17. In-vivo identification of direct electron transfer from Shewanella oneidensis MR-1 to electrodes via outer-membrane OmcA-MtrCAB protein complexes

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, Akihiro [Department of Applied Chemistry, School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Nakamura, Ryuhei, E-mail: nakamura@light.t.u-tokyo.ac.jp [Department of Applied Chemistry, School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Hashimoto, Kazuhito, E-mail: hashimoto@light.t.u-tokyo.ac.jp [Department of Applied Chemistry, School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); ERATO/JST, HASHIMOTO Light Energy Conversion Project (Japan)

    2011-06-30

    Graphical abstract: . Display Omitted Highlights: > Monolayer biofilm of Shewanella cells was prepared on an ITO electrode. > Extracellular electron transfer (EET) process was examined with series of mutants. > Direct ET was confirmed with outer-membrane-bound OmcA-MtrCAB complex. > The EET process was not prominently influenced by capsular polysaccharide. - Abstract: The direct electron-transfer (DET) property of Shewanella bacteria has not been resolved in detail due to the complexity of in vivo electrochemistry in whole-cell systems. Here, we report the in vivo assignment of the redox signal indicative of the DET property in biofilms of Shewanella oneidensis MR-1 by cyclic voltammetry (CV) with a series of mutants and a chemical marking technique. The CV measurements of monolayer biofilms formed by deletion mutants of c-type cytochromes ({Delta}mtrA, {Delta}mtrB, {Delta}mtrC/{Delta}omcA, and {Delta}cymA), and pilin ({Delta}pilD), capsular polysaccharide ({Delta}SO3177) and menaquinone ({Delta}menD) biosynthetic proteins demonstrated that the electrochemical redox signal with a midpoint potential at 50 mV (vs. SHE) was due to an outer-membrane-bound OmcA-MtrCAB protein complex of decaheme cytochromes, and did not involve either inner-membrane-bound CymA protein or secreted menaquinone. Using the specific binding affinity of nitric monoxide for the heme groups of c-type cytochromes, we further confirmed this conclusion. The heterogeneous standard rate constant for the DET process was estimated to be 300 {+-} 10 s{sup -1}, which was two orders of magnitude higher than that previously reported for the electron shuttling process via riboflavin. Experiments using a mutant unable to produce capsular polysaccharide ({Delta}SO3177) revealed that the DET property of the OmcA-MtrCAB complex was not influenced by insulating and hydrophilic extracellular polysaccharide. Accordingly, under physiological conditions, S. oneidensis MR-1 utilizes a high density of outer

  18. Reagents for astatination of biomolecules. 2. Conjugation of anionic boron cage pendant groups to a protein provides a method for direct labeling that is stable to in vivo deastatination.

    Science.gov (United States)

    Wilbur, D Scott; Chyan, Ming-Kuan; Hamlin, Donald K; Vessella, Robert L; Wedge, Timothy J; Hawthorne, M Frederick

    2007-01-01

    Cancer-targeting biomolecules labeled with 211At must be stable to in vivo deastatination, as control of the 211At distribution is critical due to the highly toxic nature of alpha-particle emission. Unfortunately, no astatinated aryl conjugates have shown in vivo stability toward deastatination when (relatively) rapidly metabolized proteins, such as monoclonal antibody Fab' fragments, are labeled. As a means of increasing the in vivo stability of 211At-labeled proteins, we have been investigating antibody conjugates of boron cage moieties. In this investigation, protein-reactive derivatives containing a nido-carborane (2), a bis-nido-carborane derivative (Venus Flytrap Complex, 3), and four 2-nonahydro-closo-decaborate(2-) derivatives (4-7) were prepared and conjugated with an antibody Fab' fragment such that subsequent astatination and in vivo tissue distributions could be obtained. To aid in determination of stability toward in vivo deastatination, the Fab'-borane conjugates were also labeled with 125I, and that material was coinjected with the 211At-labeled Fab'. For comparison, direct labeling of the Fab' with 125I and 211At was conducted. Direct labeling with Na[125I]I and Chloramine-T gave an 89% radiochemical yield. However, direct labeling of the Fab' with Na[211At]At and Chloramine-T resulted in a yield of Studies to optimize the closo-decaborate(2-) conjugates for protein labeling are underway.

  19. Comparative evaluation of effects of bleaching on color stability and marginal adaptation of discolored direct and indirect composite laminate veneers under in vivo conditions

    Science.gov (United States)

    Jain, Veena; Das, Taposh K.; Pruthi, Gunjan; Shah, Naseem; Rajendiran, Suresh

    2015-01-01

    Statement of Problem: Change in color and loss of marginal adaptation of tooth colored restorative materials is not acceptable. Bleaching is commonly used for treating discolored teeth. However, the literature is scanty regarding its effect on color and marginal adaptation of direct and indirect composite laminate veneers (CLVs) under in vivo conditions. Purpose: Purpose of the study was to determine the effect of bleaching on color change and marginal adaptation of direct and indirect CLVs over a period of time when exposed to the oral environment. Materials and Methods: For this purpose, a total of 14 subjects irrespective of age and sex indicated for CLV restorations on maxillary anterior teeth were selected following the inclusion and exclusion criteria. For each subject, indirect CLVs were fabricated and looted in the first quadrant (Group 1) and direct CLV's (Group 2), were given in the second quadrant. Color change was assessed clinically using intra-oral digital spectrophotometer and marginal adaptation was assessed on epoxy resin replica of the tooth-restoration interface under scanning electron microscope. After 6 months, the subjects underwent a home bleaching regimen for 14 days using 10% carbamide peroxide. The assessment of color change and marginal adaptation was done at 6 months after veneering (0–180 days), immediately after the bleaching regimen (0–194 days) and 3 months after the bleaching regimen (0–284 days). Results: The difference in median color change (ΔE) between the groups was tested using Wilcoxon rank sum test while the median color change with time within the groups was tested using Wilcoxon signed rank test. The difference in the rates of marginal adaptation was tested between the groups using Chi-square/Fisher's exact test. Bleaching led to statistically significant color change at cervical (CE), middle and incisal (IE) regions when direct and indirect composites were compared (P veneering materials as they have better color

  20. Rosa26-GFP direct repeat (RaDR-GFP mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo.

    Directory of Open Access Journals (Sweden)

    Michelle R Sukup-Jackson

    2014-06-01

    Full Text Available Homologous recombination (HR is critical for the repair of double strand breaks and broken replication forks. Although HR is mostly error free, inherent or environmental conditions that either suppress or induce HR cause genomic instability. Despite its importance in carcinogenesis, due to limitations in our ability to detect HR in vivo, little is known about HR in mammalian tissues. Here, we describe a mouse model in which a direct repeat HR substrate is targeted to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR-GFP mice, HR between two truncated EGFP expression cassettes can yield a fluorescent signal. In-house image analysis software provides a rapid method for quantifying recombination events within intact tissues, and the frequency of recombinant cells can be evaluated by flow cytometry. A comparison among 11 tissues shows that the frequency of recombinant cells varies by more than two orders of magnitude among tissues, wherein HR in the brain is the lowest. Additionally, de novo recombination events accumulate with age in the colon, showing that this mouse model can be used to study the impact of chronic exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating agent similar to the cancer chemotherapeutic temozolomide, shows that the colon, liver and pancreas are susceptible to DNA damage-induced HR. Finally, histological analysis of the underlying cell types reveals that pancreatic acinar cells and liver hepatocytes undergo HR and also that HR can be specifically detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model provides new understanding of how tissue and age impact susceptibility to HR, and enables future studies of genetic, environmental and physiological factors that modulate HR in mammals.

  1. Investigating the neural correlates of voice versus speech-sound directed information in pre-school children

    National Research Council Canada - National Science Library

    Raschle, Nora Maria; Smith, Sara Ashley; Zuk, Jennifer; Dauvermann, Maria Regina; Figuccio, Michael Joseph; Gaab, Nadine

    2014-01-01

    .... However, due to technical and practical challenges when neuroimaging young children, evidence of neural correlates of speech and/or voice processing in toddlers and young children remains scarce...

  2. Investigating the Neural Correlates of Voice versus Speech-Sound Directed Information in Pre-School Children: e115549

    National Research Council Canada - National Science Library

    Nora Maria Raschle; Sara Ashley Smith; Jennifer Zuk; Maria Regina Dauvermann; Michael Joseph Figuccio; Nadine Gaab

    2014-01-01

    .... However, due to technical and practical challenges when neuroimaging young children, evidence of neural correlates of speech and/or voice processing in toddlers and young children remains scarce...

  3. The effect of nanoparticle polyethylene glycol surface density on ligand-directed tumor targeting studied in vivo by dual modality imaging

    NARCIS (Netherlands)

    Hak, Sjoerd; Helgesen, Emily; Hektoen, Helga H.; Huuse, Else Marie; Jarzyna, Peter A.; Mulder, Willem J. M.; Haraldseth, Olav; de Lange Davies, Catharina

    2012-01-01

    The development and application of nanoparticles as in vivo delivery vehicles for therapeutic and/or diagnostic agents has seen a drastic growth over the last decades. Novel imaging techniques allow real-time in vivo study of nanoparticle accumulation kinetics at the level of the cell and targeted

  4. Correlation between in vitro and in vivo data on food digestion. What can we predict with static in vitro digestion models?

    Science.gov (United States)

    Bohn, T; Carriere, F; Day, L; Deglaire, A; Egger, L; Freitas, D; Golding, M; Le Feunteun, S; Macierzanka, A; Menard, O; Miralles, B; Moscovici, A; Portmann, R; Recio, I; Rémond, D; Santé-Lhoutelier, V; Wooster, T J; Lesmes, U; Mackie, A R; Dupont, D

    2017-06-14

    During the last decade, there has been a growing interest in understanding food's digestive fate in order to strengthen the possible effects of food on human health. Ideally, food digestion should be studied in vivo on humans but this is not always ethically and financially possible. Therefore, simple in vitro digestion models mimicking the gastrointestinal tract have been proposed as alternatives to in vivo experiments. Thus, it is no surprise that these models are increasingly used by the scientific community, although their various limitations to fully mirror the complexity of the digestive tract. Therefore, the objective of this article was to call upon the collective experiences of scientists involved in Infogest (an international network on food digestion) to review and reflect on the applications of in vitro digestion models, the parameters assessed in such studies and the physiological relevance of the data generated when compared to in vivo data. The authors provide a comprehensive review in vitro and in vivo digestion studies investigating the digestion of macronutrients (i.e., proteins, lipids, and carbohydrates) as well as studies of the bioaccessibility and bioavailability of micronutrients and phytochemicals. The main conclusion is that evidences show that despite the simplicity of in vitro models they are often very useful in predicting outcomes of the digestion in vivo. However, this has relies on the complexity of in vitro models and their tuning toward answering specific questions related to human digestion physiology, which leaves a vast room for future studies and improvements.

  5. Direct correlation of consecutive C Prime -N groups in proteins: a method for the assignment of intrinsically disordered proteins

    Energy Technology Data Exchange (ETDEWEB)

    Pantoja-Uceda, David; Santoro, Jorge, E-mail: jsantoro@iqfr.csic.es [CSIC, Instituto de Quimica Fisica Rocasolano (Spain)

    2013-09-15

    Two novel 3D {sup 13}C-detected experiments, hNcocaNCO and hnCOcaNCO, are proposed to facilitate the resonance assignment of intrinsically disordered proteins. The experiments correlate the {sup 15}N and {sup 13}C Prime chemical shifts of two consecutive amide moieties without involving other nuclei, thus taking advantage of the good dispersion shown by the {sup 15}N-{sup 13}C Prime correlations, even for proteins that lack a well defined tertiary structure. The new pulse sequences were successfully tested using Nupr1, an intrinsically disordered protein of 93 residues.

  6. Direct in vivo cell lineage analysis in the retrorsine and 2AAF models of liver injury after genetic labeling in adult and newborn rats.

    Directory of Open Access Journals (Sweden)

    Virginie Pichard

    Full Text Available BACKGROUNDS AND AIMS: When hepatocyte proliferation is impaired, liver regeneration proceeds from the division of non parenchymal hepatocyte progenitors. Oval cells and Small Hepatocyte-like Progenitor Cells (SHPCs represent the two most studied examples of such epithelial cells with putative stem cell capacity. In the present study we wished to compare the origin of SHPCs proliferating after retrorsine administration to the one of oval cells observed after 2-Acetyl-Amino fluorene (2-AAF treatment. METHODOLOGY/PRINCIPAL FINDINGS: We used retroviral-mediated nlslacZ genetic labeling of dividing cells to study the fate of cells in the liver. Labeling was performed either in adult rats before treatment or in newborn animals. Labeled cells were identified and characterised by immunohistochemistry. In adult-labeled animals, labeling was restricted to mature hepatocytes. Retrorsine treatment did not modify the overall number of labeled cells in the liver whereas after 2-AAF administration unlabeled oval cells were recorded and the total number of labeled cells decreased significantly. When labeling was performed in newborn rats, results after retrorsine administration were identical to those obtained in adult-labeled rats. In contrast, in the 2-AAF regimen numerous labeled oval cells were present and were able to generate new labeled hepatocytes. Furthermore, we also observed labeled biliary tracts in 2-AAF treated rats. CONCLUSIONS: Our results strongly suggest that SHPCs are derived from hepatocytes and we confirm that SHPCs and oval cells do not share the same origin. We also show that hepatic progenitors are labeled in newborn rats suggesting future directions for in vivo lineage studies.

  7. Evaluation of a gene-directed enzyme-product therapy (GDEPT in human pancreatic tumor cells and their use as in vivo models for pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Juraj Hlavaty

    Full Text Available BACKGROUND: Gene-directed enzyme prodrug therapy (GDEPT is a two-step treatment protocol for solid tumors that involves the transfer of a gene encoding a prodrug-activating enzyme followed by administration of the inactive prodrug that is subsequently activated by the enzyme to its tumor toxic form. However, the establishment of such novel treatment regimes to combat pancreatic cancer requires defined and robust animal model systems. METHODS: Here, we comprehensively compared six human pancreatic cancer cell lines (PaCa-44, PANC-1, MIA PaCa-2, Hs-766T, Capan-2, and BxPc-3 in subcutaneous and orthotopical mouse models as well as in their susceptibility to different GDEPTs. RESULTS: Tumor uptake was 83% to 100% in the subcutaneous model and 60% to 100% in the orthotopical mouse model, except for Hs-766T cells, which did not grow orthotopically. Pathohistological analyses of the orthotopical models revealed an infiltrative growth of almost all tumors into the pancreas; however, the different cell lines gave rise to tumors with different morphological characteristics. All of the resultant tumors were positive for MUC-1 staining indicating their origin from glandular or ductal epithelium, but revealed scattered pan-cytokeratin staining. Transfer of the cytochrome P450 and cytosine deaminase suicide gene, respectively, into the pancreatic cancer cell lines using retroviral vector technology revealed high level infectibility of these cell lines and allowed the analysis of the sensitivity of these cells to the chemotherapeutic drugs ifosfamide and 5-fluorocytosine, respectively. CONCLUSION: These data qualify the cell lines as part of valuable in vitro and in vivo models for the use in defined preclinical studies for pancreas tumor therapy.

  8. An in vitro-in vivo correlation study for nifedipine immediate release capsules administered with water, alcoholic and non-alcoholic beverages: Impact of in vitro dissolution media and hydrodynamics.

    Science.gov (United States)

    Mercuri, A; Fares, R; Bresciani, M; Fotaki, N

    2016-02-29

    The impact of hydrodynamics and media composition on nifedipine dissolution profile from IR (immediate release) soft capsules was investigated using dissolution apparatus USP1, USP2, USP3 and USP4 (United State Pharmacopoeia). Media composition was varied in terms of pH and content, to mimic the dosage form intake with water or non-alcoholic beverages (orange juice) and alcoholic beverages (orange juice/ethanol mixture (47% v/v)). Through construction of in vitro-in vivo correlations (IVIVC) with corresponding in vivo data from the literature, it was possible to evaluate the in vitro conditions that are likely to simulate the in vivo formulation behaviour. Both linear and nonlinear correlations were obtained depending on experimental set-ups. Testing of 20mg nifedipine capsules in FaSSGFst (Fasted State Simulated Gastric Fluid pH 1.6; water administration) produced IVIVC with the USP3 (after time scaling) and USP4 apparatus. IVIVC were obtained for USP2, USP3 and USP4 in FaSSGFoj (Fasted State Simulated Gastric Fluid pH 3.4; orange juice administration). Linear and nonlinear correlations were obtained with the USP1, USP2 and USP3 apparatus when testing the capsules in FaSSGFoj/EtOH (orange juice/ethanol administration). This study highlighted that selection of physiologically relevant dissolution set-ups is critical for predicting the in vivo impact of formulations co-administration with water, non-alcoholic and alcoholic beverages. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Intraclass Correlation Coefficients in Hierarchical Design Studies with Discrete Response Variables: A Note on a Direct Interval Estimation Procedure

    Science.gov (United States)

    Raykov, Tenko; Marcoulides, George A.

    2015-01-01

    A latent variable modeling procedure that can be used to evaluate intraclass correlation coefficients in two-level settings with discrete response variables is discussed. The approach is readily applied when the purpose is to furnish confidence intervals at prespecified confidence levels for these coefficients in setups with binary or ordinal…

  10. Development of genomic evaluations for direct measures of health in U.S. Holsteins and their correlations with fitness traits

    Science.gov (United States)

    The objectives of this research were to estimate variance components for 6 common health events recorded by producers on U.S. dairy farms, as well as investigate correlations with fitness traits currently used for selection. Producer-recorded health event data were available from Dairy Records Manag...

  11. Direct comparison of {sup 111}In-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Rosik, Daniel; Karlstroem, Amelie Eriksson [KTH Royal Institute of Technology, Division of Molecular Biotechnology, School of Biotechnology, Stockholm (Sweden); Orlova, Anna; Malmberg, Jennie; Varasteh, Zohreh [Uppsala University, Preclinical PET Platform, Uppsala (Sweden); Altai, Mohamed; Tolmachev, Vladimir [Uppsala University, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Sandstroem, Mattias [Uppsala University Hospital, Section of Medical Physics, Department of Oncology, Uppsala (Sweden)

    2012-04-15

    Radiolabelled Affibody molecules have demonstrated a potential for visualization of tumour-associated molecular targets. Affibody molecules (7 kDa) are composed of three alpha-helices. Recently, a smaller two-helix variant of Affibody molecules (5.1 kDa) was developed. The aim of this study was to compare two- and three-helix HER2-targeting Affibody molecules directly in vivo. The three-helix Affibody molecule ABY-002 and the two-helix Affibody molecule PEP09239 were labelled with {sup 111}In at the N-termini via DOTA chelator. Tumour-targeting properties were directly compared at 1 and 4 h after injection in mice bearing SKOV-3 xenografts with high HER2 expression and LS174T xenografts with low HER2 expression. The dissociation constants (K{sub D}) for HER2 binding were 78 pM for the three-helix Affibody molecule and 2.1 nM for the two-helix Affibody molecule. {sup 111}In-PEP09239 cleared more rapidly from the blood. In xenografts with high HER2 expression, the uptake of {sup 111}In-ABY-002 was significantly higher than that of {sup 111}In-PEP09239. The tumour-to-blood ratio was higher for {sup 111}In-PEP09239 at 4 h after injection, while there was no significant difference in other tumour-to-organ ratios. The tumour uptake of {sup 111}In-ABY-002 was eightfold higher than that of {sup 111}In-PEP09239 in xenografts with low expression. Tumour-to-blood ratios were equal in this case, but other tumour-to-organ ratios were appreciably higher for the three-helix variant. For tumours with high HER2 expression, two-helix HER2-targeting Affibody molecules can provide higher tumour-to-blood ratio at the cost of lower tumour uptake. In the case of low expression, both tumour uptake and tumour-to-organ ratios are appreciably higher for three-helix than for two-helix HER2-targeting Affibody molecules. (orig.)

  12. Direct observation of ultrafast many-body electron dynamics in a strongly-correlated ultracold Rydberg gas

    CERN Document Server

    Takei, Nobuyuki; Genes, Claudiu; Pupillo, Guido; Goto, Haruka; Koyasu, Kuniaki; Chiba, Hisashi; Weidemüller, Matthias; Ohmori, Kenji

    2015-01-01

    Many-body interactions govern a variety of important quantum phenomena ranging from superconductivity and magnetism in condensed matter to solvent effects in chemistry. Understanding those interactions beyond mean field is a holy grail of modern sciences. AMO physics with advanced laser technologies has recently emerged as a new platform to study quantum many-body systems. One of its latest developments is the study of long-range interactions among ultracold particles to reveal the effects of many-body correlations. Rydberg atoms distinguish themselves by their large dipole moments and tunability of dipolar interactions. Most of ultracold Rydberg experiments have been performed with narrow-band lasers in the Rydberg blockade regime. Here we demonstrate an ultracold Rydberg gas in a complementary regime, where electronic coherence is created using a broadband picosecond laser pulse, thus circumventing the Rydberg blockade to induce strong many-body correlations. The effects of long-range Rydberg interactions h...

  13. High p_T Direct Photon and pi^0 Triggered Azimuthal Jet Correlations in sqrt(s)=200 GeV p+p Collisions

    CERN Document Server

    Adare, A; Aidala, C; Ajitanand, N N; Akiba, Y; Al-Bataineh, H; Alexander, J; Aoki, K; Aphecetche, L; Armendariz, R; Aronson, S H; Asai, J; Atomssa, E T; Averbeck, R; Awes, T C; Azmoun, B; Babintsev, V; Bai, M; Baksay, G; Baksay, L; Baldisseri, A; Barish, K N; Barnes, P D; Bassalleck, B; Basye, A T; Bathe, S; Batsouli, S; Baublis, V; Baumann, C; Bazilevsky, A; Belikov, S; Bennett, R; Berdnikov, A; Berdnikov, Y; Bickley, A A; Boissevain, J G; Borel, H; Boyle, K; Brooks, M L; Buesching, H; Bumazhnov, V; Bunce, G; Butsyk, S; Camacho, C M; Campbell, S; Chang, B S; Chang, W C; Charvet, J -L; Chernichenko, S; Chiba, J; Chi, C Y; Chiu, M; Choi, I J; Choudhury, R K; Chujo, T; Chung, P; Churyn, A; Cianciolo, V; Citron, Z; Cleven, C R; Cole, B A; Comets, M P; Constantin, P; Csanád, M; Csörg\\Ho, T; Dahms, T; Dairaku, S; Das, K; David, G; Deaton, M B; Dehmelt, K; Delagrange, H; Denisov, A; d'Enterria, D; Deshpande, A; Desmond, E J; Dietzsch, O; Dion, A; Donadelli, M; Drapier, O; Drees, A; Drees, K A; Dubey, A K; Durum, A; Dutta, D; Dzhordzhadze, V; Efremenko, Y V; Egdemir, J; Ellinghaus, F; Emam, W S; Engelmore, T; Enokizono, A; En'yo, H; Esumi, S; Eyser, K O; Fadem, B; Fields, D E; Finger, M; \\,; Jr.,; Finger, M; Fleuret, F; Fokin, S L; Fraenkel, Z; Frantz, J E; Franz, A; Frawley, A D; Fujiwara, K; Fukao, Y; Fusayasu, T; Gadrat, S; Garishvili, I; Glenn, A; Gong, H; Gonin, M; Gosset, J; Goto, Y; de Cassagnac, R Granier; Grau, N; Greene, S V; Perdekamp, M Grosse; Gunji, T; Gustafsson, H -\\AA; Hachiya, T; Henni, A Hadj; Haegemann, C; Haggerty, J S; Hamagaki, H; Han, R; Harada, H; Hartouni, E P; Haruna, K; Haslum, E; Hayano, R; Heffner, M; Hemmick, T K; Hester, T; He, X; Hiejima, H; Hill, J C; Hobbs, R; Hohlmann, M; Holzmann, W; Homma, K; Hong, B; Horaguchi, T; Hornback, D; Huang, S; Ichihara, T; Ichimiya, R; Iinuma, H; Ikeda, Y; Imai, K; Imrek, J; Inaba, M; Inoue, Y; Isenhower, D; Isenhower, L; Ishihara, M; Isobe, T; Issah, M; Isupov, A; Ivanischev, D; Jacak, B V; Jia, J; Jin, J; Jinnouchi, O; Johnson, B M; Joo, K S; Jouan, D; Kajihara, F; Kametani, S; Kamihara, N; Kamin, J; Kaneta, M; Kang, J H; Kanou, H; Kapustinsky, J; Kawall, D; Kazantsev, A V; Kempel, T; Khanzadeev, A; Kijima, K M; Kikuchi, J; Kim, B I; Kim, D H; Kim, D J; Kim, E; Kim, S H; Kinney, E; Kiriluk, K; Kiss, Á; Kistenev, E; Kiyomichi, A; Klay, J; Klein-Boesing, C; Kochenda, L; Kochetkov, V; Komkov, B; Konno, M; Koster, J; Kotchetkov, D; Kozlov, A; Král, A; Kravitz, A; Kubart, J; Kunde, G J; Kurihara, N; Kurita, K; Kurosawa, M; Kweon, M J; Kwon, Y; Kyle, G S; Lacey, R; Lai, Y S; Lajoie, J G; Layton, D; Lebedev, A; Lee, D M; Lee, K B; Lee, M K; Lee, T; Leitch, M J; Leite, M A L; Lenzi, B; Liebing, P; Li\\vska, T; Litvinenko, A; Liu, H; Liu, M X; Li, X; Love, B; Lynch, D; Maguire, C F; Makdisi, Y I; Malakhov, A; Malik, M D; Manko, V I; Mannel, E; Mao, Y; Ma\\vsek, L; Masui, H; Matathias, F; McCumber, M; McGaughey, P L; Means, N; Meredith, B; Miake, Y; Mike\\vs, P; Miki, K; Miller, T E; Milov, A; Mioduszewski, S; Mishra, M; Mitchell, J T; Mitrovski, M; Mohanty, A K; Morino, Y; Morreale, A; Morrison, D P; Moukhanova, T V; Mukhopadhyay, D; Murata, J; Nagamiya, S; Nagata, Y; Nagle, J L; Naglis, M; Nagy, M I; Nakagawa, I; Nakamiya, Y; Nakamura, T; Nakano, K; Newby, J; Nguyen, M; Niita, T; Norman, B E; Nouicer, R; Nyanin, A S; O'Brien, E; Oda, S X; Ogilvie, C A; Ohnishi, H; Okada, K; Oka, M; Omiwade, O O; Onuki, Y; Oskarsson, A; Ouchida, M; Ozawa, K; Pak, R; Pal, D; Palounek, A P T; Pantuev, V; Papavassiliou, V; Park, J; Park, W J; Pate, S F; Pei, H; Peng, J -C; Pereira, H; Peresedov, V; Peressounko, D Yu; Pinkenburg, C; Purschke, M L; Purwar, A K; Qu, H; Rak, J; Rakotozafindrabe, A; Ravinovich, I; Read, K F; Rembeczki, S; Reuter, M; Reygers, K; Riabov, V; Riabov, Y; Roach, D; Roche, G; Rolnick, S D; Romana, A; Rosati, M; Rosendahl, S S E; Rosnet, P; Rukoyatkin, P; Ru\\vzi\\vcka, P; Rykov, V L; Sahlmueller, B; Saito, N; Sakaguchi, T; Sakai, S; Sakashita, K; Sakata, H; Samsonov, V; Sato, S; Sato, T; Sawada, S; Sedgwick, K; Seele, J; Seidl, R; Semenov, A Yu; Semenov, V; Seto, R; Sharma, D; Shein, I; Shevel, A; Shibata, T -A; Shigaki, K; Shimomura, M; Shoji, K; Shukla, P; Sickles, A; Silva, C L; Silvermyr, D; Silvestre, C; Sim, K S; Singh, B K; Singh, C P; Singh, V; Skutnik, S; Slune\\vcka, M; Soldatov, A; Soltz, R A; Sondheim, W E; Sorensen, S P; Sourikova, I V; Staley, F; Stankus, P W; Stenlund, E; Stepanov, M; Ster, A; Stoll, S P; Sugitate, T; Suire, C; Sukhanov, A; Sziklai, J; Tabaru, T; Takagi, S; Takagui, E M; Taketani, A; Tanabe, R; Tanaka, Y; Tanida, K; Tannenbaum, M J; Taranenko, A; Tarján, P; Themann, H; Thomas, T L; Togawa, M; Toia, A; Tojo, J; Tomá\\vsek, L; Tomita, Y; Torii, H; Towell, R S; Tram, V-N; Tserruya, I; Tsuchimoto, Y; Vale, C; Valle, H; van Hecke, H W; Veicht, A; Velkovska, J; Vértesi, R; Vinogradov, A A; Virius, M; Vrba, V; Vznuzdaev, E; Wagner, M; Walker, D; Wang, X R; Watanabe, Y; Wei, F; Wessels, J; White, S N; Winter, D; Woody, C L; Wysocki, M; Xie, W; Yamaguchi, Y L; Yamaura, K; Yang, R; Yanovich, A; Yasin, Z; Ying, J; Yokkaichi, S; Young, G R; Younus, I; Yushmanov, I E; Zajc, W A; Zaudtke, O; Zhang, C; Zhou, S; Zimányi, J; Zolin, L

    2010-01-01

    Correlations of charged hadrons of 1 < pT < 10 GeV/c with high pT direct photons and pi^ 0 mesons in the range 5 direct photon-associated hadron spectrum as well as its charge asymmetry are found to be consistent with a sample dominated by quark-gluon Compton scattering. No significant evidence of fragmentation photon correlated production is observed within experimental uncertainties.

  14. Development of a directly correlated Raman and uHPLC-MS content uniformity method for dry powder inhalers through statistical design, chemometrics and mathematical modeling.

    Science.gov (United States)

    Seabrooks, Lauren; Canfield, Nicole; Pennington, Justin

    2016-09-01

    Content uniformity (CU) is a critical quality attribute measured and monitored throughout the development and commercial supply of pharmaceutical products. Traditional high-performance liquid chromatography (HPLC) methods are time-consuming in both sample preparation and analysis. Thus, a rapid, nondestructive and preparation free spectroscopy based method such as Raman is preferred. Multiple mathematical algorithms were used to establish robust and directly correlated Raman and ultra-HPLC-mass spectrometry (uHPLC-MS) CU methods for the rapid analysis of blends and agglomerates formulated for dry powder inhalers (DPIs). Model samples included blends of caffeine and lactose; albuterol and lactose; and albuterol and lactose agglomerates. Design of experiments (DoE) was employed to optimize Raman spectra. Multivariate curve resolution (MCR) was leveraged to assess Raman method robustness. Mathematical modeling provided direct method to method correlation by allowing samples to be scanned first for Raman spectra and then dissolved for uHPLC-MS analysis. Several chemometric models were developed and evaluated for the quantitative analysis of CU. The DoE revealed Raman power and exposure time were negatively correlated when optimizing albuterol and caffeine spectra but positively correlated for lactose. MCR revealed regions in which small changes to power and time resulted in an 8-10% change in concentration predictions. A PCR model worked well for the analysis of caffeine blend samples and a PLS model worked best for both albuterol blends and agglomerates. Utilization of DoE, chemometrics and mathematical modeling provided a robust and directly correlated CU method for DPIs.

  15. Parton energy loss in heavy-ion collisions via direct-photon and charged-particle Azimuthal Correlations

    NARCIS (Netherlands)

    Abelev, B.I.; Benedosso, F.; Braidot, E|info:eu-repo/dai/nl/304840874; Mischke, A.|info:eu-repo/dai/nl/325781435; Peitzmann, T.|info:eu-repo/dai/nl/304833959; Russcher, M.J.|info:eu-repo/dai/nl/304847844

    2010-01-01

    Charged-particle spectra associated with direct photon (γdir ) and π0 are measured in p+p and Au+Au collisions at center-of-mass energy √sNN=200 GeV with the STAR detector at RHIC. A hower-shape analysis is used to partially discriminate between γdir and π0. Assuming no associated charged particles

  16. An fMRI Study of the Neural Correlates of Incidental Versus Directed Emotion Processing in Pediatric Bipolar Disorder

    Science.gov (United States)

    PAVULURI, MANI N.; PASSAROTTI, ALESSANDRA M.; HARRAL, ERIN M.; SWEENEY, JOHN A.

    2009-01-01

    Objective To use functional neuroimaging to probe the affective circuitry dysfunctions underlying disturbances in emotion processing and emotional reactivity in pediatric bipolar disorder (PBD). Method Equal numbers of controls (HC) and unmedicated patients with euthymia and PBD were matched for age, sex, race, socioeconomic status, and IQ (n = 10 per group; mean age 14.2 years [SD 2.0 years]). The task consisted of a “directed” emotion processing condition where subjects judged whether emotion in facial expression was positive or negative and an “incidental” condition where subjects judged whether faces expressing similar affect were older or younger than 35 years. Results Relative to the directed condition, the incidental condition elicited greater activation in the right amygdala and the right insula, the left middle frontal gyrus, and the left posterior cingulate cortex in patients with PBD, in contrast to the HC that showed greater activation in the right superior frontal gyrus. In both incidental and directed conditions, relative to visual fixation, patients with PBD showed less activation in the right prefrontal cortex (superior, middle, and inferior frontal gyri) and the pregenual anterior cingulate cortex and greater activation in the posterior visual and face-processing regions (i.e., right precuneus/cuneus, fusiform gyrus). Conclusions Increased amygdala activation observed in patients with PBD elicited by incidental emotional processing relative to directed emotional processing may indicate more intense automatic emotional reactivity. Furthermore, the right prefrontal systems that are believed to modulate affect seem to be less engaged in patients with PBD regardless of whether the emotion processing is incidental or directed, which may signify reduced top-down control of emotional reactivity in PBD. PMID:19242292

  17. Direct determination of two-pion correlations for $\\overline{p}p \\to 2\\pi^{+}2\\pi^{-}$ annihilation at rest

    CERN Document Server

    Angelopoulos, Angelos; Aslanides, Elie; Backenstoss, Gerhard; Bargassa, P; Behnke, O; Benelli, A; Bertin, V; Blanc, F; Bloch, P; Carlson, P J; Carroll, M; Carvalho, J; Cawley, E; Charalambous, S; Chardin, G; Chertok, M B; Cody, A; Danielsson, M; Dejardin, M; Derré, J; Ealet, A; Eleftheriadis, C; Evangelou, I; Faravel, L; Ferreira-Marques, R; Fetscher, W; Fidecaro, Maria; Filipcic, A; Francis, D; Fry, J; Gabathuler, Erwin; Gamet, R; Garreta, D; Gerber, H J; Go, A; Haselden, A; Hayman, P J; Henry-Coüannier, F; Hollander, R W; Hubert, E; Jon-And, K; Kettle, P R; Kokkas, P; Kreuger, R; Le Gac, R; Leimgruber, F; Liolios, A; Machado, E; Mandic, I; Manthos, N; Marel, Gérard; Mikuz, M; Miller, J; Montanet, François; Müller, A; Nakada, Tatsuya; Pagels, B; Papadopoulos, I M; Pavlopoulos, P; Pinto da Cunha, J; Policarpo, Armando; Polivka, G; Rickenbach, R; Roberts, B L; Ruf, T; Sakelliou, L; Sanders, P; Schäfer, M; Schaller, L A; Schietinger, T; Schopper, A; Soares, A; Tauscher, Ludwig; Thibault, C; Touchard, F; Touramanis, C; Triantis, F A; Van Beveren, E; van Eijk, C W E; Vlachos, S; Weber, P; Wigger, O; Wolter, M; Yéche, C; Zavrtanik, D; Zimmerman, D; Locher, M P; Markushin, V E

    1998-01-01

    We study $\\pi\\pi$ correlations in the exclusive reaction $\\ppb \\to 2\\pi^+2\\pi^-$ at rest measured by the CPLEAR experiment. Avoiding the introduction of an arbitrary reference sample, we analyse differential distributions for equal charge pion pairs removing the phase-space factor event by event. A peak at small relative momenta is most pronounced for large total momentum of the pair. The physical implications of bosonic symmetrization for the properties of the pion source, in particular its radius, are briefly discussed. The two extremes considered are the chaotic Hanbury-Brown--Twiss mechanism and the coherent Skyrmion model.

  18. Direct Correlation of Cell Toxicity to Conformational Ensembles of Genetic Aβ Variants

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2015-01-01

    We report a systematic analysis of conformational ensembles generated from multiseed molecular dynamics simulations of all 15 known genetic variants of Aβ42. We show that experimentally determined variant toxicities are largely explained by random coil content of the amyloid ensembles (correlation...... with smaller EC50 values; R2 = 0.54, p = 0.01), and to some extent the helix character (more helix-character is less toxic, R2 = 0.32, p = 0.07) and hydrophobic surface (R2 = 0.37, p = 0.04). Our findings suggest that qualitative structural features of the amyloids, rather than the quantitative levels...

  19. Combined In Silico and In Vitro Approach Predicts Low Wall Shear Stress Regions in a Hemofilter that Correlate with Thrombus Formation In Vivo.

    Science.gov (United States)

    Buck, Amanda K W; Groszek, Joseph J; Colvin, Daniel C; Keller, Sara B; Kensinger, Clark; Forbes, Rachel; Karp, Seth; Williams, Phillip; Roy, Shuvo; Fissell, William H

    2017-08-29

    A major challenge in developing blood-contacting medical devices is mitigating thrombogenicity of an intravascular device. Thrombi may interfere with device function or embolize from the device to occlude distant vascular beds with catastrophic consequences. Chemical interactions between plasma proteins and bioengineered surface occur at the nanometer scale; however, continuum models of blood predict local shear stresses that lead to platelet activation or aggregation and thrombosis. Here, an iterative approach to blood flow path design incorporating in silico, in vitro, and in vivo experiments predicted the occurrence and location of thrombi in an implantable hemofilter. Low wall shear stress (WSS) regions identified by computational fluid dynamics (CFD) predicted clot formation in vivo. Revised designs based on CFD demonstrated superior performance, illustrating the importance of a multipronged approach for a successful design process.

  20. In vivo in vitro correlations for a poorly soluble drug, danazol, using the flow-through dissolution method with biorelevant dissolution media

    DEFF Research Database (Denmark)

    Sunesen, Vibeke Hougaard; Pedersen, Betty Lomstein; Kristensen, Henning Gjelstrup

    2005-01-01

    phospholipids, were used as the bile source. The effect of adding different concentrations and molar ratios of monoglycerides and fatty acids to the fed state media was investigated. In vivo release profiles under fasted and fed conditions were obtained from a previous study by deconvolution [Sunesen, V......The purpose of the study was to design dissolution tests that were able to distinguish between the behaviour of danazol under fasted and fed conditions, by using biorelevant media. In vitro dissolution of 100mg danazol capsules was performed using the flow-through dissolution method. Flow rates...... were 8, 16 or 32 ml/min, corresponding to total volumes dissolution medium of 960, 1920 and 3840 ml, respectively. The media used contained bile salt and phospholipid levels relevant for either fasted or fed conditions in vivo. Crude and inexpensive bile components, Porcine Bile Extract and soybean...

  1. A Directional Gradient-Curvature method for gap filling of gridded environmental spatial data with potentially anisotropic correlations

    Science.gov (United States)

    Žukovič, Milan; Hristopulos, Dionissios T.

    2013-10-01

    We introduce the Directional Gradient-Curvature (DGC) method, a novel approach for filling gaps in gridded environmental data. DGC is based on an objective function that measures the distance between the directionally segregated normalized squared gradient and curvature energies of the sample and entire domain data. DGC employs data-conditioned simulations, which sample the local minima configuration space of the objective function instead of the full conditional probability density function. Anisotropy and non-stationarity can be captured by the local constraints and the direction-dependent global constraints. DGC is computationally efficient and requires minimal user input, making it suitable for automated processing of large (e.g., remotely sensed) spatial data sets. Various effects are investigated on synthetic data. The gap-filling performance of DGC is assessed in comparison with established classification and interpolation methods using synthetic and real satellite data, including a skewed distribution of daily column ozone values. It is shown that DGC is competitive in terms of cross validation performance.

  2. Digital Radiography for Determination of Primary Tooth Length: In Vivo and Ex Vivo Studies

    Directory of Open Access Journals (Sweden)

    Maria D. Basso

    2015-01-01

    Full Text Available Background. Methods for determining the root canal length of the primary tooth should yield accurate and reproducible results. In vitro studies show some limitations, which do not allow their findings to be directly transferred to a clinical situation. Aim. To compare the accuracy of radiographic tooth length obtained from in vivo digital radiograph with that obtained from ex vivo digital radiograph. Method. Direct digital radiographs of 20 upper primary incisors were performed in teeth (2/3 radicular resorption that were radiographed by an intraoral sensor, according to the long-cone technique. Teeth were extracted, measured, and mounted in a resin block, and then radiographic template was used to standardise the sensor-target distance (30 cm. The apparent tooth length (APTL was obtained from the computer screen by means of an electronic ruler accompanying the digital radiography software (CDR 2.0, whereas the actual tooth length (ACTL was obtained by means of a digital calliper following extraction. Data were compared to the ACTL by variance analysis and Pearson’s correlation test. Results. The values for APTL obtained from in vivo radiography were slightly underestimated, whereas those values obtained from ex vivo were slightly overestimated. No significance was observed (P≤0.48 between APTL and ACTL. Conclusion. The length of primary teeth estimated by in vivo and ex vivo comparisons using digital radiography was found to be similar to the actual tooth length.

  3. Correlation of receptor occupancy of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse brain with in vivo activity of allosteric mGluR1 antagonists.

    Science.gov (United States)

    Suzuki, Gentaroh; Kawagoe-Takaki, Hiroko; Inoue, Takao; Kimura, Toshifumi; Hikichi, Hirohiko; Murai, Takashi; Satow, Akio; Hata, Mikiko; Maehara, Shunsuke; Ito, Satoru; Kawamoto, Hiroshi; Ozaki, Satoshi; Ohta, Hisashi

    2009-07-01

    The aim of this study was to clarify the relationship between receptor occupancy and in vivo pharmacological activity of mGluR1 antagonists. The tritiated mGluR1-selective allosteric antagonist [(3)H]FTIDC (4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide) was identified as a radioligand having high affinity for mGluR1-expressing CHO cells (K(D) = 2.1 nM) and mouse cerebellum (K(D) = 3.7 nM). [(3)H]FTIDC bound to mGluR1 was displaced by structurally unrelated allosteric antagonists, suggesting there is a mutual binding pocket shared with different allosteric antagonists. The binding specificity of [(3)H]FTIDC for mGluR1 in brain sections was demonstrated by the lack of significant binding to brain sections prepared from mGluR1-knockout mice. Ex vivo receptor occupancy with [(3)H]FTIDC revealed that the receptor occupancy level by FTIDC correlated well with FTIDC dosage and plasma concentration. Intracerebroventricular administration of (S)-3,5-dihydroxyphenylglycine is known to elicit face washing behavior that is mainly mediated by mGluR1. Inhibition of this behavioral change by FTIDC correlated with the receptor occupancy level of mGluR1 in the brain. A linear relationship between the receptor occupancy and in vivo activity was also demonstrated using structurally diverse mGluR1 antagonists. The receptor occupancy assays could help provide guidelines for selecting appropriate doses of allosteric mGluR1 antagonist for examining the function of mGluR1 in vivo.

  4. Direct chemical measurement of DNA synthesis and net rates of differentiation of rat lens epithelial cells in vivo: applied to the selenium cataract.

    Science.gov (United States)

    Cenedella, R J

    1987-05-01

    This report describes a direct chemical method for rapidly estimating DNA synthesis and net rates of epithelial cell differentiation in the ocular lens in vivo. DNA synthesis in the lens of control and selenium-treated rats (12- or 13 days of age) was estimated by chemically isolating and measuring trichloroacetic acid (TCA)-insoluble 3H from the lens following injection of [3H]thymidine. Labeled substrate for DNA synthesis peaked in the lens at 1 hr after injection, decreased markedly by the third hour and was essentially gone by hour 12. Synthesis of labeled DNA in the lens was largely complete by about 3 hr. The [3H]DNA content of the whole lens, measured as TCA-insoluble 3H, remained constant for at least 4 months. The distribution of labeled epithelial cells between the epithelial-cell layer and fiber-cell mass was followed for up to 1 month after injection by measuring the ratio of [3H]DNA in the capsule (epithelial-cell layer) to lens body. Between days 2-3 and day 14 after injection, the ratio of [3H]DNA in the epithelial-cell layer to lens fiber cells decreased linearly in a semilogarithmic plot of the ratio vs. time; i.e. the rate of change of the ratio followed first-order kinetics. Thus, the rate constant (k) for the rate of change in the ratio of [3H]DNA in the capsule layer to lens body can provide an estimate of the percentage of the labeled epithelial cells which leave the capsule per day through differentiation into fiber cells. An apparent rate constant of 0.27 day-1 was estimated from the mean of five experiments; i.e. 27% of labeled epithelial cells were differentiating into cortical fiber cells per day. Therefore, about 70% of the germinative epithelial cells would be replaced every 4 days in these rats. This value is in good agreement with results of studies using autoradiographic technics. The selenium cataract is reported to involve rapid damage to lens epithelial cells. Incorporation of [3H]thymidine into DNA was decreased by at least 60

  5. Computation of Domain-Averaged Shortwave Irradiance by a One-Dimensional Algorithm Incorporating Correlations between Optical Thickness and Direct Incident Radiation

    Science.gov (United States)

    Kato, S.

    2003-01-01

    A one-dimensional radiative transfer algorithm that accounts for correlations between the optical thickness and the incident direct solar radiation is developed to compute the domain-averaged shortwave irradiance profile. It divides the direct irradiance into four components and treats the direct irradiance in two separate, clear and cloudy columns to account for the fact that clouds attenuate the direct irradiance more than clear-sky. The horizontal inhomogeneity of clouds in the cloudy column is treated by the gamma weighted two-stream approximation, which assumes that the optical thickness of clouds follows a gamma distribution. The algorithm inputs the cloud fraction, cumulative cloud fraction as a function of height, and a parameter expressing the shape of the probability density function of the cloud optical thickness distribution in addition to inputs required for a two-stream radiative transfer model. These cloud property inputs can be obtained using ground- and satellite-based instruments. Therefore, the algorithm can treat realistic cloud overlap features and horizontal inhomogeneity of clouds in a framework of one- dimensional radiative transfer. Heating rates computed by the algorithm using cloud fields generated by cloud resolving models agree with those computed with a Monte Carlo model. If optical properties in computational layers that divide a vertically extensive cloud are correlated, the irradiance profile computed by the algorithm further improves.

  6. Direct Comparison of Respiration-Correlated Four-Dimensional Magnetic Resonance Imaging Reconstructed Using Concurrent Internal Navigator and External Bellows.

    Science.gov (United States)

    Li, Guang; Wei, Jie; Olek, Devin; Kadbi, Mo; Tyagi, Neelam; Zakian, Kristen; Mechalakos, James; Deasy, Joseph O; Hunt, Margie

    2017-03-01

    To compare the image quality of amplitude-binned 4-dimensional magnetic resonance imaging (4DMRI) reconstructed using 2 concurrent respiratory (navigator and bellows) waveforms. A prospective, respiratory-correlated 4DMRI scanning program was used to acquire T2-weighted single-breath 4DMRI images with internal navigator and external bellows. After a 10-second training waveform of a surrogate signal, 2-dimensional MRI acquisition was triggered at a level (bin) and anatomic location (slice) until the bin-slice table was completed for 4DMRI reconstruction. The bellows signal was always collected, even when the navigator trigger was used, to retrospectively reconstruct a bellows-rebinned 4DMRI. Ten volunteers participated in this institutional review board-approved 4DMRI study. Four scans were acquired for each subject, including coronal and sagittal scans triggered by either navigator or bellows, and 6 4DMRI images (navigator-triggered, bellows-rebinned, and bellows-triggered) were reconstructed. The simultaneously acquired waveforms and resulting 4DMRI quality were compared using signal correlation, bin/phase shift, and binning motion artifacts. The consecutive bellows-triggered 4DMRI scan was used for indirect comparison. Correlation coefficients between the navigator and bellows signals were found to be patient-specific and inhalation-/exhalation-dependent, ranging from 0.1 to 0.9 because of breathing irregularities (>50% scans) and commonly observed bin/phase shifts (-1.1 ± 0.6 bin) in both 1-dimensional waveforms and diaphragm motion extracted from 4D images. Navigator-triggered 4DMRI contained many fewer binning motion artifacts at the diaphragm than did the bellows-rebinned and bellows-triggered 4DMRI scans. Coronal scans were faster than sagittal scans because of the fewer slices and higher achievable acceleration factors. Navigator-triggered 4DMRI contains substantially fewer binning motion artifacts than bellows-rebinned and bellows-triggered 4DMRI

  7. Investigating the neural correlates of voice versus speech-sound directed information in pre-school children.

    Directory of Open Access Journals (Sweden)

    Nora Maria Raschle

    Full Text Available Studies in sleeping newborns and infants propose that the superior temporal sulcus is involved in speech processing soon after birth. Speech processing also implicitly requires the analysis of the human voice, which conveys both linguistic and extra-linguistic information. However, due to technical and practical challenges when neuroimaging young children, evidence of neural correlates of speech and/or voice processing in toddlers and young children remains scarce. In the current study, we used functional magnetic resonance imaging (fMRI in 20 typically developing preschool children (average age  = 5.8 y; range 5.2-6.8 y to investigate brain activation during judgments about vocal identity versus the initial speech sound of spoken object words. FMRI results reveal common brain regions responsible for voice-specific and speech-sound specific processing of spoken object words including bilateral primary and secondary language areas of the brain. Contrasting voice-specific with speech-sound specific processing predominantly activates the anterior part of the right-hemispheric superior temporal sulcus. Furthermore, the right STS is functionally correlated with left-hemispheric temporal and right-hemispheric prefrontal regions. This finding underlines the importance of the right superior temporal sulcus as a temporal voice area and indicates that this brain region is specialized, and functions similarly to adults by the age of five. We thus extend previous knowledge of voice-specific regions and their functional connections to the young brain which may further our understanding of the neuronal mechanism of speech-specific processing in children with developmental disorders, such as autism or specific language impairments.

  8. Effect of chemical carcinogens on hematopoietic stem cells: temporal correlation between methyl methane sulfonate induced depression of CFU-S and potentiation of Friend viral leukemogenesis in vivo. [Mice

    Energy Technology Data Exchange (ETDEWEB)

    Raikow, R.B.; OKunewick, J.P.; Meredith, R.F.; Brozovich, B.J.; Seeman, P.R.

    1979-05-01

    Methyl methane sulfonate (MMS) was shown to reduce the number of transplantable pluripotent hematopoietic stem cells (CFU-S) in the mouse spleen. A mild depression in CFU-S numbers was seen as early as 1 hr after injection of the chemical carcinogen. Maximal depression was found to be at 5 hrs, followed by a recovery of up to 75% of normal levels by 24 hrs. Comparison of the data with earlier reslts which demonstrated a potentiating effect of MMS on viral leukemogenesis in vivo revealed a good temporal correlation, suggesting a possible relationship between the two effects.

  9. Direct correlation of charge transfer absorption with molecular donor:acceptor interfacial area via photothermal deflection spectroscopy

    KAUST Repository

    Domingo, Ester

    2015-04-09

    We show that the Charge Transfer (CT) absorption signal in bulk-heterojunction (BHJ) solar cell blends, measured by photothermal deflection spectroscopy (PDS), is directly proportional to the density of molecular donor/acceptor interfaces. Since the optical transitions from ground state to the interfacial CT state are weakly allowed at photon energies below the optical gap of both donor and acceptor, we can exploit the use of this sensitive linear absorption spectroscopy for such quantification. Moreover, we determine the absolute molar extinction coefficient of the CT transition for an archetypical polymer-fullerene interface. The latter is ~100 times lower than the extinction coefficient of the donor chromophore involved, allowing us to experimentally estimate the transition dipole moment (0.3 D) and the electronic coupling between ground state and CT state to be on the order of 30 meV.

  10. RADIO MONITORING OF THE PERIODICALLY VARIABLE IR SOURCE LRLL 54361: NO DIRECT CORRELATION BETWEEN THE RADIO AND IR EMISSIONS

    Energy Technology Data Exchange (ETDEWEB)

    Forbrich, Jan, E-mail: jan.forbrich@univie.ac.at [University of Vienna, Department of Astrophysics, Türkenschanzstraße 17, A-1180 Vienna (Austria); Rodríguez, Luis F.; Palau, Aina; Zapata, Luis A. [Instituto de Radioastronomía y Astrofísica, UNAM, Apdo. Postal 3-72 (Xangari), 58089 Morelia, Michoacán (Mexico); Muzerolle, James [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Gutermuth, Robert A. [Department of Astronomy, University of Massachusetts, Amherst, MA 01003 (United States)

    2015-11-20

    LRLL 54361 is an infrared source located in the star-forming region IC 348 SW. Remarkably, its infrared luminosity increases by a factor of 10 over roughly one week every 25.34 days. To understand the origin of these remarkable periodic variations, we obtained sensitive 3.3 cm JVLA radio continuum observations of LRLL 54361 and its surroundings in six different epochs: three of them during the IR-on state and three during the IR-off state. The radio source associated with LRLL 54361 remained steady and did not show a correlation with the IR variations. We suggest that the IR is tracing the results of fast (with a timescale of days) pulsed accretion from an unseen binary companion, while the radio traces an ionized outflow with an extent of ∼100 AU that smooths out the variability over a period of the order of a year. The average flux density measured in these 2014 observations, 27 ± 5 μJy, is about a factor of two less than that measured about 1.5 years before, 53 ± 11 μJy, suggesting that variability in the radio is present, but over larger timescales than in the IR. We discuss other sources in the field, in particular two infrared/X-ray stars that show rapidly varying gyrosynchrotron emission.

  11. β2→ 1-fructans modulate the immune system in vivo by direct interaction with the mucosa in a microbiota-independent fashion

    NARCIS (Netherlands)

    Fransen, Floris; Sahasrabudhe, Neha M.; Elderman, Marlies; Bosveld, Margaret; El Aidy, Sahar; Hugenholtz, Floor; Borghuis, Theo; Kousemaker, Ben; Winkel, Simon; Gaast-de Jongh, Christa E.; Jonge, Marien I. de; Boekschoten, Mark V.; Smidt, Hauke; Schols, Henk A.; de Vos, Paul

    2017-01-01

    It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of beta 2 -> 1-fructans on immunity via microbiota-dependent and-independent effects. To this end,

  12. Pharmacokinetics and metabolism of AMG 232, a novel orally bioavailable inhibitor of the MDM2-p53 interaction, in rats, dogs and monkeys: in vitro-in vivo correlation.

    Science.gov (United States)

    Ye, Qiuping; Jiang, Min; Huang, Wotang T; Ling, Yun; Olson, Steven H; Sun, Daqing; Xu, Guifen; Yan, Xuelei; Wong, Bradley K; Jin, Lixia

    2015-01-01

    1. AMG 232 is a novel inhibitor of the p53-MDM2 protein-protein interaction currently in Phase I clinical trials for multiple tumor indications. The objectives of the investigations reported in this article were to characterize the pharmacokinetic and drug metabolism properties of AMG 232 in pre-clinical species in vivo and in vitro, and in humans in vitro, and to predict its pharmacokinetics in humans through integrating PKDM data. 2. AMG 232 exhibited low clearance (42%), but high clearance (0.74 × Qh) and low oral exposure in dogs (18%). 3. Biotransformation was the major route of elimination of AMG 232 in rats, with only 7% of intravenously administered (14)C-labeled AMG 232 recovered as parent molecule in bile. The major metabolite was an acyl glucuronide as measured by in vivo rat studies and in vitro hepatocyte incubations in multiple species. 4. The in vitro-in vivo correlation of AMG 232 clearance was within 2-fold in pre-clinical species using hepatocytes. AMG 232 was predicted to exhibit low clearance, high volume distribution and long half-life in humans. The predictions are consistent with the preliminary human pharmacokinetic parameters of AMG 232 in clinical trials.

  13. Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non)equivalence of topical semisolids: A case study of "ready-to-use" vehicles.

    Science.gov (United States)

    Ilić, Tanja; Pantelić, Ivana; Lunter, Dominique; Đorđević, Sanela; Marković, Bojan; Ranković, Dragana; Daniels, Rolf; Savić, Snežana

    2017-08-07

    This work aimed to prove the ability of "ready-to-use" topical vehicles based on alkyl polyglucoside-mixed emulsifier (with/without co-solvent modifications) to replace the conventionally used pharmacopoeial bases (e.g., non-ionic hydrophilic cream) in compounding practice. For this purpose, considering the regulatory efforts to establish alternative, scientifically valid methods for evaluating therapeutic equivalence of topical semisolids, we performed a comparative assessment of microstructure, selected critical quality attributes (CQAs) and in vitro/in vivo product performances, by utilizing aceclofenac as a model drug. The differences in composition between investigated samples have imposed remarkable variances in monitored CQAs (particularly in the amount of aceclofenac dissolved, rheological properties and water distribution mode), reflecting the distinct differences in microstructure formed, as partially observed by polarization microscopy and confocal Raman spectral imaging. Although not fully indicative of the in vivo performances, in vitro release data (vertical diffusion vs. immersion cells) proved the microstructure peculiarities, asserting the rheological properties as decisive factor for obtained liberation profiles. Contrary, in vitro permeation results obtained using pig ear epidermis correlated well with in vivo dermatopharmacokinetic data and distinguished unequivocally between tested formulations, emphasizing the importance of skin/vehicle interactions. In summary, suggested multi-faceted approach can provide adequate proof on topical semisolids therapeutic equivalence or lack thereof. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Useful oriented immobilization of antibodies on chimeric magnetic particles: direct correlation of biomacromolecule orientation with biological activity by AFM studies.

    Science.gov (United States)

    Marciello, Marzia; Filice, Marco; Olea, David; Velez, Marisela; Guisan, José M; Mateo, Cesar

    2014-12-16

    The preparation and performance of a suitable chimeric biosensor based on antibodies (Abs) immobilized on lipase-coated magnetic particles by means of a standing orienting strategy are presented. This novel system is based on hydrophobic magnetic particles coated with modified lipase molecules able to orient and further immobilize different Abs in a covalent way without any previous site-selective chemical modification of biomacromolecules. Different key parameters attending the process were studied and optimized. The optimal preparation was performed using a controlled loading (1 nmol Ab g(-1) chimeric support) at pH 9 and a short reaction time to recover a biological activity of about 80%. AFM microscopy was used to study and confirm the Abs-oriented immobilization on lipase-coated magnetic particles and the final achievement of a highly active and recyclable chimeric immune sensor. This direct technique was demonstrated to be a powerful alternative to the indirect immunoactivity assay methods for the study of biomacromolecule-oriented immobilizations.

  15. Direct observation of cation distributions of ideal inverse spinel CoFe2O4 nanofibres and correlated magnetic properties

    KAUST Repository

    Zeng, Xue

    2017-04-25

    Low-dimensional spinel ferrites have recently attracted increasing attention because their tunable magnetic properties make them attractive candidates as spin-filtering tunnel barriers in spintronic devices and as magnetic components in artificial multiferroic heterostructures. Although we know that the distribution of cations (Fe3+ and Co2+) in a spinel structure governs its magnetic properties, their distribution in the so-called ideal inverse spinel structure of a ferrite, CoFe2O4, has not yet been imaged with sub-ångstrom resolution. In this work, we fill this gap in evidence by reporting a direct observation of the distribution of cations in an ideal inverse spinel structure of CoFe2O4 nanofibres using aberration-corrected transmission electron microscopy (TEM). The ordering of Co2+ and Fe3+ at the octahedral sites imaged along either [001], [011] or [-112] orientation was identified as 1 : 1, in accordance with the ideal inverse spinel structure. The saturation magnetisation calculated based on the crystal structure as determined from the TEM image is in good agreement with that measured experimentally on the spinel CoFe2O4 nanofibres, further confirming results from TEM.

  16. Direct relationship between cell density and FDG uptake in asymptomatic aortic aneurysm close to surgical threshold: an in vivo and in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Marini, Cecilia [CNR Institute of Bioimaging and Molecular Physiology, Milan, Genoa Section, Genoa (Italy); Oftalmologia e Genetica dell' Universita di Genova, Dipartimento di Neuroscienze, Genoa (Italy); Morbelli, Silvia; Armonino, Riccardo; Riondato, Mattia; Massollo, Michela; Augeri, Carla; Fiz, Francesco; Sambuceti, Gianmario [University of Genoa, Department Internal Medicine, Chair of Nuclear Medicine, Genoa (Italy); Spinella, Giovanni; Pane, Bianca; Palmieri, Daniela; Palombo, Domenico [San Martino University Hospital, University of Genoa, Division of Vascular and Endovascular Surgery, Genoa (Italy); Sarocchi, Francesca; Abete, Luca; Fulcheri, Ezio [University of Genoa, Department of Surgical and Diagnostic Sciences, Pathology, Genoa (Italy); Ghigliotti, Giorgio [University of Genoa, Department of Internal Medicine, Chair of Cardiology, Genoa (Italy); Cittadini, Giuseppe [Hospital San Martino, Department of Radiology, Genoa (Italy)

    2012-01-15

    Conflicting results have been reported about the clinical value of fluorodeoxyglucose (FDG) imaging in predicting the risk of rupture of abdominal aortic aneurysm (AAA). The present study tests the hypothesis that FDG uptake is low in asymptomatic noninflammatory AAA due to the low cell density in aneurysmal walls. Positron emission tomography (PET)/CT imaging was performed in 12 consecutive candidates for AAA surgical repair and in 12 age- and sex-matched controls. At intervention, aneurysmal walls were cut into three sequential blocks. Block A was frozen to cut three 5-{mu}m slices for incubation with 2-3 MBq of FDG for 5 min. Block C was first incubated with the same tracer solution for the same time and subsequently frozen to cut three 5-{mu}m slices. Autoradiographic images were coregistered with immunohistochemical pictures of cell density, type and DNA synthesis as assessed on block B. No visible uptake in abdominal aorta occurred in any patient or control subject. Immunohistochemistry documented a severe loss of wall structure, with low numbers of cells. Tracer retention directly correlated with overall cell density and with prevalence of cells synthesizing DNA. The metabolic nature of FDG uptake was confirmed by the selective effect of preliminary freezing that decreased tracer content by 90% in regions with high cell density and only by 34% in cold acellular areas. The loss of tissue structure and the marked decrease in cell density account for the low prevalence of positive findings at FDG PET imaging, at least in asymptomatic patients bearing AAAs whose diameter is close to surgical indication. (orig.)

  17. Critical dissolution tests of oral systems based on statistically designed experiments. III. In vitro/in vivo correlation for multiple-unit capsules of paracetamol based on PLS modeling.

    Science.gov (United States)

    Abuzarur-Aloul, R; Gjellan, K; Sjölund, M; Graffner, C

    1998-04-01

    The main aims of the present study were to establish an in vitro/in vivo correlation for multiple-unit capsules of paracetamol by means of statistical prediction models and to investigate the effect of a number of in vitro variables on the discussion rate of paracetamol from the formulation. A fractional factorial screening design was used to investigate the effects of the variables agitation, pH, osmolality, viscosity, and the presence of bile salt on the dissolution rate of paracetamol. The effects were evaluated in two separate partial least-squares models, in which the responses were expressed as the cumulative percentage of paracetamol dissolved at specified time-points (model I) and as the shape (beta) and scale (eta) parameters according to the Weibull function (model II). It was concluded that agitation and viscosity had significant effects on the dissolution rate of paracetamol. Statistical models based on the responses from models I and II were then used to predict the in vitro conditions most closely correlated with the in vitro dissolution of paracetamol after administration of the formulation to 10 healthy volunteers. The predicted optimal in vitro conditions were similar for the two models and not too far from what is expected from the gastrointestinal tract. The experimental verification of the in vitro conditions showed that both models were equally good, and contributed to high degrees of correlation with the in vivo dissolution behavior of the formulation during 9 hr. The relationships obtained when plotting the percentage dissolved in vitro versus in vivo were y = 1.1x (r2 = 0.98) and y = 1.1x (r2 = 0.94) for models I and II, respectively. Based on these results, it is difficult to state a preference for one of the models. Finally, the use of statistical prediction models to develop critical in vitro tests is a successful approach in the establishment of associations between dissolution behavior in vitro and in vivo for oral extended

  18. Twist-3 quark-gluon correlation contribution to single-transverse spin asymmetry for direct-photon and single-jet productions in pp collision

    Science.gov (United States)

    Kanazawa, K.; Koike, Y.

    2014-01-01

    We study the contribution of the collinear twist-3 quark-gluon correlation to the single transversespin asymmetry in direct-photon and single-jet productions in pp collision. At typical RHIC kinematics we find sizable asymmetries in the forward region of the polarized nucleon while they are almost zero in the backward region. We also find the soft-fermion pole contribution is vanishingly small, suggesting the measurement of these asymmetries provides us with an unique opportunity to determine the net soft-gluon pole function.

  19. Neuromodulatory Adaptive Combination of Correlation-based Learning in Cerebellum and Reward-based Learning in Basal Ganglia for Goal-directed Behavior Control

    DEFF Research Database (Denmark)

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational...... and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role...

  20. Correlation between lactate and neuronal cell damage in the rat brain after focal ischemia: An in vivo 1H magnetic resonance spectroscopic (1H-MRS) study.

    Science.gov (United States)

    Woo, Chul-Woong; Lee, Byong Sop; Kim, Sang Tae; Kim, Ki-Soo

    2010-04-01

    Increased levels of lactate are observed by (1)H magnetic resonance spectroscopy ((1)H-MRS) in rat brains after stroke. However, it is not known whether the changes in lactate levels are predictive of the degree of neuronal damage. To investigate the correlation between changes in lactate and lipid levels measured by (1)H-MRS and neuronal cell damage in the rat brain. A middle cerebral artery occlusion (MCAO) model was used to evaluate focal ischemia in rats (n=36). After MCAO for 90 min T2-weighted images (T2WIs), diffusion-weighted images (DWIs), and (1)H-MRS data were obtained from brains immediately, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, 3 days, and 7 days after reperfusion. Infarct volumes were measured in T2WIs obtained 4 weeks after reperfusion. The degree of neuronal damage was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining in three rats from each group at the same time as brain images were collected. Creatine (Cr)-normalized lactate + lipid levels ([Lac+Lip]/Cr) were negatively correlated with Cr-normalized N-acetyl-L-aspartate levels (NAA/Cr) and positively correlated with TUNEL-positive cell numbers up to 24 hours after reperfusion. (Lac+Lip)/Cr at 6 hours and 9 hours was significantly correlated with NAA/Cr at 7 days, but there was no significant correlation between (Lac+Lip)/Cr during the first 24 hours and infarct volume at 4 weeks. Up to 24 hours after reperfusion, (Lac+Lip)/Cr was strongly negatively correlated with NAA/Cr, and was a good predictor of neuronal damage at 7 days; however, it was not predictive of final infarct volume at 4 weeks.

  1. Penicillin (cloxacillin)-tolerant Staphylococcus aureus from bovine mastitis: identification and lack of correlation between tolerance in vitro and response to therapy in vivo.

    Science.gov (United States)

    Craven, N; Anderson, J C; Wilson, C D

    1983-05-01

    Twenty-four isolates of Staphylococcus aureus from naturally occurring cases of bovine mastitis were examined in vitro for resistance to cloxacillin. All strains produced penicillinase and none showed intrinsic resistance (methicillin resistance) to cloxacillin. The minimum inhibitory concentration of cloxacillin for all these strains was normal (low) but differences were found between them in their sensitivities to the bactericidal action. Three were considered to be tolerant to cloxacillin and a further five possibly so. In a mouse model of mastitis there was no difference in the response to intramammary therapy with cloxacillin between cloxacillin-sensitive or tolerant strains of S aureus and a known methicillin-resistant strain was similarly sensitive to cloxacillin therapy in vivo. It is concluded that cloxacillin tolerance may have little clinical significance in mastitis therapy.

  2. Neuromodulatory Adaptive Combination of Correlation-based Learning in Cerebellum and Reward-based Learning in Basal Ganglia for Goal-directed Behavior Control

    Directory of Open Access Journals (Sweden)

    Sakyasingha eDasgupta

    2014-10-01

    Full Text Available Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning and operant conditioning (reward-based learning. A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point towards their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms.

  3. Neuromodulatory adaptive combination of correlation-based learning in cerebellum and reward-based learning in basal ganglia for goal-directed behavior control.

    Science.gov (United States)

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms.

  4. Depressed glucose consumption at reperfusion following brain ischemia does not correlate with mitochondrial dysfunction and development of infarction: an in vivo positron emission tomography study.

    Science.gov (United States)

    Martín, Abraham; Rojas, Santiago; Pareto, Deborah; Santalucia, Tomàs; Millán, Olga; Abasolo, Ibane; Gómez, Vanessa; Llop, Jordi; Gispert, Joan D; Falcon, Carles; Bargalló, Núria; Planas, Anna M

    2009-05-01

    Glucose consumption is severely depressed in the ischemic core, whereas it is maintained or even increased in penumbral regions during ischemia. Conversely, glucose utilization is severely reduced early after reperfusion in spite that glucose and oxygen are available. Experimental studies suggest that glucose hypometabolism might be an early predictor of brain infarction. However, the relationship between early glucose hypometabolism with later development of infarction remains to be further studied in the same subjects. Here, glucose consumption was assessed in vivo by positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) in a rat model of ischemia/reperfusion. Perfusion was evaluated by PET with (13)NH(3) during and after 2-hour (h) middle cerebral artery occlusion, and (18)F-FDG was given after 2h of reperfusion. Brain infarction was evaluated at 24h. Mitochondrial oxygen consumption was examined ex vivo using a biochemical method. Cortical (18)F-FDG uptake was reduced by 45% and 25% in the ischemic core and periphery, respectively. However, substantial alteration of mitochondrial respiration was not apparent until 24h, suggesting that mitochondria retained the ability to consume oxygen early after reperfusion. These results show reduced glucose use at early reperfusion in regions that will later develop infarction and, to a lesser extent, in adjacent regions. Depressed glucose metabolism in the ischemic core might be attributable to reduced metabolic requirement due to irreversible cellular injury. However, reduced glucose metabolism in peripheral regions suggests either an impairment of glycolysis or reduced glucose demand. Thus, our study supports that glycolytic depression early after reperfusion is not always related to subsequent development of infarction.

  5. Tacrine-Trolox Hybrids: A Novel Class of Centrally Active, Nonhepatotoxic Multi-Target-Directed Ligands Exerting Anticholinesterase and Antioxidant Activities with Low In Vivo Toxicity.

    Science.gov (United States)

    Nepovimova, Eugenie; Korabecny, Jan; Dolezal, Rafael; Babkova, Katerina; Ondrejicek, Ales; Jun, Daniel; Sepsova, Vendula; Horova, Anna; Hrabinova, Martina; Soukup, Ondrej; Bukum, Neslihan; Jost, Petr; Muckova, Lubica; Kassa, Jiri; Malinak, David; Andrs, Martin; Kuca, Kamil

    2015-11-25

    Coupling of two distinct pharmacophores, tacrine and trolox, endowed with different biological properties, afforded 21 hybrid compounds as novel multifunctional candidates against Alzheimer's disease. Several of them showed improved inhibitory properties toward acetylcholinesterase (AChE) in relation to tacrine. These hybrids also scavenged free radicals. Molecular modeling studies in tandem with kinetic analysis exhibited that these hybrids target both catalytic active site as well as peripheral anionic site of AChE. In addition, incorporation of the moiety bearing antioxidant abilities displayed negligible toxicity on human hepatic cells. This striking effect was explained by formation of nontoxic metabolites after 1 h incubation in human liver microsomes system. Finally, tacrine-trolox hybrids exhibited low in vivo toxicity after im administration in rats and potential to penetrate across blood-brain barrier. All of these outstanding in vitro results in combination with promising in vivo outcomes highlighted derivative 7u as the lead structure worthy of further investigation.

  6. In vivo

    Science.gov (United States)

    Freudenblum, Julia; Iglesias, José A; Hermann, Martin; Walsen, Tanja; Wilfinger, Armin; Meyer, Dirk; Kimmel, Robin A

    2018-02-08

    The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time-lapse and longitudinal imaging studies to follow islet development, visualizing both naturally occurring islet cells and cells arising with an accelerated timecourse following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacological compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by phosphoinositide 3-kinase (PI3K) and G-protein-coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic exploratory filopodia establish cell-cell contacts that subsequently promote cell clustering. © 2018. Published by The Company of Biologists Ltd.

  7. In Vivo

    Science.gov (United States)

    Lau, Melissa; Li, Jianli; Cline, Hollis T

    2017-01-01

    The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet. Confocal imaging indicates that about half of the endfeet appear to appose the vasculature, and time-lapse analysis of NPC proliferation and endfeet-vascular interactions suggest that proliferative activity does not correlate with stable vascular apposition. Together, these findings characterize the neurovascular niche in the developing brain and suggest that, while signaling to NPCs may occur through vascular-derived soluble cues, stable contact between NPC endfeet and the vasculature is not required for developmental neurogenesis.

  8. Two-Particle Correlations with Neutral Pion and Direct Photon Triggers in pp and Pb+Pb Collisions with ALICE at the LHC

    CERN Document Server

    Zhu, Xiangrong; Constantinos, Loizides; Zhongbao, Yin; Loizides, Constantinos; Zhongbao, Yin

    Two-particle correlations is considered as a powerful probe for understanding the properties of the strongly interacting hot and dense medium. In such an analysis, a particle is chosen from higher $p_{\\rm T}$ region and called the trigger particle, which is presumably from jet fragmentations. The so called associated particles from lower $p_{\\rm T}$ region are always from the other fragmentation of the jet, or another production, such as collective flow. At RHIC and LHC, the measurements of the azimuthal angle distribution from two-particle correlations in A+A collisions show a strong suppression even disappeared at the high $p_{\\rm T}$ and enhancement with double-peak at the low $p_{\\rm T}$ on the away side, and ``ridge'' structure in pseudo-rapidity direction at the low $p_{\\rm T}$ on the near side compared to pp collisions. All the measurements can be explained as the effects of the hot and dense medium, and imply the Quark-Gluon Plasma is indeed formed in the heavy-ion collisions. When the direct ph...

  9. Evaluation of Diffusion Tensor Imaging-Based Tractography of the Corticospinal Tract: A Correlative Study With Intraoperative Magnetic Resonance Imaging and Direct Electrical Subcortical Stimulation.

    Science.gov (United States)

    Javadi, Seyed A; Nabavi, Arya; Giordano, Mario; Faghihzadeh, Elham; Samii, Amir

    2017-02-01

    The accuracy of intraoperative diffusion tensor imaging (DTI)–based tractography of the corticospinal tract (CST) is crucial for its use in neurosurgical planning and its implementation in image-guided surgery. To the best of our knowledge, this is the largest prospective correlative study of the intraoperative DTI tractography of the CST and intraoperative direct electrical subcortical stimulation (DESS) of the CST, with application of intraoperative magnetic resonance imaging (iMR). To evaluate intraoperatively acquired DTI-based tractography of the CST in correlation with DESS. Twenty patients with gliomas (grades II-IV) adjacent to the CST were included in this prospective study. Bilateral DTI tractography of the CST was performed pre- and intraoperatively with application of 1.5-T iMRI and the results correlated and compared with the prevailing gold standard of DESS. Sensitivity, specificity, positive predictive value, and negative predictive value were considered to quantify the correlation of DTI tractography with DESS. The intensity of DESS was correlated with the distance from the CST. Moreover, the tissue quality of stimulation points at the wall of the resection cavity was evaluated with 5-aminolevulinic acid. The clinical and volumetric outcomes at postoperative and follow-up periods were also analyzed. The mean ± SD age of the patients was 54.9 ± 12 years. A total of 40 CSTs were reconstructed and 36 stimulations were included at 20 pathological CSTs, resulting in 18 true-positive, 5 false-positive, and 13 true-negative responses. The sensitivity, specificity, positive predictive value, and negative predictive value of DTI tractography to localize the CST were 100%, 72%, 78%, and 100%, respectively. DTI-based tractography correlated well at 86% of DESSs, and a linear correlation was detected between the intensity of DESS and the distance. All of the patients improved clinically, and the mean extent of resection was 97.2%. 5-Aminolevulinic acid was

  10. Expression of protein tyrosine phosphatase alpha (RPTPalpha) in human breast cancer correlates with low tumor grade, and inhibits tumor cell growth in vitro and in vivo

    DEFF Research Database (Denmark)

    Ardini, E; Agresti, R; Tagliabue, E

    2000-01-01

    of Src family kinases, and regulation of integrin signaling, cell adhesion, and growth factor responsiveness. To explore its potential contribution to human neoplasia, we surveyed RPTPalpha protein levels in primary human breast cancer. We found RPTPalpha levels to vary widely among tumors, with 29......% of cases manifesting significant overexpression. High RPTPalpha protein levels correlated significantly with low tumor grade and positive estrogen receptor status. Expression of RPTPalpha in breast carcinoma cells led to growth inhibition, associated with increased accumulation in G0 and G1, and delayed...... tumor growth and metastasis. To our knowledge, this is the first example of a study correlating expression level of a specific bona fide PTP with neoplastic disease status in humans....

  11. Understanding the relative contributions of direct environmental effects and passive genotype-environment correlations in the association between familial risk factors and child disruptive behavior disorders.

    Science.gov (United States)

    Bornovalova, M A; Cummings, J R; Hunt, E; Blazei, R; Malone, S; Iacono, W G

    2014-03-01

    Previous work reports an association between familial risk factors stemming from parental characteristics and offspring disruptive behavior disorders (DBDs). This association may reflect (a) the direct effects of familial environment and (b) a passive gene-environment correlation (r(GE)), wherein the parents provide both the genes and the environment. The current study examined the contributions of direct environmental influences and passive r(GE) by comparing the effects of familial risk factors on child DBDs in genetically related (biological) and non-related (adoptive) families. Participants were 402 adoptive and 204 biological families. Familial environment was defined as maternal and paternal maladaptive parenting and antisociality, marital conflict and divorce; offspring DBDs included attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD). Mixed-level regressions estimated the main effects of familial environment, adoption status and the familial environment by adoption status interaction term, which tested for the presence of passive r(GE). There was a main effect of maternal and paternal maladaptive parenting and marital discord on child DBDs, indicating a direct environmental effect. There was no direct environmental effect of maternal or paternal antisociality, but maternal and paternal antisociality had stronger associations with child DBDs in biological families than adoptive families, indicating the presence of a passive r(GE). Many familial risk factors affected children equally across genetically related and non-related families, providing evidence for direct environmental effects. The relationship of parental antisociality and offspring DBDs was best explained by a passive r(GE), where a general vulnerability toward externalizing psychopathology is passed down by the parents to the children.

  12. High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children

    Science.gov (United States)

    2011-01-01

    Background Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP). Methods The study assessed the frequency of SP resistance-conferring polymorphisms in Plasmodium falciparum-positive samples from two clinical studies in Lambaréné. Their role on treatment responses and transmission potential was studied in an efficacy open-label clinical trial with a 28-day follow-up in 29 children under five with uncomplicated malaria. Results SP was well tolerated by all subjects in vivo. Three subjects were excluded from per-protocol analysis. PCR-corrected, 12/26 (46%) achieved an adequate clinical and parasitological response, 13/26 (50%) were late parasitological failures, while 1/26 (4%) had an early treatment failure, resulting in early trial discontinuation. Of 106 isolates, 98 (92%) carried the triple mutant dhfr haplotype. Three point mutations were found in dhps in a variety of haplotypic configurations. The 437G + 540E double mutant allele was found for the first time in Gabon. Conclusions There is a high prevalence of dhfr triple mutant with some dhps point mutations in Gabon, in line with treatment failures observed, and molecular markers of SP resistance should be closely monitored. Trial Registration ClinicalTrials.gov: NCT00453856 PMID:21569596

  13. Correlating Anatomy and Function with Gene Expression in Individual Neurons by Combining in Vivo Labeling, Patch Clamp, and Single Cell RNA-seq

    Directory of Open Access Journals (Sweden)

    Carsten K. Pfeffer

    2017-11-01

    Full Text Available The classification of neurons into distinct types is an ongoing effort aimed at revealing and understanding the diversity of the components of the nervous system. Recently available methods allow us to determine the gene expression pattern of individual neurons in the mammalian cerebral cortex to generate powerful categorization schemes. For a thorough understanding of neuronal diversity such genetic categorization schemes need to be combined with traditional classification parameters like position, axonal projection or response properties to sensory stimulation. Here we describe a method to link the gene expression of individual neurons with their position, axonal projection, or sensory response properties. Neurons are labeled in vivo based on their anatomical or functional properties and, using patch clamp pipettes, their RNA individually harvested in vitro for RNAseq. We validate the methodology using multiple established molecularly and anatomically distinct cell populations and explore molecular differences between uncharacterized neurons in mouse visual cortex. Gene expression patterns between L5 neurons projecting to frontal or contralateral cortex are distinct while L2 neurons differing in position, projection, or function are molecularly similar. With this method we can determine the genetic expression pattern of functionally and anatomically identified individual neurons.

  14. Correlation of Streptococcus mutans and Streptococcus sanguinis colonization and ex vivo hydrogen peroxide production in carious lesion-free and high caries adults.

    Science.gov (United States)

    Giacaman, Rodrigo A; Torres, Sebastián; Gómez, Yenifer; Muñoz-Sandoval, Cecilia; Kreth, Jens

    2015-01-01

    This study was conducted to estimate oral colonization by Streptococcus mutans and Streptococcus sanguinis in adults with high and without any caries experience. Furthermore, differences in the amount of hydrogen peroxide (H2O2) produced by S. sanguinis isolated from both groups were assessed. Forty adults were divided into: (i) carious lesion-free, without any carious lesion, assessed by the International Caries Detection and Assessment System (ICDAS), or restoration, (CF) and (ii) high caries experience (HC). Saliva samples were collected and seeded on respective agar-plates for enumeration of total streptococci, S. mutans and S. sanguinis (CFU/mL) and compared between groups. Additionally, S. sanguinis colonies obtained from both groups were inoculated on Prussian blue agar for H2O2 detection. Production of H2O2 was quantified and compared between the two groups. S. sanguinis counts were significantly higher in CF than HC individuals (pmutans showed significantly higher levels in HC than CF subjects (pmutans in saliva of adults without caries experience. In those people, S. sanguinis produces more H2O2ex vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. An In Vivo study to compare and evaluate the correlation of the facial measurements with the combined mesiodistal width of the maxillary anterior teeth between males and females

    Directory of Open Access Journals (Sweden)

    Reshma Banu

    2017-01-01

    Full Text Available Aim: The aim of this study was to compare and evaluate the correlation of the facial measurements (interalar, intercommissural, intercanthal, and interpupillary distance with the combined mesiodistal width of the maxillary anterior teeth between males and females. Objectives: The objectives of this study were: (a To evaluate the correlation of the facial measurements (interalar, intercommissural, intercanthal, and interpupillary distance and combined mesiodistal width of maxillary anterior teeth. (b To compare the correlation of the facial measurements (interalar, intercommissural, intercanthal, and interpupillary distance with the combined mesiodistal width of maxillary anterior teeth between males and females. Materials and Methods: This study was carried out on 120 dentate Subjects selected from Yenepoya Dental College, Mangalore. The vernier caliper was used to measure the interalar, intercommissural, intercanthal, and interpupillary distance. The mesiodistal width of maxillary anterior teeth was measured on the cast. For accuracy, every distance was measured three times and the mean taken. Results: Comparison of parameters between males and females was calculated using independent sample t-test. The values obtained for each variables are interalar distance: for males 38.89 ± 2.19 and for females 35.58 ± 2.33. Intercommissural distance: for males 50.96 ± 2.99 and for females 47.15 ± 2.97. Intercanthal distance: for males 31.92 ± 1.46 and for females 30.46 ± 2.07. Interpupillary distance: for males 65.15 ± 2.82 and for females 61.78 ± 3.18. Mesiodistal width of maxillary anterior teeth: for males 52.55 ± 1.82 and for females 51.33 ± 2.50. Conclusion: Within the limitations of this study, the study concluded there is a significant correlation between interalar, intercommissural, intercanthal, interpupillary distance, and mesiodistal width of maxillary anterior teeth in total subjects. In females, there is a significant correlation

  16. Correlation between visual and radiographic examinations of non-cavitated occlusal caries lesions: an in vivo study Correlação entre os exames visual e radiográfico de lesões de cárie oclusal não cavitadas: estudo in vivo

    Directory of Open Access Journals (Sweden)

    Victor Ferrás Wolwacz

    2004-06-01

    Full Text Available The aim of this study was to conduct an in vivo investigation of the correlation between the visual and radiographic scoring systems by Ekstrand et al.7 (1997 for the diagnosis of occlusal caries lesions. The study sample comprised 147 occlusal sites from 23 patients. Two trained and experienced examiners performed the clinical visual examinations. A third examiner, which was also trained, experienced and blind to the results of the visual clinical examination, performed the analysis of the bitewing radiographs. The correlation between visual and radiographic scores was assessed by Goodman & Kruskal's gamma correlation coefficient. Results showed a strong correlation between the scores for occlusal caries found in the visual and radiographic diagnosis systems used in this study.O presente estudo verificou in vivo a correlação existente entre os sistemas de escore visual e radiográfico de Ekstrand et al.7 (1997 para diagnóstico de lesões de cárie oclusal. A amostra do estudo foi constituída de 147 sítios oclusais obtidos a partir de 23 pacientes. Os exames clínicos visuais foram realizados por dois examinadores treinados e calibrados. A análise das radiografias interproximais foi realizada por um terceiro examinador também treinado e calibrado, que desconhecia os resultados do exame clínico visual. A correlação entre os escores visual e radiográfico foi avaliada por meio do coeficiente de correlação gamma de Goodman & Kruskal. Os resultados revelaram uma forte correlação existente entre os escores dos sistemas de diagnóstico visual e radiográfico de cárie oclusal adotados no presente estudo.

  17. Differential binding of Lef1 and Msx1/2 transcription factors to Dkk1 CNEs correlates with reporter gene expression in vivo

    DEFF Research Database (Denmark)

    Dr Lieven, Oliver Wilm; Dronka, Julia; Burmühl, Stephan

    2014-01-01

    Besides the active Wnt signalling itself, the extracellular inhibition by Dkk1 is important for various embryonic developmental processes, such as optic vesicle differentiation and facial outgrowth. Although a feedback crosstalk of the active Wnt/β-catenin signaling and Dkk1 regulation has been...... via Tcf/Lefs. By using site directed mutagenesis, we tested several conserved Tcf/Lef1 binding sites within Dkk1 conserved non-coding elements (CNEs) and found that these are required for tissue specific reporter expression. In addition a conserved Msx1/2 binding site is required for retinal reporter...... expression and Msx2 but not Msx1 binds its conserved binding site within CNE195 in the optic cups. Within craniofacial expression domains, Lef1 interferes with Dkk1 directly via two conserved Tcf/Lef1 binding sites in the craniofacial enhancer CNE114, both of which are required for the general craniofacial...

  18. Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis.

    Science.gov (United States)

    Kurabe, Miyuki; Furue, Hidemasa; Kohno, Tatsuro

    2016-05-18

    Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.

  19. In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells.

    Science.gov (United States)

    Rodman, C; Almeida-Porada, G; George, S K; Moon, J; Soker, S; Pardee, T; Beaty, M; Guida, P; Sajuthi, S P; Langefeld, C D; Walker, S J; Wilson, P F; Porada, C D

    2017-06-01

    Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

  20. In vitro adaptation of SAV3 in cell culture correlates with reduced in vivo replication capacity and virulence to Atlantic salmon (Salmo salar L.) parr.

    Science.gov (United States)

    Petterson, Elin; Guo, Tz-Chun; Evensen, Øystein; Haugland, Øyvind; Mikalsen, Aase B

    2015-10-01

    Salmonid alphavirus (SAV) is the causative agent of pancreas disease affecting Atlantic salmon and rainbow trout and causes a major burden to the aquaculture industry. This study describes a Norwegian subtype SAV3 virus isolate (SAV3-H10) subjected to serial passages in Chinook salmon embryo cells (CHSE-214) followed by Asian Grouper skin cells (AGK). Two passages from CHSE and one after transfer to AGK cells were chosen for further investigation, based on variation in degree and development of cytopathic effect (CPE). After plaque purification, several in vitro studies were performed. Cell viability after infection, viral replication and ability to cause morphological changes in CHSE and AGK cells was studied for the three isolates. The AGK-transferred isolate was identified with the strongest abilities to reduce cell viability, replicate more and cause more CPE in cell culture when compared with the early and late CHSE-grown isolates. Subsequently, the isolates were tested in an experimental fish challenge, showing higher viral load and higher pathological score for the least cell-cultured isolate. Full-length sequencing of the viral genome of the three isolates revealed divergence in four amino acid positions and the AGK-grown isolate also had a 3 nt deletion in the 3'UTR. In conclusion, we show that cell culture of SAV3-H10 selects for strains inducing earlier CPE in vitro with increased viral replication. In vivo, the effect is reversed, with lower replication levels and lower pathology scores in target organs. This study outlines a path to identify potential virulence motifs of SAV3.

  1. The Role of Endogenous D2 Receptor Levels in Morphine Addiction: A Correlative Study of Morphine Place Conditioning and In Vivo [3H]-Raclopride Binding

    Energy Technology Data Exchange (ETDEWEB)

    Khan, N.; Gatley, S.

    2004-01-01

    Dopamine is a neurotransmitter that has a wide array of effects on an individual’s mental state. It is vital in the regulation of motor skills and in generating the effects of substance abuse. This study examined the dopamine D2 receptors found in the striatum of the brain. The impetus for investigating this receptor lies in the perception that it plays an influential role in drug addiction. It has been conjectured on the basis of human PET studies that possession of low levels of D2 receptors will heighten an individual’s susceptibility to drug addiction. However, an alternative explanation of low D2 receptor levels in drug dependent individuals is that these levels are a consequence of drug abuse. To understand this phenomenon, the present study employed the paradigm of conditioned place preference (CPP). In CPP, individuals of an out-bred mouse strain are observed to spend time in environments where they had previously been exposed to a drug that is abused by humans. The drug chosen for our studies was morphine because it has been previously shown to generate a robust place preference in mice and is a prototypic abused drug in humans. D2 receptor levels were quantified using an in vivo binding study involving [3H]raclopride, a radioactive compound that binds to D2 receptors. The results showed a significant place preference for morphine following the conditioning procedure. Additionally, data from the binding analysis agreed with previous studies that the striatum contains high levels of D2 receptors. However, there was no consistent relationship between the extent of morphine CPP and D2 receptor levels as revealed by [3H]-RAC binding. This finding does not support the hypothesis that low levels of D2 receptors predispose a mouse to easy morphine conditioning. Further experiments are required to determine the ability to generalize our findings to other species and other drugs of abuse.

  2. Comparative evaluation of effects of bleaching on color stability and marginal adaptation of discolored direct and indirect composite laminate veneers under in vivo conditions

    National Research Council Canada - National Science Library

    Jain, Veena; Das, Taposh K; Pruthi, Gunjan; Shah, Naseem; Rajendiran, Suresh

    2015-01-01

    .... Bleaching is commonly used for treating discolored teeth. However, the literature is scanty regarding its effect on color and marginal adaptation of direct and indirect composite laminate veneers (CLVs...

  3. Peptide ligands incorporated into the threefold spike capsid domain to re-direct gene transduction of AAV8 and AAV9 in vivo.

    Directory of Open Access Journals (Sweden)

    Stefan Michelfelder

    Full Text Available Efficiency and specificity of viral vectors are vital issues in gene therapy. Insertion of peptide ligands into the adeno-associated viral (AAV capsid at receptor binding sites can re-target AAV2-derived vectors to alternative cell types. Also, the use of serotypes AAV8 and -9 is more efficient than AAV2 for gene transfer to certain tissues in vivo. Consequently, re-targeting of these serotypes by ligand insertion could be a promising approach but has not been explored so far. Here, we generated AAV8 and -9 vectors displaying peptides in the threefold spike capsid domain. These peptides had been selected from peptide libraries displayed on capsids of AAV serotype 2 to optimize systemic gene delivery to murine lung tissue and to breast cancer tissue in PymT transgenic mice (PymT. Such peptide insertions at position 590 of the AAV8 capsid and position 589 of the AAV9 capsid changed the transduction properties of both serotypes. However, both peptides inserted in AAV8 did not result in the same changes of tissue tropism as they did in AAV2. While the AAV2 peptides selected on murine lung tissue did not alter tropism of serotypes 8 and -9, insertion of the AAV2-derived peptide selected on breast cancer tissue augmented tumor gene delivery in both serotypes. Further, this peptide mediated a strong but unspecific in vivo gene transfer for AAV8 and abrogated transduction of various control tissues for AAV9. Our findings indicate that peptide insertion into defined sites of AAV8 and -9 capsids can change and improve their efficiency and specificity compared to their wild type variants and to AAV2, making these insertion sites attractive for the generation of novel targeted vectors in these serotypes.

  4. In search of genetic constraints limiting the evolution of egg size: direct and correlated responses to artificial selection on a prenatal maternal effector.

    Science.gov (United States)

    Pick, J L; Hutter, P; Tschirren, B

    2016-06-01

    Maternal effects are an important force in nature, but the evolutionary dynamics of the traits that cause them are not well understood. Egg size is known to be a key mediator of prenatal maternal effects with an established genetic basis. In contrast to theoretical expectations for fitness-related traits, there is a large amount of additive genetic variation in egg size observed in natural populations. One possible mechanism for the maintenance of this variation is through genetic constraints caused by a shared genetic basis among traits. Here we created replicated, divergent selection lines for maternal egg investment in Japanese quail (Coturnix japonica) to quantify the role of genetic constraints in the evolution of egg size. We found that egg size responds rapidly to selection, accompanied by a strong response in all egg components. Initially, we observed a correlated response in body size, but this response declined over time, showing that egg size and body size can evolve independently. Furthermore, no correlated response in fecundity (measured as the proportion of days on which a female laid an egg) was observed. However, the response to selection was asymmetrical, with egg size plateauing after one generation of selection in the high but not the low investment lines. We attribute this pattern to the presence of genetic asymmetries, caused by directional dominance or unequal allele frequencies. Such asymmetries may contribute to the evolutionary stasis in egg size observed in natural populations, despite a positive association between egg size and fitness.

  5. Tombusvirus P19 RNA silencing suppressor (RSS) activity in mammalian cells correlates with charged amino acids that contribute to direct RNA-binding.

    Science.gov (United States)

    Liu, Xiang; Houzet, Laurent; Jeang, Kuan-Teh

    2012-12-06

    Tombusvirus P19 is a protein encoded by tomato bushy stunt virus and related tombusviruses. Earlier studies have demonstrated that P19 is an RNA silencing suppressor (RSS) in plant cells. However, it has not been systematically investigated how P19 suppresses RNA interference in various mammalian cell settings. We have studied the RSS effect of P19 in mammalian cells, HEK293T, HeLa, and mouse embryonic fibroblasts. We have individually mutated 18 positively charged residues in P19 and found that 6 of these charged residues in P19 reduce its ability to suppress RNA interference. In each case, the reduction of silencing of RNA interference correlated with the reduced ability by these P19 mutants to bind siRNAs (small interfering RNAs). Our findings characterize a class of RNA-binding proteins that function as RSS moieties. We find a tight correlation between positively charged residues in P19 accounting for siRNA-binding and their RSS activity. Because P19's activity is conserved in plant and animal cells, we conclude that its RSS function unlikely requires cell type-specific co-factors and likely arises from direct RNA-binding.

  6. Medium modification of jet fragmentation in Au+Au collisions at √[s(NN)]=200 GeV measured in direct photon-hadron correlations.

    Science.gov (United States)

    Adare, A; Afanasiev, S; Aidala, C; Ajitanand, N N; Akiba, Y; Akimoto, R; Al-Bataineh, H; Al-Ta'ani, H; Alexander, J; Angerami, A; Aoki, K; Apadula, N; Aphecetche, L; Aramaki, Y; Armendariz, R; Aronson, S H; Asai, J; Asano, H; Aschenauer, E C; Atomssa, E T; Averbeck, R; Awes, T C; Azmoun, B; Babintsev, V; Bai, M; Baksay, G; Baksay, L; Baldisseri, A; Bannier, B; Barish, K N; Barnes, P D; Bassalleck, B; Basye, A T; Bathe, S; Batsouli, S; Baublis, V; Baumann, C; Baumgart, S; Bazilevsky, A; Belikov, S; Belmont, R; Bennett, R; Berdnikov, A; Berdnikov, Y; Bickley, A A; Bing, X; Blau, D S; Boissevain, J G; Bok, J S; Borel, H; Boyle, K; Brooks, M L; Buesching, H; Bumazhnov, V; Bunce, G; Butsyk, S; Camacho, C M; Campbell, S; Castera, P; Chang, B S; Chang, W C; Charvet, J-L; Chen, C-H; Chernichenko, S; Chi, C Y; Chiba, J; Chiu, M; Choi, I J; Choi, J B; Choi, S; Choudhury, R K; Christiansen, P; Chujo, T; Chung, P; Churyn, A; Chvala, O; Cianciolo, V; Citron, Z; Cleven, C R; Cole, B A; Comets, M P; Connors, M; Constantin, P; Csanád, M; Csörgő, T; Dahms, T; Dairaku, S; Danchev, I; Das, K; Datta, A; Daugherity, M S; David, G; Deaton, M B; Dehmelt, K; Delagrange, H; Denisov, A; d'Enterria, D; Deshpande, A; Desmond, E J; Dharmawardane, K V; Dietzsch, O; Ding, L; Dion, A; Donadelli, M; Drapier, O; Drees, A; Drees, K A; Dubey, A K; Durham, J M; Durum, A; Dutta, D; Dzhordzhadze, V; D'Orazio, L; Edwards, S; Efremenko, Y V; Egdemir, J; Ellinghaus, F; Emam, W S; Engelmore, T; Enokizono, A; En'yo, H; Esumi, S; Eyser, K O; Fadem, B; Fields, D E; Finger, M; Finger, M; Fleuret, F; Fokin, S L; Fraenkel, Z; Frantz, J E; Franz, A; Frawley, A D; Fujiwara, K; Fukao, Y; Fusayasu, T; Gadrat, S; Gainey, K; Gal, C; Garishvili, A; Garishvili, I; Glenn, A; Gong, H; Gong, X; Gonin, M; Gosset, J; Goto, Y; Granier de Cassagnac, R; Grau, N; Greene, S V; Grosse Perdekamp, M; Gunji, T; Guo, L; Gustafsson, H-Å; Hachiya, T; Hadj Henni, A; Haegemann, C; Haggerty, J S; Hahn, K I; Hamagaki, H; Hamblen, J; Han, R; Hanks, J; Harada, H; Hartouni, E P; Haruna, K; Hashimoto, K; Haslum, E; Hayano, R; He, X; Heffner, M; Hemmick, T K; Hester, T; Hiejima, H; Hill, J C; Hobbs, R; Hohlmann, M; Hollis, R S; Holzmann, W; Homma, K; Hong, B; Horaguchi, T; Hori, Y; Hornback, D; Huang, S; Ichihara, T; Ichimiya, R; Ide, J; Iinuma, H; Ikeda, Y; Imai, K; Imrek, J; Inaba, M; Inoue, Y; Iordanova, A; Isenhower, D; Isenhower, L; Ishihara, M; Isobe, T; Issah, M; Isupov, A; Ivanischev, D; Jacak, B V; Javani, M; Jia, J; Jiang, X; Jin, J; Jinnouchi, O; Johnson, B M; Joo, K S; Jouan, D; Jumper, D S; Kajihara, F; Kametani, S; Kamihara, N; Kamin, J; Kaneta, M; Kaneti, S; Kang, B H; Kang, J H; Kang, J S; Kanou, H; Kapustinsky, J; Karatsu, K; Kasai, M; Kawall, D; Kawashima, M; Kazantsev, A V; Kempel, T; Khanzadeev, A; Kijima, K M; Kikuchi, J; Kim, B I; Kim, C; Kim, D H; Kim, D J; Kim, E; Kim, E-J; Kim, H J; Kim, K-B; Kim, S H; Kim, Y-J; Kim, Y K; Kinney, E; Kiriluk, K; Kiss, Á; Kistenev, E; Kiyomichi, A; Klatsky, J; Klay, J; Klein-Boesing, C; Kleinjan, D; Kline, P; Kochenda, L; Kochetkov, V; Komatsu, Y; Komkov, B; Konno, M; Koster, J; Kotchetkov, D; Kotov, D; Kozlov, A; Král, A; Kravitz, A; Krizek, F; Kubart, J; Kunde, G J; Kurihara, N; Kurita, K; Kurosawa, M; Kweon, M J; Kwon, Y; Kyle, G S; Lacey, R; Lai, Y S; Lajoie, J G; Layton, D; Lebedev, A; Lee, B; Lee, D M; Lee, J; Lee, K; Lee, K B; Lee, K S; Lee, M K; Lee, S H; Lee, S R; Lee, T; Leitch, M J; Leite, M A L; Leitgab, M; Leitner, E; Lenzi, B; Lewis, B; Li, X; Liebing, P; Lim, S H; Linden Levy, L A; Liška, T; Litvinenko, A; Liu, H; Liu, M X; Love, B; Luechtenborg, R; Lynch, D; Maguire, C F; Makdisi, Y I; Makek, M; Malakhov, A; Malik, M D; Manion, A; Manko, V I; Mannel, E; Mao, Y; Mašek, L; Masui, H; Masumoto, S; Matathias, F; McCumber, M; McGaughey, P L; McGlinchey, D; McKinney, C; Means, N; Mendoza, M; Meredith, B; Miake, Y; Mibe, T; Mignerey, A C; Mikeš, P; Miki, K; Miller, T E; Milov, A; Mioduszewski, S; Mishra, D K; Mishra, M; Mitchell, J T; Mitrovski, M; Miyachi, Y; Miyasaka, S; Mohanty, A K; Moon, H J; Morino, Y; Morreale, A; Morrison, D P; Motschwiller, S; Moukhanova, T V; Mukhopadhyay, D; Murakami, T; Murata, J; Nagae, T; Nagamiya, S; Nagata, Y; Nagle, J L; Naglis, M; Nagy, M I; Nakagawa, I; Nakamiya, Y; Nakamura, K R; Nakamura, T; Nakano, K; Nattrass, C; Nederlof, A; Newby, J; Nguyen, M; Nihashi, M; Niida, T; Norman, B E; Nouicer, R; Novitzky, N; Nyanin, A S; O'Brien, E; Oda, S X; Ogilvie, C A; Ohnishi, H; Oka, M; Okada, K; Omiwade, O O; Onuki, Y; Oskarsson, A; Ouchida, M; Ozawa, K; Pak, R; Pal, D; Palounek, A P T; Pantuev, V; Papavassiliou, V; Park, B H; Park, I H; Park, J; Park, S K; Park, W J; Pate, S F; Patel, L; Pei, H; Peng, J-C; Pereira, H; Peresedov, V; Peressounko, D Yu; Petti, R; Pinkenburg, C; Pisani, R P; Proissl, M; Purschke, M L; Purwar, A K; Qu, H; Rak, J; Rakotozafindrabe, A; Ravinovich, I; Read, K F; Rembeczki, S; Reuter, M; Reygers, K; Reynolds, R; Riabov, V; Riabov, Y; Richardson, E; Roach, D; Roche, G; Rolnick, S D; Romana, A; Rosati, M; Rosen, C A; Rosendahl, S S E; Rosnet, P; Rukoyatkin, P; Ružička, P; Rykov, V L; Sahlmueller, B; Saito, N; Sakaguchi, T; Sakai, S; Sakashita, K; Sakata, H; Samsonov, V; Sano, M; Sano, S; Sarsour, M; Sato, S; Sato, T; Sawada, S; Sedgwick, K; Seele, J; Seidl, R; Semenov, A Yu; Semenov, V; Sen, A; Seto, R; Sharma, D; Shein, I; Shevel, A; Shibata, T-A; Shigaki, K; Shimomura, M; Shoji, K; Shukla, P; Sickles, A; Silva, C L; Silvermyr, D; Silvestre, C; Sim, K S; Singh, B K; Singh, C P; Singh, V; Skutnik, S; Slunečka, M; Soldatov, A; Soltz, R A; Sondheim, W E; Sorensen, S P; Soumya, M; Sourikova, I V; Sparks, N A; Staley, F; Stankus, P W; Stenlund, E; Stepanov, M; Ster, A; Stoll, S P; Sugitate, T; Suire, C; Sukhanov, A; Sun, J; Sziklai, J; Tabaru, T; Takagi, S; Takagui, E M; Takahara, A; Taketani, A; Tanabe, R; Tanaka, Y; Taneja, S; Tanida, K; Tannenbaum, M J; Tarafdar, S; Taranenko, A; Tarján, P; Tennant, E; Themann, H; Thomas, T L; Todoroki, T; Togawa, M; Toia, A; Tojo, J; Tomášek, L; Tomášek, M; Tomita, Y; Torii, H; Towell, R S; Tram, V-N; Tserruya, I; Tsuchimoto, Y; Tsuji, T; Vale, C; Valle, H; van Hecke, H W; Vargyas, M; Vazquez-Zambrano, E; Veicht, A; Velkovska, J; Vértesi, R; Vinogradov, A A; Virius, M; Vossen, A; Vrba, V; Vznuzdaev, E; Wagner, M; Walker, D; Wang, X R; Watanabe, D; Watanabe, K; Watanabe, Y; Watanabe, Y S; Wei, F; Wei, R; Wessels, J; White, S N; Winter, D; Wolin, S; Wood, J P; Woody, C L; Wright, R M; Wysocki, M; Xie, W; Yamaguchi, Y L; Yamaura, K; Yang, R; Yanovich, A; Yasin, Z; Ying, J; Yokkaichi, S; You, Z; Young, G R; Younus, I; Yushmanov, I E; Zajc, W A; Zaudtke, O; Zelenski, A; Zhang, C; Zhou, S; Zimányi, J; Zolin, L

    2013-07-19

    The jet fragmentation function is measured with direct photon-hadron correlations in p+p and Au+Au collisions at √[s(NN)]=200 GeV. The p(T) of the photon is an excellent approximation to the initial p(T) of the jet and the ratio z(T)=p(T)(h)/p(T)(γ) is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au+Au collisions while a photon isolation cut is applied in p+p. I(AA), the ratio of hadron yield opposite the photon in Au+Au to that in p+p, indicates modification of the jet fragmentation function. Suppression, most likely due to energy loss in the medium, is seen at high z(T). The associated hadron yield at low z(T) is enhanced at large angles. Such a trend is expected from redistribution of the lost energy into increased production of low-momentum particles.

  7. Evaluation of Elastin/Collagen Content in Human Dermis in-Vivo by Multiphoton Tomography—Variation with Depth and Correlation with Aging

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Pittet

    2014-08-01

    Full Text Available The aim of this study was to evaluate the influence of the depth of the dermis on the measured collagen and elastin levels and to establish the correlation between the amount of these two extracellular matrix (ECM components and age. Multiphoton Microscopy (MPM that measures the autofluorescence (AF and second harmonic generation (SHG was used to quantify the levels of elastin and collagen and to determine the SAAID (SHG-to-AF Aging Index of Dermis at two different skin depths. A 50 MHz ultrasound scanner was used for the calculation of the Sub Epidermal Non Echogenic Band (SENEB. The measurements of the skin mechanical properties were done with a cutometer. All measurements were performed on two groups of 30 healthy female volunteers. The MPM showed a decrease of the quantity of collagen and elastin as a function of depth of the dermis as well as age. The SAAID was lower for the older skin in the deeper dermis. Ultrasound imaging revealed a significant decrease of SENEB as a function of aging. The mechanical properties confirmed a loss of cutaneous elasticity and firmness. Although multiphoton microscopy is a powerful technique to study the characteristics of the dermis and its age-related damage, the location of the measurements (depth remains very important for the validation of these variations. These variations do not seem to be homogeneous according to the part of the dermis that is studied.

  8. Lower In vivo Myo-Inositol in the Anterior Cingulate Cortex Correlates with Delayed Melatonin Rhythms in Young Persons with Depression

    Directory of Open Access Journals (Sweden)

    Rébecca Robillard

    2017-06-01

    Full Text Available Myo-inositol, a second messenger glucose isomer and glial marker, is potentiated by melatonin. In addition to common abnormalities in melatonin regulation, depressive disorders have been associated with reduced myo-inositol in frontal structures. This study examined associations between myo-inositol in the anterior cingulate cortex and the timing of evening melatonin release. Forty young persons with unipolar depression were recruited from specialized mental health services (20.3 ± 3.8 years old. Healthy controls were recruited from the community (21.7 ± 2.6 years old. The timing of dim light melatonin onset (DLMO was estimated using salivary melatonin sampling. Myo-inositol concentrations (MI/CrPCr ratio in the anterior cingulate cortex were obtained using proton magnetic resonance spectroscopy. After controlling for age, sex, and CrPCr concentration the depression group had significantly lower MI/CrPCr ratios than healthy controls [F(4, 75 = 11.4, p = 0.001]. In the depression group, later DLMO correlated with lower MI/CrPCr ratio (r = −0.48, p = 0.014. These findings suggest that neurochemical changes in the frontal cortex are associated with circadian disruptions in young persons with depression.

  9. Multicontrast-weighted magnetic resonance imaging of atherosclerotic plaques at 3.0 and 1.5 Tesla: ex-vivo comparison with histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Koops, Andreas; Ittrich, Harald; Priest, Andrew; Stork, Alexander; Adam, Gerhard; Weber, Christoph [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Petri, Susan [University Medical Center Hamburg-Eppendorf, Department of Pathology, Hamburg (Germany); Lockemann, Ute [University Medical Center Hamburg-Eppendorf, Department of Forensic Medicine, Hamburg (Germany)

    2007-01-15

    The purpose was to analyze magnetic resonance (MR) plaque imaging at 3.0 Tesla and 1.5 Tesla in correlation with histopathology. MR imaging (MRI) of the abdominal aorta and femoral artery was performed on seven corpses using T1-weighted, T2-weighted, and PD-weighted sequences at 3.0 and 1.5 Tesla. Cross-sectional images at the branching of the inferior mesenteric artery and the profunda femoris were rated with respect to image quality. Corresponding cross sections of the imaged vessels were obtained at autopsy. The atherosclerotic plaques in the histological slides and MR images were classified according to the American Heart Association (AHA) and analyzed for differences. MRI at 3.0 Tesla offered superior depiction of arterial wall composition in all contrast weightings, rated best for T2-weighted images. Comparing for field strength, the highest differences were observed in T1-weighted and T2-weighted techniques (both P{<=}0.001), with still significant differences in PD-weighted sequence (P{<=}0.005). The majority of plaques were histologically classified as calcified plaques. In up to 21% of the cases, MRI at both field strengths detected signal loss characteristic of calcification although calcified plaque was absent in histology. MRI at 3.0 Tesla offers superior plaque imaging quality compared with 1.5 Tesla, but further work is necessary to determine whether this translates in superior diagnostic accuracy. (orig.)

  10. Direct Filling Golds: An In-Vitro Study of Microleakage as a Function of Condensation Force: An In-Vivo Study of Marginal Quality

    Science.gov (United States)

    1979-01-01

    properties of direct gold restorative materials. Peterson23 determined that as the annealing temperature of gold foil increases above 2000 C both the...controlled mica tray was below 2000 C. _ Spencer et a124 measured the BIN as a function of annealing temperature between 260 and 4500 C and determined that the...Pacific Society of Periodontology I i ° i - - ~ K iiI IN III I V -I I II? I F I I I I I ~~1:1 II Ii I a I pI I I I I _ _____ -~ - ____ ~ -~-~ DIRECT

  11. Fast cadmium inhibition of photosynthesis in cyanobacteria in vivo and in vitro studies using perturbed angular correlation of gamma-rays.

    Science.gov (United States)

    Sas, Klára Nárcisz; Kovács, László; Zsíros, Ottó; Gombos, Zoltán; Garab, Gyozo; Hemmingsen, Lars; Danielsen, Eva

    2006-09-01

    The effect of cadmium on the photosynthetic activity of Synechocystis PCC 6803 was monitored in this study. The oxygen evolving capacity of Synechocystis treated with 40 muM CdCl(2) was depressed to 10% of the maximum in 15 min, indicating that Cd(2+) penetrated rapidly into the cells and blocked the photosynthetic activity. However, neither photosystem II (PSII) nor photosystem I (PSI) activity showed a significant short-term decrease which would explain this fast decrease in the whole-chain electron transport. Thermoluminescence measurements have shown that the charge separation and stabilization in PSII remains essentially unchanged during the first few hours following the Cd(2+) treatment. The electron flow through PSI was monitored by following the redox changes of the P700 reaction centers of PSI. Alterations in the oxidation kinetics of P700 in the Cd(2+)-treated cells indicated that Cd(2+) treatment might affect the available electron acceptor pool of P700, including the CO(2) reduction and accumulation in the cells. Perturbed angular correlation of gamma-rays (PAC) using the radioactive (111m)Cd isotope was used to follow the Cd(2+) uptake at a molecular level. The most plausible interpretation of the PAC data is that Cd(2+) is taken up by one or more Zn proteins replacing Zn(2+) in Synechocystis PCC 6803. Using the radioactive (109)Cd isotope, a protein of approximately 30 kDa that binds Cd(2+) could be observed in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results indicate that Cd(2+) might inactivate different metal-containing enzymes, including carbonic anhydrase, by replacing the zinc ion, which would explain the rapid and almost full inhibition of the photosynthetic activity in cyanobacteria.

  12. Polyinosinic Acid Blocks Adeno-Associated Virus Macrophage Endocytosis In Vitro and Enhances Adeno-Associated Virus Liver-Directed Gene Therapy In Vivo

    NARCIS (Netherlands)

    van Dijk, Remco; Montenegro-Miranda, Paula S.; Riviere, Christel; Schilderink, Ronald; ten Bloemendaal, Lysbeth; van Gorp, Jacqueline; Duijst, Suzanne; de Waart, Dirk R.; Beuers, Ulrich; Haisma, Hidde J.; Bosma, Piter J.

    2013-01-01

    Adeno-associated virus serotype 8 (AAV8) has been demonstrated to be effective for liver-directed gene therapy in humans. Although hepatocytes are the main target cell for AAV8, there is a loss of the viral vector because of uptake by macrophages and Kupffer cells. Reducing this loss would increase

  13. Estimation of femoral bone density from trabecular direct wave and cortical guided wave ultrasound velocities measured at the proximal femur in vivo

    DEFF Research Database (Denmark)

    Barkmann, Reinhard; Dencks, Stefanie; Bremer, Alexander

    2008-01-01

    Bone mineral density (BMD) of the proximal femur is a predictor of hip fracture risk. We developed a Quantitative Ultrasound (QUS) scanner for measurements at this site with similar performance (FemUS). In this study we tested if ultrasound velocities of direct waves through trabecular bone and o...

  14. Comparative evaluation of effects of bleaching on color stability and marginal adaptation of discolored direct and indirect composite laminate veneers under in vivo conditions

    Directory of Open Access Journals (Sweden)

    Veena Jain

    2015-01-01

    Clinical Significance: Indirect composites should be preferred to direct composites as veneering materials as they have better color stability. Special attention should be given to their marginal adaptation especially in the CE region. Bleaching should be avoided in patients with composite restorations in the mouth.

  15. In vitro and in vivo evaluation of direct rhenium-188-labeled anti-CD52 monoclonal antibody alemtuzumab for radio immunotherapy of B-cell chronic lymphocytic leukemia

    NARCIS (Netherlands)

    De Decker, Mario; Bacher, Klaus; Thierens, Hubert; Slegers, Guido; Dierckx, Rudi A.; De Vos, Filip

    Alemtuzumab (Campath, Berlex) is a humanized IgG1 rat monoclonal antibody directed against the cell surface CD52 antigen, found on lymphocytes and monocytes. It is being developed for the treatment of chronic lymphocytic leukemia (CLL), autoinumme disease and for the prevention of transplant

  16. A vibration investigation of a flat surface contact to skull bone for direct bone conduction transmission in sheep skulls in vivo.

    Science.gov (United States)

    Taghavi, Hamidreza; Håkansson, Bo; Eeg-Olofsson, Måns; Johansson, Carina B; Tjellström, Anders; Reinfeldt, Sabine; Bergqvist, Tomas; Olsson, Joakim

    2013-06-01

    Bone conduction implant (BCI) attached with a flat surface contact will offer efficient and linear vibration transmission over time. Despite that percutaneous bone conduction devices (PBCD) are successful in treating patients with conductive hearing loss, there are some drawbacks related to the need of a permanent skin penetration. The BCI system is designed as an alternative to the PBCD because it leaves the skin intact. BCI dummy implants were installed in 3 sheep skulls in vivo to study the vibration transmission characteristics over time. Mechanical point impedances and vibration transfer response functions of the BCI implants were measured at the time of surgery and after a healing period of 8 months. In 1 sheep both implants healed without complications. In the other 2 sheep, the implants were either partially loose or lost to follow up. In the sheep with stable implants, it was found by the resonance frequency shift of the mechanical point impedance that a firmer integration between the implant and bone tissue as seen in osseointegrated surfaces developed over time. It was also shown that the transcranial vibration transmission remains stable and linear. Providing bone chips in the contact between the implant and the bone did not enhance vibration transmission. The surgical procedure for installing the BCI dummy implants was uneventful. The mechanical point impedances and vibration transfer response functions indicate that the BCI implants integrate and that transmission conditions remain stable over time.

  17. In vivo reorganization of the actin cytoskeleton in leaves of Nicotiana tabacum L. transformed with plastin-GFP. Correlation with light-activated chloroplast responses

    Directory of Open Access Journals (Sweden)

    Anielska-Mazur Anna

    2009-05-01

    Full Text Available Abstract Background The actin cytoskeleton is involved in the responses of plants to environmental signals. Actin bundles play the role of tracks in chloroplast movements activated by light. Chloroplasts redistribute in response to blue light in the mesophyll cells of Nicotiana tabacum. The aim of this work was to study the relationship between chloroplast responses and the organization of actin cytoskeleton in living tobacco cells. Chloroplast movements were measured photometrically as changes in light transmission through the leaves. The actin cytoskeleton, labeled with plastin-GFP, was visualised by confocal microscopy. Results The actin cytoskeleton was affected by strong blue and red light. No blue light specific actin reorganization was detected. EGTA and trifluoperazine strongly inhibited chloroplast responses and disrupted the integrity of the cytoskeleton. This disruption was reversible by Ca2+ or Mg2+. Additionally, the effect of trifluoperazine was reversible by light. Wortmannin, an inhibitor of phosphoinositide kinases, potently inhibited chloroplast responses but did not influence the actin cytoskeleton at the same concentration. Also this inhibition was reversed by Ca2+ and Mg2+. Magnesium ions were equally or more effective than Ca2+ in restoring chloroplast motility after treatment with EGTA, trifluoperazine or wortmannin. Conclusion The architecture of the actin cytoskeleton in the mesophyll of tobacco is significantly modulated by strong light. This modulation does not affect the direction of chloroplast redistribution in the cell. Calcium ions have multiple functions in the mechanism of the movements. Our results suggest also that Mg2+ is a regulatory molecule cooperating with Ca2+ in the signaling pathway of blue light-induced tobacco chloroplast movements.

  18. In vivo assessment of caries excavation with a fluorescence camera compared to direct bacteriological sampling and quantitative analysis using flow cytometry.

    Science.gov (United States)

    Stoll, Richard; Urban-Klein, Beata; Giacomin, Paul; Loukas, Alex; Jablonski-Momeni, Anahita

    2015-02-01

    The aim of this study was to assess the performance of the fluorescence camera device VistaCam iX (VC) for the control of caries excavation compared to visual assessment and bacteriological evaluation. Twenty-three patients with 32 dentinal carious lesions were included in the study. The lesions were classified using the International Caries Detection and Assessment System. Fluorescence images were taken at the surface of each lesion using the VC before excavation (stage 1), during (stage 2) and after excavation (stage 3). At each stage, dentine samples were collected. All cavities were closed after excavation using permanent fillings. Bacteria were counted within each dentine sample using flow cytometry. Significant moderate correlation between the fluorescence readings and the bacteria count was found at stage 3 (Spearman correlation coefficient rs = 0.40, p = 0.027). Area under the ROC curve (AUC) was calculated for fluorescence readings and bacteria count using the clinical status at stage 3 as a reference. AUC was 0.954 for the VC readings and 0.797 for bacteria count. Using the median bacteria count at stage 3 as a reference, the AUC for the fluorescence readings was 0.753. The results indicate that the fluorescence camera appears to be a useful supplementary tool in assessing the endpoint of caries excavation with the advantage of enabling data to be digitally visualized and stored. When an experienced dental clinician determined the excavation endpoint, the performance with respect to remaining bacteria count was good.

  19. Monitoring of radio frequency tissue ablation in an interventional magnetic resonance environment. Preliminary ex vivo and in vivo results.

    Science.gov (United States)

    Steiner, P; Botnar, R; Goldberg, S N; Gazelle, G S; Debatin, J F

    1997-11-01

    The authors evaluate the feasibility of monitoring radio frequency (RF) ablation in an interventional, open-configuration, 0.5-tesla magnetic resonance (MR) environment. Ex vivo and in vivo RF coagulation necrosis were induced in porcine paraspinal muscle tissue using a 300 kHz monopolar RF generator applying 5 to 20 W over 3 to 9 minutes. Images were acquired simultaneous to RF application, after RF application, and in an intermittent mode (60 seconds of RF followed by 15 seconds of MR imaging). Temperature changes were monitored based on amplitude (ex vivo) and phase alterations (in vivo) of a T1-weighted graded refocused echo (GRE) sequence enabling an update every 2.5 seconds. A standardized color-coded subtraction technique enhanced signal changes. Additionally, T2- and T1-weighted spin echo (SE) images were acquired with and without intravenous contrast. Macroscopic coagulation size was compared with lesion size seen on MR images. Although lesion diameters were related directly to applied RF power, the application mode had no significant impact on coagulation size (P > 0.05). As could be expected, MR imaging during RF ablation resulted in major image distortion. Radio frequency effects were seen on images acquired in the continuous and intermittent modes. Coagulation size seen on GRE images correlated well with macroscopy both ex vivo (r = 0.89) and in vivo (r = 0.92). Poorer correlation was found with postinterventional SE sequences (r = 0.78-0.84). Magnetic resonance monitoring of RF effects is feasible both ex vivo as well as in vivo using temperature-sensitive sequences in an open-configuration MR environment.

  20. Defining human mesenchymal stem cell efficacy in vivo

    Directory of Open Access Journals (Sweden)

    Lennon Donald P

    2010-10-01

    Full Text Available Abstract Allogeneic human mesenchymal stem cells (hMSCs can suppress graft versus host disease (GvHD and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma.

  1. Analysis and alternatives in two-dimensional multigrid particle image velocimetry methods: application of a dedicated weighting function and symmetric direct correlation

    Science.gov (United States)

    Nogueira, J.; Lecuona, A.; Ruiz-Rivas, U.; Rodríguez, P. A.

    2002-07-01

    Multigrid particle image velocimetry (PIV) is an open path in the search for high-resolution PIV methods. It is based on an iterative scheme that uses the information of initial processing to adapt the method parameters in order to improve the measurements. This is mainly performed by reducing the size of the interrogation windows and shifting them. In multigrid PIV, two sources of error can significantly affect the final measurement quality: (1) the error coming from the amplitude response of the initial large interrogation windows to spatial frequencies; (2) the error originating from the truncation of particles at the borders of the final small interrogation windows. By applying weighting functions and using symmetric direct correlation both errors can be reduced, respectively. These techniques have been separately tested in the past, but a joint implementation has not yet been analysed. This task is fulfilled and both sources of error are further clarified. For this purpose, a one-dimensional single wavelength displacement field is used. This gives us the opportunity to analyse the non-linear behaviour of PIV, together with the influence of basic parameters on it. In addition to this, the multigrid method, so far described, is enhanced by compensation of the particle pattern deformation. The metrological performance of this advanced method is tested using synthetic images and the results are compared with those delivered by established PIV methods. Coherence between these results and those obtained in a real image is also detailed.

  2. Jet-like correlations with direct-photon and neutral-pion triggers at sNN=200 GeV

    Directory of Open Access Journals (Sweden)

    L. Adamczyk

    2016-09-01

    Full Text Available Azimuthal correlations of charged hadrons with direct-photon (γdir and neutral-pion (π0 trigger particles are analyzed in central Au+Au and minimum-bias p+p collisions at sNN=200 GeV in the STAR experiment. The charged-hadron per-trigger yields at mid-rapidity from central Au+Au collisions are compared with p+p collisions to quantify the suppression in Au+Au collisions. The suppression of the away-side associated-particle yields per γdir trigger is independent of the transverse momentum of the trigger particle (pTtrig, whereas the suppression is smaller at low transverse momentum of the associated charged hadrons (pTassoc. Within uncertainty, similar levels of suppression are observed for γdir and π0 triggers as a function of zT (≡pTassoc/pTtrig. The results are compared with energy-loss-inspired theoretical model predictions. Our studies support previous conclusions that the lost energy reappears predominantly at low transverse momentum, regardless of the trigger energy.

  3. Potato Virus Y HCPro Suppression of Antiviral Silencing in Nicotiana benthamiana Plants Correlates with Its Ability To Bind In Vivo to 21- and 22-Nucleotide Small RNAs of Viral Sequence.

    Science.gov (United States)

    Del Toro, Francisco J; Donaire, Livia; Aguilar, Emmanuel; Chung, Bong-Nam; Tenllado, Francisco; Canto, Tomás

    2017-06-15

    We have investigated short and small RNAs (sRNAs) that were bound to a biologically active hexahistidine-tagged Potato virus Y (PVY) HCPro suppressor of silencing, expressed from a heterologous virus vector in Nicotiana benthamiana plants, and purified under nondenaturing conditions. We found that RNAs in purified preparations were differentially enriched in 21-nucleotide (nt) and, to a much lesser extent, 22-nt sRNAs of viral sequences (viral sRNAs [vsRNAs]) compared to those found in a control plant protein background bound to nickel resin in the absence of HCPro or in a purified HCPro alanine substitution mutant (HCPro mutB) control that lacked suppressor-of-silencing activity. In both controls, sRNAs were composed almost entirely of molecules of plant sequence, indicating that the resin-bound protein background had no affinity for vsRNAs and also that HCPro mutB failed to bind to vsRNAs. Therefore, PVY HCPro suppressor activity correlated with its ability to bind to 21- and 22-nt vsRNAs. HCPro constituted at least 54% of the total protein content in purified preparations, and we were able to calculate its contribution to the 21- and the 22-nt pools of sRNAs present in the purified samples and its binding strength relative to the background. We also found that in the 21-nt vsRNAs of the HCPro preparation, 5'-terminal adenines were overrepresented relative to the controls, but this was not observed in vsRNAs of other sizes or of plant sequences.IMPORTANCE It was previously shown that HCPro can bind to long RNAs and small RNAs (sRNAs) in vitro and, in the case of Turnip mosaic virus HCPro, also in vivo in arabidopsis AGO2-deficient plants. Our data show that PVY HCPro binds in vivo to sRNAs during infection in wild-type Nicotiana benthamiana plants when expressed from a heterologous virus vector. Using a suppression-of-silencing-deficient HCPro mutant that can accumulate in this host when expressed from a virus vector, we also show that sRNA binding correlates

  4. Pulpal response to nano hydroxyapatite, mineral trioxide aggregate and calcium hydroxide when used as a direct pulp capping agent: an in vivo study.

    Science.gov (United States)

    Swarup, S J; Rao, A; Boaz, K; Srikant, N; Shenoy, R

    2014-01-01

    Nano hydroxyapatite (Nano-HA) and Mineral Trioxide Aggregate (MTA) because of its better qualities can be used as an alternative to calcium hydroxide in direct pulp capping procedures. The aim of the study was to compare the response of exposed human pulp to Nano-HA, Mineral Trioxide Aggregate and calcium hydroxide. The study was done on 30 premolars, ranging from patients between 11-15 years. Intentional pulp capping was done using one of the experimental materials. The extracted teeth were then subjected to staining procedure and evaluated for dentin bridge and pulpal response after 15 and 30 days. Intragroup comparisons of the observed values were analyzed using Chi-square test. Nano-HA and MTA produced continuous dentin bridges. Dentin bridge that was formed in MTA group had regular pattern of dentinal tubules but no tubules were seen in the nano-HA group. Dentin bridge was not observed in Dycal group for the 15 days period in majority of the sample and by 30 days dentin bridge was observed that were both continuous and interrupted in equal number of samples. The initial inflammatory response and necrosis was more with Nano-HA and calcium hydroxide which reduced with time. MTA showed no inflammatory changes in majority of the samples in both the study periods. Necrosis was least observed in MTA group followed by Nano-HA. Vascularity increased in Nano-HA group in the initial periods which reduced with increasing time. Based on the ability of nano-HA to produce complete dentinal bridges, favorable cellular and vascular response, the material could be considered as an substitute and could be tried used as a direct pulp capping agent.

  5. Effects of isoflurane anesthesia on ensemble patterns of Ca2+ activity in mouse V1: reduced direction selectivity independent of increased correlations in cellular activity

    NARCIS (Netherlands)

    Goltstein, P.M.; Montijn, J.S.; Pennartz, C.M.A.

    2015-01-01

    Anesthesia affects brain activity at the molecular, neuronal and network level, but it is not well-understood how tuning properties of sensory neurons and network connectivity change under its influence. Using in vivo two-photon calcium imaging we matched neuron identity across episodes of

  6. In Vitro Activity of Simeprevir against Hepatitis C Virus Genotype 1 Clinical Isolates and Its Correlation with NS3 Sequence and Site-Directed Mutants

    Science.gov (United States)

    Fevery, Bart; Vijgen, Leen; Jacobs, Tom; De Meyer, Sandra; Lenz, Oliver

    2015-01-01

    Simeprevir (TMC435) is a once-daily, single-pill, oral hepatitis C virus (HCV) NS3 protease inhibitor approved for the treatment of chronic HCV infection. Phenotypic characterization of baseline isolates and isolates from HCV genotype 1-infected patients failing with a simeprevir-based regimen was performed using chimeric replicons carrying patient-derived NS3 protease sequences. Cutoff values differentiating between full susceptibility to simeprevir (≤2.0-fold reduction in simeprevir activity) and low-level versus high-level resistance (≥50-fold reduction in simeprevir activity) were determined. The median simeprevir fold change in the 50% effective concentration (FC) of pretreatment genotype 1a isolates, with and without Q80K, and genotype 1b isolates was 11, 0.9, and 0.4, respectively. Naturally occurring NS3 polymorphisms that reduced simeprevir activity, other than Q80K, were uncommon in the simeprevir studies and generally conferred low-level resistance in vitro. Although the proportion of patients with failure differed by HCV geno/subtype and/or presence of baseline Q80K, the level of simeprevir resistance observed at failure was similarly high irrespective of type of failure, HCV genotype 1 subtype, and presence or absence of baseline Q80K. At the end of the study, simeprevir activity against isolates that lost the emerging amino acid substitution returned to pretreatment values. Activity of simeprevir against clinical isolates and site-directed mutant replicons harboring the corresponding single or double amino acid substitutions correlated well, showing that simeprevir resistance can be attributed to these substitutions. In conclusion, pretreatment NS3 isolates were generally fully susceptible (FC, ≤2.0) or conferred low-level resistance to simeprevir in vitro (FC, >2.0 and <50). Treatment failure with a simeprevir-based regimen was associated with emergence of high-level-resistance variants (FC, ≥50). PMID:26392483

  7. Characterization of Direct Current-Electrical Penetration Graph Waveforms and Correlation With the Probing Behavior of Matsumuratettix hiroglyphicus (Hemiptera: Cicadellidae), the Insect Vector of Sugarcane White Leaf Phytoplasma.

    Science.gov (United States)

    Roddee, J; Kobori, Y; Yorozuya, H; Hanboonsong, Y

    2017-06-01

    The leafhopper Matsumuratettix hiroglyphicus (Matsumura) (Hemiptera: Cicadellidae) is an important vector of phytoplasma causing white leaf disease in sugarcane. Thus, the aim of our study was to understand and describe the stylet-probing activities of this vector while feeding on sugarcane plants, by using direct current (DC) electrical penetration graph (EPG) monitoring. The EPG signals were classified into six distinct waveforms, according to amplitude, frequency, voltage level, and electrical origin of the observed traces during stylet penetration into the host plant tissues (probing). These six EPG waveforms of probing behavior comprise no stylet penetration (NP); stylet pathway through epidermis, mesophyll, and parenchymal cells (waveform A); contact at the bundle sheath layer (waveform B); salivation into phloem sieve elements (waveform C); phloem sap ingestion (waveform D); and short ingestion time of xylem sap (waveform E). The above waveform patterns were correlated with histological data of salivary sheath termini in plant tissue generated from insect stylet tips. The key findings of this study were that M. hiroglyphicus ingests the phloem sap at a relatively higher rate and for longer duration from any other cell type, suggesting that M. hiroglyphicus is mainly a phloem-feeder. Quantitative comparison of probing behavior revealed that females typically probe more frequently and longer in the phloem than males. Thus, females may acquire and inoculate greater amounts of phytoplasma than males, enhancing the efficiency of phytoplasma transmission and potentially exacerbating disease spreading. Overall, our study provides basic information on the probing behavior and transmission mechanism of M. hiroglyphicus. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Lack of gene–language correlation due to reciprocal female but directional male admixture in Austronesians and non-Austronesians of East Timor

    Science.gov (United States)

    Gomes, Sibylle M; van Oven, Mannis; Souto, Luis; Morreira, Helena; Brauer, Silke; Bodner, Martin; Zimmermann, Bettina; Huber, Gabriela; Strobl, Christina; Röck, Alexander W; Côrte-Real, Francisco; Parson, Walther; Kayser, Manfred

    2017-01-01

    Nusa Tenggara, including East Timor, located at the crossroad between Island Southeast Asia, Near Oceania, and Australia, are characterized by a complex cultural structure harbouring speakers from two different major linguistic groups of different geographic origins (Austronesian (AN) and non-Austronesian (NAN)). This provides suitable possibilities to study gene–language relationship; however, previous studies from other parts of Nusa Tenggara reported conflicting evidence about gene–language correlation in this region. Aiming to investigate gene–language relationships including sex-mediated aspects in East Timor, we analysed the paternally inherited non-recombining part of the Y chromosome (NRY) and the maternally inherited mitochondrial (mt) DNA in a representative collection of AN- and NAN-speaking groups. Y-SNP (single-nucleotide polymorphism) data were newly generated for 273 samples and combined with previously established Y-STR (short tandem repeat) data of the same samples, and with previously established mtDNA data of 290 different samples with, however, very similar representation of geographic and linguistic coverage of the country. We found NRY and mtDNA haplogroups of previously described putative East/Southeast Asian (E/SEA) and Near Oceanian (NO) origins in both AN and NAN speakers of East Timor, albeit in different proportions, suggesting reciprocal genetic admixture between both linguistic groups for females, but directional admixture for males. Our data underline the dual genetic origin of East Timorese in E/SEA and NO, and highlight that substantial genetic admixture between the two major linguistic groups had occurred, more so via women than men. Our study therefore provides another example where languages and genes do not conform due to sex-biased genetic admixture across major linguistic groups. PMID:27485412

  9. Lack of gene-language correlation due to reciprocal female but directional male admixture in Austronesians and non-Austronesians of East Timor.

    Science.gov (United States)

    Gomes, Sibylle M; van Oven, Mannis; Souto, Luis; Morreira, Helena; Brauer, Silke; Bodner, Martin; Zimmermann, Bettina; Huber, Gabriela; Strobl, Christina; Röck, Alexander W; Côrte-Real, Francisco; Parson, Walther; Kayser, Manfred

    2017-02-01

    Nusa Tenggara, including East Timor, located at the crossroad between Island Southeast Asia, Near Oceania, and Australia, are characterized by a complex cultural structure harbouring speakers from two different major linguistic groups of different geographic origins (Austronesian (AN) and non-Austronesian (NAN)). This provides suitable possibilities to study gene-language relationship; however, previous studies from other parts of Nusa Tenggara reported conflicting evidence about gene-language correlation in this region. Aiming to investigate gene-language relationships including sex-mediated aspects in East Timor, we analysed the paternally inherited non-recombining part of the Y chromosome (NRY) and the maternally inherited mitochondrial (mt) DNA in a representative collection of AN- and NAN-speaking groups. Y-SNP (single-nucleotide polymorphism) data were newly generated for 273 samples and combined with previously established Y-STR (short tandem repeat) data of the same samples, and with previously established mtDNA data of 290 different samples with, however, very similar representation of geographic and linguistic coverage of the country. We found NRY and mtDNA haplogroups of previously described putative East/Southeast Asian (E/SEA) and Near Oceanian (NO) origins in both AN and NAN speakers of East Timor, albeit in different proportions, suggesting reciprocal genetic admixture between both linguistic groups for females, but directional admixture for males. Our data underline the dual genetic origin of East Timorese in E/SEA and NO, and highlight that substantial genetic admixture between the two major linguistic groups had occurred, more so via women than men. Our study therefore provides another example where languages and genes do not conform due to sex-biased genetic admixture across major linguistic groups.

  10. Subcortical surgical anatomy of the lateral frontal region: human white matter dissection and correlations with functional insights provided by intraoperative direct brain stimulation: laboratory investigation.

    Science.gov (United States)

    De Benedictis, Alessandro; Sarubbo, Silvio; Duffau, Hugues

    2012-12-01

    Recent neuroimaging and surgical results support the crucial role of white matter in mediating motor and higher-level processing within the frontal lobe, while suggesting the limited compensatory capacity after damage to subcortical structures. Consequently, an accurate knowledge of the anatomofunctional organization of the pathways running within this region is mandatory for planning safe and effective surgical approaches to different diseases. The aim of this dissection study was to improve the neurosurgeon's awareness of the subcortical anatomofunctional architecture for a lateral approach to the frontal region, to optimize both resection and postoperative outcome. Ten human hemispheres (5 left, 5 right) were dissected according to the Klingler technique. Proceeding lateromedially, the main association and projection tracts as well as the deeper basal structures were identified. The authors describe the anatomy and the relationships among the exposed structures in both a systematic and topographical surgical perspective. Structural results were also correlated to the functional responses obtained during resections of infiltrative frontal tumors guided by direct cortico-subcortical electrostimulation with patients in the awake condition. The eloquent boundaries crucial for a safe frontal lobectomy or an extensive lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and premotor fibers in the posterior and posteromedial part of the surgical field; 3) the inferior frontooccipital fascicle and the superior longitudinal fascicle posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the depth. Optimization of results following brain surgery, especially within the frontal lobe, requires a perfect knowledge of functional anatomy, not only at the cortical level but also with regard to subcortical white matter connectivity.

  11. Photon correlation spectroscopy in ophthalmology

    Science.gov (United States)

    Rovati, L.

    2011-05-01

    On the basis of the theory of light scattering, photon correlation spectroscopy has been used for more than three decades to study ocular tissues. From first in-vitro experiments to study cataractogenesis, this approach has been extended to characterize semi-quantitatively in-vivo all the ocular tissues from cornea to retina and choroids. In order to acquire high quality measurement data from the experiments, serious attention has to be paid to the detector and processing system performance. Detector noise, sensitivity, dead time and afterpulsing lead to a direct or indirect corruption of the acquired correlation function whereas counting range and resolution should be optimized to take into account the wide variability of the ocular tissue optical characteristics.

  12. Pharmacokinetics of Abamectin/Levamisole Combination in a Medium Chain Mono and Diglyceride-Based Vehicle and an In Vitro Release and In Vitro In Vivo Correlation Study for Levamisole.

    Science.gov (United States)

    Sari, Peyami; Sun, Jianguo; Razzak, Majid; Tucker, Ian G

    2017-05-01

    A combination of lipophilic and hydrophilic drugs in a single solution is a challenge due to their different physicochemical properties. In vitro and in vivo release studies are useful to optimize this solution. The in vitro (Franz diffusion cell) release rate of levamisole phosphate from an isotropic vehicle of medium chain mono and diglycerides (MCMDG) was significantly slower than the release from water. The injectable solution of the isotropic MCMDG-based system was prepared with 13.65% of levamisole phosphate and 0.5% of abamectin. Two milliliters/50 kg (0.04 ml/kg) was injected subcutaneously into five healthy adult sheep. None of the animals showed the signs of inflammation at injection site. Both drugs were assayed using validated HPLC methods. The absorption rates for levamisole (0.71 ± 0.32 h -1 ) and abamectin (0.24 ± 0.08 day -1 ) from the MCMDG-based formulation were considerably slower than those of other studies conducted on the commercial products. The t max was delayed for levamisole (2.20 ± 0.45 h) and abamectin (4.20 ± 1.64 days) compared with those in published studies. Longer MRT values for levamisole (6.14 ± 1.14 h) and abamectin (8.80 ± 1.39 days) were found in this study compared to those reported. A correlation was observed between in vivo fraction absorbed and in vitro fraction released for levamisole phosphate in the MCMDG-based formulation. The injection vehicle of isotropic MCMDG-based system delayed the subcutaneous absorption of levamisole phosphate and abamectin compared to the commercial subcutaneous injection products for levamisole and abamectin. Notably, this isotropic MCMDG-based vehicle system is prepared with a combination of two drugs with different physicochemical properties.

  13. In vivo

    Science.gov (United States)

    Berkowitz, Bruce A; Lenning, Jacob; Khetarpal, Nikita; Tran, Catherine; Wu, Johnny Y; Berri, Ali M; Dernay, Kristin; Haacke, E Mark; Shafie-Khorassani, Fatema; Podolsky, Robert H; Gant, John C; Maimaiti, Shaniya; Thibault, Olivier; Murphy, Geoffrey G; Bennett, Brian M; Roberts, Robin

    2017-09-01

    Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greater-than-normal 1/ T 1 that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proof-of-concept data in models of AD-like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. AD-like models showed an abnormal gradient along the CA1 dorsal-ventral axis of excessive free radical production as measured by Quest MRI, and redox-sensitive calcium dysregulation as measured by manganese-enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising in vivo paradigm for bridging brain subfield oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.-Berkowitz, B. A., Lenning, J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafie-Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. © FASEB.

  14. Information-limiting correlations

    Science.gov (United States)

    Moreno-Bote, Rubén; Beck, Jeffrey; Kanitscheider, Ingmar; Pitkow, Xaq; Latham, Peter; Pouget, Alexandre

    2015-01-01

    Computational strategies used by the brain strongly depend on the amount of information that can be stored in population activity, which in turn strongly depends on the pattern of noise correlations. In vivo, noise correlations tend to be positive and proportional to the similarity in tuning properties. Such correlations are thought to limit information, which has led to the suggestion that decorrelation increases information. In contrast, we found, analytically and numerically, that decorrelation does not imply an increase in information. Instead, the only information-limiting correlations are what we refer to as differential correlations: correlations proportional to the product of the derivatives of the tuning curves. Unfortunately, differential correlations are likely to be very small and buried under correlations that do not limit information, making them particularly difficult to detect. We found, however, that the effect of differential correlations on information can be detected with relatively simple decoders. PMID:25195105

  15. Targeting P-Selectin by Gallium-68–Labeled Fucoidan Positron Emission Tomography for Noninvasive Characterization of Vulnerable Plaques: Correlation With In Vivo 17.6T MRI

    National Research Council Canada - National Science Library

    Li, Xiang; Bauer, Wolfgang; Israel, Ina; Kreissl, Michael C; Weirather, Johannes; Richter, Dominik; Bauer, Elisabeth; Herold, Volker; Jakob, Peter; Buck, Andreas; Frantz, Stefan; Samnick, Samuel

    2014-01-01

    .... We proposed a new approach for noninvasive in vivo characterization of P-selectin on active plaques based on Ga-Fucoidan, which is a polysaccharidic ligand of P-selectin with a nanomolar affinity...

  16. Direct and indirect markers of cartilage metabolism in synovial fluid obtained from dogs with hip dysplasia and correlation with clinical and radiographic variables.

    Science.gov (United States)

    Fujita, Yukihiro; Hara, Yasushi; Nezu, Yoshinori; Yamaguchi, Shinya; Schulz, Kurt S; Tagawa, Masahiro

    2005-12-01

    To compare activities of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and matrix metalloproteinase (MMP)-3 and contents of sulfated glycosaminoglycan (S-GAG) in joint fluid obtained from dogs with hip dysplasia (HD) and clinically normal dogs, evaluate correlations among these markers in joint fluid obtained from dogs with HD, and evaluate correlations between each marker and clinical and radiographic variables. Animals-26 dogs with HD (clinical group) and 43 clinically normal Beagles (control group). Joint fluid was aseptically collected from the hip joints of all dogs. For each dog in the clinical group, age, duration of lameness, radiographic osteoarthritis (OA) score, and Norberg angle in each affected joint were recorded. Activities of IL-1beta, IL-6, TNF-alpha, and MMP-3 and S-GAG contents were measured. Values were compared between groups by use of Mann-Whitney U tests, and the Spearman rank correlation test was used to evaluate correlations among markers and between each marker and clinical or radiographic variables. Values of all markers were significantly higher for the clinical group, compared with values for the control group. There was a moderate positive correlation between lameness duration and IL-6 activity and a strong negative correlation between the Norberg angle and IL-1beta activity. Analysis of our results indicated that there was a significant increase in markers of OA in dogs with HD. Activities of IL-1beta and IL-6 in joint fluid of dogs with HD may be influenced by the severity of laxity in the hip joint and lameness duration, respectively.

  17. Correlation between the horizontal wind direction and orientation of cross-field anisotropy of small-scale irregularities in the F region of midlatitude ionosphere

    Science.gov (United States)

    Romanova, N. Yu.

    2017-07-01

    Radio sounding of midlatitude ionosphere shows that natural small-scale electron density irregularities in the F region are cross-field anisotropic. The orientation of the cross-field anisotropy is different under different geophysical conditions. The cross-field anisotropy orientation is matched with the horizontal wind direction calculated within the HWM07 model for each event. It is ascertained that natural irregularities in a plane perpendicular to the magnetic field are stretched along the horizontal wind direction under different geophysical conditions.

  18. IN VIVO

    Science.gov (United States)

    Jamila, Nargis; Khan, Naeem; Khan, Amir Atlas; Khan, Imran; Khan, Sadiq Noor; Zakaria, Zainal Amiruddin; Khairuddean, Melati; Osman, Hasnah; Kim, Kyong Su

    2017-01-01

    Garcinia hombroniana , known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract. In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl 4 )/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl 4 . Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1 H, 13 C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract. In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (pIR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents. From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.

  19. Site-directed mutagenesis, in vivo electroporation and mass spectrometry in search for determinants of the subcellular targeting of Rab7b paralogue in the model eukaryote Paramecium octaurelia.

    Science.gov (United States)

    Wyroba, E; Kwaśniak, P; Miller, K; Kobyłecki, K; Osińska, M

    2016-04-11

    Protein products of the paralogous genes resulting from the whole genome duplication may acquire new function. The role of post-translational modifications (PTM) in proper targeting of Paramecium Rab7b paralogue - distinct from that of Rab7a directly involved in phagocytosis - was studied using point mutagenesis, proteomic analysis and double immunofluorescence after in vivo electroporation of the mutagenized protein. Here we show that substitution of Thr200 by Ala200 resulted in diminished incorporation of [P32] by 37.4% and of 32 [C14-]UDP-glucose by 24%, respectively, into recombinant Rab7b_200 in comparison to the non-mutagenized control. Double confocal imaging revealed that Rab7b_200 was mistargeted upon electroporation into living cells contrary to non- mutagenized recombinant Rab7b correctly incorporated in the cytostome area. We identified the peptide ion at m/z=677.63+ characteristic for the glycan group attached to Thr200 in Rab7b using nano LC-MS/MS and comparing the peptide map of this protein with that after deglycosylation with the mixture of five enzymes of different specificity. Based on the mass of this peptide ion and quantitative radioactive assays with [P32]and  [C14-]UDP- glucose, the suggested composition of the adduct attached to Thr200 might be (Hex)1(HexNAc)1(Phos)3 or (HexNAc)1 (Deoxyhexose)1 (Phos)1 (HexA)1. These data indicate that PTM of Thr200 located in the hypervariable C-region of Rab7b in Paramecium is crucial for the proper localization/function of this protein. Moreover, these proteins differ also in other PTM: the number of phosphorylated amino acids in Rab7b is much higher than in Rab7a.

  20. Site‐directed mutagenesis, in vivo electroporation and mass spectrometry in search for determinants of the subcellular targeting of Rab7b paralogue in the model eukaryote Paramecium octaurelia

    Directory of Open Access Journals (Sweden)

    E. Wyroba

    2016-04-01

    Full Text Available Protein products of the paralogous genes resulting from the whole genome duplication may acquire new function. The role of post‐translational modifications (PTM in proper targeting of Paramecium Rab7b paralogue – distinct from that of Rab7a directly involved in phagocytosis ‐ was studied using point mutagenesis, proteomic analysis and double immunofluorescence after in vivo electroporation of the mutagenized protein. Here we show that substitution of Thr200 by Ala200 resulted in diminished incorporation of [P32] by 37.4% and of 32 [C14–]UDP‐glucose by 24%, respectively, into recombinant Rab7b_200 in comparison to the non‐mutagenized control. Double confocal imaging revealed that Rab7b_200 was mistargeted upon electroporation into living cells contrary to non‐ mutagenized recombinant Rab7b correctly incorporated in the cytostome area. We identified the peptide ion at m/z=677.63+ characteristic for the glycan group attached to Thr200 in Rab7b using nano LC‐MS/MS and comparing the peptide map of this protein with that after deglycosylation with the mixture of five enzymes of different specificity. Based on the mass of this peptide ion and quantitative radioactive assays with [P32]and  [C14‐]UDP‐ glucose, the suggested composition of the adduct attached to Thr200 might be (Hex1(HexNAc1(Phos3 or (HexNAc1 (Deoxyhexose1 (Phos1 (HexA1. These data indicate that PTM of Thr200 located in the hypervariable C‐region of Rab7b in Paramecium is crucial for the proper localization/function of this protein. Moreover, these proteins differ also in other PTM: the number of phosphorylated amino acids in Rab7b is much higher than in Rab7a.   

  1. Direct Comparison of the Performance of Commonly Employed In Vivo F-actin Markers (Lifeact-YFP, YFP-mTn and YFP-FABD2) in Tobacco Pollen Tubes.

    Science.gov (United States)

    Montes-Rodriguez, Adriana; Kost, Benedikt

    2017-01-01

    In vivo markers for F-actin organization and dynamics are extensively used to investigate cellular functions of the actin cytoskeleton, which are essential for plant development and pathogen defense. The most widely employed markers are GFP variants fused to F-actin binding domains of mouse talin (GFP-mTn), Arabidopsis fimbrin1 (GFP-FABD2) or yeast Abp140 (Lifeact-GFP). Although numerous reports describing applications of one, or occasionally more, of these markers, are available in the literature, a direct quantitative comparison of the performance of all three markers at different expression levels has been missing. Here, we analyze F-actin organization and growth rate displayed by tobacco pollen tubes expressing YFP-mTn, YFP-FABD2 or Lifeact-YFP at different levels. Results obtained establish that: (1) all markers strongly affect F-actin organization and cell expansion at high expression levels, (2) YFP-mTn and Lifeact-YFP non-invasively label the same F-actin structures (longitudinally oriented filaments in the shank, a subapical fringe) at low expression levels, (3) Lifeact-YFP displays a somewhat lower potential to affect F-actin organization and cell expansion than YFP-mTn, and (4) YFP-FABD2 generally fails to label F-actin structures at the pollen tube tip and affects F-actin organization as well as cell expansion already at lowest expression levels. As pointed out in the discussion, these observations (1) are also meaningful for F-actin labeling in other cell types, which generally respond less sensitively to F-actin perturbation than pollen tubes, (2) help selecting suitable markers for future F-actin labeling experiments, and (3) support the assessment of a substantial amount of published data resulting from such experiments.

  2. Novel instrumentation to determine peel force in vivo and preliminary studies with adhesive skin barriers.

    Science.gov (United States)

    Krueger, Evan M; Cullum, Malford E; Nichols, Thom R; Taylor, Michael G; Sexton, William L; Murahata, Richard I

    2013-11-01

    Adhesive barriers secure medical devices to skin. Laboratory adhesion models are not predictive of in vivo performance. The objectives of these studies were to validate a novel peel force device, and to investigate relationships between barrier formulations, barrier width, subjective discomfort during barrier removal, and substrates. Three hydrocolloid barrier formulations in three widths were adhered to ethylene/methyl acrylate film (EMA), VITRO-SKIN(®) and human abdominal skin. Peel force was measured using a MTS Insight™ and a cyberDERM Inc. Mini Peel Tester (CMPT). Subjects reported their discomfort. Peel forces were highly correlated between devices and highly dependent on substrate. Data suggested a weak direct association between peel force in vivo and discomfort. The 0.5″-wide barriers had the most precise peel forces measurements in vivo. A weak negative relationship between normalized peel force and barrier width on human skin was found. There was a strong positive relationship between peel force in vivo and on EMA, whereas no correlation was observed with VITRO-SKIN(®). The CMPT correlates with a standard instrument and can advantageously investigate adhesion in vivo. Barrier width and substrate impact the reliability and predictability of peel force measurements. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Correlation spectrometer

    Science.gov (United States)

    Sinclair, Michael B [Albuquerque, NM; Pfeifer, Kent B [Los Lunas, NM; Flemming, Jeb H [Albuquerque, NM; Jones, Gary D [Tijeras, NM; Tigges, Chris P [Albuquerque, NM

    2010-04-13

    A correlation spectrometer can detect a large number of gaseous compounds, or chemical species, with a species-specific mask wheel. In this mode, the spectrometer is optimized for the direct measurement of individual target compounds. Additionally, the spectrometer can measure the transmission spectrum from a given sample of gas. In this mode, infrared light is passed through a gas sample and the infrared transmission signature of the gasses present is recorded and measured using Hadamard encoding techniques. The spectrometer can detect the transmission or emission spectra in any system where multiple species are present in a generally known volume.

  4. Differences in Virulence of Marine and Freshwater Isolates of Viral Hemorrhagic Septicemia Virus In Vivo Correlate with In Vitro Ability To Infect Gill Epithelial Cells and Macrophages of Rainbow Trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Brudeseth, Bjørn E.; Skall, Helle Frank; Evensen, Øystein

    2008-01-01

    ). The strains included one low-virulence marine VHSV (ma-VHSV) strain, ma-1p8, and a highly pathogenic freshwater VHSV (fw-VHSV) strain, fw-DK-3592B. Infectivities toward trout head kidney macrophages were also studied (by a time course method), and differences in in vivo virulence were reconfirmed, the aim...

  5. In vivo and ex vivo inflammatory markers of common metabolic phenotypes in humans

    DEFF Research Database (Denmark)

    Mærkedahl, Rasmus Baadsgaard; Frøkiær, Hanne; Stenbæk, Marie Grøntved

    2018-01-01

    BACKGROUND: Low-grade systemic inflammation (LGSI) is often characterized by elevated levels of interleukin (IL)6, tumor necrosis factor (TNF)α, and C-reactive protein (CRP). Other serum proteins, ex vivo-stimulated cytokine production, and leukocyte count have, however, also been suggested LGSI-markers...... also correlated with leukocyte count. Ex vivo-produced cytokines were intercorrelated and correlated with leukocyte count, but did not correlate with the serum immune markers. MS score, body mass index, and glycated hemoglobin (HbA1c) were associated with 8%-16% higher inflammatory score per standard...... fasting serum markers of LGSI and leukocyte counts associated best with measures of MS-associated LGSI, whereas ex vivo cytokine production was only associated with prevailing glycemia and dyslipidemia. Taken together, this indicates that the relationship between in vivo and ex vivo inflammatory markers...

  6. The effect of radiofrequency ablation on different organs: Ex vivo and in vivo comparative studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Na [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Rhim, Hyunchul, E-mail: rhimhc@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Choi, Dongil; Kim, Young-sun; Lee, Min Woo; Chang, Ilsoo; Lee, Won Jae; Lim, Hyo K. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2011-11-15

    Objective: The purposes of this study are to evaluate the ex vivo and in vivo efficacy of radiofrequency ablation (RFA) on different porcine tissues by the ablation of three different sites simultaneously. Materials and methods: A multichannel RFA system, enables three separate tumors to be ablated simultaneously, was used. RFA procedures were applied to normal porcine liver, kidney, and muscle together ex vivo (n = 12) and in vivo (n = 17). Pre-impedances, defined as baseline systemic impedances of tissues before beginning RFA, and the areas of ablation zones were measured and compared. Results: The areas of ablation zones among three organs had a significant difference in decreasing order as follows: liver, muscle, and kidney in the ex vivo study (p = 0.001); muscle, liver, and kidney in the in vivo study (p < 0.0001). The areas of ablation zones between ex vivo and in vivo had a significant difference in the liver and muscle (each p < 0.05). There was no significant correlation between the areas of ablation zones and pre-impedances in both studies. Conclusions: Renal RFA produced the smallest ablation zone in both in vivo and ex vivo studies. Muscular RFA demonstrated the largest ablation zone in the in vivo study, and hepatic RFA showed the largest ablation zone in the ex vivo study. This variability in the tissues should be considered for performing an optimized RFA for each organ site.

  7. In vivo

    Science.gov (United States)

    Kim, Michele M; Penjweini, Rozhin; Zhu, Timothy C

    2015-03-02

    Macroscopic modeling of the apparent reacted singlet oxygen concentration ([ 1 O 2 ] rx ) for use with photodynamic therapy (PDT) has been developed and studied for benzoporphryin derivative monoacid ring A (BPD), a common photosensitizer. The four photophysical parameters (ξ, σ, β, δ) and threshold singlet oxygen dose ([ 1 O 2 ] rx,sh ) have been investigated and determined using the RIF model of murine fibrosarcomas and interstitial treatment delivery. These parameters are examined and verified further by monitoring tumor growth post-PDT. BPD was administered at 1 mg/kg, and mice were treated 3 hours later with fluence rates ranging between 75 - 150 mW/cm 2 and total fluences of 100 - 350 J/cm 2 . Treatment was delivered superficially using a collimated beam. Changes in tumor volume were tracked following treatment. The tumor growth rate was fitted for each treatment condition group and compared using dose metrics including total light dose, PDT dose, and reacted singlet oxygen. Initial data showing the correlation between outcomes and various dose metrics indicate that reacted singlet oxygen serves as a good dosimetric quantity for predicting PDT outcome.

  8. In-vivo

    Science.gov (United States)

    Zhu, Timothy C; Kim, Michele M; Liang, Xing; Finlay, Jarod C; Busch, Theresa M

    2015-02-01

    Dosimetry of singlet oxygen ( 1 O 2 ) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [ 1 O 2 ] rx,sh , for PDT was developed. An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [ 1 O 2 ] rx,sh . Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin ® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. The mean values (standard deviation) of the in-vivo [ 1 O 2 ] rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×10 7 and 4.6×10 7 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin ® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g , β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. In comparison, the [ 1 O 2 ] rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×10 8 per cell per 1/ e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/ e to in-vivo singlet

  9. Diagnosis of lesions of the acetabular labrum, of the labral-chondral transition zone, and of the cartilage in femoroacetabular impingement: Correlation between direct magnetic resonance arthrography and hip arthroscopy.

    Science.gov (United States)

    Crespo Rodríguez, A M; de Lucas Villarrubia, J C; Pastrana Ledesma, M A; Millán Santos, I; Padrón, M

    2015-01-01

    To determine the sensitivity and accuracy of direct MR arthrography in the diagnosis of intra-articular lesions associated with femoroacetabular impingement. We used direct MR arthrography to study 51 patients with femoroacetabular impingement who underwent arthroscopic hip surgery. Surgery demonstrated 37 labral tears, 44 lesions in the labral-chondral transitional zone, and 40 lesions of the articular cartilage. We correlated the findings at preoperative direct MR arthrography with those of hip arthroscopy and calculated the sensitivity, specificity, positive predictive value, negative predictive value, and validity index for direct MR arthrography. The sensitivity and specificity of MR arthrography were 94.5% and 100%, respectively, for diagnosing labral tears, 100% and 87.5%, respectively, for diagnosing lesions of the labral-chondral transition zone, and 92.5% and 54.5%, respectively, for diagnosing lesions of the articular cartilage. The negative predictive value of MR arthrography for lesions of the labral-chondral transitional zone was 100%. MR arthrography accurately defined extensive lesions of the cartilage and the secondary osseous changes (the main factor in poor prognosis), although its diagnostic performance was not so good in small chondral lesions. In patients with femoroacetabular impingement, direct MR arthrography can adequately detect and characterize lesions of the acetabular labrum and of the labral-chondral transitional zone as well as extensive lesions of the articular cartilage and secondary osseous changes. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  10. Nonperturbative-transverse-momentum effects and evolution in dihadron and direct photon-hadron angular correlations in $p$$+$$p$ collisions at $\\sqrt{s}$=510 GeV

    CERN Document Server

    Adare, A; Ajitanand, N N; Akiba, Y; Akimoto, R; Alexander, J; Alfred, M; Andrieux, V; Aoki, K; Apadula, N; Aramaki, Y; Asano, H; Atomssa, E T; Awes, T C; Azmoun, B; Babintsev, V; Bai, M; Bai, X; Bandara, N S; Bannier, B; Barish, K N; Bathe, S; Baublis, V; Baumann, C; Baumgart, S; Bazilevsky, A; Beaumier, M; Beckman, S; Belmont, R; Berdnikov, A; Berdnikov, Y; Black, D; Blau, D S; Bok, J S; Boyle, K; Brooks, M L; Bryslawskyj, J; Buesching, H; Bumazhnov, V; Butsyk, S; Campbell, S; Cervantes, R; Chen, C -H; Chi, C Y; Chiu, M; Choi, I J; Choi, J B; Choi, S; Christiansen, P; Chujo, T; Cianciolo, V; Citron, Z; Cole, B A; Cronin, N; Crossette, N; Csanád, M; Csörgő, T; Danley, T W; Datta, A; Daugherity, M S; David, G; DeBlasio, K; Dehmelt, K; Denisov, A; Deshpande, A; Desmond, E J; Ding, L; Dion, A; Dixit, D; Do, J H; D'Orazio, L; Drapier, O; Drees, A; Drees, K A; Durham, J M; Durum, A; Engelmore, T; Enokizono, A; En'yo, H; Esumi, S; Eyser, K O; Fadem, B; Fan, W; Feege, N; Fields, D E; Finger, M; Finger, M; Jr., \\,; Fleuret, F; Fokin, S L; Frantz, J E; Franz, A; Frawley, A D; Fukao, Y; Fukuda, Y; Fusayasu, T; Gainey, K; Gal, C; Gallus, P; Garg, P; Garishvili, A; Garishvili, I; Ge, H; Giordano, F; Glenn, A; Gong, X; Gonin, M; Goto, Y; de Cassagnac, R Granier; Grau, N; Greene, S V; Perdekamp, M Grosse; Gu, Y; Gunji, T; Guragain, H; Hachiya, T; Haggerty, J S; Hahn, K I; Hamagaki, H; Hamilton, H F; Han, S Y; Hanks, J; Hasegawa, S; Haseler, T O S; Hashimoto, K; Hayano, R; He, X; Hemmick, T K; Hester, T; Hill, J C; Hill, K; Hollis, R S; Homma, K; Hong, B; Hoshino, T; Hotvedt, N; Huang, J; Huang, S; Ichihara, T; Ikeda, Y; Imai, K; Imazu, Y; Inaba, M; Iordanova, A; Isenhower, D; Isinhue, A; Ivanishchev, D; Jacak, B V; Jeon, S J; Jezghani, M; Jia, J; Jiang, X; Johnson, B M; Joo, E; Joo, K S; Jouan, D; Jumper, D S; Kamin, J; Kanda, S; Kang, B H; Kang, J H; Kang, J S; Kapukchyan, D; Kapustinsky, J; Karthas, E; Kawall, D; Kazantsev, A V; Key, J A; Khachatryan, V; Khandai, P K; Khanzadeev, A; Kihara, K; Kijima, K M; Kim, C; Kim, D H; Kim, D J; Kim, E -J; Kim, H -J; Kim, M; Kim, Y -J; Kim, Y K; Kincses, D; Kistenev, E; Klatsky, J; Kleinjan, D; Kline, P; Koblesky, T; Kofarago, M; Komkov, B; Koster, J; Kotchetkov, D; Kotov, D; Krizek, F; Kudo, S; Kurita, K; Kurosawa, M; Kwon, Y; Lacey, R; Lai, Y S; Lajoie, J G; Lebedev, A; Lee, D M; Lee, G H; Lee, J; Lee, K B; Lee, K S; Lee, S; Lee, S H; Leitch, M J; Leitgab, M; Leung, Y H; Lewis, B; Li, X; Lim, S H; Liu, M X; Loggins, V-R; Lovasz, K; Lynch, D; Maguire, C F; Majoros, T; Makdisi, Y I; Makek, M; Manion, A; Manko, V I; Mannel, E; McCumber, M; McGaughey, P L; McGlinchey, D; McKinney, C; Meles, A; Mendoza, M; Meredith, B; Miake, Y; Mibe, T; Mignerey, A C; Miller, A J; Milov, A; Mishra, D K; Mitchell, J T; Mitsuka, G; Miyasaka, S; Mizuno, S; Mohanty, A K; Mohapatra, S; Montuenga, P; Moon, T; Morrison, D P; Moskowitz, M; Moukhanova, T V; Murakami, T; Murata, J; Mwai, A; Nagae, T; Nagai, K; Nagamiya, S; Nagashima, K; Nagashima, T; Nagle, J L; Nagy, M I; Nakagawa, I; Nakagomi, H; Nakamiya, Y; Nakamura, K R; Nakamura, T; Nakano, K; Nattrass, C; Netrakanti, P K; Nihashi, M; Niida, T; Nouicer, R; Novák, T; Novitzky, N; Nyanin, A S; O'Brien, E; Ogilvie, C A; Oide, H; Okada, K; Koop, J D Orjuela; Osborn, J D; Oskarsson, A; Ottino, G J; Ozawa, K; Pak, R; Pantuev, V; Papavassiliou, V; Park, I H; Park, J S; Park, S; Park, S K; Pate, S F; Patel, L; Patel, M; Peng, J -C; Perepelitsa, D V; Perera, G D N; Peressounko, D Yu; PerezLara, C E; Perry, J; Petti, R; Phipps, M; Pinkenburg, C; Pinson, R; Pisani, R P; Purschke, M L; Qu, H; Rak, J; Ravinovich, I; Read, K F; Reynolds, D; Riabov, V; Riabov, Y; Richardson, E; Rinn, T; Riveli, N; Roach, D; Rolnick, S D; Rosati, M; Rowan, Z; Rubin, J G; Ryu, M S; Safonov, A S; Sahlmueller, B; Saito, N; Sakaguchi, T; Sako, H; Samsonov, V; Sarsour, M; Sato, S; Sawada, S; Schaefer, B; Schmoll, B K; Sedgwick, K; Seele, J; Seidl, R; Sekiguchi, Y; Sen, A; Seto, R; Sett, P; Sexton, A; Sharma, D; Shaver, A; Shein, I; Shibata, T -A; Shigaki, K; Shimomura, M; Shioya, T; Shoji, K; Shukla, P; Sickles, A; Silva, C L; Silvermyr, D; Singh, B K; Singh, C P; Singh, V; Skolnik, M; Slunečka, M; Snowball, M; Solano, S; Soltz, R A; Sondheim, W E; Sorensen, S P; Sourikova, I V; Stankus, P W; Steinberg, P; Stenlund, E; Stepanov, M; Ster, A; Stoll, S P; Stone, M R; Sugitate, T; Sukhanov, A; Sumita, T; Sun, J; Sziklai, J; Takahara, A; Taketani, A; Tanaka, Y; Tanida, K; Tannenbaum, M J; Tarafdar, S; Taranenko, A; Tarnai, G; Tennant, E; Tieulent, R; Timilsina, A; Todoroki, T; Tomášek, M; Torii, H; Towell, C L; Towell, M; Towell, R; Towell, R S; Tserruya, I; Ueda, Y; Ujvari, B; van Hecke, H W; Vargyas, M; Vazquez-Zambrano, E; Veicht, A; Velkovska, J; Vértesi, R; Virius, M; Vrba, V; Vukman, N; Vznuzdaev, E; Wang, X R; Watanabe, D; Watanabe, K; Watanabe, Y; Watanabe, Y S; Wei, F; Whitaker, S; Wolin, S; Wong, C P; Woody, C L; Wysocki, M; Xia, B; Xu, C; Xu, Q; Xue, L; Yalcin, S; Yamaguchi, Y L; Yamamoto, H; Yanovich, A; Yokkaichi, S; Yoo, J H; Yoon, I; You, Z; Younus, I; Yu, H; Yushmanov, I E; Zajc, W A; Zelenski, A; Zhou, S; Zou, L

    2016-01-01

    Dihadron and isolated direct photon-hadron angular correlations are measured in $p$$+$$p$ collisions at $\\sqrt{s}=510$ GeV. Correlations of charged hadrons of $0.7direct photons of $7direct photon or $\\pi^0$. Nonperturbative evolution effects are extracted from Gaussian fits to the away-side inclusive-charged-hadron yields for different trigger-particle transverse momenta ($p_T^{\\rm trig}$). The Gaussian widths and root mean square of $p_{\\rm out}$ are reported as a function of the interaction hard scale $p_T^{\\rm trig}$ to investigate possible transverse-momentu...

  11. Is preoperative functional magnetic resonance imaging reliable for language areas mapping in brain tumor surgery? Review of language functional magnetic resonance imaging and direct cortical stimulation correlation studies.

    Science.gov (United States)

    Giussani, Carlo; Roux, Frank-Emmanuel; Ojemann, Jeffrey; Sganzerla, Erik Pietro; Pirillo, David; Papagno, Costanza

    2010-01-01

    Language functional magnetic resonance imaging (fMRI) has been used extensively in the past decade for both clinical and research purposes. Its integration in the preoperative imaging assessment of brain lesions involving eloquent areas is progressively more diffused in neurosurgical practice. Nevertheless, the reliability of language fMRI is unclear. To understand the reliability of preoperative language fMRI in patients operated on for brain tumors, the surgical studies that compared language fMRI with direct cortical stimulation (DCS) were reviewed. Articles comparing language fMRI with DCS of language areas were reviewed with attention to the lesion pathology, the magnetic field, the language tasks used pre- and intraoperatively, and the validation modalities adopted to establish the reliability of language fMRI. We tried to explore the effectiveness of language fMRI in gliomas. Nine language brain mapping studies compared the findings of fMRI with those of DCS. The studies are not homogeneous for tumor types, magnetic fields, pre- and intraoperative language tasks, intraoperative matching criteria, and results. Sensitivity and specificity were calculated in 5 studies (respectively ranging from 59% to 100% and from 0% to 97%). The contradictory results of these studies do not allow consideration of language fMRI as an alternative tool to DCS in brain lesions located in language areas, especially in gliomas because of the pattern of growth of these tumors. However, language fMRI conducted with high magnet fields is a promising brain mapping tool that must be validated by DCS in methodological robust studies.

  12. Ex vivo

    Science.gov (United States)

    Liang, Tao; Dolai, Subhankar; Xie, Li; Winter, Erin; Orabi, Abrahim I; Karimian, Negar; Cosen-Binker, Laura I; Huang, Ya-Chi; Thorn, Peter; Cattral, Mark S; Gaisano, Herbert Y

    2017-04-07

    A genuine understanding of human exocrine pancreas biology and pathobiology has been hampered by a lack of suitable preparations and reliance on rodent models employing dispersed acini preparations. We have developed an organotypic slice preparation of the normal portions of human pancreas obtained from cancer resections. The preparation was assessed for physiologic and pathologic responses to the cholinergic agonist carbachol (Cch) and cholecystokinin (CCK-8), including 1) amylase secretion, 2) exocytosis, 3) intracellular Ca 2+ responses, 4) cytoplasmic autophagic vacuole formation, and 5) protease activation. Cch and CCK-8 both dose-dependently stimulated secretory responses from human pancreas slices similar to those previously observed in dispersed rodent acini. Confocal microscopy imaging showed that these responses were accounted for by efficient apical exocytosis at physiologic doses of both agonists and by apical blockade and redirection of exocytosis to the basolateral plasma membrane at supramaximal doses. The secretory responses and exocytotic events evoked by CCK-8 were mediated by CCK-A and not CCK-B receptors. Physiologic agonist doses evoked oscillatory Ca 2+ increases across the acini. Supraphysiologic doses induced formation of cytoplasmic autophagic vacuoles and activation of proteases (trypsin, chymotrypsin). Maximal atropine pretreatment that completely blocked all the Cch-evoked responses did not affect any of the CCK-8-evoked responses, indicating that rather than acting on the nerves within the pancreas slice, CCK cellular actions directly affected human acinar cells. Human pancreas slices represent excellent preparations to examine pancreatic cell biology and pathobiology and could help screen for potential treatments for human pancreatitis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Registration methodology for histological sections and in vivo imaging of human prostate.

    Science.gov (United States)

    Park, Hyunjin; Piert, Morand R; Khan, Asra; Shah, Rajal; Hussain, Hero; Siddiqui, Javed; Chenevert, Thomas L; Meyer, Charles R

    2008-08-01

    Registration enables quantitative spatial correlation of features from different imaging modalities. Our objective is to register in vivo imaging with histologic sections of the human prostate so that histologic truth can be correlated with in vivo imaging features. In vivo imaging of the prostate included T2-weighted anatomic and diffusion weighted 3-T magnetic resonance imaging (MRI) as well as 11C-choline positron emission tomography (PET). In addition, ex vivo 3-T MRI of the prostate specimen, histology, and associated block face photos of the prostate specimen were obtained. A standard registration method based on mutual information (MI) and thin-plate spline (TPS) was applied. Registration among in vivo imaging modalities is well established; however, accurate registration involving histology is difficult. Our approach breaks up the difficult direct registration of histology and in vivo imaging into achievable subregistration tasks involving intermediate ex vivo modalities like block face photography and specimen MRI. Results of subregistration tasks are combined to compute the intended, final registration between in vivo imaging and histology. The methodology was applied to two patients and found to be clinically feasible. Overall registered anatomic MRI, diffusion MRI, and 11C-choline PET aligned well with histology qualitatively for both patients. There is no ground truth of registration accuracy as the scans are real patient scans. An indirect validation of the registration accuracy has been proposed comparing tumor boundary markings found in diffusion MRI and histologic sections. Registration errors for two patients between diffusion MRI and histology were 3.74 and 2.26 mm. This proof of concept paper demonstrates a method based on intrinsic image information content for successfully registering in vivo imaging of the human prostate with its post-resection histology, which does not require the use of extrinsic fiducial markers. The methodology

  14. Correlation of 3D Shift and 3D Tilt of the Patella in Patients With Recurrent Dislocation of the Patella and Healthy Volunteers: An In Vivo Analysis Based on 3-Dimensional Computer Models.

    Science.gov (United States)

    Yamada, Yuzo; Toritsuka, Yukiyoshi; Nakamura, Norimasa; Horibe, Shuji; Sugamoto, Kazuomi; Yoshikawa, Hideki; Shino, Konsei

    2017-11-01

    The concepts of lateral deviation and lateral inclination of the patella, characterized as shift and tilt, have been applied in combination to evaluate patellar malalignment in patients with patellar dislocation. It is not reasonable, however, to describe the 3-dimensional (3D) positional relation between the patella and the femur according to measurements made on 2-dimensional (2D) images. The current study sought to clarify the relation between lateral deviation and inclination of the patella in patients with recurrent dislocation of the patella (RDP) by redefining them via 3D computer models as 3D shift and 3D tilt. Descriptive laboratory study. Altogether, 60 knees from 56 patients with RDP and 15 knees from 10 healthy volunteers were evaluated. 3D shift and tilt of the patella were analyzed with 3D computer models created by magnetic resonance imaging scans obtained at 10° intervals of knee flexion (0°-50°). 3D shift was defined as the spatial distance between the patellar reference point and the midsagittal plane of the femur; it is expressed as a percentage of the interepicondylar width. 3D tilt was defined as the spatial angle between the patellar reference plane and the transepicondylar axis. Correlations between the 2 parameters were assessed with the Pearson correlation coefficient. The patients' mean Pearson correlation coefficient was 0.895 ± 0.186 (range, -0.073 to 0.997; median, 0.965). In all, 56 knees (93%) had coefficients >0.7 (strong correlation); 1 knee (2%), >0.4 (moderate correlation); 2 knees (3%), >0.2 (weak correlation); and 1 knee (2%), correlation). The mean correlation coefficient of the healthy volunteers was 0.645 ± 0.448 (range, -0.445 to 0.982; median, 0.834). A statistically significant difference was found in the distribution of the correlation coefficients between the patients and the healthy volunteers ( P = .0034). When distribution of the correlation coefficients obtained by the 3D analyses was compared with that by the 2

  15. Optical correlation

    NARCIS (Netherlands)

    Boden, J.A.

    1974-01-01

    A survey is given of the most common types of coherent optical correlators, which are classified as spatial plane correlators, frequency plane correlators and special reference correlators. Only the spatial plane correlators are dealt with rather thoroughly. Basic principles, some special features,

  16. Monitoring and quantitative assessment of tumor burden using in vivo bioluminescence imaging

    Science.gov (United States)

    Chen, Chia-Chi; Hwang, Jeng-Jong; Ting, Gann; Tseng, Yun-Long; Wang, Shyh-Jen; Whang-Peng, Jaqueline

    2007-02-01

    In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating tumor growth. In this study, the kinetic of tumor growth has been assessed in C26 colon carcinoma bearing BALB/c mouse model. The ability of BLI to noninvasively quantitate the growth of subcutaneous tumors transplanted with C26 cells genetically engineered to stably express firefly luciferase and herpes simplex virus type-1 thymidine kinase (C26/ tk-luc). A good correlation ( R2=0.998) of photon emission to the cell number was found in vitro. Tumor burden and tumor volume were monitored in vivo over time by quantitation of photon emission using Xenogen IVIS 50 and standard external caliper measurement, respectively. At various time intervals, tumor-bearing mice were imaged to determine the correlation of in vivo BLI to tumor volume. However, a correlation of BLI to tumor volume was observed when tumor volume was smaller than 1000 mm 3 ( R2=0.907). γ Scintigraphy combined with [ 131I]FIAU was another imaging modality used for verifying the previous results. In conclusion, this study showed that bioluminescence imaging is a powerful and quantitative tool for the direct assay to monitor tumor growth in vivo. The dual reporter genes transfected tumor-bearing animal model can be applied in the evaluation of the efficacy of new developed anti-cancer drugs.

  17. Correlative microscopy.

    Science.gov (United States)

    Loussert Fonta, Céline; Humbel, Bruno M

    2015-09-01

    In recent years correlative microscopy, combining the power and advantages of different imaging system, e.g., light, electrons, X-ray, NMR, etc., has become an important tool for biomedical research. Among all the possible combinations of techniques, light and electron microscopy, have made an especially big step forward and are being implemented in more and more research labs. Electron microscopy profits from the high spatial resolution, the direct recognition of the cellular ultrastructure and identification of the organelles. It, however, has two severe limitations: the restricted field of view and the fact that no live imaging can be done. On the other hand light microscopy has the advantage of live imaging, following a fluorescently tagged molecule in real time and at lower magnifications the large field of view facilitates the identification and location of sparse individual cells in a large context, e.g., tissue. The combination of these two imaging techniques appears to be a valuable approach to dissect biological events at a submicrometer level. Light microscopy can be used to follow a labelled protein of interest, or a visible organelle such as mitochondria, in time, then the sample is fixed and the exactly same region is investigated by electron microscopy. The time resolution is dependent on the speed of penetration and fixation when chemical fixatives are used and on the reaction time of the operator for cryo-fixation. Light microscopy can also be used to identify cells of interest, e.g., a special cell type in tissue or cells that have been modified by either transfections or RNAi, in a large population of non-modified cells. A further application is to find fluorescence labels in cells on a large section to reduce searching time in the electron microscope. Multiple fluorescence labelling of a series of sections can be correlated with the ultrastructure of the individual sections to get 3D information of the distribution of the marked proteins: array

  18. Human Lens Transmission of Blue Light: A Comparison of Autofluorescence-Based and Direct Spectral Transmission Determination

    DEFF Research Database (Denmark)

    Broendsted, Adam Elias; Stormly Hansen, Michael; Lund-Andersen, Henrik

    2011-01-01

    Purpose: Direct measurement of the transmission of light through the human lens is not possible in vivo unless invasive techniques are used. In the current study, a reliable in vivo estimate of the transmission of blue light through the lens was assessed by comparing an indirect and noninvasive...... method based on autofluorescence measurements with a direct method. Methods: Total transmission of blue light was measured in human donor lenses using a direct method applicable only in vitro and compared with transmittance estimates made by an in vivo applicable autofluorescence technique. Results......: Human lens transmission of blue light decreases with age by 0.7-0.8% per year at 480 nm. The comparison of methods showed that the autofluorescence-based method correlated significantly with the direct measurements (R = 0.83, p

  19. Macroeconomics correlations focused on foreign direct investments

    Directory of Open Access Journals (Sweden)

    Teodora ALECU

    2010-07-01

    Full Text Available This article is meant to reveal the way in which the theory of interconnections between systems and sub-systems partici-pating to the creation of economic value, which have been described by professor Paul Bran in his book Economics of Value is outlined in practice and how its analysis may help us to control the effects of the policies applied at the level of each macroeconomic sub-system.

  20. Measuring rat kidney glomerular number and size in vivo with MRI.

    Science.gov (United States)

    Baldelomar, Edwin J; Charlton, Jennifer R; Beeman, Scott C; Bennett, Kevin M

    2017-11-01

    Nephron number is highly variable in humans and is thought to play an important role in renal health. Chronic kidney disease (CKD) is the result of too few nephrons to maintain homeostasis. Currently, nephron number estimates can only be determined invasively or as a terminal assessment. Due to a lack of tools to measure and track nephron number in the living, the early stages of CKD often go unrecognized, preventing early intervention that might halt the progression of CKD. In this work, we present a technique to directly measure glomerular number (Nglom) and volume in vivo in the rat kidney (n=8) using MRI enhanced with the novel contrast agent cationized ferritin (CFE-MRI). Adult male rats were administered intravenous cationized ferritin (CF) and imaged in vivo with MRI. Glomerular number was measured and each glomerulus was spatially mapped in 3D in the image. Mean apparent glomerular volume (aVglom) and intra-renal distribution of the individual glomerular volume (IGV) were also measured. These metrics were compared between images of the same kidneys scanned in vivo and ex vivo with CFE-MRI. In vivo Nglom and aVglom correlated to ex vivo metrics within the same kidneys and were within 10% of Nglom and aVglom previously validated by stereologic methods. This is the first description of direct in vivo measurements of Nglom and aVglom, introducing an opportunity to investigate mechanisms of renal disease progression and therapeutic response over time. Copyright © 2017, American Journal of Physiology-Renal Physiology.

  1. Interferon-γ induced by in vitro re-stimulation of CD4+ T-cells correlates with in vivo FMD vaccine induced protection of cattle against disease and persistent infection.

    Science.gov (United States)

    Oh, Yooni; Fleming, Lucy; Statham, Bob; Hamblin, Pip; Barnett, Paul; Paton, David J; Park, Jong-Hyeon; Joo, Yi Seok; Parida, Satya

    2012-01-01

    The immune defense against FMDV has been correlated to the antibody mediated component. However, there are occasions when some animals with high virus neutralising (VN) antibody are not protected following challenge and some with low neutralising antibody which do not succumb to disease. The importance of cell mediated immunity in clinical protection is less clear and so we investigated the source and production of interferon-gamma (IFN-γ) in re-stimulated whole blood of FMDV immunized cattle and its correlation to vaccine induced protection and FMDV persistence. We were able to show a positive correlation between IFN-γ response and vaccine induced protection as well as reduction of long term persistence of FMD virus. When combining this IFN-γ response in re-stimulated blood with virus neutralizing antibody titer in serum on the day of challenge, a better correlation of vaccine-induced protection with IFN-γ and VN antibody was predicted. Our investigations also showed that CD4+ T-cells are the major proliferating phenotype and IFN-γ producing cells.

  2. In Vivo Biomolecule Corona around Blood-Circulating, Clinically Used and Antibody-Targeted Lipid Bilayer Nanoscale Vesicles.

    Science.gov (United States)

    Hadjidemetriou, Marilena; Al-Ahmady, Zahraa; Mazza, Mariarosa; Collins, Richard F; Dawson, Kenneth; Kostarelos, Kostas

    2015-08-25

    The adsorption of proteins and their layering onto nanoparticle surfaces has been called the "protein corona". This dynamic process of protein adsorption has been extensively studied following in vitro incubation of many different nanoparticles with plasma proteins. However, the formation of protein corona under dynamic, in vivo conditions remains largely unexplored. Extrapolation of in vitro formed protein coronas to predict the fate and possible toxicological burden from nanoparticles in vivo is of great interest. However, complete lack of such direct comparisons for clinically used nanoparticles makes the study of in vitro and in vivo formed protein coronas of great importance. Our aim was to study the in vivo protein corona formed onto intravenously injected, clinically used liposomes, based on the composition of the PEGylated liposomal formulation that constitutes the anticancer agent Doxil. The formation of in vivo protein corona was determined after the recovery of the liposomes from the blood circulation of CD-1 mice 10 min postinjection. In comparison, in vitro protein corona was formed by the incubation of liposomes in CD-1 mouse plasma. In vivo and in vitro formed protein coronas were compared in terms of morphology, composition and cellular internalization. The protein coronas on bare (non-PEGylated) and monoclonal antibody (IgG) targeted liposomes of the same lipid composition were also comparatively investigated. A network of linear fibrillary structures constituted the in vitro formed protein corona, whereas the in vivo corona had a different morphology but did not appear to coat the liposome surface entirely. Even though the total amount of protein attached on circulating liposomes correlated with that observed from in vitro incubations, the variety of molecular species in the in vivo corona were considerably wider. Both in vitro and in vivo formed protein coronas were found to significantly reduce receptor binding and cellular internalization of

  3. Fractional correlation.

    Science.gov (United States)

    Mendlovic, D; Ozaktas, H M; Lohmann, A W

    1995-01-10

    Recently, optical interpretations of the fractional-Fourier-transform operator have been introduced. On the basis of this operator the fractional correlation operator is defined in two different ways that are both consistent with the definition of conventional correlation. Fractional correlation is not always a shift-invariant operation. This property leads to some new applications for fractional correlation as shift-variant image detection. A bulk-optics implementation of fractional correlation is suggested and demonstrated with computer simulations.

  4. In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study.

    Science.gov (United States)

    Krishna, Somashekar G; Modi, Rohan M; Kamboj, Amrit K; Swanson, Benjamin J; Hart, Phil A; Dillhoff, Mary E; Manilchuk, Andrei; Schmidt, Carl R; Conwell, Darwin L

    2017-05-14

    To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs). In a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively. A total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a "fern pattern" of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology. In vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs.

  5. Synovial tissue hypoxia and inflammation in vivo.

    LENUS (Irish Health Repository)

    Ng, C T

    2012-02-01

    INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic\\/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

  6. Comparison of In-Vivo and Ex-Vivo Viscoelastic Behavior of the Spinal Cord.

    Science.gov (United States)

    Ramo, Nicole L; Shetye, Snehal S; Streijger, Femke; Lee, Jae H T; Troyer, Kevin L; Kwon, Brian K; Cripton, Peter; Puttlitz, Christian M

    2017-12-26

    Despite efforts to simulate the in-vivo environment, post-mortem degradation and lack of blood perfusion complicate the use of ex-vivo derived material models in computational studies of spinal cord injury. In order to quantify the mechanical changes that manifest ex-vivo, the viscoelastic behavior of in-vivo and ex-vivo porcine spinal cord samples were compared. Stress-relaxation data from each condition were fit to a non-linear viscoelastic model using a novel characterization technique called the direct fit method. To validate the presented material models, the parameters obtained for each condition were used to predict the respective dynamic cyclic response. Both ex-vivo and in-vivo samples displayed non-linear viscoelastic behavior with a significant increase in relaxation with applied strain. However, at all three strain magnitudes compared, ex-vivo samples experienced a higher stress and greater relaxation than in-vivo samples. Significant differences between model parameters also showed distinct relaxation behaviors, especially in non-linear relaxation modulus components associated with the short-term response (0.1 to 1 second). The results of this study underscore the necessity of utilizing material models developed from in-vivo experimental data for studies of spinal cord injury, where the time-dependent properties are critical. The ability of each material model to accurately predict the dynamic cyclic response validates the presented methodology and supports the use of the in-vivo model in future high-resolution finite element modeling efforts. Neural tissues (such as the brain and spinal cord) display time-dependent, or viscoelastic, mechanical behavior making it difficult to model how they respond to various loading conditions, including injury. Methods that aim to characterize the behavior of the spinal cord almost exclusively use ex-vivo cadaveric or animal samples, despite evidence that time after death affects the behavior compared to that in a

  7. Communication: direct comparison between theory and experiment for correlated angular and product-state distributions of the ground-state and stretching-excited O((3)P) + CH4 reactions.

    Science.gov (United States)

    Czakó, Gábor

    2014-06-21

    Motivated by a recent experiment [H. Pan and K. Liu, J. Chem. Phys. 140, 191101 (2014)], we report a quasiclassical trajectory study of the O((3)P) + CH4(vk = 0, 1) → OH + CH3 [k = 1 and 3] reactions on an ab initio potential energy surface. The computed angular distributions and cross sections correlated to the OH(v = 0, 1) + CH3(v = 0) coincident product states can be directly compared to experiment for O + CH4(v3 = 0, 1). Both theory and experiment show that the ground-state reaction is backward scattered, whereas the angular distributions shift toward sideways and forward directions upon antisymmetric stretching (v3) excitation of the reactant. Theory predicts similar behavior for the O + CH4(v1 = 1) reaction. The simulations show that stretching excitation enhances the reaction up to about 15 kcal/mol collision energy, whereas the O + CH4(vk = 1) reactions produce smaller cross sections for OH(v = 1) + CH3(v = 0) than those of O + CH4(v = 0) → OH(v = 0) + CH3(v = 0). The former finding agrees with experiment and the latter awaits for confirmation. The computed cold OH rotational distributions of O + CH4(v = 0) are in good agreement with experiment.

  8. Outcome of infection of C57BL/6 IL-10−/− mice with Campylobacter jejuni strains is correlated with genome content of open reading frames up- and down-regulated in vivo

    Science.gov (United States)

    Bell, J. A.; Jerome, J.P.; Plovanich-Jones, A. E.; Smith, E. J.; Gettings, J. R.; Kim, H. Y.; Landgraf, J. R.; Lefébure, T.; Kopper, J. J.; Rathinam, V. A.; St. Charles, J. L.; Buffa, B. A.; Brooks, A. P.; Poe, S. A.; Eaton, K. A.; Stanhope, M. J.; Mansfield, L. S.

    2014-01-01

    Human Campylobacter jejuni infection can result in an asymptomatic carrier state, watery or bloody diarrhea, bacteremia, meningitis, or autoimmune neurological sequelae. Infection outcomes of C57BL/6 IL-10−/− mice orally infected with twenty-two phylogenetically diverse C. jejuni sstrains were evaluated to correlate colonization and disease phenotypes with genetic composition of the strains. Variation between strains was observed in colonization, timing of development of clinical signs, and occurrence of enteric lesions. Five pathotypes of C. jejuni in C57BL/6 IL-10−/− mice were delineated: little or no colonization, colonization without disease, colonization with enteritis, colonization with hemorrhagic enteritis, and colonization with neurological signs with or without enteritis. Virulence gene content of ten sequenced strains was compared in silico; virulence gene content of twelve additional strains was compared using a C. jejuni pan-genome microarray. Neither total nor virulence gene content predicted pathotype; nor was pathotype correlated with multilocus sequence type. Each strain was unique with regard to absences of known virulence-related loci and/or possession of point mutations and indels, including phase variation, in virulence-related genes. An experiment in C. jejuni 11168-infected germ-free mice showed that expression levels of ninety open reading frames (ORFs) were significantly up- or down-regulated in the mouse cecum at least two-fold compared to in vitro growth. Genomic content of these ninety C. jejuni 11168 ORFs was significantly correlated with the capacity to colonize and cause enteritis in C57BL/6 IL-10−/− mice. Differences in gene expression levels and patterns are thus an important determinant of pathotype in C. jejuni strains in this mouse model. PMID:22960579

  9. Outcome of infection of C57BL/6 IL-10(-/-) mice with Campylobacter jejuni strains is correlated with genome content of open reading frames up- and down-regulated in vivo.

    Science.gov (United States)

    Bell, J A; Jerome, J P; Plovanich-Jones, A E; Smith, E J; Gettings, J R; Kim, H Y; Landgraf, J R; Lefébure, T; Kopper, J J; Rathinam, V A; St Charles, J L; Buffa, B A; Brooks, A P; Poe, S A; Eaton, K A; Stanhope, M J; Mansfield, L S

    2013-01-01

    Human Campylobacter jejuni infection can result in an asymptomatic carrier state, watery or bloody diarrhea, bacteremia, meningitis, or autoimmune neurological sequelae. Infection outcomes of C57BL/6 IL-10(-/-) mice orally infected with twenty-two phylogenetically diverse C. jejuni strains were evaluated to correlate colonization and disease phenotypes with genetic composition of the strains. Variation between strains was observed in colonization, timing of development of clinical signs, and occurrence of enteric lesions. Five pathotypes of C. jejuni in C57BL/6 IL-10(-/-) mice were delineated: little or no colonization, colonization without disease, colonization with enteritis, colonization with hemorrhagic enteritis, and colonization with neurological signs with or without enteritis. Virulence gene content of ten sequenced strains was compared in silico; virulence gene content of twelve additional strains was compared using a C. jejuni pan-genome microarray. Neither total nor virulence gene content predicted pathotype; nor was pathotype correlated with multilocus sequence type. Each strain was unique with regard to absences of known virulence-related loci and/or possession of point mutations and indels, including phase variation, in virulence-related genes. An experiment in C. jejuni 11168-infected germ-free mice showed that expression levels of ninety open reading frames (ORFs) were significantly up- or down-regulated in the mouse cecum at least two-fold compared to in vitro growth. Genomic content of these ninety C. jejuni 11168 ORFs was significantly correlated with the capacity to colonize and cause enteritis in C57BL/6 IL-10(-/-) mice. Differences in gene expression levels and patterns are thus an important determinant of pathotype in C. jejuni strains in this mouse model. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Where It?s at Really Matters: In Situ In Vivo Vascular Endothelial Growth Factor Spatially Correlates with Electron Paramagnetic Resonance pO2 Images in Tumors of Living Mice

    OpenAIRE

    Elas, Martyna; Hleihel, Danielle; Barth, Eugene D.; Haney, Chad R.; Ahn, Kang-Hyun; Pelizzari, Charles A; Epel, Boris; Weichselbaum, Ralph R.; Halpern, Howard J.

    2010-01-01

    Purpose Tumor microenvironments show remarkable tumor pO2 heterogeneity, as seen in prior EPR pO2 images (EPROI). pO2 correlation with hypoxia response proteins is frustrated by large rapid pO2 changes with position. Procedures To overcome this limitation, biopsies stereotactically located in the EPROI were used to explore the relationship between vascular endothelial growth factor A (VEGF) concentrations in living mouse tumors and the local EPROI pO2. Results Quantitative ELISA VEGF concentr...

  11. Overaccumulation of the chloroplast antisense RNA AS5 is correlated with decreased abundance of 5S rRNA in vivo and inefficient 5S rRNA maturation in vitro

    Science.gov (United States)

    Sharwood, Robert E.; Hotto, Amber M.; Bollenbach, Thomas J.; Stern, David B.

    2011-01-01

    Post-transcriptional regulation in the chloroplast is exerted by nucleus-encoded ribonucleases and RNA-binding proteins. One of these ribonucleases is RNR1, a 3′-to-5′ exoribonuclease of the RNase II family. We have previously shown that Arabidopsis rnr1-null mutants exhibit specific abnormalities in the expression of the rRNA operon, including the accumulation of precursor 23S, 16S, and 4.5S species and a concomitant decrease in the mature species. 5S rRNA transcripts, however, accumulate to a very low level in both precursor and mature forms, suggesting that they are unstable in the rnr1 background. Here we demonstrate that rnr1 plants overaccumulate an antisense RNA, AS5, that is complementary to the 5S rRNA, its intergenic spacer, and the downstream trnR gene, which encodes tRNAArg, raising the possibility that AS5 destabilizes 5S rRNA or its precursor and/or blocks rRNA maturation. To investigate this, we used an in vitro system that supports 5S rRNA and trnR processing. We show that AS5 inhibits 5S rRNA maturation from a 5S-trnR precursor, and shorter versions of AS5 demonstrate that inhibition requires intergenic sequences. To test whether the sense and antisense RNAs form double-stranded regions in vitro, treatment with the single-strand-specific mung bean nuclease was used. These results suggest that 5S–AS5 duplexes interfere with a sense-strand secondary structure near the endonucleolytic cleavage site downstream from the 5S rRNA coding region. We hypothesize that these duplexes are degraded by a dsRNA-specific ribonuclease in vivo, contributing to the 5S rRNA deficiency observed in rnr1. PMID:21148395

  12. A Direct in Vivo Comparison of the Melanocortin Monovalent Agonist Ac-His-DPhe-Arg-Trp-NH2 versus the Bivalent Agonist Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH2: A Bivalent Advantage.

    Science.gov (United States)

    Lensing, Cody J; Adank, Danielle N; Wilber, Stacey L; Freeman, Katie T; Schnell, Sathya M; Speth, Robert C; Zarth, Adam T; Haskell-Luevano, Carrie

    2017-06-21

    Bivalent ligands targeting putative melanocortin receptor dimers have been developed and characterized in vitro; however, studies of their functional in vivo effects have been limited. The current report compares the effects of homobivalent ligand CJL-1-87, Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH2, to monovalent ligand CJL-1-14, Ac-His-DPhe-Arg-Trp-NH2, on energy homeostasis in mice after central intracerebroventricular (ICV) administration into the lateral ventricle of the brain. Bivalent ligand CJL-1-87 had noteworthy advantages as an antiobesity probe over CJL-1-14 in a fasting-refeeding in vivo paradigm. Treatment with CJL-1-87 significantly decreased food intake compared to CJL-1-14 or saline (50% less intake 2-8 h after treatment). Furthermore, CJL-1-87 treatment decreased the respiratory exchange ratio (RER) without changing the energy expenditure indicating that fats were being burned as the primary fuel source. Additionally, CJL-1-87 treatment significantly lowered body fat mass percentage 6 h after administration (p < 0.05) without changing the lean mass percentage. The bivalent ligand significantly decreased insulin, C-peptide, leptin, GIP, and resistin plasma levels compared to levels after CJL-1-14 or saline treatments. Alternatively, ghrelin plasma levels were significantly increased. Serum stability of CJL-1-87 and CJL-1-14 (T1/2 = 6.0 and 16.8 h, respectively) was sufficient to permit physiological effects. The differences in binding affinity of CJL-1-14 compared to CJL-1-87 are speculated as a possible mechanism for the bivalent ligand's unique effects. We also provide in vitro evidence for the formation of a MC3R-MC4R heterodimer complex, for the first time to our knowledge, that may be an unexploited neuronal molecular target. Regardless of the exact mechanism, the advantageous ability of CJL-1-87 compared to CJL-1-14 to increase in vitro binding affinity, increase the duration of action in spite of decreased serum stability, decrease in

  13. Correlating Pap Smear Results and Colposcopy-Directed Large Loop Excision of the Transformation Zone Histopathology in HIV-Infected and HIV-Uninfected Women: A Case-Control Study in South Africa

    Directory of Open Access Journals (Sweden)

    Louis-J. van Bogaert

    2013-01-01

    Full Text Available Background. In low-resource settings (LRS with high HIV/AIDS and cervical cancer rates, new screening strategies face many logistic hurdles. Since cytology is there to stay, at least in the median-term future, it is important to assess to what extent HIV-HPV coinfection impacts the accuracy of screening methods and strategies. Methods. We audited the correlation between cytological diagnosis of minimal abnormality (CIN1, CIN2+, or cancer and the histological diagnosis of colposcopy-directed large loop excision of the transformation zone of 399 HIV-uninfected controls and 389 HIV-infected cases. Results. The average age at diagnosis of CIN2+ of the cases was 4.2 years younger than controls (. The endpoint used to assess the accuracy of cytology was minimal cytological abnormality (≤CIN1/LGSIL. The sensitivity, specificity, and negative and positive predictive values were 92.7, 18.5, 45.1, and 77.9%, respectively. The overall ratio of discordance/concordance between cytology and histology was similar in both groups. Conclusion. In LRS, where rapid-HPV testing is not yet part of screening algorithms, a cytological diagnosis of minimal abnormality requires visual inspection and treatment of visualized lesions especially in HIV-infected women aged 30 years. The cytological endpoint of accuracy should be set low to avoid false negative smears.

  14. In vivo evaluation of biosensors volumetric bio-distribution for measurement of metabolic activity by X-ray correlation, fluorescence, Cerenkov image and radioisotope; Evaluacion in vivo de la biodistribucion volumetrica de biosensores para medicion de la actividad metabolica por correlacion de rayos X, fluorescencia, imagen Cerenkov y radioisotopica

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez N, G. J.

    2016-07-01

    The aim of this study was to characterize the in vivo volumetric distribution of three folate based biosensors by different imaging modalities (X-ray, fluorescence, Cerenkov luminescence and radioisotopic imaging) through the development of a tri dimensional (3D) image reconstruction algorithm. The preclinical and multimodal Xtreme imaging system, with a Multimodal Animal Rotation System (Mars), was used to acquire bidimensional (2D) images, which were processed to obtain the 3D reconstruction. Images of mice at different times (biosensor distribution) were simultaneously obtained from the four imaging modalities. The filtered backprojection and inverse Radon transformation were used as main image-processing techniques. In the first instance, the algorithm developed in Mat lab was able to reconstruct in the 3D form the skeleton of the mice under study. Subsequently, the algorithm was able to get the volumetric profiles of {sup 99m}Tc-Folate-Bombesin (radioisotopic image), {sup 177}Lu-Folate-Bombesin (Cerenkov image), and FolateRSense 680 (fluorescence image) in the tumors and kidneys of the mice. No significant differences were detected between the volumetric quantifications using the standard measurement techniques and the quantifications obtained with the proposal made in this study, nor between the volumetric uptakes in the structures of interest. With the structures reconstructed in the 3D form, the fusion of anatomical (as the skeleton) and functional structures derived from the images of the biosensors uptake was achieved The imaging 3D reconstruction algorithm can be easily extrapolated to different 2D acquisition-type images. This characteristic flexibility of the algorithm developed in this study is an advantage in comparison to similar reconstruction methods. (Author)

  15. In vivo endoscopic multi-beam optical coherence tomography

    Science.gov (United States)

    Standish, Beau A.; Lee, Kenneth K. C.; Mariampillai, Adrian; Munce, Nigel R.; Leung, Michael K. K.; Yang, Victor X. D.; Vitkin, I. Alex

    2010-02-01

    A multichannel optical coherence tomography (multi-beam OCT) system and an in vivo endoscopic imaging probe were developed using a swept-source OCT system. The distal optics were micro-machined to produce a high numerical aperture, multi-focus fibre optic array. This combination resulted in a transverse design resolution of rabbit study to acquire in vivo structural images of the colon and ex vivo images of the oesophagus and trachea. A good correlation between the structural multi-beam OCT images and H&E histology was achieved, demonstrating the feasibility of this high-resolution system and its potential for in vivo human endoscopic imaging.

  16. Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis

    Directory of Open Access Journals (Sweden)

    Sanne de Jong

    2014-12-01

    Full Text Available Cardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis. Fluorescently labeled CNA35 was applied ex vivo on tissue sections of fibrotic rat, mouse, and canine myocardium. After quantification of CNA35, sections were examined with picrosirius red (PSR and compared to CNA35. Furthermore, fluorescently labeled CNA35 was administered in vivo in mice. Hearts were isolated, and CNA35 labeling was examined in tissue sections. Serial sections were histologically examined with PSR. Ex vivo application of CNA35 showed specific binding to collagen and a high correlation with PSR (Pearson r = .86 for mice/rats and r = .98 for canine; both p < .001. After in vivo administration, CNA35 labeling was observed around individual cardiomyocytes, indicating its ability to penetrate cardiac endothelium. High correlation was observed between CNA35 and PSR (r = .91, p < .001. CNA35 specifically binds to cardiac collagen and can cross the endothelial barrier. Therefore, labeled CNA35 is useful to specifically detect collagen both ex vivo and in vivo and potentially can be converted to a noninvasive method to detect cardiac fibrosis.

  17. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  18. Comparison of ex vivo stability of copeptin and vasopressin

    NARCIS (Netherlands)

    Heida, Judith E; Boesten, Lianne S M; Ettema, Esmée M; Muller Kobold, Anneke C.; Franssen, Casper F M; Gansevoort, Ron T; Zittema, Debbie

    BACKGROUND: Copeptin, part of the vasopressin precursor, is increasingly used as marker for vasopressin and is claimed to have better ex vivo stability. However, no study has directly compared the ex vivo stability of copeptin and vasopressin. METHODS: Blood of ten healthy volunteers was collected

  19. Pair Correlation Function Integrals

    DEFF Research Database (Denmark)

    Wedberg, Nils Hejle Rasmus Ingemar; O'Connell, John P.; Peters, Günther H.J.

    2011-01-01

    We describe a method for extending radial distribution functions obtained from molecular simulations of pure and mixed molecular fluids to arbitrary distances. The method allows total correlation function integrals to be reliably calculated from simulations of relatively small systems. The long......-distance behavior of radial distribution functions is determined by requiring that the corresponding direct correlation functions follow certain approximations at long distances. We have briefly described the method and tested its performance in previous communications [R. Wedberg, J. P. O’Connell, G. H. Peters......, and J. Abildskov, Mol. Simul. 36, 1243 (2010); Fluid Phase Equilib. 302, 32 (2011)], but describe here its theoretical basis more thoroughly and derive long-distance approximations for the direct correlation functions. We describe the numerical implementation of the method in detail, and report...

  20. Spreading depolarization-induced adenosine accumulation reflects metabolic status in vitro and in vivo

    Science.gov (United States)

    Lindquist, Britta E; Shuttleworth, C William

    2014-01-01

    Spreading depolarization (SD), a pathologic feature of migraine, stroke and traumatic brain injury, is a propagating depolarization of neurons and glia causing profound metabolic demand. Adenosine, the low-energy metabolite of ATP, has been shown to be elevated after SD in brain slices and under conditions likely to trigger SD in vivo. The relationship between metabolic status and adenosine accumulation after SD was tested here, in brain slices and in vivo. In brain slices, metabolic impairment (assessed by nicotinamide adenine dinucleotide (phosphate) autofluorescence and O2 availability) was associated with prolonged extracellular direct current (DC) shifts indicating delayed repolarization, and increased adenosine accumulation. In vivo, adenosine accumulation was observed after SD even in otherwise healthy mice. As in brain slices, in vivo adenosine accumulation correlated with DC shift duration and increased when DC shifts were prolonged by metabolic impairment (i.e., hypoglycemia or middle cerebral artery occlusion). A striking pattern of adenosine dynamics was observed during focal ischemic stroke, with nearly all the observed adenosine signals in the periinfarct region occurring in association with SDs. These findings suggest that adenosine accumulation could serve as a biomarker of SD incidence and severity, in a range of clinical conditions. PMID:25160669

  1. Quantitative Analysis of HER2 Receptor Expression In Vivo by Near-Infrared Optical Imaging

    Directory of Open Access Journals (Sweden)

    Victor Chernomordik

    2010-07-01

    Full Text Available Human epidermal growth factor receptor 2 (HER2 overexpression in breast cancers is associated with poor prognosis and resistance to therapy. Current techniques for estimating this important characteristic use ex vivo assays that require tissue biopsies. We suggest a novel noninvasive method to characterize HER2 expression in vivo, using optical imaging, based on HER2-specific probes (albumin-binding domain–fused-(ZHER2:3422-Cys Affibody molecules [Affibody AB, Solna, Sweden], labeled with Alexa Fluor 750 [Molecular Probes, Invitrogen, Carlsbad, CA] that could be used concomitantly with HER2-targeted therapy. Subcutaneous tumor xenografts, expressing different levels of HER2, were imaged with a near-infrared fluorescence small-animal imaging system at several times postinjection of the probe. The compartmental ligand-receptor model was used to calculate HER2 expression from imaging data. Correlation between HER2 amplification/overexpression in tumor cells and parameters, directly estimated from the sequence of optical images, was observed (eg, experimental data for BT474 xenografts indicate that initial slope, characterizing the temporal dependence of the fluorescence intensity detected in the tumor, linearly depends on the HER2 expression, as measured ex vivo by an enzyme-linked immunosorbent assay for the same tumor. The results obtained from tumors expressing different levels of HER2 substantiate a similar relationship between the initial slope and HER2 amplification/overexpression. This work shows that optical imaging, combined with mathematical modeling, allows noninvasive monitoring of HER2 expression in vivo.

  2. Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies.

    Science.gov (United States)

    Zhu, Hong; Kochevar, Irene E; Behlau, Irmgard; Zhao, Jie; Wang, Fenghua; Wang, Yucheng; Sun, Xiaodong; Hamblin, Michael R; Dai, Tianhong

    2017-01-01

    To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.

  3. A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA

    Science.gov (United States)

    Zeng, Zhengyang; Han, Shisong; Hong, Wei; Lang, Yange; Li, Fangfang; Liu, Yongxiang; Li, Zeyong; Wu, Yingliang; Li, Wenxin; Zhang, Xianzheng; Cao, Zhijian

    2016-01-01

    Hepatitis B virus (HBV) infection is a major cause of chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats to human health. However, current clinical therapies for HBV are limited by potential side effects, toxicity, and drug-resistance. In this study, a cell-penetrating peptide-conjugated peptide nucleic acid (PNA), Tat-PNA-DR, was designed to target the direct repeat (DR) sequences of HBV. Tat-PNA-DR effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the translation of hepatitis B e antigen (HBeAg), HBsAg, HBV core, hepatitis B virus x protein, and HBV reverse transcriptase (RT) and the reverse transcription of the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was similar to the effect of the widely used clinical drug Lamivudine (3TC). Additionally, a long-term hydrodynamics HBV mouse model also demonstrated Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising drug candidate against HBV. PMID:26978579

  4. La Edad Se Correlaciona Directamente con la Fuerza de los Estereotipos de Género: Evidencia Obtenida en una Tarea de Memoria de Reconocimiento Age Correlates Directly With Gender Stereotype Strength: Evidence From a Recognition Memory Task

    Directory of Open Access Journals (Sweden)

    Sergio E Chaigneau

    2012-11-01

    Full Text Available Varias teorías predicen una correlación directa entre edad y estereotipos. Sin embargo, los estudios que muestran este efecto típicamente comparan adultos mayores (> 55-60 años con adultos jóvenes. Por contraste, en el estudio que se reporta participaron 79 individuos de 18 a 60 años de nivel socioeconómico alto, alumnos y profesores de una universidad privada en Santiago de Chile que respondieron a una invitación masiva. El trabajo se enfoca en los estereotipos de género, preguntando si los adultos medios (k 40 años también muestran un nivel más elevado de estereotipos que los jóvenes. Se utilizó una tarea de memoria en la que los participantes leían listas de oraciones que describían a hombres y mujeres realizando actividades estereotipadas y neutras, y debían luego reconocerlas en listas que incluían además oraciones distractoras. Los datos se analizaron con ANOVAs mixtos, revelando que la muestra como un todo exhibía un mejor rendimiento de memoria para estímulos estereotipados para género que para estímulos neutros y que, como se predijo, los adultos medios mostraron un efecto casi 2 veces mayor que los jóvenes.Several theories predict a direct correlation between age and stereotypes. However, studies that show this effect typically compare older adults (> 55-60 years of age with young adults. Contrastingly, in the current study participants were 79 high-SES individuals between 18 and 60 years of age, students and professors of a private university in Santiago de Chile, who responded to a mass email. The work reported here focuses on gender stereotypes and asks whether middle aged adults (k 40 years of age also show a higher level of stereotypes than adolescents and young adults. A recognition memory task was used, in which participants read lists of sentences describing men and women carrying out stereotyped and neutral daily activities, and then had to recognize them intermixed with distractor sentences. Data were

  5. Dynamic impact force and association with structural damage to the knee joint: an ex-vivo study.

    Science.gov (United States)

    Brill, Richard; Wohlgemuth, Walther A; Hempfling, Harald; Bohndorf, Klaus; Becker, Ursula; Welsch, Ulrich; Kamp, Alexander; Roemer, Frank W

    2014-12-01

    No systematic, histologically confirmed data are available concerning the association between magnitude of direct dynamic impact caused by vertical impact trauma and the resulting injury to cartilage and subchondral bone. The aim of this study was to investigate the association between dynamic impact and the resulting patterns of osteochondral injury in an ex-vivo model. A mechanical apparatus was employed to perform ex-vivo controlled dynamic vertical impact experiments in 110 pig knees with the femur positioned in a holding fixture. A falling body with a thrust plate and photo sensor was applied. The direct impact to the trochlear articular surface was registered and the resulting osteochondral injuries macroscopically and histologically correlated and categorized. The relationship between magnitude of direct impact and injury severity could be classified as stage I injuries (impact 12.7MPa): osteochondral impression, histologically imprint and osteochondral macrofractures. The impact ranges and histologic injury stages determined from this vertical dynamic impact experiment allowed for a biomechanical classification of direct, acute osteochondral injury. In contrast to static load commonly applied in ex-vivo experiments, dynamic impact more realistically represents actual trauma to the knee joint.

  6. A Methodology for Registration of a Histological Slide and In Vivo MRI Volume Based on Optimizing Mutual Information

    Directory of Open Access Journals (Sweden)

    Charles R. Meyer

    2006-01-01

    Full Text Available We present a method for registering histology and in vivo imaging that requires minimal microtoming and is automatic following the user's initialization. In this demonstration, we register a single hematoxylin-and-eosin-stained histological slide of a coronal section of a rat brain harboring a 9L gliosarcoma with an in vivo 7T MR image volume of the same brain. Because the spatial resolution of the in vivo MRI is limited, we add the step of obtaining a high spatial resolution, ex vivo MRI in situ for intermediate registration. The approach taken was to maximize mutual information in order to optimize the registration between all pairings of image data whether the sources are MRI, tissue block photograph, or stained sample photograph. The warping interpolant used was thin plate splines with the appropriate basis function for either 2-D or 3-D applications. All registrations were implemented by user initialization of the approximate pose between the two data sets, followed by automatic optimization based on maximizing mutual information. Only the higher quality anatomical images were used in the registration process; however, the spatial transformation was directly applied to a quantitative diffusion image. Quantitative diffusion maps from the registered location appeared highly correlated with the H&E slide. Overall, this approach provides a robust method for coregistration of in vivo images with histological sections and will have broad applications in the field of functional and molecular imaging.

  7. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  8. ex vivo DNA assembly

    Directory of Open Access Journals (Sweden)

    Adam B Fisher

    2013-10-01

    Full Text Available Even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. Advances in cloning techniques have resulted in powerful in vitro and in vivo assembly of DNA. However, monetary and time costs have limited these approaches. Here, we report an ex vivo DNA assembly method that uses cellular lysates derived from a commonly used laboratory strain of Escherichia coli for joining double-stranded DNA with short end homologies embedded within inexpensive primers. This method concurrently shortens the time and decreases costs associated with current DNA assembly methods.

  9. In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer.

    Science.gov (United States)

    Andersen, Helene Schou; Bennedsen, Astrid Louise Bjørn; Burgdorf, Stefan Kobbelgaard; Eriksen, Jens Ravn; Eiholm, Susanne; Toxværd, Anders; Riis, Lene Buhl; Rosenberg, Jacob; Gögenur, Ismail

    2017-07-01

    Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.

  10. A default Bayesian hypothesis test for correlations and partial correlations

    NARCIS (Netherlands)

    Wetzels, R.; Wagenmakers, E.J.

    2012-01-01

    We propose a default Bayesian hypothesis test for the presence of a correlation or a partial correlation. The test is a direct application of Bayesian techniques for variable selection in regression models. The test is easy to apply and yields practical advantages that the standard frequentist tests

  11. Scaphoid kinematics in vivo

    NARCIS (Netherlands)

    Moojen, Thybout M.; Snel, Jeroen G.; Ritt, Marco J. P. F.; Venema, Henk W.; Kauer, John M. G.; Bos, Kurt E.

    2002-01-01

    The purpose of this study was to quantify 3-dimensional (3-D) in vivo scaphoid kinematics during flexion-extension motion (FEM) and radial-ulnar deviation (RUD) of the hand. The right wrists of 11 healthy volunteers were imaged by spiral computed tomography during RUD and 5 of those wrists also

  12. In vivo and ex vivo vessel wall MRI of the circle of Willis

    NARCIS (Netherlands)

    Harteveld, A.A.|info:eu-repo/dai/nl/413650286

    2017-01-01

    In recent years, several MRI sequences have been developed for direct evaluation of the intracranial vessel wall and its pathology in vivo. These MRI sequences enable detection of intracranial vessel wall abnormalities, including those that have not yet caused luminal narrowing. The research field

  13. In Vitro – In Vivo Evaluation of Sustained – Release Lithium Carbonate Matrix Tablets: Influence of Hydrophilic Matrix Materials

    Directory of Open Access Journals (Sweden)

    J Emami

    2004-04-01

    Full Text Available Background: Conventional Lithium carbonate (LC tablets produce rapid and relatively high peak blood levels resulting in adverse effects. These drawbacks can be overcome by designing a suitable sustained or controlled-release LC preparation. Methods: Sustained-release matrix tablets were therefore developed using different types and ratios of polymers including carbomer (CP, Na carboxymethylcellulose (Na CMC and hydroxypropylmethylcellulose (HPMC, to assess the release profiles and in vivo performance of the formulations. The tablets were prepared by either direct compression (DC or wet granulation (WG. In the DC method, 69% (450 mg LC, 5, 10 or 15% CP or Na CMC (of total tablet weight, lactose and /or Avicel (to maintain constant tablet weight were mixed and directly compressed. In the WG method, 450 mg LC and 10, 20, or 30% HPMC were granulated with Eudragit S100 solution, dried, and then compressed to formulate the tablets. In vitro and in vivo, newly formulated sustained-release LC tablets were compared with sustained-release commercial tablets (Eskalith and Priadel. In vivo studies were conducted in nine healthy subjects in a cross-over design, with a 3x3 Latin square sequence, and pharmacokinetic parameters were estimated using classical methods. Results: The matrix tablets containing 15% CP exhibited suitable release kinetics and uniform absorption characteristics comparable to that of Eskalith. In vivo, this formulation produced a smooth and extended absorption phase very much similar to that of Eskalith with the identical elimination half-life and extent of absorption. Conclusion: The matrix tablets containing 15% CP reduces the incidence of side effects often associated with high serum concentration of Lithium and blood level variations. Direct correlation between the dissolution profiles and the relative bioavailability of the formulations could be observed. Keywords: Lithium carbonate, Matrix tablets, Sustained-release, In vitro

  14. Mechanisms of in vivo release of triamcinolone acetonide from PLGA microspheres.

    Science.gov (United States)

    Doty, Amy C; Weinstein, David G; Hirota, Keiji; Olsen, Karl F; Ackermann, Rose; Wang, Yan; Choi, Stephanie; Schwendeman, Steven P

    2017-06-28

    Little is known about the underlying effects controlling in vitro-in vivo correlations (IVIVCs) for biodegradable controlled release microspheres. Most reports of IVIVCs that exist are empirical in nature, typically based on a mathematical relationship between in vitro and in vivo drug release, with the latter often estimated by deconvolution of pharmacokinetic data. In order to improve the ability of in vitro release tests to predict microsphere behavior in vivo and develop more meaningful IVIVCs, the in vivo release mechanisms need to be characterized. Here, two poly(lactic-co-glycolic acid) (PLGA) microsphere formulations encapsulating the model steroid triamcinolone acetonide (Tr-A) were implanted subcutaneously in rats by using a validated cage model, allowing for free fluid and cellular exchange and microsphere retrieval during release. Release kinetics, as well as mechanistic indicators of release such as hydrolysis and mass loss, was measured by direct analysis of the recovered microspheres. Release of Tr-A from both formulations was greatly accelerated in vivo compared to in vitro using agitated phosphate buffered saline +0.02% Tween 80 pH7.4, including rate of PLGA hydrolysis, mass loss and water uptake. Both microsphere formulations exhibited erosion-controlled release in vitro, indicated by similar polymer mass loss kinetics, but only one of the formulations (low molecular weight, free acid terminated) exhibited the same mechanism in vivo. The in vivo release of Tr-A from microspheres made of a higher molecular weight, ester end-capped PLGA displayed an osmotically induced/pore diffusion mechanism based on confocal micrographs of percolating pores in the polymer, not previously observed in vitro. This research indicates the need to fully understand the in vivo environment and how it causes drug release from biodegradable microspheres. This understanding can then be applied to develop in vitro release tests which better mimic this environment and cause

  15. Directed homology

    DEFF Research Database (Denmark)

    Fahrenberg, Uli

    2004-01-01

    We introduce a new notion of directed homology for semicubical sets. We show that it respects directed homotopy and is functorial, and that it appears to enjoy some good algebraic properties. Our work has applications to higher-dimensional automata.......We introduce a new notion of directed homology for semicubical sets. We show that it respects directed homotopy and is functorial, and that it appears to enjoy some good algebraic properties. Our work has applications to higher-dimensional automata....

  16. In silico vs. in vivo human intestinal permeability.

    Science.gov (United States)

    Idkaidek, N M; Najib, N

    2014-12-01

    The aim of this research is to calculate human intestinal permeability in silico and correlate results with those measured in vivo. Optimized human intestinal permeability values were calculated for 16 drugs by de-convolution of human plasma profiles using Parameter Estimation module of SimCYP program V13. Results showed high in silico-in vivo correlation coefficient of 0.89 for drugs with high/low permeability values. In silico permeability, if properly optimized, can be used as surrogate for in vivo permeability for BCS class I drugs and hence is suggested that such methodology could be employed as a support for waiver of in vivo studies. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Censored correlated cytokine concentrations

    DEFF Research Database (Denmark)

    Andersen, Andreas; Benn, Christine Stabell; Jørgensen, Mathias J

    2013-01-01

    Interest in cytokines as markers for the function of the immune system is increasing. Methods quantifying cytokine concentrations are often subject to detection limits, which lead to non-detectable observations and censored distributions. When distributions are skewed, geometric mean ratios (GMRs......) can be used to describe the relative concentration between two cytokines, and the GMR ratio (GMRR) can be used to compare two groups. The problem is how to estimate GMRRs from censored distributions.We evaluated methods, including simple deletion and substitution, in simulated and real data. One...... method applies Tobit directly to the censored difference between the two cytokine log-concentrations (Diff). However, censoring is correlated to the outcome and is therefore not independent. The correlation increases as the correlation between the two log-concentrations decreases. We propose a Tobit...

  18. Search for correlations between the arrival directions of IceCube neutrino events and ultrahigh-energy cosmic rays detected by the Pierre Auger Observatory and the Telescope Array

    NARCIS (Netherlands)

    Collaboration, The IceCube; Aartsen, M. G.; Abraham, K.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Ahrens, M.; Altmann, D.; Anderson, T.; Ansseau, I.; Archinger, M.; Arguelles, C.; Arlen, T. C.; Auffenberg, J.; Bai, X.; Barwick, S. W.; Baum, V.; Bay, R.; Beatty, J. J.; Tjus, J. Becker; Becker, K. -H.; Beiser, E.; Berghaus, P.; Berley, D.; Bernardini, E.; Bernhard, A.; Besson, D. Z.; Binder, G.; Bindig, D.; Bissok, M.; Blaufuss, E.; Blumenthal, J.; Boersma, D. J.; Bohm, C.; Börner, M.; Bos, F.; Bose, D.; Böser, S.; Botner, O.; Braun, J.; Brayeur, L.; Bretz, H. -P.; Buzinsky, N.; Casey, J.; Casier, M.; Cheung, E.; Chirkin, D.; Christov, A.; Clark, K.; Classen, L.; Coenders, S.; Cowen, D. F.; Silva, A. H. Cruz; Daughhetee, J.; Davis, J. C.; Day, M.; André, J. P. A. M. de; Clercq, C. De; Rosendo, E. del Pino; Dembinski, H.; Ridder, S. De; Desiati, P.; Vries, K. D. de; Wasseige, G. de; With, M. de; DeYoung, T.; Díaz-Vélez, J. C.; Lorenzo, V. di; Dumm, J. P.; Dunkman, M.; Eberhardt, B.; Ehrhardt, T.; Eichmann, B.; Euler, S.; Evenson, P. A.; Fahey, S.; Fazely, A. R.; Feintzeig, J.; Felde, J.; Filimonov, K.; Finley, C.; Fischer-Wasels, T.; Flis, S.; Fösig, C. -C.; Fuchs, T.; Gaisser, T. K.; Gaior, R.; Gallagher, J.; Gerhardt, L.; Ghorbani, K.; Gier, D.; Gladstone, L.; Glagla, M.; Glüsenkamp, T.; Goldschmidt, A.; Golup, G.; Gonzalez, J. G.; Góra, D.; Grant, D.; Griffith, Z.; Groß, A.; Ha, C.; Haack, C.; Ismail, A. Haj; Hallgren, A.; Halzen, F.; Hansen, E.; Hansmann, B.; Hanson, K.; Hebecker, D.; Heereman, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hignight, J.; Hill, G. C.; Hoffman, K. D.; Hoffmann, R.; Holzapfel, K.; Homeier, A.; Hoshina, K.; Huang, F.; Huber, M.; Huelsnitz, W.; Hulth, P. O.; Hultqvist, K.; In, S.; Ishihara, A.; Jacobi, E.; Japaridze, G. S.; Jeong, M.; Jero, K.; Jurkovic, M.; Kappes, A.; Karg, T.; Karle, A.; Kauer, M.; Keivani, A.; Kelley, J. L.; Kemp, J.; Kheirandish, A.; Kiryluk, J.; Kläs, J.; Klein, S. R.; Kohnen, G.; Koirala, R.; Kolanoski, H.; Konietz, R.; Köpke, L.; Kopper, C.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krings, K.; Kroll, G.; Kroll, M.; Krückl, G.; Kunnen, J.; Kurahashi, N.; Kuwabara, T.; Labare, M.; Lanfranchi, J. L.; Larson, M. J.; Lesiak-Bzdak, M.; Leuermann, M.; Leuner, J.; Lu, L.; Lünemann, J.; Madsen, J.; Maggi, G.; Mahn, K. B. M.; Mandelartz, M.; Maruyama, R.; Mase, K.; Matis, H. S.; Maunu, R.; McNally, F.; Meagher, K.; Medici, M.; Meli, A.; Menne, T.; Merino, G.; Meures, T.; Miarecki, S.; Middell, E.; Mohrmann, L.; Montaruli, T.; Morse, R.; Nahnhauer, R.; Naumann, U.; Neer, G.; Niederhausen, H.; Nowicki, S. C.; Nygren, D. R.; Pollmann, A. Obertacke; Olivas, A.; Omairat, A.; O'Murchadha, A.; Palczewski, T.; Pandya, H.; Pankova, D. V.; Paul, L.; Pepper, J. A.; Heros, C. Pérez de los; Pfendner, C.; Pieloth, D.; Pinat, E.; Posselt, J.; Price, P. B.; Przybylski, G. T.; Quinnan, M.; Raab, C.; Rädel, L.; Rameez, M.; Rawlins, K.; Reimann, R.; Relich, M.; Resconi, E.; Rhode, W.; Richman, M.; Richter, S.; Riedel, B.; Robertson, S.; Rongen, M.; Rott, C.; Ruhe, T.; Ryckbosch, D.; Sabbatini, L.; Sander, H. -G.; Sandrock, A.; Sandroos, J.; Sarkar, S.; Schatto, K.; Schimp, M.; Schmidt, T.; Schoenen, S.; Schöneberg, S.; Schönwald, A.; Schulte, L.; Schumacher, L.; Seckel, D.; Seunarine, S.; Soldin, D.; Song, M.; Spiczak, G. M.; Spiering, C.; Stahlberg, M.; Stamatikos, M.; Stanev, T.; Stasik, A.; Steuer, A.; Stezelberger, T.; Stokstad, R. G.; Stößl, A.; Ström, R.; Strotjohann, N. L.; Sullivan, G. W.; Sutherland, M.; Taavola, H.; Taboada, I.; Tatar, J.; Ter-Antonyan, S.; Terliuk, A.; Tešić, G.; Tilav, S.; Toale, P. A.; Tobin, M. N.; Toscano, S.; Tosi, D.; Tselengidou, M.; Turcati, A.; Unger, E.; Usner, M.; Vallecorsa, S.; Vandenbroucke, J.; Eijndhoven, N. van; Vanheule, S.; Santen, J. van; Veenkamp, J.; Vehring, M.; Voge, M.; Vraeghe, M.; Walck, C.; Wallace, A.; Wallraff, M.; Wandkowsky, N.; Weaver, Ch; Wendt, C.; Westerhoff, S.; Whelan, B. J.; Wiebe, K.; Wiebusch, C. H.; Wille, L.; Williams, D. R.; Wissing, H.; Wolf, M.; Wood, T. R.; Woschnagg, K.; Xu, D. L.; Xu, X. W.; Xu, Y.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Collaboration, M. Zoll The Pierre Auger; Aab, A.; Abreu, P.; Aglietta, M.; Ahn, E. J.; Samarai, I. Al; Albuquerque, I. F. M.; Allekotte, I.; Allison, P.; Almela, A.; Castillo, J. Alvarez; Alvarez-Muñiz, J.; Batista, R. Alves; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andrada, B.; Andringa, S.; Aramo, C.; Arqueros, F.; Arsene, N.; Asorey, H.; Assis, P.; Aublin, J.; Avila, G.; Awal, N.; Badescu, A. M.; Baus, C.; Beatty, J. J.; Becker, K. H.; Bellido, J. A.; Berat, C.; Bertaina, M. E.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blaess, S. G.; Blanco, A.; Blanco, M.; Blazek, J.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Borodai, N.; Botti, A. M.; Brack, J.; Brancus, I.; Bretz, T.; Bridgeman, A.; Briechle, F. L.; Buchholz, P.; Bueno, A.; Buitink, S.; Buscemi, M.; Caballero-Mora, K. S.; Caccianiga, B.; Caccianiga, L.; Candusso, M.; Caramete, L.; Caruso, R.; Castellina, A.; Cataldi, G.; Cazon, L.; Cester, R.; Chavez, A. G.; Chiavassa, A.; Chinellato, J. A.; Diaz, J. C. Chirinos; Chudoba, J.; Clay, R. W.; Colalillo, R.; Coleman, A.; Collica, L.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cooper, M. J.; Cordier, A.; Coutu, S.; Covault, C. E.; Dallier, R.; D'Amico, S.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; Almeida, R. M. de; Jong, S. J. de; Mauro, G. De; Neto, J. R. T. de Mello; Mitri, I. De; Oliveira, J. de; Souza, V. de; Debatin, J.; Peral, L. del; Deligny, O.; Dhital, N.; Giulio, C. Di; Matteo, A. Di; Castro, M. L. Díaz; Diogo, F.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dorofeev, A.; Anjos, R. C. dos; Dova, M. T.; Dundovic, A.; Ebr, J.; Engel, R.; Erdmann, M.; Erfani, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Falcke, H.; Fang, K.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fick, B.; Figueira, J. M.; Filevich, A.; Filipčič, A.; Fratu, O.; Freire, M. M.; Fujii, T.; Fuster, A.; Gallo, F.; García, B.; Garcia-Gamez, D.; Garcia-Pinto, D.; Gate, F.; Gemmeke, H.; Gherghel-Lascu, A.; Ghia, P. L.; Giaccari, U.; Giammarchi, M.; Giller, M.; Głas, D.; Glaser, C.; Glass, H.; Golup, G.; Berisso, M. Gómez; Vitale, P. F. Gómez; González, N.; Gookin, B.; Gordon, J.; Gorgi, A.; Gorham, P.; Gouffon, P.; Griffith, N.; Grillo, A. F.; Grubb, T. D.; Guarino, F.; Guedes, G. P.; Hampel, M. R.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Hasankiadeh, Q.; Haungs, A.; Hebbeker, T.; Heck, D.; Heimann, P.; Herve, A. E.; Hill, G. C.; Hojvat, C.; Hollon, N.; Holt, E.; Homola, P.; Hörandel, J. R.; Horvath, P.; Hrabovský, M.; Huege, T.; Insolia, A.; Isar, P. G.; Jandt, I.; Jansen, S.; Jarne, C.; Johnsen, J. A.; Josebachuili, M.; Kääpä, A.; Kambeitz, O.; Kampert, K. H.; Kasper, P.; Katkov, I.; Keilhauer, B.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Krause, R.; Krohm, N.; Kuempel, D.; Mezek, G. Kukec; Kunka, N.; Awad, A. Kuotb; LaHurd, D.; Latronico, L.; Lauer, R.; Lauscher, M.; Lautridou, P.; Lebrun, D.; Lebrun, P.; Oliveira, M. A. Leigui de; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; Lopes, L.; López, R.; Casado, A. López; Lucero, A.; Malacari, M.; Mallamaci, M.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, V.; Mariş, I. C.; Marsella, G.; Martello, D.; Martinez, H.; Bravo, O. Martínez; Meza, J. J. Masías; Mathes, H. J.; Mathys, S.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mayotte, E.; Mazur, P. O.; Medina, C.; Medina-Tanco, G.; Mello, V. B. B.; Melo, D.; Menshikov, A.; Messina, S.; Micheletti, M. I.; Middendorf, L.; Minaya, I. A.; Miramonti, L.; Mitrica, B.; Molina-Bueno, L.; Mollerach, S.; Montanet, F.; Morello, C.; Mostafá, M.; Moura, C. A.; Müller, G.; Muller, M. A.; Müller, S.; Naranjo, I.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Nguyen, P. H.; Niculescu-Oglinzanu, M.; Niechciol, M.; Niemietz, L.; Niggemann, T.; Nitz, D.; Nosek, D.; Novotny, V.; Nožka, H.; Núñez, L. A.; Ochilo, L.; Oikonomou, F.; Olinto, A.; Pacheco, N.; Selmi-Dei, D. Pakk; Palatka, M.; Pallotta, J.; Papenbreer, P.; Parente, G.; Parra, A.; Paul, T.; Pech, M.; Pękala, J.; Pelayo, R.; Peña-Rodriguez, J.; Pepe, I. M.; Perrone, L.; Petermann, E.; Peters, C.; Petrera, S.; Phuntsok, J.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Porowski, C.; Prado, R. R.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Quinn, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Reinert, D.; Revenu, B.; Ridky, J.; Risse, M.; Ristori, P.; Rizi, V.; Carvalho, W. Rodrigues de; Rojo, J. Rodriguez; Rodríguez-Frías, M. D.; Rogozin, D.; Rosado, J.; Roth, M.; Roulet, E.; Rovero, A. C.; Saffi, S. J.; Saftoiu, A.; Salazar, H.; Saleh, A.; Greus, F. Salesa; Salina, G.; Gomez, J. D. Sanabria; Sánchez, F.; Sanchez-Lucas, P.; Santos, E. M.; Santos, E.; Sarazin, F.; Sarkar, B.; Sarmento, R.; Sarmiento-Cano, C.; Sato, R.; Scarso, C.; Schauer, M.; Scherini, V.; Schieler, H.; Schmidt, D.; Scholten, O.; Schoorlemmer, H.; Schovánek, P.; Schröder, F. G.; Schulz, A.; Schulz, J.; Schumacher, J.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sigl, G.; Sima, O.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sonntag, S.; Sorokin, J.; Squartini, R.; Stanca, D.; Stanič, S.; Stapleton, J.; Stasielak, J.; Stephan, M.; Strafella, F.; Stutz, A.; Suarez, F.; Durán, M. Suarez; Suomijärvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Taborda, O. A.; Tapia, A.; Tepe, A.; Theodoro, V. M.; Timmermans, C.; Peixoto, C. J. Todero; Toma, G.; Tomankova, L.; Tomé, B.; Tonachini, A.; Elipe, G. Torralba; Machado, D. Torres; Travnicek, P.; Trini, M.; Ulrich, R.; Unger, M.; Urban, M.; Galicia, J. F. Valdés; Valiño, I.; Valore, L.; Aar, G. van; Bodegom, P. van; Berg, A. M. van den; Vliet, A. van; Varela, E.; Cárdenas, B. Vargas; Varner, G.; Vasquez, R.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Vorobiov, S.; Wahlberg, H.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Wiencke, L.; Wilczyński, H.; Winchen, T.; Wittkowski, D.; Wundheiler, B.; Wykes, S.; Yang, L.; Yapici, T.; Yushkov, A.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zepeda, A.; Zimmermann, B.; Ziolkowski, M.; Zong, Z.; Collaboration, F. Zuccarello The Telescope Array; Abbasi, R. U.; Abe, M.; Abu-Zayyad, T.; Allen, M.; Azuma, R.; Barcikowski, E.; Belz, J. W.; Bergman, D. R.; Blake, S. A.; Cady, R.; Chae, M. J.; Cheon, B. G.; Chiba, J.; Chikawa, M.; Cho, W. R.; Fujii, T.; Fukushima, M.; Goto, T.; Hanlon, W.; Hayashi, Y.; Hayashida, N.; Hibino, K.; Honda, K.; Ikeda, D.; Inoue, N.; Ishii, T.; Ishimori, R.; Ito, H.; Ivanov, D.; Jui, C. C. H.; Kadota, K.; Kakimoto, F.; Kalashev, O.; Kasahara, K.; Kawai, H.; Kawakami, S.; Kawana, S.; Kawata, K.; Kido, E.; Kim, H. B.; Kim, J. H.; Kim, J. H.; Kitamura, S.; Kitamura, Y.; Kuzmin, V.; Kwon, Y. J.; Lan, J.; Lim, S. I.; Lundquist, J. P.; Machida, K.; Martens, K.; Matsuda, T.; Matsuyama, T.; Matthews, J. N.; Minamino, M.; Mukai, Y.; Myers, I.; Nagasawa, K.; Nagataki, S.; Nakamura, T.; Nonaka, T.; Nozato, A.; Ogio, S.; Ogura, J.; Ohnishi, M.; Ohoka, H.; Oki, K.; Okuda, T.; Ono, M.; Oshima, A.; Ozawa, S.; Park, I. H.; Pshirkov, M. S.; Rodriguez, D. C.; Rubtsov, G.; Ryu, D.; Sagawa, H.; Sakurai, N.; Scott, L. M.; Shah, P. D.; Shibata, F.; Shibata, T.; Shimodaira, H.; Shin, B. K.; Shin, H. S.; Smith, J. D.; Sokolsky, P.; Springer, R. W.; Stokes, B. T.; Stratton, S. R.; Stroman, T. A.; Suzawa, T.; Takamura, M.; Takeda, M.; Takeishi, R.; Taketa, A.; Takita, M.; Tameda, Y.; Tanaka, H.; Tanaka, K.; Tanaka, M.; Thomas, S. B.; Thomson, G. B.; Tinyakov, P.; Tkachev, I.; Tokuno, H.; Tomida, T.; Troitsky, S.; Tsunesada, Y.; Tsutsumi, K.; Uchihori, Y.; Udo, S.; Urban, F.; Vasiloff, G.; Wong, T.; Yamane, R.; Yamaoka, H.; Yamazaki, K.; Yang, J.; Yashiro, K.; Yoneda, Y.; Yoshida, S.; Yoshii, H.; Zollinger, R.; Zundel, Z.

    2015-01-01

    This paper presents the results of different searches for correlations between very high-energy neutrino candidates detected by IceCube and the highest-energy cosmic rays measured by the Pierre Auger Observatory and the Telescope Array. We first consider samples of cascade neutrino events and of

  19. Cannabinoid antagonist in nanostructured lipid carriers (NLCs): design, characterization and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Elisabetta; Ravani, Laura [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Drechsler, Markus [BIMF/Soft Matter Electron Microscopy, University of Bayreuth (Germany); Mariani, Paolo [Department of Life and Environmental Sciences and CNISM, Università Politecnica delle Marche, I-60100 Ancona (Italy); Contado, Catia [Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Ruokolainen, Janne [Department of Applied Physics, Aalto University, 00076 Aalto (Finland); Ratano, Patrizia; Campolongo, Patrizia [Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Roma (Italy); Trezza, Viviana [Department of Science, Roma Tre University, 00146 Roma (Italy); Nastruzzi, Claudio, E-mail: nas@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Cortesi, Rita [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy)

    2015-03-01

    This study describes the preparation, characterization, and in vivo evaluation in rats of nanostructured lipid carriers (NLCs) encapsulating rimonabant (RMN) as prototypical cannabinoid antagonist. A study was conducted in order to optimize NLC production by melt and ultrasonication method. NLCs were prepared by alternatively adding the lipid phase into the aqueous one (direct protocol) or the aqueous phase into the lipid one (reverse protocol). RMN-NLCs have been characterized by cryogenic transmission electron microscopy (cryo-TEM), X-ray, photon correlation spectroscopy (PCS) and sedimentation field flow fractionation (SdFFF). Reverse NLCs were treated with polysorbate 80. RMN release kinetics have been determined in vitro by dialysis method. In vivo RMN biodistribution in rats was evaluated after intranasal (i.n.) administration of reverse RMN-NLC. The reverse protocol enabled to prevent the lost of lipid phase and to achieve higher RMN encapsulation efficacy (EE) with respect to the direct protocol (98% w/w versus 67% w/w). The use of different protocols did not affect NLC morphology and dimensional distribution. An in vitro dissolutive release rate of RMN was calculated. The in vivo data indicate that i.n. administration of RMN by reverse NLC treated with polysorbate 80 increased RMN concentration in the brain with respect to the drug in solution. The nanoencapsulation protocol presented here appears as an optimal strategy to improve the low solubility of cannabinoid compounds in an aqueous system suitable for in vivo administration. - Highlights: • Rimonabant (RMN) can be encapsulated in nanostructured lipid carriers (NLCs). • Nanoencapsulation improves RMN solubility in a stable physiologic aqueous formulation. • RMN is released in vitro from NLC by a controlled dissolutive release modality. • I.n. administration leads to higher RMN concentration in the brain with respect to plasma. • NLC increases RMN concentration in the brain with respect to

  20. Stress and strain provide positional and directional cues in development.

    Directory of Open Access Journals (Sweden)

    Behruz Bozorg

    2014-01-01

    Full Text Available The morphogenesis of organs necessarily involves mechanical interactions and changes in mechanical properties of a tissue. A long standing question is how such changes are directed on a cellular scale while being coordinated at a tissular scale. Growing evidence suggests that mechanical cues are participating in the control of growth and morphogenesis during development. We introduce a mechanical model that represents the deposition of cellulose fibers in primary plant walls. In the model both the degree of material anisotropy and the anisotropy direction are regulated by stress anisotropy. We show that the finite element shell model and the simpler triangular biquadratic springs approach provide equally adequate descriptions of cell mechanics in tissue pressure simulations of the epidermis. In a growing organ, where circumferentially organized fibers act as a main controller of longitudinal growth, we show that the fiber direction can be correlated with both the maximal stress direction and the direction orthogonal to the maximal strain direction. However, when dynamic updates of the fiber direction are introduced, the mechanical stress provides a robust directional cue for the circumferential organization of the fibers, whereas the orthogonal to maximal strain model leads to an unstable situation where the fibers reorient longitudinally. Our investigation of the more complex shape and growth patterns in the shoot apical meristem where new organs are initiated shows that a stress based feedback on fiber directions is capable of reproducing the main features of in vivo cellulose fiber directions, deformations and material properties in different regions of the shoot. In particular, we show that this purely mechanical model can create radially distinct regions such that cells expand slowly and isotropically in the central zone while cells at the periphery expand more quickly and in the radial direction, which is a well established growth pattern

  1. Effects of block copolymer properties on nanocarrier protection from in vivo clearance.

    Science.gov (United States)

    D'Addio, Suzanne M; Saad, Walid; Ansell, Steven M; Squiers, John J; Adamson, Douglas H; Herrera-Alonso, Margarita; Wohl, Adam R; Hoye, Thomas R; Macosko, Christopher W; Mayer, Lawrence D; Vauthier, Christine; Prud'homme, Robert K

    2012-08-20

    Drug nanocarrier clearance by the immune system must be minimized to achieve targeted delivery to pathological tissues. There is considerable interest in finding in vitro tests that can predict in vivo clearance outcomes. In this work, we produce nanocarriers with dense PEG layers resulting from block copolymer-directed assembly during rapid precipitation. Nanocarriers are formed using block copolymers with hydrophobic blocks of polystyrene (PS), poly-ε-caprolactone (PCL), poly-D,L-lactide (PLA), or poly-lactide-co-glycolide (PLGA), and hydrophilic blocks of polyethylene glycol (PEG) with molecular weights from 1 kg/mol to 9 kg/mol. Nanocarriers with paclitaxel prodrugs are evaluated in vivo in Foxn1(nu) mice to determine relative rates of clearance. The amount of nanocarrier in circulation after 4h varies from 10% to 85% of initial dose, depending on the block copolymer. In vitro complement activation assays are conducted to correlate in vivo circulation to the protection of the nanocarrier surface from complement binding and activation. Guidelines for optimizing block copolymer structure to maximize circulation of nanocarriers formed by rapid precipitation and directed assembly are proposed, relating to the relative sizes of the hydrophilic and hydrophobic blocks, the hydrophobicity of the anchoring block, the absolute size of the PEG block, and polymer crystallinity. The in vitro results distinguish between the poorly circulating PEG(5k)-PCL(9 k) and the better circulating nanocarriers, but could not rank the better circulating nanocarriers in order of circulation time. Analysis of PEG surface packing on monodisperse 200 nm latex spheres indicates that the size of the hydrophobic PCL, PS, and PLA blocks are correlated with the PEG blob size. Suggestions for next steps for in vitro measurements are made. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Direct Democracy

    DEFF Research Database (Denmark)

    Beramendi, Virginia; Ellis, Andrew; Kaufman, Bruno

    While many books on direct democracy have a regional or national approach, or simply focus on one of the many mechanisms associated with direct democracy, this Handbook delves into a global comparison of direct democracy mechanisms, including referendums, citizens' initiatives, agenda initiatives...... included as a chapter in the Handbook are possible measures for best practices of implementation, designed for those who wish to tailor direct democracy instruments to their specific needs. In order to further complement the best practices, a variety of global case studies detail the practical uses...... of direct democracy mechanisms in specific contexts. These country case studies allow for in depth discussion of particular issues, including signature collection and voter participation, campaign financing, media coverage, national variations in the usage of direct democracy procedures and national lessons...

  3. In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance

    OpenAIRE

    Mishkovsky, Mor; Comment, Arnaud; Gruetter, Rolf

    2012-01-01

    The Krebs (or tricarboxylic acid (TCA)) cycle has a central role in the regulation of brain energy regulation and metabolism, yet brain TCA cycle intermediates have never been directly detected in vivo. This study reports the first direct in vivo observation of a TCA cycle intermediate in intact brain, namely, 2-oxoglutarate, a key biomolecule connecting metabolism to neuronal activity. Our observation reveals important information about in vivo biochemical processes hitherto considered undet...

  4. In Vivo Bioluminescence Imaging for the Study of Intestinal Colonization by Escherichia coli in Mice▿

    Science.gov (United States)

    Foucault, M.-L.; Thomas, L.; Goussard, S.; Branchini, B. R.; Grillot-Courvalin, C.

    2010-01-01

    Bioluminescence imaging (BLI) is emerging as a powerful tool for real-time monitoring of infections in living animals. However, since luciferases are oxygenases, it has been suggested that the requirement for oxygen may limit the use of BLI in anaerobic environments, such as the lumen of the gut. Strains of Escherichia coli harboring the genes for either the bacterial luciferase from Photorhabdus luminescens or the PpyRE-TS and PpyGR-TS firefly luciferase mutants of Photinus pyralis (red and green thermostable P. pyralis luciferase mutants, respectively) have been engineered and used to monitor intestinal colonization in the streptomycin-treated mouse model. There was excellent correlation between the bioluminescence signal measured in the feces (R2 = 0.98) or transcutaneously in the abdominal region of whole animals (R2 = 0.99) and the CFU counts in the feces of bacteria harboring the luxABCDE operon. Stability in vivo of the bioluminescence signal was achieved by constructing plasmid pAT881(pGB2ΩPamiluxABCDE), which allowed long-term monitoring of intestinal colonization without the need for antibiotic selection for plasmid maintenance. Levels of intestinal colonization by various strains of E. coli could be compared directly by simple recording of the bioluminescence signal in living animals. The difference in spectra of light emission of the PpyRE-TS and PpyGR-TS firefly luciferase mutants and dual bioluminescence detection allowed direct in vitro and in vivo quantification of two bacterial populations by measurement of red and green emitted signals and thus monitoring of the two populations simultaneously. This system offers a simple and direct method to study in vitro and in vivo competition between mutants and the parental strain. BLI is a useful tool to study intestinal colonization. PMID:19880653

  5. In vivo bioluminescence imaging for the study of intestinal colonization by Escherichia coli in mice.

    Science.gov (United States)

    Foucault, M-L; Thomas, L; Goussard, S; Branchini, B R; Grillot-Courvalin, C

    2010-01-01

    Bioluminescence imaging (BLI) is emerging as a powerful tool for real-time monitoring of infections in living animals. However, since luciferases are oxygenases, it has been suggested that the requirement for oxygen may limit the use of BLI in anaerobic environments, such as the lumen of the gut. Strains of Escherichia coli harboring the genes for either the bacterial luciferase from Photorhabdus luminescens or the PpyRE-TS and PpyGR-TS firefly luciferase mutants of Photinus pyralis (red and green thermostable P. pyralis luciferase mutants, respectively) have been engineered and used to monitor intestinal colonization in the streptomycin-treated mouse model. There was excellent correlation between the bioluminescence signal measured in the feces (R2=0.98) or transcutaneously in the abdominal region of whole animals (R2=0.99) and the CFU counts in the feces of bacteria harboring the luxABCDE operon. Stability in vivo of the bioluminescence signal was achieved by constructing plasmid pAT881(pGB2OmegaPamiluxABCDE), which allowed long-term monitoring of intestinal colonization without the need for antibiotic selection for plasmid maintenance. Levels of intestinal colonization by various strains of E. coli could be compared directly by simple recording of the bioluminescence signal in living animals. The difference in spectra of light emission of the PpyRE-TS and PpyGR-TS firefly luciferase mutants and dual bioluminescence detection allowed direct in vitro and in vivo quantification of two bacterial populations by measurement of red and green emitted signals and thus monitoring of the two populations simultaneously. This system offers a simple and direct method to study in vitro and in vivo competition between mutants and the parental strain. BLI is a useful tool to study intestinal colonization.

  6. Experimental investigation of transverse velocity estimation using cross-correlation

    DEFF Research Database (Denmark)

    Bjerngaard, Rasmus; Jensen, Jørgen Arendt

    2001-01-01

    /s. The volume flow was determined by a Danfoss MAG 1100 flow meter. The velocity profiles were measured for different beam-to-flow angles of 90, 65, and 45 degrees. A Harming apodized beam focused at the vessel was transmitted using 64 elements and the received signals on all elements were sampled at 40 MHz......A technique for estimating the full flow velocity vector has previously been presented by our group. Unlike conventional estimators, that only detect the axial component of the flow, this new method is capable of estimating the transverse velocity component. The method uses focusing along the flow...... direction to produce signals that are influenced by the shift of the scatterer's position. The signals are then cross-correllated to find the shift in position and thereby the velocity. The performance of the method is investigated using both a flow phantom and in-vivo measurements. A flow phantom capable...

  7. A human in vivo study of the extent to which 31-phosphorus neurospectroscopy phosphomonoesters index cerebral cell membrane phospholipid anabolism.

    Science.gov (United States)

    Puri, B K; Treasaden, I H

    2009-01-01

    The phosphomonoester narrow resonance of human in vivo 31-phosphorus neurospectroscopy studies is believed to index the anabolism of cell membrane phospholipids and has therefore been used to study phospholipid anabolism in the brain non-invasively. However, it is an indirect measure of phospholipid metabolism and although it does contain major contributions from phosphocholine, phosphoethanolamine and L-phosphoserine, which are important precursors of membrane phospholipids, many other metabolites, including sugar phosphates, can contribute to this region of the spectrum, and separation of these different peaks is not achieved with the present in vivo methodology. Recently, it has become possible to analyze signal directly from the cell membrane motion-restricted phospholipids by analysis of a broad resonance signal. We therefore hypothesized that there should be a positive correlation between the phosphomonoester narrow resonance and the broad resonance signal if the former does indeed index cell membrane phospholipid anabolism. Cerebral 31-phosphorus magnetic resonance spectroscopy was carried out in 54 human subjects, including normal volunteers and patients with schizophrenia in order to widen the range of phosphomonoester and broad resonance values. Spectra were obtained from 70x70x70mm(3) voxels using an image-selected in vivo spectroscopy pulse sequence. There was a highly significant positive correlation between the phosphomonoester resonances and the broad resonance signals (r=0.404, Panabolism in brain studies.

  8. Cardiac biplane strain imaging: initial in vivo experience

    Energy Technology Data Exchange (ETDEWEB)

    Lopata, R G P; Nillesen, M M; Thijssen, J M; De Korte, C L [Clinical Physics Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Verrijp, C N; Lammens, M M Y; Van der Laak, J A W M [Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Singh, S K; Van Wetten, H B [Department of Cardiothoracic Surgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Kapusta, L [Pediatric Cardiology, Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)], E-mail: R.Lopata@cukz.umcn.nl

    2010-02-21

    In this study, first we propose a biplane strain imaging method using a commercial ultrasound system, yielding estimation of the strain in three orthogonal directions. Secondly, an animal model of a child's heart was introduced that is suitable to simulate congenital heart disease and was used to test the method in vivo. The proposed approach can serve as a framework to monitor the development of cardiac hypertrophy and fibrosis. A 2D strain estimation technique using radio frequency (RF) ultrasound data was applied. Biplane image acquisition was performed at a relatively low frame rate (<100 Hz) using a commercial platform with an RF interface. For testing the method in vivo, biplane image sequences of the heart were recorded during the cardiac cycle in four dogs with an aortic stenosis. Initial results reveal the feasibility of measuring large radial, circumferential and longitudinal cumulative strain (up to 70%) at a frame rate of 100 Hz. Mean radial strain curves of a manually segmented region-of-interest in the infero-lateral wall show excellent correlation between the measured strain curves acquired in two perpendicular planes. Furthermore, the results show the feasibility and reproducibility of assessing radial, circumferential and longitudinal strains simultaneously. In this preliminary study, three beagles developed an elevated pressure gradient over the aortic valve ({delta}p: 100-200 mmHg) and myocardial hypertrophy. One dog did not develop any sign of hypertrophy ({delta}p = 20 mmHg). Initial strain (rate) results showed that the maximum strain (rate) decreased with increasing valvular stenosis (-50%), which is in accordance with previous studies. Histological findings corroborated these results and showed an increase in fibrotic tissue for the hearts with larger pressure gradients (100, 200 mmHg), as well as lower strain and strain rate values.

  9. Directing Creativity

    DEFF Research Database (Denmark)

    Darsø, Lotte; Ibbotson, Piers

    2008-01-01

    In this article we argue that leaders facing complex challenges can learn from the arts, specifically that leaders can learn by examining how theatre directors direct creativity through creative constraints. We suggest that perceiving creativity as a boundary phenomenon is helpful for directing it....... Like leaders, who are caught in paradoxical situations where they have to manage production and logistics simultaneously with making space for creativity and innovation, theatre directors need to find the delicate balance between on one hand renewal of perceptions, acting and interaction...... and on the other hand getting ready for the opening night. We conclude that the art of directing creativity is linked to developing competencies of conscious presence, attention and vigilance, whereas the craft of directing creativity concerns communication, framing and choice....

  10. Titanium implant surface modification by cathodic reduction in hydrofluoric acid: surface characterization and in vivo performance.

    Science.gov (United States)

    Lamolle, Sébastien F; Monjo, Marta; Lyngstadaas, Ståle P; Ellingsen, Jan E; Haugen, Håvard J

    2009-03-01

    Etching is used for the surface modification of titanium to improve the implant performance in bone. In this study, pure titanium implants were surface modified by a cathodic reduction process by using hydrofluoric acid (HF) at various concentrations (0.001, 0.01, and 0.1 vol %) and a constant current of 1 mA/cm(2). The resulting surface microtopographies were analyzed by atomic force microscopy, scanning electron microscopy, and profilometry, while the surface chemical contents were evaluated by time of flight secondary ion mass spectrometry. The competitive forces between ionic surface implementation induced by the current direction and the HF etching effect on titanium were highlighted. The implant performance was evaluated in an in vivo rabbit model by using a pull-out test method. The group of implants modified with 0.01% HF showed the highest retention in bone. Fluoride and hydride amounts measured in the surfaces, as well as surface skewness (S(sk)), kurtosis (S(ku)), and core fluid retention (S(ci)) were positively correlated to the implant's retention in bone in vivo. Frequently used parameters for characterizing the implant, such as oxide content and the average height deviation from the mean plane (S(a)), were not correlated to implant performance, suggesting that these parameters are not the most important in predicting the implant performance. (c) 2008 Wiley Periodicals, Inc.

  11. In vivo gluten challenge in coeliac disease

    Directory of Open Access Journals (Sweden)

    HJ Ellis

    2001-01-01

    Full Text Available In vivo gluten challenge has been used since the early 1950s to study the role of cereal fractions in celiac disease. While early studies relied on crude indicators of celiac toxicity, the advent of jejunal biopsy and sophisticated immunohistochemical techniques has allowed accurate studies to be performed. Studies to determine the nature of the cereal component that is toxic to patients with celiac disease have concentrated on wheat because of its nutritional importance. A number of in vitro studies indicated the presence of one or more celiac-activating epitopes with the N-terminus of the A-gliadin molecule. In vivo challenge with three synthetic peptides subsequently indicated the toxicity of a peptide corresponding to amino acids 31 to 49 of A-gliadin. In vivo gluten challenge is the gold standard for the assessment of celiac toxicity; however, jejunal biopsy is a relatively invasive procedure, thus, other methods have been investigated. Direct infusion of the rectum with gluten has been shown to result in an increase in mucosal intraepithelial lymphocytes, occurring only in celiac patients. This method has been used to study the celiac toxicity of gliadin subfractions. The in vitro technique of small intestinal biopsy organ culture is also a useful tool and appears to give the same results as in vivo challenge. The importance of tiny amounts of gliadin in the diet, such as that which occurs in wheat starch, has been studied by in vivo challenge; this technique has clarified the position of oats in the gluten-free diet. Several studies suggest that this cereal may be included in the diet of most adult celiac patients. Studies of the transport of gliadin across the enterocyte following ingestion or challenge suggest that gliadin may be metabolized by a different pathway in celiac disease. This could result in an abnormal presentation to the immune system, triggering a pathogenic rather than a tolerogenic response.

  12. Direct and Indirect Effects of Leptin on Adipocyte Metabolism

    Science.gov (United States)

    Harris, Ruth B.S.

    2013-01-01

    Leptin is hypothesized to function as a negative feedback signal in the regulation of energy balance. It is produced primarily by adipose tissue and circulating concentrations correlate with the size of body fat stores. Administration of exogenous leptin to normal weight, leptin responsive animals inhibits food intake and reduces the size of body fat stores whereas mice that are deficient in either leptin or functional leptin receptors are hyperphagic and obese, consistent with a role for leptin in the control of body weight. This review discusses the effect of leptin on adipocyte metabolism. Because adipocytes express leptin receptors there is the potential for leptin to influence adipocyte metabolism directly. Adipocytes also are insulin responsive and receive sympathetic innervation, therefore leptin can also modify adipocyte metabolism indirectly. Studies published to date suggest that direct activation of adipocyte leptin receptors has little effect on cell metabolism in vivo, but that leptin modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. In vivo administration of leptin leads to a suppression of lipogenesis, an increase in triglyceride hydrolysis and an increase in fatty acid and glucose oxidation. Activation of central leptin receptors also contributes to the development of a catabolic state in adipocytes, but this may vary between different fat depots. Leptin reduces the size of white fat depots by inhibiting cell proliferation both through induction of inhibitory circulating factors and by contributing to sympathetic tone which suppresses adipocyte proliferation. PMID:23685313

  13. In vivo endoscopic multi-beam optical coherence tomography

    Energy Technology Data Exchange (ETDEWEB)

    Standish, Beau A; Mariampillai, Adrian; Munce, Nigel R; Leung, Michael K K; Vitkin, I Alex [Deptartment of Medical Biophysics, University of Toronto, Toronto (Canada); Lee, Kenneth K C; Yang, Victor X D [Ontario Cancer Institute/University Health Network, Toronto (Canada)], E-mail: standish@ee.ryerson.ca

    2010-02-07

    A multichannel optical coherence tomography (multi-beam OCT) system and an in vivo endoscopic imaging probe were developed using a swept-source OCT system. The distal optics were micro-machined to produce a high numerical aperture, multi-focus fibre optic array. This combination resulted in a transverse design resolution of <10 {mu}m full width half maximum (FWHM) throughout the entire imaging range, while also increasing the signal intensity within the focus of the individual channels. The system was used in a pre-clinical rabbit study to acquire in vivo structural images of the colon and ex vivo images of the oesophagus and trachea. A good correlation between the structural multi-beam OCT images and H and E histology was achieved, demonstrating the feasibility of this high-resolution system and its potential for in vivo human endoscopic imaging.

  14. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Joost Smolders

    Full Text Available BACKGROUND: In several autoimmune diseases, including multiple sclerosis (MS, a compromised regulatory T cell (Treg function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS patients. METHODOLOGY/PRINCIPAL FINDINGS: Serum levels of 25-hydroxyvitamin D (25(OHD were measured in 29 RRMS patients. The number of circulating Tregs was assessed by flow-cytometry, and their functionality was tested in vitro in a CFSE-based proliferation suppression assay. Additionally, the intracellular cytokine profile of T helper cells was determined directly ex-vivo by flow-cytometry. Serum levels of 25(OHD correlated positively with the ability of Tregs to suppress T cell proliferation (R = 0.590, P = 0.002. No correlation between 25(OHD levels and the number of Tregs was found. The IFN-gamma/IL-4 ratio (Th1/Th2-balance was more directed towards IL-4 in patients with favourable 25(OHD levels (R = -0.435, P = 0.023. CONCLUSIONS/SIGNIFICANCE: These results show an association of high 25(OHD levels with an improved Treg function, and with skewing of the Th1/Th2 balance towards Th2. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in MS patients. It is tempting to speculate that our results may not only hold for MS, but also for other autoimmune diseases. Future intervention studies will show whether modulation of vitamin D status results in modulation of the T cell response and subsequent amelioration of disease activity.

  15. In-vivo detectability index: development and validation of an automated methodology

    Science.gov (United States)

    Smith, Taylor Brunton; Solomon, Justin; Samei, Ehsan

    2017-03-01

    The purpose of this study was to develop and validate a method to estimate patient-specific detectability indices directly from patients' CT images (i.e., "in vivo"). The method works by automatically extracting noise (NPS) and resolution (MTF) properties from each patient's CT series based on previously validated techniques. Patient images are thresholded into skin-air interfaces to form edge-spread functions, which are further binned, differentiated, and Fourier transformed to form the MTF. The NPS is likewise estimated from uniform areas of the image. These are combined with assumed task functions (reference function: 10 mm disk lesion with contrast of -15 HU) to compute detectability indices for a non-prewhitening matched filter model observer predicting observer performance. The results were compared to those from a previous human detection study on 105 subtle, hypo-attenuating liver lesions, using a two-alternative-forcedchoice (2AFC) method, over 6 dose levels using 16 readers. The in vivo detectability indices estimated for all patient images were compared to binary 2AFC outcomes with a generalized linear mixed-effects statistical model (Probit link function, linear terms only, no interactions, random term for readers). The model showed that the in vivo detectability indices were strongly predictive of 2AFC outcomes (P < 0.05). A linear comparison between the human detection accuracy and model-predicted detection accuracy (for like conditions) resulted in Pearson and Spearman correlations coefficients of 0.86 and 0.87, respectively. These data provide evidence that the in vivo detectability index could potentially be used to automatically estimate and track image quality in a clinical operation.

  16. Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    D Tien Nguyen

    Full Text Available Human respiratory syncytial virus (HRSV and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These

  17. Direct marketing

    Directory of Open Access Journals (Sweden)

    Čičić Muris

    2002-01-01

    Full Text Available Direct Marketing (DM is usually treated as unworthy activity, with actions at the edge of legality and activities minded cheating. Despite obvious problems regarding ethics and privacy threat, DM with its size, importance and role in a concept of integrated marketing communication deserves respect and sufficient analysis and review

  18. Following Directions.

    Science.gov (United States)

    Bolger, Charlene

    Activities in this elementary unit focus on developing students' locational skills while strengthening their ability to read and follow instructions. Seven maps of varying complexity are accompanied by worksheets containing 8 to 13 direction exercises. Students are instructed to place buildings, landmarks, and labels in accurate locations on each…

  19. Nevomelanocytic atypia detection by in vivo reflectance confocal microscopy.

    Science.gov (United States)

    Vaišnorienė, Ingrida; Rotomskis, Ričardas; Kulvietis, Vytautas; Eidukevičius, Rimantas; Zalgevičienė, Violeta; Laurinavičienė, Aida; Venius, Jonas; Didžiapetrienė, Janina

    2014-01-01

    In vivo reflectance confocal microscopy (RCM) is a promising novel technology for non-invasive early diagnostics of cutaneous melanoma. However, the possibility to detect melanocytic atypia in nevi by means of in vivo RCM remains unknown. The aim of the study was to evaluate the significance of in vivo RCM features of melanocytic atypia for the diagnosis of melanocytic nevi, dysplastic nevi and cutaneous melanoma. A total of 138 melanocytic skin lesions comprising 25 melanocytic nevi, 69 dysplastic nevi and 44 melanomas were analyzed by means of dermoscopy, in vivo RCM and routine histopathology. In vivo RCM images were analyzed for the arrangement of keratinocytes in epidermis, pagetoid cells and junctional melanocytic nests and correlated refractivity aspects of nests with histopathology. Separately and all together taken the in vivo RCM features of melanocytic atypia were significant in differential diagnosis of benign and malignant melanocytic skin lesions, though none of the features was significant in discriminating nevi without cytologic atypia of dysplastic nevi. In vivo RCM feature of dense cell clusters corresponded with melanin containing nevomelanocytes on histopathology though exact correspondence of non-homogeneous and atypical sparse cell clusters remained questionable. Nevus with histopathologically confirmed nevomelanocytic atypia (dysplastic nevus) could not be distinguished from nevus without atypia using analyzed in vivo RCM features of melanocytic atypia. More accurate diagnostics by means of in vivo RCM needs further investigation on reflectance of single and nested cutaneous melanocytes in benign and malignant skin lesions. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Selected recent in vivo studies on chemical measurements in invertebrates.

    Science.gov (United States)

    Majdi, S; Ren, L; Fathali, H; Li, X; Ewing, A