WorldWideScience

Sample records for activities leading to information generation

  1. Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21(waf-1).

    Science.gov (United States)

    Chakraborty, Souneek; Rasool, Reyaz Ur; Kumar, Sunil; Nayak, Debasis; Rah, Bilal; Katoch, Archana; Amin, Hina; Ali, Asif; Goswami, Anindya

    2016-06-01

    Stress-induced premature senescence (SIPS) is quite similar to replicative senescence that is committed by cells exposed to various stress conditions viz. ultraviolet radiation (DNA damage), hydrogen peroxide (oxidative stress), chemotherapeutic agents (cytotoxic threat), etc. Here, we report that cristacarpin, a natural product obtained from the stem bark of Erythrina suberosa, promotes endoplasmic reticulum (ER) stress, leading to sub-lethal reactive oxygen species (ROS) generation and which eventually terminates by triggering senescence in pancreatic and breast cancer cells through blocking the cell cycle in the G1 phase. The majority of cristacarpin-treated cells responded to conventional SA-β-gal stains; showed characteristic p21(waf1) upregulation along with enlarged and flattened morphology; and increased volume, granularity, and formation of heterochromatin foci-all of these features are the hallmarks of senescence. Inhibition of ROS generation by N-acetyl-L-cysteine (NAC) significantly reduced the expression of p21(waf1), confirming that the modulation in p21(waf1) by anti-proliferative cristacarpin was ROS dependent. Further, the elevation in p21(waf1) expression in PANC-1 and MCF-7 cells was consistent with the decrease in the expression of Cdk-2 and cyclinD1. Here, we provide evidence that cristacarpin promotes senescence in a p53-independent manner. Moreover, cristacarpin treatment induced p38MAPK, indicating the ROS-dependent activation of the MAP kinase pathway, and thus abrogates the tumor growth in mouse allograft tumor model.

  2. Creating novel activated factor XI inhibitors through fragment based lead generation and structure aided drug design.

    Directory of Open Access Journals (Sweden)

    Ola Fjellström

    Full Text Available Activated factor XI (FXIa inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1'-S2' FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1'-S2' binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC50 of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1'-S2' binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds.

  3. Active Listening Improve Your Ability to Listen and Lead

    CERN Document Server

    (CCL), Center for Creative Leadership

    2011-01-01

    Active listening is a person's willingness and ability to hear and understand. At its core, active listening is a state of mind that involves paying full and careful attention to the other person, avoiding premature judgment, reflecting understanding, clarifying information, summarizing, and sharing. By learning and committing to the skills and behaviors of active listening, leaders can become more effective listeners and, over time, improve their ability to lead.

  4. Distributed patterns of brain activity that lead to forgetting

    OpenAIRE

    Ilke eOztekin; David eBadre

    2011-01-01

    HUMAN NEUROSCIENCE Distributed patterns of brain activity that lead to forgetting Ilke Öztekin1* and David Badre2,3 1 Department of Psychology, Koç University, Istanbul, Turkey 2 Department of Cognitive, Linguistic and Psychological Sciences, Brown University, Providence, RI, USA 3 Brown Institute for Brain Sciences, Brown University, Providence, RI, USA Proactive interference (PI), in which irrelevant information from prior learning disrupts memory performance, is widely...

  5. Stem Cells from Human Exfoliated Deciduous Tooth Exhibit Stromal-Derived Inducing Activity and Lead to Generation of Neural Crest Cells from Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Khadijeh Karbalaie

    2015-04-01

    Full Text Available Objective: The neural crest is a transient structure of early vertebrate embryos that generates neural crest cells (NCCs. These cells can migrate throughout the body and produce a diverse array of mature tissue types. Due to the ethical and technical problems surrounding the isolation of these early human embryo cells, researchers have focused on in vitro studies to produce NCCs and increase their knowledge of neural crest development. Materials and Methods: In this experimental study, we cultured human embryonic stem cells (hESCs on stromal stem cells from human exfoliated deciduous teeth (SHED for a two-week period. We used different approaches to characterize these differentiated cells as neural precursor cells (NPCs and NCCs. Results: In the first co-culture week, hESCs appeared as crater-like structures with marginal rosettes. NPCs derived from these structures expressed the early neural crest marker p75 in addition to numerous other genes associated with neural crest induction such as SNAIL, SLUG, PTX3 and SOX9. Flow cytometry analysis showed 70% of the cells were AP2/P75 positive. Moreover, the cells were able to self-renew, sustain multipotent differentiation potential, and readily form neurospheres in suspension culture. Conclusion: SHED, as an adult stem cell with a neural crest origin, has stromal-derived inducing activity (SDIA and can be used as an NCC inducer from hESCs. These cells provide an invaluable resource to study neural crest differentiation in both normal and disordered human neural crest development.

  6. Use of the Generating Options for Active Risk Control (GO-ARC) Technique Can Lead to More Robust Risk Control Options

    OpenAIRE

    Card, Alan J; Simsekler, Mecit Can Emre; Clark, Michael; Ward, James R.; Clarkson, P. John

    2014-01-01

    This is the author's accepted manuscript. The final version has been published in International Journal of Risk & Safety in Medicine at http://dx.doi.org/10.3233/JRS-140636 BACKGROUND: Risk assessment is widely used to improve patient safety, but healthcare workers are not trained to design robust solutions to the risks they uncover. This leads to an overreliance on the weakest category of risk control recommendations: administrative controls. Increasing the proportion of non-administrativ...

  7. Synergistic anticandidal activity of pure polyphenol curcumin I in combination with azoles and polyenes generates reactive oxygen species leading to apoptosis.

    Science.gov (United States)

    Sharma, Monika; Manoharlal, Raman; Negi, Arvind Singh; Prasad, Rajendra

    2010-08-01

    We have shown previously that pure polyphenol curcumin I (CUR-I) shows antifungal activity against Candida species. By employing the chequerboard method, filter disc and time-kill assays, in the present study we demonstrate that CUR-I at non-antifungal concentration interacts synergistically with azoles and polyenes. For this, pure polyphenol CUR-I was tested for synergy with five azole and two polyene drugs - fluconazole (FLC), miconazole, ketoconazole (KTC), itraconazole (ITR), voriconazole (VRC), nystatin (NYS) and amphotericin B (AMB) - against 21 clinical isolates of Candida albicans with reduced antifungal sensitivity, as well as a drug-sensitive laboratory strain. Notably, there was a 10-35-fold drop in the MIC(80) values of the drugs when CUR-I was used in combination with azoles and polyenes, with fractional inhibitory concentration index (FICI) values ranging between 0.09 and 0.5. Interestingly, the synergistic effect of CUR-I with FLC and AMB was associated with the accumulation of reactive oxygen species, which could be reversed by the addition of an antioxidant such as ascorbic acid. Furthermore, the combination of CUR-I and FLC/AMB triggered apoptosis that could also be reversed by ascorbic acid. We provide the first evidence that pure CUR-I in combination with azoles and polyenes represents a novel therapeutic strategy to improve the activity of common antifungals.

  8. A Simplified 3D Model of Whole Heart Electrical Activity and 12-Lead ECG Generation

    Directory of Open Access Journals (Sweden)

    Siniša Sovilj

    2013-01-01

    Full Text Available We present a computationally efficient three-dimensional bidomain model of torso-embedded whole heart electrical activity, with spontaneous initiation of activation in the sinoatrial node, incorporating a specialized conduction system with heterogeneous action potential morphologies throughout the heart. The simplified geometry incorporates the whole heart as a volume source, with heart cavities, lungs, and torso as passive volume conductors. We placed four surface electrodes at the limbs of the torso: , , and and six electrodes on the chest to simulate the Einthoven, Goldberger-augmented and precordial leads of a standard 12-lead system. By placing additional seven electrodes at the appropriate torso positions, we were also able to calculate the vectorcardiogram of the Frank lead system. Themodel was able to simulate realistic electrocardiogram (ECG morphologies for the 12 standard leads, orthogonal , , and leads, as well as the vectorcardiogram under normal and pathological heart states. Thus, simplified and easy replicable 3D cardiac bidomain model offers a compromise between computational load and model complexity and can be used as an investigative tool to adjust cell, tissue, and whole heart properties, such as setting ischemic lesions or regions of myocardial infarction, to readily investigate their effects on whole ECG morphology.

  9. Generating and reversing spin accumulation by temperature gradient in a quantum dot attached to ferromagnetic leads

    Institute of Scientific and Technical Information of China (English)

    Bai Xu-Fang; Chi Feng; Zheng Jun; Li Yi-Nan

    2012-01-01

    We propose to generate and reverse the spin accumulation in a quantum dot (QD) by using the temperature difference between the two ferromagnetic leads connected to the dot.The electrons are driven purely by the temperature gradient in the absence of an electric bias and a magnetic field.In the Coulomb blockade regime,we find two ways to reverse the spin accumulation.One is by adjusting the QD energy level with a fixed temperature gradient,and the other is by reversing the temperature gradient direction for a fixed value of the dot level.The spin accumulation in the QD can be enhanced by the magnitudes of both the leads' spin polarization and the asymmetry of the dot-lead coupling strengths.The present device is quite simple,and the obtained results may have practical usage in spintronics or quantum information processing.

  10. Leading Generation Y

    Science.gov (United States)

    Coley, David C.

    2009-01-01

    School administrators are facing the perfect storm: a growing number of baby boomers retiring each year, an absence of experienced teachers to take their place, and high turnover among young teachers. The need to hire and retain a new generation of teachers is one of the biggest challenges facing school administrators. To fill these vacancies,…

  11. Leading Generation Y

    Science.gov (United States)

    2008-04-01

    ensure the success of their child, failure is not often experienced. These successes and the ease of childhood lead to not only confidence but an...Messaging, chatting on the cell phone and working on homework is a common place scene for teens and college students. “The level of multiprocessing...to Gen Yers entering the workforce with unrealistic expectations and a sense of entitlement. Barbara Dwyer, CEO of the Job Journey, states that

  12. Who Avoids Cancer Information? Examining a Psychological Process Leading to Cancer Information Avoidance.

    Science.gov (United States)

    Chae, Jiyoung

    2016-07-01

    Although cancer information avoidance (CIA) is detrimental to public health, predictors of CIA have not been fully investigated. Based on uncertainty management theory, this study viewed CIA as a response to uncertainty related to the distress associated with cancer information and illustrated the psychological process leading to CIA. Given the current information context, it was hypothesized that cancer information overload (CIO), accompanied by confusion and stress about cancer information, causes CIA. As trait anxiety is a strong predictor of CIO, it was also hypothesized that trait anxiety has an indirect effect on CIA through CIO. Study 1 tested this relationship in a U.S. sample (N = 384); the results showed that CIO was positively associated with CIA and that trait anxiety indirectly influenced CIA through CIO. Whereas Study 1 tested the relationship with cross-sectional data in the general cancer context, Study 2 replicated Study 1 with 3-wave longitudinal data in the context of a specific cancer (i.e., stomach cancer) in South Korea (N = 1,130 at Wave 1, 813 at Wave 2, and 582 at Wave 3). Trait anxiety at Wave 1 predicted CIO at Wave 2, which in turn increased CIA at Wave 3, suggesting that some people are inherently inclined to avoid cancer information due to their trait anxiety, which results in confusion about cancer information.

  13. QCD event generators with next-to-leading order matrix-elements and parton showers

    CERN Document Server

    Kurihara, Y; Ishikawa, T; Kato, K; Kawabata, S; Munehisa, T; Tanaka, H

    2003-01-01

    A new method to construct event-generators based on next-to-leading order QCD matrix-elements and leading-logarithmic parton showers is proposed. Matrix elements of loop diagram as well as those of a tree level can be generated using an automatic system. A soft/collinear singularity is treated using a leading-log subtraction method. Higher order re-summation of the soft/collinear correction by the parton shower method is combined with the NLO matrix-element without any double-counting in this method. An example of the event generator for Drell-Yan process is given for demonstrating a validity of this method.

  14. Lead generation in crop protection research: a portfolio approach to agrochemical discovery.

    Science.gov (United States)

    Loso, Michael R; Garizi, Negar; Hegde, Vidyadhar B; Hunter, James E; Sparks, Thomas C

    2017-04-01

    The need for increased food and feed supply to support future global demand with the added challenges of resistance pressure and an evolving regulatory environment necessitates the discovery of new crop protection agents for growers of today and tomorrow. Lead generation is the critical 'engine' for maintaining a robust pipeline of new high-value products. A wide variety of approaches exist for the generation of new leads, many of which have demonstrated success. Each approach features some degree of merit or benefit while also having some inherent drawback or level of risk. While risk for any single approach can be mitigated in a variety of different ways depending on the approach, long-term viability of a successful lead generation program merits utilization of a portfolio of different approaches and methodologies for the generation of new leads. © 2016 Society of Chemical Industry.

  15. Why business credit information sharing leads to better lending decisions

    NARCIS (Netherlands)

    L. Norden (Lars)

    2014-01-01

    markdownabstract__Abstract__ Bad loans are made in boom times. Good loans are made in recessionary times. Lenders such as suppliers who provide trade credit or banks would be well advised to remember this simple dictum whenever they are approached for credit by a borrower not entirely familiar to t

  16. Activity-based analyses lead to better decision making.

    Science.gov (United States)

    Player, S

    1998-08-01

    Activity-based costing (ABC) and activity-based management (ABM) are cost-management tools that are relatively new to the healthcare industry. ABC is used for strategic decision making. It assesses the costs associated with specific activities and resources and links those costs to specific internal and external customers of the healthcare enterprise (e.g., patients, service lines, and physician groups) to determine the costs associated with each customer. This cost information then can be adjusted to account for anticipated changes and to predict future costs. ABM, on the other hand, supports operations by focusing on the causes of costs and how costs can be reduced. It assesses cost drivers that directly affect the cost of a product or service, and uses performance measures to evaluate the financial or nonfinancial benefit an activity provides. By identifying each cost driver and assessing the value the element adds to the healthcare enterprise, ABM provides a basis for selecting areas that can be changed to reduce costs.

  17. Target engagement in lead generation.

    Science.gov (United States)

    Durham, Timothy B; Blanco, Maria-Jesus

    2015-03-01

    The pharmaceutical industry is currently facing multiple challenges, in particular the low number of new drug approvals in spite of the high level of R&D investment. In order to improve target selection and assess properly the clinical hypothesis, it is important to start building an integrated drug discovery approach during Lead Generation. This should include special emphasis on evaluating target engagement in the target tissue and linking preclinical to clinical readouts. In this review, we would like to illustrate several strategies and technologies for assessing target engagement and the value of its application to medicinal chemistry efforts.

  18. Using a geographic information system to improve childhood lead-screening efforts.

    Science.gov (United States)

    Graff, Robert

    2013-06-13

    The Idaho Division of Public Health conducted a pilot study to produce a lead-exposure-risk map to help local and state agencies better target childhood lead-screening efforts. Priority lead-screening areas, at the block group level, were created by using county tax assessor data and geographic information system software. A series of maps were produced, indicating childhood lead-screening prevalence in areas in which there was high potential for exposure to lead. These maps could enable development of more systematically targeted and cost-effective childhood lead-screening efforts.

  19. Red light generation through the lead boro-telluro-phosphate glasses activated by Eu3+ ions

    Science.gov (United States)

    Selvi, S.; Marimuthu, K.; Suriya Murthy, N.; Muralidharan, G.

    2016-09-01

    Lead boro-telluro-phosphate glasses containing 0.05 to 2.0 wt% of Eu3+ ions were prepared through melt quenching technique. Structural characteristics of title glasses were identified through XRD, FTIR and Raman studies. The optical properties of the prepared glasses were studied using UV-Vis-NIR absorption and photoluminescence spectra. From the resultant spectra, we have obtained the bonding parameters (δ), nephelauxetic ratio (β), direct and indirect band gaps and Urbach energy (ΔE) values. A deep red luminescence due to 5D0 → 7F2 transition of Eu3+ ions could be observed for the title glasses. The local site symmetry around the Eu3+ ions and the degree of Eu3+-O2- covalence were assessed from the luminescence intensity ratio of 5D0 → 7F2/5D0 → 7F1 transitions. Judd-Ofelt intensity parameters, calculated from the luminescence spectra, were used to estimate the radiative parameters like transition probability (A), branching ratio (βexp, βcal) and stimulated emission cross-section (σPE) concerning the 5D0 → 7FJ (J = 0, 1, 2, 3 and 4) transitions. The important laser parameters, gain bandwidth and optical gain are also estimated. The decay curves associated with the transition from 5D0 state was found to be single-exponential at all Eu3+ ion concentrations. CIE colour coordinates and colour purity of the prepared glasses were estimated from the CIE chromaticity diagram.

  20. Oxysterol generation and liver X receptor-dependent reverse cholesterol transport: not all roads lead to Rome.

    Science.gov (United States)

    Pannu, Parveer S; Allahverdian, Sima; Francis, Gordon A

    2013-04-10

    Cell cholesterol metabolism is a tightly regulated process, dependent in part on activation of nuclear liver X receptors (LXRs) to increase expression of genes mediating removal of excess cholesterol from cells in the reverse cholesterol transport pathway. LXRs are thought to be activated predominantly by oxysterols generated enzymatically from cholesterol in different cell organelles. Defects resulting in slowed release of cholesterol from late endosomes and lysosomes or reduction in sterol-27-hydroxylase activity lead to specific blocks in oxysterol production and impaired LXR-dependent gene activation. This block does not appear to be compensated by oxysterol production in other cell compartments. The purpose of this review is to summarize current knowledge about oxysterol-dependent activation by LXR of genes involved in reverse cholesterol transport, and what these defects of cell cholesterol homeostasis can teach us about the critical pathways of oxysterol generation for expression of LXR-dependent genes.

  1. Event generation for next to leading order chargino production at the international linear collider

    Energy Technology Data Exchange (ETDEWEB)

    Robens, T.

    2006-10-15

    At the International Linear Collider (ILC), parameters of supersymmetry (SUSY) can be determined with an experimental accuracy matching the precision of next-to-leading order (NLO) and higher-order theoretical predictions. Therefore, these contributions need to be included in the analysis of the parameters. We present a Monte-Carlo event generator for simulating chargino pair production at the ILC at next-to-leading order in the electroweak couplings. We consider two approaches of including photon radiation. A strict fixed-order approach allows for comparison and consistency checks with published semianalytic results in the literature. A version with soft- and hard-collinear resummation of photon radiation, which combines photon resummation with the inclusion of the NLO matrix element for the production process, avoids negative event weights, so the program can simulate physical (unweighted) event samples. Photons are explicitly generated throughout the range where they can be experimentally resolved. In addition, it includes further higher-order corrections unaccounted for by the fixed-order method. Inspecting the dependence on the cutoffs separating the soft and collinear regions, we evaluate the systematic errors due to soft and collinear approximations for NLO and higher-order contributions. In the resummation approach, the residual uncertainty can be brought down to the per-mil level, coinciding with the expected statistical uncertainty at the ILC. We closely investigate the two-photon phase space for the resummation method. We present results for cross sections and event generation for both approaches. (orig.)

  2. Differential MSC activation leads to distinct mononuclear leukocyte binding mechanisms

    Science.gov (United States)

    Kota, Daniel J.; Dicarlo, Bryan; Hetz, Robert A.; Smith, Philippa; Cox, Charles S.; Olson, Scott D.

    2014-04-01

    Advances in the field of Multipotent Mesenchymal Stromal cell (MSC) biology have demonstrated that MSCs can improve disease outcome when `activated' to exert immunomodulatory effects. However, the precise mechanisms modulating MSC-immune cells interactions remain largely elusive. In here, we activated MSC based on a recent polarization paradigm, in which MSCs can be polarized towards a pro- or anti-inflammatory phenotype depending on the Toll-like receptor stimulated, to dissect the mechanisms through which MSCs physically interact with and modulate leukocytes in this context. Our data show that MSCs activated through the Toll-like receptor (TLR) 4 pathway increased VCAM-1 and ICAM-1 dependent binding of leukocytes. On the other hand, TLR3 stimulation strongly increases leukocytes affinity to MSC comparatively, through the formation of cable-like hyaluronic acid structures. In addition, TLR4 activation elicited secretion of pro-inflammatory mediators by MSCs, whereas TLR3-activated MSCs displayed a milder pro-inflammatory phenotype, similar to inactivated MSCs. However, the differently activated MSCs maintained their ability to suppress leukocyte activation at similar levels in our in vitro model, and this immunomodulatory property was shown here to be partially mediated by prostaglandin. These results reinforce the concept that alternate activation profiles control MSC responses and may impact the therapeutic use of MSCs.

  3. Information Transfer between Generations Linked to Biodiversity in Rock-Paper-Scissors Games

    Directory of Open Access Journals (Sweden)

    Ranjan Bose

    2015-01-01

    Full Text Available Ecological processes, such as reproduction, mobility, and interaction between species, play important roles in the maintenance of biodiversity. Classically, the cyclic dominance of species has been modelled using the nonhierarchical interactions among competing species, represented by the “Rock-Paper-Scissors” (RPS game. Here we propose a cascaded channel model for analyzing the existence of biodiversity in the RPS game. The transition between successive generations is modelled as communication of information over a noisy communication channel. The rate of transfer of information over successive generations is studied using mutual information and it is found that “greedy” information transfer between successive generations may lead to conditions for extinction. This generalized framework can be used to study biodiversity in any number of interacting species, ecosystems with unequal rates for different species, and also competitive networks.

  4. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets

    NARCIS (Netherlands)

    Tunjungputri, Rahajeng N.; De Jonge, Marien I.; De Greeff, Astrid; Van Selm, Saskia; Buys, Herma; Harders-Westerveen, Jose F.; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T.; de Groot, Phillip G.; Smith, Hilde E.; Van Der Ven, Andre J.; De Mast, Quirijn

    2016-01-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection.

  5. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets

    NARCIS (Netherlands)

    Tunjungputri, Rahajeng N.; Jonge, de Marien I.; Greeff, de Astrid; Selm, van Saskia; Buys-Bergen, Herma; Harders-Westerveen, Jose F.; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T.; Groot, De Phillip G.; Smith, Hilde E.; Ven, van der Andre J.; Mast, de Quirijn

    2016-01-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection.

  6. Fundamental Activity Constraints Lead to Specific Interpretations of the Connectome

    Science.gov (United States)

    van Albada, Sacha J.; Diesmann, Markus; Helias, Moritz

    2017-01-01

    The continuous integration of experimental data into coherent models of the brain is an increasing challenge of modern neuroscience. Such models provide a bridge between structure and activity, and identify the mechanisms giving rise to experimental observations. Nevertheless, structurally realistic network models of spiking neurons are necessarily underconstrained even if experimental data on brain connectivity are incorporated to the best of our knowledge. Guided by physiological observations, any model must therefore explore the parameter ranges within the uncertainty of the data. Based on simulation results alone, however, the mechanisms underlying stable and physiologically realistic activity often remain obscure. We here employ a mean-field reduction of the dynamics, which allows us to include activity constraints into the process of model construction. We shape the phase space of a multi-scale network model of the vision-related areas of macaque cortex by systematically refining its connectivity. Fundamental constraints on the activity, i.e., prohibiting quiescence and requiring global stability, prove sufficient to obtain realistic layer- and area-specific activity. Only small adaptations of the structure are required, showing that the network operates close to an instability. The procedure identifies components of the network critical to its collective dynamics and creates hypotheses for structural data and future experiments. The method can be applied to networks involving any neuron model with a known gain function. PMID:28146554

  7. Access to Government-Generated Information: Current Issues and Implications.

    Science.gov (United States)

    Williamson, Linda E.

    1987-01-01

    Reviews both historical and current policies for access to government information, and discusses such current trends in government information as paperwork reduction, commercialization, privatization, and electronic publishing. The possible impact of these trends on the library's ability to provide access to information is briefly considered. (CLB)

  8. WAX ActiveLibrary: a tool to manage information overload.

    Science.gov (United States)

    Hanka, R; O'Brien, C; Heathfield, H; Buchan, I E

    1999-11-01

    WAX Active-Library (Cambridge Centre for Clinical Informatics) is a knowledge management system that seeks to support doctors' decision making through the provision of electronic books containing a wide range of clinical knowledge and locally based information. WAX has been piloted in several regions in the United Kingdom and formally evaluated in 17 GP surgeries based in Cambridgeshire. The evaluation has provided evidence that WAX Active-Library significantly improves GPs' access to relevant information sources and by increasing appropriate patient management and referrals this might also lead to an improvement in clinical outcomes.

  9. Bimodal regime in young massive clusters leading to subsequent stellar generations

    CERN Document Server

    Wünsch, Richard; Tenorio-Tagle, Guillermo; Muñoz-Tuñón, Casiana; Ehlerová, Soňa

    2016-01-01

    Massive stars in young massive clusters insert tremendous amounts of mass and energy into their surroundings in the form of stellar winds and supernova ejecta. Mutual shock-shock collisions lead to formation of hot gas, filling the volume of the cluster. The pressure of this gas then drives a powerful cluster wind. However, it has been shown that if the cluster is massive and dense enough, it can evolve in the so--called bimodal regime, in which the hot gas inside the cluster becomes thermally unstable and forms dense clumps which are trapped inside the cluster by its gravity. We will review works on the bimodal regime and discuss the implications for the formation of subsequent stellar generations. The mass accumulates inside the cluster and as soon as a high enough column density is reached, the interior of the clumps becomes self-shielded against the ionising radiation of stars and the clumps collapse and form new stars. The second stellar generation will be enriched by products of stellar evolution from t...

  10. Meditation leads to reduced default mode network activity beyond an active task.

    Science.gov (United States)

    Garrison, Kathleen A; Zeffiro, Thomas A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2015-09-01

    Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.

  11. Information-theoretic approach to lead-lag effect on financial markets

    Science.gov (United States)

    Fiedor, Paweł

    2014-08-01

    Recently the interest of researchers has shifted from the analysis of synchronous relationships of financial instruments to the analysis of more meaningful asynchronous relationships. Both types of analysis are concentrated mostly on Pearson's correlation coefficient and consequently intraday lead-lag relationships (where one of the variables in a pair is time-lagged) are also associated with them. Under the Efficient-Market Hypothesis such relationships are not possible as all information is embedded in the prices, but in real markets we find such dependencies. In this paper we analyse lead-lag relationships of financial instruments and extend known methodology by using mutual information instead of Pearson's correlation coefficient. Mutual information is not only a more general measure, sensitive to non-linear dependencies, but also can lead to a simpler procedure of statistical validation of links between financial instruments. We analyse lagged relationships using New York Stock Exchange 100 data not only on an intraday level, but also for daily stock returns, which have usually been ignored.

  12. Next generation information systems

    Energy Technology Data Exchange (ETDEWEB)

    Limback, Nathan P [Los Alamos National Laboratory; Medina, Melanie A [Los Alamos National Laboratory; Silva, Michelle E [Los Alamos National Laboratory

    2010-01-01

    The Information Systems Analysis and Development (ISAD) Team of the Safeguards Systems Group at Los Alamos National Laboratory (LANL) has been developing web based information and knowledge management systems for sixteen years. Our vision is to rapidly and cost effectively provide knowledge management solutions in the form of interactive information systems that help customers organize, archive, post and retrieve nonproliferation and safeguards knowledge and information vital to their success. The team has developed several comprehensive information systems that assist users in the betterment and growth of their organizations and programs. Through our information systems, users are able to streamline operations, increase productivity, and share and access information from diverse geographic locations. The ISAD team is also producing interactive visual models. Interactive visual models provide many benefits to customers beyond the scope of traditional full-scale modeling. We have the ability to simulate a vision that a customer may propose, without the time constraints of traditional engineering modeling tools. Our interactive visual models can be used to access specialized training areas, controlled areas, and highly radioactive areas, as well as review site-specific training for complex facilities, and asset management. Like the information systems that the ISAD team develops, these models can be shared and accessed from any location with access to the internet. The purpose of this paper is to elaborate on the capabilities of information systems and interactive visual models as well as consider the possibility of combining the two capabilities to provide the next generation of infonnation systems. The collection, processing, and integration of data in new ways can contribute to the security of the nation by providing indicators and information for timely action to decrease the traditional and new nuclear threats. Modeling and simulation tied to comprehensive

  13. Impaired dendritic inhibition leads to epileptic activity in a computer model of CA3.

    Science.gov (United States)

    Sanjay, M; Neymotin, Samuel A; Krothapalli, Srinivasa B

    2015-11-01

    Temporal lobe epilepsy (TLE) is a common type of epilepsy with hippocampus as the usual site of origin. The CA3 subfield of hippocampus is reported to have a low epileptic threshold and hence initiates the disorder in patients with TLE. This study computationally investigates how impaired dendritic inhibition of pyramidal cells in the vulnerable CA3 subfield leads to generation of epileptic activity. A model of CA3 subfield consisting of 800 pyramidal cells, 200 basket cells (BC) and 200 Oriens-Lacunosum Moleculare (O-LM) interneurons was used. The dendritic inhibition provided by O-LM interneurons is reported to be selectively impaired in some TLEs. A step-wise approach is taken to investigate how alterations in network connectivity lead to generation of epileptic patterns. Initially, dendritic inhibition alone was reduced, followed by an increase in the external inputs received at the distal dendrites of pyramidal cells, and finally additional changes were made at the synapses between all neurons in the network. In the first case, when the dendritic inhibition of pyramidal cells alone was reduced, the local field potential activity changed from a theta-modulated gamma pattern to a prominently gamma frequency pattern. In the second case, in addition to this reduction of dendritic inhibition, with a simultaneous large increase in the external excitatory inputs received by pyramidal cells, the basket cells entered a state of depolarization block, causing the network to generate a typical ictal activity pattern. In the third case, when the dendritic inhibition onto the pyramidal cells was reduced and changes were simultaneously made in synaptic connectivity between all neurons in the network, the basket cells were again observed to enter depolarization block. In the third case, impairment of dendritic inhibition required to generate an ictal activity pattern was lesser than the two previous cases. Moreover, the ictal like activity began earlier in the third case

  14. Pyrolysis of cellulose under ammonia leads to nitrogen-doped nanoporous carbon generated through methane formation.

    Science.gov (United States)

    Luo, Wei; Wang, Bao; Heron, Christopher G; Allen, Marshall J; Morre, Jeff; Maier, Claudia S; Stickle, William F; Ji, Xiulei

    2014-01-01

    Here, we present a simple one-step fabrication methodology for nitrogen-doped (N-doped) nanoporous carbon membranes via annealing cellulose filter paper under NH3. We found that nitrogen doping (up to 10.3 at %) occurs during cellulose pyrolysis under NH3 at as low as 550 °C. At 700 °C or above, N-doped carbon further reacts with NH3, resulting in a large surface area (up to 1973.3 m(2)/g). We discovered that the doped nitrogen, in fact, plays an important role in the reaction, leading to carbon gasification. CH4 was experimentally detected by mass spectrometry as a product in the reaction between N-doped carbon and NH3. When compared to conventional activated carbon (1533.6 m(2)/g), the N-doped nanoporous carbon (1326.5 m(2)/g) exhibits more than double the unit area capacitance (90 vs 41 mF/m(2)).

  15. Active acoustic leak detection for LMFBR steam generators. Pt. 6. Applicability to practical steam generators

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Kazuo; Kumagai, Hiromichi; Kinoshita, Izumi [Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.

    1998-03-01

    It is necessary to develop a reliable water leak detection system for steam generators of liquid metal reactors in order to prevent the expansion of damage and to maintain the structural integrity of the steam generators. The concept of the active acoustic method is to detect the change of the ultrasonic field due to the hydrogen gas bubbles generated by a sodium-water reaction. This method has the potential for improved detection performance compared with conventional passive methods, from the viewpoint of sensitivity, response time and tolerance against the background noise. A feasibility study of the active acoustic leak detection system is being carried out. This report predicts the performance of the active acoustic method in the practical steam generators from the results of the large scale in-water experiments. The results shows that the active acoustic system can detect a 10 g/s leak within a few seconds in large-scale steam generators. (author)

  16. Research on applying physical chaos generator to spacecraft information security

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The effectiveness of a short-length message extension method based on physical chaos generator was analyzed and the entropy of the extended message was calculated in this paper.The analysis demon-strated that with the mentioned method the entropy of short-length messages,which are repeatedly used in spacecraft data systems,is obviously increased,and the security of transmission is enhanced as well.This paper also presented an improvement of the protocol for secret key agreement presented by M.J.Gander and U.M.Maurer.Instead of depending on characteristics of communication channel,this method takes advantage of the random data produced by physical chaos generator to preset the initial parameters of the procedure on both sides of communication,so that the procedure and quantity of cipher key can be precisely controlled.This method can be used to cipher key management of se-cure communication between long life-span spacecraft and ground system.

  17. Research on applying physical chaos generator to spacecraft information security

    Institute of Scientific and Technical Information of China (English)

    ZHAO HePing

    2009-01-01

    Academy of Space Technology, Beijing 100094, China (small: zhpcast@ hotmail.com) The effectiveness of a short-length message extension method based on physical chaos generator was analyzed and the entropy of the extended message was calculated in this paper. The analysis demon-strated that with the mentioned method the entropy of short-length messages, which are repeatedly used in spacecraft data systems, is obviously increased, and the security of transmission is enhanced as well. This paper also presented an improvement of the protocol for secret key agreement presented by M. J. Gander and U. M. Maurer. Instead of depending on characteristics of communication channel,this method takes advantage of the random data produced by physical chaos generator to preset the initial parameters of the procedure on both sides of communication, so that the procedure and quantity of cipher key can be precisely controlled. This method can be used to cipher key management of se-cure communication between long life-span spacecraft and ground system.

  18. Amiet theory extension to predict leading-edge generated noise in compact airfoils

    NARCIS (Netherlands)

    De Santana, L.D.; Schram, C.

    2015-01-01

    This paper extends the Amiet theory to frequencies where the airfoil can be considered a compact noise source. The original Amiet theory proposes to apply the Schwarzschild theorem in an iterative procedure, which generally leads to noise over-prediction at low-frequencies. To overcome this problem,

  19. Cutting Off Access to Government Information: Loopholes in the Access to Information Act Generated by the Information Highway.

    Science.gov (United States)

    Macaulay, Tyson

    1997-01-01

    In Canada, public access to federal government information is ruled by the Access to Information Act. This article explores loopholes in the Act, issues of data format and "tradeable" data (government information with substantial value), that could cause a conflict between its intent and effect. Tradeable data is troublesome because of…

  20. Innovated application of mechanical activation to separate lead from scrap cathode ray tube funnel glass.

    Science.gov (United States)

    Yuan, Wenyi; Li, Jinhui; Zhang, Qiwu; Saito, Fumio

    2012-04-03

    The disposal of scrap cathode ray tube (CRT) funnel glass has become a global environmental problem due to the rapid shrinkage of new CRT monitor demand, which greatly reduces the reuse for remanufacturing. To detoxificate CRT funnel glass by lead recovery with traditional metallurgical methods, mechanical activation by ball milling was introduced to pretreat the funnel glass. As a result, substantial physicochemical changes have been observed after mechanical activation including chemical breakage and defects formation in glass inner structure. These changes contribute to the easy dissolution of the activated sample in solution. High yield of 92.5% of lead from activated CRT funnel glass by diluted nitric acid leaching and successful formation of lead sulfide by sulfur sulfidization in water have also been achieved. All the results indicate that the application of mechanical activation on recovering lead from CRT funnel glass is efficient and promising, which is also probably appropriate to detoxificate any other kind of leaded glass.

  1. Lead generation using pharmacophore mapping and three-dimensional database searching: application to muscarinic M(3) receptor antagonists.

    Science.gov (United States)

    Marriott, D P; Dougall, I G; Meghani, P; Liu, Y J; Flower, D R

    1999-08-26

    By using a pharmacophore model, a geometrical representation of the features necessary for molecules to show a particular biological activity, it is possible to search databases containing the 3D structures of molecules and identify novel compounds which may possess this activity. We describe our experiences of establishing a working 3D database system and its use in rational drug design. By using muscarinic M(3) receptor antagonists as an example, we show that it is possible to identify potent novel lead compounds using this approach. Pharmacophore generation based on the structures of known M(3) receptor antagonists, 3D database searching, and medium-throughput screening were used to identify candidate compounds. Three compounds were chosen to define the pharmacophore: a lung-selective M(3) antagonist patented by Pfizer and two Astra compounds which show affinity at the M(3) receptor. From these, a pharmacophore model was generated, using the program DISCO, and this was used subsequently to search a UNITY 3D database of proprietary compounds; 172 compounds were found to fit the pharmacophore. These compounds were then screened, and 1-[2-(2-(diethylamino)ethoxy)phenyl]-2-phenylethanone (pA(2) 6.67) was identified as the best hit, with N-[2-(piperidin-1-ylmethyl)cycohexyl]-2-propoxybenz amide (pA(2) 4. 83) and phenylcarbamic acid 2-(morpholin-4-ylmethyl)cyclohexyl ester (pA(2) 5.54) demonstrating lower activity. As well as its potency, 1-[2-(2-(diethylamino)ethoxy)phenyl]-2-phenylethanone is a simple structure with limited similarity to existing M(3) receptor antagonists.

  2. Evaluating Quality of Chaotic Pseudo-Random Generators: Application to Information Hiding

    CERN Document Server

    Bahi, Jacques M; Guyeux, Christophe; Wang, Qianxue

    2011-01-01

    Guaranteeing the security of information transmitted through the Internet, against passive or active attacks, is a major concern. The discovery of new pseudo-random number generators with a strong level of security is a field of research in full expansion, due to the fact that numerous cryptosystems and data hiding schemes are directly dependent on the quality of these generators. At the conference Internet`09, we described a generator based on chaotic iterations which behaves chaotically as defined by Devaney. In this paper which is an extension of the work presented at the conference Internet`10, the proposal is to improve the speed, the security, and the evaluation of this generator, to make its use more relevant in the Internet security context. In order to do so, a comparative study between various generators is carried out and statistical results are improved. Finally, an application in the information hiding framework is presented with details, to give an illustrative example of the use of such a gener...

  3. Information Technology How Leading Firms Use It to Gain an Advantage

    CERN Document Server

    Rapp, William V

    2002-01-01

    Focuses on the strategic principles fundamental to using information technology to gain market control. This book provides case examples of how to use IT. It is designed to help managers struggling with how to harness the information revolution. It describes how non-information technology companies are employing strategic principles and using it.

  4. Targeted inactivation of GPR26 leads to hyperphagia and adiposity by activating AMPK in the hypothalamus.

    Directory of Open Access Journals (Sweden)

    Daohong Chen

    Full Text Available G-protein coupled receptor 26 (GPR26 is a brain-specific orphan GPCR with high expression in the brain region that controls satiety. Depletion of GPR26 has been shown to increase fat storage in C. elegans, whereas GPR26 deficiency in the hypothalamus is associated with high genetic susceptibility to the onset of obesity in mice. However, the metabolic function of GPR26 in mammals remains elusive. Herein, we investigated a role of GPR26 in regulating energy homeostasis by generating mice with targeted deletion of the GPR26 gene. We show that GPR26 deficiency causes hyperphagia and hypometabolism, leading to early onset of diet-induced obesity. Accordingly, GPR26 deficiency also caused metabolic complications commonly associated with obesity, including glucose intolerance, hyperinsulinemia, and dyslipidemia. Moreover, consistent with hyperphagia in GPR26 null mice, GPR26 deficiency significantly increased hypothalamic activity of AMPK, a key signaling event that stimulates appetite. In further support of a regulatory role of GPR26 in satiety, GPR26 knockout mice also demonstrate hypersensitivity to treatment of rimonabant, an endocannabinoid receptor-1 antagonist commonly used to treat obesity by suppressing appetite in humans. Together, these findings identified a key role of GPR26 as a central regulator of energy homeostasis though modulation of hypothalamic AMPK activation.

  5. Generation of monoclonal antibodies to native active human glycosyltransferases

    DEFF Research Database (Denmark)

    Vester-Christensen, Malene Bech; Bennett, Eric Paul; Clausen, Henrik;

    2013-01-01

    using monoclonal antibodies therefore provides an excellent strategy to analyze the glycosylation process in cells. A major drawback has been difficulties in generating antibodies to glycosyltransferases and validating their specificities. Here we describe a simple strategy for generating...

  6. Active Generations: An Intergenerational Approach to Preventing Childhood Obesity

    Science.gov (United States)

    Werner, Danilea; Teufel, James; Holtgrave, Peter L.; Brown, Stephen L.

    2012-01-01

    Background: Over the last 3 decades, US obesity rates have increased dramatically as more children and more adults become obese. This study explores an innovative program, Active Generations, an intergenerational nutrition education and activity program implemented in out-of-school environments (after school and summer camps). It utilizes older…

  7. A Model of First-Generation Latino/a College Students' Approach to Seeking Academic Information

    Science.gov (United States)

    Torres, Vasti; Reiser, Al; LePeau, Lucy; Davis, Laura; Ruder, Jeffrey

    2006-01-01

    Using grounded theory methodology, we examined the experiences of first-generation Latino/a college students. Themes emerged in students' interactions with and perceptions of peers, advisors, and faculty members. A model derived from the data was developed to describe the unique ways first-generation Latino/a students sought information relating…

  8. Information Behavior and Japanese Students: How Can an Understanding of the Research Process Lead to Better Information Literacy?

    Science.gov (United States)

    Ishimura, Yusuke

    2013-01-01

    Academic librarians are striving to better serve international students as this emerging population grows on university campuses. Past studies of international students generally focus on linguistic and cultural differences in relation to information literacy skills development. However, it is necessary to go beyond these factors to better serve…

  9. Introduction to the Symposium "Leading Students and Faculty to Quantitative Biology through Active Learning".

    Science.gov (United States)

    Waldrop, Lindsay D; Miller, Laura A

    2015-11-01

    The broad aim of this symposium and set of associated papers is to motivate the use of inquiry-based, active-learning teaching techniques in undergraduate quantitative biology courses. Practical information, resources, and ready-to-use classroom exercises relevant to physicists, mathematicians, biologists, and engineers are presented. These resources can be used to address the lack of preparation of college students in STEM fields entering the workforce by providing experience working on interdisciplinary and multidisciplinary problems in mathematical biology in a group setting. Such approaches can also indirectly help attract and retain under-represented students who benefit the most from "non-traditional" learning styles and strategies, including inquiry-based, collaborative, and active learning.

  10. Microbial electrolysis contribution to anaerobic digestion of waste activated sludge, leading to accelerated methane production

    DEFF Research Database (Denmark)

    Liu, Wenzong; Cai, Weiwei; Guo, Zechong;

    2016-01-01

    Methane production rate (MPR) in waste activated sludge (WAS) digestion processes is typically limitedby the initial steps of complex organic matter degradation, leading to a limited MPR due to sludgefermentation speed of solid particles. In this study, a novel microbial electrolysis AD reactor (ME......-AD) wasused to accelerate methane production for energy recovery from WAS. Carbon bioconversion wasaccelerated by ME producing H2 at the cathode. MPR was enhanced to 91.8 gCH4/m3 reactor/d in themicrobial electrolysis ME-AD reactor, thus improving the rate by 3 times compared to control conditions (30.6 gCH4......-AD reactor allowed to significantly enhance carbon degradation and methaneproduction from WAS....

  11. Microbial electrolysis contribution to anaerobic digestion of waste activated sludge, leading to accelerated methane production

    DEFF Research Database (Denmark)

    Liu, Wenzong; Cai, Weiwei; Guo, Zechong

    2016-01-01

    -AD) wasused to accelerate methane production for energy recovery from WAS. Carbon bioconversion wasaccelerated by ME producing H2 at the cathode. MPR was enhanced to 91.8 gCH4/m3 reactor/d in themicrobial electrolysis ME-AD reactor, thus improving the rate by 3 times compared to control conditions (30.6 gCH4......Methane production rate (MPR) in waste activated sludge (WAS) digestion processes is typically limitedby the initial steps of complex organic matter degradation, leading to a limited MPR due to sludgefermentation speed of solid particles. In this study, a novel microbial electrolysis AD reactor (ME....../m3 reactor/d in AD). The methane production yield reached 116.2 mg/g VSS in the ME-ADreactor. According to balance calculation on electron transfer and methane yield, the increasedmethane production was mostly dependent on electron contribution through the ME system. Thus, theuse of the novel ME...

  12. Voluntary Participation in an Active Learning Exercise Leads to a Better Understanding of Physiology

    Science.gov (United States)

    Carvalho, Helena; West, Crystal A.

    2011-01-01

    Students learn best when they are focused and thinking about the subject at hand. To teach physiology, we must offer opportunities for students to actively participate in class. This approach aids in focusing their attention on the topic and thus generating genuine interest in the mechanisms involved. This study was conducted to determine if…

  13. Activation of β-catenin signalling leads to temporomandibular joint defects

    Directory of Open Access Journals (Sweden)

    M Wang

    2014-10-01

    Full Text Available Despite extensive research in knee and hip osteoarthritis (OA, the underlying mechanism of temporomandibular joint (TMJ disorder remains largely unknown. The purpose of this study was to determine whether the constitutive activation of β-catenin in the middle and deep layers of the articular cartilage can compromise the homeostasis of this tissue in the TMJ. Col2CreERT2 transgenic mice were bred with RosamT/mG reporter mice to determine Cre recombination efficiency. Col2CreERT2 mice were then crossed with β-cateninflox(ex3+ mice to generate β-catenin conditional activation mice, β-catenin(ex3Col2ER. TMJ samples were harvested when the mice were 1-, 3- or 6-month-old and evaluated using histology, histomorphometry and immunohistochemistry. β-catenin(ex3Col2ER mice were further crossed with Mmp13flox/flox and Adamts5-/- mice to generate (β-catenin(ex3/Mmp13Col2ER and β-catenin(ex3Col2ER/Adamts5-/- double mutant mice to investigate the role of Mmp13 and Adamts5 in the development of TMJ disorder. High levels of Cre-recombination were seen in Col2CreERT2;RosamT/mGmice. Progressive TMJ defects developed in 1-, 3- and 6-month-old β-catenin(ex3Col2ER mice, as revealed by histology and histomorphometry. Results further demonstrated that the defects observed in β-catenin(ex3Col2ER mice were significantly decelerated after deletion of the Mmp13 or Adamts5 gene in (β-catenin(ex3/Mmp13Col2ER or β-catenin(ex3Col2ER/Adamts5-/- double mutant mice. In summary, we found that β-catenin is a critical gene in the induction of TMJ cartilage degeneration, and over-expressing β-catenin in TMJ cartilage leads to defects assembling an OA-like phenotype. Deletion of Mmp13 and Adamts5 in β-catenin(ex3Col2ER mice ameliorates the development of TMJ defects. This study suggests that Mmp13 and Adamts5 could be potential therapeutic targets for the treatment of TMJ disorders.

  14. 76 FR 80362 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Fuel Quality...

    Science.gov (United States)

    2011-12-23

    ... Information Collection Activities; Submission to OMB for Review and Approval; Fuel Quality Regulations for..., or financial resources expended by persons to generate, maintain, retain, or disclose or provide information to or for a Federal agency. This includes the time needed to review instructions; develop,...

  15. DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

  16. Modeling spatiotemporal information generation

    NARCIS (Netherlands)

    Scheider, Simon; Gräler, Benedikt; Stasch, Christoph; Pebesma, Edzer

    2016-01-01

    Maintaining knowledge about the provenance of datasets, that is, about how they were obtained, is crucial for their further use. Contrary to what the overused metaphors of ‘data mining’ and ‘big data’ are implying, it is hardly possible to use data in a meaningful way if information about sources an

  17. Generating Embodied Information Presentations

    NARCIS (Netherlands)

    Theune, M.; Heylen, D.; Nijholt, A.; Stock, O.; Zancanaro, M.

    2005-01-01

    The output modalities available for information presentation by embodied, human-like agents include both language and various nonverbal cues such as pointing and gesturing. These human, nonverbal modalities can be used to emphasize, extend or even replace the language output produced by the agent. T

  18. Exploring the benefits of growing bioenergy crops to activate lead-contaminated agricultural land: a case study on sweet potatoes.

    Science.gov (United States)

    Cheng, Shu-Fen; Huang, Chin-Yuan; Chen, Kuo-Lin; Lin, Sheng-Chien; Lin, Yung-Cheng

    2015-03-01

    Phytoremediation is the most environmentally friendly remediation technology for heavy metal contaminated soil. However, the phytoremediation approach requires a long time to yield results, and the plants used must be economically profitable to maintain the sustainability of the process. Because high levels of bioethanol can be produced from sweet potatoes, an experiment was conducted by planting sweet potatoes in a lead-contaminated site to observe their growth and lead-uptake capacity, thereby enabling the evaluation of the phytoremediation efficiency of sweet potatoes. The lead content in the soil was approximately 6000 mg kg(-1), and the phytoavailable Pb content was 1766 mg kg(-1). Three starch-rich sweet potato varieties, Tainung No. 10 (TNG-10), Tainung No. 31 (TNG-31), and Tainung No. 57 (TNG-57), were used in the experiment. The results indicated that TNG-10, TNG-31, and TNG-57 had fresh root tuber yields of 94.5, 133.0, and 47.5 ton ha(-1) year(-1), produced 9450, 13,297, and 4748 L ha(-1) year(-1) of bioethanol, and removed 2.68, 7.73, and 3.22 kg ha(-1) year(-1) of lead, respectively. TNG-31 yielded the highest bioethanol production and the highest lead removal in the lead-contaminated site. Therefore, implementing phytoremediation by planting TNG-31 would decrease lead content and generate income, thereby rendering the sustainable and applicable activation of contaminated soil possible.

  19. Concurrent parametrization against static and kinetic information leads to more robust coarse-grained force fields

    CERN Document Server

    Rudzinski, Joseph F

    2016-01-01

    The parametrization of coarse-grained (CG) simulation models for molecular systems often aims at reproducing static properties alone. The reduced molecular friction of the CG representation usually results in faster, albeit inconsistent, dynamics. In this work, we rely on Markov state models to simultaneously characterize the static and kinetic properties of two CG peptide force fields---one top-down and one bottom-up. Instead of a rigorous evolution of CG dynamics (e.g., using a generalized Langevin equation), we attempt to improve the description of kinetics by simply altering the existing CG models, which employ standard Langevin dynamics. By varying masses and relevant force-field parameters, we can improve the timescale separation of the slow kinetic processes, achieve a more consistent ratio of mean-first-passage times between metastable states, and refine the relative free-energies between these states. Importantly, we show that the incorporation of kinetic information into a structure-based parametriz...

  20. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.; van der Velde, Astrid E.; van den Oever, Karin; Levels, Johannes H. M.; Huet, Stephane; Elferink, Ronald P. J. Oude; Kuipers, Folkert; Groen, Albert K.

    2009-01-01

    Peroxisome proliferator-activated receptor delta (PPAR delta) is involved in regulation of energy homeostasis. Activation of PPAR delta markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobilia

  1. A Public Opinion Survey on Correctional Education: Does Additional Information on Efficacy Lead to Additional Support?

    Science.gov (United States)

    Waterland, Keri Lynn

    2009-01-01

    Though much research has been done on the efficacy of correctional education on reducing recidivism rates for prison inmates, there is little research on the effect that information about the efficacy of correctional education has on public opinion. This study examined whether providing additional information regarding the efficacy of correctional…

  2. Epilepsy-Related Slack Channel Mutants Lead to Channel Over-Activity by Two Different Mechanisms

    Directory of Open Access Journals (Sweden)

    Qiong-Yao Tang

    2016-01-01

    Full Text Available Twelve sodium-activated potassium channel (KCNT1, Slack genetic mutants have been identified from severe early-onset epilepsy patients. The changes in biophysical properties of these mutants and the underlying mechanisms causing disease remain elusive. Here, we report that seven of the 12 mutations increase, whereas one mutation decreases, the channel’s sodium sensitivity. Two of the mutants exhibit channel over-activity only when the intracellular Na+ ([Na+]i concentration is ∼80 mM. In contrast, single-channel data reveal that all 12 mutants increase the maximal open probability (Po. We conclude that these mutant channels lead to channel over-activity predominantly by increasing the ability of sodium binding to activate the channel, which is indicated by its maximal Po. The sodium sensitivity of these epilepsy causing mutants probably determines the [Na+]i concentration at which these mutants exert their pathological effects.

  3. Information systems as a tool to improve legal metrology activities

    Science.gov (United States)

    Rodrigues Filho, B. A.; Soratto, A. N. R.; Gonçalves, R. F.

    2016-07-01

    This study explores the importance of information systems applied to legal metrology as a tool to improve the control of measuring instruments used in trade. The information system implanted in Brazil has also helped to understand and appraise the control of the measurements due to the behavior of the errors and deviations of instruments used in trade, allowing the allocation of resources wisely, leading to a more effective planning and control on the legal metrology field. A study case analyzing the fuel sector is carried out in order to show the conformity of fuel dispersers according to maximum permissible errors. The statistics of measurement errors of 167,310 fuel dispensers of gasoline, ethanol and diesel used in the field were analyzed demonstrating the accordance of the fuel market in Brazil to the legal requirements.

  4. Concurrent parametrization against static and kinetic information leads to more robust coarse-grained force fields

    Science.gov (United States)

    Rudzinski, J. F.; Bereau, T.

    2016-10-01

    The parametrization of coarse-grained (CG) simulation models for molecular systems often aims at reproducing static properties alone. The reduced molecular friction of the CG representation usually results in faster, albeit inconsistent, dynamics. In this work, we rely on Markov state models to simultaneously characterize the static and kinetic properties of two CG peptide force fields—one top-down and one bottom-up. Instead of a rigorous evolution of CG dynamics (e.g., using a generalized Langevin equation), we attempt to improve the description of kinetics by simply altering the existing CG models, which employ standard Langevin dynamics. By varying masses and relevant force-field parameters, we can improve the timescale separation of the slow kinetic processes, achieve a more consistent ratio of mean-first-passage times between metastable states, and refine the relative free-energies between these states. Importantly, we show that the incorporation of kinetic information into a structure-based parametrization improves the description of the helix-coil transition sampled by a minimal CG model. While structure-based models understabilize the helical state, kinetic constraints help identify CG models that improve the ratio of forward/backward timescales by effectively hindering the sampling of spurious conformational intermediate states.

  5. Non-enzymatic Glycation of Almond Cystatin Leads to Conformational Changes and Altered Activity.

    Science.gov (United States)

    Siddiqui, Azad A; Sohail, Aamir; Bhat, Sheraz A; Rehman, Md T; Bano, Bilqees

    2015-01-01

    The non-enzymatic reaction between proteins and reducing sugars, known as glycation, leads to the formation of inter and intramolecular cross-links of proteins. Stable end products called as advanced Maillard products or advanced glycation end products (AGEs) have received tremendous attention since last decades. It was suggested that the formation of AGEs not only modify the conformation of proteins but also induces altered biological activity. In this study, cystatin purified from almond was incubated with three different sugars namely D-ribose, fructose and lactose to monitor the glycation process. Structural changes induced in cystatin on glycation were studied using UV-visible spectroscopy, fluorescence spectroscopy, CD and FTIR techniques. Glycated cystatin was found to migrate slower on electrophoresis as compared to control cystatin. Biological activity data of glycated cystatin showed that D-ribose was most effective in inducing conformational changes with maximum altered activity.

  6. Mixed-source reintroductions lead to outbreeding depression in second-generation descendents of a native North American fish

    Science.gov (United States)

    Huff, D.D.; Miller, L.M.; Chizinski, C.J.; Vondracek, B.

    2011-01-01

    Reintroductions are commonly employed to preserve intraspecific biodiversity in fragmented landscapes. However, reintroduced populations are frequently smaller and more geographically isolated than native populations. Mixing genetically, divergent sources are often proposed to attenuate potentially low genetic diversity in reintroduced populations that may result from small effective population sizes. However, a possible negative tradeoff for mixing sources is outbreeding depression in hybrid offspring. We examined the consequences of mixed-source reintroductions on several fitness surrogates at nine slimy sculpin (Cottus cognatus) reintroduction sites in south-east Minnesota. We inferred the relative fitness of each crosstype in the reintroduced populations by comparing their growth rate, length, weight, body condition and persistence in reintroduced populations. Pure strain descendents from a single source population persisted in a greater proportion than expected in the reintroduced populations, whereas all other crosstypes occurred in a lesser proportion. Length, weight and growth rate were lower for second-generation intra-population hybrid descendents than for pure strain and first-generation hybrids. In the predominant pure strain, young-of the-year size was significantly greater than any other crosstype. Our results suggested that differences in fitness surrogates among crosstypes were consistent with disrupted co-adapted gene complexes associated with beneficial adaptations in these reintroduced populations. Future reintroductions may be improved by evaluating the potential for local adaptation in source populations or by avoiding the use of mixed sources by default when information on local adaptations or other genetic characteristics is lacking. ?? 2011 Blackwell Publishing Ltd.

  7. Online integrated solution to collect data, generate information and manage events in the human biomonitoring field.

    Science.gov (United States)

    Reis, M Fátima; Tedim, João; Aguiar, Pedro; Miguel, J Pereira; Casteleyn, Ludwine; Joas, Reinhard; Van Tongelen, Birgit

    2007-05-01

    In the ambit of Work Package 1 of the ESBIO Project, an online integrated solution to collect data, to generate information, and to manage mainly information-sharing events related with human biomonitoring within Europe has been designed and is being implemented. The present paper summarises the methodological approaches used by the authors as proposers, general promoters and disseminators of this strategic concept, as well as the first outcomes and future actions to be taken, in the short and longer term, to face present and future challenges to make this innovative solution happen.

  8. WVU cooperative agreement, decontamination systems information and research program, deployment support leading to implementation

    Energy Technology Data Exchange (ETDEWEB)

    Cook, E.E.

    1996-12-31

    This program at West Virginia University is a Cooperative Agreement that focuses on R&D associated with hazardous waste remediation problems existing at DOE, Corps of Engineers, and private sector sites. The Agreement builds on a unique combination of resources coupling university researchers with DOE sponsored small businesses, leading toward field tests and large scale technology demonstrations of environmental technologies. Most of the Agreement`s projects are categorized in the Technology Maturity Levels under Gates 3-Advanced Development, Gate 4-Engineering Development, and Gate 5-Demonstration. The program includes a diversity of projects: subsurface contaminants; mixed wastes; mixed wastes/efficient separations; mixed wastes/characterization, monitoring, and sensor technologies; and decontamination and decommissioning/efficient separations.

  9. Raft disorganization leads to reduced plasmin activity in Alzheimer's disease brains.

    Science.gov (United States)

    Ledesma, Maria Dolores; Abad-Rodriguez, José; Galvan, Cristian; Biondi, Elisa; Navarro, Pilar; Delacourte, Andre; Dingwall, Colin; Dotti, Carlos G

    2003-12-01

    The serine protease plasmin can efficiently degrade amyloid peptide in vitro, and is found at low levels in the hippocampus of patients with Alzheimer's disease (AD). The cause of such paucity remains unknown. We show here that the levels of total brain plasminogen and plasminogen-binding molecules are normal in these brain samples, yet plasminogen membrane binding is greatly reduced. Biochemical analysis reveals that the membranes of these brains have a mild, still significant, cholesterol reduction compared to age-matched controls, and anomalous raft microdomains. This was reflected by the loss of raft-enriched proteins, including plasminogen-binding and -activating molecules. Using hippocampal neurons in culture, we demonstrate that removal of a similar amount of membrane cholesterol is sufficient to induce raft disorganization, leading to reduced plasminogen membrane binding and low plasmin activity. These results suggest that brain raft alterations may contribute to AD by rendering the plasminogen system inefficient.

  10. Local active information storage as a tool to understand distributed neural information processing.

    Science.gov (United States)

    Wibral, Michael; Lizier, Joseph T; Vögler, Sebastian; Priesemann, Viola; Galuske, Ralf

    2014-01-01

    Every act of information processing can in principle be decomposed into the component operations of information storage, transfer, and modification. Yet, while this is easily done for today's digital computers, the application of these concepts to neural information processing was hampered by the lack of proper mathematical definitions of these operations on information. Recently, definitions were given for the dynamics of these information processing operations on a local scale in space and time in a distributed system, and the specific concept of local active information storage was successfully applied to the analysis and optimization of artificial neural systems. However, no attempt to measure the space-time dynamics of local active information storage in neural data has been made to date. Here we measure local active information storage on a local scale in time and space in voltage sensitive dye imaging data from area 18 of the cat. We show that storage reflects neural properties such as stimulus preferences and surprise upon unexpected stimulus change, and in area 18 reflects the abstract concept of an ongoing stimulus despite the locally random nature of this stimulus. We suggest that LAIS will be a useful quantity to test theories of cortical function, such as predictive coding.

  11. Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis.

    Science.gov (United States)

    Silva, Patricio; Mendoza, Pablo; Rivas, Solange; Díaz, Jorge; Moraga, Carolina; Quest, Andrew F G; Torres, Vicente A

    2016-05-17

    Hypoxia, a common condition of the tumor microenvironment, is associated with poor patient prognosis, tumor cell migration, invasion and metastasis. Recent evidence suggests that hypoxia alters endosome dynamics in tumor cells, leading to augmented cell proliferation and migration and this is particularly relevant, because endosomal components have been shown to be deregulated in cancer. The early endosome protein Rab5 is a small GTPase that promotes integrin trafficking, focal adhesion turnover, Rac1 activation, tumor cell migration and invasion. However, the role of Rab5 and downstream events in hypoxia remain unknown. Here, we identify Rab5 as a critical player in hypoxia-driven tumor cell migration, invasion and metastasis. Exposure of A549 human lung carcinoma, ZR-75, MDA-MB-231 and MCF-7 human breast cancer and B16-F10 mouse melanoma cells to hypoxia increased Rab5 activation, followed by its re-localization to the leading edge and association with focal adhesions. Importantly, Rab5 was required for hypoxia-driven cell migration, FAK phosphorylation and Rac1 activation, as shown by shRNA-targeting and transfection assays with Rab5 mutants. Intriguingly, the effect of hypoxia on both Rab5 activity and migration was substantially higher in metastatic B16-F10 cells than in poorly invasive B16-F0 cells. Furthermore, exogenous expression of Rab5 in B16-F0 cells predisposed to hypoxia-induced migration, whereas expression of the inactive mutant Rab5/S34N prevented the migration of B16-F10 cells induced by hypoxia. Finally, using an in vivo syngenic C57BL/6 mouse model, Rab5 expression was shown to be required for hypoxia-induced metastasis. In summary, these findings identify Rab5 as a key mediator of hypoxia-induced tumor cell migration, invasion and metastasis.

  12. Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits.

    Science.gov (United States)

    Ishii, Kazuhiro; Kubo, Ken-ichiro; Endo, Toshihiro; Yoshida, Keitaro; Benner, Seico; Ito, Yukiko; Aizawa, Hidenori; Aramaki, Michihiko; Yamanaka, Akihiro; Tanaka, Kohichi; Takata, Norio; Tanaka, Kenji F; Mimura, Masaru; Tohyama, Chiharu; Kakeyama, Masaki; Nakajima, Kazunori

    2015-09-01

    Neuronal heterotopia refers to brain malformations resulting from deficits of neuronal migration. Individuals with heterotopias show a high incidence of neurological deficits, such as epilepsy. More recently, it has come to be recognized that focal heterotopias may also show a range of psychiatric problems, including cognitive and behavioral impairments. However, because focal heterotopias are not always located in the brain areas responsible for the symptoms, the causal relationship between the symptoms and heterotopias remains elusive. In this study, we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited spatial working memory deficit and low competitive dominance behavior, which have been shown to be closely associated with the activity of the medial prefrontal cortex (mPFC) in rodents. Analysis of the mPFC activity revealed that the immediate-early gene expression was decreased and the local field potentials of the mPFC were altered in the mice with heterotopias compared with the control mice. Moreover, activation of these ectopic and overlying sister neurons using the DREADD (designer receptor exclusively activated by designer drug) system improved the working memory deficits. These findings suggest that cortical regions containing focal heterotopias can affect distant brain regions and give rise to behavioral abnormalities. Significance statement: Recent studies reported that patients with heterotopias have a variety of clinical symptoms, such as cognitive disturbance, psychiatric symptoms, and autistic behavior. However, the causal relationship between the symptoms and heterotopias remains elusive. Here we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited behavioral deficits that have been shown to be associated with the mPFC activity in rodents. The existence of heterotopias indeed altered the neural activities of the mPFC, and

  13. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.

    Science.gov (United States)

    Crescenzo, Ramona; Abate, Francesco; Lasorsa, Elena; Tabbo', Fabrizio; Gaudiano, Marcello; Chiesa, Nicoletta; Di Giacomo, Filomena; Spaccarotella, Elisa; Barbarossa, Luigi; Ercole, Elisabetta; Todaro, Maria; Boi, Michela; Acquaviva, Andrea; Ficarra, Elisa; Novero, Domenico; Rinaldi, Andrea; Tousseyn, Thomas; Rosenwald, Andreas; Kenner, Lukas; Cerroni, Lorenzo; Tzankov, Alexander; Ponzoni, Maurilio; Paulli, Marco; Weisenburger, Dennis; Chan, Wing C; Iqbal, Javeed; Piris, Miguel A; Zamo', Alberto; Ciardullo, Carmela; Rossi, Davide; Gaidano, Gianluca; Pileri, Stefano; Tiacci, Enrico; Falini, Brunangelo; Shultz, Leonard D; Mevellec, Laurence; Vialard, Jorge E; Piva, Roberto; Bertoni, Francesco; Rabadan, Raul; Inghirami, Giorgio

    2015-04-13

    A systematic characterization of the genetic alterations driving ALCLs has not been performed. By integrating massive sequencing strategies, we provide a comprehensive characterization of driver genetic alterations (somatic point mutations, copy number alterations, and gene fusions) in ALK(-) ALCLs. We identified activating mutations of JAK1 and/or STAT3 genes in ∼20% of 88 [corrected] ALK(-) ALCLs and demonstrated that 38% of systemic ALK(-) ALCLs displayed double lesions. Recurrent chimeras combining a transcription factor (NFkB2 or NCOR2) with a tyrosine kinase (ROS1 or TYK2) were also discovered in WT JAK1/STAT3 ALK(-) ALCL. All these aberrations lead to the constitutive activation of the JAK/STAT3 pathway, which was proved oncogenic. Consistently, JAK/STAT3 pathway inhibition impaired cell growth in vitro and in vivo.

  14. Rph1 mediates the nutrient-limitation signaling pathway leading to transcriptional activation of autophagy.

    Science.gov (United States)

    Bernard, Amélie; Klionsky, Daniel J

    2015-04-01

    To maintain proper cellular homeostasis, the magnitude of autophagy activity has to be finely tuned in response to environmental changes. Many aspects of autophagy regulation have been extensively studied: pathways integrating signals through the master regulators TORC1 and PKA lead to multiple post-translational modifications affecting the functions, protein-protein interactions, and localization of Atg proteins. The expression of several ATG genes increases sharply upon autophagy induction conditions, and defects in ATG gene expression are associated with various diseases, pointing to the importance of transcriptional regulation of autophagy. Yet, how changes in ATG gene expression affect the rate of autophagy is not well characterized, and transcriptional regulators of the autophagy pathway remain largely unknown. To identify such regulators, we analyzed the expression of several ATG genes in a library of DNA-binding protein mutants. This led to the identification of Rph1 as a master transcriptional regulator of autophagy.

  15. Brand Coopetition with Geographical Indications: Which Information Does Lead to Brand Differentiation?

    NARCIS (Netherlands)

    Dentoni, D.; Tonsor, G.; Calantone, R.; Peterson, C.

    2013-01-01

    Farmers and managers marketing food products with Geographical Indications (GIs) have to play a brand coopetition game: they cooperate with each other to develop a collective GI equity, yet they compete to build their individual brand and to establish market channels. Based on an online experiment o

  16. Spatial analysis on impacts of mining activities leading to flood disaster in the Erai watershed, India

    Energy Technology Data Exchange (ETDEWEB)

    Katpatal, Y.B.; Patil, S.A. [Visvesvaraya National Institute of Technology, Nagpur (India). Dept. of Civil Engineering

    2010-05-15

    Decisions related to mine management, especially pertaining to dumped material, might lead to several environmental hazards including flood risks in mining areas. Excavation and mine dumps are dominant factors of land use/land cover change in the Erai River watershed of Chandrapur district in Maharashtra, India. Identification and quantification of the extent of mining activities is important for assessing how this change in land use/land cover affects ecosystem components such as aesthetics, biodiversity and mitigation of floods in the Erai watershed. The present study utilizes satellite data of Landsat TM (1989), IRS LISS-3 (1999, 2007) and CARTOSAT (2007) to study the extent of surface mines and management of mine overburden (OB) dumps of Hindustan Lalpeth coal mines, Chandrapur, India. Image processing techniques in conjunction with GIS have been used to visualize the flood scenario, the reasons for floods and area under impact. The study indicates that the development of the mine OB dump within the river channel on both the sides has been responsible for the 2006 flood within the region. Further increase in OB dump heights may result in the risk of floods of greater potential during heavy rainfall in the future. The study presents a spatial analysis to assess the impacts of OB dumps in the recent flood in the area. The study also spatially represents the area under impact leading to a disastrous situation due to floods. The study also suggests the probable measures that must be adopted to avoid such situations in future in the mining areas.

  17. Spatial analysis on impacts of mining activities leading to flood disaster in the Erai watershed, India

    Energy Technology Data Exchange (ETDEWEB)

    Y.B. Katpatal; S.A. Patil [Visvesvaraya National Institute of Technology, Nagpur (India). Civil Engineering Department

    2010-03-15

    Decisions related to mine management, especially pertaining to dumped material, might lead to several environmental hazards including flood risks in mining areas. Excavation and mine dumps are dominant factors of land use/land cover change in the Erai River watershed of Chandrapur district in Maharashtra, India. Identification and quantification of the extent of mining activities is important for assessing how this change in land use/land cover affects ecosystem components such as aesthetics, biodiversity and mitigation of floods in the Erai watershed. The present study utilizes satellite data of Landsat TM (1989), IRS LISS-3 (1999, 2007) and CARTOSAT (2007) to study the extent of surface mines and management of mine over burden (OB) dumps of Hindustan Lalpeth coal mines, Chandrapur, India. Image processing techniques in conjunction with GIS have been used to visualize the flood scenario, the reasons for floods and area under impact. The study indicates that the development of the mine OB dump within the river channel on both the sides has been responsible for the 2006 flood within the region. Further increase in OB dump heights may result in the risk of floods of greater potential during heavy rainfall in the future. The study presents a spatial analysis to assess the impacts of OB dumps in the recent flood in the area. The study also spatially represents the area under impact leading to a disastrous situation due to floods. The study also suggests the probable measures that must be adopted to avoid such situations in future in the mining areas.

  18. Leading In Context: A Review Of Leadership Styles To Inform School Effectiveness In Small Island States

    Directory of Open Access Journals (Sweden)

    Chryselda Caesar

    2013-02-01

    Full Text Available This paper examines different models and theories of leadership with a view to discern relevance, meaning and applicability to a small state, St Lucia. It reviews the evolution and distinguishing features of leadership and compares selected models in order to determine significance to St. Lucia context for achieving effective schools. Different school leadership models evolved to suit societal changes, educational reforms and demands and perceptions of educational researchers who viewed schools as organizations based on corporate -organization models, but exhibited greater complex and dynamism. Other researchers viewed schools as communities with a network of interconnecting people and relationships, with varying degrees of commitments and conflicting expectations, thus creating a unique environment in each school.  Apprehension about the degree of applicability of these models with regard to outcomes and the quality of schooling that students require in this challenging era, led to the development of new leadership theories. These new leadership models suggest that school leaders should to be driven by a noble and morale purpose.  However the literature seems to indicate that transformational models and new leadership concepts are theoretical and have not been empirically tested in schools. Then again, if available, the few empirically based theories are context specific; they are researched in developed and different countries with completely different circumstances and may not be easily transferable. Adoption and application of these models are dependent on the prevailing circumstances and environment.

  19. Unusual "ratchet syndrome": spontaneous lead retraction after a generator exchange.

    Science.gov (United States)

    Ejima, Koichiro; Shoda, Morio; Yashiro, Bun; Yoshida, Kentaro; Nuki, Toshiaki; Kato, Ken; Manaka, Tetsuyuki; Hagiwara, Nobuhisa

    2014-07-01

    A 72-year-old female with idiopathic dilated cardiomyopathy underwent a generator exchange for a cardiac resynchronization therapy defibrillator with a full-pocket capsulectomy. The lead position after the operation was identical to that before the operation on the chest X-ray. After 4 months, a subacute exacerbation of her heart failure was caused by cardiac resynchronization therapy failure due to a dislodgement of the left ventricular lead. An aggressive adhesiotomy of the connective tissue around the leads made it possible for the lead to retract by a ratchet-like movement through the suture sleeve, so-called "ratchet syndrome", after the generator exchange.

  20. 77 FR 16222 - Agency Information Collection Activities; Proposed Collection; Comment Request; Generator...

    Science.gov (United States)

    2012-03-20

    ... seq.), this document announces that EPA is planning to submit a request to the Office of Management... appropriate automated electronic, mechanical, or other technological collection techniques or other forms of... universities, and teaching hospitals and non-profit research institutes that are either owned by or...

  1. Modification of rifamycin polyketide backbone leads to improved drug activity against rifampicin-resistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Nigam, Aeshna; Almabruk, Khaled H; Saxena, Anjali; Yang, Jongtae; Mukherjee, Udita; Kaur, Hardeep; Kohli, Puneet; Kumari, Rashmi; Singh, Priya; Zakharov, Lev N; Singh, Yogendra; Mahmud, Taifo; Lal, Rup

    2014-07-25

    Rifamycin B, a product of Amycolatopsis mediterranei S699, is the precursor of clinically used antibiotics that are effective against tuberculosis, leprosy, and AIDS-related mycobacterial infections. However, prolonged usage of these antibiotics has resulted in the emergence of rifamycin-resistant strains of Mycobacterium tuberculosis. As part of our effort to generate better analogs of rifamycin, we substituted the acyltransferase domain of module 6 of rifamycin polyketide synthase with that of module 2 of rapamycin polyketide synthase. The resulting mutants (rifAT6::rapAT2) of A. mediterranei S699 produced new rifamycin analogs, 24-desmethylrifamycin B and 24-desmethylrifamycin SV, which contained modification in the polyketide backbone. 24-Desmethylrifamycin B was then converted to 24-desmethylrifamycin S, whose structure was confirmed by MS, NMR, and X-ray crystallography. Subsequently, 24-desmethylrifamycin S was converted to 24-desmethylrifampicin, which showed excellent antibacterial activity against several rifampicin-resistant M. tuberculosis strains.

  2. Emotion at Work: A Contribution to Third-Generation Cultural-Historical Activity Theory

    Science.gov (United States)

    Roth, Wolff-Michael

    2007-01-01

    Second-generation cultural-historical activity theory, which drew its inspiration from Leont'ev's work, constituted an advance over Vygotsky's first-generation theory by explicitly articulating the dialectical relation between individual and collective. As part of an effort to develop third-generation-historical activity theory, I propose in this…

  3. Multiple nucleophilic elbows leading to multiple active sites in a single module esterase from Sorangium cellulosum

    DEFF Research Database (Denmark)

    Udatha, D.B.R.K. Gupta; Madsen, Karina Marie; Panagiotou, Gianni;

    2015-01-01

    The catalytic residues in carbohydrate esterase enzyme families constitute a highly conserved triad: serine, histidine and aspartic acid. This catalytic triad is generally located in a very sharp turn of the protein backbone structure, called the nucleophilic elbow and identified by the consensus...... sequence GXSXG. An esterase from Sorangium cellulosum Soce56 that contains five nucleophilic elbows was cloned and expressed in Escherichia coli and the function of each nucleophilic elbowed site was characterized. In order to elucidate the function of each nucleophilic elbow, site directed mutagenesis...... was used to generate variants with deactivated nucleophilic elbows and the functional promiscuity was analyzed. In silico analysis together with enzymological characterization interestingly showed that each nucleophilic elbow formed a local active site with varied substrate specificities and affinities...

  4. Phase of shear vibrations within cochlear partition leads to activation of the cochlear amplifier.

    Directory of Open Access Journals (Sweden)

    Jessica S Lamb

    Full Text Available Since Georg von Bekesy laid out the place theory of the hearing, researchers have been working to understand the remarkable properties of mammalian hearing. Because access to the cochlea is restricted in live animals, and important aspects of hearing are destroyed in dead ones, models play a key role in interpreting local measurements. Wentzel-Kramers-Brillouin (WKB models are attractive because they are analytically tractable, appropriate to the oblong geometry of the cochlea, and can predict wave behavior over a large span of the cochlea. Interest in the role the tectorial membrane (TM plays in cochlear tuning led us to develop models that directly interface the TM with the cochlear fluid. In this work we add an angled shear between the TM and reticular lamina (RL, which serves as an input to a nonlinear active force. This feature plus a novel combination of previous work gives us a model with TM-fluid interaction, TM-RL shear, a nonlinear active force and a second wave mode. The behavior we get leads to the conclusion the phase between the shear and basilar membrane (BM vibration is critical for amplification. We show there is a transition in this phase that occurs at a frequency below the cutoff, which is strongly influenced by TM stiffness. We describe this mechanism of sharpened BM velocity profile, which demonstrates the importance of the TM in overall cochlear tuning and offers an explanation for the response characteristics of the Tectb mutant mouse.

  5. Eccentric Exercise Leads to Glial Activation but not Apoptosis in Mice Spinal Cords.

    Science.gov (United States)

    Pereira, B C; Lucas, G; da Rocha, A L; Pauli, J R; Ropelle, E R; Cintra, D; de Souza, C T; Bueno, C R; da Silva, A S

    2015-05-01

    The aim of this investigation was to evaluate the effects of 3 overtraining (OT) protocols on the glial activation and apoptosis in the spinal cords of mice. Rodents were divided into control (C; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR). The incremental load test, ambulation test, exhaustive test and functional behavioural assessment were used as performance evaluation parameters. 36 h after the exhaustive test, the dorsal and ventral parts of the lumbar spinal cord (L4-L6) were dissected for subsequent protein analysis by immunoblotting. The OT protocols led to similar responses of some performance parameters. The ventral glial fibrillary acidic protein (GFAP) protein levels were diminished in the OTR/up and OTR compared to CT and OTR/down groups. The ventral ionized calcium binding adaptor molecule 1 (Iba-1), and the dorsal GFAP and Iba-1 protein levels were increased in the OTR/down compared to the other groups. The ratio between the cleaved capase-3/caspase-3 and cleaved caspase-9/caspase-9 measured in the spinal cord were not sensitive to the OT protocols. In summary, the OTR/down activated the glial cells in the motor (i. e. Iba-1) and sensory (i. e. GFAP and Iba-1) neurons without leading to apoptosis.

  6. Systemic Immune Activation Leads to Neuroinflammation and Sickness Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Steven Biesmans

    2013-01-01

    Full Text Available Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and depressive-like behavior in mice. We report that systemic administration of LPS induced astrocyte activation in transgenic GFAP-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice. Furthermore, LPS treatment caused a strong but transient increase in cytokine levels in the serum and brain. In addition to studying LPS-induced neuroinflammation, we tested whether sickness could be separated from depressive-like behavior by evaluating LPS-treated mice in a panel of behavioral paradigms. Our behavioral data indicate that systemic LPS administration caused sickness and mild depressive-like behavior. However, due to the overlapping time course and mild effects on depression-related behavior per se, it was not possible to separate sickness from depressive-like behavior in the present rodent model.

  7. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

    Directory of Open Access Journals (Sweden)

    Simon Gemble

    2015-07-01

    Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

  8. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters

    Directory of Open Access Journals (Sweden)

    Tina eNetzker

    2015-04-01

    Full Text Available Microorganisms form diverse multispecies communities in various ecosystems. The high abundance of fungal and bacterial species in these consortia results in specific communication between the microorganisms. A key role in this communication is played by secondary metabolites (SMs, which are also called natural products. Recently, it was shown that interspecies ‘talk’ between microorganisms represents a physiological trigger to activate silent gene clusters leading to the formation of novel SMs by the involved species. This review focuses on mixed microbial cultivation, mainly between bacteria and fungi, with a special emphasis on the induced formation of fungal SMs in co-cultures. In addition, the role of chromatin remodeling in the induction is examined, and methodical perspectives for the analysis of natural products are presented. As an example for an intermicrobial interaction elucidated at the molecular level, we discuss the specific interaction between the filamentous fungi Aspergillus nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces rapamycinicus, which provides an excellent model system to enlighten molecular concepts behind regulatory mechanisms and will pave the way to a novel avenue of drug discovery through targeted activation of silent SM gene clusters through co-cultivations of microorganisms.

  9. Spatio-temporal regulation of Hsp90-ligand complex leads to immune activation.

    Directory of Open Access Journals (Sweden)

    Yasuaki eTamura

    2016-05-01

    Full Text Available Hsp90 is the most abundant cytosolic HSP and is known to act as a molecular chaperone. We found that an Hsp90-cancer antigen peptide complex was efficiently cross-presented by human monocyte-derived dendritic cells and induced peptide-specific cytotoxic T lymphocytes. Furthermore, we observed that the internalized Hsp90-peptide complex was strictly sorted to the Rab5+, EEA1+ static early endosome and the Hsp90-chaperoned peptide was processed and bound to MHC class I molecules through a endosome-recycling pathway. We also found that extracellular Hsp90 complexed with CpG-A or self-DNA stimulates production of a large amount of IFN-α from pDCs via static early endosome targeting. Thus, extracellular Hsp90 can target the antigen or nucleic acid to a static early endosome by spatio-temporal regulation. Moreover, we showed that Hsp90 associates with and delivers TLR7/9 from the ER to early endosomes for ligand recognition. Hsp90 inhibitor, geldanamycin derivative inhibited the Hsp90 association with TLR7/9, resulting in inhibition IFN-α production, leading to improvement of SLE symptoms. Interstingly, we observed that serum Hsp90 is clearly increased in patients with active SLE compared with that in patients with inactive disease. Serum Hsp90 detected in SLE patients binds to self-DNA and/or anti-DNA Ab, thus leading to stimulation of pDCs to produce IFN-α. Thus, Hsp90 plays a crucial role in the pathogenesis of SLE and that an Hsp90 inhibitor will therefore provide a new therapeutic approach to SLE and other nucleic acid-related autoimmune diseases. We will discuss how spatio-temporal regulation of Hsp90-ligand complexes within antigen-presenting cells affects the innate immunity and adaptive immunity.

  10. Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss.

    Science.gov (United States)

    Zhu, Y; Chen, J; Liang, C; Zong, L; Chen, J; Jones, R O; Zhao, H-B

    2015-01-22

    Connexin26 (Cx26, GJB2) mutations account for >50% of nonsyndromic hearing loss. The deafness is not always congenital. A large group of these patients (∼30%) demonstrate a late-onset hearing loss, starting in childhood. They have normal hearing early in life and are therefore good candidates for applying protective and therapeutic interventions. However, the underlying deafness mechanism is unclear. In this study, we used a time-controlled, inducible gene knockout technique to knockout Cx26 expression in the cochlea after birth. We found that deletion of Cx26 after postnatal day 5 (P5) in mice could lead to late-onset hearing loss. Similar to clinical observations, the mice demonstrated progressive, mild to moderate hearing loss. The hearing loss initiated at high frequencies and then extended to the middle- and low-frequency range. The cochlea showed normal development and had no apparent hair cell loss. However, distortion product otoacoustic emission (DPOAE) was reduced. The reduction was also progressive and large at high-frequencies. Consistent with DPOAE reduction, we found that outer hair cell electromotility-associated nonlinear capacitance was shifted to the right and the slope of voltage dependence was reduced. The endocochlear potential was reduced in Cx26 conditional knockout (cKO) mice but the reduction was not associated with progressive hearing loss. These data suggest that Cx26 deficiency may impair active cochlear amplification leading to late-onset hearing loss. Our study also helps develop newer protective and therapeutic interventions to this common nonsyndromic hearing loss.

  11. Can active-sterile neutrino oscillations lead to chaotic behavior of the cosmological lepton asymmetry?

    CERN Document Server

    Hannestad, Steen; Tram, Thomas

    2013-01-01

    While the cosmic baryon asymmetry has been measured at high accuracy to be 6.1*10^-10, a corresponding lepton asymmetry could be as large as 10^-2 if it hides in the neutrino sector. It has been known for some time that a large asymmetry can be generated from a small initial asymmetry given the existence of a sterile neutrino with a mass less than the mass of the active neutrino. While the magnitude of the final lepton asymmetry is deterministic, its sign has been conjectured to be chaotic in nature. This has been proven in the single momentum approximation, also known as the quantum rate equations, but has up to now not been established using the full momentum dependent quantum kinetic equations. Here we investigate this problem by solving the quantum kinetic equations for a system of 1 active and 1 sterile neutrino on an adaptive grid. We show that by increasing the resolution oscillations in the lepton asymmetry are eliminated and that the sign of the lepton asymmetry is in fact deterministic. This paper a...

  12. Can active-sterile neutrino oscillations lead to chaotic behavior of the cosmological lepton asymmetry?

    Energy Technology Data Exchange (ETDEWEB)

    Hannestad, Steen; Hansen, Rasmus Sloth [Department of Physics and Astronomy, University of Aarhus, 8000 Aarhus C (Denmark); Tram, Thomas, E-mail: sth@phys.au.dk, E-mail: rshansen@phys.au.dk, E-mail: thomas.tram@epfl.ch [Institut de Théorie des Phénomènes Physiques, École Polytechnique Fédérale de Lausanne, CH-1015, Lausanne (Switzerland)

    2013-04-01

    While the cosmic baryon asymmetry has been measured at high accuracy to be 6.1 × 10{sup −10}, a corresponding lepton asymmetry could be as large as 10{sup −2} if it hides in the neutrino sector. It has been known for some time that such an asymmetry could be generated from a small initial asymmetry given the existence of a sterile neutrino with a mass less than the mass of the active neutrino. While the magnitude of the final lepton asymmetry is deterministic, its sign has been conjectured to be chaotic in nature. This has been proven in the single momentum approximation, also known as the quantum rate equations, but has up to now not been established using the full momentum dependent quantum kinetic equations. Here we investigate this problem by solving the quantum kinetic equations for a system of 1 active and 1 sterile neutrino on an adaptive grid. We show that by increasing the resolution, oscillations in the lepton asymmetry can be eliminated so the sign of the final lepton asymmetry is in fact deterministic. This paper also serves as a launch paper for the adaptive solver LASAGNA which is available at http://users-phys.au.dk/steen.

  13. Saturated lipids decrease mitofusin 2 leading to endoplasmic reticulum stress activation and insulin resistance in hypothalamic cells.

    Science.gov (United States)

    Diaz, Brenda; Fuentes-Mera, Lizeth; Tovar, Armando; Montiel, Teresa; Massieu, Lourdes; Martínez-Rodríguez, Herminia Guadalupe; Camacho, Alberto

    2015-11-19

    Endoplasmic reticulum (ER) and mitochondria dysfunction contribute to insulin resistance generation during obesity and diabetes. ER and mitochondria interact through Mitofusin 2 (MTF2), which anchors in the outer mitochondrial and ER membranes regulating energy metabolism. Ablation of MTF2 leads to ER stress activation and insulin resistance. Here we determine whether lipotoxic insult induced by saturated lipids decreases MTF2 expression leading to ER stress response in hypothalamus and its effects on insulin sensitivity using in vitro and in vivo models. We found that lipotoxic stimulation induced by palmitic acid, but not the monounsaturated palmitoleic acid, decreases MTF2 protein levels in hypothalamic mHypoA-CLU192 cells. Also, palmitic acid incubation activates ER stress response evidenced by increase in the protein levels of GRP78/BIP marker at later stage than MTF2 downregulation. Additionally, we found that MTF2 alterations induced by palmitic, but not palmitoleic, stimulation exacerbate insulin resistance in hypothalamic cells. Insulin resistance induced by palmitic acid is prevented by pre-incubation of the anti-inflammatory and the ER stress release reagents, sodium salicylate and 4 phenylbutirate, respectively. Finally, we demonstrated that lipotoxic insult induced by high fat feeding to mice decreases MTF2 proteins levels in arcuate nucleus of hypothalamus. Our data indicate that saturated lipids modulate MTF2 expression in hypothalamus coordinating the ER stress response and the susceptibility to insulin resistance.

  14. A practical object-oriented approach to a development of a next generation hospital information system.

    Science.gov (United States)

    Sakamoto, N

    1998-01-01

    KIND (stands for Kyushu university hospital Information Network Database) is a five years project, which aims to provide integrated services for patients, physicians, researchers and other hospital staffs. The final product of KIND is a next generation hospital information system. A physicians' clinical workstation, for example, integrated into a secured medical information network, can electronically develop a longitudinal medical record and interface with pharmacies, laboratories, medical specialists, and radiologists, as well as develop patient census and demographic profiles, in addition to doing electronic claims. Since clinical requirements on those medical records may vary for each case, we would like to have an essential data model under the hood. We decided to introduce domain analysis method to produce a relevant domain model. A domain analysis method captures the nature of business and helps us have an essential and extensible data model. Although there are several ways to describe a domain model, we chose an object-oriented description and consequently implementation using an object-oriented database system. Once we could have a decent domain model and implemented it as an object-oriented data model, application programs can utilize those data very easy without worrying extra efforts like finding complex queries including multiple joins. More over, if an application uses decent object-oriented technologies, it allows a user to access whole aspects of data transparently. This paper describes the architecture of KIND (the system) and outlines our domain model. In this paper, we also describe a practical application of several object-oriented technologies to develop a next generation hospital information system.

  15. Collector attachment to lead-activated sphalerite – Experiments and DFT study on pH and solvent effects

    Energy Technology Data Exchange (ETDEWEB)

    Sarvaramini, A. [Department of Chemical Engineering, Université Laval, 1065 Avenue de la médecine, Québec, Québec G1V 0A6 (Canada); Larachi, F., E-mail: faical.larachi@gch.ulaval.ca [Department of Chemical Engineering, Université Laval, 1065 Avenue de la médecine, Québec, Québec G1V 0A6 (Canada); Hart, B. [Department of Earth Sciences, Surface Science Western, The University of Western Ontario, 999 Collip Circle, P.O. Box 12, London, Ontario N6G 0J3 (Canada)

    2016-03-30

    Graphical abstract: - Highlights: • DFT and experimental study of collector interactions with Pb-activated sphalerite. • Sphalerite activation in acidic media due to surface adsorption of Pb cations. • Substitution of surface zinc atoms by Pb not supported from experiments and DFT. • Collector adsorption on activated sphalerite hindered in solvated aqueous media. • Collector adsorption on surface deposited Pb(OH){sub 2} energetically favorable. - Abstract: The interactions of diisobutyl dithiophosphinate with bare (un-activated) and lead-activated sphalerite were studied both experimentally and through DFT simulations. Sphalerite activated by lead in acidic and alkaline conditions showed considerably greater affinity for diisobutyl dithiophosphinate adsorption than bare sphalerite. Experimental observations supported by DFT simulations concur in that attachment of the solvated collector to the activated sphalerite surface is through adsorbed lead cations or lead hydroxides where as for the bare sphalerite, the collector was most stable in its solvated state and not as an adsorbed specie. Accounting for solvation effects by including a swarm of water molecules in DFT simulations was necessary to infer plausible surface interactions between collector, solvent, and bare or lead-activated sphalerite. The experimental data and DFT simulations indicate, affinity of the collector toward surface-adsorbed lead species was predicted to form stable covalent bonds between collector sulfur atoms and lead.

  16. Activation of asparaginyl endopeptidase leads to Tau hyperphosphorylation in Alzheimer disease.

    Science.gov (United States)

    Basurto-Islas, Gustavo; Grundke-Iqbal, Inge; Tung, Yunn Chyn; Liu, Fei; Iqbal, Khalid

    2013-06-14

    Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2(PP2A). In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target.

  17. Waste container weighing data processing to create reliable information of household waste generation.

    Science.gov (United States)

    Korhonen, Pirjo; Kaila, Juha

    2015-05-01

    Household mixed waste container weighing data was processed by knowledge discovery and data mining techniques to create reliable information of household waste generation. The final data set included 27,865 weight measurements covering the whole year 2013 and it was selected from a database of Helsinki Region Environmental Services Authority, Finland. The data set contains mixed household waste arising in 6m(3) containers and it was processed identifying missing values and inconsistently low and high values as errors. The share of missing values and errors in the data set was 0.6%. This provides evidence that the waste weighing data gives reliable information of mixed waste generation at collection point level. Characteristic of mixed household waste arising at the waste collection point level is a wide variation between pickups. The seasonal variation pattern as a result of collective similarities in behaviour of households was clearly detected by smoothed medians of waste weight time series. The evaluation of the collection time series against the defined distribution range of pickup weights on the waste collection point level shows that 65% of the pickups were from collection points with optimally dimensioned container capacity and the collection points with over- and under-dimensioned container capacities were noted in 9.5% and 3.4% of all pickups, respectively. Occasional extra waste in containers occurred in 21.2% of the pickups indicating the irregular behaviour of individual households. The results of this analysis show that processing waste weighing data using knowledge discovery and data mining techniques provides trustworthy information of household waste generation and its variations.

  18. Exposures to lead.

    Science.gov (United States)

    Callan, Anna C; Hinwood, Andrea L

    2011-01-01

    The Pacific Basin Consortium for Environment and Health hosted a workshop on Exposures to Lead. Speakers from Australia and the United States of America addressed current research knowledge on lead exposures and health effects in children, risk assessment and communication issues in dealing with lead exposure sources, different methods for assessing exposure, and the variety of scenarios where lead still remains a pollutant of concern. Mining continues to be a source of lead for many communities, and approaches to reducing exposures in these settings present particular challenges. A Perth Declaration for the Global Reduction of Childhood Lead Exposure was signed by participants of the meeting and is aimed at increasing attention to the need to continue to assess lead in the environment and to develop strategies to reduce lead in the environment and exposure by communities.

  19. Neonatal exposure to LPS leads to heightened exploratory activity in adolescent rats.

    Science.gov (United States)

    Rico, Javier Leonardo Rodríguez; Ferraz, Denise Brufato; Ramalho-Pinto, Francisco Juarez; Morato, Silvio

    2010-12-20

    Although several reports have demonstrated physiological and behavioral changes in adult rats due to neonatal immune challenges, little is known about their effects in adolescence. Since neonatal exposure to lipopolysaccharide (LPS) alters the neural substrates involved in cognitive disorders, we tested the hypothesis that it may also alter the response to novel environments in adolescent rats. At 3 and 5 days of age, male Wistar rats received intraperitoneal injections of either vehicle solution or E. coli LPS (0.05mg/kg) or were left undisturbed. In the mid-adolescent period, between 40 and 46 days of age, the rats were exposed to the following behavioral tests: elevated plus-maze, open-field, novel-object exploration task, hole-board and the modified Porsolt forced swim test. The results showed that, in comparison with control animals, LPS-treated rats exhibited (1) less anxiety-related behaviors and enhanced patterns of locomotion and rearing in the plus-maze and the open-field tests, (2) high levels of exploration of both objects in the novel-object task and of corner and central holes in hole-board test, and (3) more time spent diving, an active behavior in the forced swim test. The present findings suggest that neonatal LPS exposure has long-lasting effects on the behavior profile adolescent rats exhibit in response to novelty. This behavioral pattern, characterized by heightened exploratory activity in novel environments, also suggests that early immune stimulation may contribute to the development of impulsive behavior in adolescent rats.

  20. Negotiating for livelihoods beyond the formal Mzuzu City, Malawi, by the urban poor: Informal settlements as spaces of income generating activities

    Directory of Open Access Journals (Sweden)

    James Gondwe

    2013-02-01

    Full Text Available This article is about how the urban poor in Mzuzu City, Malawi, redefine domestic spaces in their dwellings for supporting their livelihoods. More specifically, it argues that while street vendors negotiate for the use of public spaces within the ‘formal city’ for income generating activities, the urban poor in informal settlements negotiate for use of spaces in their dwellings for generating cash income. Spaces for income generating activities are as contested as spaces for vending in the ‘formal city.’ In this context, the urban poor become creative enough to overcome equally demanding domestic functions of their dwellings. Furthermore, power imbalance is also epitomised in home based enterprises where tenants have to negotiate with their landlords for use of dwellings for generating income and accumulation of assets. However, it is not only physical spaces whose use for income generating activities is negotiable. Rather gender relations in some households are also negotiated for and contested spaces. Despite their visibility in home based enterprises, women appear to lack control over resources which they help to generate.  The paper further argues that labeling livelihood strategies of the urban poor as ‘marginal,’ ‘vulnerable,’ and ‘survival enterprises’ is problematic because the urban poor are not a homogeneous group. Since their perceptions, motivations, skills and knowledge differ; their livelihoods outcomes are also likely to be different. Thus, the accumulation of income and assets should not be the only variables used for measuring the success or failure of home based enterprises because their outcomes are also heavily embedded in informal social security networks.

  1. Negotiating for livelihoods beyond the formal Mzuzu City, Malawi, by the urban poor: Informal settlements as spaces of income generating activities

    Directory of Open Access Journals (Sweden)

    Kossi Ayenagbo

    2013-02-01

    Full Text Available This article is about how the urban poor in Mzuzu City, Malawi, redefine domestic spaces in their dwellings for supporting their livelihoods. More specifically, it argues that while street vendors negotiate for the use of public spaces within the ‘formal city’ for income generating activities, the urban poor in informal settlements negotiate for use of spaces in their dwellings for generating cash income. Spaces for income generating activities are as contested as spaces for vending in the ‘formal city.’ In this context, the urban poor become creative enough to overcome equally demanding domestic functions of their dwellings. Furthermore, power imbalance is also epitomised in home based enterprises where tenants have to negotiate with their landlords for use of dwellings for generating income and accumulation of assets. However, it is not only physical spaces whose use for income generating activities is negotiable. Rather gender relations in some households are also negotiated for and contested spaces. Despite their visibility in home based enterprises, women appear to lack control over resources which they help to generate. The paper further argues that labeling livelihood strategies of the urban poor as ‘marginal,’ ‘vulnerable,’ and ‘survival enterprises’ is problematic because the urban poor are not a homogeneous group. Since their perceptions, motivations, skills and knowledge differ; their livelihoods outcomes are also likely to be different. Thus, the accumulation of income and assets should not be the only variables used for measuring the success or failure of home based enterprises because their outcomes are also heavily embedded in informal social security networks.

  2. Great Lakes Integrated Sciences + Assessments: Connecting Users and Generators of Scientific Information to Inform Climate Change Adaptation

    Science.gov (United States)

    Baule, W. J.; Briley, L.; Brown, D.; Gibbons, E.

    2014-12-01

    The Great Lakes Integrated Sciences + Assessments (GLISA) is one of eleven NOAA Regional Integrated Sciences and Assessments (RISAs) and is a co-hosted by the University of Michigan and Michigan State University. The Great Lakes region falls between areas that are typically defined as the Midwest and Northeast in the United States and also includes portions of Ontario in Canada. This unique and complex region holds approximately 21% of global surface fresh water and is home to 23 million people on the United States side of the basin alone. GLISA functions as a bridge between climate science researchers and boundary organizations in the Great Lakes region, with the goals of contributing to the long-term sustainability of the region in face of a changing climate and to facilitate smart decision-making backed by sound scientific knowledge. Faculty and staff associated with GLISA implement physical and social science practices in daily operations, which includes but is not limited to: activating the boundary chain model to facilitate the transfer of knowledge through the community, integrating local and historical climate data into decision-making processes, addressing uncertainty and the downscaling of climate information, and implementing network analyses to find key access points to information networks across the Great Lakes region. GLISA also provides funding for projects related to climate and climate change adaptation in the Great Lakes region, as well as expertise to partner organizations through collaborations. Information from boundary organizations, stakeholders, and collaborators also flows back to GLISA to aid in the determination of the physical and social science needs of the region. Recent findings point to GLISA playing a crucial role in the scaling information across scales of government and ensuring that federal agencies and local stakeholders are able to learn from one another and share experiences and knowledge to continue building climate ready

  3. {delta}-ALAD activity variations in red blood cells in response to lead accumulation in rock doves (Columba livia)

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, M.; Tejedor, M.C. [Universidad de Alcala de Henares (Spain)

    1992-10-01

    The enzyme {delta}-aminolevulinic acid dehydratase ({delta}-ALAD, E.C. 4.2.1.24), catalyses the second step of the haeme biosynthetic pathway and is required to maintain the haemoglobin and cytochrome content in red cells. {delta}-ALAD is not only found in bone marrow cells, the major site of haeme synthesis, but also in circulating erythrocytes and other tissues. An inverse correlation was found between {delta}-ALAD activity in red blood cells and lead concentration in the blood. The degree of {delta}-ALAD inhibition in erythrocytes has been widely accepted as a standard bioassay to detect acute and chronic lead exposure in humans and in avians. The value of this parameter as an indicator for environmental lead has been often reported in doves and Scanlon. In lead-treated rats, an increase in {delta}-ALAD activity in bone marrow cells and in blood samples was shown by radioimmunoassay at 5 and 9 days after the treatment. Similarly, the amount of {delta}-ALAD seems to be more sensitive to lead in avian species than in mammals, the usefulness of blood {delta}-ALAD activity as an index of lead exposure has already been questioned by Hutton in the pigeon and by Jaffe et al. in humans. The present investigation studied the toxic effects of lead on rock dove red blood cell {delta}-ALAD activity in two situations: in doves treated with lead acetate in the laboratory and in doves exposed to the environment of Alcala de Henares. The final lead blood concentrations were lower in the environmental than in the laboratory doves. {delta}-ALAD activity in bone marrow cells and the relationships between lead accumulation and enzyme activity in red cells, are examined. 20 refs., 5 figs., 1 tab.

  4. ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs

    Science.gov (United States)

    Cleves, Ann E.; Jain, Ajay N.

    2017-03-01

    We introduce the ForceGen method for 3D structure generation and conformer elaboration of drug-like small molecules. ForceGen is novel, avoiding use of distance geometry, molecular templates, or simulation-oriented stochastic sampling. The method is primarily driven by the molecular force field, implemented using an extension of MMFF94s and a partial charge estimator based on electronegativity-equalization. The force field is coupled to algorithms for direct sampling of realistic physical movements made by small molecules. Results are presented on a standard benchmark from the Cambridge Crystallographic Database of 480 drug-like small molecules, including full structure generation from SMILES strings. Reproduction of protein-bound crystallographic ligand poses is demonstrated on four carefully curated data sets: the ConfGen Set (667 ligands), the PINC cross-docking benchmark (1062 ligands), a large set of macrocyclic ligands (182 total with typical ring sizes of 12-23 atoms), and a commonly used benchmark for evaluating macrocycle conformer generation (30 ligands total). Results compare favorably to alternative methods, and performance on macrocyclic compounds approaches that observed on non-macrocycles while yielding a roughly 100-fold speed improvement over alternative MD-based methods with comparable performance.

  5. Mata—information generation in distributed information system

    Institute of Scientific and Technical Information of China (English)

    苏健; 高济

    2002-01-01

    The authors discuss the concept of meta-information which is the desription of information system or its subsystems,and proposes algorithms for meta-information generation.Meta-information can be generated in parallel mode and network computation can be used to accelerate meta-information generation.Most existing rough set methods assume information system to be centralized and cannot be applied directly in distributed information system.Data integration ,which is costly,is necessary for such existing methods.However,meta-information integration will eliminate the need of data integration in many cases,since many rough set operations can be done straightforward based on meta-information,and many existing methods can be modified based on meta-information.

  6. Meta-information generation in distributed information system

    Institute of Scientific and Technical Information of China (English)

    苏健; 高济

    2002-01-01

    The authors discuss the concept of meta-information which is the description of information system or its subsystems, and proposes algorithms for meta-information generation. Meta-information can be generated in parallel mode and network computation can be used to accelerate meta-information generation. Most existing rough set methods assume information system to be centralized and cannot be applied directly in distributed information system. Data integration, which is costly, is necessary for such existing methods. However, meta-information integration will eliminate the need of data integration in many cases, since many rough set operations can be done straightforward based on meta-information, and many existing methods can be modified based on meta-information.

  7. Automatic Optimizer Generation Method Based on Location and Context Information to Improve Mobile Services

    Directory of Open Access Journals (Sweden)

    Yunsik Son

    2017-01-01

    Full Text Available Several location-based services (LBSs have been recently developed for smartphones. Among these are proactive LBSs, which provide services to smartphone users by periodically collecting background logs. However, because they consume considerable battery power, they are not widely used for various LBS-based services. Battery consumption, in particular, is a significant issue on account of the characteristics of mobile systems. This problem involves a greater service restriction when performing complex operations. Therefore, to successfully enable various services based on location, this problem must be solved. In this paper, we introduce a technique to automatically generate a customized service optimizer for each application, service type, and platform using location and situation information. By using the proposed technique, energy and computing resources can be more efficiently employed for each service. Thus, users should receive more effective LBSs on mobile devices, such as smartphones.

  8. Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Retrorsine, Leading to DNA Adduct Formation In Vivo

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2005-04-01

    Full Text Available Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. The high toxicity of many pyrrolizidine alkaloids has caused considerable loss of free-ranging livestock due to liver and pulmonary lesions. Chronic exposure of toxic pyrrolizidine alkaloids to laboratory animals induces cancer. This investigation studies the metabolic activation of retrorsine, a representative naturally occurring tumorigenic pyrrolizidine alkaloid, and shows that a genotoxic mechanism is correlated to the tumorigenicity of retrorsine. Metabolism of retrorsine by liver microsomes of F344 female rats produced two metabolites, 6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, at a rate of 4.8 ± 0.1 nmol/mg/min, and retrorsine-N-oxide, at a rate of 17.6±0.5 nmol/mg/min. Metabolism was enhanced 1.7-fold by using liver microsomes prepared from dexamethasone-treated rats. DHP formation was inhibited 77% and retrorsine N-oxide formation was inhibited 29% by troleandomycin, a P450 3A enzyme inhibitor. Metabolism of retrorsine with lung, kidney, and spleen microsomes from dexamethasone-treated rats also generated DHP and the N-oxide derivative. When rat liver microsomal metabolism of retrorsine occurred in the presence of calf thymus DNA, a set of DHP-derived DNA adducts was formed; these adducts were detected and quantified by using a previously developed 32P-postlabeling/HPLC method. These same DNA adducts were also found in liver DNA of rats gavaged with retrorsine. Since DHP-derived DNA adducts are suggested to be potential biomarkers of riddelliine-induced tumorigenicity, our results indicate that (i similar to the metabolic activation of riddelliine, the mechanism of retrorsine-induced carcinogenicity in rats is also through a genotoxic mechanism involving DHP; and (ii the set of DHP-derived DNA adducts found in liver DNA of rats gavaged with retrorsine or riddelliine can serve as biomarkers for the

  9. Pupil Researchers Generation X: Educating Pupils as Active Participants--An Investigation into Gathering Sensitive Information from Early Adolescents

    Science.gov (United States)

    Symonds, Jenny E.

    2008-01-01

    Developmentally appropriate research techniques were uncovered by involving ten Year 7 pupils as researchers in a four-hour workshop that investigated the effectiveness of multiple methods in gathering sensitive information from early adolescents. The pupils learned about, tried and evaluated the methods of generating interview questions, peer and…

  10. Lead Generation and Optimization Based on Protein-Ligand Complementarity

    Directory of Open Access Journals (Sweden)

    Koji Ogata

    2010-06-01

    Full Text Available This work proposes a computational procedure for structure-based lead generation and optimization, which relies on the complementarity of the protein-ligand interactions. This procedure takes as input the known structure of a protein-ligand complex. Retaining the positions of the ligand heavy atoms in the protein binding site it designs structurally similar compounds considering all possible combinations of atomic species (N, C, O, CH3, NH,etc. Compounds are ranked based on a score which incorporates energetic contributions evaluated using molecular mechanics force fields. This procedure was used to design new inhibitor molecules for three serine/threonine protein kinases (p38 MAP kinase, p42 MAP kinase (ERK2, and c-Jun N-terminal kinase 3 (JNK3. For each enzyme, the calculations produce a set of potential inhibitors whose scores are in agreement with IC50 data and Ki values. Furthermore, the native ligands for each protein target, scored within the five top-ranking compounds predicted by our method, one of the top-ranking compounds predicted to inhibit JNK3 was synthesized and his inhibitory activity confirmed against ATP hydrolysis. Our computational procedure is therefore deemed to be a useful tool for generating chemically diverse molecules active against known target proteins.

  11. Use of air jet vortex generators leading to improved energy capture and power regulation of a wind turbine

    Energy Technology Data Exchange (ETDEWEB)

    Oliver, A.; Wootton, L.R. [City Univ., London (United Kingdom); Prats, J. [Ecotecnia SCC Ltd. (United Kingdom)

    1997-06-01

    City University and Ecotecnia have recently completed a project funded by the European Union Joule II programme on the optimisation and control of wind turbines. The blade set of a 150 kW stall regulated wind turbine was modified with air jet vortex generators and tested at full scale. This was done primarily to increase its energy yield by reducing energy loss in the region of the power curve `knee`, but also to allow a degree of power regulation in high wind speeds. Of these, the former has so far been demonstrated successfully. (author)

  12. Efficient methylammonium lead iodide perovskite solar cells with active layers from 300 to 900 nm

    Energy Technology Data Exchange (ETDEWEB)

    Momblona, C.; Malinkiewicz, O.; Soriano, A.; Gil-Escrig, L.; Bandiello, E.; Scheepers, M.; Bolink, H. J., E-mail: henk.bolink@uv.es [Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático J. Beltrán 2, 46980 Paterna, Valencia (Spain); Roldán-Carmona, C. [Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático J. Beltrán 2, 46980 Paterna, Valencia (Spain); Department of Physical Chemistry and Applied Thermodynamics, University of Córdoba, Campus Rabanales, Ed. C3, 14014, Córdoba (Spain); Edri, E. [Department of Materials and Interfaces, Weizmann Institute of Science, Herzl St. 34, Rehovot 76100 (Israel)

    2014-08-01

    Efficient methylammonium lead iodide perovskite-based solar cells have been prepared in which the perovskite layer is sandwiched in between two organic charge transporting layers that block holes and electrons, respectively. This configuration leads to stable and reproducible devices that do not suffer from strong hysteresis effects and when optimized lead to efficiencies close to 15%. The perovskite layer is formed by using a dual-source thermal evaporation method, whereas the organic layers are processed from solution. The dual-source thermal evaporation method leads to smooth films and allows for high precision thickness variations. Devices were prepared with perovskite layer thicknesses ranging from 160 to 900 nm. The short-circuit current observed for these devices increased with increasing perovskite layer thickness. The main parameter that decreases with increasing perovskite layer thickness is the fill factor and as a result optimum device performance is obtained for perovskite layer thickness around 300 nm. However, here we demonstrate that with a slightly oxidized electron blocking layer the fill factor for the solar cells with a perovskite layer thickness of 900 nm increases to the same values as for the devices with thin perovskite layers. As a result the power conversion efficiencies for the cells with 300 and 900 nm are very similar, 12.7% and 12%, respectively.

  13. Passive Reactive Berm (PRBerm) to Provide Low Maintenance Lead Containment at Active Small Arms Firing Ranges

    Science.gov (United States)

    2011-10-01

    ppm Parts per million PRBerm Passive Reactive Berm PVC Polyvinyl Chloride QA Quality assurance QC Quality control RO Reverse Osmosis Water RO...1228. Manninen, S., and N. Tanskanen. 1993. Transfer of lead from shotgun pellets to humus and three plant species in a Finnish shooting range

  14. Psychological determinants of information searching activity.

    Science.gov (United States)

    Gorunova, L

    2012-01-01

    The paper deals with the application of the activity theory in describing psychological determinants of the information searching activity. The notions of information behavior, information retrieval, information competence, information retrieval activity given in Russian and English scientific literature are compared. The research approach to the information retrieval activity based on the principles developed in the Russian theory of activity is described; and the fundamentals of G. Sukhodolsky's generalized conception of activity are presented for the first time. Analysis of empirical researches showed that specific features of information search depend on how the user evaluates information resources, information, conditions and results of search. Psychological determiners of information search may be detected as the system of evaluative alternatives, which is generated by the user during the process of his experience growth. We discovered that user's evaluation system is also related to his individual typological and personal regulative features and determines the choice of the search strategy.

  15. A Bio-inspired Collision Avoidance Model Based on Spatial Information Derived from Motion Detectors Leads to Common Routes.

    Science.gov (United States)

    Bertrand, Olivier J N; Lindemann, Jens P; Egelhaaf, Martin

    2015-11-01

    Avoiding collisions is one of the most basic needs of any mobile agent, both biological and technical, when searching around or aiming toward a goal. We propose a model of collision avoidance inspired by behavioral experiments on insects and by properties of optic flow on a spherical eye experienced during translation, and test the interaction of this model with goal-driven behavior. Insects, such as flies and bees, actively separate the rotational and translational optic flow components via behavior, i.e. by employing a saccadic strategy of flight and gaze control. Optic flow experienced during translation, i.e. during intersaccadic phases, contains information on the depth-structure of the environment, but this information is entangled with that on self-motion. Here, we propose a simple model to extract the depth structure from translational optic flow by using local properties of a spherical eye. On this basis, a motion direction of the agent is computed that ensures collision avoidance. Flying insects are thought to measure optic flow by correlation-type elementary motion detectors. Their responses depend, in addition to velocity, on the texture and contrast of objects and, thus, do not measure the velocity of objects veridically. Therefore, we initially used geometrically determined optic flow as input to a collision avoidance algorithm to show that depth information inferred from optic flow is sufficient to account for collision avoidance under closed-loop conditions. Then, the collision avoidance algorithm was tested with bio-inspired correlation-type elementary motion detectors in its input. Even then, the algorithm led successfully to collision avoidance and, in addition, replicated the characteristics of collision avoidance behavior of insects. Finally, the collision avoidance algorithm was combined with a goal direction and tested in cluttered environments. The simulated agent then showed goal-directed behavior reminiscent of components of the navigation

  16. Polyplex-induced cytosolic nuclease activation leads to differential transgene expression.

    Science.gov (United States)

    Rattan, Rahul; Vaidyanathan, Sriram; Wu, Gordon S-H; Shakya, Anisha; Orr, Bradford G; Banaszak Holl, Mark M

    2013-08-01

    Cytosolic nucleases have been proposed to play an important role in limiting the effectiveness of polyplex-based gene delivery agents. In order to explore the effect of cell membrane disruption on nuclease activation, nuclease activity upon polyplex uptake and localization, and nuclease activity upon gene expression, we employed an oligonucleotide molecular beacon (MB). The MB was incorporated as an integral part of the polymer/DNA polyplex, and two-color flow cytometry experiments were performed to explore the relationship of MB cleavage with propidium iodide (PI) uptake, protein expression, and polyplex uptake. In addition, confocal fluorescence microcopy was performed to examine both polyplex and cleaved MB localization. The impact of cell membrane disruption was also probed using whole-cell patch clamp measurement of the plasma membrane's electrical conductance. Differential activation of cytosolic nuclease was observed with substantial activity for B-PEI and G5 PAMAM dendrimer (G5), less cleavage for jetPEI, and little activity for L-PEI. jetPEI and L-PEI exhibited substantially greater transgene expression, consistent with the lower amounts of MB oligonucleotide cleavage observed. Cytosolic nuclease activity, although dependent on the choice of polymer employed, was not related to the degree of cell plasma membrane disruption that occurred as measured by PI uptake or whole-cell patch clamp.

  17. Psychological distress leads to reduced physical activity and fitness in children: the Australian longitudinal LOOK study.

    Science.gov (United States)

    Olive, L S; Telford, R M; Byrne, D G; Abhayaratna, W P; Telford, R D

    2016-08-01

    Stress and depression can affect an individual's level of physical activity and fitness, which may place them at risk of developing cardiovascular disease. This study investigates the longitudinal effects of stress and depression on physical activity and cardiorespiratory fitness among youth. Six hundred and seventy-six children, initially aged 8 years, from the LOOK study completed a modified version of the Children's Depression Inventory, the Children's Stress Questionnaire, and objective physical activity and cardiorespiratory fitness assessments on three occasions, every 4 years. Depressive symptoms had a direct effect (longitudinal) on the cardiorespiratory fitness of girls, with a similar trend for boys. In cross-sectional analyses, a child who identified with more symptoms of depression and stress was likely to be less fit and less physically active, which in girls extended to less moderate-to-vigorous physical activity. Our findings, that both physical activity and fitness are impacted by depression and stress may contribute to strategies directed towards achieving enhanced physical activity and reductions in obesity.

  18. Information from leading neutrons at HERA

    CERN Document Server

    Khoze, V A; Ryskin, M G

    2006-01-01

    In principle, leading neutrons produced in photoproduction and deep-inelastic scattering at HERA have the potential to determine the pion structure function, the neutron absorptive cross section and the form of the pion flux. To explore this potential we compare theoretical predictions for the x_L and p_t spectra of leading neutrons, and the Q^2 dependence of the cross section, with the existing ZEUS data.

  19. The generation of purinome-targeted libraries as a means to diversify ATP-mimetic chemical classes for lead finding.

    Science.gov (United States)

    Felder, Eduard R; Badari, Alessandra; Disingrini, Teresa; Mantegani, Sergio; Orrenius, Christian; Avanzi, Nilla; Isacchi, Antonella; Salom, Barbara

    2012-02-01

    The generation of novel chemotypes in support of our oncology research projects expanded in recent years from a canonical design of kinase-targeted compound libraries to a broader interpretation of purinome-targeted libraries (PTL) addressing the specificity of cancer relevant targets such as kinases and ATPases. Successful screening of structurally diverse ATP-binding targets requires compound libraries covering multiple design elements, which may include phosphate surrogate moieties in ATPase inhibitors or far reaching lipophilic residues stabilizing inactive kinase conformations. Here, we exemplify the design and preparation of drug-like combinatorial libraries and report significantly enhanced screening performance on purinomic targets. We compared overall hit rates of PTL with a simultaneously tested unbiased collection of 200,000 compounds and found consistent superiority of the targeted libraries in all cases. We also analyzed the performance of the largest targeted libraries in comparison with each other and often found striking differences in how a specific target responds to various chemotypes and to whole collections.

  20. Instructional leadership in elementary science: How are school leaders positioned to lead in a next generation science standards era?

    Science.gov (United States)

    Winn, Kathleen Mary

    The Next Generation Science Standards (NGSS) are the newest K-12 science content standards created by a coalition of educators, scientists, and researchers available for adoption by states and schools. Principals are important actors during policy implementation especially since principals are charged with assuming the role of an instructional leader for their teachers in all subject areas. Science poses a unique challenge to the elementary curricular landscape because traditionally, elementary teachers report low levels of self-efficacy in the subject. Support in this area therefore becomes important for a successful integration of a new science education agenda. This study analyzed self-reported survey data from public elementary principals (N=667) to address the following three research questions: (1) What type of science backgrounds do elementary principals have? (2) What indicators predict if elementary principals will engage in instructional leadership behaviors in science? (3) Does self-efficacy mediate the relationship between science background and a capacity for instructional leadership in science? The survey data were analyzed quantitatively. Descriptive statistics address the first research question and inferential statistics (hierarchal regression analysis and a mediation analysis) answer the second and third research questions.The sample data show that about 21% of elementary principals have a formal science degree and 26% have a degree in a STEM field. Most principals have not had recent experience teaching science, nor were they every exclusively a science teacher. The analyses suggests that demographic, experiential, and self-efficacy variables predict instructional leadership practices in science.

  1. Si-H activation of hydrosilanes leading to hydrido silyl and bis(silyl) nickel complexes.

    Science.gov (United States)

    Zell, Thomas; Schaub, Thomas; Radacki, Krzysztof; Radius, Udo

    2011-03-07

    A general route for the synthesis of novel NHC stabilized nickel bis(silyl) and nickel hydrido silyl complexes is presented. The reaction of [Ni(2)((i)Pr(2)Im)(4)(COD)] 1 ((i)Pr(2)Im = 1,3-di-isopropyl-imidazolin-2-ylidene) with hydrosilanes H(n)SiR(4-n) leads to complexes of the type [Ni((i)Pr(2)Im)(2)(SiH(n-1)R(4-n))(H)] or [Ni((i)Pr(2)Im)(2)(SiH(n-1)R(4-n))(2)].

  2. Chronic Cadmium Exposure Lead to Inhibition of Serum and Hepatic Alkaline Phosphatase Activity in Wistar Rats.

    Science.gov (United States)

    Treviño, Samuel; Andrade-García, Alejandra; Herrera Camacho, Irma; León-Chavez, Bertha Alicia; Aguilar-Alonso, Patricia; Flores, Gonzalo; Brambila, Eduardo

    2015-12-01

    Alkaline phosphatase (ALP) activity in the serum and liver from rats administered with cadmium (Cd) in drinking water was studied. After metal administration, Cd showed a time-dependent accumulation in the liver, meanwhile metallothionein had a maximum increase at 1 month, remaining in this level until the end of the study. On the other hand, serum and liver ALP activity was decreased after 3 months exposure. To determine if Cd produced an inhibition on enzyme, apo-ALP prepared from both nonexposed and exposed rats was reactivated with Zn, showing 60% more activity as compared with the enzyme isolated from nonexposed rats. In vitro assays showed that Cd-ALP was partially reactivated with Zn; however, in the presence of cadmium, Zn-ALP was completely inhibited. Kinetic studies indicate a noncompetitive inhibition by Cd; these results suggest that Cd can substitute Zn, and/or Cd can interact with nucleophilic ligands essential for the enzymatic activity.

  3. New generation NMR bioreactor coupled with high-resolution NMR spectroscopy leads to novel discoveries in Moorella thermoaceticum metabolic profiles

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Junfeng; Isern, Nancy G.; Ewing, R James; Liyu, Andrey V.; Sears, Jesse A.; Knapp, Harlan; Iversen, Jens; Sisk, Daniel R.; Ahring, Birgitte K.; Majors, Paul D.

    2014-06-20

    An in-situ nuclear magnetic resonance (NMR) bioreactor was developed and employed to monitor microbial metabolism under batch-growth conditions in real time. We selected Moorella thermoacetica ATCC 49707 as a test case. M. thermoacetica (formerly Clostridium thermoaceticum) is a strictly anaerobic, thermophilic, acetogenic, gram-positive bacterium with potential for industrial production of chemicals. The metabolic profiles of M. thermoacetica were characterized during growth in batch mode on xylose (a component of lignocellulosic biomass) using the new generation NMR bioreactor in combination with high-resolution, high sensitivity NMR (HR-NMR) spectroscopy. In-situ NMR measurements were performed using water-suppressed H-1 NMR spectroscopy at an NMR frequency of 500 MHz, and aliquots of the bioreactor contents were taken for 600 MHz HR-NMR spectroscopy at specific intervals to confirm metabolite identifications and expand metabolite coverage. M. thermoacetica demonstrated the metabolic potential to produce formate, ethanol and methanol from xylose, in addition to its known capability of producing acetic acid. Real-time monitoring of bioreactor conditions showed a temporary pH decrease, with a concomitant increase in formic acid during exponential growth. Fermentation experiments performed outside of the magnet showed that the strong magnetic field employed for NMR detection did not significantly affect cell metabolism. Use of the in-situ NMR bioreactor facilitated monitoring of the fermentation process in real time, enabling identification of intermediate and end-point metabolites and their correlation with pH and biomass produced during culture growth. Real-time monitoring of culture metabolism using the NMR bioreactor in combination with the HR-NMR spectroscopy will allow optimization of the metabolism of microorganisms producing valuable bioproducts.

  4. New generation NMR bioreactor coupled with high-resolution NMR spectroscopy leads to novel discoveries in Moorella thermoacetica metabolic profiles.

    Science.gov (United States)

    Xue, Junfeng; Isern, Nancy G; Ewing, R James; Liyu, Andrei V; Sears, Jesse A; Knapp, Harlan; Iversen, Jens; Sisk, Daniel R; Ahring, Birgitte K; Majors, Paul D

    2014-10-01

    An in situ nuclear magnetic resonance (NMR) bioreactor was developed and employed to monitor microbial metabolism under batch growth conditions in real time. We selected Moorella thermoacetica ATCC 49707 as a test case. M. thermoacetica (formerly Clostridium thermoaceticum) is a strictly anaerobic, thermophilic, acetogenic, gram-positive bacterium with potential for industrial production of chemicals. The metabolic profiles of M. thermoacetica were characterized during growth in batch mode on xylose (a component of lignocellulosic biomass) using the new generation NMR bioreactor in combination with high-resolution NMR (HR-NMR) spectroscopy. In situ NMR measurements were performed using water-suppressed H-1 NMR spectroscopy at 500 MHz, and aliquots of the bioreactor contents were taken for 600-MHz HR-NMR spectroscopy at specific intervals to confirm metabolite identifications and expand metabolite coverage. M. thermoacetica demonstrated the metabolic potential to produce formate, ethanol, and methanol from xylose, in addition to its known capability of producing acetic acid. Real-time monitoring of bioreactor conditions showed a temporary pH decrease, with a concomitant increase in formic acid during exponential growth. Fermentation experiments performed outside of the magnet showed that the strong magnetic field employed for NMR detection did not significantly affect cell metabolism. Use of the in situ NMR bioreactor facilitated monitoring of the fermentation process, enabling identification of intermediate and endpoint metabolites and their correlation with pH and biomass produced during culture growth. Real-time monitoring of culture metabolism using the NMR bioreactor in combination with HR-NMR spectroscopy will allow optimization of the metabolism of microorganisms producing valuable bioproducts.

  5. Stress-activated signaling responses leading to apoptosis following photodynamic therapy

    Science.gov (United States)

    Oleinick, Nancy L.; He, Jin; Xue, Liang-yan; Separovic, Duska

    1998-05-01

    Photodynamic treatment with the phthalocyanine Pc 4, a mitochondrially localizing photosensitizer, is an efficient inducer of cell death by apoptosis, a cell suicide pathway that can be triggered by physiological stimuli as well as by various types of cellular damage. Upon exposure of the dye- loaded cells to red light, several stress signalling pathways are rapidly activated. In murine L5178Y-R lymphoblasts, caspase activation and other hallmarks of the final phase of apoptosis are observed within a few minutes post-PDT. In Chinese hamster CHO-K1 cells, the first signs of apoptosis are not observed for 1 - 2 hours. The possible involvement of three parallel mitogen-activated protein kinase (MAPK) signalling pathways has been investigated. The extracellular- regulated kinases (ERK-1 and ERK-2), that are thought to promote cell growth, are not appreciably altered by PDT. However, PDT causes marked activation of the stress-activated protein kinase (SAPK) cascade in both cell types and of the p38/HOG-type kinase in CHO cells. Both of these latter pathways have been demonstrated to be associated with apoptosis. A specific inhibitor of the ERK pathway did not alter PDT-induced apoptosis; however, an inhibitor of the p38 pathway partially blocked PDT-induced apoptosis. Blockage of the SAPK pathway is being pursued by a genetic approach. It appears that the SAPK and p38 pathways may participate in signaling apoptosis in response to PDT with Pc 4.

  6. Lead from hunting activities and its potential environmental threat to wildlife in a protected wetland in Yucatan, Mexico.

    Science.gov (United States)

    Arcega-Cabrera, Flor; Noreña-Barroso, Elsa; Oceguera-Vargas, Ismael

    2014-02-01

    This study provides insights into the status of lead in the protected wetland of El Palmar, located on the northwestern littoral of the Yucatan Peninsula. This reserve is ecologically and economically important because it provides feeding and breeding habitats for many species, as well as being an ecotourism destination (especially for bird watching). Although it is a protected area, duck species are heavily hunted within the reserve during the winter. As a result, animals feeding or living in sediments could be exposed to anthropogenic lead. Total lead and its geochemical fractionated forms were measured in sediment cores from six selected sites in "El Palmar" wetland, during pre- and post-hunting seasons, to approximate the potential environmental threat (especially for benthonic living/feeding organisms). Anthropogenic lead concentrations detected in soil cores ranged from below the minimum infaunal community effect level (30.24 μg g(-1)) during the pre-hunting season, to bordering the probable infaunal community effect level (112.18 μg g(-1)) during the post-hunting season, according to SquiiRTs NOAA guidelines. Yet, these results were lower than expected based on the intensity of hunting. Consequently, this article explores the possibility that the lower than expected lead concentration in sediments results from (1) degradation of shot and transformation to soluble or particulate forms; or (2) ingestion of lead shot by benthic and other lacustrine species living in the protected area. Geochemical fractionation of lead demonstrated that in the top 6 cm of the soil column at heavily active hunting sites (EP5 and EP6), lead was associated with the lithogenic fraction (average 45 percent) and with the organic fraction (average 20 percent). Bioavailable lead (sum of lead adsorbed to the carbonates, Fe/Mn oxyhydroxides and organic fractions) in sediments was lower than 50 percent for the heavily active hunting areas and higher for the rest of the sites

  7. Biochemical and molecular effects of gestational and lactational coexposure to lead and cadmium on ovarian steroidogenesis are associated with oxidative stress in F1 generation rats.

    Science.gov (United States)

    Pillai, Prakash; Pandya, Chirayu; Gupta, Sharad; Gupta, Sarita

    2010-01-01

    Few studies have characterized the molecular and biochemical mechanisms involved in ovarian steroidogenesis disruption by heavy metals, such as lead and cadmium coexposure, on F1 generation offspring. In this study, adult pregnant female rats were treated subcutaneously (0.05 mg/kg of body weight per day) with sodium acetate (control), lead acetate, and cadmium acetate separately and in combination throughout gestational and lactational period, and all animals from each of the experimental groups were sacrificed by decapitation on postnatal day 56 for various assays. The activities of key steroidogenic enzymes (17β-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase) decreased in all the metal-treated groups. But the most significant decrease in the activities was observed in the cadmium-treated group, whereas the combined exposure group showed an intermediate effect. Serum estradiol and progesterone levels were also significantly altered in all the metal-treated groups, with the cadmium-exposed group showing maximum reductions as compared with the control group. The inhibitory effects of lead and cadmium on ovarian steroidogenic acute regulatory protein (StAR) mRNA levels along with CYP11 mRNA levels were also observed. Ovarian cholesterol content measured also showed significant depletion in all the metal-treated groups, with the cadmium-exposed group showing the maximum depletion. The activities of ovarian enzymatic antioxidants, such as superoxide dismutase, catalase, and glutathione peroxidase, were all significantly diminished along with significant depletion in nonenzymatic antioxidants. Lipid peroxidation was elevated significantly in all the metal-treated groups. In conclusion, lead and cadmium inhibit ovarian steroidogenesis by downregulating StAR gene expression along with inhibiting activities of steroidogenic enzymes and antioxidant system.

  8. Leading into the future: coaching and mentoring Generation X employees.

    Science.gov (United States)

    Weston, M J

    2001-09-01

    Managers who recognize that Generation X employees are looking for workplaces that allow them to develop their competencies as well as have a balance in their personal and professional lives, are more successful in attracting and retaining employees in this age group. Savvy managers understand that adapting to meet the needs of Generation X employees also assists the manager in transitioning into the Information Age and the workplace of the future.

  9. Adipocyte Mineralocorticoid Receptor Activation Leads to Metabolic Syndrome and Induction of Prostaglandin D2 Synthase.

    Science.gov (United States)

    Urbanet, Riccardo; Nguyen Dinh Cat, Aurelie; Feraco, Alessandra; Venteclef, Nicolas; El Mogrhabi, Soumaya; Sierra-Ramos, Catalina; Alvarez de la Rosa, Diego; Adler, Gail K; Quilliot, Didier; Rossignol, Patrick; Fallo, Francesco; Touyz, Rhian M; Jaisser, Frédéric

    2015-07-01

    Metabolic syndrome is a major risk factor for the development of diabetes mellitus and cardiovascular diseases. Pharmacological antagonism of the mineralocorticoid receptor (MR), a ligand-activated transcription factor, limits metabolic syndrome in preclinical models, but mechanistic studies are lacking to delineate the role of MR activation in adipose tissue. In this study, we report that MR expression is increased in visceral adipose tissue in a preclinical mouse model of metabolic syndrome and in obese patients. In vivo conditional upregulation of MR in mouse adipocytes led to increased weight and fat mass, insulin resistance, and metabolic syndrome features without affecting blood pressure. We identified prostaglandin D2 synthase as a novel MR target gene in adipocytes and AT56, a specific inhibitor of prostaglandin D2 synthase enzymatic activity, blunted adipogenic aldosterone effects. Moreover, translational studies showed that expression of MR and prostaglandin D2 synthase is strongly correlated in adipose tissues from obese patients.

  10. Active and Non-Active Volumetric Information Spaces to Supplement Traditional Rehabilitation

    DEFF Research Database (Denmark)

    Brooks, Anthony Lewis

    2013-01-01

    , a noninvasive (non-wearable/gesture-based) motion-sensitive sensor system enabling human performance control of computer- generated multimedia was originated. Digital music making via motion data was originally investigated as a strategy to train physical impairment. Gesture-control of painting, robot control...... with an intervention approach to maximize a participant’s development. Emergent are models toward establishing valid and replicable techniques and methods to evolve new digital test batteries to assess clinical evidence. Human-machine, human-human interactions, and information exchange are core of the research...

  11. Design of a leading indicator for Costa Rican economic activity

    Directory of Open Access Journals (Sweden)

    Carlos Chaverri Morales

    2014-08-01

    Full Text Available This paper presents the results of estimating three leading indicators for the turning points of the economic activity in Costa Rica. This was done following the methodology proposed by the Organization for Economic Cooperation and Development (OECD. The Monthly Economic Activity Index (IMAE in Spanish was selected as the reference variable.  A total of 270 data series were analyzed including monetary, real and job market variables, as well as price indices, external sector indicators and fiscal sector variables. The real sector information was disaggregated into three levels, which included the classification of data at an industrial level using the International Standard Industrial Classification (ISIC with two digits, information from the agricultural sector based on the Central Product Classification (CPC and information from the manufacturing sector.  A leading indicator was developed for each level of aggregation, resulting in average leads of 7 to 12 months compared to the reference variable.

  12. Spanish Young Generation (JJNN) Activities

    Energy Technology Data Exchange (ETDEWEB)

    Millan, Miguel [INITEC Nuclear- Westinghouse, Padilla 17, 28006 Madrid (Spain)

    2008-07-01

    Spanish Young Generation has been very active during 2006-2008. JJNN have mainly focused on communication activities, as conferences at universities, schools and nuclear companies. Lately, becoming in referent of the young politics, journalist and the young people in Nuclear Subjects is the new and most challenging target of the Spanish Young Generation. In order to accomplish with their objects and commitments with their members, JJNN are developing all kinds of activities focused in the young people and the JJNN members. (authors)

  13. 78 FR 13052 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2013-02-26

    ... information; search data sources; complete and review the collection of information; and transmit or otherwise... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Agency Information Collection Activities; Submission to OMB for Review and Approval;...

  14. U.S. Government Activities to Protect the Information Infrastructure

    Science.gov (United States)

    2007-11-02

    policy recommendations for "global information infrastructure - global information society ", and the ICCP is currently preparing a substantial background...report. • Telecommunications • Economics of the Information Society • High Performance Computing and Networking • Security, privacy...projects are directed toward demonstrating the potential of the Information Society and stimulate its deployment. The projects support the goal of

  15. An Activity Theory Approach to Analyze Barriers to a Virtual Management Information Systems (MIS) Curriculum

    Science.gov (United States)

    Jaradat, Suhair; Qablan, Ahmad; Barham, Areej

    2011-01-01

    This paper explains how the activity theory is used as a framework to analyze the barriers to a virtual Management Information Stream (MIS) Curriculum in Jordanian schools, from both the sociocultural and pedagogical perspectives. Taking the activity system as a unit of analysis, this study documents the processes by which activities shape and are…

  16. The conversion of fibrinogen to fibrin at the surface of curliated Escherichia coli bacteria leads to the generation of proinflammatory fibrinopeptides.

    Science.gov (United States)

    Persson, Kristin; Russell, Wayne; Mörgelin, Matthias; Herwald, Heiko

    2003-08-22

    The inflammatory response to bacterial infection is the result of a complex interplay between bacterial products and host effector systems, such as the immune and complement systems. Here we show that Escherichia coli bacteria expressing fibrous surface proteins, known as curli, assemble and activate factors of the human coagulation cascade at their surface. As a result of this interaction, fibrinogen is converted to fibrin and fibrinogen-derived peptides, termed fibrinopeptides, are generated. The molecular mechanisms behind the bacteria-induced formation of fibrinopeptides were investigated and shown to be triggered by the activation of the contact system, also known as the kallikrein/kinin system or the intrinsic pathway of coagulation. Samples containing fibrinopeptides generated by the interaction between bacteria and plasma were injected into animals and the inflammatory response was monitored. We found that this treatment provoked an infiltration of white blood cells, and the induction of the proinflammatory cytokine MCP-1 at the inflamed site. Our results therefore demonstrate that activation of the coagulation system at the bacterial surface contributes to the pathophysiology of bacterial infectious diseases.

  17. Transcriptome profiling of radish (Raphanus sativus L.) root and identification of genes involved in response to Lead (Pb) stress with next generation sequencing.

    Science.gov (United States)

    Wang, Yan; Xu, Liang; Chen, Yinglong; Shen, Hong; Gong, Yiqin; Limera, Cecilia; Liu, Liwang

    2013-01-01

    Lead (Pb), one of the most toxic heavy metals, can be absorbed and accumulated by plant roots and then enter the food chain resulting in potential health risks for human beings. The radish (Raphanus sativus L.) is an important root vegetable crop with fleshy taproots as the edible parts. Little is known about the mechanism by which radishes respond to Pb stress at the molecular level. In this study, Next Generation Sequencing (NGS)-based RNA-seq technology was employed to characterize the de novo transcriptome of radish roots and identify differentially expressed genes (DEGs) during Pb stress. A total of 68,940 assembled unique transcripts including 33,337 unigenes were obtained from radish root cDNA samples. Based on the assembled de novo transcriptome, 4,614 DEGs were detected between the two libraries of untreated (CK) and Pb-treated (Pb1000) roots. Gene Ontology (GO) and pathway enrichment analysis revealed that upregulated DEGs under Pb stress are predominately involved in defense responses in cell walls and glutathione metabolism-related processes, while downregulated DEGs were mainly involved in carbohydrate metabolism-related pathways. The expression patterns of 22 selected genes were validated by quantitative real-time PCR, and the results were highly accordant with the Solexa analysis. Furthermore, many candidate genes, which were involved in defense and detoxification mechanisms including signaling protein kinases, transcription factors, metal transporters and chelate compound biosynthesis related enzymes, were successfully identified in response to heavy metal Pb. Identification of potential DEGs involved in responses to Pb stress significantly reflected alterations in major biological processes and metabolic pathways. The molecular basis of the response to Pb stress in radishes was comprehensively characterized. Useful information and new insights were provided for investigating the molecular regulation mechanism of heavy metal Pb accumulation and

  18. Neuronal c-Abl activation leads to induction of cell cycle and interferon signaling pathways

    Directory of Open Access Journals (Sweden)

    Schlatterer Sarah D

    2012-08-01

    Full Text Available Abstract Background Expression of active c-Abl in adult mouse forebrain neurons in the AblPP/tTA mice resulted in severe neurodegeneration, particularly in the CA1 region of the hippocampus. Neuronal loss was preceded and accompanied by substantial microgliosis and astrocytosis. In contrast, expression of constitutively active Arg (Abl-related gene in mouse forebrain neurons (ArgPP/tTA mice caused no detectable neuronal loss or gliosis, although protein expression and kinase activity were at similar levels to those in the AblPP/tTA mice. Methods To begin to elucidate the mechanism of c-Abl-induced neuronal loss and gliosis, gene expression analysis of AblPP/tTA mouse forebrain prior to development of overt pathology was performed. Selected results from gene expression studies were validated with quantitative reverse transcription PCR , immunoblotting and bromodeoxyuridine (BrdU labeling, and by immunocytochemistry. Results Two of the top pathways upregulated in AblPP/tTA mice with c-Abl expression for 2 weeks were cell cycle and interferon signaling. However, only the expression of interferon signaling pathway genes remained elevated at 4 weeks of c-Abl induction. BrdU incorporation studies confirm that, while the cell cycle pathway is upregulated in AblPP/tTA mice at 2 weeks of c-Abl induction, the anatomical localization of the pathway is not consistent with previous pathology seen in the AblPP/tTA mice. Increased expression and activation of STAT1, a known component of interferon signaling and interferon-induced neuronal excitotoxicity, is an early consequence of c-Abl activation in AblPP/tTA mice and occurs in the CA1 region of the hippocampus, the same region that goes on to develop severe neurodegenerative pathology and neuroinflammation. Interestingly, no upregulation of gene expression of interferons themselves was detected. Conclusions Our data suggest that the interferon signaling pathway may play a role in the pathologic processes

  19. Dual-action Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

    Science.gov (United States)

    Abdolmalekia, Azizeh; Ghasemi, Jahan B

    2016-09-27

    Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as a selective multi-target chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mt-drugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included.

  20. UNESCO active learning approach in optics and photonics leads to significant change in Morocco

    Science.gov (United States)

    Berrada, K.; Channa, R.; Outzourhit, A.; Azizan, M.; Oueriagli, A.

    2014-07-01

    There are many difficulties in teaching science and technology in developing countries. Several different teaching strategies have to be applied in these cases. More specifically, for developing countries competencies in teaching science in the introductory classroom has attracted much attention. As a specific example we will consider the Moroccan system. In most developing countries everything is moving so slowly that the progress stays static for development. Also, any change needs time, effort and engagement. In our case we discovered that many teachers feel uncomfortable when introducing new teaching methods and evaluation in classes at introductory physics. However, the introduction of an Active Learning in our curricula showed difficulties that students have in understanding physics and especially concepts. Students were interested in having Active Learning courses much more than passive and traditional ones. Changing believes on physical phenomena and reality of the world students become more attractive and their way of thinking Science changed. The main philosophy of fostering modern hands-on learning techniques -adapted to local needs and availability of teaching resources- is elaborated. The Active Learning program provides the teachers with a conceptual evaluation instrument, drawn from relevant physics education research, giving teachers an important tool to measure student learning. We will try to describe the UNESCO Chair project in physics created in 2010 at Cadi Ayyad University since our first experience with UNESCO ALOP program. Many efforts have been done so far and the project helps now to develop more national and international collaborations between universities and Regional Academies of Education and Training. As a new result of these actions and according to our local needs, the translation of the ALOP program into Arabic is now available under the auspice of UNESCO and encouragement of international partners SPIE, ICTP, ICO and OSA.

  1. Design and Synthesis of (+)-Discodermolide-Paclitaxel Hybrids Leading to Enhanced Biological Activity1

    Science.gov (United States)

    Smith, Amos B.; Sugasawa, Keizo; Atasoylu, Onur; Yang, Chia-Ping Huang; Horwitz, Susan Band

    2011-01-01

    Potential binding modes of (+)-discodermolide at the paclitaxel binding site of tubulin have been identified by computational studies based on earlier structural and SAR data. Examination of the prospective binding modes reveal that the aromatic pocket occupied by the paclitaxel side-chain is unoccupied by (+)-discodermolide. Based on these findings, a small library of (+)-discodermolide-paclitaxel hybrids have been designed and synthesized. Biological evaluation reveals a two- to eight- fold increase in antiproliferative activity compared to the parent molecule using the A549 and MCF-7 cancer cell lines. PMID:21870795

  2. Design and synthesis of (+)-discodermolide-paclitaxel hybrids leading to enhanced biological activity.

    Science.gov (United States)

    Smith, Amos B; Sugasawa, Keizo; Atasoylu, Onur; Yang, Chia-Ping Huang; Horwitz, Susan Band

    2011-09-22

    Potential binding modes of (+)-discodermolide at the paclitaxel binding site of tubulin have been identified by computational studies based on earlier structural and SAR data. Examination of the prospective binding modes reveal that the aromatic pocket occupied by the paclitaxel side chain is unoccupied by (+)-discodermolide. Based on these findings, a small library of (+)-discodermolide-paclitaxel hybrids have been designed and synthesized. Biological evaluation reveals a two- to eight-fold increase in antiproliferative activity compared to the parent molecule using the A549 and MCF-7 cancer cell lines.

  3. Uptake of Optional Activities Leads to Improved Performance in a Biomedical Sciences Class

    Science.gov (United States)

    Verkade, Heather; Lim, Saw Hoon

    2015-01-01

    Optional (non-assessed) learning activities are a learning tool that may help students achieve their desired grade, or help students with lower levels of previous experience in the topic. This study examines the implementation of, and outcomes from, two optional activities, one online and one paper-based. The activities complemented the lectures…

  4. The TECS model leads to active use of technology in home care

    DEFF Research Database (Denmark)

    Jensen, Ulla Gars; Skov, Hanne

    2016-01-01

    Digitization in healthcare is accelerating worldwide. This article focuses on the X-Changery development project involving home-care nurses and their use of the iPad as a new tool in patients’ homes. The goal of the project was to bring knowledge from recent research on technological literacy...... in working life back to a work setting, thus giving nurses new technology competencies with the aim of enhancing their professionalism through the use of the iPad as a work tool. Through field observations, learning labs and focus-group interviews we can see that X-Changery gave home-care nurses a common...... language to exchange experiences and share knowledge about the iPad as a work tool. Use of the iPad in patients’ homes led to new habits and routines. Nurses acquired relational expertise, implying active use of technology. The results show the importance of focusing on and funding reflection...

  5. Generation of priority research questions to inform conservation policy and management at a national level.

    Science.gov (United States)

    Rudd, Murray A; Beazley, Karen F; Cooke, Steven J; Fleishman, Erica; Lane, Daniel E; Mascia, Michael B; Roth, Robin; Tabor, Gary; Bakker, Jiselle A; Bellefontaine, Teresa; Berteaux, Dominique; Cantin, Bernard; Chaulk, Keith G; Cunningham, Kathryn; Dobell, Rod; Fast, Eleanor; Ferrara, Nadia; Findlay, C Scott; Hallstrom, Lars K; Hammond, Thomas; Hermanutz, Luise; Hutchings, Jeffrey A; Lindsay, Kathryn E; Marta, Tim J; Nguyen, Vivian M; Northey, Greg; Prior, Kent; Ramirez-Sanchez, Saudiel; Rice, Jake; Sleep, Darren J H; Szabo, Nora D; Trottier, Geneviève; Toussaint, Jean-Patrick; Veilleux, Jean-Philippe

    2011-06-01

    Integrating knowledge from across the natural and social sciences is necessary to effectively address societal tradeoffs between human use of biological diversity and its preservation. Collaborative processes can change the ways decision makers think about scientific evidence, enhance levels of mutual trust and credibility, and advance the conservation policy discourse. Canada has responsibility for a large fraction of some major ecosystems, such as boreal forests, Arctic tundra, wetlands, and temperate and Arctic oceans. Stressors to biological diversity within these ecosystems arise from activities of the country's resource-based economy, as well as external drivers of environmental change. Effective management is complicated by incongruence between ecological and political boundaries and conflicting perspectives on social and economic goals. Many knowledge gaps about stressors and their management might be reduced through targeted, timely research. We identify 40 questions that, if addressed or answered, would advance research that has a high probability of supporting development of effective policies and management strategies for species, ecosystems, and ecological processes in Canada. A total of 396 candidate questions drawn from natural and social science disciplines were contributed by individuals with diverse organizational affiliations. These were collaboratively winnowed to 40 by our team of collaborators. The questions emphasize understanding ecosystems, the effects and mitigation of climate change, coordinating governance and management efforts across multiple jurisdictions, and examining relations between conservation policy and the social and economic well-being of Aboriginal peoples. The questions we identified provide potential links between evidence from the conservation sciences and formulation of policies for conservation and resource management. Our collaborative process of communication and engagement between scientists and decision makers for

  6. Rhabdomyolysis-Associated Mutations in Human LPIN1 Lead to Loss of Phosphatidic Acid Phosphohydrolase Activity.

    Science.gov (United States)

    Schweitzer, George G; Collier, Sara L; Chen, Zhouji; Eaton, James M; Connolly, Anne M; Bucelli, Robert C; Pestronk, Alan; Harris, Thurl E; Finck, Brian N

    2015-01-01

    Rhabdomyolysis is an acute syndrome due to extensive injury of skeletal muscle. Recurrent rhabdomyolysis is often caused by inborn errors in intermediary metabolism, and recent work has suggested that mutations in the human gene encoding lipin 1 (LPIN1) may be a common cause of recurrent rhabdomyolysis in children. Lipin 1 dephosphorylates phosphatidic acid to form diacylglycerol (phosphatidic acid phosphohydrolase; PAP) and acts as a transcriptional regulatory protein to control metabolic gene expression. Herein, a 3-year-old boy with severe recurrent rhabdomyolysis was determined to be a compound heterozygote for a novel c.1904T>C (p.Leu635Pro) substitution and a previously reported genomic deletion of exons 18-19 (E766-S838_del) in LPIN1. Western blotting with patient muscle biopsy lysates demonstrated a marked reduction in lipin 1 protein, while immunohistochemical staining for lipin 1 showed abnormal subcellular localization. We cloned cDNAs to express recombinant lipin 1 proteins harboring pathogenic mutations and showed that the E766-S838_del allele was not expressed at the RNA or protein level. Lipin 1 p.Leu635Pro was expressed, but the protein was less stable, was aggregated in the cytosol, and was targeted for proteosomal degradation. Another pathogenic single amino acid substitution, lipin 1 p.Arg725His, was well expressed and retained its transcriptional regulatory function. However, both p.Leu635Pro and p.Arg725His proteins were found to be deficient in PAP activity. Kinetic analyses demonstrated a loss of catalysis rather than diminished substrate binding. These data suggest that loss of lipin 1-mediated PAP activity may be involved in the pathogenesis of rhabdomyolysis in lipin 1 deficiency.

  7. Human Platelets Utilize Cycloxygenase-1 to Generate Dioxolane A3, a Neutrophil-activating Eicosanoid.

    Science.gov (United States)

    Hinz, Christine; Aldrovandi, Maceler; Uhlson, Charis; Marnett, Lawrence J; Longhurst, Hilary J; Warner, Timothy D; Alam, Saydul; Slatter, David A; Lauder, Sarah N; Allen-Redpath, Keith; Collins, Peter W; Murphy, Robert C; Thomas, Christopher P; O'Donnell, Valerie B

    2016-06-24

    Eicosanoids are important mediators of fever, pain, and inflammation that modulate cell signaling during acute and chronic disease. We show by using lipidomics that thrombin-activated human platelets generate a new type of eicosanoid that both stimulates and primes human neutrophil integrin (Mac-1) expression, in response to formylmethionylleucylphenylalanine. Detailed characterization proposes a dioxolane structure, 8-hydroxy-9,11-dioxolane eicosatetraenoic acid (dioxolane A3, DXA3). The lipid is generated in nanogram amounts by platelets from endogenous arachidonate during physiological activation, with inhibition by aspirin in vitro or in vivo, implicating cyclooxygenase-1 (COX). Pharmacological and genetic studies on human/murine platelets revealed that DXA3 formation requires protease-activated receptors 1 and 4, cytosolic phospholipase A2 (cPLA2), Src tyrosine kinases, p38 MAPK, phospholipase C, and intracellular calcium. From data generated by purified COX isoforms and chemical oxidation, we propose that DXA3 is generated by release of an intermediate from the active site followed by oxygenation at C8. In summary, a new neutrophil-activating platelet-derived lipid generated by COX-1 is presented that can activate or prime human neutrophils, suggesting a role in innate immunity and acute inflammation.

  8. Human Platelets Utilize Cycloxygenase-1 to Generate Dioxolane A3, a Neutrophil-activating Eicosanoid*

    Science.gov (United States)

    Hinz, Christine; Aldrovandi, Maceler; Uhlson, Charis; Marnett, Lawrence J.; Longhurst, Hilary J.; Warner, Timothy D.; Alam, Saydul; Slatter, David A.; Lauder, Sarah N.; Allen-Redpath, Keith; Collins, Peter W.; Murphy, Robert C.; Thomas, Christopher P.; O'Donnell, Valerie B.

    2016-01-01

    Eicosanoids are important mediators of fever, pain, and inflammation that modulate cell signaling during acute and chronic disease. We show by using lipidomics that thrombin-activated human platelets generate a new type of eicosanoid that both stimulates and primes human neutrophil integrin (Mac-1) expression, in response to formylmethionylleucylphenylalanine. Detailed characterization proposes a dioxolane structure, 8-hydroxy-9,11-dioxolane eicosatetraenoic acid (dioxolane A3, DXA3). The lipid is generated in nanogram amounts by platelets from endogenous arachidonate during physiological activation, with inhibition by aspirin in vitro or in vivo, implicating cyclooxygenase-1 (COX). Pharmacological and genetic studies on human/murine platelets revealed that DXA3 formation requires protease-activated receptors 1 and 4, cytosolic phospholipase A2 (cPLA2), Src tyrosine kinases, p38 MAPK, phospholipase C, and intracellular calcium. From data generated by purified COX isoforms and chemical oxidation, we propose that DXA3 is generated by release of an intermediate from the active site followed by oxygenation at C8. In summary, a new neutrophil-activating platelet-derived lipid generated by COX-1 is presented that can activate or prime human neutrophils, suggesting a role in innate immunity and acute inflammation. PMID:27129261

  9. Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism.

    Directory of Open Access Journals (Sweden)

    Erik Södersten

    2014-09-01

    Full Text Available Polycomb group (PcG proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq in combination with expression analysis by RNA-sequencing (RNA-seq showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease.

  10. To Lead or Not to Lead?

    Science.gov (United States)

    Bertenshaw, Maria; Bradford, Katie; Burns, Natalie; Flux, Rachel; Horan, Danielle

    2013-01-01

    The authors of this article, as student teachers, explored becoming facilitators in lessons focusing on micro-organisms. They elicited ideas from their students and found that even the brightest children held some misconceptions about micro-organisms. The students had some knowledge, but they had not learned how to apply this to investigations…

  11. 75 FR 57384 - Rescission of Rules Pertaining to the Payment of Bounties for Information Leading to the Recovery...

    Science.gov (United States)

    2010-09-21

    ... Act (``APA'') generally requires an agency to publish notice of a proposed rulemaking in the Federal... authority citation for part 201 continues to read as follows: Authority: 15 U.S.C. 77s, 77sss, 78w, 78x,...

  12. Optimization leads to symmetry

    Institute of Scientific and Technical Information of China (English)

    Chenghong WANG; Yuqian GUO; Daizhan CHENG

    2004-01-01

    The science of complexity studies the behavior and properties of complex systems in nature and human society.Particular interest has been put on their certain simple common properties.Symmetry is one of such properties.Symmetric phenomena can be found in many complex systems.The purpose of this paper is to reveal the internal reason of the symmetry.Using some physical systems and geometric objects,the paper shows that many symmetries are caused by optimization under certain criteria.It has also been revealed that an evolutional process may lead to symmetry.

  13. 78 FR 79408 - Agency Information Collection Activities; Notice of Intent To Renew Collection: Procedural...

    Science.gov (United States)

    2013-12-30

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities; Notice of Intent To Renew Collection: Procedural... Register whenever it seeks to renew a collection of information previously ] approved by OMB,...

  14. 76 FR 55665 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2011-09-08

    ... INFORMATION CONTACT: Peggy Vyas, Environmental Protection Agency Office of Solid Waste and Emergency Response... generates or transports regulated waste or who owns or operates a facility for the treatment, storage, or... Request; 2011 Hazardous Waste Report, Notification of Regulated Waste Activity, and Part A Hazardous...

  15. 32 CFR Appendix D to Part 169a - Commercial Activities Management Information System (CAMIS)

    Science.gov (United States)

    2010-07-01

    ... to Part 169a—Commercial Activities Management Information System (CAMIS) Each DoD Component shall... 32 National Defense 1 2010-07-01 2010-07-01 false Commercial Activities Management Information... American Standard Code Information Interchange text file format on a MicroSoft-Disk Operating...

  16. THE RELEVANCE OF ACCOUNTING INFORMATION GENERATED BY THE APPLICATION OF IAS 29 RELATED TO SHAREHOLDERS CAPITAL

    Directory of Open Access Journals (Sweden)

    Bunget Ovidiu Constantin

    2013-07-01

    The objective of IAS 29 is to establish specific standards for entities reporting in the currency of a hyperinflationary economy, so that the financial information provided is meaningful. Our empirical analysis encompasses a hyperinflationary economy covering a wide variety of hyperinflationary conditions.

  17. When 'fit' leads to fit, and when 'fit' leads to fat: how message framing and intrinsic vs. extrinsic exercise outcomes interact in promoting physical activity.

    Science.gov (United States)

    Gallagher, Kristel M; Updegraff, John A

    2011-07-01

    A unique aspect of exercise is that people may choose to engage in it to achieve a variety of outcomes, ranging from extrinsic (appearance, health) to intrinsic (satisfaction, enjoyment). We examined how the impact of gain- vs. loss-framed messages depends on the type of outcome emphasised. Drawing from regulatory focus theory (Higgins, E.T. (1997). Beyond pleasure and pain. American Psychologist, 52, 1280-1300; Higgins, E.T. (2000). Making a good decision: Value from fit. American Psychologist, 55, 1217-1230), we predicted that gain-framed messages would 'fit' with intrinsic outcomes and loss-framed messages would 'fit' with extrinsic outcomes, but the effect of such fit on physical activity would depend on the participants' need for cognition (NC). We tested these hypotheses with a sample of 176 sedentary young adults who read an exercise message with randomly assigned frame (gain/loss) and outcome (intrinsic/extrinsic). Participants provided daily reports of exercise over the following week. The predicted interaction between frame, outcome and NC was found (p=0.001) such that a 'fit' message promoted somewhat, but not significantly, greater exercise for those with high NC, but a 'non-fit' message promoted significantly greater exercise for those with low NC. Furthermore, differences in physical activity were partially mediated by attitudes towards exercise. Findings shed light on how the outcomes and motivations associated with physical activity shape people's behavioural responses to framed health communications.

  18. Central station applications planning activities and supporting studies. [application of photovoltaic technology to power generation plants

    Science.gov (United States)

    Leonard, S. L.; Siegel, B.

    1980-01-01

    The application of photovoltaic technology in central station (utility) power generation plants is considered. A program of data collection and analysis designed to provide additional information about the subset of the utility market that was identified as the initial target for photovoltaic penetration, the oil-dependent utilities (especially muncipals) of the U.S. Sunbelt, is described along with a series of interviews designed to ascertain utility industry opinions about the National Photovoltaic Program as it relates to central station applications.

  19. Information Superiority generated through proper application of Geoinformatics

    Science.gov (United States)

    Teichmann, F.

    2012-04-01

    Information Superiority generated through proper application of Geoinformatics Information management and especially geoscience information delivery is a very delicate task. If it is carried out successfully, geoscientific data will provide the main foundation of Information Superiority. However, improper implementation of geodata generation, assimilation, distribution or storage will not only waste valuable resources like manpower or money, but could also give rise to crucial deficiency in knowledge and might lead to potentially extremely harmful disasters or wrong decisions. Comprehensive Approach, Effect Based Operations and Network Enabled Capabilities are the current buzz terms in the security regime. However, they also apply to various interdisciplinary tasks like catastrophe relief missions, civil task operations or even in day to day business operations where geo-science data is used. Based on experience in the application of geoscience data for defence applications the following procedure or tool box for generating geodata should lead to the desired information superiority: 1. Understand and analyse the mission, the task and the environment for which the geodata is needed 2. Carry out a Information Exchange Requirement between the user or customer and the geodata provider 3. Implementation of current interoperability standards and a coherent metadata structure 4. Execute innovative data generation, data provision, data assimilation and data storage 5. Apply a cost-effective and reasonable data life cycle 6. Implement IT security by focusing of the three pillar concepts Integrity, Availability and Confidentiality of the critical data 7. Draft and execute a service level agreement or a memorandum of understanding between the involved parties 8. Execute a Continuous Improvement Cycle These ideas from the IT world should be transferred into the geoscience community and applied in a wide set of scenarios. A standardized approach of how to generate, provide

  20. 77 FR 65541 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2012-10-29

    ..., Office of Management, publishes this notice containing proposed information collection requests at the... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for...

  1. 78 FR 16842 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-03-19

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... professional development on fourth grade teachers' content knowledge, classroom practice, and their students... Collection Clearance Division, Privacy, Information and Records Management Services, Office of...

  2. 78 FR 48430 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-08-08

    ..., Information and Records Management Services, Office of Management. BILLING CODE 4000-01-P ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review and Approval; Comment Request; Integrated Postsecondary Education Data System (IPEDS) 2013-...

  3. 76 FR 60810 - Agency Information Collection Activities: Notice of Intent To Renew Collection, Copies of Crop...

    Science.gov (United States)

    2011-09-30

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection, Copies of Crop and Market Information Reports AGENCY: Commodity Futures Trading Commission. ACTION: Notice. SUMMARY:...

  4. 77 FR 22571 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-04-16

    ...; search data sources; complete and review the collection of information; and transmit or otherwise... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Agency Information Collection Activities; Submission to OMB for Review and Approval;...

  5. Adaptation of influenza A viruses to cells expressing low levels of sialic acid leads to loss of neuraminidase activity.

    Science.gov (United States)

    Hughes, M T; McGregor, M; Suzuki, T; Suzuki, Y; Kawaoka, Y

    2001-04-01

    Influenza A viruses possess two virion surface proteins, hemagglutinin (HA) and neuraminidase (NA). The HA binds to sialyloligosaccharide viral receptors, while the NA removes sialic acids from the host cell and viral sialyloligosaccarides. Alterations of the HA occur during adaptation of influenza viruses to new host species, as in the 1957 and 1968 influenza pandemics. To gain a better understanding of the contributions of the HA and possibly the NA to this process, we generated cell lines expressing reduced levels of the influenza virus receptor determinant, sialic acid, by selecting Madin-Darby canine kidney cells resistant to a lectin specific for sialic acid linked to galactose by alpha(2-3) or alpha(2-6) linkages. One of these cell lines had less than 1/10 as much N-acetylneuraminic acid as its parent cell line. When serially passaged in this cell line, human H3N2 viruses lost sialidase activity due to a large internal deletion in the NA gene, without alteration of the HA gene. These findings indicate that NA mutations can contribute to the adaptation of influenza A virus to new host environments and hence may play a role in the transmission of virus across species.

  6. You and me, how (in-)active are we? The potential of sharing physical activity information to increase motivation

    NARCIS (Netherlands)

    Van Wijngaarden, J.; Van Halteren, A.T.

    2009-01-01

    This report describes the theoretical background and development of an application to share physical activity information, as well as the results of a four-week field study in which people shared physical activity information as measured by the Philips Activity Monitor. The existing web-service Dir

  7. Technology solutions to support supervisory activities and also to provide information access to the society

    Science.gov (United States)

    Paladini, D.; Mello, A. B.

    2016-07-01

    Inmetro's data about the conformity of certificated products, process and services are, usually, displayed at fragmented databases of difficult access for several reasons, for instance, the lack of computational solutions which allow this kind of access to its users. A discussion about some of the technological solutions to support supervisory activities by the appropriate regulatory bodies and also to provide information access to society in general is herein presented, along with a theoretical explanation of the pros and cons of such technologies to the conclusion that a mobile platform seems to be the best tool for the requirements of Inmetro.

  8. Cumulant generating function formula of heat transfer in ballistic systems with lead-lead coupling

    Science.gov (United States)

    Li, Huanan; Agarwalla, Bijay Kumar; Wang, Jian-Sheng

    2012-10-01

    Based on a two-time observation protocol, we consider heat transfer in a given time interval tM in a lead-junction-lead system taking coupling between the leads into account. In view of the two-time observation, consistency conditions are carefully verified in our specific family of quantum histories. Furthermore, its implication is briefly explored. Then using the nonequilibrium Green's function method, we obtain an exact formula for the cumulant generating function for heat transfer between the two leads, valid in both transient and steady-state regimes. Also, a compact formula for the cumulant generating function in the long-time limit is derived, for which the Gallavotti-Cohen fluctuation symmetry is explicitly verified. In addition, we briefly discuss Di Ventra's repartitioning trick regarding whether the repartitioning procedure of the total Hamiltonian affects the nonequilibrium steady-state current fluctuation. All kinds of properties of nonequilibrium current fluctuations, such as the fluctuation theorem in different time regimes, could be readily given according to these exact formulas.

  9. A control architecture to coordinate distributed generators and active power filters coexisting in a microgrid

    DEFF Research Database (Denmark)

    Hashempour, Mohammad M.; Savaghebi, Mehdi; Quintero, Juan Carlos Vasquez

    2016-01-01

    This paper proposes a control architecture of distributed generators (DGs) inverters and shunt active power filters (APFs) in microgrids to compensate voltage harmonics in a coordinated way. For this, a hierarchical control structure is proposed that includes two control levels. The primary (local...

  10. A Control Architecture to Coordinate Distributed Generators and Active Power Filters Coexisting in a Microgrid

    DEFF Research Database (Denmark)

    Hashempour, Mohammad M.; Firoozabadi, Mehdi Savaghebi; Quintero, Juan Carlos Vasquez

    2016-01-01

    This paper proposes a control architecture of distributed generators (DGs) inverters and shunt active power filters (APFs) in microgrids to compensate voltage harmonics in a coordinated way. For this, a hierarchical control structure is proposed that includes two control levels. The primary (local...

  11. An ethanol extract of Artemisia iwayomogi activates PPARδ leading to activation of fatty acid oxidation in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Si Young Cho

    Full Text Available Although Artemisia iwayomogi (AI has been shown to improve the lipid metabolism, its mode of action is poorly understood. In this study, a 95% ethanol extract of AI (95EEAI was identified as a potent ligand of peroxisome proliferator-activated receptorδ (PPARδ using ligand binding analysis and cell-based reporter assay. In cultured primary human skeletal muscle cells, treatment of 95EEAI increased expression of two important PPARδ-regulated genes, carnitine palmitoyl-transferase-1 (CPT1 and pyruvate dehydrogenase kinase isozyme 4 (PDK4, and several genes acting in lipid efflux and energy expenditure. Furthermore, 95EEAI stimulated fatty acid oxidation in a PPARδ-dependent manner. High-fat diet-induced obese mice model further indicated that administration of 95EEAI attenuated diet-induced obesity through the activation of fatty acid oxidation in skeletal muscle. These results suggest that a 95% ethanol extract of AI may have a role as a new functional food material for the prevention and/or treatment of hyperlipidermia and obesity.

  12. Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism

    DEFF Research Database (Denmark)

    Södersten, Erik; Feyder, Michael; Lerdrup, Mads

    2014-01-01

    Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. ...... and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease....

  13. ICTS AND ENTERPRISE: CONCEPTUAL PROPOSALS TO GENERATE INDICATORS FOR THE INFORMATION SOCIETY

    Directory of Open Access Journals (Sweden)

    Fernando Peirano

    2006-11-01

    Full Text Available This paper is an attempt to deepen the reflection on how Information and Communication Technologies (ICTs diffusion among firms takes place. It adds to author’s previous works on the different strategies adopted by small and medium enterprises (SMEs in Argentina in order to adopt ICTs. The paper is focused in the stylization of the different stages along the evolutive path while incorporating these tools and identifying the factors that influence its dynamics, with special attention to costs. The paper is also an attempt to make progress in the description of the paths or ways through which ICTs can improve firms’ performance. Four alternatives are pointed out, named “Economies through Information”: automation, access to information, learning and innovation processes facilitation and reduction of transaction costs. Authors try to make operable some notions frequently used by other authors interested in these issues and to formulate some hypothesis which still need further elaboration, but which will probably stimulate and inspire the debate around these matters.

  14. Dynamic fracturing by successive coseismic loadings leads to pulverization in active fault zones

    Science.gov (United States)

    Aben, F. M.; Doan, M.-L.; Mitchell, T. M.; Toussaint, R.; Reuschlé, T.; Fondriest, M.; Gratier, J.-P.; Renard, F.

    2016-04-01

    Previous studies show that pulverized rocks observed along large faults can be created by single high-strain rate loadings in the laboratory, provided that the strain rate is higher than a certain pulverization threshold. Such loadings are analogous to large seismic events. In reality, pulverized rocks have been subject to numerous seismic events rather than one single event. Therefore, the effect of successive "milder" high-strain rate loadings on the pulverization threshold is investigated by applying loading conditions below the initial pulverization threshold. Single and successive loading experiments were performed on quartz-monzonite using a Split Hopkinson Pressure Bar apparatus. Damage-dependent petrophysical properties and elastic moduli were monitored by applying incremental strains. Furthermore, it is shown that the pulverization threshold can be reduced by successive "milder" dynamic loadings from strain rates of ~180 s-1 to ~90 s-1. To do so, it is imperative that the rock experiences dynamic fracturing during the successive loadings prior to pulverization. Combined with loading conditions during an earthquake rupture event, the following generalized fault damage zone structure perpendicular to the fault will develop: furthest from the fault plane, there is a stationary outer boundary that bounds a zone of dynamically fractured rocks. Closer to the fault, a pulverization boundary delimits a band of pulverized rock. Consecutive seismic events will cause progressive broadening of the band of pulverized rocks, eventually creating a wider damage zone observed in mature faults.

  15. Data-driven magnetohydrodynamic modelling of a flux-emerging active region leading to solar eruption.

    Science.gov (United States)

    Jiang, Chaowei; Wu, S T; Feng, Xuesheng; Hu, Qiang

    2016-05-16

    Solar eruptions are well-recognized as major drivers of space weather but what causes them remains an open question. Here we show how an eruption is initiated in a non-potential magnetic flux-emerging region using magnetohydrodynamic modelling driven directly by solar magnetograms. Our model simulates the coronal magnetic field following a long-duration quasi-static evolution to its fast eruption. The field morphology resembles a set of extreme ultraviolet images for the whole process. Study of the magnetic field suggests that in this event, the key transition from the pre-eruptive to eruptive state is due to the establishment of a positive feedback between the upward expansion of internal stressed magnetic arcades of new emergence and an external magnetic reconnection which triggers the eruption. Such a nearly realistic simulation of a solar eruption from origin to onset can provide important insight into its cause, and also has the potential for improving space weather modelling.

  16. 78 FR 63980 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-10-25

    ... information, to search data sources, to complete and review the collection of information, and to transmit or... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Agency Information Collection Activities; Submission to OMB...

  17. Loss of ATM kinase activity leads to embryonic lethality in mice

    DEFF Research Database (Denmark)

    Daniel, J.A.; Pellegrini, M.; Filsuf, D.

    2012-01-01

    Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine...

  18. Disruption of Fractalkine Signaling Leads to Microglial Activation and Neuronal Damage in the Diabetic Retina

    Directory of Open Access Journals (Sweden)

    Sandra M. Cardona

    2015-10-01

    Full Text Available Fractalkine (CX3CL1 or FKN is a membrane-bound chemokine expressed on neuronal membranes and is proteolytically cleaved to shed a soluble chemoattractant domain. FKN signals via its unique receptor CX3CR1 expressed on microglia and other peripheral leukocytes. The aim of this study is to determine the role of CX3CR1 in inflammatory-mediated damage to retinal neurons using a model of diabetic retinopathy. For this, we compared neuronal, microglial, and astroglial densities and inflammatory response in nondiabetic and diabetic (Ins2Akita CX3CR1-wild-type and CX3CR1-deficient mice at 10 and 20 weeks of age. Our results show that Ins2Akita CX3CR1-knockout mice exhibited (a decreased neuronal cell counts in the retinal ganglion cell layer, (b increased microglial cell numbers, and (c decreased astrocyte responses comparable with Ins2Akita CX3CR1-Wild-type mice at 20 weeks of age. Analyses of the inflammatory response using PCR arrays showed several inflammatory genes differentially regulated in diabetic tissues. From those, the response in Ins2Akita CX3CR1-deficient mice at 10 weeks of age revealed a significant upregulation of IL-1β at the transcript level that was confirmed by enzyme-linked immunosorbent assay in soluble retinal extracts. Overall, IL-1β, VEGF, and nitrite levels as a read out of nitric oxide production were abundant in Ins2Akita CX3CR1-deficient retina. Notably, double immunofluorescence staining shows that astrocytes act as a source of IL-1β in the Ins2Akita retina, and CX3CR1-deficient microglia potentiate the inflammatory response via IL-1β release. Collectively, these data demonstrate that dysregulated microglial responses in absence of CX3CR1 contribute to inflammatory-mediated damage of neurons in the diabetic retina.

  19. Design and Synthesis of (+)-Discodermolide-Paclitaxel Hybrids Leading to Enhanced Biological Activity1

    OpenAIRE

    Smith, Amos B.; Sugasawa, Keizo; Atasoylu, Onur; Yang, Chia-Ping Huang; Horwitz, Susan Band

    2011-01-01

    Potential binding modes of (+)-discodermolide at the paclitaxel binding site of tubulin have been identified by computational studies based on earlier structural and SAR data. Examination of the prospective binding modes reveal that the aromatic pocket occupied by the paclitaxel side-chain is unoccupied by (+)-discodermolide. Based on these findings, a small library of (+)-discodermolide-paclitaxel hybrids have been designed and synthesized. Biological evaluation reveals a two- to eight- fold...

  20. Extending dynamic segmentation with lead generation: A latent class Markov analysis of financial product portfolios

    OpenAIRE

    Paas, L.J.; Bijmolt, T.H.A.; Vermunt, J.K.

    2004-01-01

    A recent development in marketing research concerns the incorporation of dynamics in consumer segmentation.This paper extends the latent class Markov model, a suitable technique for conducting dynamic segmentation, in order to facilitate lead generation.We demonstrate the application of the latent Markov model for these purposes using a database containing information on the ownership of twelve financial products and demographics for explaining (changes in) consumer product portfolios.Data we...

  1. Auditory evoked fields to vocalization during passive listening and active generation in adults who stutter.

    Science.gov (United States)

    Beal, Deryk S; Cheyne, Douglas O; Gracco, Vincent L; Quraan, Maher A; Taylor, Margot J; De Nil, Luc F

    2010-10-01

    We used magnetoencephalography to investigate auditory evoked responses to speech vocalizations and non-speech tones in adults who do and do not stutter. Neuromagnetic field patterns were recorded as participants listened to a 1 kHz tone, playback of their own productions of the vowel /i/ and vowel-initial words, and actively generated the vowel /i/ and vowel-initial words. Activation of the auditory cortex at approximately 50 and 100 ms was observed during all tasks. A reduction in the peak amplitudes of the M50 and M100 components was observed during the active generation versus passive listening tasks dependent on the stimuli. Adults who stutter did not differ in the amount of speech-induced auditory suppression relative to fluent speakers. Adults who stutter had shorter M100 latencies for the actively generated speaking tasks in the right hemisphere relative to the left hemisphere but the fluent speakers showed similar latencies across hemispheres. During passive listening tasks, adults who stutter had longer M50 and M100 latencies than fluent speakers. The results suggest that there are timing, rather than amplitude, differences in auditory processing during speech in adults who stutter and are discussed in relation to hypotheses of auditory-motor integration breakdown in stuttering.

  2. Endothelin-1 activation of ETB receptors leads to a reduced cellular proliferative rate and an increased cellular footprint

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Jamie L.; Taylor, Linda; Polgar, Peter, E-mail: peterp@bu.edu

    2012-06-10

    Endothelin-1 (ET-1) is a vasoactive peptide which signals through two G-protein coupled receptors, endothelin receptor A (ETA) and B (ETB). We determined that ET-1 activation of its ETB receptor in stably cDNA transfected CHO cells leads to a 55% reduction in cell number by end-point cell counting and a 35% decrease in cell growth by a real-time cell-substrate impedance-based assay after 24 h of cell growth. When CHO ETB cells were synchronized in the late G1 cell cycle phase, ET-1 delayed their S phase progression compared to control by 30% as determined by [{sup 3}H]-thymidine incorporation. On the other hand, no such delay was observed during late G2/M to G1 transit when cells were treated with ET-1 after release from mitotic arrest. Using the cell-substrate impedance-based assay, we observed that ET-1 induces opposing morphological changes in CHO ETA and CHO ETB cells with ETB causing an increase in the cell footprint and ETA a decrease. Likewise, in pulmonary artery smooth muscle cells, which express both ETA and ETB receptors, ET-1 induces an ETA-dependent contraction and an ETB dependent dilation. These results are shedding light on a possible beneficial role for ETB in diseases involving ET-1 dysfunction such as pulmonary hypertension. -- Highlights: Black-Right-Pointing-Pointer ET- hinders cell proliferation in CHO cells transfected with ETB. Black-Right-Pointing-Pointer ET-1 also decreases the rate of DNA synthesis in CHO ETB cells. Black-Right-Pointing-Pointer JNK and PI3K appear to be involved in this reduction of DNA synthesis. Black-Right-Pointing-Pointer ETB activation in CHO ETB cells and hSMCs leads to dilatory morphological changes. Black-Right-Pointing-Pointer In CHO ETA and hSMCs, ETA activation leads to constrictive morphological changes.

  3. Suppression of dynamin GTPase activity by sertraline leads to inhibition of dynamin-dependent endocytosis.

    Science.gov (United States)

    Takahashi, Kiyofumi; Miyoshi, Hiroshi; Otomo, Masahiro; Osada, Kenichi; Yamaguchi, Noboru; Nakashima, Hideki

    2010-01-01

    Dynamin (Dyn) 1 plays a role in recycling of synaptic vesicles, and thus in nervous system function. We previously showed that sertraline, a selective serotonin reuptake inhibitor (SSRI), is a mixed-type inhibitor of Dyn 1 with respect to both GTP and L-alpha-phosphatidyl-L-serine (PS) in vitro, and we suggested that it may regulate the neurotransmitter transport by modulating synaptic vesicle endocytosis via inhibition of Dyn 1 GTPase. Here, we investigated the effect of sertraline on endocytosis of marker proteins in human neuroblastoma SH-Sy5Y cells and HeLa cells. Sertraline inhibited endocytosis in both cell lines. Western blotting showed that SH-Sy5Y expresses Dyn 1 and Dyn 2, while HeLa expresses only Dyn 2. GTPase assay showed that sertraline inhibited Dyn 2 as well as Dyn 1. Therefore, the effect of sertraline on endocytosis was mediated by Dyn 2, at least in HeLa cells, as well as by Dyn 1 in cell lines that express it. Moreover, the inhibition mechanism of transferrin (Tf) uptake by sertraline differed from that in cells expressing Dyn 1 K44A, a GTP binding-defective variant, and sertraline did not interfere with the interaction between Dyn 1 and PS-liposomes.

  4. Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.

    Directory of Open Access Journals (Sweden)

    Paulo M F Cunha

    2010-07-01

    Full Text Available Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2 or the zinc-finger transcription factor lame duck (lmd lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.

  5. Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.

    Science.gov (United States)

    Cunha, Paulo M F; Sandmann, Thomas; Gustafson, E Hilary; Ciglar, Lucia; Eichenlaub, Michael P; Furlong, Eileen E M

    2010-07-01

    Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2) or the zinc-finger transcription factor lame duck (lmd) lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.

  6. Mapping epidemiology's past to inform its future: metaknowledge analysis of epidemiologic topics in leading journals, 1974-2013.

    Science.gov (United States)

    Trinquart, Ludovic; Galea, Sandro

    2015-07-15

    An empiric perspective on what epidemiology has studied over time might inform discussions about future directions for the discipline. We aimed to identify the main areas of epidemiologic inquiry and determine how they evolved over time in 5 high-impact epidemiologic journals. We analyzed the titles and abstracts of 20,895 articles that were published between 1974 and 2013. In 5 time periods that reflected approximately equal numbers of articles, we identified the main topics by clustering terms based on co-occurrence. Infectious disease and cardiovascular disease epidemiology were the prevailing topics over the 5 periods. Cancer epidemiology was a major topic from 1974 to 2001 but disappeared thereafter. Nutritional epidemiology gained relative importance from 1974 to 2013. Environmental epidemiology appeared during 1996-2001 and continued to be important, whereas 2 clusters related to methodology and meta-analysis in genetics appeared during 2008-2013. Several areas of epidemiology, including injury or psychiatric epidemiology, did not make an appearance as major topics at any time. In an ancillary analysis of 6 high-impact general medicine journals, we found patterns of epidemiologic articles that were overall consistent with the findings in epidemiologic journals. This metaknowledge investigation allowed identification of the dominant topics in and conversely those that were absent from 5 major epidemiologic journals. We discuss implications for the field.

  7. Exploring the clinical information system implementation readiness activities to support nursing in hospital settings.

    Science.gov (United States)

    Piscotty, Ronald J; Tzeng, Huey-Ming

    2011-11-01

    The implementation of clinical information systems can have a profound impact on nurses and their productivity. Poorly implemented systems can lead to unintended consequences that may have a negative impact on clinical processes and patient outcomes. Executives must have adequate knowledge to address nurses' concerns related to implementation. This study explored the clinical information system implementation readiness activities adopted by chief nurse executivesin hospital settings. A descriptive qualitative design was used, including interviews with six chief nurse executives, held from December 2003 through March 2004. The constant comparative method was used to analyze the interviews to extract readiness activity themes and compare these to the literature. The synthesized themes showed that the executives were knowledgeable about and engaged in several key areas, but not all, of the implementation readiness process. The majority of responses were classified into the thematic areas of champion support, staff preparation for change, training, organizational alignment, planning, and vendor support. The theme of a lack of vendor support was not identified in previous studies but was clear in the responses of the chief nurse executives interviewed.

  8. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance.

    Science.gov (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E

    2013-01-01

    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  9. Images as Orienting Activity: Using Theory to Inform Classroom Practices

    Science.gov (United States)

    Feryok, Anne; Pryde, Michael

    2012-01-01

    Conceptualizations of teacher knowledge have shifted to focusing on the role of experiential rather than theoretical knowledge. There are different approaches to this, but the idea of an image that guides practice is widespread. One approach to images that has not been frequently investigated in studies of second language teachers is through…

  10. Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses.

    Directory of Open Access Journals (Sweden)

    Benjamin Schwessinger

    2015-03-01

    Full Text Available Plant plasma membrane localized pattern recognition receptors (PRRs detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24, two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components.

  11. 78 FR 16509 - Amendment to Information Collection Activity; Comment Request

    Science.gov (United States)

    2013-03-15

    ..., which is testing the effect of combining transitional jobs with enhanced services to assist ex-offenders... here will be used for sites in the STED project that target young adults (aged 18 to 25). It is being... alternate versions of the 6 and 12 month surveys for use at study sites whose population consists of...

  12. PileLine: a toolbox to handle genome position information in next-generation sequencing studies

    Directory of Open Access Journals (Sweden)

    Fdez-Riverola Florentino

    2011-01-01

    Full Text Available Abstract Background Genomic position (GP files currently used in next-generation sequencing (NGS studies are always difficult to manipulate due to their huge size and the lack of appropriate tools to properly manage them. The structure of these flat files is based on representing one line per position that has been covered by at least one aligned read, imposing significant restrictions from a computational performance perspective. Results PileLine implements a flexible command-line toolkit providing specific support to the management, filtering, comparison and annotation of GP files produced by NGS experiments. PileLine tools are coded in Java and run on both UNIX (Linux, Mac OS and Windows platforms. The set of tools comprising PileLine are designed to be memory efficient by performing fast seek on-disk operations over sorted GP files. Conclusions Our novel toolbox has been extensively tested taking into consideration performance issues. It is publicly available at http://sourceforge.net/projects/pilelinetools under the GNU LGPL license. Full documentation including common use cases and guided analysis workflows is available at http://sing.ei.uvigo.es/pileline.

  13. Mobilization of Copper ions by Flavonoids in Human Peripheral Lymphocytes Leads to Oxidative DNA Breakage: A Structure Activity Study

    Directory of Open Access Journals (Sweden)

    Hussain Arif

    2015-11-01

    Full Text Available Epidemiological studies have linked dietary consumption of plant polyphenols with lower incidence of various cancers. In particular, flavonoids (present in onion, tomato and other plant sources induce apoptosis and cytotoxicity in cancer cells. These can therefore be used as lead compounds for the synthesis of novel anticancer drugs with greater bioavailability. In the present study, we examined the chemical basis of cytotoxicity of flavonoids by studying the structure–activity relationship of myricetin (MN, fisetin (FN, quercetin (QN, kaempferol (KL and galangin (GN. Using single cell alkaline gel electrophoresis (comet assay, we established the relative efficiency of cellular DNA breakage as MN > FN > QN > KL > GN. Also, we determined that the cellular DNA breakage was the result of mobilization of chromatin-bound copper ions and the generation of reactive oxygen species. The relative DNA binding affinity order was further confirmed using molecular docking and thermodynamic studies through the interaction of flavonoids with calf thymus DNA. Our results suggest that novel anti-cancer molecules should have ortho-dihydroxy groups in B-ring and hydroxyl groups at positions 3 and 5 in the A-ring system. Additional hydroxyl groups at other positions further enhance the cellular cytotoxicity of the flavonoids.

  14. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Stein, Jürgen [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main (Germany); Fürst, Robert [Institute of Pharmaceutical Biology, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Steinhilber, Dieter [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Ulrich-Rückert, Sandra, E-mail: sandra.ulrich@em.uni-frankfurt.de [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany)

    2015-08-15

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like

  15. Criteria to assess the quality of the Dutch Informal Pro-active Approach Model

    NARCIS (Netherlands)

    Marseille, A.T.; de Graaf, K.J.; Dragos, D.C.; Lafarge, F.

    2012-01-01

    If citizens in the Netherlands do not agree with a decision of a public authority, they can submit a written objection. The Informal Pro-active Approach Model (or “informal approach”) provides an alternative for the traditional conflict resolution procedures. This informal approach has led to a redu

  16. Human platelets utilize cycloxygenase-1 to generate dioxolane A3, a neutrophil activating eicosanoid

    OpenAIRE

    Hinz, Christine; Aldrovandi, MacEler; Alam, Saydul; Slatter, David; Lauder, Sarah Nicol; Allen-Redpath, Keith; Collins, Peter William; Thomas, Christopher P.; O'Donnell, Valerie Bridget

    2016-01-01

    Eicosanoids are important mediators of fever, pain, and inflammation that modulate cell signaling during acute and chronic disease. We show by using lipidomics that thrombin-activated human platelets generate a new type of eicosanoid that both stimulates and primes human neutrophil integrin (Mac-1) expression, in response to formylmethionylleucylphenylalanine. Detailed characterization proposes a dioxolane structure, 8-hydroxy-9,11-dioxolane eicosatetraenoic acid (dioxolane A3, DXA3). The lip...

  17. Identification of intrinsic catalytic activity for electrochemical reduction of water molecules to generate hydrogen

    KAUST Repository

    Shinagawa, Tatsuya

    2015-01-01

    Insufficient hydronium ion activities at near-neutral pH and under unbuffered conditions induce diffusion-limited currents for hydrogen evolution, followed by a reaction with water molecules to generate hydrogen at elevated potentials. The observed constant current behaviors at near neutral pH reflect the intrinsic electrocatalytic reactivity of the metal electrodes for water reduction. This journal is © the Owner Societies.

  18. PERK Utilizes Intrinsic Lipid Kinase Activity To Generate Phosphatidic Acid, Mediate Akt Activation, and Promote Adipocyte Differentiation

    Science.gov (United States)

    Bobrovnikova-Marjon, Ekaterina; Pytel, Dariusz; Riese, Matthew J.; Vaites, Laura Pontano; Singh, Nickpreet; Koretzky, Gary A.; Witze, Eric S.

    2012-01-01

    The endoplasmic reticulum (ER) resident PKR-like kinase (PERK) is necessary for Akt activation in response to ER stress. We demonstrate that PERK harbors intrinsic lipid kinase, favoring diacylglycerol (DAG) as a substrate and generating phosphatidic acid (PA). This activity of PERK correlates with activation of mTOR and phosphorylation of Akt on Ser473. PERK lipid kinase activity is regulated in a phosphatidylinositol 3-kinase (PI3K) p85α-dependent manner. Moreover, PERK activity is essential during adipocyte differentiation. Because PA and Akt regulate many cellular functions, including cellular survival, proliferation, migratory responses, and metabolic adaptation, our findings suggest that PERK has a more extensive role in insulin signaling, insulin resistance, obesity, and tumorigenesis than previously thought. PMID:22493067

  19. PERK utilizes intrinsic lipid kinase activity to generate phosphatidic acid, mediate Akt activation, and promote adipocyte differentiation.

    Science.gov (United States)

    Bobrovnikova-Marjon, Ekaterina; Pytel, Dariusz; Riese, Matthew J; Vaites, Laura Pontano; Singh, Nickpreet; Koretzky, Gary A; Witze, Eric S; Diehl, J Alan

    2012-06-01

    The endoplasmic reticulum (ER) resident PKR-like kinase (PERK) is necessary for Akt activation in response to ER stress. We demonstrate that PERK harbors intrinsic lipid kinase, favoring diacylglycerol (DAG) as a substrate and generating phosphatidic acid (PA). This activity of PERK correlates with activation of mTOR and phosphorylation of Akt on Ser473. PERK lipid kinase activity is regulated in a phosphatidylinositol 3-kinase (PI3K) p85α-dependent manner. Moreover, PERK activity is essential during adipocyte differentiation. Because PA and Akt regulate many cellular functions, including cellular survival, proliferation, migratory responses, and metabolic adaptation, our findings suggest that PERK has a more extensive role in insulin signaling, insulin resistance, obesity, and tumorigenesis than previously thought.

  20. Simulations of Active Vortex Generators

    Science.gov (United States)

    Mansour, N. N.; Koumoutsakos, P.; Merriam, Marshal (Technical Monitor)

    1996-01-01

    We are interested in the study, via numerical simulations, of active vortex generators. Vortex generators may be used to modify the inner part of the boundary layer or to control separation thus enhancing the performance and maneuverability of aerodynamic configurations. We consider generators that consist of a surface cavity elongated in the streamwise direction and partially covered with a moving lid that at rest lies flush with the boundary. Streamwise voracity is generated and ejected due to the oscillatory motion of the lid. The present simulations c Implement relevant experimental investigations of active vortex generators that have been conducted at NASA Ames Research Center and Stanford University. Jacobson and Reynolds used a piezoelectric device in water, allowing for small amplitude high frequency oscillations. They placed the lid asymmetrically on the cavity and observed a strong outward velocity at the small gap of the cavity. Saddoughi used a larger mechanically driven device in air to investigate this flow and observed a jet emerging from the wide gap of the configuration, contrary to the findings of Jacobson and Reynolds. More recently, Lachowiez and Wlezien are investigating the flow generated by an electro-mechanically driven lid to be used for assertion control in aerodynamic applications. We are simulating the flows generated by these devices and we are conducting a parametric study that would help us elucidate the physical mechanisms present in the flow. Conventional computational schemes encounter difficulties when simulating flows around complex configurations undergoing arbitrary motions. Here we present a formulation that achieves this task on a purely Lagrangian frame by extending the formulation presented by Koumoutsakos, Leonard and Pepin. The viscous effects are taken into account by modifying the strength of the particles, whereas fast multipole schemes employing hundreds of thousands ol'particle's allow for high resolution simulations

  1. Adaptation of Influenza A Viruses to Cells Expressing Low Levels of Sialic Acid Leads to Loss of Neuraminidase Activity

    OpenAIRE

    2001-01-01

    Influenza A viruses possess two virion surface proteins, hemagglutinin (HA) and neuraminidase (NA). The HA binds to sialyloligosaccharide viral receptors, while the NA removes sialic acids from the host cell and viral sialyloligosaccarides. Alterations of the HA occur during adaptation of influenza viruses to new host species, as in the 1957 and 1968 influenza pandemics. To gain a better understanding of the contributions of the HA and possibly the NA to this process, we generated cell lines ...

  2. Therapeutic intraspinal stimulation to generate activity and promote long-term recovery

    Directory of Open Access Journals (Sweden)

    Sarah E. Mondello

    2014-02-01

    Full Text Available Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury. This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

  3. Automatic Building Information Model Query Generation

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yufei; Yu, Nan; Ming, Jiang; Lee, Sanghoon; DeGraw, Jason; Yen, John; Messner, John I.; Wu, Dinghao

    2015-12-01

    Energy efficient building design and construction calls for extensive collaboration between different subfields of the Architecture, Engineering and Construction (AEC) community. Performing building design and construction engineering raises challenges on data integration and software interoperability. Using Building Information Modeling (BIM) data hub to host and integrate building models is a promising solution to address those challenges, which can ease building design information management. However, the partial model query mechanism of current BIM data hub collaboration model has several limitations, which prevents designers and engineers to take advantage of BIM. To address this problem, we propose a general and effective approach to generate query code based on a Model View Definition (MVD). This approach is demonstrated through a software prototype called QueryGenerator. By demonstrating a case study using multi-zone air flow analysis, we show how our approach and tool can help domain experts to use BIM to drive building design with less labour and lower overhead cost.

  4. Information Transfer between Generations Linked to Biodiversity in Rock-Paper-Scissors Games

    OpenAIRE

    Ranjan Bose

    2015-01-01

    Ecological processes, such as reproduction, mobility, and interaction between species, play important roles in the maintenance of biodiversity. Classically, the cyclic dominance of species has been modelled using the nonhierarchical interactions among competing species, represented by the “Rock-Paper-Scissors” (RPS) game. Here we propose a cascaded channel model for analyzing the existence of biodiversity in the RPS game. The transition between successive generations is modelled as communic...

  5. From "Scuba Diving" to "Jet Skiing"? Information Behavior, Political Science, and the Google Generation

    Science.gov (United States)

    Thornton, Stephen

    2010-01-01

    It is often suggested that the swift arrival of a world shaped by information superabundance--symbolized by the astonishing growth in popularity of the digital search engine Google--has changed the manner in which many learn. A particular concern of some is the perception that younger people have turned away from books and long articles and have…

  6. Chronic Activation of Heme Free Guanylate Cyclase Leads to Renal Protection in Dahl Salt-Sensitive Rats.

    Directory of Open Access Journals (Sweden)

    Linda S Hoffmann

    Full Text Available The nitric oxide (NO/soluble guanylate cyclase (sGC/cyclic guanosine monophasphate (cGMP-signalling pathway is impaired under oxidative stress conditions due to oxidation and subsequent loss of the prosthetic sGC heme group as observed in particular in chronic renal failure. Thus, the pool of heme free sGC is increased under pathological conditions. sGC activators such as cinaciguat selectively activate the heme free form of sGC and target the disease associated enzyme. In this study, a therapeutic effect of long-term activation of heme free sGC by the sGC activator cinaciguat was investigated in an experimental model of salt-sensitive hypertension, a condition that is associated with increased oxidative stress, heme loss from sGC and development of chronic renal failure. For that purpose Dahl/ss rats, which develop severe hypertension upon high salt intake, were fed a high salt diet (8% NaCl containing either placebo or cinaciguat for 21 weeks. Cinaciguat markedly improved survival and ameliorated the salt-induced increase in blood pressure upon treatment with cinaciguat compared to placebo. Renal function was significantly improved in the cinaciguat group compared to the placebo group as indicated by a significantly improved glomerular filtration rate and reduced urinary protein excretion. This was due to anti-fibrotic and anti-inflammatory effects of the cinaciguat treatment. Taken together, this is the first study showing that long-term activation of heme free sGC leads to renal protection in an experimental model of hypertension and chronic kidney disease. These results underline the promising potential of cinaciguat to treat renal diseases by targeting the disease associated heme free form of sGC.

  7. 77 FR 70443 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2012-11-26

    ... train personnel and to be able to respond to a collection of information, to search data sources, to... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Agency Information Collection Activities; Submission to OMB...

  8. 78 FR 63979 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-10-25

    ... train personnel and to be able to respond to a collection of information, to search data sources, to... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Agency Information Collection Activities; Submission to OMB...

  9. Exploring stakeholder perceptions of conservation outcomes from alternative income generating activities in Tanzanian villages adjacent to Eastern Arc Mountain forests

    DEFF Research Database (Denmark)

    Sainsbury, K.; Burgess, Neil David; Sabuni, F.;

    2015-01-01

    Critical evaluation of the impact of conservation actions is essential to meet the challenges posed by the biodiversity crisis. Conservationists need to understand which interventions work or fail, and how to improve them in order to invest limited funds wisely. Alternative income-generating acti...... impact assessment, to incorporate perspectives of all stakeholders, and provides important insights in data-poor situations and where baselines are not available.......-generating activities (IGAs) are widely implemented within conservation and development projects, but their impact is rarely evaluated. The "ranked outcomes" evaluation methodology converts qualitative information on planned and realised outcomes into a score for comparison between projects. We test this methodology...... evaluations rated Tree Planting as the most socially beneficial IGA, followed by Fish Farming. However, there was a high level of heterogeneity of perception between and within stakeholder groups (implementers and target communities), both in terms of which outcomes were most important and how well they had...

  10. 78 FR 44097 - Agency Information Collection Activities: Proposed Collection; Submission to OMB for Review and...

    Science.gov (United States)

    2013-07-23

    ... service delivery. This feedback will provide insights into customer or stakeholder perceptions... proposed information collection activity provides a means to garner qualitative customer and stakeholder... and its customers and stakeholders. It will also allow feedback to contribute directly to...

  11. 77 FR 77073 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-12-31

    ... subsequently changed; train personnel to be able to respond to a collection of information; search data sources... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Agency Information Collection Activities; Submission to OMB for Review and Approval;...

  12. 77 FR 30523 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-05-23

    ...; train personnel to be able to respond to a collection of information; search data sources; complete and... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Agency Information Collection Activities; Submission to OMB for Review and Approval;...

  13. 78 FR 42947 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-18

    ... respond to a collection of information, to search data sources, to complete and review the collection of... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency Information Collection Activities; Submission to OMB for Review and...

  14. Glutamine enema regulates colonic ubiquitinated proteins but not proteasome activities during TNBS-induced colitis leading to increased mitochondrial activity.

    Science.gov (United States)

    Bertrand, Julien; Marion-Letellier, Rachel; Azhar, Saïda; Chan, Philippe; Legrand, Romain; Goichon, Alexis; Ghouzali, Ibtissem; Aziz, Moutaz; Vaudry, David; Savoye, Guillaume; Déchelotte, Pierre; Coëffier, Moïse

    2015-07-01

    Ubiquitin proteasome system contributes to the regulation of intestinal inflammatory response as its inhibition is associated with tissue damage improvement. We aimed to evaluate whether glutamine is able to limit inflammation by targeting ubiquitin proteasome system in experimental colitis. Colitis was induced in male rats by intrarectal instillation of 2-4-6-trinitrobenzen sulfonic acid (TNBS) at day 1. From day 2 to day 6, rats daily received either an intrarectal instillation of PBS (TNBS/PBS group) or glutamine (TNBS/Gln). Rats were euthanized at day 7 and colonic samples were taken to evaluate ubiqutinated proteins by proteomic approach combining 2D electrophoresis and immunoblots directed against ubiquitin. Results were then confirmed by evaluating total expression of proteins and mRNA levels. Survival rate, TNFα, and IL-1β mRNA were improved in TNBS/Gln compared with TNBS/PBS (p TNBS but not by glutamine. We identified eight proteins that were less ubiquitinated in TNBS/PBS compared with controls with no effect of glutamine. Four proteins were more ubiquitinated in TNBS/PBS group and restored in TNBS/Gln group. Finally, 12 ubiquitinated proteins were only affected by glutamine. Among proteins affected by glutamine, eight proteins (GFPT1, Gapdh, Pkm2, LDH, Bcat2, ATP5a1, Vdac1, and Vdac2) were involved in metabolic pathways. In conclusion, glutamine may regulate ubiquitination process during intestinal inflammation.

  15. 78 FR 42949 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-18

    ... sources, to complete and review the collection of information, and to transmit or otherwise disclose the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Agency Information Collection Activities; Submission to OMB...

  16. 78 FR 48679 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-08-09

    ... sources, to complete and review the collection of information, and to transmit or otherwise disclose the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Agency Information Collection Activities; Submission to OMB...

  17. 78 FR 42948 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-18

    ... sources, to complete and review the collection of information, and to transmit or otherwise disclose the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Agency Information Collection Activities; Submission to OMB...

  18. 77 FR 3487 - Agency Information Collection Activities: Transfer of Cargo to a Container Station

    Science.gov (United States)

    2012-01-24

    ... Information Collection Activities: Transfer of Cargo to a Container Station AGENCY: U.S. Customs and Border... information collection requirement concerning Transfer of Cargo to a Container Station. This request for...: Title: Transfer of Cargo to a Container Station. OMB Number: 1651-0096. Form Number: None....

  19. Entropy generation in Gaussian quantum transformations: applying the replica method to continuous-variable quantum information theory

    Science.gov (United States)

    Gagatsos, Christos N.; Karanikas, Alexandros I.; Kordas, Georgios; Cerf, Nicolas J.

    2016-02-01

    In spite of their simple description in terms of rotations or symplectic transformations in phase space, quadratic Hamiltonians such as those modelling the most common Gaussian operations on bosonic modes remain poorly understood in terms of entropy production. For instance, determining the quantum entropy generated by a Bogoliubov transformation is notably a hard problem, with generally no known analytical solution, while it is vital to the characterisation of quantum communication via bosonic channels. Here we overcome this difficulty by adapting the replica method, a tool borrowed from statistical physics and quantum field theory. We exhibit a first application of this method to continuous-variable quantum information theory, where it enables accessing entropies in an optical parametric amplifier. As an illustration, we determine the entropy generated by amplifying a binary superposition of the vacuum and a Fock state, which yields a surprisingly simple, yet unknown analytical expression.

  20. Basic Information about Lead in Drinking Water

    Science.gov (United States)

    Jump to main content US EPA United States Environmental Protection Agency Search Search Ground Water and Drinking Water ... per deciliter (µg/dL) or more. It is important to recognize all the ways a child can ...

  1. Expansion of chemical space for collaborative lead generation and drug discovery: the European Lead Factory Perspective.

    Science.gov (United States)

    Karawajczyk, Anna; Giordanetto, Fabrizio; Benningshof, Jorg; Hamza, Daniel; Kalliokoski, Tuomo; Pouwer, Kees; Morgentin, Remy; Nelson, Adam; Müller, Gerhard; Piechot, Alexander; Tzalis, Dimitrios

    2015-11-01

    High-throughput screening (HTS) represents a major cornerstone of drug discovery. The availability of an innovative, relevant and high-quality compound collection to be screened often dictates the final fate of a drug discovery campaign. Given that the chemical space to be sampled in research programs is practically infinite and sparsely populated, significant efforts and resources need to be invested in the generation and maintenance of a competitive compound collection. The European Lead Factory (ELF) project is addressing this challenge by leveraging the diverse experience and know-how of academic groups and small and medium enterprises (SMEs) engaged in synthetic and/or medicinal chemistry. Here, we describe the novelty, diversity, structural complexity, physicochemical characteristics and overall attractiveness of this first batch of ELF compounds for HTS purposes.

  2. CCR7 Deficiency Leads to Leukocyte Activation and Increased Clearance in Response to Pulmonary Pseudomonas aeruginosa Infection▿

    OpenAIRE

    Eppert, Bryan L.; Motz, Gregory T.; Wortham, Brian W.; Flury, Jennifer L.; Borchers, Michael T.

    2010-01-01

    CCR7 is a chemokine receptor expressed on the surfaces of T cells, B cells, and mature dendritic cells that controls cell migration in response to the cognate ligands CCL19 and CCL21. CCR7 is critical for the generation of an adaptive T cell response. However, the roles of CCR7 in the host defense against pulmonary infection and innate immunity are not well understood. We investigated the role of CCR7 in the host defense against acute pulmonary infection with Pseudomonas aeruginosa. We intran...

  3. 78 FR 16842 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-03-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... Education (EASIE) AGENCY: Office of Elementary and Secondary Education (OESE), Department of Education...

  4. 78 FR 45917 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-07-30

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for Review...) Performance Reports AGENCY: Department of Education (ED), Office of Vocational and Adult Education...

  5. 77 FR 69813 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2012-11-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... Continuing Education Program AGENCY: Department of Education (ED), Office of Special Education...

  6. 78 FR 48862 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-08-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... of Education Progress (NAEP) 2014-2016 System Clearance AGENCY: Institute of Education...

  7. 78 FR 30900 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-05-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... Education Act (1894-0001) AGENCY: Office of Special Education and Rehabilitative Services...

  8. 78 FR 57846 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-09-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... Final Performance Reports AGENCY: Office of Postsecondary Education (OPE), Department of Education...

  9. 75 FR 75665 - Agency Information Collection Activities Under OMB Review: Notice of Intent To Renew Collection...

    Science.gov (United States)

    2010-12-06

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities Under OMB Review: Notice of Intent To Renew Collection 3038-0054, Establishing Procedures for Entities Operating as Exempt Markets AGENCY: Commodity...

  10. 75 FR 60088 - Agency Information Collection Activities: Notice of Intent To Renew Collection 3038-0025...

    Science.gov (United States)

    2010-09-29

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection 3038-0025, Practice by Former Members and Employees of the Commission AGENCY: Commodity Futures Trading...

  11. 78 FR 35261 - Agency Information Collection Activities; Notice of Intent To Renew Collection: Market Surveys

    Science.gov (United States)

    2013-06-12

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities; Notice of Intent To Renew Collection: Market Surveys AGENCY: Commodity Futures Trading Commission ACTION: Notice. SUMMARY: The Commodity Futures...

  12. 76 FR 36525 - Agency Information Collection Activities: Notice of Intent To Renew Collection, Exemptions From...

    Science.gov (United States)

    2011-06-22

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection, Exemptions From Speculative Limits AGENCY: Commodity Futures Trading Commission. ACTION: Notice. SUMMARY: The...

  13. 76 FR 81481 - Agency Information Collection Activities: Notice of Intent to Renew Collection, Large Trader Reports

    Science.gov (United States)

    2011-12-28

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent to Renew Collection, Large Trader Reports AGENCY: Commodity Futures Trading Commission. ACTION: Notice SUMMARY: The Commodity...

  14. 77 FR 69806 - Agency Information Collection Activities: Notice of Intent To Renew Collection, Procurement...

    Science.gov (United States)

    2012-11-21

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection, Procurement Contracts AGENCY: Commodity Futures Trading Commission. ACTION: Notice SUMMARY: The Commodity...

  15. 75 FR 60087 - Agency Information Collection Activities: Notice of Intent To Renew Collection 3038-0049...

    Science.gov (United States)

    2010-09-29

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection 3038-0049, Procedural Requirements for Requests for Interpretative, No-Action, and Exemptive Letters AGENCY:...

  16. 76 FR 81916 - Agency Information Collection Activities: Notice of Intent To Renew Collection, Regulations...

    Science.gov (United States)

    2011-12-29

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection, Regulations Governing Bankruptcies of Commodity Brokers AGENCY: Commodity Futures Trading Commission. ACTION:...

  17. 77 FR 58616 - Pipeline Safety: Information Collection Activities, Revision to Gas Transmission and Gathering...

    Science.gov (United States)

    2012-09-21

    ... Systems'' and the ``Incident Report--Natural and Other Gas Transmission and Gathering Pipeline Systems... Safety: Information Collection Activities, Revision to Gas Transmission and Gathering Pipeline Systems... Natural Gas Association of America (INGAA)--Trade Association (11) Northeast Gas Association...

  18. 75 FR 64724 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-10-20

    ... Information Collection Activities; Submission to OMB for Review and Approval; Comment Request; Performance... that perform chemical, microbiological and whole effluent toxicity (WET) analyses required in the NPDES... permitting responsibility and laboratories doing chemical/microbiological analysis and...

  19. 78 FR 60864 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-10-02

    ... time measure to assist students and their parents in the college selection process. Award information... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review..., tuition and fees, average net price, student financial aid, graduation rates, revenues and...

  20. 77 FR 5778 - Agency Information Collection Activities: Rules Relating to Regulation of Domestic Exchange...

    Science.gov (United States)

    2012-02-06

    ... COMMISSION Agency Information Collection Activities: Rules Relating to Regulation of Domestic Exchange-Traded... extension of the collection. The collection covers rules related to risk disclosure concerning exchange... INFORMATION: In the notice of Extension of an Existing Collection, FR Doc. 2011-33841, on page 477 in...

  1. 78 FR 72688 - Information Collection Activities: Application for Permit To Drill; Proposed Collection; Comment...

    Science.gov (United States)

    2013-12-03

    ..., casing setting depths, drilling fluid (mud) programs, cementing programs and blowout preventer (BOP...; 134E1700D2 EEEE500000 ET1SF0000.DAQ000] Information Collection Activities: Application for Permit To Drill... data and information that is submitted with an Application for Permit to Drill (APD), a Revised...

  2. 78 FR 66344 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-11-05

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... to their performance in the classroom. The study will examine data from a teacher survey and data..., Information and Records Management Services, Office of Management. BILLING CODE 4000-01-P...

  3. 78 FR 79470 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-12-30

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... about data information systems will be used to support the development of a technical assistance tracker... development of a technical assistance tracker for RWHAP grantees to monitor and assess changes in the mix...

  4. Reflecting on Earlier Experiences with Unsolicited Findings: Points to Consider for Next-Generation Sequencing and Informed Consent in Diagnostics

    Science.gov (United States)

    Rigter, Tessel; Henneman, Lidewij; Kristoffersson, Ulf; Hall, Alison; Yntema, Helger G; Borry, Pascal; Tönnies, Holger; Waisfisz, Quinten; Elting, Mariet W; Dondorp, Wybo J; Cornel, Martina C

    2013-01-01

    High-throughput nucleotide sequencing (often referred to as next-generation sequencing; NGS) is increasingly being chosen as a diagnostic tool for cases of expected but unresolved genetic origin. When exploring a higher number of genetic variants, there is a higher chance of detecting unsolicited findings. The consequential increased need for decisions on disclosure of these unsolicited findings poses a challenge for the informed consent procedure. This article discusses the ethical and practical dilemmas encountered when contemplating informed consent for NGS in diagnostics from a multidisciplinary point of view. By exploring recent similar experiences with unsolicited findings in other settings, an attempt is made to describe what can be learned so far for implementing NGS in standard genetic diagnostics. The article concludes with a set of points to consider in order to guide decision-making on the extent of return of results in relation to the mode of informed consent. We hereby aim to provide a sound basis for developing guidelines for optimizing the informed consent procedure. PMID:23784691

  5. Active acoustic leak detection for LMFBR steam generator. Sound attenuation due to bubbles

    Energy Technology Data Exchange (ETDEWEB)

    Kumagai, Hiromichi; Sakuma, Toshio [Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.

    1995-06-01

    In the steam generators (SG) of LMFBR, it is necessary to detect the leakage of water from tubes of heat exchangers as soon as it occurs. The active acoustic detection method has drawn general interest owing to its short response time and reduction of the influence of background noise. In this paper, the application of the active acoustic detection method for SG is proposed, and sound attenuation by bubbles is investigated experimentally. Furthermore, using the SG sector model, sound field characteristics and sound attenuation characteristics due to injection of bubbles are studied. It is clarified that the sound attenuation depends upon bubble size as well as void fraction, that the distance attenuation of sound in the SG model containing heat transfer tubes is 6dB for each two-fold increase of distance, and that emitted sound attenuates immediately upon injection of bubbles. (author).

  6. Two Ways to Lead

    Science.gov (United States)

    Cody, Anthony

    2013-01-01

    One popular approach to teacher leadership is to identify certain teachers as particularly successful, then have others learn from them. Collaborative leadership, in contrast, looks at leadership as a quality that anyone can have. In this model, the goal is not to figure out who is best. Instead, teachers share their unique talents and interests…

  7. Lead Agency Responsibilities to Keep Informed of Personnel Needs in the Food and Agricultural Sciences are not being Fully Met.

    Science.gov (United States)

    1981-12-28

    managers told us that various experiences in hiring and retaining personnel can be attributed to several causes, such as the degree of technology needed...General Foods Corp. - processors of packaged grocery products Hershey Foods Corp. - chocolates and confectionary products and pasta International...Placement Service National Academy of Sciences National Institutes of Health National Science Foundation Office of Technology Assessment Rockefeller

  8. 76 FR 9776 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2011-02-22

    ... surveys, tracking and monitoring of classroom activities and school policies, and consultation with... disclose the information. Respondents/Affected Entities: Elementary and middle school students, parents... announces that an Information Collection Request (ICR) has been forwarded to the Office of Management...

  9. Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability.

    Science.gov (United States)

    Pattabiraman, Diwakar R; Bierie, Brian; Kober, Katharina Isabelle; Thiru, Prathapan; Krall, Jordan A; Zill, Christina; Reinhardt, Ferenc; Tam, Wai Leong; Weinberg, Robert A

    2016-03-04

    The epithelial-to-mesenchymal transition enables carcinoma cells to acquire malignancy-associated traits and the properties of tumor-initiating cells (TICs). TICs have emerged in recent years as important targets for cancer therapy, owing to their ability to drive clinical relapse and enable metastasis. Here, we propose a strategy to eliminate mesenchymal TICs by inducing their conversion to more epithelial counterparts that have lost tumor-initiating ability. We report that increases in intracellular levels of the second messenger, adenosine 3',5'-monophosphate, and the subsequent activation of protein kinase A (PKA) induce a mesenchymal-to-epithelial transition (MET) in mesenchymal human mammary epithelial cells. PKA activation triggers epigenetic reprogramming of TICs by the histone demethylase PHF2, which promotes their differentiation and loss of tumor-initiating ability. This study provides proof-of-principle for inducing an MET as differentiation therapy for TICs and uncovers a role for PKA in enforcing and maintaining the epithelial state.

  10. Does Structured Quizzing with Process Specific Feedback Lead to Learning Gains in an Active Learning Geoscience Classroom?

    Science.gov (United States)

    Palsole, S.; Serpa, L. F.

    2013-12-01

    There is a great realization that efficient teaching in the geosciences has the potential to have far reaching effects in outreach to decision and policy makers (Herbert, 2006; Manduca & Mogk, 2006). This research in turn informs educators that the geosciences by the virtue of their highly integrative nature play an important role in serving as an entry point into STEM disciplines and helping developing a new cadre of geoscientists, scientists and a general population with an understanding of science. Keeping these goals in mind we set to design introductory geoscience courses for non-majors and majors that move away from the traditional lecture models which don't necessarily contribute well to knowledge building and retention ((Handelsman et al., 2007; Hake, 1997) to a blended active learning classroom where basic concepts and didactic information is acquired online via webquests, lecturettes and virtual field trips and the face to face portions of the class are focused on problem solving exercises. The traditional way to ensure that students are prepared for the in-class activity is to have the students take a quiz online to demonstrate basic competency. In the process of redesign, we decided to leverage the technology to build quizzes that are highly structured and map to a process (formation of divergent boundaries for example) or sets of earth processes that we needed the students to know before in-class activities. The quizzes can be taken multiple times and provide process specific feedback, thus serving as a heuristic to the students to ensure they have acquired the necessary competency. The heuristic quizzes were developed and deployed over a year with the student data driving the redesign process to ensure synchronicity. Preliminary data analysis indicates a positive correlation between higher student scores on in-class application exercises and time spent on the process quizzes. An assessment of learning gains also indicate a higher degree of self

  11. Cognitive tasks in information analysis: Use of event dwell time to characterize component activities

    Energy Technology Data Exchange (ETDEWEB)

    Sanquist, Thomas F.; Greitzer, Frank L.; Slavich, Antoinette L.; Littlefield, Rik J.; Littlefield, Janis S.; Cowley, Paula J.

    2004-09-28

    Technology-based enhancement of information analysis requires a detailed understanding of the cognitive tasks involved in the process. The information search and report production tasks of the information analysis process were investigated through evaluation of time-stamped workstation data gathered with custom software. Model tasks simulated the search and production activities, and a sample of actual analyst data were also evaluated. Task event durations were calculated on the basis of millisecond-level time stamps, and distributions were plotted for analysis. The data indicate that task event time shows a cyclic pattern of variation, with shorter event durations (< 2 sec) reflecting information search and filtering, and longer event durations (> 10 sec) reflecting information evaluation. Application of cognitive principles to the interpretation of task event time data provides a basis for developing “cognitive signatures” of complex activities, and can facilitate the development of technology aids for information intensive tasks.

  12. A time course assessment of changes in reactive oxygen species generation and antioxidant defense in hydroponically grown wheat in response to lead ions (Pb2+).

    Science.gov (United States)

    Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2012-10-01

    We examined the effect of Pb(2+) (8 and 40 mg l(-1)) on reactive oxygen species generation and alterations in antioxidant enzymes in hydroponically grown wheat at 24, 72, and 120 h after exposure. Pb(2+) toxicity was more pronounced on root growth, and it correlated with the greater Pb accumulation in roots. Pb exposure (40 mg l(-1)) enhanced superoxide anion, H(2)O(2), and MDA content in wheat roots by 1.9- to 2.2-folds, 56-255%, and 41-90%, respectively, over the control. Pb-induced loss of membrane integrity was confirmed by the enhanced electrolyte leakage and in vivo histochemical localization. Activities of scavenging enzymes, superoxide dismutases and catalases, enhanced in Pb-treated wheat roots by 1.4- to 5.7-folds over that in the control. In contrast, the activities of ascorbate and guaiacol peroxidases and glutathione reductases decreased significantly, suggesting their non-involvement in detoxification process. The study concludes that Pb(2+)-induced oxidative damage in wheat roots involve greater H(2)O(2) accumulation and the deactivation of the related scavenging enzymes.

  13. Alternate Reading Frame Protein (F Protein) of Hepatitis C Virus: Paradoxical Effects of Activation and Apoptosis on Human Dendritic Cells Lead to Stimulation of T Cells

    Science.gov (United States)

    Samrat, Subodh Kumar; Li, Wen; Singh, Shakti; Kumar, Rakesh; Agrawal, Babita

    2014-01-01

    Hepatitis C virus (HCV) leads to chronic infection in the majority of infected individuals due to lack, failure, or inefficiency of generated adaptive immune responses. In a minority of patients, acute infection is followed by viral clearance. The immune correlates of viral clearance are not clear yet but have been extensively investigated, suggesting that multispecific and multifunctional cellular immunity is involved. The generation of cellular immunity is highly dependent upon how antigen presenting cells (APCs) process and present various viral antigens. Various structural and non-structural HCV proteins derived from the open reading frame (ORF) have been implicated in modulation of dendritic cells (DCs) and APCs. Besides the major ORF proteins, the HCV core region also encodes an alternate reading frame protein (ARFP or F), whose function in viral pathogenesis is not clear. In the current studies, we sought to determine the role of HCV-derived ARFP in modulating dendritic cells and stimulation of T cell responses. Recombinant adenovirus vectors containing F or core protein derived from HCV (genotype 1a) were prepared and used to endogenously express these proteins in dendritic cells. We made an intriguing observation that endogenous expression of F protein in human DCs leads to contrasting effects on activation and apoptosis of DCs, allowing activated DCs to efficiently internalize apoptotic DCs. These in turn result in efficient ability of DCs to process and present antigen and to prime and stimulate F protein derived peptide-specific T cells from HCV-naive individuals. Taken together, our findings suggest important aspects of F protein in modulating DC function and stimulating T cell responses in humans. PMID:24475147

  14. Alternate reading frame protein (F protein of hepatitis C virus: paradoxical effects of activation and apoptosis on human dendritic cells lead to stimulation of T cells.

    Directory of Open Access Journals (Sweden)

    Subodh Kumar Samrat

    Full Text Available Hepatitis C virus (HCV leads to chronic infection in the majority of infected individuals due to lack, failure, or inefficiency of generated adaptive immune responses. In a minority of patients, acute infection is followed by viral clearance. The immune correlates of viral clearance are not clear yet but have been extensively investigated, suggesting that multispecific and multifunctional cellular immunity is involved. The generation of cellular immunity is highly dependent upon how antigen presenting cells (APCs process and present various viral antigens. Various structural and non-structural HCV proteins derived from the open reading frame (ORF have been implicated in modulation of dendritic cells (DCs and APCs. Besides the major ORF proteins, the HCV core region also encodes an alternate reading frame protein (ARFP or F, whose function in viral pathogenesis is not clear. In the current studies, we sought to determine the role of HCV-derived ARFP in modulating dendritic cells and stimulation of T cell responses. Recombinant adenovirus vectors containing F or core protein derived from HCV (genotype 1a were prepared and used to endogenously express these proteins in dendritic cells. We made an intriguing observation that endogenous expression of F protein in human DCs leads to contrasting effects on activation and apoptosis of DCs, allowing activated DCs to efficiently internalize apoptotic DCs. These in turn result in efficient ability of DCs to process and present antigen and to prime and stimulate F protein derived peptide-specific T cells from HCV-naive individuals. Taken together, our findings suggest important aspects of F protein in modulating DC function and stimulating T cell responses in humans.

  15. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue.

    Science.gov (United States)

    Bolus, W Reid; Gutierrez, Dario A; Kennedy, Arion J; Anderson-Baucum, Emily K; Hasty, Alyssa H

    2015-10-01

    Adipose tissue (AT) inflammation during obesity is mediated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alternative macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2(-/-) AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2(-/-) mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2(-/-) bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2(-/-) mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2(-/-) mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation.

  16. Mutability of bifunctional thigh muscle activity in pedaling due to contralateral leg force generation.

    Science.gov (United States)

    Kautz, S A; Brown, D A; Van der Loos, H F M; Zajac, F E

    2002-09-01

    other transition (i.e., flexion-to-extension; predominantly by rectus femoris), hamstrings activity and work output increased in the pedaling leg during its extension-to-flexion transition. Therefore rhythmic isometric force generation in the contralateral leg supported the ongoing bifunctional muscle activity and resulting work output in the pedaling leg. The results suggest that neural interlimb coordinating mechanisms fine-tune bifunctional muscle activity in rhythmic lower-limb tasks to ensure limb flexion/extension transitions are executed successfully.

  17. Matrine induction of reactive oxygen species activates p38 leading to caspase-dependent cell apoptosis in non-small cell lung cancer cells.

    Science.gov (United States)

    Tan, Caihong; Qian, Xiaoqiang; Jia, Rongdi; Wu, Min; Liang, Zhongqin

    2013-11-01

    Non-small cell lung carcinoma (NSCLC) is one of the most refractory cancers in the clinic; it is insensitive to chemotherapy and is usually excised. However, screening natural compounds from herbs is also considered a possible method for its therapy. In the present study, we investigated whether matrine, a natural compound isolated from Sophora flavescens Ait. and exerting an inhibitory effect on lung cancer cells, also indicates inhibition on NSCLC cells and elucidated its molecular mechanism. Firstly, it is confirmed that matrine induces apoptosis of human NSCLC cells with anti-apoptotic factors inhibited and dependent on caspase activity. In addition, we found that matrine increases the phosphorylation of p38 but not its total protein, and inhibition of the p38 pathway with SB202190 partially prevents matrine-induced apoptosis. Furthermore, matrine generates reactive oxygen species (ROS) in a dose- and time-dependent manner, which is reversed by pretreatment with N-acetyl-L-cysteine (NAC). Additionally, inhibition of cell proliferation and increase of phosphorylation of p38 was also partially reversed by NAC. Collectively, matrine activates p38 pathway leading to a caspase-dependent apoptosis by inducing generation of ROS in NSCLC cells and may be a potential chemical for NSCLC.

  18. Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity

    Directory of Open Access Journals (Sweden)

    Leticia Corrales

    2015-05-01

    Full Text Available Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that IFN-β expression was dependent upon activation of the host STING pathway, we hypothesized that direct engagement of STING through intratumoral (IT administration of specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using the mouse STING agonist DMXAA showed a potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN derivatives that activated all human STING alleles as well as murine STING. IT injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory. Synthetic CDNs have high translational potential as a cancer therapeutic.

  19. Neutron Activation Foil and Thermoluminescent Dosimeter Responses to a Lead Reflected Pulse of the CEA Valduc SILENE Critical Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Thomas Martin [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Celik, Cihangir [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Isbell, Kimberly McMahan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lee, Yi-kang [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Gagnier, Emmanuel [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Authier, Nicolas [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Piot, Jerome [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Jacquet, Xavier [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Rousseau, Guillaume [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Reynolds, Kevin H. [Y-12 National Security Complex, Oak Ridge, TN (United States)

    2016-09-01

    This benchmark experiment was conducted as a joint venture between the US Department of Energy (DOE) and the French Commissariat à l'Energie Atomique (CEA). Staff at the Oak Ridge National Laboratory (ORNL) in the US and the Centre de Valduc in France planned this experiment. The experiment was conducted on October 13, 2010 in the SILENE critical assembly facility at Valduc. Several other organizations contributed to this experiment and the subsequent evaluation, including CEA Saclay, Lawrence Livermore National Laboratory (LLNL), the Y-12 National Security Complex (NSC), Babcock International Group in the United Kingdom, and Los Alamos National Laboratory (LANL). The goal of this experiment was to measure neutron activation and thermoluminescent dosimeter (TLD) doses from a source similar to a fissile solution critical excursion. The resulting benchmark can be used for validation of computer codes and nuclear data libraries as required when performing analysis of criticality accident alarm systems (CAASs). A secondary goal of this experiment was to qualitatively test performance of two CAAS detectors similar to those currently and formerly in use in some US DOE facilities. The detectors tested were the CIDAS MkX and the Rocky Flats NCD-91. The CIDAS detects gammas with a Geiger-Muller tube, and the Rocky Flats detects neutrons via charged particles produced in a thin 6LiF disc, depositing energy in a Si solid-state detector. These detectors were being evaluated to determine whether they would alarm, so they were not expected to generate benchmark quality data.

  20. Neonatal morphine administration leads to changes in hippocampal BDNF levels and antioxidant enzyme activity in the adult life of rats.

    Science.gov (United States)

    Rozisky, J R; Laste, G; de Macedo, I C; Santos, V S; Krolow, R; Noschang, C; Vanzella, C; Bertoldi, K; Lovatel, G A; de Souza, I C C; Siqueira, I R; Dalmaz, C; Caumo, W; Torres, I L S

    2013-03-01

    It is know that repeated exposure to opiates impairs spatial learning and memory and that the hippocampus has important neuromodulatory effects after drug exposure and withdrawal symptoms. Thus, the aim of this investigation was to assess hippocampal levels of BDNF, oxidative stress markers associated with cell viability, and TNF-α in the short, medium and long term after repeated morphine treatment in early life. Newborn male Wistar rats received subcutaneous injections of morphine (morphine group) or saline (control group), 5 μg in the mid-scapular area, starting on postnatal day 8 (P8), once daily for 7 days, and neurochemical parameters were assessed in the hippocampus on postnatal days 16 (P16), 30 (P30), and 60 (P60). For the first time, we observed that morphine treatment in early life modulates BDNF levels in the medium and long term and also modulates superoxide dismutase activity in the long term. In addition, it was observed effect of treatment and age in TNF-α levels, and no effects in lactate dehydrogenase levels, or cell viability. These findings show that repeated morphine treatment in the neonatal period can lead to long-lasting neurochemical changes in the hippocampus of male rats, and indicate the importance of cellular and intracellular adaptations in the hippocampus after early-life opioid exposure to tolerance, withdrawal and addiction.

  1. Modification of carbonic anhydrase II with acetaldehyde, the first metabolite of ethanol, leads to decreased enzyme activity.

    OpenAIRE

    2008-01-01

    Abstract Background Acetaldehyde, the first metabolite of ethanol, can generate covalent modifications of proteins and cellular constituents. However, functional consequences of such modification remain poorly defined. In the present study, we examined acetaldehyde reaction with human carbonic anhydrase (CA) isozyme II, which has several features that make it a suitable target protein: It is widely expressed, its enzymatic activity can be monitored, its structural and catalytic properties are...

  2. Mitotic defects lead to pervasive aneuploidy and accompany loss of RB1 activity in mouse LmnaDhe dermal fibroblasts.

    Directory of Open Access Journals (Sweden)

    C Herbert Pratt

    Full Text Available BACKGROUND: Lamin A (LMNA is a component of the nuclear lamina and is mutated in several human diseases, including Emery-Dreifuss muscular dystrophy (EDMD; OMIM ID# 181350 and the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS; OMIM ID# 176670. Cells from progeria patients exhibit cell cycle defects in both interphase and mitosis. Mouse models with loss of LMNA function have reduced Retinoblastoma protein (RB1 activity, leading to aberrant cell cycle control in interphase, but how mitosis is affected by LMNA is not well understood. RESULTS: We examined the cell cycle and structural phenotypes of cells from mice with the Lmna allele, Disheveled hair and ears (Lmna(Dhe. We found that dermal fibroblasts from heterozygous Lmna(Dhe (Lmna(Dhe/+ mice exhibit many phenotypes of human laminopathy cells. These include severe perturbations to the nuclear shape and lamina, increased DNA damage, and slow growth rates due to mitotic delay. Interestingly, Lmna(Dhe/+ fibroblasts also had reduced levels of hypophosphorylated RB1 and the non-SMC condensin II-subunit D3 (NCAP-D3, a mitosis specific centromere condensin subunit that depends on RB1 activity. Mitotic check point control by mitotic arrest deficient-like 1 (MAD2L1 also was perturbed in Lmna(Dhe/+ cells. Lmna(Dhe/+ fibroblasts were consistently aneuploid and had higher levels of micronuclei and anaphase bridges than normal fibroblasts, consistent with chromosome segregation defects. CONCLUSIONS: These data indicate that RB1 may be a key regulator of cellular phenotype in laminopathy-related cells, and suggest that the effects of LMNA on RB1 include both interphase and mitotic cell cycle control.

  3. Tracking the critical offshore conditions leading to marine inundation via active learning of full-process based models

    Science.gov (United States)

    Rohmer, Jeremy; Idier, Deborah; Bulteau, Thomas; Paris, François

    2016-04-01

    From a risk management perspective, it can be of high interest to identify the critical set of offshore conditions that lead to inundation on key assets for the studied territory (e.g., assembly points, evacuation routes, hospitals, etc.). This inverse approach of risk assessment (Idier et al., NHESS, 2013) can be of primary importance either for the estimation of the coastal flood hazard return period or for constraining the early warning networks based on hydro-meteorological forecast or observations. However, full-process based models for coastal flooding simulation have very large computational time cost (typically of several hours), which often limits the analysis to a few scenarios. Recently, it has been shown that meta-modelling approaches can efficiently handle this difficulty (e.g., Rohmer & Idier, NHESS, 2012). Yet, the full-process based models are expected to present strong non-linearities (non-regularities) or shocks (discontinuities), i.e. dynamics controlled by thresholds. For instance, in case of coastal defense, the dynamics is characterized first by a linear behavior of the waterline position (increase with increasing offshore conditions), as long as there is no overtopping, and then by a very strong increase (as soon as the offshore conditions are energetic enough to lead to wave overtopping, and then overflow). Such behavior might make the training phase of the meta-model very tedious. In the present study, we propose to explore the feasibility of active learning techniques, aka semi-supervised machine learning, to track the set of critical conditions with a reduced number of long-running simulations. The basic idea relies on identifying the simulation scenarios which should both reduce the meta-model error and improve the prediction of the critical contour of interest. To overcome the afore-described difficulty related to non-regularity, we rely on Support Vector Machines, which have shown very high performance for structural reliability

  4. Saturation mutagenesis of lysine 12 leads to the identification of derivatives of nisin A with enhanced antimicrobial activity.

    Directory of Open Access Journals (Sweden)

    Evelyn M Molloy

    Full Text Available It is becoming increasingly apparent that innovations from the "golden age" of antibiotics are becoming ineffective, resulting in a pressing need for novel therapeutics. The bacteriocin family of antimicrobial peptides has attracted much attention in recent years as a source of potential alternatives. The most intensively studied bacteriocin is nisin, a broad spectrum lantibiotic that inhibits gram-positive bacteria including important food pathogens and clinically relevant antibiotic resistant bacteria. Nisin is gene-encoded and, as such, is amenable to peptide bioengineering, facilitating the generation of novel derivatives that can be screened for desirable properties. It was to this end that we used a site-saturation mutagenesis approach to create a bank of producers of nisin A derivatives that differ with respect to the identity of residue 12 (normally lysine; K12. A number of these producers exhibited enhanced bioactivity and the nisin A K12A producer was deemed of greatest interest. Subsequent investigations with the purified antimicrobial highlighted the enhanced specific activity of this modified nisin against representative target strains from the genera Streptococcus, Bacillus, Lactococcus, Enterococcus and Staphylococcus.

  5. TERT promoter mutations lead to high transcriptional activity under hypoxia and temozolomide treatment and predict poor prognosis in gliomas.

    Directory of Open Access Journals (Sweden)

    Chen Chen

    Full Text Available This study explored the effects of telomerase reverse transcriptase (TERT promoter mutations on transcriptional activity of the TERT gene under hypoxic and temozolomide (TMZ treatment conditions, and investigated the status and prognostic value of these mutations in gliomas.The effect of TERT promoter mutations on the transcriptional activity of the TERT gene under hypoxic and TMZ treatment conditions was investigated in glioma cells using the luciferase assay. TERT promoter mutations were detected in 101 glioma samples (grades I-IV and 49 other brain tumors by sequencing. TERT mRNA expression in gliomas was examined by real-time PCR. Hazard ratios from survival analysis of glioma patients were determined relative to the presence of TERT promoter mutations.Mutations in the TERT promoter enhanced gene transcription even under hypoxic and TMZ treatment conditions, inducing upregulation of TERT mRNA expression. Mutations were detected in gliomas, but not in meningiomas, pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, or peripheral blood of glioma patients. Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.TERT promoter mutations were specific to gliomas. TERT promoter mutations maintained its ability of inducing high transcriptional activity even under hypoxic and TMZ treatment conditions, and the presence of mutations was associated with poor prognosis in glioma patients. These findings demonstrate that TERT promoter mutations are novel prognostic markers for gliomas that can inform prospective therapeutic strategies.

  6. 77 FR 74667 - Agency Information Collection Activities; Proposed Collection; Comment Request; Information To...

    Science.gov (United States)

    2012-12-17

    ... annual distribution number (ADN). DATES: Submit either electronic or written comments on the collection... that the Secretary of Health and Human Services (the Secretary) will assign an ADN for devices that meet the eligibility criteria to be permitted to be sold for profit. The ADN is defined as the...

  7. Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3',4',5'-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities.

    Science.gov (United States)

    Srinivasan, Balasubramanian; Johnson, Thomas E; Lad, Rahul; Xing, Chengguo

    2009-11-26

    Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

  8. Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection.

    Science.gov (United States)

    Hardbower, Dana M; Asim, Mohammad; Murray-Stewart, Tracy; Casero, Robert A; Verriere, Thomas; Lewis, Nuruddeen D; Chaturvedi, Rupesh; Piazuelo, M Blanca; Wilson, Keith T

    2016-10-01

    We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2 (-/-) mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill H. pylori. We now bred Arg2 (-/-) to Nos2 (-/-) mice, and infected them with H. pylori. Compared to wild-type mice, both Arg2 (-/-) and Arg2 (-/-) ;Nos2 (-/-) mice exhibited increased gastritis and decreased colonization, the latter indicating that the effect of ARG2 deletion on bacterial burden was not mediated by NO. While Arg2 (-/-) mice demonstrated enhanced M1 macrophage activation, Nos2 (-/-) and Arg2 (-/-) ;Nos2 (-/-) mice did not demonstrate these changes, but exhibited increased CXCL1 and CXCL2 responses. There was an increased expression of the Th1/Th17 cytokines, interferon gamma and interleukin 17, in gastric tissues and splenic T-cells from Arg2 (-/-), but not Nos2 (-/-) or Arg2 (-/-) ;Nos2 (-/-) mice. Gastric tissues from infected Arg2 (-/-) mice demonstrated increased expression of arginase 1, ornithine decarboxylase, adenosylmethionine decarboxylase 1, spermidine/spermine N (1)-acetyltransferase 1, and spermine oxidase, along with increased spermine levels. These data indicate that ARG2 deletion results in compensatory upregulation of gastric polyamine synthesis and catabolism during H. pylori infection, which may contribute to increased gastric inflammation and associated decreased bacterial load. Overall, the finding of this study is that ARG2 contributes to the immune evasion of H. pylori by restricting M1 macrophage activation and polyamine metabolism.

  9. An Automated Approach to the Generation of Structured Building Information Models from Unstructured 3d Point Cloud Scans

    DEFF Research Database (Denmark)

    Tamke, Martin

    2016-01-01

    In this paper we present and evaluate an approach for the automatic generation of building models in IFC BIM format from unstructured Point Clouds scans, as they result from 3D laser scans of buildings. While the actual measurement process is relatively fast, 85% of the overall time are spend...... on the interpretation and transformation of the resulting Point Cloud data into information, which can be used in architectural and engineering design workflows. Our approach to tackle this problem, is in contrast to existing ones which work on the levels of points, based on the detection of building elements......, such as walls, ceilings, doors, windows, and spaces and the relation between these. We present use cases with our software prototype, evaluate the results, and discuss future work, that will bring the research further towards the aim to create automatically semantic links between the conception of building...

  10. An Automated Approach to the Generation of Structured Building Information Models from Unstructured 3d Point Cloud Scans

    DEFF Research Database (Denmark)

    Tamke, Martin; Evers, Henrik Leander; Wessel, Raoul

    2016-01-01

    , such as walls, ceilings, doors, windows, and spaces and the relation between these. We present use cases with our software prototype, evaluate the results, and discuss future work, that will bring the research further towards the aim to create automatically semantic links between the conception of building......In this paper we present and evaluate an approach for the automatic generation of building models in IFC BIM format from unstructured Point Cloud scans, as they result from 3dlaser scans of buildings. While the actual measurement process is relatively fast, 85% of the overall time are spend...... on the interpretation and transformation of the resulting Point Cloud data into information, which can be used in architectural and engineering design workflows. Our approach to tackle this problem, is in contrast to existing ones which work on the levels of points, based on the detection of building elements...

  11. "Life without nuclear power": A nuclear plant retirement formulation model and guide based on economics. San Onofre Nuclear Generating Station case: Economic impacts and reliability considerations leading to plant retirement

    Science.gov (United States)

    Wasko, Frank

    assessment review and then on to the stakeholder cost benefit analysis (if model qualifications are met) leading to a final plant retirement decision. This application via the model and guide, in turn, will lead electric utilities to explore system upgrade import opportunities and mitigation measures versus building new replacement generation facilities. United States nuclear reactors are licensed for 40 years with a 20 year extension available prior to the expiration date (EIA, 2013). Since late 2012, electric power companies have announced the early retirement of four uneconomical nuclear power plants while other studies have indicated that as many as 70 percent of United States nuclear power plants are potentially at risk for early retirement (Crooks, 2014 and Cooper, 2013). A high percentage of these aforementioned nuclear plants have operating licenses that will not expire until 2030 and beyond. Thus, for the most part, replacement power contingency planning has not been initiated for these plants or is still in preliminary stages. The recent nuclear plant retirements are the first since 1998 (EIA, 2013). Decisions to retire the plants involved concerns over maintenance and repair costs as well as declining profitability (EIA, 2013). In addition, the Energy Information Administration (2010-2012) released data that demonstrated that the worst 25 percent of United States nuclear plants are far more expensive to operate and generate electricity than new gas plants. It is equally important to understand and explain the economic and power replacement implications to both ratepayers and end-users. A SONGS case study analysis will review the economic, operational and political challenges that SCE faced leading to the retirement decision of SONGS. As preface to the case study, replacement steam generators (RSGs) were installed in Unit 2 in 2009 and in Unit 3 in 2010. In January 2012, while Unit 2 was down for routine maintenance, a small leak was discovered inside a steam

  12. Periowave demonstrates bactericidal activity against periopathogens and leads to improved clinical outcomes in the treatment of adult periodontitis

    Science.gov (United States)

    Street, Cale N.; Andersen, Roger; Loebel, Nicolas G.

    2009-02-01

    Periodontitis affects half of the U.S. population over 50, and is the leading cause of tooth loss after 35. It is believed to be caused by growth of complex bacterial biofilms on the tooth surface below the gumline. Photodynamic therapy, a technology used commonly in antitumor applications, has more recently been shown to exhibit antimicrobial efficacy. We have demonstrated eradication of the periopathogens Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans in vitro using PeriowaveTM; a commercial photodisinfection system. In addition, several clinical studies have now demonstrated the efficacy of this treatment. A pilot study in the U.S. showed that 68% of patients treated with PeriowaveTM adjunctively to scaling and root planing (SRP) showed clinical attachment level increase of >1 mm, as opposed to 30% with SRP alone. In a subsequent larger study, a second PeriowaveTM treatment 6 weeks after initial treatment led to pocket depth improvements of >1.5 mm in 89% of patients. Finally, in the most recent multicenter, randomized, examiner-blinded study conducted on 121 subjects in Canada, PeriowaveTM treatment produced highly significant gains in attachment level (0.88 mm vs. 0.57 mm; p=0.003) and pocket depth (0.87 mm vs. 0.63 mm; p=0.01) as compared to SRP alone. In summary, PeriowaveTM demonstrated strong bactericidal activity against known periopathogens, and treatment of periodontitis using this system produced significantly better clinical outcomes than SRP alone. This, along with the absence of any adverse events in patients treated to date demonstrates that PDT is a safe and effective treatment for adult chronic periodontitis.

  13. Lead stress effects on physiobiochemical activities of higher plants.

    Science.gov (United States)

    Sengar, Rakesh Singh; Gautam, Madhu; Sengar, Rajesh Singh; Garg, Sanjay Kumar; Sengar, Kalpana; Chaudhary, Reshu

    2008-01-01

    Lead is a metallic pollutant emanating from various environmental sources including industrial wastes, combustion of fossil fuels, and use of agrochemicals. Lead may exist in the atmosphere as dusts, fumes, mists, and vapors, and in soil as a mineral. Soils along roadsides are rich in lead because vehicles burn leaded gasoline, which contributes to environmental lead pollution. Other important sources of lead pollution are geological weathering, industrial processing of ores and minerals, leaching of lead from solid wastes, and animal and human excreta. Lead is nondegradable, readily enters the food chain, and can subsequently endanger human and animal health. Lead is one of the most important environment pollutants and deserves the increasing attention it has received in recent decades. The present effort was undertaken to review lead stress effects on the physiobiochemical activity of higher plants. Lead has gained considerable attention as a potent heavy metal pollutant because of growing anthropogenic pressure on the environment. Lead-contaminated soils show a sharp decline in crop productivity. Lead is absorbed by plants mainly through the root system and in minor amounts through the leaves. Within the plants, lead accumulates primarily in roots, but some is translocated to aerial plant parts. Soil pH, soil particle size, cation-exchange capacity, as well as root surface area, root exudation, and mycorrhizal transpiration rate affect the availability and uptake of lead by plants. Only a limited amount of lead is translocated from roots to other organs because there are natural plant barriers in the root endodermis. At lethal concentrations, this barrier is broken and lead may enter vascular tissues. Lead in plants may form deposits of various sizes, present mainly in intercellular spaces, cell walls, and vacuoles. Small deposits of this metal are also seen in the endoplasmic reticulum, dictyosome, and dictyosome-derived vesicles. After entering the cells, lead

  14. Neutron Activation Foil and Thermoluminescent Dosimeter Responses to a Lead Reflected Pulse of the CEA Valduc SILENE Critical Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Thomas Martin [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Celik, Cihangir [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Isbell, Kimberly McMahan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lee, Yi-kang [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Gagnier, Emmanuel [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Authier, Nicolas [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Piot, Jerome [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Jacquet, Xavier [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Rousseau, Guillaume [Commissariat a l' Energie Atomique et aux Energies Alternatives (CEA-Saclay), Gif-sur-Yvette (France); Reynolds, Kevin H. [Y-12 National Security Complex, Oak Ridge, TN (United States)

    2016-09-01

    This benchmark experiment was conducted as a joint venture between the US Department of Energy (DOE) and the French Commissariat à l'Energie Atomique (CEA). Staff at the Oak Ridge National Laboratory (ORNL) in the US and the Centre de Valduc in France planned this experiment. The experiment was conducted on October 13, 2010 in the SILENE critical assembly facility at Valduc. Several other organizations contributed to this experiment and the subsequent evaluation, including CEA Saclay, Lawrence Livermore National Laboratory (LLNL), the Y-12 National Security Complex (NSC), Babcock International Group in the United Kingdom, and Los Alamos National Laboratory (LANL). The goal of this experiment was to measure neutron activation and thermoluminescent dosimeter (TLD) doses from a source similar to a fissile solution critical excursion. The resulting benchmark can be used for validation of computer codes and nuclear data libraries as required when performing analysis of criticality accident alarm systems (CAASs). A secondary goal of this experiment was to qualitatively test performance of two CAAS detectors similar to those currently and formerly in use in some US DOE facilities. The detectors tested were the CIDAS MkX and the Rocky Flats NCD-91. The CIDAS detects gammas with a Geiger-Muller tube, and the Rocky Flats detects neutrons via charged particles produced in a thin 6LiF disc, depositing energy in a Si solid-state detector. These detectors were being evaluated to determine whether they would alarm, so they were not expected to generate benchmark quality data.

  15. Cu(II)-coumestrol interaction leads to ROS-mediated DNA damage and cell death: a putative mechanism for anticancer activity.

    Science.gov (United States)

    Zafar, Atif; Singh, Swarnendra; Naseem, Imrana

    2016-07-01

    Phytoestrogens have attracted considerable interest as natural alternatives to hormone replacement therapy and their potential as cancer therapeutic agents. Among phytoestrogens, coumestrol has shown multipharmacological properties such as antiinflammatory, neuroprotective, osteoblastic differentiation and anticancer. Though several studies have described anticancer effects of coumestrol, a clear underlying molecular mechanism has not been elucidated. Unlike normal cells, cancer cells contain elevated copper levels that play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper in cancer cells can serve as effective anticancer strategy. Using human peripheral lymphocytes, we assessed lipid peroxidation, protein carbonylation, reactive oxygen species (ROS) generation, DNA damage and apoptosis by coumestrol in the presence of exogenously added Cu(II) in cells to simulate malignancy-like condition. Results showed that Cu(II)-coumestrol interaction leads to lipid peroxidation and protein carbonylation (markers of oxidative stress), DNA fragmentation and apoptosis in treated lymphocytes. Further, incubation of lymphocytes with ROS scavengers and membrane-permeant copper chelator, neocuproine, resulted in inhibition of DNA damage and apoptosis. This suggests that coumestrol engages in redox cycling of Cu(II) to generate ROS that leads to DNA fragmentation and apoptosis. In conclusion, this is the first report showing that coumestrol targets cellular copper to induce prooxidant death in malignant cells. We believe that such a prooxidant cytotoxic mechanism better explains the anticancer activity of coumestrol. These findings will provide significant insights into the development of new chemical molecules with better copper-chelating and prooxidant properties against cancer cells.

  16. Inconspicuous anchoring effects generated by false information

    Institute of Scientific and Technical Information of China (English)

    Chen Qu; Jun Wang; Yuejia Luo

    2008-01-01

    The impact of false information on numerical judgments was examined on young normal subjects by an event-related potential (ERP) experiment. To imitate the judgments in real world, we ensured the subjects acknowledged of the target task. The behavioral results found that both uncertain information and false information assimilated the final estimates: higher after higher anchors and lower after lower anchors; and false information caused a weaker anchoring bias than uncertain information. ERP results provided further electrophysiological evidence for the mechanism of anchoring. In the early phrase, it was an accessibility-dominated process in which two kinds of anchors elicited an N300 component related to the accessibility of anchors propositions. The knowledge relevant to targets joined the process in the late phrase, which caused a larger amplitude of late positive component (LPC) for implausible lower anchors than that for plausible higher anchors. Source analysis showed that medial frontal gyrus, whose activity was suggested to signal the need of adjustment, was more reliable to explain the LPC elicited by implausible lower anchors. Therefore, we suggest that accessibility is facilitated when the external anchor is consistent with the world knowledge, and adjustment is initiated when the external anchor is inconsistent.

  17. Using visual information analysis to explore complex patterns in the activity of designers

    DEFF Research Database (Denmark)

    Cash, Philip; Stanković, Tino; Štorga, Mario

    2014-01-01

    the temporality of interrelations between interlinked variables and, as such, can be applied to a range of datasets. By providing a statistical analysis of the networks’ growth the proposed method allows for the modelling of complex patterns of activity. Throughout, the method is demonstrated with respect......The analysis of complex interlinked datasets poses a significant problem for design researchers. This is addressed by proposing an information visualisation method for analysing patterns of design activity, qualitatively and quantitatively, with respect to time. This method visualises...... to a fully realised example of information seeking activity. The core contribution of the proposed method is in supporting the analysis of activity with respect to both macro and micro level temporal interactions between variables....

  18. Leading to distraction: Driver distraction, lead car, and road environment.

    Science.gov (United States)

    Kountouriotis, G K; Merat, N

    2016-04-01

    Driver distraction is strongly associated with crashes and near-misses, and despite the attention this topic has received in recent years, the effect of different types of distracting task on driving performance remains unclear. In the case of non-visual distractions, such as talking on the phone or other engaging verbal tasks that do not require a visual input, a common finding is reduced lateral variability in steering and gaze patterns where participants concentrate their gaze towards the centre of the road and their steering control is less variable. In the experiments presented here, we examined whether this finding is more pronounced in the presence of a lead car (which may provide a focus point for gaze) and whether the behaviour of the lead car has any influence on the driver's steering control. In addition, both visual and non-visual distraction tasks were used, and their effect on different road environments (straight and curved roadways) was assessed. Visual distraction was found to increase variability in both gaze patterns and steering control, non-visual distraction reduced gaze and steering variability in conditions without a lead car; in the conditions where a lead car was present there was no significant difference from baseline. The lateral behaviour of the lead car did not have an effect on steering performance, a finding which indicates that a lead car may not necessarily be used as an information point. Finally, the effects of driver distraction were different for straight and curved roadways, indicating a stronger influence of the road environment in steering than previously thought.

  19. Deficiency of MALT1 paracaspase activity results in unbalanced regulatory and effector T and B cell responses leading to multiorgan inflammation.

    Science.gov (United States)

    Bornancin, Frédéric; Renner, Florian; Touil, Ratiba; Sic, Heiko; Kolb, Yeter; Touil-Allaoui, Ismahane; Rush, James S; Smith, Paul A; Bigaud, Marc; Junker-Walker, Ursula; Burkhart, Christoph; Dawson, Janet; Niwa, Satoru; Katopodis, Andreas; Nuesslein-Hildesheim, Barbara; Weckbecker, Gisbert; Zenke, Gerhard; Kinzel, Bernd; Traggiai, Elisabetta; Brenner, Dirk; Brüstle, Anne; St Paul, Michael; Zamurovic, Natasa; McCoy, Kathy D; Rolink, Antonius; Régnier, Catherine H; Mak, Tak W; Ohashi, Pamela S; Patel, Dhavalkumar D; Calzascia, Thomas

    2015-04-15

    The paracaspase MALT1 plays an important role in immune receptor-driven signaling pathways leading to NF-κB activation. MALT1 promotes signaling by acting as a scaffold, recruiting downstream signaling proteins, as well as by proteolytic cleavage of multiple substrates. However, the relative contributions of these two different activities to T and B cell function are not well understood. To investigate how MALT1 proteolytic activity contributes to overall immune cell regulation, we generated MALT1 protease-deficient mice (Malt1(PD/PD)) and compared their phenotype with that of MALT1 knockout animals (Malt1(-/-)). Malt1(PD/PD) mice displayed defects in multiple cell types including marginal zone B cells, B1 B cells, IL-10-producing B cells, regulatory T cells, and mature T and B cells. In general, immune defects were more pronounced in Malt1(-/-) animals. Both mouse lines showed abrogated B cell responses upon immunization with T-dependent and T-independent Ags. In vitro, inactivation of MALT1 protease activity caused reduced stimulation-induced T cell proliferation, impaired IL-2 and TNF-α production, as well as defective Th17 differentiation. Consequently, Malt1(PD/PD) mice were protected in a Th17-dependent experimental autoimmune encephalomyelitis model. Surprisingly, Malt1(PD/PD) animals developed a multiorgan inflammatory pathology, characterized by Th1 and Th2/0 responses and enhanced IgG1 and IgE levels, which was delayed by wild-type regulatory T cell reconstitution. We therefore propose that the pathology characterizing Malt1(PD/PD) animals arises from an immune imbalance featuring pathogenic Th1- and Th2/0-skewed effector responses and reduced immunosuppressive compartments. These data uncover a previously unappreciated key function of MALT1 protease activity in immune homeostasis and underline its relevance in human health and disease.

  20. Autism-associated R451C mutation in neuroligin3 leads to activation of the unfolded protein response in a PC12 Tet-On inducible system.

    Science.gov (United States)

    Ulbrich, Lisa; Favaloro, Flores Lietta; Trobiani, Laura; Marchetti, Valentina; Patel, Vruti; Pascucci, Tiziana; Comoletti, Davide; Marciniak, Stefan J; De Jaco, Antonella

    2016-02-15

    Several forms of monogenic heritable autism spectrum disorders are associated with mutations in the neuroligin genes. The autism-linked substitution R451C in neuroligin3 induces local misfolding of its extracellular domain, causing partial retention in the ER (endoplasmic reticulum) of expressing cells. We have generated a PC12 Tet-On cell model system with inducible expression of wild-type or R451C neuroligin3 to investigate whether there is activation of the UPR (unfolded protein response) as a result of misfolded protein retention. As a positive control for protein misfolding, we also expressed the mutant G221R neuroligin3, which is known to be completely retained within the ER. Our data show that overexpression of either R451C or G221R mutant proteins leads to the activation of all three signalling branches of the UPR downstream of the stress sensors ATF6 (activating transcription factor 6), IRE1 (inositol-requiring enzyme 1) and PERK [PKR (dsRNA-dependent protein kinase)-like endoplasmic reticulum kinase]. Each branch displayed different activation profiles that partially correlated with the degree of misfolding caused by each mutation. We also show that up-regulation of BiP (immunoglobulin heavy-chain-binding protein) and CHOP [C/EBP (CCAAT/enhancer-binding protein)-homologous protein] was induced by both mutant proteins but not by wild-type neuroligin3, both in proliferative cells and cells differentiated to a neuron-like phenotype. Collectively, our data show that mutant R451C neuroligin3 activates the UPR in a novel cell model system, suggesting that this cellular response may have a role in monogenic forms of autism characterized by misfolding mutations.

  1. 77 FR 477 - Agency Information Collection Activities: Rules Relating to Regulation of Domestic Exchange...

    Science.gov (United States)

    2012-01-05

    ... COMMISSION Agency Information Collection Activities: Rules Relating to Regulation of Domestic Exchange-Traded...., permitting electronic submission of responses. Rules Relating to Regulation of Domestic Exchange-Traded... solicits comments on rules related to risk disclosure concerning exchange traded commodity options....

  2. 75 FR 33324 - MMS Information Collection Activity: 1010-NEW, Study of Sharing To Assess Community Resilience...

    Science.gov (United States)

    2010-06-11

    ... Federal Register notice (75 FR 1648) announcing that we would submit this ICR to OMB for approval. The... Minerals Management Service MMS Information Collection Activity: 1010--NEW, Study of Sharing To Assess... collection (1010--NEW). SUMMARY: To comply with the Paperwork Reduction Act of 1995 (PRA), we are...

  3. 77 FR 32593 - Agency Information Collection Activities; Notice of Intent To Renew Collection: Rules Relating To...

    Science.gov (United States)

    2012-06-01

    .... And Office of Information and Regulatory Affairs, Office of Management and Budget, Attention: Desk... or requirements that members of the public submit reports, keep records, or provide information to a..., mechanical, or other technological collection techniques or other forms of information technology;...

  4. Guanine nucleotide exchange factor αPIX leads to activation of the Rac 1 GTPase/glycogen phosphorylase pathway in interleukin (IL)-2-stimulated T cells

    DEFF Research Database (Denmark)

    Llavero, Francisco; Urzelai, Bakarne; Osinalde, Nerea;

    2015-01-01

    Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation. In the lymphoid system, Rac 1 and in general other small GTPases of the Rho family participate....... More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation...... first Rac 1 and subsequently PYGM. These results demonstrate that the IL-2 receptor activation, among other early events, leads to activation of PKCθ. To activate Rac 1 and consequently PYGM, PKCθ phosphorylates αPIX in T cells. The biological significance of this PKCθ/αPIX/Rac 1 GTPase/PYGM signaling...

  5. 75 FR 51520 - Information Collection Activities

    Science.gov (United States)

    2010-08-20

    ... Pipeline and Hazardous Materials Safety Administration Information Collection Activities AGENCY: Pipeline... change is being made; (2) OMB control number; (3) summary of the information collection activity; (4... information collections pertaining to hazardous materials transportation for which PHMSA intends to...

  6. 78 FR 47424 - Agency Information Collection Activities: Submission to OMB for Reinstatement, With Change, of a...

    Science.gov (United States)

    2013-08-05

    ....S.C. Chapter 35). This information collection is published to obtain comments from the public. The... accompanying services. TISA also requires NCUA to promulgate implementing regulations governing all credit... activity, in advertisements, and upon a member or potential member's request. The disclosures are for...

  7. 78 FR 59378 - Agency Information Collection Activities: Submission to OMB for Reinstatement, With Change, of a...

    Science.gov (United States)

    2013-09-26

    ....S.C. Chapter 35). This information collection is published to obtain comments from the public. The... accompanying services. TISA also requires NCUA to promulgate implementing regulations governing all credit... activity, in advertisements, and upon a member or potential member's request. The disclosures are for...

  8. A Content Analysis of Turkish Newspapers: Prevalence of Articles Containing Health Information Related to Physical Activity

    Science.gov (United States)

    Koksal, Leyla; Subasi, Feryal; Luleci, Emel; Hey, William

    2012-01-01

    This study was retrospective in design and the purpose was to review health information related to PA (physical activity) in articles of Turkish newspapers. The search covered newspaper articles printed between January 1, 2002 and December 31, 2004 in all Turkish newspapers that are accessible via the electronic newspaper database. Four daily…

  9. 78 FR 33077 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-06-03

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review...) AGENCY: Office of Innovation and Improvement (OII), Department of Education (ED). ACTION: Notice. SUMMARY... comment addressing the following issues: (1) Is this collection necessary to the proper functions of...

  10. 78 FR 76851 - Agency Information Collection Activities: BP Regulations Pertaining to Customs Brokers

    Science.gov (United States)

    2013-12-19

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: BP Regulations Pertaining to Customs Brokers AGENCY: U.S. Customs and Border Protection (CBP), Department of Homeland... requirement concerning the CBP Regulations Pertaining to Customs Brokers (19 CFR Part 111). This request...

  11. 75 FR 67094 - Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers

    Science.gov (United States)

    2010-11-01

    ... SECURITY Customs and Border Protection Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers AGENCY: U.S. Customs and Border Protection, Department of Homeland Security... concerning the: CBP Regulations Pertaining to Customs Brokers (19 CFR Part 111). This request for comment...

  12. Noble metals on anodic TiO2 nanotubes mouths: Thermal dewetting of minimal Pt co-catalyst loading leads to significantly enhanced photocatalytic H2 generation

    CERN Document Server

    Nguyen, Nhat Truong; Yoo, JeongEun; Taccardi, Nicola; Schmuki, Patrik

    2016-01-01

    The least is the best. We introduce a technique to strongly reduce Pt use for photocatalytic hydrogen generation from TiO2 nanotubes. By site-selectively depositing thin layers of Pt only at the mouth of the nanotubes and by a subsequent thermal dewetting step, we achieve an outstanding photocatalytic improvement with minimal amounts of co-catalyst.

  13. Transient Thermoelectric Generator: An Active Load Story

    Science.gov (United States)

    Stockholm, J. G.; Goupil, C.; Maussion, P.; Ouerdane, H.

    2015-06-01

    Under stationary conditions, the optimization of maximum power output and efficiency of thermoelectric generators (TEG) is a well-known subject. Use of a finite-time thermodynamics (FTT) approach to the description of TEGs has demonstrated that there exists a closed feedback effect between the output electrical load value and the entering heat current. From the practical point of view, this effect is strongly evidenced by the use of direct current (DC-to-DC) converters as active loads. Both transient conditions and FTT contribute to a complex landscape of the optimization of the power and efficiencies of a TEG. It has been claimed that the use of inductive load may lead to a strong enhancement of the efficiency, and the frequency response of a TEG as a band-pass filter has also been recently reported. We consider these results using a classical linear Onsager approach of a TEG operating under transient conditions. We show that a trans-admittance may be defined as a coupling element between the input and the output, leading to the observed electric-to-thermal feedback. We discuss recent experiments on a TEG connected to an active load, which is reported to boast an efficiency exceeding the usual stationary DC thermoelectric efficiency.

  14. 78 FR 16519 - Agency Information Collection Activities: Application for Advance Permission To Return to...

    Science.gov (United States)

    2013-03-15

    ... SECURITY U.S. Citizenship and Immigration Services Agency Information Collection Activities: Application... Security (DHS), U.S. Citizenship and Immigration Services (USCIS) invites the general public and other... provided in comments from public viewing that it determines may impact the privacy of an individual or...

  15. Generation of clinical grade dendritic cells with capacity to produce biologically active IL-12p70

    Directory of Open Access Journals (Sweden)

    Bigalke Iris

    2007-04-01

    Full Text Available Abstract Background For optimal T cell activation it is desirable that dendritic cells (DCs display peptides within MHC molecules as signal 1, costimulatory molecules as signal 2 and, in addition, produce IL-12p70 as signal 3. IL-12p70 polarizes T cell responses towards CD4+ T helper 1 cells, which then support the development of CD8+ cytotoxic T lymphocytes. We therefore developed new maturation cocktails allowing DCs to produce biologically active IL-12p70 for large-scale cancer vaccine development. Methods After elutriation of leukapheresis products in a closed bag system, enriched monocytes were cultured with GM-CSF and IL-4 for six days to generate immature DCs that were then matured with cocktails, containing cytokines, interferon-gamma, prostaglandin E2, and a ligand for Toll-like receptor 8, with or without poly (I:C. Results Mature DCs expressed appropriate maturation markers and the lymph node homing chemokine receptor, CCR7. They retained full maturity after culture for two days without maturation cocktails and following cryopreservation. TLR ligand stimulation induced DCs capable of secreting IL-12p70 in primary cultures and after one day of coculture with CD40L-expressing fibroblasts, mimicking an encounter with T cells. DCs matured with our new cocktails containing TLR8 ligand, with or without poly (I:C, induced alloresponses and stimulated virus-specific T cells after peptide-pulsing. DCs matured in cocktails containing TLR8 ligand without poly (I:C could also be loaded with RNA as a source of antigen, whereas DCs matured in cocktails containing poly (I:C were unable to express proteins following RNA transfer by electroporation. Conclusion Our new maturation cocktails allowed easy DC harvesting, stable maturation and substantial recoveries of mature DCs after cryopreservation. Our procedure for generating DCs is easily adaptable for GMP-compliance and yields IL-12p70-secreting DCs suitable for development of cancer vaccines using

  16. 78 FR 61346 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-10-03

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review and Approval; Comment Request; Student Assistance General Provisions--Subpart K--Cash Management...--Subpart K--Cash Management. OMB Control Number: 1845-0106. Type of Review: Extension without change of...

  17. 78 FR 63973 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-10-25

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review and Approval; Comment Request; Student Assistance General Provisions--Subpart K--Cash Management...--Subpart K--Cash Management OMB Control Number: 1845-0038 Type of Review: Revision of an...

  18. 78 FR 64206 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-10-28

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review and Approval; Comment Request; Student Assistance General Provisions--Subpart K--Cash Management...--Subpart K--Cash Management. OMB Control Number: 1845-0049. Type of Review: Revision of an...

  19. 78 FR 3410 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-01-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... Secondary Education Act of 1965, as Amended AGENCY: Department of Education (ED), Office of Elementary...

  20. 77 FR 72870 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2012-12-06

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... integration of certain functions and the sharing of skills, resources, and data to improve health center... section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995 (44 U.S.C. Chapter 35), the Health...

  1. 78 FR 21118 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-04-09

    ... NCES collection of basic data from the universe of private elementary and secondary schools in the... includes all schools that are not supported primarily by public funds, that provide classroom instruction... Agency Information Collection Activities; Submission to the Office of Management and Budget for...

  2. 78 FR 78375 - Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers

    Science.gov (United States)

    2013-12-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers Correction In notice document 2013-30220 appearing on page 76851 of the...

  3. 76 FR 163 - Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers

    Science.gov (United States)

    2011-01-03

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers AGENCY: U.S. Customs and Border Protection, Department of Homeland Security...-0034. SUMMARY: U.S. Customs and Border Protection (CBP) of the Department of Homeland Security will...

  4. 77 FR 6566 - Agency Information Collection Activities; Proposed Collection; Comment Request; Revisions to...

    Science.gov (United States)

    2012-02-08

    ...The Food and Drug Administration (FDA) is correcting a notice that appeared in the Federal Register of December 30, 2011. In the Federal Register of December 30, 2011, FDA published a notice entitled ``Agency Information Collection Activities; Proposed Collection; Comment Request; Revisions to Labeling Requirements for Blood and Blood Components, Including Source Plasma,'' which provided......

  5. 78 FR 64049 - Information Collection Activities

    Science.gov (United States)

    2013-10-25

    ... Pipeline and Hazardous Materials Safety Administration Information Collection Activities AGENCY: Pipeline... information collection activity and, when approved by OMB, publish a notice of the approval in the Federal... invites comments on certain information collections pertaining to hazardous materials transportation...

  6. Lead generation strategy as a multichannel mechanism of growth of a modern enterprise

    Directory of Open Access Journals (Sweden)

    Łukowski Wojciech

    2016-09-01

    Full Text Available Lead generation strategy describes the marketing process of involvement and capture of interest in a product or service which is aimed at developing sales plans and, as a consequence, soliciting new clients. Lead generation is becoming an increasingly popular demand-generating strategy, which – through its multichannelled dissemination of the generated message – gives it a much greater reach. Lead generation assists organisations in achieving a greater brand awareness, building relationships and attracting more potential clients to fill their sales pipeline. The primary purpose of this publication is identifying the possibilities that the implementation of lead generation strategies provides to modern enterprises. It discusses the key aspects of this issue, demonstrating how the significance of organisations change, how their value effectively increases as a result of the implementation of tools furnished by processes that form an integral part of lead generation. The article defines the factors and processes that affect the effective course of actions undertaken within lead generation campaigns.

  7. Monitoring the effects of exposure to lead and cadmium in working and living environment through standard biochemical blood parameters and liver endonucleases activity

    Directory of Open Access Journals (Sweden)

    Nikolić Ružica S.

    2011-01-01

    Full Text Available Heavy metals as pollutants in the working and living environment are a serious health and environmental problem because they are toxic, non-biodegradable, accumulate in living systems and have a long half-life in soil. Sources of lead contamination are combustion products in the chemical industry and metallurgy, industrial waste water, landfills, traffic etc. Lead enters into the body via the food chain and drinking water. In the body lead is deposited in the liver, kidneys, brain and mineral tissues. Excretion of lead causes damage to the epithelial cells of certain organs. High level exposure to cadmium is usually the result of environmental pollution by human activities. Exposure to cadmium can lead to acute and chronic tissue damage of various organs, including liver and kidneys in humans and in animals. In this paper we analyzed the effects of lead and cadmium exposure, in working and living environment, on the model system of experimental animals, particularly the activity of certain liver enzymes, acid and alkaline DNase, and standard biochemical blood parameters. The study showed that lead and cadmium significantly affect the protein content, red blood cells, hemoglobin and hematocrit, and the activity of liver enzymes. This harmful effect of this toxic metal can be reduced by the supplements.

  8. Myocardial ischemia and reperfusion-induced cell death depends on JNK activation and leads to phosphorylation of mitochondrial p46

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ Multiple signaling pathways, including the c-Jun N-terminal kinase (JNK) pathway, are activated in myocardial ischemia and reperfusion (MI/R) and correlate with cell death. However, the role of the JNK pathway with respect to protection or destruction in MI/R-induced cell death is poorly understood. In a rabbit model, we found that ischemia followed by reperfusion resulted in JNK activation which could be detected in cytosol as well as in mitochondria. To address the functional role of the JNK activation, we examined the consequences of blockade of JNK activation in isolated cardiomyocytes under conditions of simulated ischemia. The JNK activity was stimulated ~6-fold by simulated ischemia and reperfusion (simulated MI). When a dominant negative mutant of JNK kinase-2(dnJNKK2), an upstream regulator of JNK, and JNK-interacting protein-1 (JIP-1) were expressed in myocytes by recombinant adenovirus, the activation of JNK by simulated MI was reduced 53%. Furthermore, the TNFα-activated JNK activity in H9c2 cells was completely abolished by dnJNKK2 and JIP-1. In correlation, when dnJNKK2 and JIP-1 were expressed in cardiomyocytes, both constructs significantly reduced cell death after simulated MI compared to vector controls.

  9. Combinatorial Screening Identifies Novel Promiscuous Matrix Metalloproteinase Activities that Lead to Inhibition of the Therapeutic Target IL-13

    NARCIS (Netherlands)

    Urbach, Carole; Gordon, Nathaniel C; Strickland, Ian; Lowne, David; Joberty-Candotti, Cathy; May, Richard; Herath, Athula; Hijnen, DirkJan; Thijs, Judith L; Bruijnzeel-Koomen, Carla A; Minter, Ralph R; Hollfelder, Florian; Jermutus, Lutz

    2015-01-01

    The practical realization of disease modulation by catalytic degradation of a therapeutic target protein suffers from the difficulty to identify candidate proteases, or to engineer their specificity. We identified 23 measurable, specific, and new protease activities using combinatorial screening of

  10. Securing information using optically generated biometric keys

    Science.gov (United States)

    Verma, Gaurav; Sinha, Aloka

    2016-11-01

    In this paper, we present a new technique to obtain biometric keys by using the fingerprint of a person for an optical image encryption system. The key generation scheme uses the fingerprint biometric information in terms of the amplitude mask (AM) and the phase mask (PM) of the reconstructed fingerprint image that is implemented using the digital holographic technique. Statistical tests have been conducted to check the randomness of the fingerprint PM key that enables its usage as an image encryption key. To explore the utility of the generated biometric keys, an optical image encryption system has been further demonstrated based on the phase retrieval algorithm and the double random phase encoding scheme in which keys for the encryption are used as the AM and the PM key. The advantage associated with the proposed scheme is that the biometric keys’ retrieval requires the simultaneous presence of the fingerprint hologram and the correct knowledge of the reconstruction parameters at the decryption stage, which not only verifies the authenticity of the person but also protects the valuable fingerprint biometric features of the keys. Numerical results are carried out to prove the feasibility and the effectiveness of the proposed encryption system.

  11. Erythrocyte arginase activity as an indicator of lead exposure

    OpenAIRE

    Fukumoto, K.; Karai, I; NISHIKAWA, Y.; Horiguchi, S

    1983-01-01

    ABSTRACT A semi-automated method has been developed for the determination of the arginase activity of erythrocytes using dried blood spots, which are easy to prepare on site in a factory for later laboratory analysis. The mean arginase activity of erythrocytes in 49 men occupationally exposed to lead was 62·9 IU/g·Hb (SD, 14·4 IU/g·Hb); in 45 men not exposed to lead the mean was 44·6 IU/g·Hb (SD, 11·6 IU/g·Hb). A significantly higher mean arginase activity was found in the specimens from lead...

  12. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production

    NARCIS (Netherlands)

    Kauffman, HF; Tomee, JFC; van de Riet, MA; Timmerman, AJB; Borger, P

    2000-01-01

    Background: Proteases in extracts of Aspergillus fumigatus cause epithelial cell desquamation and release of proinflammatory cytokines. Objective: We sought to assess protease activity in Alternaria alternata, Cladosporium herbarum, and Aspergillus fumigatus extracts and study the ability of these e

  13. Lead-induced nitric oxide generation plays a critical role in lead uptake by Pogonatherum crinitum root cells.

    Science.gov (United States)

    Yu, Qin; Sun, Lian; Jin, Haihong; Chen, Qian; Chen, Zunwei; Xu, Maojun

    2012-10-01

    The effects of lead (Pb) on endogenous nitric oxide (NO) generation, the role of NO in Pb uptake and the origin of Pb-induced NO production in Pogonatherum crinitum root cells were evaluated. Pb treatment induced rapid NO generation, showing that Pb exposure triggered endogenous NO signaling of the cells. Pre-treatment of the cells with the NO-specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline -1-oxyl-3-oxide (cPTIO) not only abolished the Pb-triggered NO burst but also reduced Pb contents of the cells. Moreover, Pb exposure enhanced nitrate reductase (NR) activity of the cells. The NR inhibitors tungstate and glutamine not only suppressed the Pb-enhanced NR activities but also reduced the Pb-triggered NO generation. Pre-treatment of the cells with tungstate and glutamine suppressed Pb accumulation and the suppression could be restored by application of exogenous NO via its donors sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO). Together, our results indicated that Pb exposure enhanced NR activity and triggered the NO burst of P. crinitum root cells. Furthermore, the data demonstrated that NR was responsible for the Pb-triggered NO burst and that NR-mediated NO generation played a critical role in Pb uptake by P. crinitum root cells. Thus, our results suggest a potential strategy for controlling Pb uptake by plants by targeting NR as a source of Pb-triggered NO production.

  14. Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow

    OpenAIRE

    L. ZENG; Zampetaki, A.; Margariti, A.; Pepe, A. E.; Alam, S.; MARTIN, D; Xiao, Q; Wang, W; Jin, Z.-G.; Cockerill, G.; MORI, K; Li, Y.-s. J.; Hu, Y.; Chien, S.; Xu, Q.

    2009-01-01

    X-box binding protein 1 (XBP1) is a key signal transducer in endoplasmic reticulum stress response, and its potential role in the atherosclerosis development is unknown. This study aims to explore the impact of XBP1 on maintaining endothelial integrity related to atherosclerosis and to delineate the underlying mechanism. We found that XBP1 was highly expressed at branch points and areas of atherosclerotic lesions in the arteries of ApoE−/− mice, which was related to the severity of lesion dev...

  15. The 6th Asia cancer forum: what should we do to place cancer on the global health agenda? Sharing information leads to human security.

    Science.gov (United States)

    Kawahara, Norie; Sugimura, Haruhiko; Nakagawara, Akira; Masui, Tohru; Miyake, Jun; Akiyama, Masanori; Wahid, Ibrahim A; Hao, Xishan; Akaza, Hideyuki

    2011-05-01

    This forum discussed issues relating to the inclusion of cancer on the global health agenda, with the ultimate aim of achieving human security for all people. The forum discussed what methods are available to the cancer community in attempts to create a common data system for the rapidly growing Asian region. Discussions also focused on the preparations that can be made to consider and respond to the obstacles to the creation of an Asia-wide data and information network. It was also noted that in order to create a cancer information network, support would need to be provided to low- and middle-income countries and efforts made to ensure that data are comparable.

  16. Defects in the Expression of Chloroplast Proteins Leads to H2O2 Accumulation and Activation of Cyclic Electron Flow around Photosystem I

    Science.gov (United States)

    Strand, Deserah D.; Livingston, Aaron K.; Satoh-Cruz, Mio; Koepke, Tyson; Enlow, Heather M.; Fisher, Nicholas; Froehlich, John E.; Cruz, Jeffrey A.; Minhas, Deepika; Hixson, Kim K.; Kohzuma, Kaori; Lipton, Mary; Dhingra, Amit; Kramer, David M.

    2017-01-01

    We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 (hcef2) shows strongly increased CEF activity through the NADPH dehydrogenase complex (NDH), accompanied by increases in thylakoid proton motive force (pmf), activation of the photoprotective qE response, and the accumulation of H2O2. Surprisingly, hcef2 was mapped to a non-sense mutation in the TADA1 (tRNA adenosine deaminase arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome bf complex, and the ATP synthase, suggests that inefficient translation of hcef2 leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome bf hemes, and the decay kinetics of the flash-induced thylakoid electric field suggest that these defect lead to accumulation of H2O2 in hcef2, which we have previously shown leads to activation of NDH-related CEF. We observed similar increases in CEF, as well as increases in H2O2 accumulation, in other translation defective mutants. This suggests that loss of coordination in plastid protein levels lead to imbalances in photosynthetic energy balance that leads to an increase in CEF. These results taken together with a large body of previous observations, support a general model in which processes that lead to imbalances in chloroplast energetics result in the production of H2O2, which in turn activates CEF. This activation could be from either H2O2 acting as a redox signal, or by a secondary effect from H2O2 inducing a deficit in ATP. PMID:28133462

  17. 78 FR 26086 - Agency Information Collection Activities: Submission to OMB for Revision to a Currently Approved...

    Science.gov (United States)

    2013-05-03

    ... Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995 (Pub. L. 104... Recoveries, Liquidity, Commitments and Sources, Purchased Credit Impaired Loans, and Supplemental Investment... information. Additionally, these fields provide information for offsite monitoring of risks to the...

  18. 78 FR 15382 - Agency Information Collection Activities: Submission to OMB for Revision to a Currently Approved...

    Science.gov (United States)

    2013-03-11

    ... Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995 (Pub. L. 104... Recoveries, Liquidity, Commitments and Sources, Purchased Credit Impaired Loans, and Supplemental Investment... information. Additionally, these fields provide information for offsite monitoring of risks to the...

  19. System Supporting Automatic Generation of Finite Element Using Image Information

    Institute of Scientific and Technical Information of China (English)

    J; Fukuda

    2002-01-01

    A mesh generating system has been developed in orde r to prepare large amounts of input data which are needed for easy implementation of a finite element analysis. This system consists of a Pre-Mesh Generator, an Automatic Mesh Generator and a Mesh Modifier. Pre-Mesh Generator produces the shape and sub-block information as input data of Automatic Mesh Generator by c arrying out various image processing with respect to the image information of th e drawing input using scanner. Automatic Mesh Generato...

  20. Ruby coloured lead glasses by generation of silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Gil, C. [Fundacion Centro Nacional del Vidrio, Pocillo, 1, 40100 La Granja de San Ildefonso (Segovia) (Spain); Villegas, M.A. [Centro Nacional de Investigaciones Metalurgicas (CENIM), Spanish Council for Scientific Research (CSIC), Avda. Gregorio del Amo, 8, 28040 Madrid (Spain)]. E-mail: mavillegas@cenim.csic.es

    2004-11-15

    Both yellow and red superficial ruby lead crystal glasses have been obtained by Ag{sup +} ion-exchange. For red ruby colouring lead glass substrates were previously doped with reducing oxides (arsenic, antimony, cerium and tin). The best experimental conditions for silver ion-exchange were determined. The optical absorption behaviour of the samples was studied to point out the influence of the parameters involved in the ion-exchange process. Moreover, other parameters affecting the final colouring of the glasses (kind of dopant, dopant concentration, etc.) were also analysed. The dopant percentage added to the lead crystal glass is the most important factor for developing superficial red ruby colouring. Antimony oxide doped lead glass ion-exchanged with silver showed the most intense red ruby colouring, even for a doping concentration lower than those of arsenic oxide doped samples able to enhance similar colour. Spectral saturation appeared for the highest doping concentration and for the most severe ion-exchange conditions. Chromatic coordinates were calculated from the corresponding transmission visible spectra. The colour purity showed by the samples obtained satisfies the ornamental requirements that motivated this research.

  1. Recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma

    Science.gov (United States)

    Kannan, Kalpana; Coarfa, Cristian; Chao, Pei-Wen; Luo, Liming; Wang, Yan; Brinegar, Amy E.; Hawkins, Shannon M.; Milosavljevic, Aleksandar; Matzuk, Martin M.; Yen, Laising

    2015-01-01

    High-grade serous ovarian cancer (HGSC) is among the most lethal forms of cancer in women. Excessive genomic rearrangements, which are expected to create fusion oncogenes, are the hallmark of this cancer. Here we report a cancer-specific gene fusion between BCAM, a membrane adhesion molecule, and AKT2, a key kinase in the PI3K signaling pathway. This fusion is present in 7% of the 60 patient cancers tested, a significant frequency considering the highly heterogeneous nature of this malignancy. Further, we provide direct evidence that BCAM-AKT2 is translated into an in-frame fusion protein in the patient’s tumor. The resulting AKT2 fusion kinase is membrane-associated, constitutively phosphorylated, and activated as a functional kinase in cells. Unlike endogenous AKT2, whose activity is tightly regulated by external stimuli, BCAM-AKT2 escapes the regulation from external stimuli. Moreover, a BCAM-AKT2 fusion gene generated via chromosomal translocation using the CRISPR/Cas9 system leads to focus formation in both OVCAR8 and HEK-293T cell lines, suggesting that BCAM-AKT2 is oncogenic. Together, the results indicate that BCAM-AKT2 expression is a new mechanism of AKT2 kinase activation in HGSC. BCAM-AKT2 is the only fusion gene in HGSC that is proven to translate an aberrant yet functional kinase fusion protein with oncogenic properties. This recurrent genomic alteration is a potential therapeutic target and marker of a clinically relevant subtype for tailored therapy of HGSC. PMID:25733895

  2. NIH Research Leads to Cervical Cancer Vaccine

    Science.gov (United States)

    ... Current Issue Past Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents For ... mystery. Most important, however, is to have a vaccine which potentially can ... focusing their research on helping to produce second-generation HPV vaccines ...

  3. 20 CFR 670.965 - What procedures apply to disclosure of information about Job Corps students and program activities?

    Science.gov (United States)

    2010-04-01

    ... information about Job Corps students and program activities? 670.965 Section 670.965 Employees' Benefits... information about Job Corps students and program activities? (a) The Secretary develops procedures to respond to requests for information or records or other necessary disclosures pertaining to students. (b)...

  4. MHC class I signaling in T cells leads to tyrosine kinase activity and PLC-gamma 1 phosphorylation

    DEFF Research Database (Denmark)

    Skov, S; Odum, Niels; Claesson, M H

    1995-01-01

    phosphorylation and the subsequent calcium response. The early tyrosine kinase activity was found to be dependent on expression of the TCR/CD3 complex and the CD45 molecule on the surface of the T cells. Furthermore, MHC-I cross-linking was shown to tyrosine phosphorylate PLC-gamma 1 (phospholipase C-gamma 1...

  5. Repeated Radionuclide therapy in metastatic paraganglioma leading to the highest reported cumulative activity of 131I-MIBG

    Directory of Open Access Journals (Sweden)

    Ezziddin Samer

    2012-01-01

    Full Text Available Abstract 131I-MIBG therapy for neuroendocrine tumours may be dose limited. The common range of applied cumulative activities is 10-40 GBq. We report the uneventful cumulative administration of 111 GBq (= 3 Ci 131I-MIBG in a patient with metastatic paraganglioma. Ten courses of 131I-MIBG therapy were given within six years, accomplishing symptomatic, hormonal and tumour responses with no serious adverse effects. Chemotherapy with cisplatin/vinblastine/dacarbazine was the final treatment modality with temporary control of disease, but eventually the patient died of progression. The observed cumulative activity of 131I-MIBG represents the highest value reported to our knowledge, and even though 12.6 GBq of 90Y-DOTATOC were added intermediately, no associated relevant bone marrow, hepatic or other toxicity were observed. In an individual attempt to palliate metastatic disease high cumulative activity alone should not preclude the patient from repeat treatment.

  6. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block

    DEFF Research Database (Denmark)

    Kirstetter, Peggy; Anderson, Kristina; Porse, Bo T;

    2006-01-01

    of hematopoietic stem cell function was associated with decreased expression of Cdkn1a (encoding the cell cycle inhibitor p21(cdk)), Sfpi1, Hoxb4 and Bmi1 (encoding the transcription factors PU.1, HoxB4 and Bmi-1, respectively) and altered integrin expression in Lin(-)Sca-1(+)c-Kit(+) cells, whereas PU.1......Wnt signaling increases hematopoietic stem cell self-renewal and is activated in both myeloid and lymphoid malignancies, indicating involvement in both normal and malignant hematopoiesis. We report here activated canonical Wnt signaling in the hematopoietic system through conditional expression...... of a stable form of beta-catenin. This enforced expression led to hematopoietic failure associated with loss of myeloid lineage commitment at the granulocyte-macrophage progenitor stage; blocked erythrocyte differentiation; disruption of lymphoid development; and loss of repopulating stem cell activity. Loss...

  7. Effective Teachers for Students with Emotional/Behavioral Disorders: Active Ingredients Leading to Positive Teacher and Student Outcomes

    Science.gov (United States)

    Conroy, Maureen A.; Sutherland, Kevin S.

    2012-01-01

    Teachers of students with emotional/behavioral disorders (E/BD) have varied skills and abilities. Within the field there are some teachers, who teach students with E/BD by actively engaging them in learning tasks and who have few behavior problems in comparison to other teachers, who struggle with classroom management. Many researchers have found…

  8. Xanthohumol inhibits STAT3 activation pathway leading to growth suppression and apoptosis induction in human cholangiocarcinoma cells.

    Science.gov (United States)

    Dokduang, Hasaya; Yongvanit, Puangrat; Namwat, Nisana; Pairojkul, Chawalit; Sangkhamanon, Sakkarn; Yageta, Mika Sakurai; Murakami, Yoshinori; Loilome, Watcharin

    2016-04-01

    STAT3 plays a significant role in the development of cholangiocarcinoma (CCA) associated with the liver fluke (Opisthorchis viverrini; Ov). Xanthohumol (XN), a prenylated flavonoid extracted from hops, has known anticancer activity and could potentially target STAT3. The present study determined the effect of XN on STAT3, as well as ascertained its usefulness against CCA. The CCA cell proliferation at 20 µM and 50 µM of XN was shown to inhibited, while 20 µM partially inhibited IL-6-induced STAT3 activation. At 50 µM, the inhibition was complete. The reduction in STAT3 activity at 20 and 50 µM was associated with a significant reduction of CCA cell growth and apoptosis. We also found that the administration of 50 µM XN orally in drinking water to nude mice inoculated with CCA led to a reduction in tumor growth in comparison with controls. In addition, apoptosis of cancer cells increased although there was no visible toxicity. The present study shows that XN can inhibit STAT3 activation both in vivo and in vitro due to suppression of the Akt-NFκB signaling pathway. XN should be considered as a possible therapeutic agent against CCA.

  9. Application of Geographical Information Systems to Lahar Hazard Assessment on an Active Volcanic System

    OpenAIRE

    2010-01-01

    Lahars (highly dynamic mixtures of volcanic debris and water) have been responsible for some of the most serious volcanic disasters and have killed tens of thousands of people in recent decades. Despite considerable lahar model development in the sciences, many research tools have proved wholly unsuitable for practical application on an active volcanic system where it is difficult to obtain field measurements. In addition, geographic information systems are tools that offer a great potenti...

  10. Activity cliffs and activity cliff generators based on chemotype-related activity landscapes.

    Science.gov (United States)

    Pérez-Villanueva, Jaime; Méndez-Lucio, Oscar; Soria-Arteche, Olivia; Medina-Franco, José L

    2015-11-01

    Activity cliffs have large impact in drug discovery; therefore, their detection and quantification are of major importance. This work introduces the metric activity cliff enrichment factor and expands the previously reported activity cliff generator concept by adding chemotype information to representations of the activity landscape. To exemplify these concepts, three molecular databases with multiple biological activities were characterized. Compounds in each database were grouped into chemotype classes. Then, pairwise comparisons of structure similarities and activity differences were calculated for each compound and used to construct chemotype-based structure-activity similarity (SAS) maps. Different landscape distributions among four major regions of the SAS maps were observed for different subsets of molecules grouped in chemotypes. Based on this observation, the activity cliff enrichment factor was calculated to numerically detect chemotypes enriched in activity cliffs. Several chemotype classes were detected having major proportion of activity cliffs than the entire database. In addition, some chemotype classes comprising compounds with smooth structure activity relationships (SAR) were detected. Finally, the activity cliff generator concept was applied to compounds grouped in chemotypes to extract valuable SAR information.

  11. Adaptive integration of local region information to detect fine-scale brain activity patterns

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    With the rapid development of functional magnetic resonance imaging (fMRI) technology, the spatial resolution of fMRI data is continuously growing. This pro- vides us the possibility to detect the fine-scale patterns of brain activities. The es- tablished univariate and multivariate methods to analyze fMRI data mostly focus on detecting the activation blobs without considering the distributed fine-scale pat- terns within the blobs. To improve the sensitivity of the activation detection, in this paper, multivariate statistical method and univariate statistical method are com- bined to discover the fine-grained activity patterns. For one voxel in the brain, a local homogenous region is constructed. Then, time courses from the local ho- mogenous region are integrated with multivariate statistical method. Univariate statistical method is finally used to construct the interests of statistic for that voxel. The approach has explicitly taken into account the structures of both activity pat- terns and existing noise of local brain regions. Therefore, it could highlight the fine-scale activity patterns of the local regions. Experiments with simulated and real fMRI data demonstrate that the proposed method dramatically increases the sensitivity of detection of fine-scale brain activity patterns which contain the subtle information about experimental conditions.

  12. Adaptive intesration of local resion information to detect fine-scale brain activity patterns

    Institute of Scientific and Technical Information of China (English)

    ZHEN ZongLei; TIAN Jie; ZHANG Hui

    2008-01-01

    With the rapid development of functional magnetic resonance imaging (fMRI) technology, the spatial resolution of fMRI data is continuously growing. This pro-vides us the possibility to detect the fine-scale patterns of brain activities. The es-tablished univariate and multivariate methods to analyze fMRI data mostly focus on detecting the activation blobs without considering the distributed fine-scale pat-terns within the blobs. To improve the sensitivity of the activation detection, in this paper, multivariate statistical method and univariate statistical method are com-bined to discover the fine-grained activity patterns. For one voxel in the brain, a local homogenous region is constructed. Then, time courses from the local ho-mogenous region are integrated with multivariate statistical method. Univariate statistical method is finally used to construct the interests of statistic for that voxel. The approach has explicitly taken into account the structures of both activity pat-terns and existing noise of local brain regions. Therefore, it could highlight the fine-scale activity patterns of the local regions. Experiments with simulated and real fMRI data demonstrate that the proposed method dramatically increases the sensitivity of detection of fine-scale brain activity patterns which contain the subtle information about experimental conditions.

  13. Silencing AML1-ETO gene expression leads to simultaneous activation of both pro-apoptotic and proliferation signaling.

    Science.gov (United States)

    Spirin, P V; Lebedev, T D; Orlova, N N; Gornostaeva, A S; Prokofjeva, M M; Nikitenko, N A; Dmitriev, S E; Buzdin, A A; Borisov, N M; Aliper, A M; Garazha, A V; Rubtsov, P M; Stocking, C; Prassolov, V S

    2014-11-01

    The t(8;21)(q22;q22) rearrangement represents the most common chromosomal translocation in acute myeloid leukemia (AML). It results in a transcript encoding for the fusion protein AML1-ETO (AE) with transcription factor activity. AE is considered to be an attractive target for treating t(8;21) leukemia. However, AE expression alone is insufficient to cause transformation, and thus the potential of such therapy remains unclear. Several genes are deregulated in AML cells, including KIT that encodes a tyrosine kinase receptor. Here, we show that AML cells transduced with short hairpin RNA vector targeting AE mRNAs have a dramatic decrease in growth rate that is caused by induction of apoptosis and deregulation of the cell cycle. A reduction in KIT mRNA levels was also observed in AE-silenced cells, but silencing KIT expression reduced cell growth but did not induce apoptosis. Transcription profiling of cells that escape cell death revealed activation of a number of signaling pathways involved in cell survival and proliferation. In particular, we find that the extracellular signal-regulated kinase 2 (ERK2; also known as mitogen-activated protein kinase 1 (MAPK1)) protein could mediate activation of 23 out of 29 (79%) of these upregulated pathways and thus may be regarded as the key player in establishing the t(8;21)-positive leukemic cells resistant to AE suppression.

  14. E-Waste Informal Recycling: An Emerging Source of Lead Exposure in South America

    OpenAIRE

    Pascale, Antonio; Sosa, Adriana; Bares, Cristina; Battocletti, Alejandra; Moll, María José; Pose, Darío; Laborde, Amalia; GONZÁLEZ, HUGO; Feola, Gabriella

    2016-01-01

    BACKGROUND Primitive electronic waste (e-waste) recycling creates exposures to several hazardous substances including lead. In Uruguay, primitive recycling procedures are a significant source of lead exposure. OBJECTIVES The aim of this study was to examine lead exposure in blood lead levels (BLLs) in low-income children exposed to lead through burning cables. METHODS A sample of children and adolescents exposed to lead through burning cable activities were assessed at the Department of Toxic...

  15. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

    Directory of Open Access Journals (Sweden)

    Victoria Kegel

    2015-01-01

    Full Text Available Drug induced liver injury (DILI is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2±0.9×106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay and cell activity (XTT assay. The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  16. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI.

    Science.gov (United States)

    Kegel, Victoria; Pfeiffer, Elisa; Burkhardt, Britta; Liu, Jia L; Zeilinger, Katrin; Nüssler, Andreas K; Seehofer, Daniel; Damm, Georg

    2015-01-01

    Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 10(6) cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  17. Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon

    OpenAIRE

    Natalia López-del Hoyo; Lucrezia Fazioli; Santiago López-Begines; Laura Fernández-Sánchez; Nicolás Cuenca; Jordi Llorens; Pedro de la Villa; Ana Méndez

    2012-01-01

    Guanylate cyclase activating proteins are EF-hand containing proteins that confer calcium sensitivity to retinal guanylate cyclase at the outer segment discs of photoreceptor cells. By making the rate of cGMP synthesis dependent on the free intracellular calcium levels set by illumination, GCAPs play a fundamental role in the recovery of the light response and light adaptation. The main isoforms GCAP1 and GCAP2 also localize to the synaptic terminal, where their function is not known. Based o...

  18. Blocking NF-kB nuclear translocation leads to p53-related autophagy activation and cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Bao-Song Zhu; Chun-Gen Xing; Fang Lin; Xiao-Qing Fan; Kui Zhao; Zheng-Hong Qin

    2011-01-01

    AIM: To investigate the anti-tumor effects of nuclear factor-κB (NF-κB) inhibitor SN50 and related mechanisms of SGC7901 human gastric carcinoma cells. METHODS: MTT assay was used to determine the cytotoxic effects of SN50 in gastric cancer cell line SGC7901. Hoechst 33258 staining was used to detect apoptosis morphological changes after SN50 treatment. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after SN50 treatment.Immunofluorescence staining was used to detect the expression of light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Western blotting analysis were used to determine the expression of proteins involved in apoptosis and autophagy including p53, p53 upregulated modulator of apoptosis (PUMA), damage-regulated autophagy modulator (DRAM), LC3 and Beclin 1. We detected the effects of p53-mediated autophagy activation on the apoptosis of SGC7901 cells with the p53 inhibitor pifithrin-α. RESULTS: The viability of SGC7901 cells was inhibited after SN50 treatment. Inductions in the expression of apoptotic protein p53 and PUMA as well as autophagic protein DRAM, LC3 and Beclin 1 were detected with Western blotting analysis. SN50-treated cells exhibited punctuate microtubule-associated protein 1 LC3 in immunoreactivity and MDC-labeled vesicles increased after treatment of SN50 by MDC staining. Collapse of mitochondrial membrane potential Δψ were detected for 6 to 24 h after SN50 treatment. SN50-induced increases in PUMA, DRAM, LC3 and Beclin 1 and cell death were blocked by the p53 specific inhibitor pifithrin-α. CONCLUSION: The anti-tumor activity of NF-κB inhibitors is associated with p53-mediated activation of autophagy.

  19. 78 FR 38060 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-06-25

    ... collection of information; to search data sources; to complete and review the collection of information; and... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Agency Information Collection...

  20. 78 FR 31562 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-05-24

    ... collection of information; to search data sources; to complete and review the collection of information; and... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Agency Information Collection...

  1. An Introduction to the Latest-generation Spatial Database of Active Tectonics of China

    Institute of Scientific and Technical Information of China (English)

    Qu Chunyan; Deng Qidong

    2009-01-01

    Based on ArcGIS and MapInfo software, we digitized the active tectonics map (1:4,000,000) of China, which was compiled and revised by academician Deng Qidong, and built the spatial database of active tectonics of China. The database integrates rich active tectonic data, such as a catalogue of earthquakes with magnitude above 6.0, active faults, Quaternary basins, active folds and their associated attribute parameters, and implements scientific and effective management to this data. At the same time, the spatial database joins the spatial map data and the associated attribute data together, which implements the data query between spatial properties and attribute parameters and also makes it possible to perform spatial analysis with different data layers. These provide much convenience for earthquake study and allows engineering construction institutions to use this data in practical applications.

  2. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    DEFF Research Database (Denmark)

    Helin, K; Wu, C L; Fattaey, A R;

    1993-01-01

    the hypophosphorylated form of the retinoblastoma protein (pRB). The other protein, murine DP-1, was purified from an E2F DNA-affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 and DP-1, we have now isolated a cDNA for the human...... is required for stable interaction with pRB in vivo and that trans-activation by E2F-1/DP-1 heterodimers is inhibited by pRB. We suggest that "E2F" is the activity that is formed when an E2F-1-related protein and a DP-1-related protein dimerize....

  3. Ecdysteroids Elicit a Rapid Ca2+ Flux Leading to Akt Activation and Increased Protein Synthesis in Skeletal Muscle Cells

    OpenAIRE

    Gorelick-Feldman, Jonathan; Cohick, Wendie; Raskin, Ilya

    2010-01-01

    Phytoecdysteroids, structurally similar to insect molting hormones, produce a range of effects in mammals, including increasing growth and physical performance. In skeletal muscle cells, phytoecdysteroids increase protein synthesis. In this study we show that in a mouse skeletal muscle cell line, C2C12, 20-hydroxyecdysone (20HE), a common phytoecdysteroid in both insects and plants, elicited a rapid elevation in intracellular calcium, followed by sustained Akt activation and increased protein...

  4. Defects in the Expression of Chloroplast Proteins Leads to H2O2 Accumulation and Activation of Cyclic Electron Flow around Photosystem I

    Energy Technology Data Exchange (ETDEWEB)

    Strand, Deserah D.; Livingston, Aaron K.; Satoh-Cruz, Mio; Koepke, Tyson; Enlow, Heather M.; Fisher, Nicholas; Froehlich, John E.; Cruz, Jeffrey A.; Minhas, Deepika; Hixson, Kim K.; Kohzuma, Kaori; Lipton, Mary; Dhingra, Amit; Kramer, David M.

    2017-01-13

    We describe a new member of the class of mutants in Arabidopsis exhibiting high rates of cyclic electron flow around photosystem I (CEF), a light-driven process that produces ATP but not NADPH. High cyclic electron flow 2 (hcef2) shows strongly increased CEF activity through the NADPH dehydrogenase complex (NDH), accompanied by increases in thylakoid proton motive force (pmf), activation of the photoprotective qE response, and the accumulation of H2O2 . Surprisingly, hcef2 was mapped to a nonsense mutation in the TADA1 (tRNA adenosine deaminase arginine) locus, coding for a plastid targeted tRNA editing enzyme required for efficient codon recognition. Comparison of protein content from representative thylakoid complexes, the cytochrome bf complex and the ATP synthase, suggests that inefficient translation of hcef2 leads to compromised complex assembly or stability leading to alterations in stoichiometries of major thylakoid complexes as well as their constituent subunits. Altered subunit stoichiometries for photosystem I, ratios and properties of cytochrome bf hemes, and the decay kinetics of the flash induced thylakoid electric field suggest that these defect lead to accumulation of H2O2 in hcef2, which we have previously shown leads to activation of NDHrelated CEF. We observed similar increases in CEF and H2O2 accumulation in other translation defective mutants, suggesting that loss of coordination in plastid protein levels lead to imbalances in the photosynthetic energy balance that leads to increased CEF. These results, together with a large body of previous observations, support a general model in which processes that imbalances in chloroplast energetics result in the production of H2O2 , which activates CEF, either as a redox signal or by inducing deficits in ATP levels.

  5. Information literacy competency standards for higher education and their correlation with the cycle of knowledge generation

    Directory of Open Access Journals (Sweden)

    Alejandro Uribe Tirado

    2012-11-01

    Full Text Available This article considers the cycle of knowledge generation proposed by Nonaka and Takeuchi and sets out how the different indicators and expected results within the information literacy (IL standards used in higher education contribute to this cycle. After analyzing each standard and its interrelation with the four options to generate knowledge of Nonaka's cycle, it was identified that these standards are more geared to the generation of explicit knowledge, and therefore, it is necessary to work on other activities, and new proposed standards of IL that promote the generation of tacit knowledge and information processes needed.

  6. Substrate Shuttling Between Active Sites of Uroporphyrinogen Decarboxylase in Not Required to Generate Coproporphyrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, J.; Warby, C; Whitby, F; Kushner, J; Hill, C

    2009-01-01

    Uroporphyrinogen decarboxylase (URO-D; EC 4.1.1.37), the fifth enzyme of the heme biosynthetic pathway, is required for the production of heme, vitamin B12, siroheme, and chlorophyll precursors. URO-D catalyzes the sequential decarboxylation of four acetate side chains in the pyrrole groups of uroporphyrinogen to produce coproporphyrinogen. URO-D is a stable homodimer, with the active-site clefts of the two subunits adjacent to each other. It has been hypothesized that the two catalytic centers interact functionally, perhaps by shuttling of reaction intermediates between subunits. We tested this hypothesis by construction of a single-chain protein (single-chain URO-D) in which the two subunits were connected by a flexible linker. The crystal structure of this protein was shown to be superimposable with wild-type activity and to have comparable catalytic activity. Mutations that impaired one or the other of the two active sites of single-chain URO-D resulted in approximately half of wild-type activity. The distributions of reaction intermediates were the same for mutant and wild-type sequences and were unaltered in a competition experiment using I and III isomer substrates. These observations indicate that communication between active sites is not required for enzyme function and suggest that the dimeric structure of URO-D is required to achieve conformational stability and to create a large active-site cleft.

  7. 75 FR 43536 - Agency Information Collection Activities: Permit To Transfer Containers to a Container Station

    Science.gov (United States)

    2010-07-26

    ... Containers to a Container Station AGENCY: U.S. Customs and Border Protection, Department of Homeland Security... review and approval in accordance with the Paperwork Reduction Act: Permit to Transfer Containers to a Container Station. This is a proposed extension of an information collection that was previously...

  8. 77 FR 7236 - Information Collection Activities

    Science.gov (United States)

    2012-02-10

    ... Surface Transportation Board Information Collection Activities AGENCY: Surface Transportation Board, DOT... to seek from the Office of Management and Budget (OMB) approval of the information collections... railroad owning the rail line subject to abandonment must, in some circumstances, provide information...

  9. SOPHIE: Social, Open Pro-active Hub for Information Exchange to Support Intelligence Communities

    NARCIS (Netherlands)

    Streefkerk, J.W.; Eikelboom, A.; Paulissen, R.; Bemmel, I.E. van; Hemmer, A.F.; Venrooij, W.; Hollander, C.J. den

    2014-01-01

    Military intelligence communities need to collect, process and disseminate information as quickly and efficiently as possible, for example in answering requests for information by commanders. Currently, the flow of information between the field and intelligence communities is hampered by disparities

  10. Modifications on the hydrogen bond network by mutations of Escherichia coli copper efflux oxidase affect the process of proton transfer to dioxygen leading to alterations of enzymatic activities

    Energy Technology Data Exchange (ETDEWEB)

    Kajikawa, Takao; Kataoka, Kunishige [Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920-1192 (Japan); Sakurai, Takeshi, E-mail: tsakurai@se.kanazawa-u.ac.jp [Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920-1192 (Japan)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer Proton transfer pathway to dioxygen in CueO was identified. Black-Right-Pointing-Pointer Glu506 is the key amino acid to transport proton. Black-Right-Pointing-Pointer The Ala mutation at Glu506 formed a compensatory proton transfer pathway. Black-Right-Pointing-Pointer The Ile mutation at Glu506 shut down the hydrogen bond network. -- Abstract: CueO has a branched hydrogen bond network leading from the exterior of the protein molecule to the trinuclear copper center. This network transports protons in the four-electron reduction of dioxygen. We replaced the acidic Glu506 and Asp507 residues with the charged and uncharged amino acid residues. Peculiar changes in the enzyme activity of the mutants relative to the native enzyme indicate that an acidic amino acid residue at position 506 is essential for effective proton transport. The Ala mutation resulted in the formation of a compensatory hydrogen bond network with one or two extra water molecules. On the other hand, the Ile mutation resulted in the complete shutdown of the hydrogen bond network leading to loss of enzymatic activities of CueO. In contrast, the hydrogen bond network without the proton transport function was constructed by the Gln mutation. These results exerted on the hydrogen bond network in CueO are discussed in comparison with proton transfers in cytochrome oxidase.

  11. THE PARKINSONIAN NEUROTOXIN ROTENONE ACTIVATES CALPAIN AND CASPASE-3 LEADING TO MOTONEURON DEGENERATION IN SPINAL CORD OF LEWIS RATS

    Science.gov (United States)

    SAMANTARAY, S.; KNARYAN, V. H.; GUYTON, M. K.; MATZELLE, D. D.; RAY, S. K.; BANIK, N. L.

    2007-01-01

    Exposure to environmental toxins increases the risk of neurodegenerative diseases including Parkinson’s disease (PD). Rotenone is a neurotoxin that has been used to induce experimental parkinsonism in rats. We used the rotenone model of experimental parkinsonism to explore a novel aspect of extra-nigral degeneration, the neurodegeneration of spinal cord (SC), in PD. Rotenone administration to male Lewis rats caused significant neuronal cell death in cervical and lumbar SC as compared to control animals. Dying neurons were motoneurons as identified by double immunofluorescent labeling for TUNEL+ cells and ChAT-immunoreactivity. Neuronal death was accompanied by abundant astrogliosis and microgliosis as evidenced from GFAP-immunoreactivity and OX-42-immunoreactivity, respectively, implicating an inflammatory component during neurodegeneration in SC. However, the integrity of the white matter in SC was not affected by rotenone administration as evidenced from the non co-localization of any TUNEL+ cells with GFAP-immunoreactivity and MBP-immunoreactivity, the selective markers for astrocytes and oligodendrocytes, respectively. Increased activities of 76 kD active m-calpain and 17/19 kD active caspase-3 further demonstrated involvement of these enzymes in cell death in SC. The finding of ChAT+ cell death also suggested degeneration of SC motoneurons in rotenone-induced experimental parkinsonism. Thus, this is the first report of its kind in which the selective vulnerability of a putative parkinsonian target outside of nigrostriatal system has been tested using an environmental toxin to understand the pathophysiology of PD. Moreover, rotenone-induced degeneration of SC motoneuron in this model of experimental parkinsonism progressed with upregulation of calpain and caspase-3. PMID:17367952

  12. Metabolic activation of pyrrolizidine alkaloids leading to phototoxicity and photogenotoxicity in human HaCaT keratinocytes.

    Science.gov (United States)

    Wang, Chia-Chi; Xia, Qingsu; Li, Meng; Wang, Shuguang; Zhao, Yuewei; Tolleson, William H; Yin, Jun-Jie; Fu, Peter P

    2014-01-01

    Pyrrolizidine alkaloids, produced by a large number of poisonous plants with wide global distribution, are associated with genotoxicity, tumorigenicity, and hepatotoxicity in animals and humans. Mammalian metabolism converts pyrrolizidine alkaloids to reactive pyrrolic metabolites (dehydropyrrolizidine alkaloids) that form covalent protein and DNA adducts. Although a mechanistic understanding is currently unclear, pyrrolizidine alkaloids can cause secondary (hepatogenous) photosensitization and induce skin cancer. In this study, the phototoxicity of monocrotaline, riddelliine, dehydromonocrotaline, dehydroriddelliine, and dehydroretronecine (DHR) in human HaCaT keratinocytes under ultraviolet A (UVA) irradiation was determined. UVA irradiation of HaCaT cells treated with dehydromonocrotaline, dehydroriddelline, and DHR resulted in increased release of lactate dehydrogenase and enhanced photocytotoxicity proportional to the UVA doses. UVA-induced photochemical DNA damage also increased proportionally with dehydromonocrotaline and dehydroriddelline. UVA treatment potentiated the formation of 8-hydroxy-2'-deoxyguanosine DNA adducts induced by dehydromonocrotaline in HaCaT skin keratinocytes. Using electron spin resistance trapping, we found that UVA irradiation of dehydromonocrotaline and dehydroriddelliine generates reactive oxygen species (ROS), including hydroxyl radical, singlet oxygen, and superoxide, and electron transfer reactions, indicating that cytotoxicity and genotoxicity of these compounds could be mediated by ROS. Our results suggest that dehydropyrrolizidine alkaloids formed or delivered to the skin cause pyrrolizidine alkaloid-induced secondary photosensitization and possible skin cancer.

  13. Next Generation , Lightweight, Durable Boot Materials to Provide Active & Passive Thermal Protection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this NASA Phase I SBIR program is to leverage lightweight, durable materials developed by NanoSonic for use within extra vehicular activity (EVA)...

  14. Resolving Early Signaling Events in T-Cell Activation Leading to IL-2 and FOXP3 Transcription

    Directory of Open Access Journals (Sweden)

    Jeffrey P. Perley

    2014-11-01

    Full Text Available Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1 SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2 CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3 elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs, is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.

  15. Recovering lead from cupel waste generated in gold analysis by Pb-Fire assay.

    Science.gov (United States)

    Cerceau, Cristiane Isaac; Carvalho, Cornélio de Freitas; Rabelo, Ana Carolina Silveira; Dos Santos, Cláudio Gouvea; Gonçalves, Sabrina Mayra Dias; Varejão, Eduardo Vinícius Vieira

    2016-12-01

    Because of its precision and accuracy, Pb-Fire assay is the most employed method for gold analysis in geological materials. At the second stage of the method, namely cupellation, lead is oxidized to PbO which is absorbed by the cupel, leading to metallic gold as a tiny bend at the bottom of the recipient. After cupellation, cupel becomes highly contaminated with lead, making its disposal a serious risk of environmental contamination. In the present work, a leaching process for removing lead from cupel waste is proposed, which allowed for removing 96% of PbO by weight. After a precipitation step, 92.0% of lead was recovered from leachates in the form of PbSO4. Lead in the solid wastes left by the extraction was above the limit established by Brazilian legislation and these were classified as non-hazardous. Finally, secondary effluents generated after the precipitation step presented lead content more than twenty times lower than that of leachates from cupel waste. Tons of cupel waste are annually generated from gold analysis by Pb-Fire assay. Thus, the proposed method can contribute to prevent the discharge of high amounts of lead into the environment. Also, recovery of lead can help to partially meet the industrial demand for lead compounds.

  16. Taking the Lead : Gender, Social Context and Preference to Lead

    NARCIS (Netherlands)

    Hong, A.P.C.I.; Schaafsma, J.; van der Wijst, P.J.

    2014-01-01

    Previous research has demonstrated that women tend to emerge as leaders less often than men. In the present study, we examined to what extent women's and men's preference to lead is influenced by social context. It was hypothesized that women have a less strong preference to lead than men in a compe

  17. Blocking of Exchange Proteins Directly Activated by cAMP Leads to Reduced Replication of Middle East Respiratory Syndrome Coronavirus

    Science.gov (United States)

    Tao, Xinrong; Mei, Feng; Agrawal, Anurodh; Peters, Clarence J.; Ksiazek, Thomas G.

    2014-01-01

    The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infections and diseases represents a potential threat for worldwide spread and requires development of effective therapeutic strategies. In this study, we revealed a novel positive function of an exchange protein directly activated by cyclic AMP 1 (cAMP-1; Epac-1) on MERS-CoV replication. Specifically, we have shown that Epac-specific inhibitor treatment or silencing Epac-1 gene expression rendered cells resistant to viral infection. We believe Epac-1 inhibitors deserve further study as potential therapeutic agents for MERS-CoV infection. PMID:24453361

  18. Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xi; Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Du, Libo [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Liu, Wenlan [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Yang [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Hudson, Laurie G. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2014-01-15

    Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

  19. Activation of VCAM-1 and Its Associated Molecule CD44 Leads to Increased Malignant Potential of Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Pei-Chen Wang

    2014-02-01

    Full Text Available VCAM-1 (CD106, a transmembrane glycoprotein, was first reported to play an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (α4β1. In the present study, we observed that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation in vitro and its up-regulation directly correlated with advanced clinical breast cancer stage. We found that VCAM-1 over-expression in the NMuMG breast epithelial cells controls the epithelial and mesenchymal transition (EMT program to increase cell motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the established MDAMB231 metastatic breast cancer cell line, we confirmed that knockdown of endogenous VCAM-1 expression reduced cell proliferation and inhibited TGFβ1 or IL-6 mediated cell migration, and increased chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse model. Signaling studies showed that VCAM-1 physically associates with CD44 and enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism of VCAM-1 activation facilitating breast cancer progression, and suggest that targeting VCAM-1 is an attractive strategy for therapeutic intervention.

  20. Restoring KLF5 in esophageal squamous cell cancer cells activates the JNK pathway leading to apoptosis and reduced cell survival.

    Science.gov (United States)

    Tarapore, Rohinton S; Yang, Yizeng; Katz, Jonathan P

    2013-05-01

    Esophageal cancer is the eighth most common cancer in the world and has an extremely dismal prognosis, with a 5-year survival of less than 20%. Current treatment options are limited, and thus identifying new molecular targets and pathways is critical to derive novel therapies. Worldwide, more than 90% of esophageal cancers are esophageal squamous cell cancer (ESCC). Previously, we identified that Krüppel-like factor 5 (KLF5), a key transcriptional regulator normally expressed in esophageal squamous epithelial cells, is lost in human ESCC. To examine the effects of restoring KLF5 in ESCC, we transduced the human ESCC cell lines TE7 and TE15, both of which lack KLF5 expression, with retrovirus to express KLF5 upon doxycycline induction. When KLF5 was induced, ESCC cells demonstrated increased apoptosis and decreased viability, with up-regulation of the proapoptotic factor BAX. Interestingly, c-Jun N-terminal kinase (JNK) signaling, an important upstream mediator of proapoptotic pathways including BAX, was also activated following KLF5 induction. KLF5 activation of JNK signaling was mediated by KLF5 transactivation of two key upstream regulators of the JNK pathway, ASK1 and MKK4, and inhibition of JNK blocked apoptosis and normalized cell survival following KLF5 induction. Thus, restoring KLF5 in ESCC cells promotes apoptosis and decreases cell survival in a JNK-dependent manner, providing a potential therapeutic target for human ESCC.

  1. Aberrant glomerular filtration of urokinase-type plasminogen activator in nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine

    DEFF Research Database (Denmark)

    Staehr, Mette; Buhl, Kristian B; Andersen, René F

    2015-01-01

    (uPA) in vitro. It was hypothesized that uPA is abnormally filtered to pre-urine and is inhibited in urine by amiloride in nephrotic syndrome. This was tested by determination of Na+-balance, uPA protein and activity and amiloride concentration in urine from rats with puromycin aminonucleoside (PAN......In nephrotic syndrome, aberrant glomerular filtration of plasminogen and conversion to active plasmin in pre-urine is thought to activate proteolytically ENaC and contribute to sodium retention and edema. The ENaC blocker amiloride is an off-target inhibitor of urokinase-type plasminogen activator......) induced nephrotic syndrome. Urine samples from 6 adult and 18 pediatric patients with nephrotic syndrome were analyzed for uPA activity and protein. PAN-treatment induced significant proteinuria in rats which coincided with increased urine uPA protein and activity, increased urine protease activity...

  2. 76 FR 77312 - Information Collection Activities

    Science.gov (United States)

    2011-12-12

    ... Surface Transportation Board Information Collection Activities AGENCY: Surface Transportation Board, DOT... to seek from the Office of Management and Budget (OMB) approval of the information collections...-control arrangement. The relevant information collections are described in more detail below. Comments...

  3. 75 FR 5638 - Information Collection Activities

    Science.gov (United States)

    2010-02-03

    ... Pipeline and Hazardous Materials Safety Administration Information Collection Activities AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT. ACTION: Notice of information collection... affected agencies have an opportunity to comment on information collection and recordkeeping...

  4. 77 FR 64376 - Information Collection Activities

    Science.gov (United States)

    2012-10-19

    ... Surface Transportation Board Information Collection Activities AGENCY: Surface Transportation Board, DOT... to seek from the Office of Management and Budget (OMB) approval of the information collections.... 13702(b) and 49 CFR part 1312 (water carrier tariffs). The relevant information collections...

  5. Targeting Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts To Lead Small Molecule Inhibitors to Clinical Trials.

    Science.gov (United States)

    Fiore, Mario; Forli, Stefano; Manetti, Fabrizio

    2016-04-28

    The p38/MAPK-activated kinase 2 (MK2) pathway is involved in a series of pathological conditions (inflammation diseases and metastasis) and in the resistance mechanism to antitumor agents. None of the p38 inhibitors entered advanced clinical trials because of their unwanted systemic side effects. For this reason, MK2 was identified as an alternative target to block the pathway but avoiding the side effects of p38 inhibition. However, ATP-competitive MK2 inhibitors suffered from low solubility, poor cell permeability, and scarce kinase selectivity. Fortunately, non-ATP-competitive inhibitors of MK2 have been already discovered that allowed circumventing the selectivity issue. These compounds showed the additional advantage to be effective at lower concentrations in comparison to the ATP-competitive inhibitors. Therefore, although the significant difficulties encountered during the development of these inhibitors, MK2 is still considered as an attractive target to treat inflammation and related diseases to prevent tumor metastasis and to increase tumor sensitivity to chemotherapeutics.

  6. Student Activities Can Generate Positive PR.

    Science.gov (United States)

    Armistead, Lew

    1985-01-01

    To counter negative news about education it is important to make sure that positive school activities receive their fair share of exposure in the news media. Presents tips on how to generate positive public relations. Includes a list of newsworthy activities ideas. (MD)

  7. Cooperative activation of cyclobutanones and olefins leads to bridged ring systems by a catalytic [4 + 2] coupling

    Science.gov (United States)

    Ko, Haye Min; Dong, Guangbin

    2014-08-01

    Bridged ring systems are widely found in natural products, and successful syntheses of them frequently feature intramolecular Diels-Alder reactions. These reactions are subclassified as either type I or type II depending on how the diene motif is tethered to the rest of the substrate (type I are tethered at the 1-position of the diene and type II at the 2-position). Although the type I reaction has been used with great success, the molecular scaffolds accessible by the type II reactions are limited by the strain inherent in the formation of an sp2 carbon at a bridgehead position. Here, we describe a complementary approach that provides access to these structures through the C-C activation of cyclobutanones and their coupling with olefins. Various alkenes have been coupled with cyclobutanones to provide a range of bridged skeletons. The ketone group of the products serves as a convenient handle for downstream functionalization.

  8. Cumulant generating function formula of heat transfer in ballistic systems with lead-lead coupling and general nonlinear systems

    Science.gov (United States)

    Li, Huanan

    2013-03-01

    Based on a two-time observation protocol, we consider heat transfer in a given time interval tM in a lead-junction-lead system taking coupling between the leads into account. In view of the two-time observation, consistency conditions are carefully verified in our specific family of quantum histories. Furthermore, its implication is briefly explored. Then using the nonequilibrium Green's function method, we obtain an exact formula for the cumulant generating function for heat transfer between the two leads, valid in both transient and steady-state regimes. Also, a compact formula for the cumulant generating function in the long-time limit is derived, for which the Gallavotti-Cohen fluctuation symmetry is explicitly verified. In addition, we briefly discuss Di Ventra's repartitioning trick regarding whether the repartitioning procedure of the total Hamiltonian affects the nonequilibrium steady-state current fluctuation. All kinds of properties of nonequilibrium current fluctuations, such as the fluctuation theorem in different time regimes, could be readily given according to these exact formulas. Finally a practical formalism dealing with cumulants of heat transfer across general nonlinear quantum systems is established based on field theoretical/algebraic method.

  9. Using Citizen Scientists to Gather, Analyze, and Disseminate Information About Neighborhood Features That Affect Active Living.

    Science.gov (United States)

    Winter, Sandra J; Goldman Rosas, Lisa; Padilla Romero, Priscilla; Sheats, Jylana L; Buman, Matthew P; Baker, Cathleen; King, Abby C

    2016-10-01

    Many Latinos are insufficiently active, partly due to neighborhoods with little environmental support for physical activity. Multi-level approaches are needed to create health-promoting neighborhoods in disadvantaged communities. Participant "citizen scientists" were adolescent (n = 10, mean age = 12.8 ± 0.6 years) and older adult (n = 10, mean age = 71.3 ± 6.5 years), low income Latinos in North Fair Oaks, California. Citizen scientists conducted environmental assessments to document perceived barriers to active living using the Stanford Healthy Neighborhood Discovery Tool, which records GPS-tracked walking routes, photographs, audio narratives, and survey responses. Using a community-engaged approach, citizen scientists subsequently attended a community meeting to engage in advocacy training, review assessment data, prioritize issues to address and brainstorm potential solutions and partners. Citizen scientists each conducted a neighborhood environmental assessment and recorded 366 photographs and audio narratives. Adolescents (n = 4), older adults (n = 7) and community members (n = 4) collectively identified reducing trash and improving personal safety and sidewalk quality as the priority issues to address. Three adolescent and four older adult citizen scientists volunteered to present study findings to key stakeholders. This study demonstrated that with minimal training, low-income, Latino adolescent and older adult citizen scientists can: (1) use innovative technology to gather information about features of their neighborhood environment that influence active living, (2) analyze their information and identify potential solutions, and (3) engage with stakeholders to advocate for the development of healthier neighborhoods.

  10. Using Active Learning to Identify Health Information Technology Related Patient Safety Events.

    Science.gov (United States)

    Fong, Allan; Howe, Jessica L; Adams, Katharine T; Ratwani, Raj M

    2017-01-18

    The widespread adoption of health information technology (HIT) has led to new patient safety hazards that are often difficult to identify. Patient safety event reports, which are self-reported descriptions of safety hazards, provide one view of potential HIT-related safety events. However, identifying HIT-related reports can be challenging as they are often categorized under other more predominate clinical categories. This challenge of identifying HIT-related reports is exacerbated by the increasing number and complexity of reports which pose challenges to human annotators that must manually review reports. In this paper, we apply active learning techniques to support classification of patient safety event reports as HIT-related. We evaluated different strategies and demonstrated a 30% increase in average precision of a confirmatory sampling strategy over a baseline no active learning approach after 10 learning iterations.

  11. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities.

    Science.gov (United States)

    Abraham, Paul E; Giannone, Richard J; Xiong, Weili; Hettich, Robert L

    2014-06-17

    Contemporary microbial ecology studies usually employ one or more "omics" approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other "meta-omic" approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool.

  12. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, Paul E [ORNL; Giannone, Richard J [ORNL; Xiong, Weili [ORNL; Hettich, Robert {Bob} L [ORNL

    2014-01-01

    Contemporary microbial ecology studies usually employ one or more omics approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other meta-omic approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool.

  13. 77 FR 37696 - Notice of Proposed Information Collection: Survey and Collection of Information From HUD Lead...

    Science.gov (United States)

    2012-06-22

    ... HUD Lead Hazard Control Grantees To Support HUD and EPA Requirements To Study the Lowering of the Lead Hazard Standards and the Lead-Based Paint Standard AGENCY: Office of Healthy Homes and Lead Hazard... of selected lead hazard control grantees funded by HUD will be submitted to the Office of...

  14. Ameloblasts require active RhoA to generate normal dental enamel.

    Science.gov (United States)

    Xue, Hui; Li, Yong; Everett, Eric T; Ryan, Kathleen; Peng, Li; Porecha, Rakhee; Yan, Yan; Lucchese, Anna M; Kuehl, Melissa A; Pugach, Megan K; Bouchard, Jessica; Gibson, Carolyn W

    2013-08-01

    RhoA plays a fundamental role in regulation of the actin cytoskeleton, intercellular attachment, and cell proliferation. During amelogenesis, ameloblasts (which produce the enamel proteins) undergo dramatic cytoskeletal changes and the RhoA protein level is up-regulated. Transgenic mice were generated that express a dominant-negative RhoA transgene in ameloblasts using amelogenin gene-regulatory sequences. Transgenic and wild-type (WT) molar tooth germs were incubated with sodium fluoride (NaF) or sodium chloride (NaCl) in organ culture. Filamentous actin (F-actin) stained with phalloidin was elevated significantly in WT ameloblasts treated with NaF compared with WT ameloblasts treated with NaCl or with transgenic ameloblasts treated with NaF, thereby confirming a block in the RhoA/Rho-associated protein kinase (ROCK) pathway in the transgenic mice. Little difference in quantitative fluorescence (an estimation of fluorosis) was observed between WT and transgenic incisors from mice provided with drinking water containing NaF. We subsequently found reduced transgene expression in incisors compared with molars. Transgenic molar teeth had reduced amelogenin, E-cadherin, and Ki67 compared with WT molar teeth. Hypoplastic enamel in transgenic mice correlates with reduced expression of the enamel protein, amelogenin, and E-cadherin and cell proliferation are regulated by RhoA in other tissues. Together these findings reveal deficits in molar ameloblast function when RhoA activity is inhibited.

  15. Activation of vasopressin neurons leads to phenotype progression in a mouse model for familial neurohypophysial diabetes insipidus.

    Science.gov (United States)

    Hiroi, Maiko; Morishita, Yoshiaki; Hayashi, Masayuki; Ozaki, Nobuaki; Sugimura, Yoshihisa; Nagasaki, Hiroshi; Shiota, Akira; Oiso, Yutaka; Arima, Hiroshi

    2010-02-01

    Familial neurohypophysial diabetes insipidus (FNDI) is a rare disease that is inherited in an autosomal dominant manner. In a previous study, we made a mouse model for FNDI, which showed progressive polyuria accompanied by inclusion bodies in the arginine vasopressin (AVP) neurons formed by aggregates in the endoplasmic reticulum. The present study was conducted to determine whether the activities of AVP neurons are related to the phenotype progression in the FNDI model. In the first experiment, female heterozygous mice were administered either desmopressin (dDAVP) or a vehicle (control) subcutaneously with osmotic minipumps for 30 days. The dDAVP treatment significantly decreased the urine volume, AVP mRNA expression, and inclusion bodies in the AVP neurons. Urine volume in the dDAVP group remained significantly less than the control for 14 days even after the minipumps were removed. In the second experiment, the males were fed either a 0.2% Na or 2.0% Na diet for 6 mo. Urine AVP excretion was significantly increased in the 2.0% Na group compared with the 0.2% Na group for the first 2 mo but gradually decreased thereafter. Throughout the experiments, urine volume increased progressively in the 2.0% Na group but not in the 0.2% Na group. Immunohistochemical analyses revealed that inclusion bodies in the AVP cells had significantly increased in the 2.0% Na compared with the 0.2% Na group. These data demonstrated that activation of AVP neurons could accelerate the aggregate formation as well as the progression of the polyuria in the FNDI model mice.

  16. Passive Reactive Berm to Provide Low Maintenance Lead Containment at Active Small Arms Firing Ranges: Field Demonstration

    Science.gov (United States)

    2012-08-01

    Calcium Cr Chromium Cu Copper Fe Iron Mn Manganese Mo Molybdenum Ni Nickel P Phosphorus Pb Lead Sb Antimony V...the toxicity characteristic leaching procedure (TCLP) extraction solution against control soils with no amendments, the amended soils decreased the...passed through the lysimeter walls using water-tight bulkhead fittings sealed with a solvent -weld (Figure 11). The existing drain openings in the

  17. Characterization of nano-lead-doped active carbon and its application in lead-acid battery

    Science.gov (United States)

    Hong, Bo; Jiang, Liangxing; Xue, Haitao; Liu, Fangyang; Jia, Ming; Li, Jie; Liu, Yexiang

    2014-12-01

    In this paper, nano-lead-doped active carbon (nano-Pb/AC) composite with low hydrogen evolution current for lead-acid battery was prepared by ultrasonic-absorption and chemical-precipitate method. The nano-Pb/AC composite was characterized by SEM, EDS and TEM. The electrochemical characterizations are performed by linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) in a three-electrode system. Since intermediate adsorption is the rate-determining step, the hydrogen evolution reaction (HER) is markedly inhibited as the intermediate adsorption impedance of nano-Pb/AC increased. Meanwhile, the working potential of nano-Pb/AC is widened to the whole potential region of Pb negative plate (from -1.36 V to -0.86 V vs. Hg/HgSO4) in lead-acid battery. In addition, nano-Pb can improve the interfacial compatibility between AC and Pb paste, accordingly relieve the symptoms of carbon floatation. Finally, 2.0 V single-cell flooded lead-acid batteries with 1.0 wt.% nano-Pb/AC or 1.0 wt.% AC addition in negative active materials are assembled. The cell performances test results show that the 3 h rate capacity, quick charging performance, high current discharging performance and cycling performance of nano-Pb/AC modified battery are all improved compared with regular lead-acid battery and AC modified lead-acid battery.

  18. A new APE1/Ref-1-dependent pathway leading to reduction of NF-kappaB and AP-1, and activation of their DNA-binding activity.

    Science.gov (United States)

    Ando, Kozue; Hirao, Satoshi; Kabe, Yasuaki; Ogura, Yuji; Sato, Iwao; Yamaguchi, Yuki; Wada, Tadashi; Handa, Hiroshi

    2008-08-01

    APE1/Ref-1 is thought to be a multifunctional protein involved in reduction-oxidation (redox) regulation and base excision DNA repair, and is required for early embryonic development in mice. APE1/Ref-1 has redox activity and AP endonuclease activity, and is able to enhance DNA-binding activity of several transcription factors, including NF-kappaB, AP-1 and p53, through reduction of their critical cysteine residues. However, it remains elusive exactly how APE1/Ref-1 carries out its essential functions in vivo. Here, we show that APE1/Ref-1 not only reduces target transcription factors directly but also facilitates their reduction by other reducing molecules such as glutathione or thioredoxin. The new activity of APE1/Ref-1, termed redox chaperone activity, is exerted at concentration significantly lower than that required for its redox activity and is neither dependent on its redox activity nor on its AP endonuclease activity. We also show evidence that redox chaperone activity of APE1/Ref-1 is critical to NF-kappaB-mediated gene expression in human cells and is mediated through its physical association with target transcription factors. Thus, APE1/Ref-1 may play multiple roles in an antioxidative stress response pathway through its different biochemical activities. These findings also provide new insight into the mechanism of intracellular redox regulation.

  19. All roads lead to Rome

    DEFF Research Database (Denmark)

    Ottosen, Thorsten Jørgen; Vomlel, Jiri

    2012-01-01

    for existing methods to use the treewidth criterion for optimality of a triangulation. However, this criterion may lead to a somewhat harder inference problem than the total table size criterion. We therefore investigate new methods for depth-first search and best-first search for finding optimal total table...... is generic in the sense that it can be used with other algorithms than just Bron-Kerbosch. The algorithms for finding optimal triangulations are mainly supposed to be off-line methods, but they may form the basis for efficient any-time heuristics. Furthermore, the methods make it possible to evaluate...

  20. Subfailure overstretch injury leads to reversible functional impairment and purinergic P2X7 receptor activation in intact vascular tissue

    Directory of Open Access Journals (Sweden)

    Weifeng Luo

    2016-09-01

    Full Text Available Vascular stretch injury is associated with blunt trauma, vascular surgical procedures, and harvest of human saphenous vein for use in vascular bypass grafting. A model of subfailure overstretch in rat abdominal aorta was developed to characterize surgical vascular stretch injury. Longitudinal stretch of rat aorta was characterized ex vivo. Stretch to the haptic endpoint where the tissues would no longer lengthen, occurred at twice the resting length. The stress produced at this length was greater than physiologic mechanical forces but well below the level of mechanical disruption. Functional responses were determined in a muscle bath and this subfailure overstretch injury led to impaired smooth muscle function that was partially reversed by treatment with purinergic receptor (P2X7R antagonists. These data suggest that vasomotor dysfunction caused by subfailure overstretch injury may be due to activation of P2X7R. These studies have implications for our understanding of mechanical stretch injury of blood vessels and offer novel therapeutic opportunities.

  1. Options to Improve the Quality of Wind Generation Output Forecasting with the Use of Available Information as Explanatory Variables

    Directory of Open Access Journals (Sweden)

    Rafał Magulski

    2015-06-01

    Full Text Available Development of wind generation, besides its positive aspects related to the use of renewable energy, is a challenge from the point of view of power systems’ operational security and economy. The uncertain and variable nature of wind generation sources entails the need for the for the TSO to provide adequate reserves of power, necessary to maintain the grid’s stable operation, and the actors involved in the trading of energy from these sources incur additional of balancing unplanned output deviations. The paper presents the results of analyses concerning the options to forecast a selected wind farm’s output exercised by means of different methods of prediction, using a different range of measurement and forecasting data available on the farm and its surroundings. The analyses focused on the evaluation of forecast errors, and selection of input data for forecasting models and assessment of their impact on prediction quality improvement.

  2. Optimal Lead-lag Controller for Distributed Generation Unit in Island Mode Using Simulated Annealing

    Directory of Open Access Journals (Sweden)

    A. Akbarimajd

    2014-07-01

    Full Text Available Active and reactive power components of a Distributed Generation (DG is normally controlled by a conventional dq-current control strategy however, after islanding the dq-current which is not able to successfully complete the control task is disabled and a lead-lag control strategy based optimized by simulated annealing is proposed for control of DG unit in islanding mode. Integral of Time multiply by Absolute Error (ITEA criterion is used as cost function of simulated annealing in order to achieve smooth response and robust behavior. The proposed controller improved robust stability margins of the system. Simulations with different load and input operating conditions verify advantages of the proposed controller in comparison with a previously developed classic controller in terms of robustness and response time.

  3. Lead generation strategy as a multichannel mechanism of growth of a modern enterprise

    OpenAIRE

    Łukowski Wojciech; Świeczak Witold

    2016-01-01

    Lead generation strategy describes the marketing process of involvement and capture of interest in a product or service which is aimed at developing sales plans and, as a consequence, soliciting new clients. Lead generation is becoming an increasingly popular demand-generating strategy, which – through its multichannelled dissemination of the generated message – gives it a much greater reach. Lead generation assists organisations in achieving a greater brand awareness, building relationships ...

  4. Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon.

    Directory of Open Access Journals (Sweden)

    Natalia López-del Hoyo

    Full Text Available Guanylate cyclase activating proteins are EF-hand containing proteins that confer calcium sensitivity to retinal guanylate cyclase at the outer segment discs of photoreceptor cells. By making the rate of cGMP synthesis dependent on the free intracellular calcium levels set by illumination, GCAPs play a fundamental role in the recovery of the light response and light adaptation. The main isoforms GCAP1 and GCAP2 also localize to the synaptic terminal, where their function is not known. Based on the reported interaction of GCAP2 with Ribeye, the major component of synaptic ribbons, it was proposed that GCAP2 could mediate the synaptic ribbon dynamic changes that happen in response to light. We here present a thorough ultrastructural analysis of rod synaptic terminals in loss-of-function (GCAP1/GCAP2 double knockout and gain-of-function (transgenic overexpression mouse models of GCAP2. Rod synaptic ribbons in GCAPs-/- mice did not differ from wildtype ribbons when mice were raised in constant darkness, indicating that GCAPs are not required for ribbon early assembly or maturation. Transgenic overexpression of GCAP2 in rods led to a shortening of synaptic ribbons, and to a higher than normal percentage of club-shaped and spherical ribbon morphologies. Restoration of GCAP2 expression in the GCAPs-/- background (GCAP2 expression in the absence of endogenous GCAP1 had the striking result of shortening ribbon length to a much higher degree than overexpression of GCAP2 in the wildtype background, as well as reducing the thickness of the outer plexiform layer without affecting the number of rod photoreceptor cells. These results indicate that preservation of the GCAP1 to GCAP2 relative levels is relevant for maintaining the integrity of the synaptic terminal. Our demonstration of GCAP2 immunolocalization at synaptic ribbons at the ultrastructural level would support a role of GCAPs at mediating the effect of light on morphological remodeling changes of

  5. UV irradiation-induced apoptosis leads to activation of a 36-kDa myelin basic protein kinase in HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lu, M.L.; Sato, Mitsuhiro; Cao, Boliang; Richie, J.P. [Harvard Medical School, Boston, MA (United States)

    1996-08-20

    UV irradiation induces apoptosis (or programmed cell death) in HL-60 promyelocytic leukemia cells within 3 h. UV-induced apoptosis is accompanied by activation of a 36-kDa myelin basic protein kinase (p36 MBP kinase). This kinase is also activated by okadaic acid and retinoic acid-induced apoptosis. Irrespective of the inducing agent, p36 MBP kinase activation is restricted to the subpopulation of cells actually undergoing apoptosis. Activation of p36 MBP kinase occurs in enucleated cytoplasts, indicating no requirements for a nucleus or fragmented DNA in signaling. We also demonstrate the activation of p36 kinase in tumor necrosis factor-{alpha}-and serum starvation-induced cell death using the human prostatic tumor cell line LNCap and NIH 3T3 fibroblasts, respectively. We postulate that p36 MBP kinase is a common component in diverse signaling pathways leading to apoptosis. 40 refs., 5 figs.

  6. All Roads Lead To Rome

    CERN Document Server

    Li, Xin

    2011-01-01

    This short article presents a class of projection-based solution algorithms to the problem considered in the pioneering work on compressed sensing - perfect reconstruction of a phantom image from 22 radial lines in the frequency domain. Under the framework of projection-based image reconstruction, we will show experimentally that several old and new tools of nonlinear filtering (including Perona-Malik diffusion, Total-Variation diffusion, Translation-Invariant thresholding and SA-DCT thresholding) all lead to perfect reconstruction of the phantom image.

  7. 37 years of scientific activity in a Biochemistry Department in Brazil: patterns of growth and factors leading to increased productivity.

    Science.gov (United States)

    Gomes, Urubatã E; Oliveira, Diogo L de; Berti, Luciana C; Amaral, Olavo; Souza, Diogo O; Wofchuk, Susana T

    2011-09-01

    Scientific activity in Brazil has experienced an accelerated growth in the past decades, with an increase in productivity that greatly surpasses the international average. This growth has occurred mostly at the expense of centers of excellence in public universities, which account for the vast majority of the country's scientific output. The aim of this study was to evaluate the production of the Department of Biochemistry of a large public university in southern Brazil (Universidade Federal do Rio Grande do Sul), as well as to identify internal and external policies that have influenced this growing production profile. We have performed a historical analysis of the scientific output of this Department of Biochemistry, which accounts for a considerable share of the indexed scientific production at this university. By focusing on the temporal course of its growth and drawing correlations between scientific output and important events in the history of the Department of Biochemistry and of the Brazilian science policies, we concluded that internal factors (as the creation of a postgraduation program, collaboration among researchers, experienced abroad researchers, qualification of faculty members) and external factors (as investments in the postgraduate education, the establishment of national scientific policies, such as financial stimuli for productive researchers and evaluation systems) influence scientific productivity in Brazil.

  8. Ordered cleavage of myeloperoxidase ester bonds releases active site heme leading to inactivation of myeloperoxidase by benzoic acid hydrazide analogs.

    Science.gov (United States)

    Huang, Jiansheng; Smith, Forrest; Panizzi, Peter

    2014-04-15

    Myeloperoxidase (MPO) catalyzes the breakdown of hydrogen peroxide and the formation of the potent oxidant hypochlorous acid. We present the application of the fluorogenic peroxidase substrate 10-acetyl-3,7-dihydroxyphenoxazine (ADHP) in steady-state and transient kinetic studies of MPO function. Using initial kinetic parameters for the MPO system, we characterized under the same conditions a number of gold standards for MPO inhibition, namely 4-amino benzoic acid hydrazide (4-ABAH), isoniazid and NaN3 before expanding our focus to isomers of 4-ABAH and benzoic acid hydrazide analogs. We determined that in the presence of hydrogen peroxide that 4-ABAH and its isomer 2-ABAH are both slow-tight binding inhibitors of MPO requiring at least two steps, whereas NaN3 and isoniazid-based inhibition has a single observable step. We also determined that MPO inhibition by benzoic acid hydrazide and 4-(trifluoromethyl) benzoic acid hydrazide was due to hydrolysis of the ester bond between MPO heavy chain Glu 242 residue and the heme pyrrole A ring, freeing the light chain and heme b fragment from the larger remaining MPO heavy chain. This new mechanism would essentially indicate that the benzoic acid hydrazide analogs impart inhibition through initial ejection of the heme catalytic moiety without prior loss of the active site iron.

  9. Silver ion mediated shape control of platinum nanoparticles: Removal of silver by selective etching leads to increased catalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Grass, Michael E.; Yue, Yao; Habas, Susan E.; Rioux, Robert M.; Teall, Chelsea I.; Somorjai, G.A.

    2008-01-09

    A procedure has been developed for the selective etching of Ag from Pt nanoparticles of well-defined shape, resulting in the formation of elementally-pure Pt cubes, cuboctahedra, or octahedra, with a largest vertex-to-vertex distance of {approx}9.5 nm from Ag-modified Pt nanoparticles. A nitric acid etching process was applied Pt nanoparticles supported on mesoporous silica, as well as nanoparticles dispersed in aqueous solution. The characterization of the silica-supported particles by XRD, TEM, and N{sub 2} adsorption measurements demonstrated that the structure of the nanoparticles and the mesoporous support remained conserved during etching in concentrated nitric acid. Both elemental analysis and ethylene hydrogenation indicated etching of Ag is only effective when [HNO{sub 3}] {ge} 7 M; below this concentration, the removal of Ag is only {approx}10%. Ethylene hydrogenation activity increased by four orders of magnitude after the etching of Pt octahedra that contained the highest fraction of silver. High-resolution transmission electron microscopy of the unsupported particles after etching demonstrated that etching does not alter the surface structure of the Pt nanoparticles. High [HNO{sub 3}] led to the decomposition of the capping agent, polyvinylpyrollidone (PVP); infrared spectroscopy confirmed that many decomposition products were present on the surface during etching, including carbon monoxide.

  10. 28 CFR 5.210 - Amount of detail required in information relating to registrant's activities and expenditures.

    Science.gov (United States)

    2010-07-01

    ... § 5.210 Amount of detail required in information relating to registrant's activities and expenditures... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Amount of detail required in information relating to registrant's activities and expenditures. 5.210 Section 5.210 Judicial...

  11. All roads lead to Meyrin

    CERN Multimedia

    Communication locale

    2011-01-01

    Tous les chemins mènent à Meyrin - All roads lead to Meyrin From 29 September to 16 October, 2011, come to the Salle Antoine Verchère in Meyrin for Tous les chemins mènent à Meyrin. The celebration will include an exposition as well as a theatrical performance about Meyrin, the first satellite city in Switzerland. With the help of the memories and testimonies from the people of Meyrin, Tous les chemins mènent à Meyrin is putting the collective memories of the commune on display. It is an occasion for everyone, whether you're from near or far, to find out how all the roads lead to Meyrin.  Salle Antoine-Verchère Route de Meyrin 294 – 1217 Meyrin Tram 18 – Stop: Meyrin Village Thursdays / Fridays / Saturdays at 8pm Sundays at 5pm Regular ticket: CHF 15.- Concession ticket (students, chômeurs, AVS, AI): CHF 12.- Children up to 16: CHF 10.- Family ticket: CHF 35.-

  12. Informal Face-to-Face Interaction Improves Mood State Reflected in Prefrontal Cortex Activity

    Science.gov (United States)

    Watanabe, Jun-ichiro; Atsumori, Hirokazu; Kiguchi, Masashi

    2016-01-01

    Recent progress with wearable sensors has enabled researchers to capture face-to-face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to-face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS). We also observed that the verbal working memory (WM) task performance of participants who did not have face-to-face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC) activity accompanied by WM tasks measured by near-infrared spectroscopy (NIRS). PMID:27199715

  13. Informal face-to-face interaction improves mood state reflected in prefrontal cortex activity

    Directory of Open Access Journals (Sweden)

    Jun-Ichiro eWatanabe

    2016-05-01

    Full Text Available Recent progress with wearable sensors has enabled researchers to capture face-to-face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to-face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS.We also observed that the verbal WM task performance of participants who did not have face-to-face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC activity accompanied by working memory (WM tasks measured by near-infrared spectroscopy (NIRS.

  14. The generation of meaningful information in molecular systems.

    Science.gov (United States)

    Wills, Peter R

    2016-03-13

    The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. The origin and evolution of genetic information (nucleic acid sequences) is reasonably well understood, but scant attention has been paid to the origin and evolution of the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. We take the origin of genetic coding as a paradigm of the emergence of computation in natural systems, focusing on the requirement that the molecular components of an interpreter be synthesized autocatalytically. Within this context, it is seen that interpreters of increasing complexity are generated by series of transitions through stepped dynamic instabilities (non-equilibrium phase transitions). The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it.

  15. Doubly Fed Induction Generator Based Wind Turbine Associated to a Shunt Active Power Filter for Current Harmonics Mitigation

    Directory of Open Access Journals (Sweden)

    Samira Dib,

    2011-04-01

    Full Text Available Integration of wind turbine based on doubly fed induction generator (DFIG into the electrical grid has become an important part of electrical generation in many countries and its importance is continuing to increase. The advantages of using a DFIG instead of other generators are already well known. A few of them are variousspeed generations, the decoupled control of active and reactive power and high power capacity. However, the ever-growing proliferation of power electronics based devices for source conditioning and motion control in modern industrial applications has increased the occurrence of harmonic currents in distribution systems. This harmonics have harmful and costly effects on DFIG such as, the increase of stator and rotor core losses and the increase of the operating temperature. In this paper, a shunt active power filter (SAPF is proposed to mitigate current harmonics generated by nonlinear loads and keeps the current at the point of common coupling (PCC sinusoidal. The simulation results using MATLAB/SIMULINK show a good performance of the SAPF for current harmonics mitigation.

  16. Generative Graph Prototypes from Information Theory.

    Science.gov (United States)

    Han, Lin; Wilson, Richard C; Hancock, Edwin R

    2015-10-01

    In this paper we present a method for constructing a generative prototype for a set of graphs by adopting a minimum description length approach. The method is posed in terms of learning a generative supergraph model from which the new samples can be obtained by an appropriate sampling mechanism. We commence by constructing a probability distribution for the occurrence of nodes and edges over the supergraph. We encode the complexity of the supergraph using an approximate Von Neumann entropy. A variant of the EM algorithm is developed to minimize the description length criterion in which the structure of the supergraph and the node correspondences between the sample graphs and the supergraph are treated as missing data. To generate new graphs, we assume that the nodes and edges of graphs arise under independent Bernoulli distributions and sample new graphs according to their node and edge occurrence probabilities. Empirical evaluations on real-world databases demonstrate the practical utility of the proposed algorithm and show the effectiveness of the generative model for the tasks of graph classification, graph clustering and generating new sample graphs.

  17. Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers.

    Science.gov (United States)

    Peng, Sheng-Bin; Henry, James R; Kaufman, Michael D; Lu, Wei-Ping; Smith, Bryan D; Vogeti, Subha; Rutkoski, Thomas J; Wise, Scott; Chun, Lawrence; Zhang, Youyan; Van Horn, Robert D; Yin, Tinggui; Zhang, Xiaoyi; Yadav, Vipin; Chen, Shih-Hsun; Gong, Xueqian; Ma, Xiwen; Webster, Yue; Buchanan, Sean; Mochalkin, Igor; Huber, Lysiane; Kays, Lisa; Donoho, Gregory P; Walgren, Jennie; McCann, Denis; Patel, Phenil; Conti, Ilaria; Plowman, Gregory D; Starling, James J; Flynn, Daniel L

    2015-09-14

    LY3009120 is a pan-RAF and RAF dimer inhibitor that inhibits all RAF isoforms and occupies both protomers in RAF dimers. Biochemical and cellular analyses revealed that LY3009120 inhibits ARAF, BRAF, and CRAF isoforms with similar affinity, while vemurafenib or dabrafenib have little or modest CRAF activity compared to their BRAF activities. LY3009120 induces BRAF-CRAF dimerization but inhibits the phosphorylation of downstream MEK and ERK, suggesting that it effectively inhibits the kinase activity of BRAF-CRAF heterodimers. Further analyses demonstrated that LY3009120 also inhibits various forms of RAF dimers including BRAF or CRAF homodimers. Due to these unique properties, LY3009120 demonstrates minimal paradoxical activation, inhibits MEK1/2 phosphorylation, and exhibits anti-tumor activities across multiple models carrying KRAS, NRAS, or BRAF mutation.

  18. A case of delayed cardiac perforation of active ventricular lead

    Directory of Open Access Journals (Sweden)

    Hangyuan Guo

    2011-12-01

    Full Text Available A 65-year-old man was admitted as for one month of repetitive dizziness and one episode of syncope. Electrocardiogram showed sinus bradycardia and his Holter monitoring also showed sinus bradycardia with sinus arrest, sino-atrial block and a longest pause of 4.3 s. Then sick sinus syndrome and Adam-Stokes syndrome were diagnosed. Then a dual chamber pacemaker (Medtronic SDR303 was implanted and the parameters were normal by detection. The patient was discharged 1 week later with suture removed. Then 1.5 month late the patient was presented to hospital once again for sudden onset of chest pain with exacerbation after taking deep breath. Pacemaker programming showed both pacing and sensing abnormality with threshold of?5.0V and resistance of 1200?. Lead perforation was revealed by chest X-ray and confirmed by echocardiogram. Considering the fact that there was high risk to remove ventricular lead, spiral tip of previous ventricular lead was withdrew followed by implantation of a new ventricular active lead to the septum. Previous ventricular lead was maintained. As we know that the complications of lead perforation in the clinic was rare. Here we discuss the clinical management and the possible reasons for cardiac perforation of active ventricular lead.

  19. 77 FR 71425 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2012-11-30

    ... collection of information, to search data sources, to complete and review the collection of information, and... information requested, and to complete the online survey. ADDRESSES: Submit your comments to the desk officer... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH...

  20. Revenue generation in the information era: Opportunities and challenges

    Directory of Open Access Journals (Sweden)

    Sreelata Jonnalagedda

    2011-03-01

    Full Text Available In an information economy, innovative revenue generating models are as critical for the sustenance of a firm as is bringing cutting edge technology to the market. In its first part, this article surveys the characteristics of the information goods market and identifies the opportunities and challenges that the information era presents. Further, it surveys the existing business models for information goods and maps them to the market characteristics to arrive at the viability of these models. The second part of the article presents the views and experiences of a panel of practitioners who face these challenges in the field of information goods.

  1. Cidal activity of oral third-generation cephalosporins against Streptococcus pneumoniae in relation to cefotaxime intrinsic activity.

    Science.gov (United States)

    Cafini, F; Aguilar, L; Alou, L; Giménez, M J; Sevillano, D; Torrico, M; González, N; Granizo, J J; Martín-Herrero, J E; Prieto, J

    2008-08-01

    This study explores the killing kinetics within 12 h of four oral third-generation cephalosporins against ten Streptococcus pneumoniae strains exhibiting cefotaxime minimum inhibitory concentrations (MICs) from 0.03 to 2 microg/ml. Killing curves were performed with concentrations achievable in serum after standard doses (0.015-4 microg/ml). Reductions of 90% were achieved with all compounds at serum-achievable concentrations for strains exhibiting cefotaxime MIC cefotaxime MIC > or = 1 microg/ml, only cefditoren reached a 90% reduction with concentrations of 0.5-1 microg/ml doses. At 4 microg/ml, cefditoren and cefotaxime reached 99.9% reduction in seven of the ten strains studied. At serum-achievable concentrations, cefdinir and cefixime were not bactericidal against strains exhibiting cefotaxime MIC > or = 0.25 microg/ml and > or = 0.5 microg/ml, respectively. Cefditoren showed the best killing kinetic profiles and this observation may be important when choosing an oral third-generation cephalosporin as initial or sequential therapy.

  2. Glyphosate-based herbicides reduce the activity and reproduction of earthworms and lead to increased soil nutrient concentrations

    OpenAIRE

    Mailin Gaupp-Berghausen; Martin Hofer; Boris Rewald; Zaller, Johann G.

    2015-01-01

    Herbicide use is increasing worldwide both in agriculture and private gardens. However, our knowledge of potential side-effects on non-target soil organisms, even on such eminent ones as earthworms, is still very scarce. In a greenhouse experiment, we assessed the impact of the most widely used glyphosate-based herbicide Roundup on two earthworm species with different feeding strategies. We demonstrate, that the surface casting activity of vertically burrowing earthworms (Lumbricus terrestris...

  3. 77 FR 50497 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-08-21

    ..., DC 20503. FOR FURTHER INFORMATION CONTACT: Norma Abdul-Malik, Environmental Protection Agency, 1200... address: abdul-malik.norma@epa.gov . SUPPLEMENTARY INFORMATION: EPA has submitted the following ICR to...

  4. 77 FR 14781 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-03-13

    ... material, Confidential Business Information (CBI), or other information whose public disclosure is... standard has increased due to industry growth in the past three years. Second, this ICR uses updated labor..., Collection Strategies Division. BILLING CODE 6560-50-P...

  5. Theoretical Implications for Inform and Influence Activities

    Science.gov (United States)

    2013-05-23

    CEMA Cyber Electromagnetic Activities CA Civil Affairs DOD Department of Defense DSB Defense Science Board IIA Inform and Influence Activities IO...23 Figure 3. CEMA Lines of Effort .................................................................................................... 23 Figure 4...capabilities into IIA and cyber electromagnetic activities ( CEMA ) 3. A name change from PSYOP to military information support activities (MISO) 4

  6. Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection.

    Science.gov (United States)

    Choi, Bongseo; Moon, Hyojin; Hong, Sung Joon; Shin, Changsik; Do, Yoonkyung; Ryu, Seongho; Kang, Sebyung

    2016-08-23

    In cancer immunotherapy, robust and efficient activation of cytotoxic CD8(+) T cell immune responses is a promising, but challenging task. Dendritic cells (DCs) are well-known professional antigen presenting cells that initiate and regulate antigen-specific cytotoxic CD8(+) T cells that kill their target cells directly as well as secrete IFN-γ, a cytokine critical in tumor rejection. Here, we employed recently established protein cage nanoparticles, encapsulin (Encap), as antigenic peptide nanocarriers by genetically incorporating the OT-1 peptide of ovalbumin (OVA) protein to the three different positions of the Encap subunit. With them, we evaluated their efficacy in activating DC-mediated antigen-specific T cell cytotoxicity and consequent melanoma tumor rejection in vivo. DCs efficiently engulfed Encap and its variants (OT-1-Encaps), which carry antigenic peptides at different positions, and properly processed them within phagosomes. Delivered OT-1 peptides were effectively presented by DCs to naïve CD8(+) T cells successfully, resulting in the proliferation of antigen-specific cytotoxic CD8(+) T cells. OT-1-Encap vaccinations in B16-OVA melanoma tumor bearing mice effectively activated OT-1 peptide specific cytotoxic CD8(+) T cells before or even after tumor generation, resulting in significant suppression of tumor growth in prophylactic as well as therapeutic treatments. A large number of cytotoxic CD8(+) T cells that actively produce both intracellular and secretory IFN-γ were observed in tumor-infiltrating lymphocytes collected from B16-OVA tumor masses originally vaccinated with OT-1-Encap-C upon tumor challenges. The approaches we describe herein may provide opportunities to develop epitope-dependent vaccination systems that stimulate and/or modulate efficient and epitope-specific cytotoxic T cell immune responses in nonpathogenic diseases.

  7. 37 years of scientific activity in a Biochemistry Department in Brazil: patterns of growth and factors leading to increased productivity

    Directory of Open Access Journals (Sweden)

    Urubatã E. Gomes

    2011-09-01

    Full Text Available Scientific activity in Brazil has experienced an accelerated growth in the past decades, with an increase in productivity that greatly surpasses the international average. This growth has occurred mostly at the expense of centers of excellence in public universities, which account for the vast majority of the country's scientific output. The aim of this study was to evaluate the production of the Department of Biochemistry of a large public university in southern Brazil (Universidade Federal do Rio Grande do Sul, as well as to identify internal and external policies that have influenced this growing production profile. We have performed a historical analysis of the scientific output of this Department of Biochemistry, which accounts for a considerable share of the indexed scientific production at this university. By focusing on the temporal course of its growth and drawing correlations between scientific output and important events in the history of the Department of Biochemistry and of the Brazilian science policies, we concluded that internal factors (as the creation of a postgraduation program, collaboration among researchers, experienced abroad researchers, qualification of faculty members and external factors (as investments in the postgraduate education, the establishment of national scientific policies, such as financial stimuli for productive researchers and evaluation systems influence scientific productivity in Brazil.A atividade científica no Brasil apresentou um crescimento acelerado nas últimas décadas, com um aumento na produtividade que ultrapassou os valores médios internacionais. Este crescimento tem ocorrido através dos centros de excelência em pesquisa nas Universidades Públicas, as quais são responsáveis pela maior parte da produção científica do país. O presente estudo tem como objetivo avaliar a produção do Departamento de Bioquímica de uma grande universidade pública do sul do Brasil (Universidade Federal

  8. Different Pathways Leading to Integrase Inhibitors Resistance

    Science.gov (United States)

    Thierry, Eloïse; Deprez, Eric; Delelis, Olivier

    2017-01-01

    Integrase strand-transfer inhibitors (INSTIs), such as raltegravir (RAL), elvitegravir, or dolutegravir (DTG), are efficient antiretroviral agents used in HIV treatment in order to inhibit retroviral integration. By contrast to RAL treatments leading to well-identified mutation resistance pathways at the integrase level, recent clinical studies report several cases of patients failing DTG treatment without clearly identified resistance mutation in the integrase gene raising questions for the mechanism behind the resistance. These compounds, by impairing the integration of HIV-1 viral DNA into the host DNA, lead to an accumulation of unintegrated circular viral DNA forms. This viral DNA could be at the origin of the INSTI resistance by two different ways. The first one, sustained by a recent report, involves 2-long terminal repeat circles integration and the second one involves expression of accumulated unintegrated viral DNA leading to a basal production of viral particles maintaining the viral information. PMID:28123383

  9. 77 FR 77038 - Agency Information Collection Activities: Notice of Intent to Renew Collection, Futures Volume...

    Science.gov (United States)

    2012-12-31

    ..., and Office of Information and Regulatory Affairs, Office of Management and Budget, Attention: Desk... of the public submit reports, keep records, or provide information to a third party. Section 3506(c... collection techniques or other forms of information technology; e.g., permitting electronic submission...

  10. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline

    DEFF Research Database (Denmark)

    Hardies, Katia; Cai, Yiying; Jardel, Claude;

    2016-01-01

    SYNJ1 encodes a polyphosphoinositide phosphatase, synaptojanin 1, which contains two consecutive phosphatase domains and plays a prominent role in synaptic vesicle dynamics. Autosomal recessive inherited variants in SYNJ1 have previously been associated with two different neurological diseases...... with intractable epilepsy and tau pathology. We performed whole exome or genome sequencing in three independent sib pairs with early onset refractory seizures and progressive neurological decline, and identified novel segregating recessive SYNJ1 defects. A homozygous missense variant resulting in an amino acid...... function, our results provide evidence that a critical reduction of the dual phosphatase activity of SYNJ1 underlies a severe disorder with neonatal refractory epilepsy and a neurodegenerative disease course. These findings further expand the clinical spectrum of synaptic dysregulation in patients...

  11. Introduction to information science

    CERN Document Server

    Bawden, David

    2012-01-01

    This landmark textbook takes a whole subject approach to Information Science as a discipline. Introduced by leading international scholars and offering a global perspective on the discipline, this is designed to be the standard text for students worldwide. The authors' expert narrative guides you through each of the essential building blocks of information science offering a concise introduction and expertly chosen further reading and resources.Critical topics covered include:foundations: concepts, theories and historical perspectivesorganising and retrieving Information information behaviour,

  12. Information Portals: The Next Generation Catalog

    Science.gov (United States)

    Allison, DeeAnn

    2010-01-01

    Libraries today face an increasing challenge: to provide relevant information to diverse populations with differing needs while competing with Web search engines like Google. In 2009, a large group of libraries, including the University of Nebraska-Lincoln Libraries, joined with Innovative Interfaces as development partners to design a new type of…

  13. 78 FR 41406 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-07-10

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... care, coordinating a wide range of medical, dental, behavioral, and social services. More than 1,200....0 4,800 Form 4: Community 650 1 650 1.0 650 Characteristics Form 5A: Services Provided...... 1,600...

  14. 75 FR 31432 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-06-03

    ... Request; Voluntary Cover Sheet for TSCA Submissions; EPA ICR No. 1780.05, OMB Control No. 2070-0156 AGENCY... Sheet for TSCA Submissions; ICR No. 1780.05, OMB No. 2070-0156. The ICR, which is abstracted below, describes the nature of the information collection activity and its expected burden and costs....

  15. Pinitol targets nuclear factor-kappaB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis.

    Science.gov (United States)

    Sethi, Gautam; Ahn, Kwang Seok; Sung, Bokyung; Aggarwal, Bharat B

    2008-06-01

    Pinitol (3-O-methyl-chiroinositol), a component of traditional Ayurvedic medicine (talisapatra), has been shown to exhibit anti-inflammatory and antidiabetic activities through undefined mechanisms. Because the transcription factor nuclear factor-kappaB (NF-kappaB) has been linked with inflammatory diseases, including insulin resistance, we hypothesized that pinitol must mediate its effects through modulation of NF-kappaB activation pathway. We found that pinitol suppressed NF-kappaB activation induced by inflammatory stimuli and carcinogens. This suppression was not specific to cell type. Besides inducible, pinitol also abrogated constitutive NF-kappaB activation noted in most tumor cells. The suppression of NF-kappaB activation by pinitol occurred through inhibition of the activation of IkappaBalpha kinase, leading to sequential suppression of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Pinitol also suppressed the NF-kappaB reporter activity induced by tumor necrosis factor receptor (TNFR)-1, TNFR-associated death domain, TNFR-associated factor-2, transforming growth factor-beta-activated kinase-1 (TAK-1)/TAK1-binding protein-1, and IkappaBalpha kinase but not that induced by p65. The inhibition of NF-kappaB activation thereby led to down-regulation of gene products involved in inflammation (cyclooxygenase-2), proliferation (cyclin D1 and c-myc), invasion (matrix metalloproteinase-9), angiogenesis (vascular endothelial growth factor), and cell survival (cIAP1, cIAP2, X-linked inhibitor apoptosis protein, Bcl-2, and Bcl-xL). Suppression of these gene products by pinitol enhanced the apoptosis induced by TNF and chemotherapeutic agents and suppressed TNF-induced cellular invasion. Our results show that pinitol inhibits the NF-kappaB activation pathway, which may explain its ability to suppress inflammatory cellular responses.

  16. 78 FR 79561 - Information Collection Activities

    Science.gov (United States)

    2013-12-30

    ... Pipeline and Hazardous Materials Safety Administration Information Collection Activities AGENCY: Pipeline... information collection activity and, when approved by OMB, publish a notice of the approval in the Federal... notice announces that the Information Collection Requests (ICR) abstracted below will be forwarded to...

  17. 75 FR 66185 - Information Collection Activities

    Science.gov (United States)

    2010-10-27

    ... Pipeline and Hazardous Materials Safety Administration Information Collection Activities AGENCY: Pipeline... information collection activity and, when approved by OMB, publish notice of the approval in the Federal... Information Collection Requests (ICR) abstracted below will be forwarded to the Office of Management...

  18. Extending dynamic segmentation with lead generation : A latent class Markov analysis of financial product portfolios

    NARCIS (Netherlands)

    Paas, L.J.; Bijmolt, T.H.A.; Vermunt, J.K.

    2004-01-01

    A recent development in marketing research concerns the incorporation of dynamics in consumer segmentation.This paper extends the latent class Markov model, a suitable technique for conducting dynamic segmentation, in order to facilitate lead generation.We demonstrate the application of the latent M

  19. Electronic coupling in iron oxide-modified TiO2 leads to a reduced band gap and charge separation for visible light active photocatalysis.

    Science.gov (United States)

    Nolan, Michael

    2011-10-28

    In recent experiments Tada et al. have shown that TiO(2) surfaces modified with iron oxide display visible light photocatalytic activity. This paper presents first principles simulations of iron oxide clusters adsorbed at the rutile TiO(2) (110) surface to elucidate the origin of the visible light photocatalytic activity of iron oxide modified TiO(2). Small iron oxide clusters adsorb at rutile (110) surface and their presence shifts the valence band so that the band gap of the composite is narrowed towards the visible, thus confirming the origin of the visible light activity of this composite material. The presence of iron oxide at the TiO(2) surface leads to charge separation, which is the origin of enhanced photocatalytic efficiency, consistent with experimental photoluminesence and photocurrent data. Surface modification of a metal oxide is thus an interesting route in the development of visible light photocatalytic materials.

  20. Effect of lead (Pb) exposure on the activity of superoxide dismutase and catalase in battery manufacturing workers (BMW) of Western Maharashtra (India) with reference to heme biosynthesis.

    Science.gov (United States)

    Patil, Arun J; Bhagwat, Vinod R; Patil, Jyotsna A; Dongre, Nilima N; Ambekar, Jeevan G; Jailkhani, Rama; Das, Kusal K

    2006-12-01

    The aim of this study was to estimate the activity of superoxide dismutase (SOD) and catalase in erythrocytes and malondialdehyde (MDA) in plasma of battery manufacturing workers (BMW) of Western Maharashtra (India) who were occupationally exposed to lead (Pb) over a long period of time (about 15 years). This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28) was found to be in the range of 25.8 - 78.0 microg/dL (mean + SD, 53.63 + 16.98) whereas in Pb unexposed control group (n = 35) the range was 2.8 - 22.0 microg/dL (mean + SD, 12.52 + 4.08). The blood level (Pb-B) and urinary lead level (Pb-U) were significantly increased in BMW group as compared to unexposed control. Though activated d- aminolevulinic acid dehydratase (ALAD) activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte - ALAD activities in BMW group showed a significant increase. Erythrocyte- zinc protoporphyrin (ZPP), urinary daminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p BMW group but no such significant correlation (r = 0.02, p> 1.0) were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (%) and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p BMW group as compared to control group. A positive correlation (r = 0.45, p BMW group (Pb-B range 25.8 - 78.0 microg / dL) but such significant correlation did not notice in control group (Pb-B range 2.8 - 22.0 microg / dL). The study clearly showed an adverse effect of heme biosynthesis and imbalance of pro-oxidant / antioxidant status in lead exposed battery manufacturing

  1. 75 FR 35452 - Agency Information Collection Activities; Submission To OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-06-22

    ... to their introduction into commerce. Registration involves providing a chemical description of the fuel or additive, and certain technical, marketing, and health-effects information. The development...

  2. Interaction of operational and physicochemical factors leading to Gordonia amarae-like foaming in an incompletely nitrifying activated sludge plant.

    Science.gov (United States)

    Asvapathanagul, Pitiporn; Huang, Zhonghua; Gedalanga, Phillip B; Baylor, Amber; Olson, Betty H

    2012-12-01

    The overgrowth of Gordonia amarae-like bacteria in the mixed liquor of an incompletely nitrifying water reclamation plant was inversely correlated with temperature (r = -0.78; P < 0.005) and positively correlated with the solids retention time (SRT) obtained a week prior to sampling (r = 0.67; P < 0.005). Drops followed by spikes in the food-to-mass ratio (0.18 to 0.52) and biochemical oxygen demand concentrations in primary effluent (94 to 298 mg liter(-1)) occurred at the initiation of G. amarae-like bacterial growth. The total bacterial concentration did not increase as concentrations of G. amarae-like cells increased, but total bacterial cell concentrations fluctuated in a manner similar to that of G. amarae-like bacteria in the pseudo-steady state. The ammonium ion removal rate (percent) was inversely related to G. amarae-like cell concentrations during accelerated growth and washout phases. The dissolved oxygen concentration decreased as the G. amarae-like cell concentration decreased. The concentrations of G. amarae-like cells peaked (2.47 × 10(9) cells liter(-1)) approximately 1.5 months prior to foaming. Foaming occurred during the late pseudo-steady-state phase, when temperature declines reversed. These findings suggested that temperature changes triggered operational and physicochemical changes favorable to the growth of G. amarae-like bacteria. Fine-scale quantitative PCR (qPCR) monitoring at weekly intervals allowed a better understanding of the factors affecting this organism and indicated that frequent sampling was required to obtain statistical significance with factors changing as the concentrations of this organism increased. Furthermore, the early identification of G. amarae-like cells when they are confined to mixed liquor (10(7) cells liter(-1)) allows management strategies to prevent foaming.

  3. Induction of tissue inhibitor of matrix metalloproteinase-2 by cholesterol depletion leads to the conversion of proMMP-2 into active MMP-2 in human dermal fibroblasts.

    Science.gov (United States)

    Kim, Sangmin; Oh, Jang-Hee; Lee, Youngae; Lee, Jeongyoon; Cho, Kwang Hyun; Chung, Jin Ho

    2010-01-31

    Cholesterol is one of major components of cell membrane and plays a role in vesicular trafficking and cellular signaling. We investigated the effects of cholesterol on matrix metalloproteinase-2 (MMP-2) activation in human dermal fibroblasts. We found that tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression and active form MMP-2 (64 kD) were dose-dependently increased by methyl-beta-cyclodextrin (MbetaCD), a cholesterol depletion agent. In contrast, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation were suppressed by cholesterol repletion. Then we investigated the regulatory mechanism of TIMP-2 expression by cholesterol depletion. We found that the phosphorylation of JNK as well as ERK was significantly increased by cholesterol depletion. Moreover, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation was significantly decreased by MEK inhibitor U0126, and JNK inhibitor SP600125, respectively. While a low dose of recombinant TIMP-2 (100 ng/ml) increased the level of active MMP-2 (64 kD), the high dose of TIMP-2 (>or=200 ng/ml) decreased the level of active MMP-2 (64 kD). Taken together, we suggest that the induction of TIMP-2 by cholesterol depletion leads to the conversion of proMMP-2 (72 kD) into active MMP-2 (64 kD) in human dermal fibroblasts.

  4. Laminin Interactions with Head and Neck Cancer Cells under Low Fluid Shear Conditions Lead to Integrin Activation and Binding*

    Science.gov (United States)

    Fennewald, Susan M.; Kantara, Carla; Sastry, Sarita K.; Resto, Vicente A.

    2012-01-01

    Lymphatic metastasis of cancer cells involves movement from the primary tumor site to the lymph node, where the cells must be able to productively lodge and grow. It is there that tumor cells encounter cellular and non-cellular constituent elements that make up the lymph node parenchyma. Our work shows that head and neck squamous cell carcinoma (HNSCC) cell lines are able to bind to laminin, fibronectin, vitronectin, and hyaluronic acid, which are extracellular matrix elements within the lymph node parenchyma. HNSCC cell lines bound to laminin under lymphodynamic low shear stress (0.07 dynes/cm2), consistent with lymph flow via β1 integrins, including α2β1, α3β1, and α6β1. Binding occurred in the presence of shear stress and not in the absence of flow. Additionally, tumor cell binding to laminin under flow did result in calcium signaling. Our data indicate a novel role for β1 integrin-mediated binding of HNSCC cells to laminin under conditions of lymphodynamic flow that results in intracellular calcium signaling within the cancer cell. PMID:22547070

  5. Myeloma cell-induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast-myeloma hybrid cells

    DEFF Research Database (Denmark)

    Andersen, Thomas L; Søe, Kent; Søndergaard, Teis Esben

    2010-01-01

    Osteolytic lesions are a hallmark of multiple myeloma. They are due to the hyperactivity of bone resorbing osteoclasts and hypoactivity of bone forming osteoblasts, in response to neighbouring myeloma cells. This study identified a structure that deeply affects this response, because of its impac...

  6. 78 FR 70308 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-11-25

    ... be able to respond to a collection of information; to search data sources; to complete and review the... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Agency Information Collection...

  7. 78 FR 21380 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-04-10

    ... be able to respond to a collection of information, to search data sources, to complete and review the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Agency Information Collection...

  8. 78 FR 27973 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-05-13

    ... be able to respond to a collection of information; to search data sources; to complete and review the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Agency Information Collection...

  9. Image encryption using random sequence generated from generalized information domain

    Science.gov (United States)

    Xia-Yan, Zhang; Guo-Ji, Zhang; Xuan, Li; Ya-Zhou, Ren; Jie-Hua, Wu

    2016-05-01

    A novel image encryption method based on the random sequence generated from the generalized information domain and permutation-diffusion architecture is proposed. The random sequence is generated by reconstruction from the generalized information file and discrete trajectory extraction from the data stream. The trajectory address sequence is used to generate a P-box to shuffle the plain image while random sequences are treated as keystreams. A new factor called drift factor is employed to accelerate and enhance the performance of the random sequence generator. An initial value is introduced to make the encryption method an approximately one-time pad. Experimental results show that the random sequences pass the NIST statistical test with a high ratio and extensive analysis demonstrates that the new encryption scheme has superior security.

  10. Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase.

    Directory of Open Access Journals (Sweden)

    David G Warnock

    Full Text Available Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT with either agalsidase alfa (Replagal or agalsidase beta (Fabrazyme. Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%. Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified.ClinicalTrials.gov NCT01196871.

  11. Activating mutation in a mucolipin transient receptor potential channel leads to melanocyte loss in varitint-waddler mice.

    Science.gov (United States)

    Xu, Haoxing; Delling, Markus; Li, Linyu; Dong, Xianping; Clapham, David E

    2007-11-13

    Transient receptor potential (TRP) genes of the mucolipin subfamily (TRPML1-3 and MCOLN1-3) are presumed to encode ion channel proteins of intracellular endosomes and lysosomes. Mutations in human TRPML1 (mucolipin 1/MCOLN1) result in mucolipidosis type IV, a severe inherited neurodegenerative disease associated with defective lysosomal biogenesis and trafficking. A mutation in mouse TRPML3 (A419P; TRPML3(Va)) results in the varitint-waddler (Va) phenotype. Va mice are deaf, exhibit circling behavior due to vestibular defects, and have variegated/dilute coat color as a result of pigmentation defects. Prior electrophysiological studies of presumed TRPML plasma membrane channels are contradictory and inconsistent with known TRP channel properties. Here, we report that the Va mutation produces a gain-of-function that allows TRPML1 and TRPML3 to be measured and identified as inwardly rectifying, proton-impermeant, Ca(2+)-permeant cation channels. TRPML3 is highly expressed in normal melanocytes. Melanocyte markers are lost in the Va mouse, suggesting that their variegated and hypopigmented fur is caused by severe alteration of melanocyte function or cell death. TRPML3(Va) expression in melanocyte cell lines results in high resting Ca(2+) levels, rounded, poorly adherent cells, and loss of membrane integrity. We conclude that the Va phenotype is caused by mutation-induced TRPML3 gain-of-function, resulting in cell death.

  12. Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation- sensitivity in breast cancer cells

    LENUS (Irish Health Repository)

    Thewes, Verena

    2010-05-11

    Abstract Background Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the

  13. 75 FR 13575 - Agency Information Collection Activities

    Science.gov (United States)

    2010-03-22

    ... of Justice Programs Agency Information Collection Activities ACTION: 30-Day Notice of Information... Department of Justice (DOJ), Office of Justice Programs (OJP) will be submitting the following information... the Paperwork Reduction Act of 1995. The proposed information collection is published to...

  14. Can systemically generated reactive oxygen species help to monitor disease activity in generalized vitiligo? A pilot study

    Directory of Open Access Journals (Sweden)

    Richeek Pradhan

    2014-01-01

    Full Text Available Background: Generalized vitiligo is a disease with unpredictable bursts of activity, goal of treatment during the active phase being to stabilize the lesions. This emphasizes the need for a prospective marker for monitoring disease activity to help decide the duration of therapy. Aims and Objectives: In the present study, we examined whether reactive oxygen species (ROS generated in erythrocytes can be translated into a marker of activity in vitiligo. Materials and Methods: Level of intracellular ROS was measured flow cytometrically in erythrocytes from venous blood of 21 patients with generalized vitiligo and 21 healthy volunteers using the probe dichlorodihydrofluorescein diacetate. Results: The levels of ROS differed significantly between patients and healthy controls, as well as between active versus stable disease groups. In the active disease group, ROS levels were significantly lower in those being treated with systemic steroids than those that were not. ROS levels poorly correlated with disease duration or body surface area involved. Conclusion: A long-term study based on these findings can be conducted to further validate the potential role of ROS in monitoring disease activity vitiligo.

  15. Rapid microsatellite marker development using next generation pyrosequencing to inform invasive Burmese python -- Python molurus bivittatus -- management

    Science.gov (United States)

    Hunter, Margaret E.; Hart, Kristen M.

    2013-01-01

    Invasive species represent an increasing threat to native ecosystems, harming indigenous taxa through predation, habitat modification, cross-species hybridization and alteration of ecosystem processes. Additionally, high economic costs are associated with environmental damage, restoration and control measures. The Burmese python, Python molurus bivittatus, is one of the most notable invasive species in the US, due to the threat it poses to imperiled species and the Greater Everglades ecosystem. To address population structure and relatedness, next generation sequencing was used to rapidly produce species-specific microsatellite loci. The Roche 454 GS-FLX Titanium platform provided 6616 di-, tri- and tetra-nucleotide repeats in 117,516 sequences. Using stringent criteria, 24 of 26 selected tri- and tetra-nucleotide loci were polymerase chain reaction (PCR) amplified and 18 were polymorphic. An additional six cross-species loci were amplified, and the resulting 24 loci were incorporated into eight PCR multiplexes. Multi-locus genotypes yielded an average of 61% (39%–77%) heterozygosity and 3.7 (2–6) alleles per locus. Population-level studies using the developed microsatellites will track the invasion front and monitor population-suppression dynamics. Additionally, cross-species amplification was detected in the invasive Ball, P. regius, and Northern African python, P. sebae. These markers can be used to address the hybridization potential of Burmese pythons and the larger, more aggressive P. sebae.

  16. Solid Adsorbents for Low Temperature CO2 Capture with Low Energy Penalties Leading to More Effective Integrated Solutions for Power Generation and Industrial Processes

    Directory of Open Access Journals (Sweden)

    Nannan eSun

    2015-03-01

    Full Text Available CO2 capture represents the key technology for CO2 reduction within the framework of CO2 capture, utilization, and storage (CCUS. In fact, the implementation of CO2 capture extends far beyond CCUS since it will link the CO2 emission and recycling sectors, and when renewables are used to provide necessary energy input, CO2 capture would enable a profitable zero- or even negative-emitting and integrated energy-chemical solution. To this end, highly efficient CO2 capture technologies are needed, and adsorption using solid adsorbents has the potential to be one of the ideal options. Currently, the greatest challenge in this area is the development of adsorbents with high performance that balances a range of optimization-needed factors, those including costs, efficiency, and engineering feasibility. In this review, recent advances on the development of carbon-based and immobilized organic amines-based CO2 adsorbents are summarized, the selection of these particular categories of materials is because they are among the most developed low temperature (<100 oC CO2 adsorbents up to date, which showed important potential for practical deployment at pilot-scale in the near future. Preparation protocols, adsorption behaviors as well as pros and cons of each type of the adsorbents are presented, it was concluded that encouraging results have been achieved already, however, the development of more effective adsorbents for CO2 capture remains challenging and further innovations in the design and synthesis of adsorbents are needed.

  17. Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects.

    Science.gov (United States)

    Yang, Peixin; Li, Xuezheng; Xu, Cheng; Eckert, Richard L; Reece, E Albert; Zielke, Horst Ronald; Wang, Fang

    2013-08-27

    Neural tube defects result from failure to completely close neural tubes during development. Maternal diabetes is a substantial risk factor for neural tube defects, and available evidence suggests that the mechanism that links hyperglycemia to neural tube defects involves oxidative stress and apoptosis. We demonstrated that maternal hyperglycemia correlated with activation of the apoptosis signal-regulating kinase 1 (ASK1) in the developing neural tube, and Ask1 gene deletion was associated with reduced neuroepithelial cell apoptosis and development of neural tube defects. ASK1 activation stimulated the activity of the transcription factor FoxO3a, which increased the abundance of the apoptosis-promoting adaptor protein TRADD, leading to activation of caspase 8. Hyperglycemia-induced apoptosis and the development of neural tube defects were reduced with genetic ablation of either FoxO3a or Casp8 or inhibition of ASK1 by thioredoxin. Examination of human neural tissues affected by neural tube defects revealed increased activation or abundance of ASK1, FoxO3a, TRADD, and caspase 8. Thus, activation of an ASK1-FoxO3a-TRADD-caspase 8 pathway participates in the development of neural tube defects, which could be prevented by inhibiting intermediates in this cascade.

  18. Population information activities in Hungary.

    Science.gov (United States)

    Csahok, I

    1984-12-01

    The focal point for all population information activities in Hungary is the Central Statistical Office which is responsible for the organization and implementation of the decennial population censuses and of the intercensal population surveys and other data collection activities. The Central Statistical Office publishes a large volume of population information. The results of the censuses are presented partly in special census volumes and partly in statistical yearbooks. The Demographic Yearbook and other publications present results of population studies and Hungarian statistics. The Demographic Research Institute, which is part of the Central Statistical Office, is primarily responsible for research activity. The main task of the Institute is to study and analyze population processes and phenomena, as well as explore main demographic trends, carried out by using Hungarian and international demographic data. Demografia and serial publications present results of research activities of the Institute. The Library and Documentation Service, also part of the Central Statistical Office, provides conventional library services. Its main activity is the collection of both Hungarian and foreign and international official statistical publications, as well as theoretical and methodological works. Of a stock of 650,000 volumes covering a wide range of social and economic sciences, in addition to data material, the library has nearly 120,000 official statistical publications consisting mainly of population statistics and demographic data. Another activity of the Library is the processing and dissemination of documentation and it acts as a 2dary source of both Hungarian and foreign publications, especially on demography. The documentation consists of translating articles, book chapters or documents of international organizations, editing annotated bibliographies and disseminating custom-made, user-oriented profiles. This computerized information retrieval system uses Text

  19. 77 FR 42303 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-07-18

    ... the collection of information while this submission is pending at OMB. Abstract: The New Source... subsequently changed; train personnel to be able to respond to a collection of information; search data sources... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL...

  20. 75 FR 81650 - Agency Information Collection Activities:

    Science.gov (United States)

    2010-12-28

    ... Bureau of Alcohol, Tobacco, Firearms, and Explosives Agency Information Collection Activities: Proposed Collection; Comments Requested ACTION: 30-Day Notice of Information Collection Under Review: Open Letter to...), Bureau of Alcohol, Tobacco, Firearms, and Explosives (ATF) will be submitting the following...

  1. How to lead complex situations

    DEFF Research Database (Denmark)

    Hansen, Michael Pingel

    2013-01-01

    The military leader is experiencing increasingly more complex situations, whether it is as leader in a foreign combat environment or in the home-based public administration. Complex situations like these call for a special set of managerial responses and a special way of leading organisations...

  2. The Role of JNK and p38 MAPK Activities in UVA-Induced Signaling Pathways Leading to AP-1 Activation and c-Fos Expression

    Directory of Open Access Journals (Sweden)

    Amy L. Silvers

    2003-07-01

    Full Text Available To further delineate ultraviolet A (UVA signaling pathways in the human keratinocyte cell line HaCaT, we examined the potential role of mitogen-activated protein kinases (MAPKs in UVA-induced activator protein-1 (AP-1 transactivation and c-Fos expression. UVA-induced phosphorylation of p38 and c-Jun N-terminal kinase (JNK proteins was detected immediately after irradiation and disappeared after approximately 2 hours. Conversely, phosphorylation of extracellular signal-regulated kinase was significantly inhibited for up to 1 hour post-UVA irradiation. To examine the role of p38 and JNK MAPKs in UVA-induced AP-1 and c-fos transactivations, the selective pharmacologic MAPK inhibitors, SB202190 (p38 inhibitor and SP600125 (JNK inhibitor, were used to independently treat stably transfected HaCaT cells in luciferase reporter assays. Both SB202190 and SP600125 dose-dependently inhibited UVA-induced AP-1 and c-fos transactivations. SB202190 (0.25–0.5 MM and SP600125 (62-125 nM treatments also primarily inhibited UVA-induced c-Fos expression. These results demonstrated that activation of both JNK and p38 play critical role in UVA-mediated AP-1 transactivation and c-Fos expression in these human keratinocyte cells. Targeted inhibition of these MAPKs with their selective pharmacologic inhibitors may be effective chemopreventive strategies for UVA-induced nonmelanoma skin cancer.

  3. 76 FR 21379 - Agency Information Collection Activities; Proposed Collection; Comment Request; Experiment To...

    Science.gov (United States)

    2011-04-15

    ... of the public submit reports, keep records, or provide information to a third party. Section 3506(c... of information on respondents, including through the use of automated collection techniques, when... to the attention of public health authorities. When the outbreaks are large in scale or...

  4. Providing Access to Local Government Information: The Nature of Public Library Activity.

    Science.gov (United States)

    Durrance, Joan C.

    1988-01-01

    Describes a survey of public libraries that examined problems associated with access to local government information. Findings are reported on the nature of requests received, the types of responses given and sources used, and reasons given by librarians for providing access to local government information. (14 notes with references) (CLB)

  5. 75 FR 18824 - Agency Information Collection Activities: Notice of Intent To Renew Collection 3038-0019, Stocks...

    Science.gov (United States)

    2010-04-13

    ... From the Federal Register Online via the Government Publishing Office ] COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection 3038-0019, Stocks of Grain in Licensed Warehouses AGENCY: Commodity Futures Trading Commission. ACTION: Notice....

  6. Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance.

    Science.gov (United States)

    Crowley, Maeve P; Kevane, Barry; O'Shea, Susan I; Quinn, Shane; Egan, Karl; Gilligan, Oonagh M; Ní Áinle, Fionnuala

    2016-09-01

    The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P < .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies.

  7. 78 FR 61366 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-10-03

    ..., the Northern Mariana Islands, American Samoa, Guam, the U.S. Virgin Islands, the Federated States of... be able to respond to a collection of information; to search data sources; to complete and review...

  8. Sortilin-related receptor 1 interacts with amyloid precursor protein and is activated by 6-shogaol, leading to inhibition of the amyloidogenic pathway.

    Science.gov (United States)

    Na, Ji-Young; Song, Kibbeum; Lee, Ju-Woon; Kim, Sokho; Kwon, Jungkee

    2017-03-18

    Sortilin-related receptor 1 (SORL1) is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate amyloid beta (Aβ). Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, research regarding the activation of SORL1 has not yet been reported. Here, we aimed to investigate whether 6-shogaol contributes to the increases in SORL1 that are related to Alzheimer's disease (AD). To clarify the effect of 6-shogaol as a possible activator of SORL1, we used SORL1 siRNA as a blockade of SORL1 in hippocampal neuronal cells (HT22). We found that SORL1 siRNA treatment naturally inhibited SORL1 and led to increases in β-secretase APP cleaving enzyme (BACE), secreted APP-β (sAPPβ) and Aβ. In contrast, 6-shogaol-mediated activation of SORL1 significantly downregulated BACE, sAPPβ, and Aβ in both in vitro HT22 cells and in vivo APPSw/PS1-dE9 Tg mice. Therefore, SORL1 activation by 6-shogaol provides neuronal cell survival through the inhibition of Aβ production. These results indicate that 6-shogaol should be regarded as an SORL1 activator and a potential preventive agent for the treatment of AD.

  9. Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviours in aged mice.

    Science.gov (United States)

    Dworkin, Sebastian; Auden, Alana; Partridge, Darren D; Daglas, Maria; Medcalf, Robert L; Mantamadiotis, Theo; Georgy, Smitha R; Darido, Charbel; Jane, Stephen M; Ting, Stephen B

    2016-12-01

    The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here we show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviours. Using both Grhl3-knockout mice (Grhl3(-/-) ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3(flox/flox) ), we performed histological expression analyses and behavioural tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety and stress. We found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain, however aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviours suggestive of decreased fear and anxiety. We conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behaviour or hyperactivity. This article is protected by copyright. All rights reserved.

  10. 75 FR 1648 - MMS Information Collection Activity: 1010-NEW Study of Sharing To Assess Community Resilience...

    Science.gov (United States)

    2010-01-12

    ... the Interior; Minerals Management Service; Attention: Cheryl Blundon; 381 Elden Street, MS-4024... use of automated collection techniques or other forms of information technology. Agencies must also... other than to provide information or keep records for the Government; or (iv) as part of customary...

  11. 76 FR 27080 - Agency Information Collection Activities: Application To Pay Off or Discharge an Alien Crewman

    Science.gov (United States)

    2011-05-10

    ... Off or Discharge an Alien Crewman AGENCY: U.S. Customs and Border Protection, Department of Homeland... Discharge an Alien Crewman (Form I-408). This is a proposed extension of an information collection that was... techniques or other forms of information. Title: Application To Pay Off or Discharge an Alien Crewman....

  12. 77 FR 28381 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-05-14

    ... copyrighted material, Confidential Business Information (CBI), or other information whose public disclosure is... from the most recently approved ICR. The increase is due to a growth in the respondent universe in the... labor categories when estimating burden costs. John Moses, Director, Collection Strategies...

  13. 78 FR 41060 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2013-07-09

    ... contains copyrighted material, Confidentiality of Business Information (CBI), or other information whose... anticipated to change over the next three years; and (2) the growth rate for the industry is non-existent, so..., Collection Strategies Division. BILLING CODE 6560-50-P...

  14. 77 FR 16833 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-03-22

    ... copyrighted material, Confidential Business Information (CBI), or other information whose public disclosure is... to industry growth in the past three years, resulting in additional number of respondents that are... Labor Statistics in calculating the labor costs. John Moses, Director, Collection Strategies...

  15. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.

    Science.gov (United States)

    Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung

    The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

  16. 78 FR 69121 - Information Collection Activities: Open and Nondiscriminatory Access to Oil and Gas Pipelines...

    Science.gov (United States)

    2013-11-18

    ... regulations will apply to all operations conducted under a lease, right-of-way, or a right-of-use and easement... financial information submitted to the Department of the Interior relative to minerals removed from...

  17. 76 FR 26305 - Agency Information Collection Activities; Proposed Collection; Comment Request; Certification To...

    Science.gov (United States)

    2011-05-06

    ... the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A... mentioned statutory requirement. The importance of obtaining these data relates to adherence to the...

  18. Activation of protein kinase C delta following cerebral ischemia leads to release of cytochrome C from the mitochondria via bad pathway.

    Directory of Open Access Journals (Sweden)

    Kunjan R Dave

    Full Text Available BACKGROUND: The release of cytochrome c from the mitochondria following cerebral ischemia is a key event leading to cell death. The goal of the present study was to determine the mechanisms involved in post-ischemic activation of protein kinase c delta (δPKC that lead to cytochrome c release. METHODS/FINDINGS: We used a rat model of cardiac arrest as an in vivo model, and an in vitro analog, oxygen glucose deprivation (OGD in rat hippocampal synaptosomes. Cardiac arrest triggered translocation of δPKC to the mitochondrial fraction at 1 h reperfusion. In synaptosomes, the peptide inhibitor of δPKC blocked OGD-induced translocation to the mitochondria. We tested two potential pathways by which δPKC activation could lead to cytochrome c release: phosphorylation of phospholipid scramblase-3 (PLSCR3 and/or protein phosphatase 2A (PP2A. Cardiac arrest increased levels of phosphorlyated PLSCR3; however, inhibition of δPKC translocation failed to affect the OGD-induced increase in PLSCR3 in synaptosomal mitochondria suggesting the post-ischemic phosphorylation of PLSCR3 is not mediated by δPKC. Inhibition of either δPKC or PP2A decreased cytochrome c release from synaptosomal mitochondria. Cardiac arrest results in the dephosphorylation of Bad and Bax, both downstream targets of PP2A promoting apoptosis. Inhibition of δPKC or PP2A prevented OGD-induced Bad, but not Bax, dephosphorylation. To complement these studies, we used proteomics to identify novel mitochondrial substrates of δPKC. CONCLUSIONS: We conclude that δPKC initiates cytochrome c release via phosphorylation of PP2A and subsequent dephosphorylation of Bad and identified δPKC, PP2A and additional mitochondrial proteins as potential therapeutic targets for ischemic neuroprotection.

  19. Pattern Recognition-Assisted Infrared Library Searching of the Paint Data Query Database to Enhance Lead Information from Automotive Paint Trace Evidence.

    Science.gov (United States)

    Lavine, Barry K; White, Collin G; Allen, Matthew D; Weakley, Andrew

    2017-03-01

    Multilayered automotive paint fragments, which are one of the most complex materials encountered in the forensic science laboratory, provide crucial links in criminal investigations and prosecutions. To determine the origin of these paint fragments, forensic automotive paint examiners have turned to the paint data query (PDQ) database, which allows the forensic examiner to compare the layer sequence and color, texture, and composition of the sample to paint systems of the original equipment manufacturer (OEM). However, modern automotive paints have a thin color coat and this layer on a microscopic fragment is often too thin to obtain accurate chemical and topcoat color information. A search engine has been developed for the infrared (IR) spectral libraries of the PDQ database in an effort to improve discrimination capability and permit quantification of discrimination power for OEM automotive paint comparisons. The similarity of IR spectra of the corresponding layers of various records for original finishes in the PDQ database often results in poor discrimination using commercial library search algorithms. A pattern recognition approach employing pre-filters and a cross-correlation library search algorithm that performs both a forward and backward search has been used to significantly improve the discrimination of IR spectra in the PDQ database and thus improve the accuracy of the search. This improvement permits inter-comparison of OEM automotive paint layer systems using the IR spectra alone. Such information can serve to quantify the discrimination power of the original automotive paint encountered in casework and further efforts to succinctly communicate trace evidence to the courts.

  20. Leveraging multi-generational workforce values in interactive information societies

    Directory of Open Access Journals (Sweden)

    Sophie van der Walt

    2010-08-01

    Full Text Available Background: The success of organisations relies on various factors including the ability of its multi-generational workforce to collaborate within the interactive information society. By developing an awareness of the different values of a diverse workforce, organisations may benefit from diversity. Various diversity factors, such as ethnicity, age and gender, impact on the way people interact, especially in the interactive information society.Objectives: This article advocates the need for generational awareness and addresses how this awareness presents benefits to companies, such as, increased productivity, improved succession planning policies and strategies to recruit and retain a diverse workforce. The research problem is directed at how diversity management influences Traditionalists, Baby Boomers, Generation X and Generation Y in terms of their work performance and co-worker relationships.Method: The research design combines Critical Theory and Generational Theory within the mixed-method paradigm. The sequential exploratory design was decided upon as it studies the unknown relationships between different generations of employees. The literature review was followed by a quantitative empirical research component and data was collected by means of a questionnaire. Results: The findings highlight specific differences between generations regarding their perspectives on work values and co-worker relationships, rewards, work-life balance and retirement.Conclusion: The article concludes with recommendations on the role diversity management plays in terms of work performance and co-worker relationships. By leveraging generational awareness in the interactive information society organizations with a multi-generational workforce will succeed in the competitive business environment.

  1. 75 FR 27791 - Agency Information Collection Activities; Proposed Collection; Comment Request; Invitation to...

    Science.gov (United States)

    2010-05-18

    ... caregivers-- will have continuous access to home use labeling information and instructions for use to help... . The digital certificate binds together the owner's name and a pair of electronic keys (a public and...

  2. Photochemical vapor generation of lead for inductively coupled plasma mass spectrometric detection

    Science.gov (United States)

    Duan, Hualing; Zhang, Ningning; Gong, Zhenbin; Li, Weifeng; Hang, Wei

    2016-06-01

    Photochemical vapor generation (PCVG) of lead was successfully achieved with a simplified and convenient system, in which only low molecular weight organic acid and a high-efficiency photochemical reactor were needed. The reactor was used to generate lead volatile species when a solution of lead containing a small amount of low molecular weight organic acid was pumped through. Several factors, including the concentration of acetic acid, the concentration of hydrochloride acid, and the irradiation time of UV light were optimized. Under the optimal conditions, including the addition of 0.90% (v/v) acetic acid and 0.03% (v/v) hydrochloride acid, and irradiation time of 28 s, intense and repeatable signal of lead volatile species was successfully obtained and identified with inductively coupled plasma mass spectrometry (ICPMS). In addition, the effects from inorganic anions and transition metal ions, including Cl-, NO3-, SO42 -, Cu2 +, Fe3 +, Co2 + and Ni2 +, were investigated, which suggests that their suppression to the PCVG of lead was in the order of Cl- anions and Ni2 +, Co2 + < Fe3 + < Cu2 + for transition metal ions. Under optimized conditions, relative standard derivation (RSD) of 4.4% was achieved from replicate measurements (n = 5) of a standard solution of 0.1 μg L- 1 lead. And, the limit of quantitation (LOQ, 10σ) of 0.012 μg L- 1 lead was obtained using this method and the method blank could be easily controlled down to 0.023 μg L- 1. To validate applicability of this method, it was also employed for the determination of lead in tap water, rain water and lake water.

  3. ONTOGRABBING: Extracting Information from Texts Using Generative Ontologies

    DEFF Research Database (Denmark)

    Nilsson, Jørgen Fischer; Szymczak, Bartlomiej Antoni; Jensen, P.A.

    2009-01-01

    We describe principles for extracting information from texts using a so-called generative ontology in combination with syntactic analysis. Generative ontologies are introduced as semantic domains for natural language phrases. Generative ontologies extend ordinary finite ontologies with rules...... for producing recursively shaped terms representing the ontological content (ontological semantics) of NL noun phrases and other phrases. We focus here on achieving a robust, often only partial, ontology-driven parsing of and ascription of semantics to a sentence in the text corpus. The aim of the ontological...

  4. Lead time TTO: leading to better health state valuations?

    Science.gov (United States)

    Attema, Arthur E; Versteegh, Matthijs M; Oppe, Mark; Brouwer, Werner B F; Stolk, Elly A

    2013-04-01

    Preference elicitation tasks for better than dead (BTD) and worse than dead (WTD) health states vary in the conventional time trade-off (TTO) procedure, casting doubt on uniformity of scale. 'Lead time TTO' (LT-TTO) was recently introduced to overcome the problem. We tested different specifications of LT-TTO in comparison with TTO in a within-subject design. We elicited preferences for six health states and employed an intertemporal ranking task as a benchmark to test the validity of the two methods. We also tested constant proportional trade-offs (CPTO), while correcting for discounting, and the effect of extending the lead time if a health state is considered substantially WTD. LT-TTO produced lower values for BTD states and higher values for WTD states. The validity of CPTO varied across tasks, but it was higher for LT-TTO than for TTO. Results indicate that the ratio of lead time to disease time has a greater impact on results than the total duration of the time frame. The intertemporal ranking task could not discriminate between TTO and LT-TTO.

  5. Inhibition of Stat3 activation suppresses caspase-3 and the ubiquitin-proteasome system, leading to preservation of muscle mass in cancer cachexia.

    Science.gov (United States)

    Silva, Kleiton Augusto Santos; Dong, Jiangling; Dong, Yanjun; Dong, Yanlan; Schor, Nestor; Tweardy, David J; Zhang, Liping; Mitch, William E

    2015-04-24

    Cachexia occurs in patients with advanced cancers. Despite the adverse clinical impact of cancer-induced muscle wasting, pathways causing cachexia are controversial, and clinically reliable therapies are not available. A trigger of muscle protein loss is the Jak/Stat pathway, and indeed, we found that conditioned medium from C26 colon carcinoma (C26) or Lewis lung carcinoma cells activates Stat3 (p-Stat3) in C2C12 myotubes. We identified two proteolytic pathways that are activated in muscle by p-Stat3; one is activation of caspase-3, and the other is p-Stat3 to myostatin, MAFbx/Atrogin-1, and MuRF-1 via CAAT/enhancer-binding protein δ (C/EBPδ). Using sequential deletions of the caspase-3 promoter and CHIP assays, we determined that Stat3 activation increases caspase-3 expression in C2C12 cells. Caspase-3 expression and proteolytic activity were stimulated by p-Stat3 in muscles of tumor-bearing mice. In mice with cachexia caused by Lewis lung carcinoma or C26 tumors, knock-out of p-Stat3 in muscle or with a small chemical inhibitor of p-Stat3 suppressed muscle mass losses, improved protein synthesis and degradation in muscle, and increased body weight and grip strength. Activation of p-Stat3 stimulates a pathway from C/EBPδ to myostatin and expression of MAFbx/Atrogin-1 and increases the ubiquitin-proteasome system. Indeed, C/EBPδ KO decreases the expression of MAFbx/Atrogin-1 and myostatin, while increasing muscle mass and grip strength. In conclusion, cancer stimulates p-Stat3 in muscle, activating protein loss by stimulating caspase-3, myostatin, and the ubiquitin-proteasome system. These results could lead to novel strategies for preventing cancer-induced muscle wasting.

  6. Prion proteins leading to neurodegeneration.

    Science.gov (United States)

    La Mendola, D; Mendola, D L; Pietropaolo, A; Pappalardo, G; Zannoni, C; Rizzarelli, E

    2008-12-01

    Prion diseases are fatal neurodegenerative disorders related to the conformational alteration of the prion protein (PrP C) into a pathogenic and protease-resistant isoform PrP(Sc). PrP(C) is a cell surface glycoprotein expressed mainly in the central nervous system and despite numerous efforts to elucidate its physiological role, the exact biological function remains unknown. Many lines of evidences indicate that prion is a copper binding protein and thus involved in the copper metabolism. Prion protein is not expressed only in mammals but also in other species such as birds, reptiles and fishes. However, it is noteworthy to point out that prion diseases are only observed in mammals while they seem to be spared to other species. The chicken prion protein (chPrP C) shares about 30% of identity in its primary sequence with mammal PrP C. Both types of proteins have an N-terminal domain endowed with tandem amino acid repeats (PHNPGY in the avian protein, PHGGGWQ in mammals), followed by a highly conserved hydrophobic core. Furthermore, NMR studies have highlighted a similar globular domain containing three alpha-helices, one short 3(10)-helix and a short antiparallel beta-sheet. Despite this structural similarity, it should be noted that the normal isoform of mammalian PrP C is totally degraded by proteinase K, while avian PrP C is not, thereby producing N-terminal domain peptide fragments stable to further proteolysis. Notably, the hexarepeat domain is considered essential for protein endocytosis, and it is supposed to be the analogous copper-binding octarepeat region of mammalian prion proteins. The number of copper binding sites, the affinity and the coordination environment of metal ions are still matter of discussion for both mammal and avian proteins. In this review, we summarize the similarities and the differences between mammalian and avian prion proteins, as revealed by studies carried out on the entire protein and related peptide fragments, using a range of

  7. Time-dependent complete-active-space self-consistent-field method for atoms: Application to high-harmonic generation

    CERN Document Server

    Sato, Takeshi; Brezinova, Iva; Lackner, Fabian; Nagele, Stefan; Burgdorfer, Joachim

    2016-01-01

    We present the numerical implementation of the time-dependent complete-active-space self-consistent-field (TD-CASSCF) method [Phys. Rev. A, 88, 023402 (2013)] for atoms driven by a strong linearly polarized laser pulse. The present implementation treats the problem in its full dimensionality and introduces a gauge-invariant frozen-core approximation, an efficient evaluation of the Coulomb mean field scaling linearly with the number of basis functions, and a split-operator method specifically designed for stable propagation of stiff spatial derivative operators. We apply this method to high-harmonic generation in helium, beryllium, and neon and explore the role of electron correlations.

  8. 75 FR 35454 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-06-22

    ... Request; Aerospace Manufacturing and Rework Industry Information Request Questionnaire; EPA ICR Number... and rework facilities. The North American Industrial Classification Codes (NAICS) associated with this... manufacturing and rework facilities and has been tailored to the processes at aerospace facilities....

  9. 78 FR 75356 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-12-11

    ... research and resources devoted to autism spectrum disorders (ASD) and other developmental disabilities (DD... (LEND) training programs with forty-three grantees; Developmental Behavioral Pediatrics (DBP) training...: December 5, 2013. Bahar Niakan, Director, Division of Policy and Information Coordination. BILLING...

  10. 75 FR 76979 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-12-10

    ... to collect capital investment need information from community water systems serving more than 3,300... capital investment or operations and maintenance costs. Changes in the Estimates: There is no...

  11. Genome-wide survey of yeast mutations leading to activation of the yeast cell integrity MAPK pathway: Novel insights into diverse MAPK outcomes

    Directory of Open Access Journals (Sweden)

    Arias Patricia

    2011-08-01

    Full Text Available Abstract Background The yeast cell wall integrity mitogen-activated protein kinase (CWI-MAPK pathway is the main regulator of adaptation responses to cell wall stress in yeast. Here, we adopt a genomic approach to shed light on two aspects that are only partially understood, namely, the characterization of the gene functional catalog associated with CWI pathway activation and the extent to which MAPK activation correlates with transcriptional outcomes. Results A systematic yeast mutant deletion library was screened for constitutive transcriptional activation of the CWI-related reporter gene MLP1. Monitoring phospho-Slt2/Mpk1 levels in the identified mutants revealed sixty-four deletants with high levels of phosphorylation of this MAPK, including mainly genes related to cell wall construction and morphogenesis, signaling, and those with unknown function. Phenotypic analysis of the last group of mutants suggests their involvement in cell wall homeostasis. A good correlation between levels of Slt2 phosphorylation and the magnitude of the transcriptional response was found in most cases. However, the expression of CWI pathway-related genes was enhanced in some mutants in the absence of significant Slt2 phosphorylation, despite the fact that functional MAPK signaling through the pathway was required. CWI pathway activation was associated to increased deposition of chitin in the cell wall - a known survival compensatory mechanism - in about 30% of the mutants identified. Conclusion We provide new insights into yeast genes related to the CWI pathway and into how the state of activation of the Slt2 MAPK leads to different outcomes, discovering the versatility of this kind of signaling pathways. These findings potentially have broad implications for understanding the functioning of other eukaryotic MAPKs.

  12. Lessons learned from four years of actively using River Forecast Center Ensemble Streamflow Predictions to inform reservoir management

    Science.gov (United States)

    Polebitski, A.; Palmer, R.; Meaker, B.

    2012-12-01

    The National Weather Service's River Forecast Centers (RFCs), located throughout the US, produce operational streamflow forecasts for short term application and long-term lead forecasts at selected locations. These forecasts are targeted for a variety of users, including water supply management, flood control, hydropower production, navigation, and recreation. This presentation highlights the challenges and successes associated with the use of RFC produced ensemble streamflow predictions (ESP) in generating system operations forecasts over the past four years for Snohomish County Public Utility District #1's (SnoPUD) Henry Jackson hydropower system. This research documents a multiyear collaboration between SnoPUD and academic researchers. The collaboration began with a proof of concept study in 2007 and evolved into a weekly decision support activity that has been ongoing since 2008 ( documented in Alemu et al. 2010). The Alemu et al. paper demonstrates the usefulness of ESP forecasts in hydropower operations decision making. This paper focuses on the value of forecasts and a decision support system (DSS) in improving skills in operating reservoir systems. During the application period, the model provided weekly guidance on meeting operational objectives and a probabilistic approach to quantifying system vulnerability during critical periods such as floods and drought. The ESP forecasts and the DSS were heavily used during periods of uncertainty and less so during periods of high system constraint or low system risk.

  13. Comprehensive program and plan for federal energy education, extension, and information activities: Fiscal Year 1981. Fifth report to congress

    Energy Technology Data Exchange (ETDEWEB)

    1981-12-01

    The activities conducted solely in Fiscal Year (FY) 1981 in the areas of Federal energy education, extension service, and information dissemination are reported. The broad purpose of the FY 1981 activities addressed has been to inform governmental and private sectors about the methods and technologies to conserve energy and to utilize renewable energy sources. With the increase in awareness on the part of energy users and decisionmakers, as well as additional information sources available from the private sector, the emphasis of the various Federal energy information activities is being focused on reporting results of Federal programs. The course of activities related to conservation and renewable energy information has been one of consolidation, both in terms of programmatic substance and methods. The practical impetus has been the redirection of Federal progrms and related budgetary revisions for FY 1981 and FY 1982. Further, products conveying information on conservation and renewable energy technologies have been examined extensively, pursuant to the Administration's directive in April 1981 on elimination of wasteful spending on periodicals, audiovisuals and similar materials. Efforts in coordination of conservation and renewable energy information activities of the Department of Energy (DOE) as well as other Federal agencies have adjusted to timetables for review and redirection of programs initially planned for FY 1981. Mechanisms to coordinate existing Federal energy information activities employed in previous fiscal years were continued in FY 1981 to the extent applicable under current Administration policy and the above-noted circumstances of redirection. Coordinating actions requiring convening of groups were held in abeyance pending resolution of programmatic issues.

  14. Activities of information retrieval in Daicel Corporation : The roles and efforts of information retrieval team

    Science.gov (United States)

    Yamazaki, Towako

    In order to stabilize and improve quality of information retrieval service, the information retrieval team of Daicel Corporation has given some efforts on standard operating procedures, interview sheet for information retrieval, structured format for search report, and search expressions for some technological fields of Daicel. These activities and efforts will also lead to skill sharing and skill tradition between searchers. In addition, skill improvements are needed not only for a searcher individually, but also for the information retrieval team totally when playing searcher's new roles.

  15. Twitter as a Teaching Practice to Enhance Active and Informal Learning in Higher Education: The Case of Sustainable Tweets

    Science.gov (United States)

    Kassens-Noor, Eva

    2012-01-01

    With the rise of Web 2.0, a multitude of new possibilities on how to use these online technologies for active learning has intrigued researchers. While most instructors have used Twitter for in-class discussions, this study explores the teaching practice of Twitter as an active, informal, outside-of-class learning tool. Through a comparative…

  16. Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles.

    Science.gov (United States)

    Tonkin, Daniel R; Whitmore, Alan; Johnston, Robert E; Barro, Mario

    2012-06-22

    Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells. VRP preferentially infected these inflammatory DCs as well as classical DCs and macrophages, with less efficient infection of other cell types. DC depletion suggested that the interaction of VRP with classical DCs was required for recruitment of inflammatory DCs, induction of high levels of many cytokines, and for stable transport of VRP to the draining lymph node. Additionally, in vitro-infected DCs enhanced antigen-specific responses by CD4 and CD8 T cells. By transfer of VRP-infected DCs into mice we showed that these DCs generated an inflammatory state in the draining lymph node similar to that achieved by VRP injection. Most importantly, VRP-infected DCs were sufficient to establish robust adjuvant activity in mice comparable to that produced by VRP injection. These findings indicate that VRP infect, recruit and activate both classical and inflammatory DCs, and those DCs become mediators of the VRP adjuvant activity.

  17. An improved model for fragment-based lead generation at AstraZeneca.

    Science.gov (United States)

    Fuller, Nathan; Spadola, Loredana; Cowen, Scott; Patel, Joe; Schönherr, Heike; Cao, Qing; McKenzie, Andrew; Edfeldt, Fredrik; Rabow, Al; Goodnow, Robert

    2016-08-01

    Modest success rates in fragment-based lead generation (FBLG) projects at AstraZeneca (AZ) prompted operational changes to improve performance. In this review, we summarize these changes, emphasizing the construction and composition of the AZ fragment library, screening practices and working model. We describe the profiles of the screening method for specific fragment subsets and statistically assess our ability to follow up on fragment hits through near-neighbor selection. Performance analysis of our second-generation fragment library (FL2) in screening campaigns illustrates the complementary nature of flat and 3D fragments in exploring protein-binding pockets and highlights our ability to deliver fragment hits using multiple screening techniques for various target classes. The new model has had profound impact on the successful delivery of lead series to drug discovery projects.

  18. Effect of Lead (Pb Exposure on the Activity of Superoxide Dismutase and Catalase in Battery Manufacturing Workers (BMW of Western Maharashtra (India with Reference to Heme biosynthesis

    Directory of Open Access Journals (Sweden)

    Kusal K. Das

    2006-12-01

    Full Text Available The aim of this study was to estimate the activity of superoxide dismutase (SOD and catalase in erythrocytes and malondialdehyde (MDA in plasma of battery manufacturing workers (BMW of Western Maharashtra (India who were occupationally exposed to lead (Pb over a long period of time (about 15 years. This study was also aimed to determine the Pb intoxication resulted in a disturbance of heme biosynthesis in BMW group. The blood Pb level of BMW group (n = 28 was found to be in the range of 25.8 – 78.0 μg/dL (mean + SD, 53.63 + 16.98 whereas in Pb unexposed control group (n = 35 the range was 2.8 – 22.0 μg/dL (mean + SD, 12.52 + 4.08. The blood level (Pb-B and urinary lead level (Pb-U were significantly increased in BMW group as compared to unexposed control. Though activated d- aminolevulinic acid dehydratase (ALAD activities in BMW group did not show any significant change when compared to control group but activated / non activated erythrocyte – ALAD activities in BMW group showed a significant increase. Erythrocyte- zinc protoporphyrin (ZPP, urinary daminolevulinic acid (ALA-U and porphobilinogen (PBG-U of BMW groups elevated significantly as compared to control. A positive correlation (r = 0.66, p 1.0 were observed in control group. Hematological study revealed a significant decrease of hemoglobin concentration, packed cell volume (% and other blood indices and a significant increase of total leucocytes count in BMW group in comparison to control group. The serum MDA content was significantly increased (p< 0.001 and the activities of antioxidant enzymes such as erythrocyte- SOD (p< 0.001 and erythrocytecatalase (p< 0.001 were significantly reduced in BMW group as compared to control group. A positive correlation (r = 0.45, p<0.02 between Pb-B and serum MDA level was observed in BMW group (Pb-B range 25.8 – 78.0 μg / dL but such significant correlation did not notice in

  19. Generation of optical coherent state superpositions for quantum information processing

    DEFF Research Database (Denmark)

    Tipsmark, Anders

    2012-01-01

    I dette projektarbejde med titlen “Generation of optical coherent state superpositions for quantum information processing” har målet været at generere optiske kat-tilstande. Dette er en kvantemekanisk superpositions tilstand af to koherente tilstande med stor amplitude. Sådan en tilstand er...

  20. Fragment-based designing for the generation of novel leads against BACE1.

    Science.gov (United States)

    Das, Sucharita; Chakraborty, Sandipan; Basu, Soumalee

    2015-01-01

    BACE1, the aspartate protease that generates amyloid-β peptide (Aβ) in the brain of AD (Alzheimer's disease) patients, has emerged as a pharmaceutically relevant target. Here, a fragment-based in silico approach has been adopted to design novel compounds with increased ligand efficiency for BACE1, before screening for brain permeability and toxicity. Fragments docked to the active site of BACE1 and sorted into two groups using binding energy cut-off, were joined to create novel ligands with binding energy lying in the range between -11.36 kcal/mol and -8.56 kcal/mol. Interestingly, QIN, a known inhibitor of BACE1 with an IC50 of 11nM, when docked to BACE1, shows a binding energy (-9.43 kcal/mol) lying within the range of the novel ligand-BACE1 complexes. The present strategy thus enabled the design of four novel inhibitors of BACE1 with favourable binding energy, brain permeability and no toxicity that might show promise as leads in future.

  1. Fragment Screening of Soluble Epoxide Hydrolase for Lead Generation-Structure-Based Hit Evaluation and Chemistry Exploration.

    Science.gov (United States)

    Xue, Yafeng; Olsson, Thomas; Johansson, Carina A; Öster, Linda; Beisel, Hans-Georg; Rohman, Mattias; Karis, David; Bäckström, Stefan

    2016-03-04

    Soluble epoxide hydrolase (sEH) is involved in the regulation of many biological processes by metabolizing the key bioactive lipid mediator, epoxyeicosatrienoic acids. For the development of sEH inhibitors with improved physicochemical properties, we performed both a fragment screening and a high-throughput screening aiming at an integrated hit evaluation and lead generation. Followed by a joint dose-response analysis to confirm the hits, the identified actives were then effectively triaged by a structure-based hit-classification approach to three prioritized series. Two distinct scaffolds were identified as tractable starting points for potential lead chemistry work. The oxoindoline series bind at the right-hand side of the active-site pocket with hydrogen bonds to the protein. The 2-phenylbenzimidazole-4-sulfonamide series bind at the central channel with significant induced fit, which has not been previously reported. On the basis of the encouraging initial results, we envision that a new lead series with improved properties could be generated if a vector is found that could merge the cyclohexyl functionality of the oxoindoline series with the trifluoromethyl moiety of the 2-phenylbenzimidazole-4-sulfonamide series.

  2. Zinc-induced modulation of SRSF6 activity alters Bim splicing to promote generation of the most potent apoptotic isoform BimS.

    Science.gov (United States)

    Hara, Hirokazu; Takeda, Tatsuya; Yamamoto, Nozomi; Furuya, Keisuke; Hirose, Kazuya; Kamiya, Tetsuro; Adachi, Tetsuo

    2013-07-01

    Bim is a member of the pro-apoptotic BH3-only Bcl-2 family of proteins. Bim gene undergoes alternative splicing to produce three predominant splicing variants (BimEL, BimL and BimS). The smallest variant BimS is the most potent inducer of apoptosis. Zinc (Zn(2+)) has been reported to stimulate apoptosis in various cell types. In this study, we examined whether Zn(2+) affects the expression of Bim in human neuroblastoma SH-SY5Y cells. Zn(2+) triggered alterations in Bim splicing and induced preferential generation of BimS, but not BimEL and BimL, in a dose- and time-dependent manner. Other metals (cadmium, cobalt and copper) and stresses (oxidative, endoplasmic reticulum and genotoxic stresses) had little or no effect on the expression of BimS. To address the mechanism of Zn(2+)-induced preferential generation of BimS, which lacks exon 4, we developed a Bim mini-gene construct. Deletion analysis using the Bim mini-gene revealed that predicted binding sites of the SR protein SRSF6, also known as SRp55, are located in the intronic region adjacent to exon 4. We also found that mutations in the predicted SRSF6-binding sites abolished generation of BimS mRNA from the mutated Bim mini-gene. In addition, a UV cross-linking assay followed by Western blotting showed that SRSF6 directly bound to the predicted binding site and Zn(2+) suppressed this binding. Moreover, Zn(2+) stimulated SRSF6 hyper-phosphorylation. TG003, a cdc2-like kinase inhibitor, partially prevented Zn(2+)-induced generation of BimS and SRSF6 hyper-phosphorylation. Taken together, our findings suggest that Zn(2+) inhibits the activity of SRSF6 and promotes elimination of exon 4, leading to preferential generation of BimS.

  3. Incorporating Duration Information in Activity Recognition

    Science.gov (United States)

    Chaurasia, Priyanka; Scotney, Bryan; McClean, Sally; Zhang, Shuai; Nugent, Chris

    Activity recognition has become a key issue in smart home environments. The problem involves learning high level activities from low level sensor data. Activity recognition can depend on several variables; one such variable is duration of engagement with sensorised items or duration of intervals between sensor activations that can provide useful information about personal behaviour. In this paper a probabilistic learning algorithm is proposed that incorporates episode, time and duration information to determine inhabitant identity and the activity being undertaken from low level sensor data. Our results verify that incorporating duration information consistently improves the accuracy.

  4. Sustainability in the family home – which generation is leading the way?

    DEFF Research Database (Denmark)

    Grønhøj, Alice

    2014-01-01

    Family members note the choices and behaviour of each other, Alice Grønhøj explores which generation is leading environmentally-minded domestic behaviour......Family members note the choices and behaviour of each other, Alice Grønhøj explores which generation is leading environmentally-minded domestic behaviour...

  5. Method and apparatus for lead-unity-lag electric power generation system

    Science.gov (United States)

    Ganev, Evgeni (Inventor); Warr, William (Inventor); Salam, Mohamed (Arif) (Inventor)

    2013-01-01

    A method employing a lead-unity-lag adjustment on a power generation system is disclosed. The method may include calculating a unity power factor point and adjusting system parameters to shift a power factor angle to substantially match an operating power angle creating a new unity power factor point. The method may then define operation parameters for a high reactance permanent magnet machine based on the adjusted power level.

  6. Who Gets to Lead the Multinational Team?

    DEFF Research Database (Denmark)

    Paunova, Minna

    2016-01-01

    This article examines the emergence of informal leadership in multinational teams. Building on and extending status characteristics theory, the article proposes and tests a model that describes how global inequalities reproduce in multinational teams, and accounts for who gets to lead these teams...... of their core self-evaluations. A study of over 230 individuals from 46 nationalities working in 36 self-managing teams generally supports the expected main and moderation effects. Individual core self-evaluations enhance an otherwise weak effect of English proficiency, but compensate for low levels of national...

  7. Wittig Derivatization of Sesquiterpenoid Polygodial Leads to Cytostatic Agents with Activity Against Drug Resistant Cancer Cells and Capable of Pyrrolylation of Primary Amines

    Science.gov (United States)

    Dasari, Ramesh; De Carvalho, Annelise; Medellin, Derek C.; Middleton, Kelsey N.; Hague, Frédéric; Volmar, Marie N. M.; Frolova, Liliya V.; Rossato, Mateus F.; De La Chapa, Jorge J.; Dybdal-Hargreaves, Nicholas F.; Pillai, Akshita; Kälin, Roland E.; Mathieu, Véronique; Rogelj, Snezna; Gonzales, Cara B.; Calixto, João B.; Evidente, Antonio; Gautier, Mathieu; Munirathinam, Gnanasekar; Glass, Rainer; Burth, Patricia; Pelly, Stephen C.; van Otterlo, Willem A. L.; Kiss, Robert; Kornienko, Alexander

    2015-01-01

    Many types of cancer, including glioma, melanoma, non-small cell lung cancer (NSCLC), among others, are resistant to proapoptotic stimuli and thus poorly responsive to current therapies based on the induction of apoptosis in cancer cells. The current investigation describes the synthesis and anticancer evaluation of unique C12-Wittig derivatives of polygodial, a terpenenoid dialdehyde isolated from Persicaria hydropiper (L.) Delabre. These compounds were found to undergo an unprecedented pyrrole formation with primary amines in a chemical model system, a reaction that could be relevant in the biological environment and lead to the pyrrolation of lysine residues in the target proteins. The anticancer evaluation of these compounds revealed their promising activity against cancer cells displaying various forms of drug resistance, including resistance to proapoptotic agents. Mechanistic studies indicated that compared to the parent polygodial, which displays fixative general cytotoxic action against human cells, the C12-Wittig derivatives exerted their antiproliferative action mainly through cytostatic effects explaining their activity against apoptosis-resistant cancer cells. The possibility for an intriguing covalent modification of proteins through a novel pyrrole formation reaction, as well as useful activities against drug resistant cancer cells, make the described polygodial-derived chemical scaffold an interesting new chemotype warranting thorough investigation. PMID:26360047

  8. Verification of muscle fatigue detection capability of unipolar and bipolar lead systems using surface EMG generation model

    OpenAIRE

    堀田, 優; 小浦方, 裕騎; 伊藤, 建一; Hotta, Yu; Kourakata, Yuki; Ito, Kenichi

    2013-01-01

    In this study, we constructed a simulation model to generate a surface EMG during isometric exercise. The surface EMG was detected using both unipolar and bipolar lead systems, and the measurement performance of both systems was compared. When detecting surface EMGs using the unipolar lead system, low-frequency components were increased to a greater extent than in the bipolar lead system, suggesting that the unipolar lead system is more suitable for the detection of surface EMGs

  9. Effects of cadium, zinc and lead on soil enzyme activities

    Institute of Scientific and Technical Information of China (English)

    YANG Zhi-xin; LIU Shu-qing; ZHENG Da-wei; FENG Sheng-dong

    2006-01-01

    Heavy metal (HM) is a major hazard to the soil-plant system. This study investigated the combined effects of cadium (Cd),zinc (Zn) and lead (Pb) on activities of four enzymes in soil, including calatase, urease, invertase and alkalin phosphatase. HM content in tops of canola and four enzymes activities in soil were analyzed at two months after the metal additions to the soil. Pb was not significantly inhibitory than the other heavy metals for the four enzyme activities and was shown to have a protective role on calatase activity in the combined presence of Cd, Zn and Pb; whereas Cd significantly inhibited the four enzyme activities, and Zn only inhibited urease and calatase activities. The inhibiting effect of Cd and Zn on urease and calatase activities can be intensified significantly by the additions of Zn and Cd. There was a negative synergistic inhibitory effect of Cd and Zn on the two enzymes in the presence of Cd, Zn and Pb. The urease activity was inhibited more by the HM combinations than by the metals alone and reduced approximately 20%-40% of urease activity. The intertase and alkaline phosphatase activities significantly decreased only with the increase of Cd concentration in the soil. It was shown that urease was much more sensitive to HM than the other enzymes. There was a obvious negative correlation between the ionic impulsion of HM in soil, the ionic impulsion of HM in canola plants tops and urease activity. It is concluded that the soil urease activity may be a sensitive tool for assessing additive toxic combination effect on soil biochemical parameters.

  10. 78 FR 56241 - Agency Information Collection Activities:

    Science.gov (United States)

    2013-09-12

    ... SECURITY U.S. Citizenship and Immigration Services Agency Information Collection Activities: Notice of... submitting the following information collection request to the Office of Management and Budget (OMB) for review and clearance in accordance with the Paperwork Reduction Act of 1995. The information...

  11. 78 FR 3968 - Information Collection Activities

    Science.gov (United States)

    2013-01-17

    ... Surface Transportation Board Information Collection Activities AGENCY: Surface Transportation Board, DOT... quality, utility, and clarity of the information collected; and (4) ways to minimize the burden of the collection of information on the respondents, including the use of automated collection techniques or...

  12. 75 FR 26268 - Agency Information Collection Activities: Permit To Transfer Containers to a Container Station

    Science.gov (United States)

    2010-05-11

    ... Containers to a Container Station AGENCY: U.S. Customs and Border Protection, Department of Homeland Security... concerning the: Permit to Transfer Containers to a Container Station. This request for comment is being made... Containers to a Container Station. OMB Number: 1651-0049. Form Number: None. Abstract: This...

  13. INFORMATION SUPPORT OF ANTITERRORIST ACTIVITY

    Directory of Open Access Journals (Sweden)

    Arthur Muradinovich Shamaev

    2015-01-01

    Full Text Available The article discusses the possibilities and the problematic issues of the information support of anti-terrorist activities. Among the main measures are called: PRsupport of speeches by leaders and officials of the state executive authorities, prosecutors, law enforcement agencies in the media; countering terrorism and extremism in the information space; press conferences, round tables and conferences on anti-terrorist and antiextremist topics; utilization of social advertising; monitoring of Internet resources to the development of the social networks of anti-terrorist direction.Terrorism can not be regarded as a problem of a single country. International and domestic experience in combating these phenomena indicates failure only of force feedback, which at any stage of the problem only to show the ability of temporal localization of specific threats and prevent individual acts of terrorism without affecting the situation as a whole.Terrorist offenses, is widespread in modern society is a complex system of balances is included in the set of complementary processes. These processes are not only, as is commonly believed, criminal and economic background, although any even minor manifestations of a terrorist nature no doubt be regarded as an attack on the security of society and the state.

  14. Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Breuker, C; Amouzou, C

    2014-01-01

    with palmitate, a saturated free fatty acid (FFA) known to induce inflammation and oxidative stress via TLR4 activation. While RNase L and RLI levels remained unchanged, OAS level was decreased in primary myotubes from insulin-resistant obese subjects (OB-IR) compared with myotubes from insulin-sensitive obese......Obesity is associated with chronic low-grade inflammation and oxidative stress that blunt insulin response in its target tissues, leading to insulin resistance (IR). IR is a characteristic feature of type 2 diabetes. Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake......; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Interestingly, some obese people stay insulin-sensitive and metabolically healthy. With the aim of understanding this difference and identifying the mechanisms responsible for insulin sensitivity maintenance...

  15. 78 FR 8699 - Pipeline Safety: Information Collection Activities, Revision to Annual Report for Hazardous...

    Science.gov (United States)

    2013-02-06

    .... PHMSA proposes to additionally collect information in PART D ``Miles of Steel Pipe by Corrosion Protection'' and PART E ``Miles of Electric Resistance Welded (ERW) Pipe'' by state. PHMSA believes that most... Request: Revision. Abstract: To ensure adequate public protection from exposure to potential...

  16. 78 FR 55280 - Agency Information Collection Activities: Distribution of Continued Dumping and Subsidy Offset to...

    Science.gov (United States)

    2013-09-10

    ... Continued Dumping and Subsidy Offset to Affected Domestic Producers AGENCY: U.S. Customs and Border...: Distribution of Continued Dumping and Subsidy Offset to Affected Domestic Producers (ADPs). This is a proposed... forms of information. Title: Distribution of Continued Dumping and Subsidy Offset to Affected...

  17. 76 FR 76159 - Agency Information Collection Activities; Proposed Collection; Comment Request; Revisions to the...

    Science.gov (United States)

    2011-12-06

    ... announces that EPA is planning to submit a request to the Office of Management and Budget (OMB) to renew an existing approved Information Collection Request (ICR) concerning the definition of Solid Waste. This ICR... RCRA Definition of Solid Waste AGENCY: Environmental Protection Agency (EPA). ACTION: Notice....

  18. Next-to-leading order corrections to the valon model

    Indian Academy of Sciences (India)

    G R Bouroun; E Esfandyari

    2016-01-01

    A seminumerical solution to the valon model at next-to-leading order (NLO) in the Laguerre polynomials is presented. We used the valon model to generate the structure of proton with respect to the Laguerre polynomials method. The results are compared with H1 data and other parametrizations.

  19. 77 FR 65018 - Agency Information Collection Activities: Submission to OMB for Revision to a Currently Approved...

    Science.gov (United States)

    2012-10-24

    ... Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995 (Pub. L. 104... board members. Additionally, NCUA is planning to add a question to the Regulatory section of the Profile... modified loans and target data collection efforts on loans meeting the definition of a troubled...

  20. 77 FR 31400 - Agency Information Collection Activities: Submission to OMB for Revision to a Currently Approved...

    Science.gov (United States)

    2012-05-25

    ... Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995 (Pub. L. 104... board members. Additionally, NCUA is planning to add a question to the Regulatory section of the Profile... modified loans and target data collection efforts on loans meeting the definition of a troubled...