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. Providing clinicians with information on laboratory test costs leads to ...

    African Journals Online (AJOL)

    Providing clinicians with information on laboratory test costs leads to ... Log in or Register to get access to full text downloads. ... For the intervention and control groups, pre- and postintervention cost and days in hospital were estimated.

  4. 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.

  5. Activation of electrophilicity of stable Y-delocalized carbamate cations in intramolecular aromatic substitution reaction: evidence for formation of diprotonated carbamates leading to generation of isocyanates.

    Science.gov (United States)

    Kurouchi, Hiroaki; Kawamoto, Kyoko; Sugimoto, Hiromichi; Nakamura, Satoshi; Otani, Yuko; Ohwada, Tomohiko

    2012-10-19

    Although cations with three heteroatoms, such as monoprotonated guanidine and urea, are stabilized by Y-shaped conjugation and such Y-conjugated cations are sufficiently basic to be further protonated (or protosolvated) to dications in strongly acid media, only O-monoprotonated species have been detected in the case of carbamates even in magic acid. We found that the trifluoromethanesulfonic acid-catalyzed cyclization of arylethylcarbamates proceeds to afford dihydroisoquinolones in high yield. In strong acids, methyl carbamates are fully O-monoprotonated, and these monocations do not undergo cyclization even under heating. But, as the acidity of the reaction medium is further increased, the cyclization reaction of methyl phenethylcarbamates starts to proceed as a first-order reaction, with a linear relationship between rate and acidity. The sign and magnitude of the entropy of activation ΔS(‡) were found to be similar to those of other A(Ac)1 reactions. These results strongly support the idea that further protonation of the O-protonated carbamates is involved in the cyclization, but the concentration of the dications is very low and suggests that the rate-determining step is dissociation of methanol from the diprotonated carbamate to generate protonated isocyanate, which reacts with the aromatic ring. Therefore, O-protonated carbamates are weak bases in sharp contrast to other Y-shaped monocations.

  6. 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...

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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,…

  13. 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

  14. Generativity as a Route to Active Ageing

    Directory of Open Access Journals (Sweden)

    Andreas Kruse

    2012-01-01

    Full Text Available We elucidate the significance of active ageing from an individual as well as from a societal perspective. Taking an individual perspective, maintaining activity in later years is linked to successful ageing because of empirical relationships to positive self-perception, satisfaction with life, and development of competences, whereas from a societal perspective, active ageing implies usage of older people’s life competences as a human capital of society—a societal imperative, particularly in times of demographic change but also more basically substantiated in an ethics of responsibility, intergenerational solidarity, and generation equity. We focus on the psychological construct of generativity which is interpreted as an aspect of the philosophical-anthropological category of joint responsibility. Our own research in Mexico and the Baltic States supports the notion that maintaining access to the public sphere and active engagement for others is a more basic individual concern than a life-stages specific developmental task. We report background and results of a Dialogue Forum Project Funding, a research cooperation between our institute and the Foundation Remembrance, Responsibility, and Future aimed to improve generativity in Belarus, Russia, and Ukraine by implementing and supporting local initiatives offering opportunities for intergenerational dialogue.

  15. 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.

  16. 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.

  17. 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.

  18. Privileged scaffolds in lead generation.

    Science.gov (United States)

    Zhao, Hongyu; Dietrich, Justin

    2015-07-01

    The term "privileged scaffold" was coined in 1988 and the strategy was to construct high-affinity ligands from core structures that can bind more than one receptor. Since then, the privileged scaffold-based design has evolved from a stand-alone technology to an integral component of various lead generation platforms. In this review, the authors discuss the applications of the privileged scaffold concept in current lead generation. Specifically, the authors cover the role that privileged scaffolds have played in the mass production of compounds to feed high-throughput screening (HTS) and its role in the design of ligands targeting protein-protein interactions, multiple ligands and warhead-based ligands. It is not the intention of the authors to review all privileged scaffolds known to date. Rather, the aim of this review is to highlight the strategic value of the concept of privileged scaffolds in various contemporary lead generation platforms. The privileged scaffolds as described by the original definition proved abundant in the available chemical space. HTS and other screening methods, in addition to greatly enhanced compound collections, make privileged scaffold-based design less relevant in finding high-affinity ligands than originally envisioned. However, the principle of privileged scaffolds has greatly enhanced and empowered current lead generation technologies.

  19. 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

  20. Generating all two-MOS-transistor amplifiers leads to new wide-band LNAs

    NARCIS (Netherlands)

    Bruccoleri, F.; Klumperink, Eric A.M.; Nauta, Bram

    This paper presents a methodology that systematically generates all 2-MOS-transistor wide-band amplifiers, assuming that MOSFET is exploited as a voltage-controlled current source. This leads to new circuits. Their gain and noise factor have been compared to well-known wide-band amplifiers. One of

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.)

  7. 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.

  8. 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)

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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)).

  1. 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)

  2. 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

  3. Gene Ontology synonym generation rules lead to increased performance in biomedical concept recognition.

    Science.gov (United States)

    Funk, Christopher S; Cohen, K Bretonnel; Hunter, Lawrence E; Verspoor, Karin M

    2016-09-09

    Gene Ontology (GO) terms represent the standard for annotation and representation of molecular functions, biological processes and cellular compartments, but a large gap exists between the way concepts are represented in the ontology and how they are expressed in natural language text. The construction of highly specific GO terms is formulaic, consisting of parts and pieces from more simple terms. We present two different types of manually generated rules to help capture the variation of how GO terms can appear in natural language text. The first set of rules takes into account the compositional nature of GO and recursively decomposes the terms into their smallest constituent parts. The second set of rules generates derivational variations of these smaller terms and compositionally combines all generated variants to form the original term. By applying both types of rules, new synonyms are generated for two-thirds of all GO terms and an increase in F-measure performance for recognition of GO on the CRAFT corpus from 0.498 to 0.636 is observed. Additionally, we evaluated the combination of both types of rules over one million full text documents from Elsevier; manual validation and error analysis show we are able to recognize GO concepts with reasonable accuracy (88 %) based on random sampling of annotations. In this work we present a set of simple synonym generation rules that utilize the highly compositional and formulaic nature of the Gene Ontology concepts. We illustrate how the generated synonyms aid in improving recognition of GO concepts on two different biomedical corpora. We discuss other applications of our rules for GO ontology quality assurance, explore the issue of overgeneration, and provide examples of how similar methodologies could be applied to other biomedical terminologies. Additionally, we provide all generated synonyms for use by the text-mining community.

  4. 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,

  5. 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…

  6. Crossing the Generations: Learning to Lead Across the Leadership Life Cycle

    Science.gov (United States)

    Phelan, Daniel J.

    2005-01-01

    To fully understand the continuing evolution of the community college movement, one must also consider the evolution of its leadership, its changing environment, as well as changing societal needs. This monograph provides some experiential insight into the leadership aspect of the community college, particularly with regard to generational change.…

  7. 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...

  8. 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.

  9. 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.

  10. Determination of informed choice and pathways leading to selection of the Environmental Studies major

    Science.gov (United States)

    Dierberger, Betsy S.

    The reasons why students select the Environmental Studies (ES) major at the University of Nebraska were investigated. A survey was used to determine factors of influence and career awareness as measures for making an informed choice in selection of a major. In addition, pathways of selection of the ES major were determined. Thirty-five students with ES majors and 14 faculty advisors completed the survey. Seven students participated in interviews. Student interviews were conducted to determine the "life-world" of the students during the decision making process leading to the selection of major. Interest in environmental issues, the challenge of solving environmental problems and a desire to make a difference in the environment were factors identified as positively influencing selection of this major. Environmental career attributes which influenced choice of major were variety of tasks and use of science skills. Faculty advisor perception of careers and advisor understanding of why students select the ES major were explored. Faculty advisors recommended selection of the ES major to students who demonstrated a clear interest in natural resources. Faculty advisors and students selected career categories appropriate to the ES curriculum indicating an awareness of career and job requirements. Informed choice was defined as evidence of student self-knowledge of interests, abilities and aptitudes and evidence of awareness of career opportunities in environmentally related areas. Students expressed self- knowledge of factors influential in major selection and career awareness. Therefore, the students did make informed decisions for selection of the ES major. Interview themes suggested three pathways for the selection of the ES major: (1) Direct Choice, (2) Focused Choice, and (3) Delayed Choice. Direct Choice occurs Men a student with ES interest selects the major and enrolls as a new student. Focused Choice occurs when students have life or school experiences that narrow

  11. The Agent of extracting Internet Information with Lead Order

    Science.gov (United States)

    Mo, Zan; Huang, Chuliang; Liu, Aijun

    In order to carry out e-commerce better, advanced technologies to access business information are in need urgently. An agent is described to deal with the problems of extracting internet information that caused by the non-standard and skimble-scamble structure of Chinese websites. The agent designed includes three modules which respond to the process of extracting information separately. A method of HTTP tree and a kind of Lead algorithm is proposed to generate a lead order, with which the required web can be retrieved easily. How to transform the extracted information structuralized with natural language is also discussed.

  12. 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.

  13. 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...

  14. 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.

  15. 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…

  16. 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…

  17. 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…

  18. 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...

  19. 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

  20. What if ethical buying behavior leads to boycotts? : The buying behavior of Generation Z

    OpenAIRE

    Helmersson, Filip; Svensson, Amanda

    2016-01-01

    The care for the environment has been a hot topic during the last fifteen years. Ecological and Fairtrade products made from sustainable materials and methods can be found in almost every store. It seems like awareness regarding our environmental impact has increased and therefore changed our purchase behavior. The awareness has also created pressure on the companies to behave in an ethical manner, if the consumers feel that their ethical needs are not acknowledged, they will tend to stop pur...

  1. 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…

  2. 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

  3. 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,...

  4. 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....

  5. 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…

  6. 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.

  7. 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.

  8. Can pluralistic approaches based upon unknown languages enhance learner engagement and lead to active social inclusion?

    Science.gov (United States)

    Dahm, Rebecca

    2017-08-01

    One way to foster active social inclusion is to enable students to develop a positive attitude to "foreignness". Creating a situation where mainstream students are less wary of foreign languages and cultures, and where newcomers feel their linguistic background is being valued, provides favourable conditions for the inclusion of these newcomers in the classroom and in society. However, language classrooms in French schools rarely take any previously acquired linguistic knowledge into account, thus unconsciously contributing to the rift between multilingual learners (e.g. 1st- and 2nd-generation immigrant children, refugees, children of parents with different mother tongues) and French learners. Native French learners' first experience of learning another language is usually when English is added as a subject to their curriculum in primary school. In some schools in France, English lessons now include the simulation of multilingual situations, designed in particular for the French "quasi-monolingual" students to lose their fear of unknown languages and "foreignness" in general. But the overall aim is to help both groups of learners become aware of the positive impact of multilingualism on cognitive abilities. However, to achieve long-term effects, this awareness-raising needs to be accompanied by maximum engagement on the part of the students. This article explores an instructional strategy termed Pluralistic Approaches based upon Unknown Languages (PAUL), which was designed to develop learning strategies of quasi-monolingual students in particular and to increase learner engagement more generally. The results of a small-scale PAUL study discussed by the author seem to confirm an increase in learner engagement leading to an enhancement of learning outcomes. Moreover, PAUL seems indeed suitable for helping to prepare the ground for social inclusion.

  9. Can pluralistic approaches based upon unknown languages enhance learner engagement and lead to active social inclusion?

    Science.gov (United States)

    Dahm, Rebecca

    2017-04-01

    One way to foster active social inclusion is to enable students to develop a positive attitude to "foreignness". Creating a situation where mainstream students are less wary of foreign languages and cultures, and where newcomers feel their linguistic background is being valued, provides favourable conditions for the inclusion of these newcomers in the classroom and in society. However, language classrooms in French schools rarely take any previously acquired linguistic knowledge into account, thus unconsciously contributing to the rift between multilingual learners (e.g. 1st- and 2nd-generation immigrant children, refugees, children of parents with different mother tongues) and French learners. Native French learners' first experience of learning another language is usually when English is added as a subject to their curriculum in primary school. In some schools in France, English lessons now include the simulation of multilingual situations, designed in particular for the French "quasi-monolingual" students to lose their fear of unknown languages and "foreignness" in general. But the overall aim is to help both groups of learners become aware of the positive impact of multilingualism on cognitive abilities. However, to achieve long-term effects, this awareness-raising needs to be accompanied by maximum engagement on the part of the students. This article explores an instructional strategy termed Pluralistic Approaches based upon Unknown Languages (PAUL), which was designed to develop learning strategies of quasi-monolingual students in particular and to increase learner engagement more generally. The results of a small-scale PAUL study discussed by the author seem to confirm an increase in learner engagement leading to an enhancement of learning outcomes. Moreover, PAUL seems indeed suitable for helping to prepare the ground for social inclusion.

  10. The Socioeconomic Pathways Leading to Romantic Relationship Outcomes: A Genetically Informed Early Life Course Investigation.

    Science.gov (United States)

    Wickrama, Kandauda K A S; O'Neal, Catherine W

    2016-09-01

    The present study tests a multilevel comprehensive model incorporating both life course processes and genetic influences leading to young adults' romantic relationship quality using data from 1,560 adolescents over 13 years in the nationally representative Add Health sample. Results provided evidence of a socioeconomic mediating pathway linking early family and community contexts to young adults' romantic relationship quality, and novel evidence for both direct and interactive genetic associations that relate to these mediating pathways. A cumulative genetic index showed (a) direct associations with young adults' socioeconomic attainment and (b) interactions with community adversity and mothers' marital stability on young adults' achieved socioeconomic context and relationship quality. © 2015 The Authors. Journal of Research on Adolescence © 2015 Society for Research on Adolescence.

  11. 77 FR 74667 - Agency Information Collection Activities; Proposed Collection; Comment Request; Information To...

    Science.gov (United States)

    2012-12-17

    ... HUMAN SERVICES Food and Drug Administration Agency Information Collection Activities; Proposed Collection; Comment Request; Information To Accompany Humanitarian Device Exemption Applications and Annual... Information-- 520(m)(6)(A)(i) and (ii) of the FD&C Act Request for Determination of 2 1 2 10 20 Eligibility...

  12. 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

    whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice...

  13. Information Extraction to Generate Visual Simulations of Car Accidents from Written Descriptions

    NARCIS (Netherlands)

    Nugues, P.; Dupuy, S.; Egges, A.

    2003-01-01

    This paper describes a system to create animated 3D scenes of car accidents from written reports. The text-to-scene conversion process consists of two stages. An information extraction module creates a tabular description of the accident and a visual simulator generates and animates the scene. We

  14. 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.

  15. 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...

  16. 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…

  17. 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.

  18. 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.

  19. Events that lead university students to change their major to Information Systems: A retroductive South African case

    Directory of Open Access Journals (Sweden)

    Lisa Florence Seymour

    2016-07-01

    Full Text Available Shortage of computing skills is a global concern as it affects national development and business success. Yet, despite high job availability and high salaries in computing professions, insufficient numbers of students are choosing to study the various computing disciplines. This South African study looks at the Information Systems (IS major which is misunderstood by high school students. This retroductive case study identifies the events which lead students to change their major to IS. The study confirms the importance of interest in a major as well as the perceived high value of a major, which feature as dominant factors in the literature. Yet these are not the initial events that lead to students changing their major to IS. Events that initiate the process include losing passion for a previous major, experiencing difficulty in a previous major as well as enjoying the introductory IS course. The paper has practical advice for IS Departments and argues for a generic first year for students as well as a focus on enjoyment and skills aligned to IS professional practice in introductory IS courses. These findings can be generalised to other majors and, hence, the theoretical contribution adds to the literature on career choice in general.

  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. 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.

  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. 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.

  4. Generating Leading Practices through Professional Learning

    Science.gov (United States)

    Edwards Groves, Christine; Ronnerman, Karin

    2013-01-01

    In this paper we show how practices of professional learning and practices of leading can be understood as related in ecologies of practices. We will present findings from an international empirical research project that directs us to the connectivity between professional learning and leading practices that emerged as "adventitious",…

  5. Utility and safety of temporary pacing using active fixation leads and externalized re-usable permanent pacemakers after lead extraction

    National Research Council Canada - National Science Library

    Kawata, Hiro; Pretorius, Victor; Phan, Huy; Mulpuru, Siva; Gadiyaram, Varuna; Patel, Jigar; Steltzner, Dawna; Krummen, David; Feld, Gregory; Birgersdotter-Green, Ulrika

    2013-01-01

    .... The use of an externalized permanent active-fixation pacemaker lead connected to a permanent pacemaker generator for temporary pacing may be beneficial because of improved lead stability, and greater...

  6. Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research

    Directory of Open Access Journals (Sweden)

    Facio Flavia M

    2012-10-01

    Full Text Available Abstract Background Massively-parallel sequencing (MPS technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results. Discussion We propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of our hypothesis-testing study is to elucidate the etiology of rare phenotypes using MPS. The purpose of our hypothesis-generating study is to test the feasibility of using MPS to generate clinical hypotheses, and to approach the return of results as an experimental manipulation. Issues to consider in both designs include: volume and nature of the potential results, primary versus secondary results, return of individual results, duty to warn, length of interaction, target population, and privacy and confidentiality. Summary The categorization of MPS studies as hypothesis-testing versus hypothesis-generating can help to clarify the issue of so-called incidental or secondary results for the consent process, and aid the communication of the research goals to study participants.

  7. 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.

  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. The need to generate realistic strain signals at an automotive coil spring for durability simulation leading to fatigue life assessment

    Science.gov (United States)

    Putra, T. E.; Abdullah, S.; Schramm, D.; Nuawi, M. Z.; Bruckmann, T.

    2017-09-01

    This study aims to accelerate fatigue tests using simulated strain signals. Strain signals were acquired from a coil spring involving car movements. Using a mathematical expression, the measured strain signals yielded acceleration signals, and were considered as disturbances on generating strain signals. The simulated strain signals gave the testing time deviation by only 1.5%. The wavelet-based data editing was applied to shorten the strain signals time up to 36.7% and reduced the testing time up to 33.9%. In conclusion, the simulated strain signals were able to maintain the majority of fatigue damage and decreased the testing time.

  10. Defective molecular timer in the absence of nucleotides leads to inefficient caspase activation.

    Science.gov (United States)

    Zhang, Honghao; Gogada, Raghu; Yadav, Neelu; Lella, Ravi K; Badeaux, Mark; Ayres, Mary; Gandhi, Varsha; Tang, Dean G; Chandra, Dhyan

    2011-01-27

    In the intrinsic death pathway, cytochrome C (CC) released from mitochondria to the cytosol triggers Apaf-1 apoptosome formation and subsequent caspase activation. This process can be recapitulated using recombinant Apaf-1 and CC in the presence of nucleotides ATP or dATP [(d)ATP] or using fresh cytosol and CC without the need of exogenous nucleotides. Surprisingly, we found that stored cytosols failed to support CC-initiated caspase activation. Storage of cytosols at different temperatures led to the loss of all (deoxy)nucleotides including (d)ATP. Addition of (d)ATP to such stored cytosols partially restored CC-initiated caspase activation. Nevertheless, CC could not induce complete caspase-9/3 activation in stored cytosols, even with the addition of (d)ATP, despite robust Apaf-1 oligomerization. The Apaf-1 apoptosome, which functions as a proteolytic-based molecular timer appeared to be defective as auto-processing of recruited procaspase-9 was inhibited. Far Western analysis revealed that procaspase-9 directly interacted with Apaf-1 and this interaction was reduced in the presence of physiological levels of ATP. Co-incubation of recombinant Apaf-1 and procaspase-9 prior to CC and ATP addition inhibited CC-induced caspase activity. These findings suggest that in the absence of nucleotide such as ATP, direct association of procaspase-9 with Apaf-1 leads to defective molecular timer, and thus, inhibits apoptosome-mediated caspase activation. Altogether, our results provide novel insight on nucleotide regulation of apoptosome.

  11. How to change GEBCO outreach activities with Information technologies?

    Science.gov (United States)

    Chang, E.; Park, K.

    2014-12-01

    Since 1995, when National Geographic Information Project began, we have great advance in mapping itself and information service on the earth surface in Korea whether paper maps or online service map. By reviewing geological and mine-related information service in current and comparisons of demands, GEBCO outreach master plan has been prepared. Information service cannot be separated from data production and on dissemination policies. We suggest the potential impact of the changes in information technologies such as mobile service and data fusion, and big data on GEBCO maps based. Less cost and high performance in data service will stimulate more information service; therefore it is necessary to have more customer-oriented manipulation on the data. By inquiring questionnaire, we can draw the potential needs on GEBCO products in various aspects: such as education, accessibility. The gap between experts and non-experts will decrease by digital service from the private and public organizations such as international academic societies since research funds and policies tend to pursue "openness" and "interoperability" among the domains. Some background why and how to prepare outreach activities in GEBCO will be shown.

  12. 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.

  13. 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.

  14. 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...

  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. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Informal Peer-Assisted Learning Groups Did Not Lead to Better Performance of Saudi Dental Students.

    Science.gov (United States)

    AbdelSalam, Maha; El Tantawi, Maha; Al-Ansari, Asim; AlAgl, Adel; Al-Harbi, Fahad

    2017-01-01

    To describe peer-assisted learning (PAL) groups formed by dental undergraduate students in a biomedical course and to investigate the association of individual and group characteristics with academic performance. In 2015, 92 fourth-year students (43 males and 49 females) in the College of Dentistry, University of Dammam, Saudi Arabia, were invited to form PAL groups to study a unit of a biomedical course. An examination was used to assess their knowledge after 2 weeks. In addition, a questionnaire and social network analysis were used to investigate (1) individual student attributes: gender, role, subject matter knowledge, grade in previous year, teaming with friends, previous communication with teammates, and content discussion, and (2) group attributes: group teacher's previous grade, number of colleagues with whom a student connected, teaming with friends, similarity of teammates' previous grades, and teacher having higher previous grades than other teammates. Regression analysis was used to assess the association of examination scores with individual and group attributes. The response rate was 80.4% (74 students: 36 males and 38 females). Students who previously scored grades A and B had higher examination scores than students with grades C/less (regression coefficient = 18.50 and 13.39) within the groups. Higher scores were not associated with working in groups including friends only (regression coefficient = 1.17) or when all students had similar previous grades (regression coefficient = 0.85). Students with previous high grades benefited to a greater extent from working in PAL groups. Similarity of teammates in PAL groups was not associated with better scores. © 2017 S. Karger AG, Basel.

  3. 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.

  4. Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation

    National Research Council Canada - National Science Library

    Szutorisz, Henrietta; DiNieri, Jennifer A; Sweet, Eric; Egervari, Gabor; Michaelides, Michael; Carter, Jenna M; Ren, Yanhua; Miller, Michael L; Blitzer, Robert D; Hurd, Yasmin L

    2014-01-01

    ... (THC), the main psychoactive component of cannabis, results in behavioral and neurobiological abnormalities in the subsequent generation of rats as a consequence of parental germline exposure to the drug...

  5. 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.

  6. 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…

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Systemic overexpression of TNFα-converting enzyme does not lead to enhanced shedding activity in vivo.

    Directory of Open Access Journals (Sweden)

    Masaki Yoda

    Full Text Available TNFα-converting enzyme (TACE/ADAM17 is a membrane-bound proteolytic enzyme with a diverse set of target molecules. Most importantly, TACE is indispensable for the release and activation of pro-TNFα and the ligands for epidermal growth factor receptor in vivo. Previous studies suggested that the overproduction of TACE is causally related to the pathogenesis of inflammatory diseases and cancers. To test this hypothesis, we generated a transgenic line in which the transcription of exogenous Tace is driven by a CAG promoter. The Tace-transgenic mice were viable and exhibited no overt defects, and the quantitative RT-PCR and Western blot analyses confirmed that the transgenically introduced Tace gene was highly expressed in all of the tissues examined. The Tace-transgenic mice were further crossed with Tace⁻/⁺ mice to abrogate the endogenous TACE expression, and the Tace-transgenic mice lacking endogenous Tace gene were also viable without any apparent defects. Furthermore, there was no difference in the serum TNFα levels after lipopolysaccharide injection between the transgenic mice and control littermates. These observations indicate that TACE activity is not necessarily dependent on transcriptional regulation and that excess TACE does not necessarily result in aberrant proteolytic activity in vivo.

  12. 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.

  13. 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...

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons

    Science.gov (United States)

    Canetta, Sarah; Bolkan, Scott; Padilla-Coreano, Nancy; Song, LouJin; Sahn, Ryan; Harrison, Neil; Gordon, Joshua A.; Brown, Alan; Kellendonk, Christoph

    2015-01-01

    Summary Abnormalities in prefrontal GABAergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Improper activation of D1 and D2 receptors leads to excess noise in prefrontal cortex

    Science.gov (United States)

    Avery, Michael C.; Krichmar, Jeffrey L.

    2015-01-01

    The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC) and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC. PMID:25814948

  5. Improper activation of D1 and D2 receptors leads to excess noise in prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Michael eAvery

    2015-03-01

    Full Text Available The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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…

  18. 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.

  19. 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.

  20. 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.

  1. 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)

  2. Unintentional activation of translation equivalents in bilinguals leads to attention capture in a cross-modal visual task

    National Research Council Canada - National Science Library

    Singh, Niharika; Mishra, Ramesh Kumar

    2015-01-01

    Using a variant of the visual world eye tracking paradigm, we examined if language non-selective activation of translation equivalents leads to attention capture and distraction in a visual task in bilinguals...

  3. Unintentional Activation of Translation Equivalents in Bilinguals Leads to Attention Capture in a Cross-Modal Visual Task: e0120131

    National Research Council Canada - National Science Library

    Niharika Singh; Ramesh Kumar Mishra

    2015-01-01

      Using a variant of the visual world eye tracking paradigm, we examined if language non- selective activation of translation equivalents leads to attention capture and distraction in a visual task in bilinguals...

  4. {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.

  5. Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis

    Directory of Open Access Journals (Sweden)

    Lin Shin-Jen

    2012-06-01

    Full Text Available Abstract Background Early studies suggested that TR4 nuclear receptor might play important roles in the skeletal development, yet its detailed mechanism remains unclear. Methods We generated TR4 knockout mice and compared skeletal development with their wild type littermates. Primary bone marrow cells were cultured and we assayed bone differentiation by alkaline phosphatase and alizarin red staining. Primary calvaria were cultured and osteoblastic marker genes were detected by quantitative PCR. Luciferase reporter assays, chromatin immunoprecipitation (ChIP assays, and electrophoretic mobility shift assays (EMSA were performed to demonstrate TR4 can directly regulate bone differentiation marker osteocalcin. Results We first found mice lacking TR4 might develop osteoporosis. We then found that osteoblast progenitor cells isolated from bone marrow of TR4 knockout mice displayed reduced osteoblast differentiation capacity and calcification. Osteoblast primary cultures from TR4 knockout mice calvaria also showed higher proliferation rates indicating lower osteoblast differentiation ability in mice after loss of TR4. Mechanism dissection found the expression of osteoblast markers genes, such as ALP, type I collagen alpha 1, osteocalcin, PTH, and PTHR was dramatically reduced in osteoblasts from TR4 knockout mice as compared to those from TR4 wild type mice. In vitro cell line studies with luciferase reporter assay, ChIP assay, and EMSA further demonstrated TR4 could bind directly to the promoter region of osteocalcin gene and induce its gene expression at the transcriptional level in a dose dependent manner. Conclusions Together, these results demonstrate TR4 may function as a novel transcriptional factor to play pathophysiological roles in maintaining normal osteoblast activity during the bone development and remodeling, and disruption of TR4 function may result in multiple skeletal abnormalities.

  6. 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

  7. Detecting the Elusive P-Wave: A New ECG Lead to Improve the Recording of Atrial Activity.

    Science.gov (United States)

    Kennedy, Alan; Finlay, Dewar D; Guldenring, Daniel; Bond, Raymond R; McLaughlin, James

    2016-02-01

    In this study, we report on a lead selection method that was developed to detect the optimal bipolar electrode placement for recording of the P-wave. The study population consisted of 117 lead body surface potential maps recorded from 229 healthy subjects. The optimal bipolar lead was developed using the training set (172 subjects) then extracted from the testing dataset (57 subjects) and compared to other lead systems previously reported for improved recording of atrial activity. All leads were assessed in terms of P-wave, QRS, and STT root mean square (RMS). The P/QRST RMS ratio was also investigated to determine the atrioventricular RMS ratio. Finally, the effect of minor electrode misplacements on the P-lead was investigated. The P-lead discovered in this study outperformed all other investigated leads in terms of P-wave RMS. The P-lead showed a significant improvement in median P-wave RMS (93 versus 72 μV, p STT RMS was also observed from the P-lead in comparison to lead II (668 versus 573 μV, p STT RMS making it an appropriate choice for atrial arrhythmia monitoring. Given the improvement in signal-to-noise ratio, an improvement in algorithms that rely on P-wave analysis may be achieved.

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

    Directory of Open Access Journals (Sweden)

    C. Momblona

    2014-08-01

    Full Text Available 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.

  9. 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.

  10. Basic Information about Lead in Drinking Water

    Science.gov (United States)

    ... control treatment to prevent lead and copper from contaminating drinking water. Corrosion control treatment means utilities must ... Page How EPA Requires States and Public Water Systems to Protect Drinking Water The Safe Drinking Water ...

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. The Influence of Lead on Generation of Signalling Molecules and Accumulation of Flavonoids in Pea Seedlings in Response to Pea Aphid Infestation.

    Science.gov (United States)

    Woźniak, Agnieszka; Drzewiecka, Kinga; Kęsy, Jacek; Marczak, Łukasz; Narożna, Dorota; Grobela, Marcin; Motała, Rafał; Bocianowski, Jan; Morkunas, Iwona

    2017-08-24

    The aim of this study was to investigate the effect of an abiotic factor, i.e., lead at various concentrations (low causing a hormesis effect and causing high toxicity effects), on the generation of signalling molecules in pea (Pisum sativum L. cv. Cysterski) seedlings and then during infestation by the pea aphid (Acyrthosiphon pisum Harris). The second objective was to verify whether the presence of lead in pea seedling organs and induction of signalling pathways dependent on the concentration of this metal trigger defense responses to A. pisum. Therefore, the profile of flavonoids and expression levels of genes encoding enzymes of the flavonoid biosynthesis pathway (phenylalanine ammonialyase and chalcone synthase) were determined. A significant accumulation of total salicylic acid (TSA) and abscisic acid (ABA) was recorded in the roots and leaves of pea seedlings growing on lead-supplemented medium and next during infestation by aphids. Increased generation of these phytohormones strongly enhanced the biosynthesis of flavonoids, including a phytoalexin, pisatin. This research provides insights into the cross-talk between the abiotic (lead) and biotic factor (aphid infestation) on the level of the generation of signalling molecules and their role in the induction of flavonoid biosynthesis.

  16. 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.

  17. Experimental pain leads to reorganisation of trapezius electromyography during computer work with active and passive pauses

    DEFF Research Database (Denmark)

    Samani, Afshin; Holtermann, Andreas; Søgaard, Karen

    2009-01-01

    in one day, with passive (relax) and active (30% maximum voluntary contraction of shoulder elevation) pauses given every 40 s without and with presence of experimental pain. Surface EMG signals were recorded from four parts of the trapezius. The centroid of exposure variation analysis along the time axis......The aim of this laboratory study was to investigate acute effects of experimental muscle pain on spatial electromyographic (EMG) activity of the trapezius muscle during computer work with active and passive pauses. Twelve healthy male subjects performed four sessions of computer work for 2 min...... was lower during computer work with active pauses when compared with passive one in all muscle parts (P

  18. Digital imaging information technology for biospeckle activity assessment relative to bacteria and parasites.

    Science.gov (United States)

    Ramírez-Miquet, Evelio E; Cabrera, Humberto; Grassi, Hilda C; de J Andrades, Efrén; Otero, Isabel; Rodríguez, Dania; Darias, Juan G

    2017-08-01

    This paper reports on the biospeckle processing of biological activity using a visualization scheme based upon the digital imaging information technology. Activity relative to bacterial growth in agar plates and to parasites affected by a drug is monitored via the speckle patterns generated by a coherent source incident on the microorganisms. We present experimental results to demonstrate the potential application of this methodology for following the activity in time. The digital imaging information technology is an alternative visualization enabling the study of speckle dynamics, which is correlated to the activity of bacteria and parasites. In this method, the changes in Red-Green-Blue (RGB) color component density are considered as markers of the growth of bacteria and parasites motility in presence of a drug. The RGB data was used to generate a two-dimensional surface plot allowing an analysis of color distribution on the speckle images. The proposed visualization is compared to the outcomes of the generalized differences and the temporal difference. A quantification of the activity is performed using a parameterization of the temporal difference method. The adopted digital image processing technique has been found suitable to monitor motility and morphological changes in the bacterial population over time and to detect and distinguish a short term drug action on parasites.

  19. 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.

  20. 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.

  1. 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.

  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

    homolog of DP-1. Human DP-1 and E2F-1 associate both in vivo and in vitro, and this interaction leads to enhanced binding to E2F DNA-binding sites. The association of E2F-1 and DP-1 leads to cooperative activation of an E2F-responsive promoter. Finally, we demonstrate that E2F-1 and DP-1 association...

  3. 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.

  4. 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.

  5. 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)

  6. Cybersecurity Activities Support to DoD Information Network Operations

    Science.gov (United States)

    2016-03-07

    Overall ISCM furnishes ongoing observation, assessment, analysis, and diagnosis of an organization’s cybersecurity posture , cyber hygiene , and...audit and assessment processes in coordination with CDRUSSTRATCOM. m. Reviews the cybersecurity posture of systems authorized to operate outside...d. Supports the RMF by providing ongoing awareness and security status of the posture of an organization’s information and systems. This

  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. Inactivation of Geminin in neural crest cells affects the generation and maintenance of enteric progenitor cells, leading to enteric aganglionosis.

    Science.gov (United States)

    Stathopoulou, Athanasia; Natarajan, Dipa; Nikolopoulou, Pinelopi; Patmanidi, Alexandra L; Lygerou, Zoi; Pachnis, Vassilis; Taraviras, Stavros

    2016-01-15

    Neural crest cells comprise a multipotent, migratory cell population that generates a diverse array of cell and tissue types, during vertebrate development. Enteric Nervous System controls the function of the gastrointestinal tract and is mainly derived from the vagal and sacral neural crest cells. Deregulation on self-renewal and differentiation of the enteric neural crest cells is evident in enteric nervous system disorders, such as Hirschsprung disease, characterized by the absence of ganglia in a variable length of the distal bowel. Here we show that Geminin is essential for Enteric Nervous System generation as mice that lacked Geminin expression specifically in neural crest cells revealed decreased generation of vagal neural crest cells, and enteric neural crest cells (ENCCs). Geminin-deficient ENCCs showed increased apoptosis and decreased cell proliferation during the early stages of gut colonization. Furthermore, decreased number of committed ENCCs in vivo and the decreased self-renewal capacity of enteric progenitor cells in vitro, resulted in almost total aganglionosis resembling a severe case of Hirschsprung disease. Our results suggest that Geminin is an important regulator of self-renewal and survival of enteric nervous system progenitor cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. 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...

  10. 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)].

  11. 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.

  12. Can Pluralistic Approaches Based upon Unknown Languages Enhance Learner Engagement and Lead to Active Social Inclusion?

    Science.gov (United States)

    Dahm, Rebecca

    2017-01-01

    One way to foster active social inclusion is to enable students to develop a positive attitude to "foreignness". Creating a situation where mainstream students are less wary of foreign languages and cultures, and where newcomers feel their linguistic background is being valued, provides favourable conditions for the inclusion of these…

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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…

  3. 78 FR 61368 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-10-03

    ... nonprofit entities determined appropriate by the Secretary that submit an application and are accredited for... the time expended by persons to generate, maintain, retain, disclose or provide the information... maintaining information, and disclosing and providing information; to train personnel and to be able to...

  4. 77 FR 30278 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-05-22

    ... is pending at OMB. Abstract: The affected entities are subject to the General Provisions of the... expended by persons to generate, maintain, retain, or disclose or provide information to or for a Federal... maintaining information, and disclosing and providing information; adjust the existing ways to comply with any...

  5. Do all sedentary activities lead to weight gain: sleep does not.

    Science.gov (United States)

    Chaput, Jean-Philippe; Klingenberg, Lars; Sjödin, Anders

    2010-11-01

    To discuss the benefits of having a good night's sleep for body weight stability. Experimental studies have shown that short-term partial sleep restriction decreases glucose tolerance, increases sympathetic tone, elevates cortisol concentrations, decreases the satiety hormone leptin, increases the appetite-stimulating hormone ghrelin, and increases hunger and appetite. Short sleep duration might increase the risk of becoming obese, because it does not allow the recovery of a hormonal profile facilitating appetite control. Lack of sleep could also lead to weight gain and obesity by increasing the time available for eating and by making the maintenance of a healthy lifestyle more difficult. Furthermore, the increased fatigue and tiredness associated with sleeping too little could lessen one's resolve to follow exercise regimens. Short sleep duration appears to be a novel and independent risk factor for obesity. With the growing prevalence of chronic sleep restriction, any causal association between reduced sleep and obesity would have substantial importance from a public health standpoint. Future research is needed to determine whether sleep extension in sleep-deprived obese individuals will influence appetite control and/or reduce the amount of body fat.

  6. 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.

  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.

    2016-01-01

    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

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

    Science.gov (United States)

    2012-01-01

    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 caused by c-Abl expression in

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity.

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria; Fritz, Teresa; Angle, Amanda; Kielian, Tammy

    2011-01-12

    Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, astrocytes bordering the abscess demonstrated hemichannel activity as evident by enhanced ethidium bromide (EtBr) uptake that could be blocked by several pharmacological inhibitors, including the connexin 43 (Cx43) mimetic peptide Gap26, carbenoxolone, the pannexin1 (Panx1) mimetic peptide (10)Panx1, and probenecid. However, hemichannel opening was transient with astrocytic EtBr uptake observed near the abscess at day 3 but not day 7 after infection. The region-dependent pattern of hemichannel activity at day 3 directly correlated with increases in Cx43, Cx30, Panx1, and glutamate transporter expression (glial L-glutamate transporter and L-glutamate/L-aspartate transporter) along the abscess margins. Changes in astrocyte resting membrane potential and input conductance correlated with the observed changes in GJ communication and hemichannel activity. Collectively, these findings indicate that astrocyte coupling and electrical properties are most dramatically affected near the primary inflammatory site and reveal an opposing relationship between the open states of GJ channels versus hemichannels during acute infection. This relationship may extend to other CNS diseases typified with an inflammatory component.

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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,...

  19. 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…

  20. 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…

  1. 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

  2. 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...

  3. Genetic model for the chronic activation of skeletal muscle AMP-activated protein kinase leads to glycogen accumulation.

    Science.gov (United States)

    Barré, Laura; Richardson, Christine; Hirshman, Michael F; Brozinick, Joseph; Fiering, Steven; Kemp, Bruce E; Goodyear, Laurie J; Witters, Lee A

    2007-03-01

    The AMP-activated protein kinase (AMPK) is an important metabolic sensor/effector that coordinates many of the changes in mammalian tissues during variations in energy availability. We have sought to create an in vivo genetic model of chronic AMPK activation, selecting murine skeletal muscle as a representative tissue where AMPK plays important roles. Muscle-selective expression of a mutant noncatalytic gamma1 subunit (R70Qgamma) of AMPK activates AMPK and increases muscle glycogen content. The increase in glycogen content requires the presence of the endogenous AMPK catalytic alpha-subunit, since the offspring of cross-breeding of these mice with mice expressing a dominant negative AMPKalpha subunit have normal glycogen content. In R70Qgamma1-expressing mice, there is a small, but significant, increase in muscle glycogen synthase (GSY) activity associated with an increase in the muscle expression of the liver isoform GSY2. The increase in glycogen content is accompanied, as might be expected, by an increase in exercise capacity. Transgene expression of this mutant AMPKgamma1 subunit may provide a useful model for the chronic activation of AMPK in other tissues to clarify its multiple roles in the regulation of metabolism and other physiological processes.

  4. 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,...

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  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. 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.

  12. 77 FR 65541 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

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    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...

  13. 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:...

  14. 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-...

  15. 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

  16. 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.

  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. © 2011 Taylor & Francis

  18. 78 FR 61366 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-10-03

    ..., state or local governments, and other public or private nonprofit entities determined appropriate by the... context means the time expended by persons to generate, maintain, retain, disclose or provide the..., processing and maintaining information, and disclosing and providing information; to train personnel and to...

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. Fabrication Processes to Generate Concentration Gradients in Polymer Solar Cell Active Layers.

    Science.gov (United States)

    Inaba, Shusei; Vohra, Varun

    2017-05-09

    Polymer solar cells (PSCs) are considered as one of the most promising low-cost alternatives for renewable energy production with devices now reaching power conversion efficiencies (PCEs) above the milestone value of 10%. These enhanced performances were achieved by developing new electron-donor (ED) and electron-acceptor (EA) materials as well as finding the adequate morphologies in either bulk heterojunction or sequentially deposited active layers. In particular, producing adequate vertical concentration gradients with higher concentrations of ED and EA close to the anode and cathode, respectively, results in an improved charge collection and consequently higher photovoltaic parameters such as the fill factor. In this review, we relate processes to generate active layers with ED-EA vertical concentration gradients. After summarizing the formation of such concentration gradients in single layer active layers through processes such as annealing or additives, we will verify that sequential deposition of multilayered active layers can be an efficient approach to remarkably increase the fill factor and PCE of PSCs. In fact, applying this challenging approach to fabricate inverted architecture PSCs has the potential to generate low-cost, high efficiency and stable devices, which may revolutionize worldwide energy demand and/or help develop next generation devices such as semi-transparent photovoltaic windows.

  4. Fabrication Processes to Generate Concentration Gradients in Polymer Solar Cell Active Layers

    Science.gov (United States)

    Inaba, Shusei; Vohra, Varun

    2017-01-01

    Polymer solar cells (PSCs) are considered as one of the most promising low-cost alternatives for renewable energy production with devices now reaching power conversion efficiencies (PCEs) above the milestone value of 10%. These enhanced performances were achieved by developing new electron-donor (ED) and electron-acceptor (EA) materials as well as finding the adequate morphologies in either bulk heterojunction or sequentially deposited active layers. In particular, producing adequate vertical concentration gradients with higher concentrations of ED and EA close to the anode and cathode, respectively, results in an improved charge collection and consequently higher photovoltaic parameters such as the fill factor. In this review, we relate processes to generate active layers with ED–EA vertical concentration gradients. After summarizing the formation of such concentration gradients in single layer active layers through processes such as annealing or additives, we will verify that sequential deposition of multilayered active layers can be an efficient approach to remarkably increase the fill factor and PCE of PSCs. In fact, applying this challenging approach to fabricate inverted architecture PSCs has the potential to generate low-cost, high efficiency and stable devices, which may revolutionize worldwide energy demand and/or help develop next generation devices such as semi-transparent photovoltaic windows. PMID:28772878

  5. 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...

  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. 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.

  8. 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…

  9. 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....

  10. 75 FR 41171 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2010-07-15

    ... other information whose public disclosure is restricted by statute. For further information about the... limit to minimize risks to human health and the environment. Regulations promulgated under SNAP require... AGENCY Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

  11. Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with Metabolic Disease.

    Science.gov (United States)

    Friesen, Max; Camahort, Raymond; Lee, Youn-Kyoung; Xia, Fang; Gerszten, Robert E; Rhee, Eugene P; Deo, Rahul C; Cowan, Chad A

    2017-05-09

    The striking rise of obesity-related metabolic disorders has focused attention on adipocytes as critical mediators of disease phenotypes. To better understand the role played by excess adipose in metabolic dysfunction it is crucial to decipher the transcriptional underpinnings of the low-grade adipose inflammation characteristic of diseases such as type 2 diabetes. Through employing a comparative transcriptomics approach, we identified IRF1 as differentially regulated between primary and in vitro-derived genetically matched adipocytes. This suggests a role as a mediator of adipocyte inflammatory phenotypes, similar to its function in other tissues. Utilizing adipose-derived mesenchymal progenitors we subsequently demonstrated that expression of IRF1 in adipocytes indeed contributes to upregulation of inflammatory processes, both in vitro and in vivo. This highlights IRF1's relevance to obesity-related inflammation and the resultant metabolic dysregulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. 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.

  13. 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.

  14. Fourth generation CP violation effects on B-->Kpi, phiK, and rhoK in next-to-leading-order perturbative QCD.

    Science.gov (United States)

    Hou, Wei-Shu; Li, Hsiang-nan; Mishima, Satoshi; Nagashima, Makiko

    2007-03-30

    We study the effect from a sequential fourth generation quark on penguin-dominated two-body nonleptonic B meson decays in the next-to-leading order perturbative QCD formalism. With an enhancement of the color-suppressed tree amplitude and possibility of a new CP phase in the electroweak penguin amplitude, we can account better for A(CP)(B(0)-->K+ pi-)-A(CP)(B+-->K+ pi0). Taking |V(t's)V(t'b)| approximately 0.02 with a phase just below 90 degrees, which is consistent with the b-->sl+ l- rate and the B(s) mixing parameter Deltam(B)(s), we find a downward shift in the mixing-induced CP asymmetries of B(0)-->K(S)(pi 0) and phi(K)(S). The predicted behavior for B(0)-->rho(0)(K)(S) is opposite.

  15. 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...

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. Dopamine D1 receptor activation leads to object recognition memory in a coral reef fish.

    Science.gov (United States)

    Hamilton, Trevor J; Tresguerres, Martin; Kline, David I

    2017-07-01

    Object recognition memory is the ability to identify previously seen objects and is an adaptive mechanism that increases survival for many species throughout the animal kingdom. Previously believed to be possessed by only the highest order mammals, it is now becoming clear that fish are also capable of this type of memory formation. Similar to the mammalian hippocampus, the dorsolateral pallium regulates distinct memory processes and is modulated by neurotransmitters such as dopamine. Caribbean bicolour damselfish (Stegastes partitus) live in complex environments dominated by coral reef structures and thus likely possess many types of complex memory abilities including object recognition. This study used a novel object recognition test in which fish were first presented two identical objects, then after a retention interval of 10 min with no objects, the fish were presented with a novel object and one of the objects they had previously encountered in the first trial. We demonstrate that the dopamine D1-receptor agonist (SKF 38393) induces the formation of object recognition memories in these fish. Thus, our results suggest that dopamine-receptor mediated enhancement of spatial memory formation in fish represents an evolutionarily conserved mechanism in vertebrates. © 2017 The Author(s).

  1. User-Generated Terrain Information

    Science.gov (United States)

    2013-04-26

    socioeconomic patterns in the use of Twitter and Flickr, Cartography and Geographic Information Science, (03 2013): 0. doi: 10.1080...15230406.2013.777139 04/26/2013 12.00 Michael F. Goodchild. The future of Digital Earth, Annals of GIS , (06 2012): 0. doi: 10.1080/19475683.2012.668561 08/15/2011...Geographers, (08 2012): 571. doi: 08/22/2012 9.00 Daniel Sui, Michael Goodchild. The convergence of GIS and social media: challenges for GIScience

  2. 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.

  3. 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...

  4. 76 FR 27380 - Proposed Information Collection (Offer To Purchase and Contract of Sale) Activity: Comment Request

    Science.gov (United States)

    2011-05-11

    ... AFFAIRS Proposed Information Collection (Offer To Purchase and Contract of Sale) Activity: Comment Request...) for each collection of information they conduct or sponsor. This request for comment is being made... techniques or the use of other forms of information technology. Titles a. Offer to Purchase and Contract of...

  5. 76 FR 40454 - Proposed Information Collection (VSO Access to VHA Electronic Health Records) Activity; Comment...

    Science.gov (United States)

    2011-07-08

    ... AFFAIRS Proposed Information Collection (VSO Access to VHA Electronic Health Records) Activity; Comment... attorney by veterans who have medical information recorded in VHA electronic health records system... techniques or the use of other forms of information technology. Title: VSO Access to VHA Electronic Health...

  6. Forest inventories generate scientifically sound information on the forest resource, but do our data and information really matter?

    Science.gov (United States)

    Christoph Keinn; Goran Stahl

    2009-01-01

    Current research in forest inventory focuses very much on technical-statistical problems geared mainly to the optimization of data collection and information generation. The basic assumption is that better information leads to better decisions and, therefore, to better forest management and forest policy. Not many studies, however, strive to explicitly establish the...

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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…

  14. 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.

  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. 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.

  17. 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

  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; 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.

  19. 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.

  20. Can multi-generational exposure to ocean warming and acidification lead to the adaptation of life history and physiology in a marine metazoan?

    Science.gov (United States)

    Gibbin, Emma M; Chakravarti, Leela J; Jarrold, Michael D; Christen, Felix; Turpin, Vincent; Massamba N'Siala, Gloria; Blier, Pierre U; Calosi, Piero

    2017-02-15

    Ocean warming and acidification are concomitant global drivers that are currently threatening the survival of marine organisms. How species will respond to these changes depends on their capacity for plastic and adaptive responses. Little is known about the mechanisms that govern plasticity and adaptability or how global changes will influence these relationships across multiple generations. Here, we exposed the emerging model marine polychaete Ophryotrocha labronica to conditions simulating ocean warming and acidification, in isolation and in combination over five generations to identify: (i) how multiple versus single global change drivers alter both juvenile and adult life-history traits; (ii) the mechanistic link between adult physiological and fitness-related life-history traits; and (iii) whether the phenotypic changes observed over multiple generations are of plastic and/or adaptive origin. Two juvenile (developmental rate; survival to sexual maturity) and two adult (average reproductive body size; fecundity) life-history traits were measured in each generation, in addition to three physiological (cellular reactive oxygen species content, mitochondrial density, mitochondrial capacity) traits. We found that multi-generational exposure to warming alone caused an increase in juvenile developmental rate, reactive oxygen species production and mitochondrial density, decreases in average reproductive body size and fecundity, and fluctuations in mitochondrial capacity, relative to control conditions. Exposure to ocean acidification alone had only minor effects on juvenile developmental rate. Remarkably, when both drivers of global change were present, only mitochondrial capacity was significantly affected, suggesting that ocean warming and acidification act as opposing vectors of stress across multiple generations. © 2017. Published by The Company of Biologists Ltd.

  1. 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

  2. High-surface step density on dendritic pd leads to exceptional catalytic activity for formic acid oxidation.

    Science.gov (United States)

    Patra, S; Viswanath, B; Barai, K; Ravishankar, N; Munichandraiah, N

    2010-11-01

    Dendritic Pd with corrugated surfaces, obtained by a novel AC technique, exhibits an exceptionally high catalytic activity for the oxidation of formic acid because of the presence of a high density of surface steps. The formation of twinned dendrites leads to a predominance of exposed 111 facets with a high density of surface steps as evident from high resolution electron microscopy investigations. These surface sites provide active sites for the adsorption of the formic acid molecules, thereby enhancing the reaction rate. Control experiments by varying the time of deposition reveal the formation of partially grown dendrites at shorter times indicating that the dendrites were formed by growth rather than particle attachment. Our deposition method opens up interesting possibilities to produce anisotropic nanostructures with corrugated surfaces by exploiting the perturbations involved in the growth process.

  3. Prenatal malnutrition leads to deficits in attentional set shifting and decreases metabolic activity in prefrontal subregions that control executive function.

    Science.gov (United States)

    McGaughy, Jill A; Amaral, Ana C; Rushmore, R Jarrett; Mokler, David J; Morgane, Peter J; Rosene, Douglas L; Galler, Janina R

    2014-01-01

    Globally, over 25% of all children under the age of 5 years experience malnutrition leading to cognitive and emotional impairments that can persist into adulthood and beyond. We use a rodent model to determine the impact of prenatal protein malnutrition on executive functions in an attentional set-shifting task and metabolic activity in prefrontal cortex (PFC) subregions critical to these behaviors. Long-Evans dams were provided with a low (6% casein) or adequate (25% casein) protein diet 5 weeks before mating and during pregnancy. At birth, the litters were culled to 8 pups and fostered to control dams on the 25% casein diet. At postnatal day 90, prenatally malnourished rats were less able to shift attentional set and reverse reward contingencies than controls, demonstrating cognitive rigidity. Naive same-sexed littermates were assessed for regional brain activity using the metabolic marker (14)C-2-deoxyglucose (2DG). The prenatally malnourished rats had lower metabolic activity than controls in prelimbic, infralimbic, anterior cingulate, and orbitofrontal cortices, but had comparable activity in the nearby piriform cortex and superior colliculus. This study demonstrates that prenatal protein malnutrition in a well-described animal model produces cognitive deficits in tests of attentional set shifting and reversal learning, similar to findings of cognitive inflexibility reported in humans exposed to early childhood malnutrition. © 2014 S. Karger AG, Basel.

  4. 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.

  5. 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...

  6. Pathologic Active mTOR Mutation in Brain Malformation with Intractable Epilepsy Leads to Cell-Autonomous Migration Delay.

    Science.gov (United States)

    Hanai, Sae; Sukigara, Sayuri; Dai, Hongmei; Owa, Tomoo; Horike, Shin-Ichi; Otsuki, Taisuke; Saito, Takashi; Nakagawa, Eiji; Ikegaya, Naoki; Kaido, Takanobu; Sato, Noriko; Takahashi, Akio; Sugai, Kenji; Saito, Yuko; Sasaki, Masayuki; Hoshino, Mikio; Goto, Yu-Ichi; Koizumi, Schuichi; Itoh, Masayuki

    2017-05-01

    The activation of phosphatidylinositol 3-kinase-AKTs-mammalian target of rapamycin cell signaling pathway leads to cell overgrowth and abnormal migration and results in various types of cortical malformations, such as hemimegalencephaly (HME), focal cortical dysplasia, and tuberous sclerosis complex. However, the pathomechanism underlying abnormal cell migration remains unknown. With the use of fetal mouse brain, we performed causative gene analysis of the resected brain tissues from a patient with HME and investigated the pathogenesis. We obtained a novel somatic mutation of the MTOR gene, having approximately 11% and 7% mutation frequency in the resected brain tissues. Moreover, we revealed that the MTOR mutation resulted in hyperphosphorylation of its downstream molecules, S6 and 4E-binding protein 1, and delayed cell migration on the radial glial fiber and did not affect other cells. We suspect cell-autonomous migration arrest on the radial glial foot by the active MTOR mutation and offer potential explanations for why this may lead to cortical malformations such as HME. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells.

    Science.gov (United States)

    Rhein, V; Baysang, G; Rao, S; Meier, F; Bonert, A; Müller-Spahn, F; Eckert, A

    2009-09-01

    Evidence suggests that amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Here we investigated the specific effects of Abeta on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y). Mitochondrial respiratory capacity of mitochondrial electron transport chain (ETC) in vital cells was measured with a high-resolution respirometry system (Oxygraph-2k). In addition, we determined the individual activities of mitochondrial complexes I-IV that compose ETC and ATP cellular levels. While the activities of complexes I and II did not change between cell types, complex IV activity was significantly reduced in APP cells. In contrast, activity of complex III was significantly enhanced in APP cells, as compensatory response in order to balance the defect of complex IV. However, this compensatory mechanism could not prevent the strong impairment of total respiration in vital APP cells. As a result, the respiratory control ratio (state3/state4) together with ATP production decreased in the APP cells in comparison with the control cells. Chronic exposure to soluble Abeta protein may result in an impairment of energy homeostasis due to a decreased respiratory capacity of mitochondrial electron transport chain which, in turn, may accelerate neurons demise.

  8. 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.

  9. 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

    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......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...... design in BIM and simulations with the build environment....

  10. 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 ...

  11. 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...

  12. 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...

  13. 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...

  14. Coronary Sinus Lead Removal: A Comparison between Active and Passive Fixation Leads.

    Directory of Open Access Journals (Sweden)

    Simon Pecha

    Full Text Available Implantation of coronary sinus (CS leads may be a difficult procedure due to different vein anatomies and a possible lead dislodgement. The mode of CS lead fixation has changed and developed in recent years.We compared the removal procedures of active and passive fixation leads.Between January 2009 and January 2014, 22 patients at our centre underwent CS lead removal, 6 active and 16 passive fixation leads were attempted using simple traction or lead locking devices with or without laser extraction sheaths. Data on procedural variables and success rates were collected and retrospectively analyzed.The mean patient age was 67.2 ± 9.8 years, and 90.9% were male. The indication for lead removal was infection in all cases. All active fixation leads were Medtronic® Attain StarFix™ Model 4195 (Medtronic Inc., Minneapolis, MN, USA. The mean time from implantation for the active and passive fixation leads was 9.9 ± 11.7 months (range 1.0-30.1 and 48.7 ± 33.6 months (range 5.7-106.4, respectively (p = 0.012. Only 3 of 6 StarFix leads were successfully removed (50% compared to 16 of 16 (100% of the passive fixation CS leads (p = 0.013. No death or complications occurred during the 30-day follow-up.According to our experience, removal of the Starfix active fixation CS leads had a higher procedural failure rate compared to passive.

  15. 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

  16. 77 FR 22571 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2012-04-16

    ... total time, effort, 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... specifies certain public notices (i.e., radio, newspaper, and a letter to relevant agencies) that EPA must...

  17. Performance Assessment of the Lead User Idea-Generation Process for New Product Development

    OpenAIRE

    Gary L. Lilien; Morrison, Pamela D.; Kathleen Searls; Mary Sonnack; Eric von Hippel

    2002-01-01

    Traditional idea generation techniques based on customer input usually collect information on new product needs from a random or typical set of customers. The "lead user process" takes a different approach. It collects information about both needs and solutions from users at the leading edges of the target market, as well as from users in other markets that face similar problems in a more extreme form. This paper reports on a natural experiment conducted within the 3M Company on the effect of...

  18. Support-dependent active species formation for CuO catalysts: Leading to efficient pollutant degradation in alkaline conditions.

    Science.gov (United States)

    Li, Yibing; Guo, Lianshuang; Huang, Dekang; Jawad, Ali; Chen, Zhuqi; Yang, Jiakuan; Liu, Weidong; Shen, Yan; Wang, Mingkui; Yin, Guochuan

    2017-04-15

    Redox metal ions play the crucial role in versatile advanced oxidation technologies, in which controlling the active species formation through catalyst design is one of the key challenges in oxidant utilization. This work describes an example of different active species formations in CuO-mediated degradation just because of supporting material differences. Although three CuO catalysts were prepared by similar procedures, it was found that CuO-MgO catalyst demonstrated high efficiency in phenol degradation with bicarbonate activated H2O2, in which the superoxide radical is crucial, while hydroxyl radical and singlet oxygen are ignorable. For the CuO-MgO-Al2O3 and CuO-Al2O3 catalysts, the degradation proceeds by popular hydroxyl radical based process, however, the efficiency was poor. The EPR experiments also confirmed the absence of hydroxyl radical in CuO-MgO system but its presence in CuO-MgO-Al2O3 and CuO-Al2O3 system. The high catalytic efficiency with ignorable hydroxyl radical in the CuO-MgO system leads us to propose that an alternative Cu(III) species dominates the degradation. The basic MgO support may facilitate the formation of the Cu(III) species, whereas the neutral MgO-Al2O3 and acidic Al2O3 supports are unable to stabilize the high valent Cu(III) species, leading to the common hydroxyl radical mechanism with low efficiency of H2O2 in alkaline conditions. Copyright © 2016. Published by Elsevier B.V.

  19. 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.

  20. 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.

  1. 77 FR 64339 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2012-10-19

    ... health records (PHRs). ONC intends to revise the project to use the same focus group and cognitive... the notice be written in plain language, but studies have shown that these notices are often difficult... time expended by persons to generate, maintain, retain, disclose or provide the information requested...

  2. 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;...

  3. 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;...

  4. 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...

  5. 76 FR 40920 - Agency Information Collection Activities; Proposed Collection; Comment Request; Data To Support...

    Science.gov (United States)

    2011-07-12

    ... HUMAN SERVICES Food and Drug Administration Agency Information Collection Activities; Proposed Collection; Comment Request; Data To Support Communications To Educate Consumers on How To Safely Purchase... information by the Agency. Under the Paperwork Reduction Act of 1995 (the PRA), Federal Agencies are required...

  6. 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...

  7. 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....

  8. 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).

  9. Beyond IgE—When Do IgE-Crosslinking and Effector Cell Activation Lead to Clinical Anaphylaxis?

    Directory of Open Access Journals (Sweden)

    Lars K. Poulsen

    2017-08-01

    Full Text Available Anaphylaxis in humans is inherently difficult to study due to the acuteness of symptoms and the lack of biomarkers serving as risk predictors. Most cases are related to IgE sensitizations to foods, insect venoms, and drugs with mastocytosis patients forming a smaller risk group. However, identifying the relatively small fraction of persons at risk has been exceedingly difficult. In this review, we propose to describe anaphylaxis in a broader context than defined by IgE sensitization alone. Exposure to a trigger, such as an allergen, may lead to anaphylaxis, but in particular, the internal dose sensed by the immune system needs to be established. Moreover, intrinsic patient factors as well as the specific circumstances of the exposure, i.e., the extrinsic factors, need to be thoroughly accounted for. More controversially, other triggers of anaphylaxis, such as increased sensitivity to or reduced catabolism of histamine (“histamine intolerance” or mast cell activation syndrome also named mast cell activation disorder have been suggested, but still with very limited epidemiological evidence that a significant proportion of the observed reactions are caused by these alleged conditions. Thus, when all conditions are considered, it seems as if IgE-mediated reactions are responsible for the vast majority of anaphylactic conditions.

  10. 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.

  11. 78 FR 59941 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

    Science.gov (United States)

    2013-09-30

    ... HUMAN SERVICES Health Resources and Services Administration Agency Information Collection Activities... best practices, leveraging the influence of national associations and organizations related to... identify best practices that can be shared with all hospital partners on monthly webinars. Likely...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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:...

  20. 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:...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  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. 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...

  9. 76 FR 56503 - Agency Information Collection Activity (VSO Access to VHA Electronic Health Records) Under OMB...

    Science.gov (United States)

    2011-09-13

    ... AFFAIRS Agency Information Collection Activity (VSO Access to VHA Electronic Health Records) Under OMB... INFORMATION: Title: VSO Access to VHA Electronic Health Records, VA Form 10- 0400. OMB Control Number: 2900... recorded in VHA electronic health records system. An agency may not conduct or sponsor, and a person is not...

  10. 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...

  11. 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...

  12. 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...

  13. 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 ...

  14. Using Electronic Neutron Generators in Active Interrogation to Detect Shielded Fissionable Material

    Energy Technology Data Exchange (ETDEWEB)

    D. L. Chichester; E. H. Seabury

    2008-10-01

    Experiments have been performed at Idaho National Laboratory to study methodology and instrumentation for performing neutron active interrogation die-away analyses for the purpose of detecting shielded fissionable material. Here we report initial work using a portable DT electronic neutron generator with a He-3 fast neutron detector to detect shielded fissionable material including >2 kg quantities of enriched uranium and plutonium. Measurements have been taken of bare material as well as of material hidden within a large plywood cube. Results from this work have demonstrated the efficacy of the die-away neutron measurement technique for quickly detecting the presence of special nuclear material hidden within plywood shields by analyzing the time dependent neutron signals in-between neutron generator pulses. Using a DT electronic neutron generator operating at 300 Hz with a yield of approximately 0.36 x 10**8 neutrons per second, 2.2 kg of enriched uranium hidden within a 0.60 m x 0.60 m x 0.70 m volume of plywood was positively detected with a measurement signal 2-sigma above the passive background within 1 second. Similarly, for a 500 second measurement period a lower detection limit of approaching the gram level could be expected with the same simple set-up.

  15. 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.

  16. 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...

  17. 78 FR 34112 - Agency Information Collection Activities: Request for Expressions of Interest (EOI) To Perform a...

    Science.gov (United States)

    2013-06-06

    ... Homeland Security, Office of Health Affairs, Chemical Defense Program will submit the following information... SECURITY Agency Information Collection Activities: Request for Expressions of Interest (EOI) To Perform a... contact: The Department of Homeland Security (DHS), Office of Health Affairs, Chemical Defense Program...

  18. 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.

  19. 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…

  20. 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…

  1. 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.

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

    Science.gov (United States)

    Chen, Chen; Han, Sheng; Meng, Lingxuan; Li, Zhonghua; Zhang, Xue; Wu, Anhua

    2014-01-01

    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.

  3. 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.

  4. 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...

  5. 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

  6. 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.

  7. 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

  8. An Active RBSE Framework to Generate Optimal Stimulus Sequences in a BCI for Spelling

    Science.gov (United States)

    Moghadamfalahi, Mohammad; Akcakaya, Murat; Nezamfar, Hooman; Sourati, Jamshid; Erdogmus, Deniz

    2017-10-01

    A class of brain computer interfaces (BCIs) employs noninvasive recordings of electroencephalography (EEG) signals to enable users with severe speech and motor impairments to interact with their environment and social network. For example, EEG based BCIs for typing popularly utilize event related potentials (ERPs) for inference. Presentation paradigm design in current ERP-based letter by letter typing BCIs typically query the user with an arbitrary subset characters. However, the typing accuracy and also typing speed can potentially be enhanced with more informed subset selection and flash assignment. In this manuscript, we introduce the active recursive Bayesian state estimation (active-RBSE) framework for inference and sequence optimization. Prior to presentation in each iteration, rather than showing a subset of randomly selected characters, the developed framework optimally selects a subset based on a query function. Selected queries are made adaptively specialized for users during each intent detection. Through a simulation-based study, we assess the effect of active-RBSE on the performance of a language-model assisted typing BCI in terms of typing speed and accuracy. To provide a baseline for comparison, we also utilize standard presentation paradigms namely, row and column matrix presentation paradigm and also random rapid serial visual presentation paradigms. The results show that utilization of active-RBSE can enhance the online performance of the system, both in terms of typing accuracy and speed.

  9. Approach for Estimating Exposures and Incremental Health Effects from Lead Due to Renovation Repair and Painting Activities in Public and Commercial Buildings

    Science.gov (United States)

    Approach for Estimating Exposures and Incremental Health Effects from Lead Due to Renovation Repair and Painting Activities in Public and Commercial Buildings: links to documents at www.regulations.gov, links to PDFs related to Approach document

  10. 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.

  11. Electrical stimulation at distinct peripheral sites in spinal nerve injured rats leads to different afferent activation profiles.

    Science.gov (United States)

    Yang, Fei; Chung, Chih-Yang; Wacnik, Paul W; Carteret, Alene F; McKelvy, Alvin D; Meyer, Richard A; Raja, Srinivasa N; Guan, Yun

    2011-11-07

    The neurophysiological basis by which neuromodulatory techniques lead to relief of neuropathic pain remains unclear. We investigated whether electrical stimulation at different peripheral sites induces unique profiles of A-fiber afferent activation in nerve-injured rats. At 4-6weeks after subjecting rats to L5 spinal nerve injury (SNL) or sham operation, we recorded the orthodromic compound action potential (AP) at the ipsilateral L4 dorsal root in response to (1) transcutaneous electrical nerve stimulation (TENS, a patch electrode placed on the dorsum of the foot), (2) subcutaneous electrical stimulation (SQS, electrode inserted subcutaneously along the dorsum of the foot), (3) peroneal nerve stimulation (PNS, electrode placed longitudinally abutting the nerve), and (4) sciatic nerve stimulation (SNS). The area under the Aα/β compound AP was measured as a function of the bipolar, constant-current stimulus intensity (0.02-6.0 mA, 0.2 ms). In both nerve-injured and sham-operated groups, the stimulus-response (S-R) functions of the Aα/β compound APs differed substantially with the stimulation site; SNS having the lowest threshold and largest compound AP waveform, followed by PNS, SQS, and TENS. The S-R function to PNS was shifted to the right in the SNL group, compared to that in the sham-operated group. The Aα/β-threshold to PNS was higher in the SNL group than in the sham-operated group. The S-R functions and Aα/β-thresholds to TENS and SQS were comparable between the two groups. Electrical stimulation of different peripheral targets induced distinctive profiles of A-fiber afferent activation, suggesting that the neuronal substrates for the various forms of peripheral neuromodulatory therapies may differ. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. Cochrane Rapid Reviews Methods Group to play a leading role in guiding the production of informed high-quality, timely research evidence syntheses.

    Science.gov (United States)

    Garritty, Chantelle; Stevens, Adrienne; Gartlehner, Gerald; King, Valerie; Kamel, Chris

    2016-10-28

    Policymakers and healthcare stakeholders are increasingly seeking evidence to inform the policymaking process, and often use existing or commissioned systematic reviews to inform decisions. However, the methodologies that make systematic reviews authoritative take time, typically 1 to 2 years to complete. Outside the traditional SR timeline, "rapid reviews" have emerged as an efficient tool to get evidence to decision-makers more quickly. However, the use of rapid reviews does present challenges. To date, there has been limited published empirical information about this approach to compiling evidence. Thus, it remains a poorly understood and ill-defined set of diverse methodologies with various labels. In recent years, the need to further explore rapid review methods, characteristics, and their use has been recognized by a growing network of healthcare researchers, policymakers, and organizations, several with ties to Cochrane, which is recognized as representing an international gold standard for high-quality, systematic reviews. In this commentary, we introduce the newly established Cochrane Rapid Reviews Methods Group developed to play a leading role in guiding the production of rapid reviews given they are increasingly employed as a research synthesis tool to support timely evidence-informed decision-making. We discuss how the group was formed and outline the group's structure and remit. We also discuss the need to establish a more robust evidence base for rapid reviews in the published literature, and the importance of promoting registration of rapid review protocols in an effort to promote efficiency and transparency in research. As with standard systematic reviews, the core principles of evidence-based synthesis should apply to rapid reviews in order to minimize bias to the extent possible. The Cochrane Rapid Reviews Methods Group will serve to establish a network of rapid review stakeholders and provide a forum for discussion and training. By facilitating

  18. 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.

  19. "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

  20. 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.

  1. 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.

  2. 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

  3. The First Negative Allosteric Modulator for Dopamine D2 and D3 Receptors, SB269652 May Lead to a New Generation of Antipsychotic Drugs.

    Science.gov (United States)

    Rossi, Mario; Fasciani, Irene; Marampon, Francesco; Maggio, Roberto; Scarselli, Marco

    2017-06-01

    D2 and D3 dopamine receptors belong to the largest family of cell surface proteins in eukaryotes, the G protein-coupled receptors (GPCRs). Considering their crucial physiologic functions and their relatively accessible cellular locations, GPCRs represent one of the most important classes of therapeutic targets. Until recently, the only strategy to develop drugs regulating GPCR activity was through the identification of compounds that directly acted on the orthosteric sites for endogenous ligands. However, many efforts have recently been made to identify small molecules that are able to interact with allosteric sites. These sites are less well-conserved, therefore allosteric ligands have greater selectivity on the specific receptor. Strikingly, the use of allosteric modulators can provide specific advantages, such as an increased selectivity for GPCR subunits and the ability to introduce specific beneficial therapeutic effects without disrupting the integrity of complex physiologically regulated networks. In 2010, our group unexpectedly found that N-[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide (SB269652), a compound supposed to interact with the orthosteric binding site of dopamine receptors, was actually a negative allosteric modulator of D2- and D3-receptor dimers, thus identifying the first allosteric small molecule acting on these important therapeutic targets. This review addresses the progress in understanding the molecular mechanisms of interaction between the negative modulator SB269652 and D2 and D3 dopamine receptor monomers and dimers, and surveys the prospects for developing new dopamine receptor allosteric drugs with SB269652 as the leading compound. U.S. Government work not protected by U.S. copyright.

  4. 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.

  5. 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.

  6. Anesthesia-related changes in information transfer may be caused by reduction in local information generation.

    Science.gov (United States)

    Wollstadt, Patricia; Sellers, Kristin K; Hutt, Axel; Frohlich, Flavio; Wibral, Michael

    2015-08-01

    In anesthesia research it is an open question how general anesthetics lead to loss of consciousness (LOC). It has been proposed that LOC may be caused by the disruption of cortical information processing, preventing information integration. Therefore, recent studies investigating information processing under anesthesia focused on changes in information transfer, measured by transfer entropy (TE). However, often this complex technique was not applied rigorously, using time series in symbolic representation, or using TE differences without accounting for neural conduction delays, or without accounting for signal history. Here, we used current best-practice in TE estimation to investigate information transfer under anesthesia: We conducted simultaneous recordings in primary visual cortex (V1) and prefrontal cortex (PFC) of head-fixed ferrets in a dark environment under different levels of anesthesia (awake, 0.5% isoflurane, 1.0 % isoflurane). To elucidate reasons for changes in TE, we further quantified information processing within brain areas by estimating active information storage (AIS) as an estimator of predictable information, and Lempel-Ziv complexity (LZC) as an estimator of signal entropy. Under anesthesia, we found a reduction in information transfer (TE) between PFC and V1 with a stronger reduction for the feedback direction (PFC to V1), validating previous results. Furthermore, entropy (LZC) was reduced and activity became more predictable as indicated by higher values of AIS. We conclude that higher anesthesia concentrations indeed lead to reduced inter-areal information transfer, which may be partly caused by decreases in local entropy and increases in local predictability. In revealing a possible reason for reduced TE that is potentially independent of inter-areal coupling, we demonstrate the value of directly quantifying information processing in addition to focusing on dynamic properties such as coupling strength.

  7. 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

  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. 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.

  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. 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.

  12. 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.

  13. 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....

  14. 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.

  15. 77 FR 477 - Agency Information Collection Activities: Rules Relating to Regulation of Domestic Exchange...

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    2012-01-05

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  17. 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.

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    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;...

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  20. 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.

  1. 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

  2. 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.

  3. 78 FR 47424 - Agency Information Collection Activities: Submission to OMB for Reinstatement, With Change, of a...

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    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...

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    ... types of financial services) as a more efficient way to bring information about suspicious activity to... regulations requiring other types of financial institutions, such as brokers or dealers in securities and... Financial Crimes Enforcement Network (FinCEN) transitioned from a system originally designed for collecting...

  6. 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...

  7. 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...

  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. KID - an algorithm for fast and efficient text mining used to automatically generate a database containing kinetic information of enzymes

    Directory of Open Access Journals (Sweden)

    Schomburg Dietmar

    2010-07-01

    Full Text Available Abstract Background The amount of available biological information is rapidly increasing and the focus of biological research has moved from single components to networks and even larger projects aiming at the analysis, modelling and simulation of biological networks as well as large scale comparison of cellular properties. It is therefore essential that biological knowledge is easily accessible. However, most information is contained in the written literature in an unstructured way, so that methods for the systematic extraction of knowledge directly from the primary literature have to be deployed. Description Here we present a text mining algorithm for the extraction of kinetic information such as KM, Ki, kcat etc. as well as associated information such as enzyme names, EC numbers, ligands, organisms, localisations, pH and temperatures. Using this rule- and dictionary-based approach, it was possible to extract 514,394 kinetic parameters of 13 categories (KM, Ki, kcat, kcat/KM, Vmax, IC50, S0.5, Kd, Ka, t1/2, pI, nH, specific activity, Vmax/KM from about 17 million PubMed abstracts and combine them with other data in the abstract. A manual verification of approx. 1,000 randomly chosen results yielded a recall between 51% and 84% and a precision ranging from 55% to 96%, depending of the category searched. The results were stored in a database and are available as "KID the KInetic Database" via the internet. Conclusions The presented algorithm delivers a considerable amount of information and therefore may aid to accelerate the research and the automated analysis required for today's systems biology approaches. The database obtained by analysing PubMed abstracts may be a valuable help in the field of chemical and biological kinetics. It is completely based upon text mining and therefore complements manually curated databases. The database is available at http://kid.tu-bs.de. The source code of the algorithm is provided under the GNU General Public

  11. 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.

  12. 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.

  13. 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...

  14. 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...

  15. 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......

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 76 FR 9776 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Science.gov (United States)

    2011-02-22

    ... announces that an Information Collection Request (ICR) has been forwarded to the Office of Management and... Affairs, Office of Management and Budget, Attention: Desk Officer for EPA, 725 17th Street, NW... surveys, tracking and monitoring of classroom activities and school policies, and consultation with...

  3. 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 in the sig...

  4. 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.

  5. Enriching step-based product information models to support product life-cycle activities

    Science.gov (United States)

    Sarigecili, Mehmet Ilteris

    The representation and management of product information in its life-cycle requires standardized data exchange protocols. Standard for Exchange of Product Model Data (STEP) is such a standard that has been used widely by the industries. Even though STEP-based product models are well defined and syntactically correct, populating product data according to these models is not easy because they are too big and disorganized. Data exchange specifications (DEXs) and templates provide re-organized information models required in data exchange of specific activities for various businesses. DEXs show us it would be possible to organize STEP-based product models in order to support different engineering activities at various stages of product life-cycle. In this study, STEP-based models are enriched and organized to support two engineering activities: materials information declaration and tolerance analysis. Due to new environmental regulations, the substance and materials information in products have to be screened closely by manufacturing industries. This requires a fast, unambiguous and complete product information exchange between the members of a supply chain. Tolerance analysis activity, on the other hand, is used to verify the functional requirements of an assembly considering the worst case (i.e., maximum and minimum) conditions for the part/assembly dimensions. Another issue with STEP-based product models is that the semantics of product data are represented implicitly. Hence, it is difficult to interpret the semantics of data for different product life-cycle phases for various application domains. OntoSTEP, developed at NIST, provides semantically enriched product models in OWL. In this thesis, we would like to present how to interpret the GD & T specifications in STEP for tolerance analysis by utilizing OntoSTEP.

  6. 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.

  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. 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.

  11. 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...

  12. 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...

  13. 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...

  14. Could low level laser therapy and highly active antiretroviral therapy lead to complete eradication of HIV-1 in vitro?

    CSIR Research Space (South Africa)

    Lugongolo, Masixole Y

    2017-01-01

    Full Text Available Human immunodeficiency virus (HIV-1) infection remains a major health problem despite the use of highly active antiretroviral therapy (HAART), which has greatly reduced mortality rates. Due to the unavailability of an effective vaccine or a...

  15. 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

  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. 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...

  18. Strategies for conducting ADME studies during lead generation in the drug discovery process.

    Science.gov (United States)

    Cramer, Jeffrey W; Mattioni, Brian E; Savin, Kenneth A

    2010-12-01

    Although the benefit of early ADME screening is widely recognized in the pharmaceutical industry, the implementation of this paradigm is often performed with insufficient resources and poor collaboration between functions. Dedicated and consistent integration efforts of ADME knowledge during the lead generation (LG) phase of drug discovery enables informed resourcing decisions and also increases the quality of initial starting points for discovery projects. To facilitate the efficient and consistent application of ADME resources to early projects at Eli Lilly and Co, a team of scientists was formed to provide dedicated ADME support to the LG phase of the discovery portfolio. This feature review discusses the working construct of the team, the general philosophy that was employed, and the outcomes of this endeavor.

  19. 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)...

  20. Lead transformation to pyromorphite by fungi.

    Science.gov (United States)

    Rhee, Young Joon; Hillier, Stephen; Gadd, Geoffrey Michael

    2012-02-07

    Lead (Pb) is a serious environmental pollutant in all its chemical forms [1]. Attempts have been made to immobilize lead in soil as the mineral pyromorphite using phosphate amendments (e.g., rock phosphate, phosphoric acid, and apatite [2-5]), although our work has demonstrated that soil fungi are able to transform pyromorphite into lead oxalate [6, 7]. Lead metal, an important structural and industrial material, is subject to weathering, and soil contamination also occurs through hunting and shooting [8, 9]. Although fungi are increasingly appreciated as geologic agents [10-12], there is a distinct lack of knowledge about their involvement in lead geochemistry. We examined the influence of fungal activity on lead metal and discovered that metallic lead can be transformed into chloropyromorphite, the most stable lead mineral that exists. This is of geochemical significance, not only regarding lead fate and cycling in the environment but also in relation to the phosphate cycle and linked with microbial transformations of inorganic and organic phosphorus. This paper provides the first report of mycogenic chloropyromorphite formation from metallic lead and highlights the significance of this phenomenon as a biotic component of lead biogeochemistry, with additional consequences for microbial survival in lead-contaminated environments and bioremedial treatments for Pb-contaminated land. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Insertional activation of cepA leads to high-level beta-lactamase expression in Bacteroides fragilis clinical isolates.

    Science.gov (United States)

    Rogers, M. B.; Bennett, T. K.; Payne, C. M.; Smith, C. J.

    1994-01-01

    Bacteroides fragilis is an important opportunistic pathogen of humans and is resistant to many drugs commonly used to treat anaerobic infections, including beta-lactams. A strain set comprised of B. fragilis isolates producing either low or high levels of the endogenous cephalosporinase activity, CepA, has been described previously (M. B. Rogers, A. C. Parker, and C. J. Smith, Antimicrob. Agents Chemother. 37:2391-2400, 1993). Clones containing cepA genes from each of seven representative strains were isolated, and the DNA sequences were determined. Nucleotide sequence comparisons revealed that there were few differences between the cepA coding sequences of the low- and high-activity strains. The cepA coding sequences were cloned into an expression vector, pFD340, and analyzed in a B. fragilis 638 cepA mutant. The results of beta-lactamase assays and ampicillin MICs showed that there was no significant difference in the enzymatic activity of structural genes from the high- or low-activity strains. Comparison of sequences upstream of the cepA coding region revealed that 50 bp prior to the translation start codon, the sequence for high-activity strains change dramatically. This region of the high-activity strains shared extensive homology with IS21, suggesting that an insertion was responsible for the increased expression of cepA in these isolates. Northern (RNA) blot analysis of total RNA by using cepA-specific DNA probes supported the idea that differential cepA expression in low- and high-activity strains was controlled at the level of transcription. However, the insertion did not alter the cepA transcription start site, which occurred 27 bp upstream of the ATG translation start codon in both expression classes. Possible mechanisms of cepA activation are discussed. Images PMID:7517394

  2. 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

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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.

  8. 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.

  9. Improved side information generation for distributed video coding

    DEFF Research Database (Denmark)

    Huang, Xin; Forchhammer, Søren

    2008-01-01

    information generation method, fewer bits will be requested from the encoder and more reliable decoded frames will be obtained. In this paper, a side information generation method is introduced to further improve the rate-distortion (RD) performance of transform domain distributed video coding. This algorithm......As a new coding paradigm, distributed video coding (DVC) deals with lossy source coding using side information to exploit the statistics at the decoder to reduce computational demands at the encoder. The performance of DVC highly depends on the quality of side information. With a better side...

  10. 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...

  11. 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.

  12. Generating passive NIR images from active LIDAR

    Science.gov (United States)

    Hagstrom, Shea; Broadwater, Joshua

    2016-05-01

    Many modern LIDAR platforms contain an integrated RGB camera for capturing contextual imagery. However, these RGB cameras do not collect a near-infrared (NIR) color channel, omitting information useful for many analytical purposes. This raises the question of whether LIDAR data, collected in the NIR, can be used as a substitute for an actual NIR image in this situation. Generating a LIDAR-based NIR image is potentially useful in situations where another source of NIR, such as satellite imagery, is not available. LIDAR is an active sensing system that operates very differently from a passive system, and thus requires additional processing and calibration to approximate the output of a passive instrument. We examine methods of approximating passive NIR images from LIDAR for real-world datasets, and assess differences with true NIR images.

  13. 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.

  14. 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...

  15. 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: a...... with severe epilepsy, and emphasize the importance of this biological pathway in seizure pathophysiology....... 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...... in a large cohort of 543 patients with a wide phenotypical range of epilepsies and intellectual disability revealed no additional pathogenic variants, showing that SYNJ1 deficiency is rare and probably linked to a specific phenotype. While variants leading to early onset parkinsonism selectively abolish Sac1...

  16. Catalase (CAT) promoter and 5'-UTR genetic variants lead to its altered expression and activity in vitiligo.

    Science.gov (United States)

    Mansuri, M S; Jadeja, S D; Singh, M; Laddha, N C; Dwivedi, M; Begum, R

    2017-05-25

    Oxidative stress is considered to be the initial event during the course of vitiligo. Catalase is mainly involved in the defense against oxidizing agents in the cell through detoxifying H2 O2 . Aims of the present study were 1) to assess the erythrocyte catalase activity and LPO levels, as well as CAT mRNA expression in skin and blood; 2) to investigate CAT promoter rs7943316, rs1001179; 5'-UTR rs1049982 and exon (rs17886350, rs11032709, rs17880442, rs35677492) polymorphisms and; 3) to perform genotype-phenotype/ haplotype correlation analyses, in vitiligo patients and controls from Gujarat. Catalase activity and lipid peroxidation levels were measured spectrophotometrically. CAT mRNA levels were estimated using Real-time PCR by SYBR-Green method. SNP genotyping was performed using PCR-RFLP/ ARMS-PCR methods. Vitiligo patients showed significantly decreased CAT mRNA-expression in lesional, non-lesional skin and in blood with reduced catalase activity compared to that of controls. CAT -89A/T and -20T/C polymorphisms were significantly associated with patients, especially with active and generalized vitiligo whereas, no association was observed for -262G/A and exon polymorphisms. 'A-262 T-89 C-20 ' haplotype with variant alleles was found to be associated with 6.4-fold risk of vitiligo. Genotype/ haplotype-phenotype correlation analyses revealed that individuals with susceptible genotypes/ haplotype for CAT -89 A/T and -20 T/C polymorphisms showed significantly decreased catalase mRNA/activity, and only -89 A/T polymorphisms showed significantly increased lipid peroxidation levels, as compared to wild type genotypes/ haplotype. In conclusion, the present study proposes the crucial role of catalase and its allelic variants in oxidative stress mediated pathogenesis of vitiligo. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. 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.

  18. 78 FR 15378 - Agency Information Collection Activities: Submission to OMB for Revision to a Currently Approved...

    Science.gov (United States)

    2013-03-11

    .... Frequency of Response: Once. Estimated Total Annual Burden Hours: 167 hours. Estimated Total Annual Cost: $3... to annually report to Congress the total amounts paid to minority- and women-owned businesses. In.... The information provided will be used to assign an ownership status to the vendor (i.e., minority...

  19. 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.

  20. 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…

  1. 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...

  2. 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...

  3. 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.

  4. 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.

  5. Lead removal in aqueous solution by activated carbons prepared ...

    African Journals Online (AJOL)

    AJL

    Langmuir models with the correlation coefficients higher than 0.9. ... generated from combustion of fuel lead content, in waters ... is realizable using many methods such as: ion exchange, ... consists of heating and cleaning of the small hydrated pieces of ... was used to control the temperature with an uncertainly of 0.1°C.

  6. 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...

  7. 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...

  8. 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)...

  9. Attention to Physical Activity-Equivalent Calorie Information on Nutrition Facts Labels: An Eye-Tracking Investigation.

    Science.gov (United States)

    Wolfson, Julia A; Graham, Dan J; Bleich, Sara N

    2017-01-01

    Investigate attention to Nutrition Facts Labels (NFLs) with numeric only vs both numeric and activity-equivalent calorie information, and attitudes toward activity-equivalent calories. An eye-tracking camera monitored participants' viewing of NFLs for 64 packaged foods with either standard NFLs or modified NFLs. Participants self-reported demographic information and diet-related attitudes and behaviors. Participants came to the Behavioral Medicine Lab at Colorado State University in spring, 2015. The researchers randomized 234 participants to view NFLs with numeric calorie information only (n = 108) or numeric and activity-equivalent calorie information (n = 126). Attention to and attitudes about activity-equivalent calorie information. Differences by experimental condition and weight loss intention (overall and within experimental condition) were assessed using t tests and Pearson's chi-square tests of independence. Overall, participants viewed numeric calorie information on 20% of NFLs for 249 ms. Participants in the modified NFL condition viewed activity-equivalent information on 17% of NFLs for 231 ms. Most participants indicated that activity-equivalent calorie information would help them decide whether to eat a food (69%) and that they preferred both numeric and activity-equivalent calorie information on NFLs (70%). Participants used activity-equivalent calorie information on NFLs and found this information helpful for making food decisions. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  10. Recycling of lead solder dross, Generated from PCB manufacturing

    Science.gov (United States)

    Lucheva, Biserka; Tsonev, Tsonio; Iliev, Peter

    2011-08-01

    The main purpose of this work is to analyze lead solder dross, a waste product from manufacturing of printed circuit boards by wave soldering, and to develop an effective and environmentally sound technology for its recycling. A methodology for determination of the content and chemical composition of the metal and oxide phases of the dross is developed. Two methods for recycling of lead solder dross were examined—carbothermal reduction and recycling using boron-containing substances. The influence of various factors on the metal yield was studied and the optimal parameters of the recycling process are defined. The comparison between them under the same parameters-temperature and retention time, showed that recycling of dross with a mixture of borax and boric acid in a 1:2 ratio provides higher metal yield (93%). The recycling of this hazardous waste under developed technology gets glassy slag and solder, which after correction of the chemical composition can be used again for production of PCB.

  11. Positional information generated by spatially distributed signaling cascades.

    Directory of Open Access Journals (Sweden)

    Javier Muñoz-García

    2009-03-01

    Full Text Available The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate analytical solution that relates the maximal amplitude and propagation length of each activation profile with the cascade level, protein diffusivity, and the ratio of the opposing enzyme activities. The control of the spatial signal propagation appears to be very different from the control of transient temporal responses for spatially homogenous cascades. For spatially distributed cascades where activating and deactivating enzymes operate far from saturation, the ratio of the opposing enzyme activities is shown to be a key parameter controlling signal propagation. The signaling gradients characteristic for robust signal propagation exemplify a pattern formation mechanism that generates precise spatial guidance for multiple cellular processes and conveys information about the cell size to the nucleus.

  12. 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...

  13. 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...

  14. 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

  15. 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)

  16. Collaboration leads to enhanced curriculum.

    Science.gov (United States)

    Valerius, J; Mohan, V; Doctor, D; Hersh, W

    2015-01-01

    In 2007, we initiated a health information management (HIM) track of our biomedical informatics graduate program, and subsequent ongoing program assessment revealed a confluence of topics and courses within HIM and clinical informatics (CI) tracks. We completed a thorough comparative analysis of competencies derived from AMIA, AHIMA, and CAHIIM. Coupled with the need to streamline course offerings, the process, described in this paper allowed new opportunities for faculty collaboration, resulted in the creation of a model assessment for best practice in courses, and led to new avenues of growth within the program. The objective of the case study is to provide others in the informatics educational community with a model for analysis of curriculum in order to improve quality of student learning. We describe a case study where an academic informatics program realigned its course offerings to better reflect the HIM of today, and prepare for challenges of the future. Visionary leadership, intra-departmental self-analysis and alignment of the curriculum through defined mapping process reduced overlap within the CI and HIM tracks. Teaching within courses was optimized through the work of core faculty collaboration. The analysis of curriculum resulted in reduction of overlap within course curriculum. This allowed for additional and new course content to be added to existing courses. Leadership fostered an environment where top-down as well as bottom-up collaborative assessment activities resulted in a model to consolidate learning and reduce unnecessary duplication within courses. A focus on curriculum integration, emphasis on course alignment and strategic consolidation of course content raised the quality of informatics education provided to students. Faculty synergy was an essential component of this redesign process. Continuous quality improvement strategy included an ongoing alignment of curriculum and competencies through a comparative analysis approach. Through

  17. 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.

  18. 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.

  19. 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.

  20. The information activity of rail passenger information staff: a foundation for information system requirements

    Directory of Open Access Journals (Sweden)

    Martin Rose

    2006-01-01

    Full Text Available Introduction. This paper examines the goal-directed information activity of passenger information staff, working in the dynamic environment of rail network control. The explicit aim is to define a meaningful set of information system requirements. The report shows how dynamic situations may lead us to question a number of established theories of information science. Method. Passenger information officers (PIOs were observed on duty within the rail command and control headquarters. Observation sessions totally eight hours involved the manual recording of sequential information flows and the associated activity of PIOs. A semi-structured management interview was also conducted to provide further insight into the organizational context. Analysis. A viewpoint-oriented analysis technique was used to analyse sequential data captured during observation sessions. Event sequences that represent and explain the viewpoints were identified and elaborated into detailed scenario descriptions. Results. The analysis both supports and contests a number of established theories from information science. Additionally, a range of 'mandatory' and 'desirable' system requirements are derived from the scenario and viewpoint analyses. Conclusion. Dynamic situations have a significant impact on information behaviour which is not always predicted by current theories of information science.

  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. All Roads Lead To Rome

    DEFF Research Database (Denmark)

    Ottosen, Thorsten Jørgen; Vomlel, Jiri

    2010-01-01

    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 size triangulations...

  3. 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....

  4. 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.

  5. Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels

    Science.gov (United States)

    Delorme-Walker, Violaine; Seo, Ji-Yeon; Gohla, Antje; Fowler, Bruce; Bohl, Ben; DerMardirossian, Céline

    2015-01-01

    Cofilin, a critical player of actin dynamics, is spatially and temporally regulated to control the direction and force of membrane extension required for cell locomotion. In carcinoma cells, although the signaling pathways regulating cofilin activity to control cell direction have been established, the molecular machinery required to generate the force of the protrusion remains unclear. We show that the cofilin phosphatase chronophin (CIN) spatiotemporally regulates cofilin activity at the cell edge to generate persistent membrane extension. We show that CIN translocates to the leading edge in a PI3-kinase–, Rac1-, and cofilin-dependent manner after EGF stimulation to activate cofilin, promotes actin free barbed end formation, accelerates actin turnover, and enhances membrane protrusion. In addition, we establish that CIN is crucial for the balance of protrusion/retraction events during cell migration. Thus, CIN coordinates the leading edge dynamics by controlling active cofilin levels to promote MTLn3 cell protrusion. PMID:26324884

  6. 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.

  7. 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...

  8. 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.

  9. 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...

  10. Treatment of Nuclear Data Covariance Information in Sample Generation.

    Energy Technology Data Exchange (ETDEWEB)

    Swiler, Laura Painton; Adams, Brian M.; Wieselquist, William (ORNL)

    2017-10-01

    This report summarizes a NEAMS (Nuclear Energy Advanced Modeling and Simulation) project focused on developing a sampling capability that can handle the challenges of generating samples from nuclear cross-section data. The covariance information between energy groups tends to be very ill-conditioned and thus poses a problem using traditional methods for generated correlated samples. This report outlines a method that addresses the sample generation from cross-section matrices.

  11. 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...

  12. 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...

  13. 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...

  14. Sentinel-1 data exploitation for geohazard activity map generation

    Science.gov (United States)

    Barra, Anna; Solari, Lorenzo; Béjar-Pizarro, Marta; Monserrat, Oriol; Herrera, Gerardo; Bianchini, Silvia; Crosetto, Michele; María Mateos, Rosa; Sarro, Roberto; Moretti, Sandro

    2017-04-01

    This work is focused on geohazard mapping and monitoring by exploiting Sentinel-1 (A and B) data and the DInSAR (Differential interferometric SAR (Synthetic Aperture Radar)) techniques. Sometimes the interpretation of the DInSAR derived product (like the velocity map) can be complex, mostly for a final user who do not usually works with radar. The aim of this work is to generate, in a rapid way, a clear product to be easily exploited by the authorities in the geohazard management: intervention planning and prevention activities. Specifically, the presented methodology has been developed in the framework of the European project SAFETY, which is aimed at providing Civil Protection Authorities (CPA) with the capability of periodically evaluating and assessing the potential impact of geohazards (volcanic activity, earthquakes, landslides and subsidence) on urban areas. The methodology has three phases, the interferograms generation, the activity map generation, in terms of velocity and accumulated deformation (with time-series), and the Active Deformation Area (ADA) map generation. The last one is the final product, derived from the original activity map by analyzing the data in a Geographic Information System (GIS) environment, which isolate only the true deformation areas over the noise. This product can be more easily read by the authorities than the original activity map, i.e. can be better exploited to integrate other information and analysis. This product also permit an easy monitoring of the active areas.

  15. 78 FR 54681 - Agency Information Collection Activities: Submission to OMB for Reinstatement, With Change, of a...

    Science.gov (United States)

    2013-09-05

    ...: Request for comment. SUMMARY: The NCUA intends to submit the following information collection to the... purchases. This data collection enables NCUA to evaluate waiver requests of these limits. DATES: Comments... 20503. FOR FURTHER INFORMATION CONTACT: Requests for additional information, a copy of the information...

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 78 FR 33075 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-06-03

    ... areas, such as mathematics, reading, writing, science, U.S. history, civics, geography, economics, and... activities, including the collection of information on students with disabilities (SD) and English language...

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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 ...

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Identification of a novel component leading to anti-tumor activity besides the major ingredient cordycepin in Cordyceps militaris extract.

    Science.gov (United States)

    Wada, Takeharu; Sumardika, I Wayan; Saito, Shingo; Ruma, I Made Winarsa; Kondo, Eisaku; Shibukawa, Masami; Sakaguchi, Masakiyo

    2017-09-01

    In accordance with our previous study that was carried out to identify novel anti-tumor ingredients, chromatographic separation in combination with an anti-tumor activity assay was used for analysis of Cordyceps militaris extract in this study. Various modes of chromatography including reversed-phase, cation-exchange and anion-exchange were used to separate components of Cordyceps militaris, which showed various chemical properties. Anti-tumor activity of each fraction was assessed by a Hoechst staining-based apoptosis assay using malignant melanoma MeWo cells. By these repeated approaches through chromatographic segregation and cell biological assay, we finally succeeded in identifying the target substance from a certain fraction that included neutral hydrophilic components using a pre-column and post-column chlorine adduct ionization LC-APCI-MS method. The target substance was a mono-carbohydrate, xylitol, that induced apoptotic cell death in MeWo cells but not in normal human OUMS-24 fibroblasts. This is the first study showing that Cordyceps militaris extract contains a large amount of xylitol. Thus, our results will contribute greatly to uncovering the mysterious multifunctional herbal drug Cordyceps militaris as an anti-tumor agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Postural changes associated with public speech tests lead to mild and selective activation of stress hormone release.

    Science.gov (United States)

    Mlynarik, M; Makatsori, A; Dicko, I; Hinghofer-Szalkay, H G; Jezova, D

    2007-03-01

    We tested whether simulation of postural changes, which occur during public speech test procedures, activates cardiovascular system and stress hormone release that could interfere with the effect of psychosocial stress load. Young healthy male volunteers (n=8) underwent procedure imitating exactly all postural changes present in the psychosocial stress model based on public speech used in this laboratory (namely changes from sitting to standing and repeated sitting). Postural changes were associated with increases in heart rate, blood pressure, plasma concentrations of noradrenaline and aldosterone and elevation in plasma renin activity. In contrast to cardiovascular parameters, adrenocorticotropic hormone, cortisol and adrenaline, the main characteristics of hormonal response during mental stress, were not significantly influenced. The overall magnitude of all observed alterations was much smaller than that seen following mental stress procedures in our previous studies. This study provides evidence that changes in body posture during public speech test procedure influence hemodynamics and endocrine responses in a mild manner. Though this influence may represent a source of unspecific variance, substantial confounding effects on responses to the psychosocial component of the procedure are unlikely. In any case, models combining mental stressors and changes in body posture must be interpreted as complex stress stimuli.

  15. 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.

  16. 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

  17. 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...

  18. 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.

  19. Adherence to Physical Activity Among Older Adults Using a Geographic Information System: Korean National Health and Nutrition Examinations Survey IV.

    Science.gov (United States)

    Yeom, Hye-A; Jung, Dukyoo; Choi, Mona

    2011-06-01

    The purpose of this study was to examine the adherence to physical activity (PA) among older adults in Korea using data from the Fourth Korean National Health and Nutrition Examination Survey (KNHANESIV), and to illustrate geographic variations in PA using Geographic Information Systems (GIS). A secondary analysis of the KNHANES IV data from 2007 to 2008 was used for this study. Participants of the study included 2,241 older adults over the age of 65. Estimates on adherence to PA were obtained for vigorous, moderate, walking, strengthening, and stretching activities. All estimates were weighted to represent Korean population. The association between participants' characteristics and PA was analyzed using Wald chi-square test. Maps depicting regional variations in PA were created using GIS software. Adherence to PA among Korean older adults who met national recommendations during the period of year 2007-2008 was about 9% in vigorous activity, 10% in moderate activity, and 48% in walking. The most common type of PA was walking. A higher level of PA was associated with male gender, younger age, high level of income and education, and living with family. The majority of older adults did not meet the national PA recommendations, suggesting that consistent surveillance and intervention for PA in the geriatric population are needed in the future. Maps generated using GIS visually showed regional differences in PA among the study participants. Copyright © 2011 Korean Society of Nursing Science. Published by Elsevier B.V. All rights reserved.

  20. Who Gets to Lead the Multinational Team?

    DEFF Research Database (Denmark)

    Paunova, Minna

    2017-01-01

    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...

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Could low level laser therapy and highly active antiretroviral therapy lead to complete eradication of HIV-1 in vitro?

    Science.gov (United States)

    Lugongolo, Masixole Yvonne; Manoto, Sello Lebohang; Ombinda-Lemboumba, Saturnin; Maaza, Malik; Mthunzi-Kufa, Patience

    2017-02-01

    Human immunodeficiency virus (HIV-1) infection remains a major health problem despite the use of highly active antiretroviral therapy (HAART), which has greatly reduced mortality rates. Due to the unavailability of an effective vaccine or a treatment that would completely eradicate the virus, the quest for new and combination therapies continues. In this study we explored the influence of Low Level Laser Therapy (LLLT) in HIV-1 infected and uninfected cells. Literature reports LLLT as widely used to treat different medical conditions such as diabetic wounds, sports injuries and others. The technique involves exposure of cells or tissue to low levels of red and near infrared laser light. Both HIV infected and uninfected cells were laser irradiated at a wavelength of 640 nm with fluencies ranging from 2 to 10 J/cm2 and cellular responses were assessed 24 hours post laser treatment. In our studies, laser therapy had no inhibitory effects in HIV-1 uninfected cells as was indicated by the cell morphology and proliferation results. However, laser irradiation enhanced cell apoptosis in HIV-1 infected cells as the laser fluencies increased. This led to further studies in which laser irradiation would be conducted in the presence of HAART to determine whether HAART would minimise the detrimental effects of laser irradiation in infected cells.

  6. Decreased mitochondrial activities of malate dehydrogenase and fumarase in tomato lead to altered root growth and architecture via diverse mechanisms.

    Science.gov (United States)

    van der Merwe, Margaretha J; Osorio, Sonia; Moritz, Thomas; Nunes-Nesi, Adriano; Fernie, Alisdair R

    2009-02-01

    Transgenic tomato (Solanum lycopersicum) plants in which either mitochondrial malate dehydrogenase or fumarase was antisense inhibited have previously been characterized to exhibit altered photosynthetic metabolism. Here, we demonstrate that these manipulations also resulted in differences in root growth, with both transgenics being characterized by a dramatic reduction of root dry matter deposition and respiratory activity but opposite changes with respect to root area. A range of physiological, molecular, and biochemical experiments were carried out in order to determine whether changes in root morphology were due to altered metabolism within the root itself, alterations in the nature of the transformants' root exudation, consequences of alteration in the efficiency of photoassimilate delivery to the root, or a combination of these factors. Grafting experiments in which the transformants were reciprocally grafted to wild-type controls suggested that root length and area were determined by the aerial part of the plant but that biomass was not. Despite the transgenic roots displaying alteration in the expression of phytohormone-associated genes, evaluation of the levels of the hormones themselves revealed that, with the exception of gibberellins, they were largely unaltered. When taken together, these combined experiments suggest that root biomass and growth are retarded by root-specific alterations in metabolism and gibberellin contents. These data are discussed in the context of current models of root growth and biomass partitioning.

  7. 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.

  8. 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…

  9. 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.

  10. 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

  11. Access to hands-on mathematics measurement activities using robots controlled via speech generating devices: three case studies.

    Science.gov (United States)

    Adams, Kim; Cook, Al

    2014-07-01

    To examine how using a robot controlled via a speech generating device (SGD) influences the ways students with physical and communication limitations can demonstrate their knowledge in math measurement activities. Three children with severe physical disabilities and complex communication needs used the robot and SGD system to perform four math measurement lessons in comparing, sorting and ordering objects. The performance of the participants was measured and the process of using the system was described in terms of manipulation and communication events. Stakeholder opinions were solicited regarding robot use. Robot use revealed some gaps in the procedural knowledge of the participants. Access to both the robot and SGD was shown to provide several benefits. Stakeholders thought the intervention was important and feasible for a classroom environment. The participants were able to participate actively in the hands-on and communicative measurement activities and thus meet the demands of current math instruction methods. Current mathematics pedagogy encourages doing hands-on activities while communicating about concepts. Adapted Lego robots enabled children with severe physical disabilities to perform hands-on length measurement activities. Controlling the robots from speech generating devices (SGD) enabled the children, who also had complex communication needs, to reflect and report on results during the activities. By using the robots combined with SGDs, children both exhibited their knowledge of and experienced the concepts of mathematical measurements.

  12. 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...

  13. Arene activation by a nonheme iron(III)-hydroperoxo complex: pathways leading to phenol and ketone products.

    Science.gov (United States)

    Faponle, Abayomi S; Banse, Frédéric; de Visser, Sam P

    2016-07-01

    Iron(III)-hydroperoxo complexes are found in various nonheme iron enzymes as catalytic cycle intermediates; however, little is known on their catalytic properties. The recent work of Banse and co-workers on a biomimetic nonheme iron(III)-hydroperoxo complex provided evidence of its involvement in reactivity with arenes. This contrasts the behavior of heme iron(III)-hydroperoxo complexes that are known to be sluggish oxidants. To gain insight into the reaction mechanism of the biomimetic iron(III)-hydroperoxo complex with arenes, we performed a computational (density functional theory) study. The calculations show that iron(III)-hydroperoxo reacts with substrates via low free energies of activation that should be accessible at room temperature. Moreover, a dominant ketone reaction product is observed as primary products rather than the thermodynamically more stable phenols. These product distributions are analyzed and the calculations show that charge interaction between the iron(III)-hydroxo group and the substrate in the intermediate state pushes the transferring proton to the meta-carbon atom of the substrate and guides the selectivity of ketone formation. These studies show that the relative ratio of ketone versus phenol as primary products can be affected by external interactions of the oxidant with the substrate. Moreover, iron(III)-hydroperoxo complexes are shown to selectively give ketone products, whereas iron(IV)-oxo complexes will react with arenes to form phenols instead.

  14. All Roads Lead To Rome

    DEFF Research Database (Denmark)

    Ottosen, Thorsten Jørgen; Vomlel, Jiri

    2010-01-01

    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 size triangulations....... The search methods are made faster by eficient dynamic maintenance of the cliques of a graph. The algorithms are mainly sup- posed to be off-line methods, but they may form the basis for ecient any-time heuristics. Furthermore, the methods make it possible to evaluate the quality of heuristics precisely....

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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

  20. TERT Promoter Mutations Lead to High Transcriptional Activity under Hypoxia and Temozolomide Treatment and Predict Poor Prognosis in Gliomas

    OpenAIRE

    Chen Chen; Sheng Han; Lingxuan Meng; Zhonghua Li; Xue Zhang; Anhua Wu

    2014-01-01

    Objective 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. Methods 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 promo...