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).

    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. PMID:27246693

  2. Leading Undergraduate Students to Big Data Generation

    Yang, Jianjun; Shen, Ju

    2015-01-01

    People are facing a flood of data today. Data are being collected at unprecedented scale in many areas, such as networking, image processing, virtualization, scientific computation, and algorithms. The huge data nowadays are called Big Data. Big data is an all encompassing term for any collection of data sets so large and complex that it becomes difficult to process them using traditional data processing applications. In this article, the authors present a unique way which uses network simula...

  3. Cool horizons lead to information loss

    Chowdhury, Borun D.

    2013-10-01

    There are two evidences for information loss during black hole evaporation: (i) a pure state evolves to a mixed state and (ii) the map from the initial state to final state is non-invertible. Any proposed resolution of the information paradox must address both these issues. The firewall argument focuses only on the first and this leads to order one deviations from the Unruh vacuum for maximally entangled black holes. The nature of the argument does not extend to black holes in pure states. It was shown by Avery, Puhm and the author that requiring the initial state to final state map to be invertible mandates structure at the horizon even for pure states. The proof works if black holes can be formed in generic states and in this paper we show that this is indeed the case. We also demonstrate how models proposed by Susskind, Papadodimas et al. and Maldacena et al. end up making the initial to final state map non-invertible and thus make the horizon "cool" at the cost of unitarity.

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

    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.

  5. Active Listening Improve Your Ability to Listen and Lead

    (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.

  6. Distributed patterns of brain activity that lead to forgetting

    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. Next-generation science information network for leading-edge applications

    High-speed networks are definitely essential tools for leading-edge applications in many research areas, including nuclear fusion research. This paper describes a number of advanced features in the Japanese next-generation science information network, called SINET3, and gives researchers clues on the uses of advanced high-speed network for their applications. The network services have four categories, multiple layer transfer, enriched virtual private network, enhanced quality-of-service, and bandwidth on demand services, and comprise a versatile service platform. The paper also describes the network architecture and advanced networking capabilities that enable economical service accommodation and flexible network resource assignment as well as effective use of Japan's first 40-Gbps lines

  8. 75 FR 66087 - Agency Information Collection Activities; Proposed Collection; Comment Request; Residential Lead...

    2010-10-27

    ... Information Collection Activities; Proposed Collection; Comment Request; Residential Lead-Based Paint Hazard... Office of Management and Budget (OMB). This ICR, entitled: ``Residential Lead-Based Paint Hazard... parties. Title: Residential Lead-Based Paint Hazard Disclosure Requirements. ICR numbers: EPA ICR No....

  9. 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

    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.

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

    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.

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

    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. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

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

    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. PMID:10182280

  13. An Information Structural Approach to Spoken Language Generation

    Prevost, S

    1996-01-01

    This paper presents an architecture for the generation of spoken monologues with contextually appropriate intonation. A two-tiered information structure representation is used in the high-level content planning and sentence planning stages of generation to produce efficient, coherent speech that makes certain discourse relationships, such as explicit contrasts, appropriately salient. The system is able to produce appropriate intonational patterns that cannot be generated by other systems which rely solely on word class and given/new distinctions.

  14. Distributed patterns of brain activity that lead to forgetting

    Öztekin Gillam, İlke; Badre, David

    2011-01-01

    Proactive interference (PI), in which irrelevant information from prior learning disrupts memory performance, is widely viewed as a major cause of forgetting. However, the hypothesized spontaneous recovery (i.e., automatic retrieval) of interfering information presumed to be at the base of PI remains to be demonstrated directly. Moreover, it remains unclear at what point during learning and/or retrieval interference impacts memory performance. In order to resolve these open questions, we empl...

  15. Depurinating estrogen-DNA adducts, generators of cancer initiation: their minimization leads to cancer prevention.

    Cavalieri, Ercole L; Rogan, Eleanor G

    2016-12-01

    Estrogens can initiate cancer by reacting with DNA. Specific metabolites of endogenous estrogens, the catechol estrogen-3,4-quinones, react with DNA to form depurinating estrogen-DNA adducts. Loss of these adducts leaves apurinic sites in the DNA, generating mutations that can lead to the initiation of cancer. A variety of endogenous and exogenous factors can disrupt estrogen homeostasis, which is the normal balance between estrogen activating and protective enzymes. In fact, if estrogen metabolism becomes unbalanced and generates excessive catechol estrogen 3,4-quinones, formation of depurinating estrogen-DNA adducts increases and the risk of initiating cancer is greater. The levels of depurinating estrogen-DNA adducts are high in women diagnosed with breast cancer and those at high risk for the disease. High levels of depurinating estrogen-DNA adducts before the presence of breast cancer indicates that adduct formation is a critical factor in breast cancer initiation. Women with thyroid or ovarian cancer also have high levels of estrogen-DNA adducts, as do men with prostate cancer or non-Hodgkin lymphoma. Depurinating estrogen-DNA adducts are initiators of many prevalent types of human cancer. These findings and other discoveries led to the recognition that reducing the levels of estrogen-DNA adducts could prevent the initiation of human cancer. The dietary supplements N-acetylcysteine and resveratrol inhibit formation of estrogen-DNA adducts in cultured human breast cells and in women. These results suggest that the two supplements offer an approach to reducing the risk of developing various prevalent types of human cancer. Graphical abstract Major metabolic pathway in cancer initiation by estrogens. PMID:26979321

  16. 77 FR 65414 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Lead in...

    2012-10-26

    ... published in the Federal Register on August 10, 2012 (77 FR 47883). Interested parties are encouraged to...; Lead in Construction Standard ACTION: Notice. SUMMARY: The Department of Labor (DOL) is submitting the..., ``Lead in Construction Standard,'' to the Office of Management and Budget (OMB) for review and...

  17. 77 FR 65415 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Lead in...

    2012-10-26

    ... notice published in the Federal Register on August 10, 2012 (77 FR 47882). Interested parties are...; Lead in General Industry Standard ACTION: Notice. SUMMARY: The Department of Labor (DOL) is submitting...) titled, ``Lead in General Industry Standard,'' to the Office of Management and Budget (OMB) for...

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

    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.)

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

    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.)

  20. Bacterial recognition pathways that lead to inflammasome activation

    Storek, Kelly M.; Monack, Denise M.

    2015-01-01

    Inflammasomes are multi-protein signaling platforms that upon activation trigger the maturation of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and IL-18, and cell death. Inflammasome sensors detect microbial and host-derived molecules. Here, we review the mechanisms of inflammasome activation triggered by bacterial infection, primarily focusing on two model intracellular bacterial pathogens, Francisella novicida and Salmonella typhimurium. We discuss the complex relationship betwee...

  1. Using geographic information systems to assess risk for elevated blood lead levels in children.

    Roberts, James R.; Hulsey, Thomas C.; Curtis, Gerald B.; Reigart, J. Routt

    2003-01-01

    OBJECTIVES: Targeted screening for childhood lead poisoning depends on assessment of risk factors including housing age. Using a geographic information system (GIS), we aim to determine high-risk regions in Charleston County, South Carolina, to assist public health officials in developing targeted lead-screening. METHODS: Properties built before 1978 were geocoded (assigned latitude and longitude coordinates) from tax assessor data. Addresses of Charleston County children who have been screen...

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

    Pawe{\\l} Fiedor

    2014-01-01

    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 of those analyses are concentrated only on Pearson's correlation coefficient and thus intraday lead-lag relationships associated with such. Under Efficient Market Hypothesis such relationships are not possible as all information is embedded in the prices. In this paper we analyse lead-lag relationships of f...

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

    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. PMID:10662094

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

    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...

  5. Does ionizing radiation lead to activation of oncogenes

    Attention has been focused on the action of ionizing radiation on genes (DNA), this being a critical first step in radiation carcinogenesis. Here, experiments have been carried out where isolated BALB/c DNA in solution was subjected to different doses of gamma radiation and subsequently assayed by means of the NIH transfection system. At doses higher than 3 Gy, a rapid loss of focus formation was found. However, with doses between 0.3 and 1 Gy, focus formation was consistently higher, e.g., by about a factor of two, than with DNA that was not irradiated. (Auth.)

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

    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.

  7. Nitric oxide reactivity of [2Fe-2S] clusters leading to H2S generation.

    Tran, Camly T; Williard, Paul G; Kim, Eunsuk

    2014-08-27

    The crosstalk between two biologically important signaling molecules, nitric oxide (NO) and hydrogen sulfide (H2S), proceeds via elusive mechanism(s). Herein we report the formation of H2S by the action of NO on synthetic [2Fe-2S] clusters when the reaction environment is capable of providing a formal H(•) (e(-)/H(+)). Nitrosylation of (NEt4)2[Fe2S2(SPh)4] (1) in the presence of PhSH or (t)Bu3PhOH results in the formation of (NEt4)[Fe(NO)2(SPh)2] (2) and H2S with the concomitant generation of PhSSPh or (t)Bu3PhO(•). The amount of H2S generated is dependent on the electronic environment of the [2Fe-2S] cluster as well as the type of H(•) donor. Employment of clusters with electron-donating groups or H(•) donors from thiols leads to a larger amount of H2S evolution. The 1/NO reaction in the presence of PhSH exhibits biphasic decay kinetics with no deuterium kinetic isotope effect upon PhSD substitution. However, the rates of decay increase significantly with the use of 4-MeO-PhSH or 4-Me-PhSH in place of PhSH. These results provide the first chemical evidence to suggest that [Fe-S] clusters are likely to be a site for the crosstalk between NO and H2S in biology. PMID:25113815

  8. Control approach to the load frequency regulation of a Generation IV Lead-cooled Fast Reactor

    Highlights: • Dedicated control strategy for adjusting the electrical power according to the grid requirements. • Decoupling of the Balance of Plant from the reactor primary circuit thanks to effective feedback regulators. • Primary frequency regulation and islanding simulations assessed with an object-oriented model. - Abstract: One of the most pressing issues in the study of the power generation and distribution is the characterization of the grid behavior, whether a relevant fraction of the connected power plants relies on Renewable Energy Sources. Indeed, because of the discontinuous power supply and the limited presence of energy accumulators, concerning power imbalances may take place on the grid. The power plants ensuring high reliability performance should be ready to feed the loads when the Renewable Energy Sources are not available. In order to ensure the grid stability and the sustainability of nuclear energy, the possibility of operating Generation-IV nuclear reactors in a flexible way should be considered, i.e., the Nuclear Power Plants should adjust the mechanical power produced so as to comply with the sudden grid frequency variations. In the present work, this opportunity is assessed for the Lead-cooled Fast Reactors, adopting the Advanced Lead Fast Reactor European Demonstrator (ALFRED) as a representative of Lead-cooled Fast Reactor technology. For this reactor concept, because of the large thermal inertia that characterizes the system, the adoption of the “reactor-follows-turbine” scheme (currently employed in the Pressurized Water Reactors) is not feasible. An alternative solution is proposed, i.e., the set-point for the thermal power produced in the core is kept constant at the nominal value (or slowly variable), and the set-point for the mechanical power available to the alternator is adjusted according to the load demands. In order to assess the performance of the developed control scheme, two case studies are simulated. In the

  9. Artificial association of pre-stored information to generate a qualitatively new memory.

    Ohkawa, Noriaki; Saitoh, Yoshito; Suzuki, Akinobu; Tsujimura, Shuhei; Murayama, Emi; Kosugi, Sakurako; Nishizono, Hirofumi; Matsuo, Mina; Takahashi, Yukari; Nagase, Masashi; Sugimura, Yae K; Watabe, Ayako M; Kato, Fusao; Inokuchi, Kaoru

    2015-04-14

    Memory is thought to be stored in the brain as an ensemble of cells activated during learning. Although optical stimulation of a cell ensemble triggers the retrieval of the corresponding memory, it is unclear how the association of information occurs at the cell ensemble level. Using optogenetic stimulation without any sensory input in mice, we found that an artificial association between stored, non-related contextual, and fear information was generated through the synchronous activation of distinct cell ensembles corresponding to the stored information. This artificial association shared characteristics with physiologically associated memories, such as N-methyl-D-aspartate receptor activity and protein synthesis dependence. These findings suggest that the association of information is achieved through the synchronous activity of distinct cell ensembles. This mechanism may underlie memory updating by incorporating novel information into pre-existing networks to form qualitatively new memories. PMID:25843716

  10. Investigation of reasons leading to destruction of Rovno NPP steam generator flanges

    Destruction of templets taken from hot collector flanges of Rovno NPP steam generator was investigated. With the help of fractographic, micro roentgen spectral, metallographic and other methods it was shown that the main reason of steam generator flanges destruction is the high concentration of stresses in threaded joints. Increased concentration of impurities (sulphur, phosphorous) also contributes to such a destruction

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

    Fiedor, Paweł

    2014-08-01

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

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

    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. PMID:10464008

  13. State and provincial governments to lead by example : survey of public sector climate change activities

    A Climate Change Action Plan was adopted in August 2001 at the Conference of New England Governors and Eastern Canadian Premiers (NEG/ECP). The action plan recognizes the need for government to lead by example in areas of energy efficiency and clean energy technologies. This survey is the first attempt at gathering information on climate change activities in the public sector across 11 jurisdictions of the Northeast. It reports on 45 activities that have been initiated by government departments to either reduce greenhouse gas (GHG) emissions or to address the issue of adaptation and carbon sinks. The main objective to reduce energy consumption in buildings is being met through improved management systems, use of new technologies such as alternative fuels and low-emissions vehicles, and financial incentives. This report presents an outline for reducing GHG emissions from government activities by 25 per cent by 2012. The survey identifies areas where more work is needed in measuring impacts and progress. refs., tabs., figs

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

    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....../m3 reactor/d in AD). The methane production yield reached 116.2 mg/g VSS in the ME-ADreactor. According to balance calculation on electron transfer and methane yield, the increasedmethane production was mostly dependent on electron contribution through the ME system. Thus, theuse of the novel ME...

  15. Next generation information systems

    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. Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity.

    Samuel García-Nieto

    proliferation, inclusion of ECM proteins could lead to development of more sensitive assays.

  17. The Agent of extracting Internet Information with Lead Order

    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.

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

    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.

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

    Steven Biesmans; Meert, Theo F.; Jan A. Bouwknecht; Acton, Paul D.; Nima Davoodi; Patrick De Haes; Jacobine Kuijlaars; Xavier Langlois; Liam J. R. Matthews; Luc Ver Donck; Niels Hellings; Rony Nuydens

    2013-01-01

    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 an...

  20. [Active selection of afferent information--the principle underlying peripheral correction of the function of spinal generators of rhythmic movements].

    Baev, K V

    1984-01-01

    The paper presents data obtained in experiments on the study of primary afferent depolarization and retuning of segmental reactions to afferent signals during fictitious locomotion and fictitious scratching in immobilized decorticated, decerebrated and spinal cats. Fictitious locomotion was accompanied by sustained hyperpolarization, while fictitious scratching--by sustained depolarization of primary afferent central terminals. On the background of tonic changes periodic waves of primary afferent depolarization coinciding with the rhythm of efferent activity were observed. In different ipsilateral lumbosacral segments these periodic waves occurred in phase. The data are presented about the groups of afferent fibres in which central endings display tonic and phasic changes of primary afferent depolarization. Fictitious locomotion led to tonic increase and fictitious scratching--to tonic decrease in a number of evoked segmental reflex reactions. These tonic changes served as the background on which segmental reactions were modulated with the rhythm of locomotor and scratching generators. It is shown that the modulation of polarization of central primary endings by locomotor and scratching generators is the reason for many changes in reflex reactions. The conclusion is made that due to modulation of presynaptic inhibition the generators perform an active tonic and phase-dependent selection of afferent information. The role of such active selection in the peripheral correction of the function of locomotor and scratching generators is discussed. PMID:6462286

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

    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…

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

    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.

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

    Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regulatoryfactor...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of... interferon regulatoryfactor 3. Authors Servant MJ, Grandvaux N, Hiscott J. Publication Biochem Pharmacol. 2

  4. β-lactam antibiotic-induced release of lipoteichoic acid from Staphylococcus aureus leads to activation of neutrophil granulocytes

    Hartung Thomas

    2006-06-01

    Full Text Available Abstract Background Polymorphonuclear neutrophil granulocytes (PMN are phagocytes of the first line of antimicrobial defense. Previously we demonstrated that lipoteichoic acid (LTA from Staphylococcus aureus (S. aureus directly activates neutrophil granulocytes. Others have reported that exposure of S. aureus to β-lactam antibiotics leads to LTA release. In the present study we addressed the question whether exposure of S. aureus to β-lactam antibiotics or antibiotics of other groups results in the generation of PMN-stimulating activity and whether this activity can be attributed to LTA. Methods S. aureus were exposed to flucloxacillin, a β-lactam antibiotic or to the protein synthesis-inhibitors erythromycin and gentamicin, or to ciprofloxacin, a gyrase inhibitor. Supernatants of the antibiotic-treated bacteria were assayed for their LTA content and for their effect on PMN functions. Results We observed that exposure of S. aureus to flucloxacillin and, to a lesser degree to ciprofloxacin, but not to erythromycin or gentamicin led to LTA release. Co-incubation of neutrophil granulocytes with LTA-containing supernatants led to PMN activation as assed by morphological changes, release of IL-8, delay of spontaneous apoptosis and enhanced phagocytic activity. Depletion of LTA from the supernatants markedly reduced their PMN-activating capacity. Conclusion The findings suggest that, via the activation of PMN, antibiotic-induced LTA release from S. aureus leads to enhanced antimicrobial activity of the innate immune defense mechanisms.

  5. 77 FR 74667 - Agency Information Collection Activities; Proposed Collection; Comment Request; Information To...

    2012-12-17

    ... Act ( http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCAct... HUMAN SERVICES Food and Drug Administration Agency Information Collection Activities; Proposed Collection; Comment Request; Information To Accompany Humanitarian Device Exemption Applications and...

  6. Activity System Theory Approach to Healthcare Information System

    Bai, Guohua

    2004-01-01

    Healthcare information system is a very complex system and has to be approached from systematic perspectives. This paper presents an Activity System Theory (ATS) approach by integrating system thinking and social psychology. First part of the paper, the activity system theory is presented, especially a recursive model of human activity system is introduced. A project ‘Integrated Mobile Information System for Diabetic Healthcare (IMIS)’ is then used to demonstrate a practical application of th...

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

    Tang, Qiong-Yao; Zhang, Fei-Fei; Xu, Jie; Wang, Ran; Chen, Jian; Logothetis, Diomedes E; Zhang, Zhe

    2016-01-01

    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. PMID:26725113

  8. Does subgroup membership information lead to better estimation of true subscores?

    Haberman, Shelby J; Sinharay, Sandip

    2013-11-01

    Haberman (2008) suggested a method to determine if subtest scores have added value over the total score. The method is based on classical test theory and considers the estimation of the true subscores. Performance of subgroups, for example, those based on gender or ethnicity, on subtests is often of interest. Researchers such as Stricker (1993) and Livingston and Rupp (2004) found that the difference in performance between the subgroups often varies over the different subtests. We suggest a method to examine whether the knowledge of the subgroup membership of the examinees leads to a better estimation of the true subscores. We apply our suggested method to data from two operational testing programmes. The knowledge of the subgroup membership of the examinees does not lead to a better estimation of the true subscore for the data sets. PMID:23106170

  9. Utilizing online video to lead an organizational culture in the digitalized world of the information age

    Harki, N. (Niklas)

    2016-01-01

    This thesis looks at online video leadership and leading an organizational culture through online video. In this study organizational culture is taken a look at from the leadership perspective and the concept of online video is seen as an internal video ecosystem that connects to for example social business networks. The study aims at finding out how the true values of the organization could be embraced through online video. Furthermore, the study makes an attempt at finding out how significa...

  10. Leading the Pickering A Return to Service Project through effective information management and performance reporting

    On a project of this magnitude, timely, consistent and accurate information on the status of critical project parameters is a must. This information is used to make important decisions on project progress at the working level all the way to the Executive level. Within the Pickering A Return to Service Project, the Project Support Division has developed several information systems to facilitate decision making at all levels on the project, and these systems form the foundation of the performance metrics that are issued each week. Unit 1 is a model of effective use of Information Technology to engage and focus all functional groups from Engineering to Construction on progressing work in the field safely, on schedule and on budget. Project Support established itself as a key element to the successful completion of the Unit 1 project. In order to report reliable, high quality metrics, you need a reliable, high quality source of data. Multi-dimensional systems have been developed to provide key information to various levels of the project organization. Our systems are now being recognized by other parts of the corporation. If we can effectively monitor, control and report on a multi-unit, multi-year, multi-billion dollar project then, perhaps others could benefit from our processes and systems. Outages, conventional projects and day-to-day operations can apply the same management processes. The single biggest breakthrough was the development of the Project Work Management System (PWMS) and the Construction Completion Declaration (CCD) report builder. PWMS allows users to monitor the modification and non-modification scope from engineering products to work order tasks (23,000 tasks) to the execution status in the field and finally to the design modification closeout. CCD Builder is an application that builds a report detailing the status of a piece of work prior to Construction turning it over to Operations. (author)

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

    Sarvaramini, A.; Larachi, F.; Hart, B.

    2016-03-01

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

    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…

  13. Inhibition of Rb Phosphorylation Leads to mTORC2-Mediated Activation of Akt.

    Zhang, Jinfang; Xu, Kai; Liu, Pengda; Geng, Yan; Wang, Bin; Gan, Wenjian; Guo, Jianping; Wu, Fei; Chin, Y Rebecca; Berrios, Christian; Lien, Evan C; Toker, Alex; DeCaprio, James A; Sicinski, Piotr; Wei, Wenyi

    2016-06-16

    The retinoblastoma (Rb) protein exerts its tumor suppressor function primarily by inhibiting the E2F family of transcription factors that govern cell-cycle progression. However, it remains largely elusive whether the hyper-phosphorylated, non-E2F1-interacting form of Rb has any physiological role. Here we report that hyper-phosphorylated Rb directly binds to and suppresses the function of mTORC2 but not mTORC1. Mechanistically, Rb, but not p107 or p130, interacts with Sin1 and blocks the access of Akt to mTORC2, leading to attenuated Akt activation and increased sensitivity to chemotherapeutic drugs. As such, inhibition of Rb phosphorylation by depleting cyclin D or using CDK4/6 inhibitors releases Rb-mediated mTORC2 suppression. This, in turn, leads to elevated Akt activation to confer resistance to chemotherapeutic drugs in Rb-proficient cells, which can be attenuated with Akt inhibitors. Therefore, our work provides a molecular basis for the synergistic usage of CDK4/6 and Akt inhibitors in treating Rb-proficient cancer. PMID:27237051

  14. Leading article: Use of smartphones to pass on information about patients - what are the current issues?

    Rokadiya, S; McCaul, J A; Mitchell, D A; Brennan, P A

    2016-07-01

    Many doctors now use mobile devices such as smartphones to communicate with one another about their patients, and sometimes this is without the knowledge and approval of their employer. We know of little information about the use of texting and other web-based messaging services by doctors in hospitals, so we reviewed relevant published studies to assess the safety and usefulness of current methods of digital communication. PMID:27185230

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

    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. PMID:25873174

  16. What Leads Students to Adopt Information from Wikipedia? An Empirical Investigation into the Role of Trust and Information Usefulness

    Shen, Xiao-Liang; Cheung, Christy M. K.; Lee, Matthew K. O.

    2013-01-01

    With the prevalence of the Internet, it has become increasingly easy and common for students to seek information from various online sources. Wikipedia is one of the largest and most popular reference websites that university students may heavily rely on in completing their assignments and other course-related projects. Based on the information…

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

    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

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

    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.

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

    Momblona, C.; O. Malinkiewicz; Roldán-Carmona, C.; Soriano, A; L. Gil-Escrig; Bandiello, E.; Scheepers, M.; Edri, E.; Bolink, H. J.

    2014-01-01

    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...

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

    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.

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

    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...

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

    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.

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

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

    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. To...

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

    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.

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

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

    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.

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

    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.

  8. Can Miracles Lead to Crises? An Informational Frictions Explanation of Emerging Markets Crises

    Emine Boz

    2006-01-01

    Emerging market financial crises are abrupt and dramatic, usually occurring after a period of high output growth, massive capital flows, and a boom in asset markets. This paper develops an equilibrium asset pricing model with informational frictions in which vulnerability and the crisis itself are consequences of the investor optimism in the period preceding the crisis. The model features two sets of investors, domestic and foreign. Both sets of investors are imperfectly informed about the tr...

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

    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.

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

    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...

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

    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.

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

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

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

    This program at West Virginia University is a Cooperative Agreement that focuses on R ampersand 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

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

    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.

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

    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…

  16. Biochar amendment to lead-contaminated soil: Effects on fluorescein diacetate hydrolytic activity and phytotoxicity to rice.

    Tan, Xiaofei; Liu, Yunguo; Gu, Yanling; Zeng, Guangming; Hu, Xinjiang; Wang, Xin; Hu, Xi; Guo, Yiming; Zeng, Xiaoxia; Sun, Zhichao

    2015-09-01

    The amendment effects of biochar on total microbial activity was measured by fluorescein diacetate (FDA) hydrolytic activity, and phytotoxicity in Pb(II)-contaminated soils was examined by the application of 4 different biochars to soil, with rice as a test plant. The FDA hydrolytic activities of biochar-amended soils were much higher than that of the control. The survival rate of rice in lead-contaminated biochar-amended soils showed significant improvement over the control, especially for bamboo biochar-amended soil (93.3%). In addition, rice grown in lead-contaminated control sediment displayed lower biomass production than that in biochar-amended soil. The immobilization of Pb(II) and the positive effects of biochar amendment on soil microorganisms may account for these effects. The results suggest that biochar may have an excellent ability to mitigate the toxic effects of Pb(II) on soil microorganisms and rice. PMID:25900615

  17. Informal Economic Activities

    Bühn, Andreas

    2010-01-01

    The dissertation “Informal Economic Activities” takes a comprehensive approach to the informal economy by studying traditional shadow economic activities, household DIY activities, and the smuggling of illegal and legal goods. Chapter 2 analyzes shadow economic and DIY activities and presents a dual estimation for the development of both types of informal economic activities in Germany from 1970 to 2005. It also considers the impact of German reunification on shadow economic and DIY activ...

  18. Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.

    Canetta, S; Bolkan, S; Padilla-Coreano, N; Song, L J; Sahn, R; Harrison, N L; Gordon, J A; Brown, A; Kellendonk, C

    2016-07-01

    Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic 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, resulted from a decrease in release probability 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 MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

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

    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

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

    Chryselda Caesar

    2013-01-01

    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 schoo...

  1. Lead assisted stress corrosion cracking of nuclear steam generator tubing materials

    There have been a few field failures of nuclear steam generator tubes which were attributed to lead assisted stress corrosion. Because of the propensity of lead compounds to be found in nuclear generator sludge, considerable laboratory effort has been focused on lead assisted stress corrosion. This paper reviews the literature to organize the current knowledge about this phenomenon in terms of important parameters. It also reviews the literature in terms of current thoughts on degradation mechanisms which might explain lead assisted corrosion. Finally, this paper identifies areas where information is lacking

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

    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.

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

    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

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

    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

  5. Generation of ROS by CAY10598 leads to inactivation of STAT3 signaling and induction of apoptosis in human colon cancer HCT116 cells.

    Chae, I G; Kim, D-H; Kundu, J; Jeong, C-H; Kundu, J K; Chun, K-S

    2014-11-01

    Prostaglandin E2 (PGE2) has been reported to play critical roles in cell fate decision by interacting with four types of prostanoid receptors such as EP1, EP2, EP3 and EP4. The present study was aimed at investigating the effect of the EP4-specific agonist CAY10598 in human colon cancer HCT116 cells. Our study revealed that treatment with CAY10598 significantly reduced the cell viability and induced apoptosis in HCT116 cells, as evidenced by the induction of p53 and Bax, release of cytochrome c, cleavage of caspase-9, -7, and -3, and PARP, and the inhibition of Bcl-2, Bcl-xL and survivin expression. Moreover, treatment with CAY10598 diminished the phosphorylation of JAK2, leading to the attenuation of STAT3 activation in HCT116 cells. CAY10598-induced apoptosis in cells which were transiently transfected with EP4 siRNA or treated with an EP4 antagonist prior to incubation with the compound remained unaffected, suggesting an EP4-independent mechanism of apoptosis induction by CAY10598. We found that treatment with CAY10598 generated reactive oxygen species (ROS) and pretreatment of cells with N-acetyl cysteine rescued cells from apoptosis by abrogating the inhibitory effect of CAY10598 on the activation of JAK2/STAT3 signaling. In conclusion, CAY10598 induced apoptosis in HCT116 cells in an EP4-independent manner, but through the generation of ROS and inactivation of JAK2/STAT3 signaling. PMID:25096910

  6. Understanding Interactions between Manganese Oxide and Gold That Lead to Enhanced Activity for Electrocatalytic Water Oxidation

    Gorlin, Yelena; Chung, Chia-Jung; Benck, Jesse D.; Nordlund, Dennis; Seitz, Linsey; Weng, Tsu-Chien; Sokaras, Dimosthenis; Clemens, Bruce M.; Jaramillo, Thomas F.

    2014-01-01

    To develop active nonprecious metal-based electrocatalysts for the oxygen evolution reaction (OER), a limiting reaction in several emerging renewable energy technologies, a deeper understanding of the activity of the first row transition metal oxides is needed. Previous studies of these catalysts have reported conflicting results on the influence of noble metal supports on the OER activity of the transition metal oxides. Our study aims to clarify the interactions between a transition metal ox...

  7. Use of a relational reinforcement learning algorithm to generate dynamic activity-travel patterns

    VANHULSEL, Marlies; Janssens, Davy; Wets, Geert

    2007-01-01

    In the course of the past decade activity-based models have entered the area of transportation modelling. Such models simulate the generation of individual activity-travel patterns while deciding simultaneously on the different dimensions of activity-travel behaviour, such as the type of activity, the activity location, the transport mode used to reach this location, the starting time and duration of the activity, etc. However, as real-world activity-travel patterns prove not to be static due...

  8. Risk informed maintenance activity

    In recent years, risk informed activities are being investigated as scientifically rational measures. Some Risk informed activities using Core Damage Frequency (CDF) have been already employed. Examples are extraction of accident management strategies, risk informed maintenance importance and such. This paper describes risk information such as CDF, risk profile, risk importance of equipments' contribution to risk, gained from Probabilistic Analysis (PSA). Furthermore, risk informed activities conducted and/or considered are also introduced. The examples are investigation of accident management strategies, on-line maintenance and risk informed In Service Inspection (ISI). In the end, open issues for further employment of risk information in the NPP activities are summarized. Technical quality of PSA methodology is one of these issues and it should be continuously addressed, however, the risk information as it is still useful for better activities in NPP. (author)

  9. Using a digital multimeter to capture spectral information generated by a spectrophotometer broadcast / atomic absorption

    Spectral analysis capability of the information generated by a spectrophotometer broadcast / shimadzu AA 640-13 atomic absorption has increased, through the capture of data, using a digital multimeter as the interface between the spectrophotometer and a computer. To facilitate the identification of analytes was created Chromulan format files for the 99 chemical elements reported in the literature, and covering the region between 200 nm and 900 nm, the subject of this study. (author)

  10. Aberrant glomerular filtration of urokinase-plasminogen activator in nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine

    Stæhr, Mette; Buhl, Kristian Bergholt; Andersen, René F;

    2015-01-01

    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...

  11. A Correlation Study of Meteorological Dynamics and Thunderstorm Activity Leading to Terrestrial Gamma-Ray Flashes

    Barnes, Daniel Edward

    The Terrestrial Gamma-ray Flash (TGF) was first discovered by Fishman et al. in 1994. The TGF is an emission of highly energetic radiation produced by or at least in close association with lightning. Fishman theorized that the TGFs were spawned at Sprite altitudes, however, Dwyer and Smith, utilizing detailed Monte Carlo calculations found the production level was within the troposphere, particularly in the altitude range of 15-21 km. This altitude places the TGF generating mechanism within thunderstorm cloud height. Current investigations tend to study the TGF itself in an attempt to isolate the production mechanism and production level while the thunderstorm characteristics have largely been ignored. The investigation into thunderstorms and their characteristics will utilize temporal and spatial coincident passes between the Ramatay High-energy Solar Spectroscopic Imager (RHESSI) and the Tropical Rainfall Measuring Mission (TRMM) in order to ascertain the bulk or footprint overlap fundamental storm properties of two types of events, the TGF generating thunderstorm (Yes case) and the non-TGF generating thunderstorm (Null case). Common components to each case are the presence of lightning during the coincident pass, spatial overlap of sub-satellite footprint within 500km and temporal difference of no more than one-hour. The defining difference is the Yes case has a RHESSI recorded TGF event while the Null case has no RHESSI recorded TGF event. Data presented will show that TGF storms possesses identifiable differences in the hydrometeor concentrations at different levels of the atmosphere. The Yes storm possesses elevated zero-degree isotherms, storm tops, increased occurrence of lower flash rates, low flash rate density and fairly uniform occurrence of lower optical radiance. These properties have statistically significant differences from their Null counterparts. It may be possible to identify potential TGF storms utilizing these storm characteristics and ground

  12. 78 FR 16509 - Amendment to Information Collection Activity; Comment Request

    2013-03-15

    ... data and information on the subject's work and education history. 2--Follow-Up Surveys. There are three... contacted once by mail to provide updated contact information. 3--Implementation Research and Site Visits... of automated collection techniques or other forms of information technology. Consideration will...

  13. MALT LYMPHOMA: MANY ROADS LEAD TO NF-kB ACTIVATION

    Du, Ming-Qing

    2011-01-01

    Abstract Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is genetically characterised by several recurrent, but mutually exclusive chromosome translocations. To date, it has been shown that at least the oncogenic products of t(1;14)(p22;q32)/BCL10-IGH, t(14;18)(q32;21)/IGH-MALT1 and t(11;18)(q21;q21)/API2-MALT1 activate the NF-kB activation pathway. Recently, A20, an essential global NF-kB inhibitor, was found to be inactivated by somatic d...

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

    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

  15. Less precise motor control leads to increased agonist-antagonist muscle activation during stick balancing.

    Reeves, N Peter; Popovich, John M; Vijayanagar, Vilok; Pathak, Pramod K

    2016-06-01

    Human motor control has constraints in terms of its responsiveness, which limit its ability to successfully perform tasks. In a previous study, it was shown that the ability to balance an upright stick became progressively more challenging as the natural frequency (angular velocity without control) of the stick increased. Furthermore, forearm and trunk agonist and antagonist muscle activation increased as the natural frequency of the stick increased, providing evidence that the central nervous system produces agonist-antagonist muscle activation to match task dynamics. In the present study, visual feedback of the stick position was influenced by changing where subject focused on the stick during stick balancing. It was hypothesized that a lower focal height would degrade motor control (more uncertainty in tracking stick position), thus making balancing more challenging. The probability of successfully balancing the stick at four different focal heights was determined along with the average angular velocity of the stick. Electromyographic signals from forearm and trunk muscles were also recorded. As expected, the probability of successfully balancing the stick decreased and the average angular velocity of the stick increased as subjects focused lower on the stick. In addition, changes in the level of agonist and antagonist muscle activation in the forearm and trunk was linearly related to changes in the angular velocity of the stick during balancing. One possible explanation for this is that the central nervous system increases muscle activation to account for less precise motor control, possibly to improve the responsiveness of human motor control. PMID:27010497

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

    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.

  17. Risk informed approach to the in-service inspection activities

    In the present paper, the aspects of Risk Informed In-Service Inspection (RI-ISI) are discussed. Slovenian Nuclear Safety Administration (SNSA) and its authorized organization for the ISI activities, Institute of Metals and Technologies (IMT), are actually permanently involved in the ISI processes of the nuclear power plant (NPP) Krsko. Based on the previous experience on the ISI activities, evaluation of the results and review of the existing practice in nuclear world, the activities are started to asses the piping of systems in the light of probability of failure. This is so called Risk Informed approach. By the design established criteria, standards and practice gives good fundaments for the improvements implementation. Improvements can be done on the way that the more broad knowledge about safety important components of the systems shall bee added to the basic practice. It is necessary to identify conditions of the safety important components, such as realistic stress and fatigue conditions, material properties changes due aging processes, the temperature cycling effects, existing flaws characterization in the light of the previous detection and equipment technique used, assessment of the measurement accuracy on the results etc. In addition to this deterministic approach, the principles of risk evaluation methods should be used. NPP Krsko has, as practically majority of NPP's, probabilistic risk assessment (PRA) studies for all safety important systems and components. The methods and results from these studies can be efficiently used to upgrade classical deterministic results, based on which the in-service program as a whole is usually done. In addition to the above mentioned, risk assessment and evaluation of the piping shall be done, which is not covered by the existing PRA analysis. To do this it is necessary to made risk evaluation of the piping segments, based on previous structural element probability assessment. Probabilistic risk assessment is important

  18. Oxidant stress leads to transcriptional activation of the human heme oxygenase gene in cultured skin fibroblasts

    Treatment of cultured human skin fibroblasts with near-UV radiation, hydrogen peroxide, and sodium arsenite induces accumulation of heme oxygenase mRNA and protein. In this study, these treatments led to a dramatic increase in the rate of RNA transcription from the heme oxygenase gene but had no effect on mRNA stability. Transcriptional activation, therefore, appears to be the major mechanism of stimulation of expression of this gene by either oxidative stress or sulfydryl reagents

  19. Oxidant stress leads to transcriptional activation of the human heme oxygenase gene in cultured skin fibroblasts.

    Keyse, S M; Applegate, L. A.; Tromvoukis, Y; Tyrrell, R M

    1990-01-01

    Treatment of cultured human skin fibroblasts with near-UV radiation, hydrogen peroxide, and sodium arsenite induces accumulation of heme oxygenase mRNA and protein. In this study, these treatments led to a dramatic increase in the rate of RNA transcription from the heme oxygenase gene but had no effect on mRNA stability. Transcriptional activation, therefore, appears to be the major mechanism of stimulation of expression of this gene by either oxidative stress or sulfydryl reagents.

  20. Activation of mutant protein kinase Cγ leads to aberrant sequestration and impairment of its cellular function

    Mutations in protein kinase Cγ (PKCγ) cause the neurodegenerative disease spinocerebellar ataxia type 14 (SCA14). In this study, expression of an extensive panel of known SCA14-associated PKCγ mutations as fusion proteins in cell culture led to the consistent formation of cytoplasmic aggregates in response to purinoceptor stimulation. Aggregates co-stained with antibodies to phosphorylated PKCγ and the early endosome marker EEA1 but failed to redistribute to the cell membrane under conditions of oxidative stress. These studies suggest that Purkinje cell damage in SCA14 may result from a reduction of PKCγ activity due its aberrant sequestration in the early endosome compartment

  1. Structure Guided Development of Novel Thymidine Mimetics targeting Pseudomonas aeruginosa Thymidylate Kinase: from Hit to Lead Generation

    Choi, Jun Yong; Plummer, Mark S.; Starr, Jeremy; Desbonnet, Charlene R.; Soutter, Holly; Chang, Jeanne; Miller, J. Richard; Dillman, Keith; Miller, Alita A.; Roush, William R.

    2012-01-01

    Thymidylate kinase (TMK) is a potential chemotherapeutic target because it is directly involved in the synthesis of an essential component, thymidine triphosphate, in DNA replication. All reported TMK inhibitors are thymidine analogs, which might retard their development as potent therapeutics due to cell permeability and off-target activity against human TMK. A small molecule hit (1, IC50 = 58 μM), which has reasonable inhibition potency against Pseudomonas aeruginosa TMK (PaTMK), was identi...

  2. Reduced expression of PNUTS leads to activation of Rb-phosphatase and caspase-mediated apoptosis.

    De Leon, Gabriel; Sherry, Tara C; Krucher, Nancy A

    2008-06-01

    There is abundant evidence that Retinoblastoma (Rb) activity is important in the control of cell proliferation and apoptosis. Reversible phosphorylation of the Rb protein that is carried out by cyclin dependent kinases and Protein phosphatase 1 (PP1) regulates its functions. A PP1 interacting protein, PNUTS (Phosphatase Nuclear Targeting Subunit) is proposed to be a regulator of Rb phosphorylation. In this study, PNUTS knockdown in MCF7, SKA and HCT116 cancer cells causes a reduction in viability due to increased apoptosis. However, normal cells (MCF10A breast and CCD-18Co colon) do not exhibit reduced viability when PNUTS expression is diminished. PNUTS knockdown has no effect in Rb-null Saos-2 cells. However, when Rb is stably expressed in Saos-2 cells, PNUTS knockdown reduces cell number. Knockdown of PNUTS in p53-/- HCT116 cells indicates that p53 is dispensable for the induction of apoptosis. Loss of PNUTS expression results in increased Rb-phosphatase activity and Rb dephosphorylation. E2F1 dissociates from Rb in cells depleted of PNUTS and the resulting apoptosis is dependent on caspase-8. These results indicate that Rb phosphorylation state can be manipulated by targeting Rb phosphatase activity and suggest that PNUTS may be a potential target for therapeutic pro-apoptotic strategies. PMID:18360108

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

    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...... 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...

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

    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.

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

    S. Li; Xie, W.; Shen, J; H-J Im; JD Holz; Wang, M.; TGH Diekwisch; Chen, D.

    2014-01-01

    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 th...

  6. Detection of metabolic activation leading to drug-induced phospholipidosis in rat hepatocyte spheroids.

    Takagi, Masashi; Sanoh, Seigo; Santoh, Masataka; Ejiri, Yoko; Kotake, Yaichiro; Ohta, Shigeru

    2016-02-01

    Drug-induced phospholipidosis (PLD) is one of the adverse reactions to treatment with cationic amphiphilic drugs. Recently, simple and reliable evaluation methods for PLD have been reported. However, the predictive power of these methods for in vivo PLD induction is insufficient in some cases. To accurately predict PLD, we focused on drug metabolism and used three-dimensional cultures of hepatocytes known as spheroids. Here we used the fluorescent phospholipid dye N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (NBD-PE) to detect PLD induction. After 48 hr exposure to 20 µM amiodarone and amitriptyline, PLD inducers, NBD-PE fluorescence in the spheroids was significantly higher than that in the control. In contrast, 1 mM acetaminophen, as a negative control, did not increase fluorescence. Furthermore, the combination of NBD-PE fluorescence and LysoTracker Red fluorescence and the accumulation of intrinsic phospholipids reflected PLD induction in spheroids. To evaluate metabolic activation, we assessed PLD induction by loratadine. NBD-PE fluorescence intensity was significantly increased by 50 µM loratadine treatment. However, the fluorescence was markedly decreased by co-treatment with 500 µM 1-aminobenzotriazole, a broad cytochrome P450 inhibitor. The formation of desloratadine, a metabolite of loratadine, was observed in spheroids after treatment with loratadine alone. These results showed that metabolic activation is the key factor in PLD induction by treatment with loratadine. We demonstrated that rat primary hepatocyte spheroid culture is a useful model for evaluating drug-induced PLD induction mediated by metabolic activation of the drug using the fluorescence probe technique. PMID:26763403

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

    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. PMID:22350112

  8. AREVA NP Inc next generation fresh UO2 fuel assembly shipping cask: SCALE - CRISTAL comparisons lead to safety criticality confidence

    AREVA NP as a worldwide PWR fuel provider has to have a fleet of fresh UO2 shipping casks being agreed within a lot of countries including USA (France), Germany, Belgium, Sweden, China, and South Africa... and to accommodate foreseen EPR Nuclear Power Plants fuel buildings. To reach this target the AREVA NP Fuel Sector decided to develop an up to date shipping cask gathering experience feedback of the today fleet and an improved safety allowing the design to comply with international regulations (NRC and IAEA) and local Safety Authorities. Based on pre design features a safety case was set up to highlight safety margins. Criticality hypothetical accidental assumptions were defined: -Preferential flooding - Fuel rod lattice pitch expansion for full length of fuel assemblies - Neutron absorber penalty -... Well known computer codes, American SCALE package and French CRISTAL package, were used to check configurations reactivity and to ensure that both codes lead to coherent results. Basic spectral calculations are based on similar algorithms with specific microscopic cross sections ENDF/BV for SCALE and JEF2.2 for CRISTAL. The main differences between the two packages is on one hand SCALE's three dimensional fuel assembly geometry is described by a pin by pin model while an homogenized fuel assembly description is used by CRISTAL and on the other hand SCALE is working with either 44 or 238 neutron energy groups while CRISTAL is with a 172 neutron energy groups. Those two computer packages rely on a wide validation process helping defining uncertainties as required by regulations in force. The shipping cask with two fuel assemblies is designed to maximize fuel isolation inside a cask and with neighboring ones even for large array configuration cases. Proven industrial products are used: - BoralTM as neutron absorber - High density polyethylene (HDPE) or Nylon as neutron moderator - Foam as thermal and mechanical protection The cask is designed to handle the complete

  9. AREVA NP next generation fresh UO2 fuel assembly shipping cask: SCALE - CRISTAL comparisons lead to safety criticality confidence

    AREVA NP as a worldwide PWR fuel provider has to have a fleet of fresh UO2 shipping casks being agreed within a lot of countries including USA, France, Germany, Belgium, Sweden, China, and South Africa - and to accommodate foreseen EPR Nuclear Power Plants fuel buildings. To reach this target the AREVA NP Fuel Sector decided to develop an up-to-date shipping cask (so called MAP project) gathering experience feedback of the today fleet and an improved safety allowing the design to comply with international regulations (NRC and IAEA) and local Safety Authorities. Based on pre design features a safety case was set up to highlight safety margins. Criticality hypothetical accidental assumptions were defined: - Preferential flooding; - Fuel rod lattice pitch expansion for full length of fuel assemblies; - Neutron absorber penalty; -... Well known computer codes, American SCALE package and French CRISTAL package, were used to check configurations reactivity and to ensure that both codes lead to coherent results. Basic spectral calculations are based on similar algorithms with specific microscopic cross sections ENDF/BV for SCALE and JEF2.2 for CRISTAL. The main differences between the two packages is on one hand SCALE's three dimensional fuel assembly geometry is described by a pin by pin model while an homogenized fuel assembly description is used by CRISTAL and on the other hand SCALE is working with either 44 or 238 neutron energy groups while CRISTAL is with a 172 neutron energy groups. Those two computer packages rely on a wide validation process helping defining uncertainties as required by regulations in force. The shipping cask with two fuel assemblies is designed to maximize fuel isolation inside a cask and with neighboring ones even for large array configuration cases. Proven industrial products are used: - BoralTM as neutron absorber; - High density polyethylene (HDPE) or Nylon as neutron moderator; - Foam as thermal and mechanical protection. The cask is

  10. Activation of Human Neutrophils by the Anti-Inflammatory Mediator Esenbeckia leiocarpa Leads to Atypical Apoptosis

    Rafael de Liz

    2012-01-01

    Full Text Available Despite the fact that Esenbeckia leiocarpa, a Brazilian plant, possesses potential anti-inflammatory properties, its effect in neutrophils, key players in inflammation, has never been investigated. In this study, a crude hydroalcoholic extract (CHE was used to evaluate the potential toxic or agonistic effect of E. leiocarpa in human neutrophils. At a noncytotoxic concentration of 500 μg/mL, CHE increased actin polymerization and cell signaling events, especially p38 MAPK. Its modulatory activity on neutrophil cell apoptosis was investigated by cytology and by flow cytometry and, although CHE increased the apoptotic rate (by cytology and increased annexin-V binding, it did not, unexpectedly, increase CD16 shedding. CHE increased the degradation of the cytoskeletal proteins gelsolin and paxillin but, surprisingly, not of vimentin. The proapoptotic activity of CHE was reversed by a pan-caspase inhibitor but not by a p38 inhibitor. We conclude that CHE is a novel human neutrophil agonist that induces apoptosis by a caspase-dependent and p38-independent mechanism in an atypical fashion based on its lack of effect on CD16 shedding and vimentin degradation. Since the resolution of inflammation occurs by elimination of apoptotic neutrophils, the ability of CHE to induce neutrophil apoptosis correlates well with its anti-inflammatory properties, as previously reported.

  11. Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis.

    Gieseck, Richard L; Ramalingam, Thirumalai R; Hart, Kevin M; Vannella, Kevin M; Cantu, David A; Lu, Wei-Yu; Ferreira-González, Sofía; Forbes, Stuart J; Vallier, Ludovic; Wynn, Thomas A

    2016-07-19

    Fibroproliferative diseases are driven by dysregulated tissue repair responses and are a major cause of morbidity and mortality because they affect nearly every organ system. Type 2 cytokine responses are critically involved in tissue repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis are not well understood. Here, we have shown that the type 2 effector cytokine interleukin-13 simultaneously, yet independently, directed hepatic fibrosis and the compensatory proliferation of hepatocytes and biliary cells in progressive models of liver disease induced by interleukin-13 overexpression or after infection with Schistosoma mansoni. Using transgenic mice with interleukin-13 signaling genetically disrupted in hepatocytes, cholangiocytes, or resident tissue fibroblasts, we have revealed direct and distinct roles for interleukin-13 in fibrosis, steatosis, cholestasis, and ductular reaction. Together, these studies show that these mechanisms are simultaneously controlled but distinctly regulated by interleukin-13 signaling. Thus, it may be possible to promote interleukin-13-dependent hepatobiliary expansion without generating pathological fibrosis. VIDEO ABSTRACT. PMID:27421703

  12. Another road leads to HIF-1 activation: implications for prostate cancer progression

    Yao Dai1; Kyungmi Bae2; Dietmar W Siemann1

    2012-01-01

    Hypoxia has been identified as a common environmental stress factor associated with therapeutic resistance and metastasis in human cancers.A major player in regulating the response to hypoxia is the transcriptional factor hypoxia-inducible factor 1 alpha (HIF-1α).Although HIF-1α is well known to be stabilized under hypoxia,the regulatory mechanism of HIF-1α signaling in malignant cells is not fully understood.In a recent paper,Yuan et al.1 identified a novel pathway that acts as a ‘vicious cycle'to amplify HIF- 1 activation in prostate cancer cells,hence suggesting potential biomarkers that may predict progression and poor prognosis in human prostate cancer (Figure 1).

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

    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. PMID:25967228

  14. Contribution to the Active Generator Principle: the Gate-commutated Polyphased Matrix Converter

    Béguin, Antoine

    2012-01-01

    This work is part of the innovative "Active Generator" (AG) project. AG is a concept that suggests a new arrangement of the turbine-generator line of a high power utility (a few hundred of MW) in order to de-synchronize the rotation speed of the turbine-generator group from the fixed grid frequency (50 Hz or 60 Hz). This de-synchronization has essentially two advantages. First, the variable speed of the group enables the operation of the turbine...

  15. Improving the way to communicate learning activities to an informal learning collector

    Casany Guerrero, María José; Hierro, Nélida; Galanis, Nikolaos; Mayol Sarroca, Enric; Alier Forment, Marc

    2015-01-01

    Lifelong Learning has been a growing interest in e-learning research communities, in a similar way as other related kinds of learning (formal, non-formal and informal) already had. In fact, the Tagging Recognition and Acknowledgment of Informal Learning Experiences project proposes a framework to manage these types of learning, giving special attention to informal learning. This project gathers informal learning activities with an Informal Learning Collector. The main way for registering i...

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

    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.

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

    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. PMID:24946863

  18. 78 FR 64927 - Agency Information Collection Activities; Agency Information Collection Activities; Submission to...

    2013-10-30

    ..., income, and debt, among other measures. Data from BPS are used to help researchers and policymakers... collection. Respondents/Affected Public: Individuals or households. Total Estimated Number of...

  19. Supercontinuum generation up to 2.5 μm in photonic crystal fiber made of lead-bismuth-galate glass

    In this paper we report on successful supercontinuum generation extending from the near to the mid-infrared region in the range 700–2500 nm in a micro-structured fiber made of lead-bismuth-galate glass and pumped in the femtosecond regime with a wavelength of 1540 nm. The flatness of 5 dB is observed in most of the registered spectrum 1000 – 2500 nm. The improved spectral and thermo-physical properties of this custom made lead-bismuth-galate glass against tellurite and commercially available heavy oxide SF-57 glasses are presented

  20. Interneuron Activity Leads to Initiation of Low-Voltage Fast-Onset Seizures

    Shiri, Zahra; Manseau, Frédéric; Lévesque, Maxime; Williams, Sylvain; Avoli, Massimo

    2016-01-01

    Seizures in temporal lobe epilepsy can be classified as hypersynchronous and low-voltage fast according to their onset patterns. Experimental evidence suggests that low-voltage fast-onset seizures mainly result from the synchronous activity of γ-aminobutyric acid–releasing cells. In this study, we tested this hypothesis using the optogenetic control of parvalbumin-positive interneurons in the entorhinal cortex, in the in vitro 4-aminopyridine model. We found that both spontaneous and optogenetically induced seizures had similar low-voltage fast-onset patterns. In addition, both types of seizures presented with higher ripple than fast ripple rates. Our data demonstrate the involvement of interneuronal networks in the initiation of low-voltage fast-onset seizures. PMID:25546300

  1. Seasonal Variation of Lead in Fish Pond Waters of High Hunting Activity Area and Relation to Metals and Ions.

    Binkowski, Lukasz J; Rzonca, Bartłomiej

    2014-01-01

    Anthropogenic activities such as industry, agriculture, and daily life are related to metal pollution of the environment. Places known of the highest impact are fishponds where intensive fish farming is believed to input a significant amount of various elements to water. Additionally, many studies suspect wetland hunting activity of water lead pollution. The present paper aims to check if hunting is a significant source of lead (Pb) in water as well as to study the temporal trends of numerous parameters (pH, SEC, Cd, Cu, Zn, Ca, Mg, Na, K, NH4+, HCO3 (-), SO4 (2-), Cl(-), NO3 (-), F(-)) in ponds (n = 48) and inflow (n = 24) waters near Zator in southern Poland, Europe. Most concentrations were measured with ion chromatography and electrothermal atomic absorption spectrometry. Lead concentrations in pond waters were low and found not to be linked with hunting activity, as well as they did not differ from the ones found in the inflow water. Moreover, it could be stated that activities led on ponds did not enrich rivers in the studied ions and elements. PMID:25419011

  2. Spanish Young Generation (JJNN) Activities

    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)

  3. Spanish Young Generation (JJNN) Activities

    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)

  4. Increased Plp1 gene expression leads to massive microglial cell activation and inflammation throughout the brain

    Carrie L Tatar

    2010-09-01

    Full Text Available PMD (Pelizaeus–Merzbacher disease is a rare neurodegenerative disorder that impairs motor and cognitive functions and is associated with a shortened lifespan. The cause of PMD is mutations of the PLP1 [proteolipid protein 1 gene (human] gene. Transgenic mice with increased Plp1 [proteolipid protein 1 gene (non-human] copy number model most aspects of PMD patients with duplications. Hypomyelination and demyelination are believed to cause the neurological abnormalities in mammals with PLP1 duplications. We show, for the first time, intense microglial reactivity throughout the grey and white matter of a transgenic mouse line with increased copy number of the native Plp1 gene. Activated microglia in the white and grey matter of transgenic mice are found as early as postnatal day 7, before myelin commences in normal cerebra. This finding indicates that degeneration of myelin does not cause the microglial response. Microglial numbers are doubled due to in situ proliferation. Compared with the jp (jimpy mouse, which has much more oligodendrocyte death and hardly any myelin, microglia in the overexpressors show a more dramatic microglial reactivity than jp, especially in the grey matter. Predictably, many classical markers of an inflammatory response, including TNF-α (tumour necrosis factor-α and IL-6, are significantly up-regulated manyfold. Because inflammation is believed to contribute to axonal degeneration in multiple sclerosis and other neurodegenerative diseases, inflammation in mammals with increased Plp1 gene dosage may also contribute to axonal degeneration described in patients and rodents with PLP1 increased gene dosage.

  5. To Lead or Not to Lead?

    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…

  6. Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro-B cells.

    Pasquarella, Alessandra; Ebert, Anja; Pereira de Almeida, Gustavo; Hinterberger, Maria; Kazerani, Maryam; Nuber, Alexander; Ellwart, Joachim; Klein, Ludger; Busslinger, Meinrad; Schotta, Gunnar

    2016-05-15

    The H3K9me3-specific histone methyltransferase Setdb1 impacts on transcriptional regulation by repressing both developmental genes and retrotransposons. How impaired retrotransposon silencing may lead to developmental phenotypes is currently unclear. Here, we show that loss of Setdb1 in pro-B cells completely abrogates B cell development. In pro-B cells, Setdb1 is dispensable for silencing of lineage-inappropriate developmental genes. Instead, we detect strong derepression of endogenous murine leukemia virus (MLV) copies. This activation coincides with an unusual change in chromatin structure, with only partial loss of H3K9me3 and unchanged DNA methylation, but strongly increased H3K4me3. Production of MLV proteins leads to activation of the unfolded protein response pathway and apoptosis. Thus, our data demonstrate that B cell development depends on the proper repression of retrotransposon sequences through Setdb1. PMID:27013243

  7. Lead telluride with increased mechanical stability for cylindrical thermoelectric generators

    The aim of this work is to improve the mechanical stability of lead telluride (PbTe), trying to vary its mechanical properties independently from its thermoelectric properties. Thus the influence of material preparation as well as different dopants on the mechanical and thermoelectric properties of lead telluride is being analysed. When using appropriately set process parameters, milling and sintering of lead telluride increases the material's hardness. With sintering temperatures exceeding 300 C stable material of high relative density can be achieved. Milling lead telluride generates lattice defects leading to a reduction of the material's charge carrier density. These defects can be reduced by increased sintering temperatures. Contamination of the powder due to the milling process leads to bloating during thermal cycling and thus reduced density of the sintered material. In addition to that, evaporation of tellurium at elevated temperatures causes instability of the material's thermoelectric properties. Based on the experimental results obtained in this work, the best thermoelectric and mechanical properties can be obtained by sintering coarse powders at around 400 C. Within this work a concept was developed to vary the mechanical properties of lead telluride via synthesis of PbTe with electrically nondoping elements, which thus may keep the thermoelectric properties unchanged. Therefore, the mechanical and thermoelectric properties of Pb1-xCaxTe were investigated. Doping pure PbTe with calcium causes a significant increase of the material's hardness while only slightly decreasing the charge carrier density and thus keeping the thermoelectric properties apart from a slight reduction of the electrical conductivity nearly unchanged. The abovementioned concept is proven using sodium doped lead telluride, as it is used for thermoelectric generators: The additional doping with calcium again increases the material's hardness while its thermoelectric properties remain

  8. Information from leading neutrons at HERA

    Khoze, V. A.; Martin, A. D.; 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.

  9. ERK Activation by Fucoidan Leads to Inhibition of Melanogenesis in Mel-Ab Cells

    Song, Yu Seok; Balcos, Marie Carmel; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Kim, Myo-Kyoung; Kim, Dong-Seok

    2014-01-01

    Fucoidan, a fucose-rich sulfated polysaccharide derived from brown seaweed in the class Phaeophyceae, has been widely studied for its possible health benefits. However, the potential of fucoidan as a possible treatment for hyperpigmentation is not fully understood. This study investigated the effects of fucoidan on melanogenesis and related signaling pathways using Mel-Ab cells. Fucoidan significantly decreased melanin content. While fucoidan treatment decreased tyrosinase activity, it did no...

  10. Aryl hydrocarbon receptor activation leads to impairment of estrogen-driven chicken vitellogenin promoter activity in LMH cells.

    Bussmann, Ursula A; Pérez Sáez, Juan M; Bussmann, Leonardo E; Barañao, J Lino

    2013-03-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates most of the toxic effects of environmental contaminants. Among the multiple pleiotropic responses elicited by AHR agonists, the antiestrogenic and endocrine-disrupting action of the receptor activation is one of the most studied. It has been demonstrated that some AHR agonists disrupt estradiol-induced vitellogenin synthesis in the fish liver via a mechanism that involves crosstalk between the AHR and the estrogen receptor (ER). Chicken hepatocytes have become a model for the study of AHR action in birds and the induction of the signal and its effect in these cells are well established. However, the impact of AHR activation on estradiol-regulated responses in the chicken liver remains to be demonstrated. The aim of the present study was, therefore, to determine the effect of AHR action on ER-driven transcription in a convenient model of chicken liver cells. For this purpose, we designed a reporter construct bearing the 5' regulatory region of the chicken vitellogenin II gene and used it to transfect chicken hepatoma LMH cells. We found that β-naphthoflavone represses ER-driven vitellogenin promoter activity and that this action is mediated by the AHR. This inhibitory crosstalk between both pathways appears to be unidirectional, since estradiol did not alter the transcript levels of an AHR target gene. Besides, and highly relevant, we show that LMH cell line transfected with a reporter construct bearing the chicken vitellogenin promoter sequence is a useful and convenient model for the study of AHR-ER interaction in chicken liver-derived cells. PMID:23103859

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

    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...

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

    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…

  13. 78 FR 33075 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    2013-06-03

    ... Agency Information Collection Activities; Submission to the Office of Management and Budget for Review... questionnaires. Wave 2 will contain technology and engineering literacy (TEL) and science ICT (interactive... Director, Information Collection Clearance Division, Privacy, Information and Records Management...

  14. Meta-information generation in distributed information system

    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. Mata—information generation in distributed information system

    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.

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

    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.

  17. Plasminogen Acquisition and Activation at the Surface of Leptospira Species Lead to Fibronectin Degradation ▿

    Vieira, Monica L.; Vasconcellos, Silvio A.; Gonçales, Amane P.; de Morais, Zenaide M.; Nascimento, Ana L. T. O.

    2009-01-01

    Pathogenic Leptospira species are the etiological agents of leptospirosis, a widespread disease of human and veterinary concern. In this study, we report that Leptospira species are capable of binding plasminogen (PLG) in vitro. The binding to the leptospiral surface was demonstrated by indirect immunofluorescence confocal microscopy with living bacteria. The PLG binding to the bacteria seems to occur via lysine residues because the ligation is inhibited by addition of the lysine analog 6-ami...

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

    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 ge...

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

    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. ...

  20. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

    Helin, K; Wu, C L; Fattaey, A R;

    1993-01-01

    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...... 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 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....

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

    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.

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

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

    2016-05-01

    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.

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

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

    2016-01-01

    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. PMID:27181846

  4. Transcriptome Profiling of Radish (Raphanus sativus L.) Root and Identification of Genes Involved in Response to Lead (Pb) Stress with Next Generation Sequencing

    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 ...

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

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

    2012-01-01

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

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

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

    2011-01-01

    Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we utilized 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 GFP-positive astrocytes in acute brain slices from GFAP-GFP mice at 3 or 7 days following S. aureus infection in the striatum. Astrocyte GJ communication was signific...

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

    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...

  8. DMSO triggers the generation of ROS leading to an increase in artemisinin and dihydroartemisinic acid in Artemisia annua shoot cultures

    Mannan, Abdul; Liu, Chunzhao; Arsenault, Patrick R.; Towler, Melissa J.; Vail, Dan R.; Lorence, Argelia; Weathers, Pamela J.

    2009-01-01

    The antimalarial sesquiterpene, artemisinin, is in short supply; demand is not being met, and the role of artemisinin in the plant is not well established. Prior work showed that addition of dimethyl sulfoxide (DMSO) to seedlings increased artemisinin in their shoots and this study further investigated that serendipitous observation. When in vitro-cultured Artemisia annua rooted shoots were fed different amounts of DMSO (0–2.0% v/v), artemisinin levels doubled and showed biphasic optima at 0....

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

    Bunget Ovidiu Constantin; Dumitrescu Alin Constantin; Deliu Delia

    2013-01-01

    The current economic environment evolves under globalization circumstances, and it stands for the markets' globalization trend. Under these circumstances, information has a primordial role. The content of the transmitted information has changed significantly. As part of the economic information, the accounting information evolved as well and its whole circuit has been continuously modernized in the rhythm of the global changes. Thus, it had to adapt to the swing of capital markets worldwide a...

  10. Bacteroides fragilis interferes with iNOS activity and leads to pore formation in macrophage surface

    Bacteroides fragilis is the anaerobe most commonly recoverable from clinical specimens. The wide genetic diversity of this bacterium related with virulence potential is still an open question. In this study, we analyzed the morphological aspects and microbicide action of MO during interactions with B. fragilis. A filamentous cytoplasm content release and a different actin organization colocalized with iNOS were detected. It was also possible to observe the reduction of NO production in the same conditions. The scanning electron microscopy showed the formation of pore-like structures in the surface of macrophages in the bacterial presence and by transmission electron microscopy we could observe the extrusion of cytoplasm contents as well as the condensation of chromatin in the nucleus periphery. These data suggest the existence of an inhibitory mechanism developed by B. fragilis strains for one of the macrophage microbicide actions

  11. Loss of Frataxin induces iron toxicity, sphingolipid synthesis, and Pdk1/Mef2 activation, leading to neurodegeneration

    Chen, Kuchuan; Lin, Guang; Haelterman, Nele A; Ho, Tammy Szu-Yu; Li, Tongchao; Li, Zhihong; Duraine, Lita; Graham, Brett H; Jaiswal, Manish; Yamamoto, Shinya; Rasband, Matthew N; Bellen, Hugo J

    2016-01-01

    Mutations in Frataxin (FXN) cause Friedreich’s ataxia (FRDA), a recessive neurodegenerative disorder. Previous studies have proposed that loss of FXN causes mitochondrial dysfunction, which triggers elevated reactive oxygen species (ROS) and leads to the demise of neurons. Here we describe a ROS independent mechanism that contributes to neurodegeneration in fly FXN mutants. We show that loss of frataxin homolog (fh) in Drosophila leads to iron toxicity, which in turn induces sphingolipid synthesis and ectopically activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2). Dampening iron toxicity, inhibiting sphingolipid synthesis by Myriocin, or reducing Pdk1 or Mef2 levels, all effectively suppress neurodegeneration in fh mutants. Moreover, increasing dihydrosphingosine activates Mef2 activity through PDK1 in mammalian neuronal cell line suggesting that the mechanisms are evolutionarily conserved. Our results indicate that an iron/sphingolipid/Pdk1/Mef2 pathway may play a role in FRDA. DOI: http://dx.doi.org/10.7554/eLife.16043.001 PMID:27343351

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

    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.

  13. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

    Aarti eNagayach

    2014-10-01

    Full Text Available Behavioural impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45mg/ kg body weight; intraperitoneally. Motor function alterations were studied using Rotarod test (motor coordination and grip strength (muscle activity at 2nd, 4th, 6th, 8th, 10th and 12th week post diabetic confirmation. Scenario of glial (astroglia and microglia activation, cell death and glutamate transportation was gauged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labelling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioural alterations following STZ-induced diabetes.

  14. Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation.

    Kim, Hyun Ji; Kang, Gyeoung Jin; Kim, Eun Ji; Park, Mi Kyung; Byun, Hyun Jung; Nam, Seungyoon; Lee, Ho; Lee, Chang Hoon

    2016-09-01

    Sphingosylphosphorylcholine (SPC) participates in several cellular processes including metastasis. SPC induces keratin reorganization and regulates the viscoelasticity of metastatic cancer cells including PANC-1 cancer cells leading to enhanced migration and invasion. The role of SPC and the relevant mechanism in invasion of breast cell are as yet unknown. SPC dose-dependently induces invasion of breast cancer cells or breast immortalized cells. Reverse transcription polymerase chain reaction and Western blot analyses of MCF10A and ZR-75-1 cells indicated that SPC induces expression and secretion of matrix metalloproteinase-3 (MMP3). From online KMPLOT, relapse free survival is high in patients having low MMP3 expressed basal breast cancer (n=581, p=0.032). UK370106 (MMP3 inhibitor) or gene silencing of MMP3 markedly inhibited the SPC-induced invasion of MCF10A cells. An extracellular signal-regulated kinase (ERK) inhibitor, PD98059, significantly suppressed the secretion and the gelatinolytic activity of MMP3, and invasion in MCF10A cells. Over-expression of ERK1 and ERK2 promoted both the expression and secretion of MMP3. In contrast, gene silencing of ERK1 and ERK2 attenuated the secretion of MMP3 in MCF10A cells. The effects of SPC-induced MMP3 secretion on β-catenin and TCF/lymphoid enhancer factor (LEF) promoter activity were examined since MMP3 indirectly activates canonical Wnt signaling. SPC induced translocation of β-catenin to nucleus and increased TCF/LEF promoter activity. These events were suppressed by UK370106 or PD98059. Wnt inhibitor, FH535 inhibited SPC-induced MMP3 secretion and invasion. Taken together, these results suggest that SPC induces MMP3 expression and secretion via ERK leading to Wnt activation. PMID:27216977

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

    (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 IC50 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 G2/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 PDEs, SIRT1, or

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

    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

  17. Col1a1-cre mediated activation of β-catenin leads to aberrant dento-alveolar complex formation

    Kim, Tak-Heun; Bae, Cheol-Hyeon; Jang, Eun-Ha; Yoon, Chi-Young; Bae, Young; Ko, Seung-O; Taketo, Makoto M.; Cho, Eui-Sic

    2012-01-01

    Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/β-catenin signaling in the dento-alveolar complex formation, we generated conditional β-catenin activation mice through intercross of Catnb+/lox(ex3) mice with Col1a1-cre...

  18. Generating superposition of up-to three photons for continuous variable quantum information processing.

    Yukawa, Mitsuyoshi; Miyata, Kazunori; Mizuta, Takahiro; Yonezawa, Hidehiro; Marek, Petr; Filip, Radim; Furusawa, Akira

    2013-03-11

    We develop an experimental scheme based on a continuous-wave (cw) laser for generating arbitrary superpositions of photon number states. In this experiment, we successfully generate superposition states of zero to three photons, namely advanced versions of superpositions of two and three coherent states. They are fully compatible with developed quantum teleportation and measurement-based quantum operations with cw lasers. Due to achieved high detection efficiency, we observe, without any loss correction, multiple areas of negativity of Wigner function, which confirm strongly nonclassical nature of the generated states. PMID:23482124

  19. 78 FR 53506 - Agency Information Collection (HUD/VA Addendum to Uniform Residential Loan Application) Activity...

    2013-08-29

    ....rennie@va.gov . Please refer to ``OMB Control No. 2900-0144.'' SUPPLEMENTARY INFORMATION: Title: HUD/VA... AFFAIRS Agency Information Collection (HUD/VA Addendum to Uniform Residential Loan Application) Activity... information through www.Regulations.gov , or to Office of Information and Regulatory Affairs, Office...

  20. Chibby drives β catenin cytoplasmic accumulation leading to activation of the unfolded protein response in BCR-ABL1+ cells.

    Mancini, Manuela; Leo, Elisa; Takemaru, Ken-Ichi; Campi, Virginia; Borsi, Enrica; Castagnetti, Fausto; Gugliotta, Gabriele; Santucci, Maria Alessandra; Martinelli, Giovanni

    2013-09-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the constitutive tyrosine kinase (TK) activity of the BCR-ABL fusion protein. However, the phenotype of leukemic stem cells (LSC) is sustained by β catenin rather than by the BCR-ABL TK. β catenin activity in CML is contingent upon its stabilization proceeding from the BCR-ABL-induced phosphorylation at critical residues for interaction with the Adenomatous polyposis coli (APC)/Axin/glycogen synthase kinase 3 (GSK3) destruction complex or GSK3 inactivating mutations. Here we studied the impact of β catenin antagonist Chibby (CBY) on β catenin signaling in BCR-ABL1+ cells. CBY is a small conserved protein which interacts with β catenin and impairs β catenin-mediated transcriptional activation through two distinct molecular mechanisms: 1) competition with T cell factor (TCF) or lymphoid enhancer factor (LEF) for β catenin binding; and 2) nuclear export of β catenin via interaction with 14-3-3. We found that its enforced expression in K562 cell line promoted β catenin cytoplasmic translocation resulting in inhibition of target gene transcription. Moreover, cytoplasmic accumulation of β catenin activated the endoplasmic reticulum (ER) stress-associated pathway known as unfolded protein response (UPR). CBY-driven cytoplasmic accumulation of β catenin is also a component of BCR-ABL1+ cell response to the TK inhibitor Imatinib (IM). It evoked the UPR activation leading to the induction of BCL2-interacting mediator of cell death (BIM) by UPR sensors. BIM, in turn, contributed to the execution phase of apoptosis in the activation of ER resident caspase 12 and mobilization of Ca(2+) stores. PMID:23707389

  1. Legal framework related to access to information and public participation on nuclear activity

    The right of access to information by citizens about activities related to scientific and technological development of nuclear energy for peaceful uses, has evolved over time. Governments began to perceive the necessity and the benefits of informing the community, who manifested certain prejudices about nuclear activity as a consequence of the propelling of nuclear bombs in Nagasaki and Hiroshima. With the advent of environmental law and the influence of its principles, the idea of transparency of information in the nuclear field was imposed, and also the importance of both the inhabitants of countries with nuclear developments and neighbouring countries who may be affected by the bordering effects of ionizing radiation, could have access to information and to participate actively. The access to information and citizen participation has been institutionalized and reflected in international regulations through international conventions subscribed by our country and nationally through the National Constitution, the Provincials Constitutions, the City of Buenos Aires Constitution, Laws No. 25.675, 25.831 and PEN Decree No. 1172/03, among others. The present work aims to make an overview of the legal framework related to access to information on nuclear activity. (authors)

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

    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.

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

    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.

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

    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...

  5. Using Route and Survey Information to Generate Cognitive Maps: Differences Between Normally Sighted and Visually Impaired Indiviuals

    Steyvers, Frank J.J.M.; Kooijman, Aart C.

    2008-01-01

    Visually impaired people (VIP) have to rely on different information to generate a cognitive map of their environment than normally sighted people. This study explored the extent to which a cognitive map could be generated by auditory information of route-type and survey-type descriptions of a fictitious environment. A total of 27 visually impaired and 28 normally sighted participants listened to either a survey-type or a route-type description of a fictitious zoo. They then answered both rou...

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

    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.

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

    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.

  8. Research on the response of various persons to information about nuclear power generation

    The author surveyed blogs readily available on the Internet for three purposes: (1) to grasp the public response to nuclear problems after the accident at the Fukushima Daiichi Nuclear Power Station, (2) to determine changes in the number of blogs based on an article search, and (3) to identify the stance of bloggers on the necessity of nuclear power generation based on reading contribution contents. Furthermore the author conducted a questionnaire survey of public response in reference to the results of the blog survey. From the blog survey, it was found that immediately after the accident, the number of blogs which were negative toward nuclear power generation drastically increased, but as time has passed, blogs which are positive are increasing in number somewhat in expectation of stabilized economic and living conditions. The main results of the questionnaire survey are as follows. (1) Many persons want power generation that is non-nuclear; this is because they have good expectations for renewable energy sources or new thermal power generation as an alternative energy and they strongly feel anxious about the issue of disposal of spent nuclear fuel. (2) Because of the risk of negative impacts which electricity shortages bring on the economy and lifestyles, some persons do not want immediate decommissioning of nuclear power reactors, they favor a phase-out of nuclear power generation. Though public opinion about nuclear problems includes the expectation that one alternative energy can be selected, there is a possibility that this opinion will shift to find an optimum energy mix of plural energy sources. (author)

  9. Internalization of Clostridium perfringens α-toxin leads to ERK activation and is involved on its cytotoxic effect.

    Monturiol-Gross, Laura; Flores-Díaz, Marietta; Campos-Rodríguez, Diana; Mora, Rodrigo; Rodríguez-Vega, Mariela; Marks, David L; Alape-Girón, Alberto

    2014-04-01

    Clostridium perfringens phospholipase C (CpPLC), also called α-toxin, plays a key role in the pathogenesis of gas gangrene. CpPLC may lead to cell lysis at concentrations that cause extensive degradation of plasma membrane phospholipids. However, at sublytic concentrations it induces cytotoxicity without inducing evident membrane damage. The results of this work demonstrate that CpPLC becomes internalized in cells by a dynamin-dependent mechanism and in a time progressive process: first, CpPLC colocalizes with caveolin both at the plasma membrane and in vesicles, and later it colocalizes with early and late endosomes and lysosomes. Lysosomal damage in the target cells is evident 9 h after CpPLC exposure. Our previous work demonstrated that CpPLCinduces ERK1/2 activation, which is involved in its cytotoxic effect. In this work we found that cholesterol sequestration, dynamin inhibition, as well as inhibition of actin polymerization, prevent CpPLC internalization and ERK1/2 activation, involving endocytosis in the signalling events required for CpPLC cytotoxic effect at sublytic concentrations. These results provide new insights about the mode of action of this bacterial phospholipase C, previously considered to act only locally on cell membrane. PMID:24245664

  10. The GUINEVERE-project: the first zero-power fast lead reactor coupled to a 14 MeV neutron generator (GENEPI)

    The GUINEVERE project is an European project in the framework of FP6 IP-EUROTRANS. The IP-EUROTRANS project aims at addressing the main issues for ADS development in the framework of partitioning and transmutation for nuclear waste volume and radio toxicity reduction. The GUINEVERE-project is carried out in the context of domain 2 of IP-EUROTRANS, ECATS, devoted to specific experiments for the coupling of an accelerator, a target and a subcritical core. These experiments should provide an answer to the questions of on-line reactivity monitoring, sub-criticality determination and operational procedures (loading, start-up, shut-down) in an ADS by 2009-2010. During the definition of the experimental programme ECATS, it was judged that there was a strong need for a European managed experiment in the line of the FP5 MUSE-project. Reanalyzing the outcome of MUSE, two points were left open for significant improvement. To validate the methodology for reactivity monitoring, a continuous beam is needed, which was not present in the MUSE-project. In the definition of the MUSE-project, from the beginning a strong request was made for a lead core in order to have representative conditions of a lead-cooled ADS which was only partially answered by the MUSE-programme. Therefore, there is a need for a lead fast critical facility connected to a continuous beam accelerator. Since such a programme/installation is not present at the European nor at the international level, SCK-CEN has proposed to use a modified VENUS critical facility located at its Mol-site and to couple it to a modified GENEPI deuteron accelerator (used in MUSE) working in current mode delivering 14 MeV neutrons by bombardment of deuterons on a tritium-target: the GUINEVERE-project (Generator of Uninterrupted Intense NEutrons at the lead VEnus REactor). This proposal was formally accepted by the Governing Council of IP-Eurotrans in December 2006. This project represents a close collaboration between SCK-CEN, CEA and

  11. Renal ischemia-reperfusion leads to long term infiltration of activated and effector-memory T lymphocytes

    Ascon, Miguel; Ascon, Dolores B.; Liu, Manchang; Cheadle, Chris; Sarkar, Chaitali; Racusen, Lorraine; Hassoun, Heitham T.; Rabb, Hamid

    2009-01-01

    It is well-established that significant ischemia-reperfusion injury during kidney transplantation results in increased incidence of long-term fibrosis and rejection. To test for a role of T cell infiltration and activation following ischemic injury, we induced both bilateral and unilateral renal ischemia in mice, followed by reperfusion, and then isolated mononuclear cells. Analysis of these cells by flow cytometry showed that 2 weeks after bilateral ischemia there was a significant increase of CD8 + T cells. Furthermore, both CD4 + and CD8 + T cells infiltrated the injured kidney 6 weeks after unilateral ischemia. These T cells had increased expression of CD69 + and CD44hiCD62L −, markers of activation and effector-memory, respectively. CD4 + NK1.1 + and CD19 + B cells were decreased in percentage both 6 and 11 weeks after bilateral or unilateral injury. There was a significant upregulation of IL-1β, IL-6, TNF-α, IFN-γ, MIP-2, and RANTES expression, measured by real-time PCR, 6 weeks after unilateral renal ischemia, further indicating T cell activation. Depletion of CD4 + and CD8 + T cells before ischemia caused less medullary damage and reduced kidney IFN-γ expression, whereas their depletion following ischemia increased kidney IL-1β; however, depletion of these cells had no effect on histological damage to the kidney. Our study demonstrates that moderate or severe kidney ischemia induces long-term T lymphocyte infiltration and cytokine/chemokine upregulation, leading to kidney structural changes. PMID:19092796

  12. Inhibition of Phosphatase Activity Follows Decline in Sulfatase Activity and Leads to Transcriptional Effects through Sustained Phosphorylation of Transcription Factor MITF.

    Bhattacharyya, Sumit; Feferman, Leo; Tobacman, Joanne K

    2016-01-01

    Arylsulfatase B (B-acetylgalactosamine 4-sulfatase; ARSB) is the enzyme that removes 4-sulfate groups from the non-reducing end of the glycosaminoglycans chondroitin 4-sulfate and dermatan sulfate. Decline in ARSB has been shown in malignant prostate, colonic, and mammary cells and tissues, and decline in ARSB leads to transcriptional events mediated by galectin-3 with AP-1 and Sp1. Increased mRNA expression of GPNMB (transmembrane glycoprotein NMB) in HepG2 cells and in hepatic tissue from ARSB-deficient mice followed decline in expression of ARSB and was mediated by the microphthalmia-associated transcription factor (MITF), but was unaffected by silencing galectin-3. Since GPNMB is increased in multiple malignancies, studies were performed to determine how decline in ARSB increased GPNMB expression. The mechanism by which decline in ARSB increased nuclear phospho-MITF was due to reduced activity of SHP2, a protein tyrosine phosphatase with Src homology (SH2) domains that regulates multiple cellular processes. SHP2 activity declined due to increased binding with chondroitin 4-sulfate when ARSB was reduced. When SHP2 activity was inhibited, phosphorylations of p38 mitogen-associated phosphokinase (MAPK) and of MITF increased, leading to GPNMB promoter activation. A dominant negative SHP2 construct, the SHP2 inhibitor PHSP1, and silencing of ARSB increased phospho-p38, nuclear MITF, and GPNMB. In contrast, constitutively active SHP2 and overexpression of ARSB inhibited GPNMB expression. The interaction between chondroitin 4-sulfate and SHP2 is a novel intersection between sulfation and phosphorylation, by which decline in ARSB and increased chondroitin 4-sulfation can inhibit SHP2, thereby regulating downstream tyrosine phosphorylations by sustained phosphorylations with associated activation of signaling and transcriptional events. PMID:27078017

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

    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

  14. 76 FR 40454 - Proposed Information Collection (VSO Access to VHA Electronic Health Records) Activity; Comment...

    2011-07-08

    ... techniques or the use of other forms of information technology. Title: VSO Access to VHA Electronic Health... Information Systems Technology Architecture (VistA). DATES: Written comments and recommendations on the... AFFAIRS Proposed Information Collection (VSO Access to VHA Electronic Health Records) Activity;...

  15. Two Ways to Lead

    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…

  16. Leading to transformation?

    Salinas Lanao, G.

    2007-01-01

    Participation in development claims to have a transformative potential. Does it really live up to such claim? To answer such question we must look at how change occurs in spaces where citizen participation is encouraged. This paper studies the case of participatory budgeting at local level in Ayacucho, Peru. Through this case the author assesses whether and how political capabilities of citizens are enhanced, as well as the change in dynamics of power relations that occur in regularized and i...

  17. Traces lead to politics

    The carbon quota sale scandal remains at the center of media and public attention mostly thanks to various documents that have started to leak out and are generally hard to verify. One such document was behind the Interblue Group's project manager Rastislav Bilas introduction to the scene. And gradually more and more traces are showing that the story is no longer just about the government's bad deal but the whole case might be turning into a feud among the shadowy figures behind political parties. It is even possible to detect internal tension within Premier Minister Robert Fico's Smer-SD, the strongest ruling party. TREND has documents showing cash transfers from the Interblue Group's account. According to them, former Interblue executive Jana Luetken ordered several transfers totaling 10.65 million euros into the account of a company Ossian Establishment, based in St. Vincent. A person named Jozef Brhel was shown as the final receiver of the money. This is the name of a big unofficial sponsor of Smer. Mr. Bilas refused to confirm Mr. Brhel's involvement in the transaction. Instead, he showed TREND a confirmation of the receipt of transfer that has his name on it rather than Mr. Brhel's. This document cannot be verified either. The group around the Czech entrepreneur Milan Ruzicka seems to be part of the story too. He claims to have acquired Interblue Group Europe. The Czech group is convinced they are the legal successor to Interblue Group and therefore have a valid contract with Slovakia. The Ministry of Environment says the opposite, saying the contract expired once the U.S.A.-based Interblue was closed down. According to Mr. Bilas, Mr. Ruzicka took over Interblue with more than 10 million euros in bank accounts, but they still need to deal with the Japanese buyers of the carbon credits. That cannot be realized without Slovak green investment scheme projects. (author)

  18. Lead and zinc concentrations in plasma, erythrocytes, and urine in relation to ALA-D activity after intravenous infusion of Ca-EDTA.

    Ishihara, N; Shiojima, S; Hasegawa, K.

    1984-01-01

    Lead and zinc concentrations in plasma, erythrocytes, and urine, urinary ALA concentration, and ALA-D activity in blood were studied for four hours in two male lead workers during and after a one hour infusion of Ca-EDTA 2Na. Urinary and plasma lead concentrations increased as a result of administering Ca-EDTA 2Na, and the ratios of lead concentrations in plasma to those in urine were greatly increased. The increase of plasma lead concentration was not due to the haemolytic effect of Ca-EDTA ...

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

    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.

  20. 32 CFR Appendix D to Part 169a - Commercial Activities Management Information System (CAMIS)

    2010-07-01

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

  1. Negotiation Leads to Stability

    2006-01-01

    As the Palestinian people face many challenges, the international community, including China, is paying a great deal of attention. Diab N.M. Allouh, the Palestinian Ambassador to China, shares his views on the current Middle East situation in an interview with Beijing Review reporter Ding Ying.

  2. Total contribution of airborne lead to blood lead.

    Manton, W I

    1985-01-01

    A nine year study of blood lead concentrations and isotope ratios carried out on a married couple shows that pulmonary deposition cannot account for all the airborne lead in blood; that lead from bone may comprise 70% of blood lead; and that during pregnancy blood lead may double due to mobilisation of lead from bone.

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

    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…

  4. Information Superiority generated through proper application of Geoinformatics

    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

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

    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.

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

    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.

  7. How shall we hand over the atomic energy to the next generation? Publicity activities to the youth

    Kudo, Kazuhiko [Kyushu Univ., Fukuoka (Japan). Faculty of Engineering; Kaji, Yoshiyuki; Kumagaya, Akira; Shibata, Toshikazu; Watanabe, Tamaki; Murakami, Masatoshi; Nishina, Kojiro

    1995-05-01

    It is important for Atomic Energy Society of Japan which covers the wide fields related to atomic energy to know exactly what the youths who bear the next generation learn about atomic energy and what feeling they have. However, the attitude or the attempt of meeting young generation from such viewpoint was not sufficient so far. In the phenomena of `away from atomic energy` recently pointed out frequently, the root seems to have existed long ago. In this feature article, from such critical mind, the present status and the plan for hereafter of atomic energy publicity activities for young generation and those concerned to education are made clear. The publicity activities for school education and young generation, the publicity activities for those concerned to education, the questionnaire of the consciousness about energy and environment, the open school activity of Atomic Energy Society of Japan, the nuclear reactor experiment and study for middle and high school teachers, the assembling of simplified GM counters and the experiment of measuring radiation, the activities of Plasnet for young generation and the exercise and seminar on radiation for high school students are reported. Japanese social system is at the root of atomic energy problem, and the effort to improve it contributes to innovate the constitution of whole Japan. (K.I.).

  8. How shall we hand over the atomic energy to the next generation? Publicity activities to the youth

    It is important for Atomic Energy Society of Japan which covers the wide fields related to atomic energy to know exactly what the youths who bear the next generation learn about atomic energy and what feeling they have. However, the attitude or the attempt of meeting young generation from such viewpoint was not sufficient so far. In the phenomena of 'away from atomic energy' recently pointed out frequently, the root seems to have existed long ago. In this feature article, from such critical mind, the present status and the plan for hereafter of atomic energy publicity activities for young generation and those concerned to education are made clear. The publicity activities for school education and young generation, the publicity activities for those concerned to education, the questionnaire of the consciousness about energy and environment, the open school activity of Atomic Energy Society of Japan, the nuclear reactor experiment and study for middle and high school teachers, the assembling of simplified GM counters and the experiment of measuring radiation, the activities of Plasnet for young generation and the exercise and seminar on radiation for high school students are reported. Japanese social system is at the root of atomic energy problem, and the effort to improve it contributes to innovate the constitution of whole Japan. (K.I.)

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

    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

  10. Classical complement pathway activation by antipneumococcal antibodies leads to covalent binding of C3b to antibody molecules.

    Brown, E J; Berger, M.; Joiner, K A; Frank, M. M.

    1983-01-01

    We have examined whether or not a physical relationship exists between antipneumococcal antibodies (Ab) and C3b when Ab activate the classical complement pathway on the surface of pneumococci (Pn). After sensitization with 125I-labeled Ab, Pn were sequentially incubated with purified C1, C4, C2, and biotinylated C3. Ab molecules were then eluted from Pn, and C3b-associated molecules were purified on avidin-Sepharose. Both 125I-labeled immunoglobulin G (IgG) and [125I]IgM bound to C3b; the ass...

  11. Fast neutron induced reactions leading to activation products: selected cases relevant to development of low activation materials, transmutation and hazard assessment of nuclear wastes

    Neutron induced cross sections are of interest for practical applications and for testing nuclear models. In this work (n,p), (n,np), (n,α), (n,nα), (n,n'γ), (n,2n) and (n,3n) reactions on vanadium, molybdenum, technetium and lead have been measured in the energy range of 0.5 to 20.6 MeV using the activation technique. The radioactive reaction products with half-lives between 58 seconds and 20300 years have been measured offline via high-resolution γ-ray-spectrometry and Liquid Scintillation Counting, the latter in combination with radiochemical separation. Irradiations with neutron energies in the range of 0.5 to 6 MeV were done using the 3H(p,n)3He reaction with a solid-state Ti/T target while energies between 7.4 and 12.5 MeV were covered with the 2H(d,n)3He reaction utilizing a D2 gas target. Irradiations in the energy range from 13.4 to 20.6 MeV were performed using the 3H(d,n)4He reaction, again with a solid Ti/T target. Most of the reactions were investigated using a light mass setup to minimise scattering effects, but for short half-lives a pneumatic sample transport system was used as well. A special sample holder was developed for the measurement of the natMo(n,x)94Nb reaction. All cross sections were measured relative to the 27Al(n,β)24Na standard cross section and all necessary corrections due to the irradiation process and the measurement of the induced activity have been applied. Nuclear model calculations were performed for all investigated reactions. For reactions on 99Tc and Pb the original STAPRE code was used, while for reactions on V and Mo a modified version STAPRE-H was employed. As a result of this thesis work an extended database for neutron induced cross sections on four elements was obtained. It was possible to establish first excitation functions for reactions on a radioactive target nucleus, one very long-lived product and one purely β- emitting product. It was found that existing evaluations are not always reliable in the

  12. New Generation of Europium- and Terbium-Activated Phosphors From Syntheses to Applications

    Nazarov, Mihail

    2011-01-01

    This book concentrates on the luminescence and structural properties of the new generation of europium and terbium activated phosphors, associated phenomena, and related topics, from basic principles to the most recent discoveries. It summarizes the present state of the art in this rapidly growing field. The authors describe recent developments in the areas of rare earth doped phosphors and of some new materials or well-known materials with improved properties that open up new possibilities. The areas of focus include X-ray phosphors, phosphors for light-emitting devices, emissive displays, an

  13. The central electricity generating board approach to low level waste activity assessment

    Assessment of the activity of low level waste (LLW) within Central Electricity Generating Board (CEGB) has historically been achieved by a combination of dose rate measurements and empirical isotopic composition data. Because of changes in regulatory requirements and the increased costs of disposal, it became clear in 1986/87 that fundamental changes in the method of assay of LLW were needed. This paper describes the approach adopted by CEGB to introduce these changes. Details of the philosophy of 'area fingerprints' and the programme of work for their determination are outlined together with a description of an on-site monitoring system which represents a practical implementation of the approach

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

    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. PMID:26429298

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

    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.

  16. A Curriculum Activities Guide to Electric Power Generation and the Environment.

    Tully, Randolph R., Jr., Ed.

    This guide was developed by teachers involved in a workshop on "Electric Power Generation and the Environment." Activity topics are: (1) Energy and the Consumer; (2) Energy and Water Pollution; and (3) Energy and Air Pollution. Within these topics, the activities are classified as awareness level, transitional level, or operational level. Each…

  17. Antitumor activity of the immunomodulatory lead Cumaside.

    Aminin, D L; Chaykina, E L; Agafonova, I G; Avilov, S A; Kalinin, V I; Stonik, V A

    2010-06-01

    A new immunomodulatory lead Cumaside that is a complex of monosulfated triterpene glycosides from the sea cucumber Cucumaria japonica and cholesterol possesses significantly less cytotoxic activity against sea urchin embryos and Ehrlich carcinoma cells than the corresponding glycosides. Nevertheless Cumaside has an antitumor activity against different forms of experimental mouse Ehrlich carcinoma in vivo both independently and in combination with cytostatics. The highest effect occurs at a treatment once a day for 7 days before the tumor inoculation followed by Cumaside treatment once a day for 7 days. Prophylactic treatment with Cumaside and subsequent therapeutic application of 5-fluorouracil suppressed the tumor growth by 43%. PMID:20227525

  18. Student-generated behavioral guidelines to inform ethical practice: a quality improvement project.

    Wilk, Nancy; Bowllan, Nancy

    2011-01-01

    Nursing faculty members have become increasingly concerned with student incidences of cheating and the associated lack of commitment to ethical conduct. Our faculty believed that actively engaging students in the development of specific behavioral guidelines would result in improved ethical conduct and provide a bridge to future professional ethical practice. The authors discuss the use of focus groups to establish clear behavioral guidelines that align with the American Nurses Association Code of Ethics. PMID:22024685

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

    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.

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

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

    2015-01-01

    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 ...

  1. Generating Explanatory Captions for Information Graphics

    Mittal, Vibhu O.; Roth, Steven F.; Moore, Johanna D.; Mattis, Joe; Carenini, Giuseppe

    1995-01-01

    Graphical presentations can be used to communicate information in relational data sets succinctly and effectively. However, novel graphical presentationsabout numerous attributes and their relationships are often difficult to understand completely until explained. Automatically generated graphical presentations must therefore either be limited to simple, conventional ones, or risk incomprehensibility. One way of alleviating this problem is to design graphical presentation systems that can wor...

  2. Public information activities in Japan

    This is a slide presentation dealing with the public information (PI) activities in Japan. At present in Japan 51 nuclear power plants are in commercial operation contributing with a capacity of about 440 G We, i.e. 1/3 of the total electricity is produced by nuclear power. An investigation conducted by Advisory Committee for Energy resulted in the following guidelines in the advancing the Nuclear Power Policy: - maintain transparency in determining policy and reflect the voice of people, making information available to the public; - promote mutual understanding between areas that produce electricity by nuclear power and those that consume electricity; - cultivate an awareness of energy issues amongst the public to encourage them to take issues regarding Japan's energy policy to heart. Concerning the current PI, the following actions are undertaken at a nationwide scale: - for all people, supplying information by mass media, internet and holding lecture meetings and panel discussions etc; - for women, advertisements in journals; - for youth, educational materials, exhibition of energy etc; - for teachers, seminars; for opinion leaders, sending newsletters on nuclear energy. In areas for planned or constructed nuclear plants the PI actions are addressed to all people, women, fishermen, farmers and opinion leaders. There are given the responses to the following three questions addressed to the public concerning the nuclear power: - do you think whether we need nuclear power plants? - do you think whether nuclear power plants are safe? - what mechanism do you think generates energy during the production of nuclear power. A discussion of the results is presented. As future objectives of PI activities the following are in view: to cultivate reliability, to aware of information about nuclear power, to promote awareness of nuclear power, to promote mutual understanding of nuclear power. In conclusion, the need is stressed to make the PI activities more effective, to find

  3. 76 FR 3883 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Willingness...

    2011-01-21

    ... Information Collection Activities; Submission to OMB for Review and Approval; Willingness To Pay Survey for... 1320.12. On July 21, 2010 (74 FR 42438), EPA sought comments on this ICR pursuant to 5 CFR 1320.8(d... information about the electronic docket, go to http://www.regulations.gov . Title: Willingness to Pay...

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

    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

  5. From information to education

    In my papers at the previous conferences I brought forth examples of arguments, methods and tools, which the Information Center of OAO 'Mashinostroitelny zavod' resorts to, when dealing with the population of the town of Electrostal, where the OAO 'MSZ' is located. Since the Information Center is visited mainly by pupils and students, we try to inform them during their visits not only of the technique and technologies applied in nuclear industry but of the professions of the specialists working in these spheres. Lately we try another way to communicate the nuclear power to the young generation. At the end of a school year we invite pupils leaving secondary schools, colleges and technical schools, who intend to continue their education at higher technical schools, to meet the leading teachers of the Moscow State Technical University, the faculty of energy and machine-building, preparing the specialists for the enterprises of nuclear power complex of our country. The experience proves that such meetings predetermine the young people's choice of a profession associated with the atomic energy. Our activities resulted in attracting the attention of school-leavers not only from our town but from the neighbour towns of our region as well. We use another kind of communication with higher institutions. The Electrostal Department of the Moscow Institute of Steel and Alloys under the agreement with our enterprise every year picks out 15-20 students to specialize in the power metallurgy applied in the UO2 pellet production technology used in the nuclear fuel production. This specialization begins when students visit our center, and during 2- or 3-hour lecture they are getting acquainted with the principles of the nuclear technique and nuclear technologies. Generally speaking we have come to a conclusion that in schools and colleges pupils get poor knowledge in the field of nuclear physics and atomic energy. Due to that meetings with them are organized in the form of an open

  6. 77 FR 37897 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    2012-06-25

    ... Right- To-Know Act (Renewal) AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: In... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Agency Information Collection Activities; Submission to OMB for Review and Approval;...

  7. 75 FR 82030 - Agency Information Collection Activities; Proposed Collection; Comment Request; Data to Support...

    2010-12-29

    ... food products and related materials, including but not limited to, food advertising, food and nutrition... materials, including but not limited to, food advertising, food and nutrition labeling, emerging risk... HUMAN SERVICES Food and Drug Administration Agency Information Collection Activities;...

  8. A hypothesis-generating study to evaluate platelet activity in diabetics with chronic kidney disease

    Martin rika J

    2005-03-01

    Full Text Available Abstract Background It is well described that diabetes mellitus is a hypercoagulable state. It is also known that patients with renal dysfunction have impaired platelet aggregation and function. It is not well described how renal dysfunction affects the hypercoagulability associated with diabetes. This post-hoc sub-group analysis compares platelet function, clot structure and thrombin generation time at baseline, and following enoxaparin exposure in three groups of subjects. Methods 30 total subjects were evaluated in the three groups: Group I: normal controls (n = 10, Group II: subjects with renal dysfunction but without diabetes (n = 13, and Group III: subjects with concomitant diabetes and renal dysfunction (n = 7. For each subject, platelet contractile force (PCF, clot elastic modulus (CEM and thrombin generation time (TGT were simultaneously measured in whole blood at baseline, and following increasing enoxaparin antifactor Xa activity exposure. The group means for each parameter were determined and compared using one-way analysis of variance, with post-hoc Tukey-Kramer test. Results At baseline, subjects in Group III (diabetics with concomitant renal dysfunction display significantly enhanced platelet activity, as measured by PCF (p = 0.003 and CEM (p = 0.03, relative to the non-diabetic Groups I and II. Subjects in Group II (renal dysfunction without diabetes had significantly prolonged TGT values relative to controls when the antifactor Xa activity concentration reached 0.5 (p = 0.007, 1.0 (p = 0.005 and 3.0 IU/mL (p Conclusion This hypothesis-generating sub-group analysis suggests that at baseline, patients with concomitant diabetes and renal dysfunction have significantly enhanced platelet activity (PCF, and form more rigid blood clots (CEM compared to controls and subjects with renal dysfunction but no diabetes. This may suggest that the presence of renal dysfunction does not ameliorate the hypercoagulable state associated with

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

    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. PMID:27260464

  10. 78 FR 46418 - Proposed Information Collection (Obligation To Report Factors Affecting Entitlement) Activity...

    2013-07-31

    ... AFFAIRS Proposed Information Collection (Obligation To Report Factors Affecting Entitlement) Activity... techniques or the use of other forms of information technology. Title: Obligation to Report Factors Affecting... dependents, may affect the amount of benefit that he or she receives or affect the right to receive...

  11. 76 FR 27380 - Proposed Information Collection (Offer To Purchase and Contract of Sale) Activity: Comment Request

    2011-05-11

    ... AFFAIRS Proposed Information Collection (Offer To Purchase and Contract of Sale) Activity: Comment Request... techniques or the use of other forms of information technology. Titles a. Offer to Purchase and Contract of... Offer to Purchase and Contract of Sale, VA Form 26- 6705d. OMB Control Number: 2900-0029. Type of...

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

    Fdez-Riverola Florentino

    2011-01-01

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

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

    Cash, Philip; Stanković, Tino; Štorga, Mario

    2014-01-01

    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 the tempora...

  14. Inhibition of cyclooxygenase-2 activity by celecoxib does not lead to radiosensitization of human prostate cancer cells in vitro

    Purpose: To evaluate the potential radiosensitizing effect of the specific COX-2 inhibitor celecoxib (Celebrex[reg]) on prostate carcinoma cells in vitro. Materials and methods: The influence of celecoxib (concentration range 5 to 75 μM) on radiation-induced cellular and clonogenic survival was investigated in prostate carcinoma cell lines PC-3, DU145, LNCaP and normal prostate epithelial cells (PrEC). Western blot analysis and ELISA were used to determine the impact of radiation alone or radiation combined with celecoxib treatment on COX-2 expression and prostaglandin E2 synthesis. To evaluate induction of celecoxib-induced apoptosis cell cycle analysis has been performed. Results: Celecoxib (5, 10 and 25 μM) in combination with single-dose irradiation of 2 Gy induced a significant radiosensitization in normal prostate epithelial cells which could not be observed for any of the prostate carcinoma cell lines investigated. Increased COX-2 protein expression in PC-3 cells was obvious only after IR with 15 Gy, while PGE2 production was elevated following irradiation (2-15 Gy) in a dose-dependent manner. Treatment with celecoxib alone or in combination with IR led to a dose-dependent increase in COX-2 protein expression. Nevertheless pre-treatment with celecoxib caused a marked reduction of radiation-induced enzyme activity as tested at the level of PGE2 production, both in PC-3 and DU145 cells. Following fractionated irradiation with single doses of 2 Gy, elevated COX-2 protein expression as well as enhanced PGE2 production was observed already after the second fraction in PC-3 cells. Pre-treatment with celecoxib reduced the amount of PGE2 significantly, but not of COX-2 protein. Conclusions: Our data obtained for the human prostate cancer cell lines do not indicate that a marked inhibition of prostaglandin E2 synthesis by celecoxib leads to enhanced radiosensitization. Thus, in terms of radiosensitization the analysed prostate cancer cells can be classified as non

  15. Inhibition of carnitine palmitoyltransferase leads to induction of 3-hydroxymethylglutaryl coenzyme A reductase activity in rat liver

    Jansen, Hans; Hoogerbrugge van der Linden, N.; Hülsmann, William

    1990-01-01

    markdownabstractAbstract The relation between carnitine palmitoyltransferase (CPT) activity and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity was investigated. Rats were treated with aminocarnitine or 1-carnitine overnight. In rats, in which CPT activity was inhibited by aminocarnitine, plasma and hepatic triacylglycerol contents were increased 5- to 6-fold. The plasma cholesterol concentration was unchanged, while the hepatic cholesterol content was lowered (−16%). Hepat...

  16. Modulation of de novo purine biosynthesis leads to activation of AMPK and results in improved glucose handling and insulin sensitivity

    Sadasivan, Satish Kumar; Vasamsetti, Balamuralikrishna; Singh, Jaideep; Siddaraju, Nethra; Khan, Khaiser Mehdi; Oommen, Anup Mammen; Jagannath, Madanalli R; Rao, Raghavendra Pralhada

    2014-01-01

    Background AMP activated protein kinase (AMPK) regulates key metabolic reactions and plays a major role in glucose homeostasis. Activating the AMPK is considered as one of the potential therapeutic strategies in treating type-2 diabetes. However, targeting AMPK by small molecule mediated approach can be challenging owing to diverse isoforms of the enzyme and their varied combination in different tissues. In the current study we employ a novel strategy of achieving AMPK activation through incr...

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

    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. PMID:26785327

  18. Validation of an hourly resolved global aerosol model in answer to solar electricity generation information needs

    M. Schroedter-Homscheidt

    2012-12-01

    Full Text Available Solar energy applications need global aerosol optical depth (AOD information to derive historic surface solar irradiance databases from geostationary meteorological satellites reaching back to the 1980's. This paper validates the MATCH/DLR model originating in the climate community against AERONET ground measurements. Hourly or daily mean AOD model output is evaluated individually for all stations in Europe, Africa and the Middle East – an area highly interesting for solar energy applications being partly dominated by high aerosol loads. Overall, a bias of 0.02 and a root mean square error of 0.23 are found for daily mean AOD values, while the RMSE increases to 0.28 for hourly mean AOD values. Large differences between various regions and stations are found providing a feedback loop for the aerosol modelling community. The difference in using daily means versus hourly resolved modelling with respect to hourly resolved observations is evaluated. Nowadays state of the art in solar resource assessment relies on monthly turbidity or AOD climatologies while at least hourly resolved irradiance time series are needed by the solar sector. Therefore, the contribution of higher temporally modelled AOD is evaluated.

  19. Personal digital assistants: Essential tools for preparing dietetics professionals to use new generation information technology

    Jang, Miyoung; Won O. Song

    2007-01-01

    Rapid integration of information technology into health care systems has included the use of highly portable systems-in particular, personal digital assistants (PDAs). With their large built-in memories, fast processors, wireless connectivity, multimedia capacity, and large library of applications, PDAs have been widely adopted by physicians and nurses for patient tracking, disease management, medical references and drug information, enhancing a quality of health care. Many health-related PDA...

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

    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.

  1. Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy

    Wagner, Kay-Dietrich; Vukolic, Ana; Baudouy, Delphine; Michiels, Jean-François

    2016-01-01

    Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δ overexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δ induces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δ activation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease. PMID:27057154

  2. Activation of the complement system by Cryptococcus neoformans leads to binding of iC3b to the yeast.

    Kozel, T R; Pfrommer, G S

    1986-01-01

    The complement system plays a key role in resistance to cryptococcosis. In the present study, we examined several factors that influence the binding of C3 cleavage fragments to Cryptococcus neoformans. Binding of C3 was determined by using normal human serum supplemented with 125I-labeled C3. Incubation of encapsulated cryptococci in 20% serum led to the binding of approximately 3.2 X 10(6) molecules of C3 to each cell. The binding of C3 was markedly inhibited by heating the serum at 56 degre...

  3. Lead uptake and lead loss in the fresh water field crab, Barytelphusa guerini, on exposure to organic and inorganic lead

    Tulasi, S.J.; Yasmeen, R.; Reddy, C.P.; Rao, J.V.R.

    1987-07-01

    Lead is a heavy metal which is widely used in paint industry, pigments, dyes, electrical components and electronics, plastic chemicals and in various other things. Since some of the lead salts are soluble in water, lead presents a potential threat to aquatic organisms. Studies dealing with invertebrates include those on mortality, growth and lead uptake in Lymnaea palustris and bioaccumulation of heavy metals in oysters and mussels. Little information exists regarding the effect of lead on the fresh water crustaceans. Hence the present investigation has been undertaken to study the uptake and loss of lead on exposure to subtoxic levels or organic and inorganic lead.

  4. Putting Information in Perspective: A Mapping Activity to Help Students Understand the California Dilemma.

    Gersmehl, Philip J.

    1997-01-01

    Asserts that, to participate in a modern economy, every region needs at least one "bigjob" (basic income generating-job). Describes a mapping activity that helps students identify bigjobs in state economies. Uses California as an example and reveals that, contrary to popular opinion, real estate is California's bigjob. (MJP)

  5. Neutrophil elastase cleaves VEGF to generate a VEGF fragment with altered activity

    Kurtagic, Elma; Jedrychowski, Mark P.; Nugent, Matthew A.

    2009-01-01

    Excessive neutrophil elastase (NE) activity and altered vascular endothelial growth factor (VEGF) signaling have independently been implicated in the development and progression of pulmonary emphysema. In the present study, we investigated the potential link between NE and VEGF. We noted that VEGF165 is a substrate for NE. Digestion of purified VEGF165 with NE generated a partially degraded disulfide-linked fragment of VEGF. Mass spectrometric analysis revealed that NE likely cleaves VEGF165 ...

  6. Reflecting on earlier experiences with unsolicited findings: points to consider for next-generation sequencing and informed consent in diagnostics.

    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

    2013-10-01

    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

  7. Lead transformation to pyromorphite by fungi.

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

    2012-02-01

    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. PMID:22245002

  8. Stress corrosion cracking susceptibility of steam generator tube materials in AVT chemistry contaminated with lead

    The existence of lead is steam generator detected during analysis of deposits in the damaged areas of tube and in the fracture surfaces of existing cracks, bears out the hypothesis that lead may contribute to the secondary stress corrosion problems of steam generator tubes. The lead present in a steam generator which comes from the turbine, pump seals, valve packing, liners, etc. may form concentration from 0.02% to 0.2% in the sludge (1). The ubiquity of the major sources of lead limits the scope for controlling this contaminant and make difficult to remove it from steam generator. Taking this fact into account, it seems necessary to count on lead being present in new steam generator and to consider the influence of this contaminant on the behaviour of the materials considered as substitutes for Inconel 600. An extensive experimental work has been carried out in order to determine the stress corrosion crackings susceptibility of Inconel 690 TT, Incoloy 800 and Inconel 600 MA and TT in caustic and acidic environments contaminated with lead oxide. The results from this work, in particular for Incoloy 800, raised some concerns about the effect of minor amount of lead oxide in AVT environment. This paper presents the experimental work conducted with a view to determine the influence of lead oxide concentration in AVT conditions on the stress corrosion resistance of nickel alloys used in the fabrication of steam generator tubing. (authors). 3 tabs., 6 refs

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

    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...

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

    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

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

    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

  12. Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report

    Berle, Jan Øystein; Løberg, Else-Marie; Fasmer, Ole Bernt

    2013-01-01

    Background: In patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched fr...

  13. The CCR4-NOT deadenylase activity contributes to generation of induced pluripotent stem cells.

    Zukeran, Ari; Takahashi, Akinori; Takaoka, Shohei; Mohamed, Haytham Mohamed Aly; Suzuki, Toru; Ikematsu, Shinya; Yamamoto, Tadashi

    2016-05-27

    Somatic cells can be reprogrammed as induced pluripotent stem cells (iPSCs) by introduction of the transcription factors, OCT3/4, KLF4, SOX2, and c-MYC. The CCR4-NOT complex is the major deadenylase in eukaryotes. Its subunits Cnot1, Cnot2, and Cnot3 maintain pluripotency and self-renewal of mouse and human embryonic stem (ES) cells and contribute to the transition from partial to full iPSCs. However, little is known about how the CCR4-NOT complex post-transcriptionally regulates the reprogramming process. Here, we show that the CCR4-NOT deadenylase subunits Cnot6, Cnot6l, Cnot7, and Cnot8, participate in regulating iPSC generation. Cnot1 knockdown suppresses expression levels of Cnot6, Cnot6l, Cnot7, and Cnot8 in mouse embryonic fibroblasts (MEFs) and decreases the number of alkaline phosphatase (ALP)-positive colonies after iPSC induction. Intriguingly, Cnot1 depletion allows Eomes and p21 mRNAs to persist, increasing their expression levels. Both mRNAs have longer poly(A) tails in Cnot1-depleted cells. Conversely, forced expression of a combination of Cnot6, Cnot6l, Cnot7, and Cnot8 increases the number of ALP-positive colonies after iPSC induction and decreases expression levels of Eomes and p21 mRNAs. Based on these observations, we propose that the CCR4-NOT deadenylase activity contributes to iPSC induction. PMID:27037025

  14. Considerations for Using a Geographic Information System to Assess Environmental Supports for Physical Activity

    Dwayne E. Porter

    2004-10-01

    Full Text Available The use of a geographic information system (GIS to study environmental supports for physical activity raises several issues, including acquisition and development, quality, and analysis. We recommend to public health professionals interested in using GIS that they investigate available data, plan for data development where none exists, ensure the availability of trained personnel and sufficient time, and consider issues such as data quality, analyses, and confidentiality. This article shares information about data-related issues that we encountered when using GIS to validate responses to a questionnaire about environmental supports for physical activity.

  15. Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer

    Although omic-based discovery approaches can provide powerful tools for biomarker identification, several reservations have been raised regarding the clinical applicability of gene expression studies, such as their prohibitive cost. However, the limited availability of antibodies is a key barrier to the development of a lower cost alternative, namely a discrete collection of immunohistochemistry (IHC)-based biomarkers. The aim of this study was to use a systematic approach to generate and screen affinity-purified, mono-specific antibodies targeting progression-related biomarkers, with a view towards developing a clinically applicable IHC-based prognostic biomarker panel for breast cancer. We examined both in-house and publicly available breast cancer DNA microarray datasets relating to invasion and metastasis, thus identifying a cohort of candidate progression-associated biomarkers. Of these, 18 antibodies were released for extended analysis. Validated antibodies were screened against a tissue microarray (TMA) constructed from a cohort of consecutive breast cancer cases (n = 512) to test the immunohistochemical surrogate signature. Antibody screening revealed 3 candidate prognostic markers: the cell cycle regulator, Anillin (ANLN); the mitogen-activated protein kinase, PDZ-Binding Kinase (PBK); and the estrogen response gene, PDZ-Domain Containing 1 (PDZK1). Increased expression of ANLN and PBK was associated with poor prognosis, whilst increased expression of PDZK1 was associated with good prognosis. A 3-marker signature comprised of high PBK, high ANLN and low PDZK1 expression was associated with decreased recurrence-free survival (p < 0.001) and breast cancer-specific survival (BCSS) (p < 0.001). This novel signature was associated with high tumour grade (p < 0.001), positive nodal status (p = 0.029), ER-negativity (p = 0.006), Her2-positivity (p = 0.036) and high Ki67 status (p < 0.001). However, multivariate Cox regression demonstrated that the signature was

  16. TravelBehavior.com: Activity Approaches to Modeling the Effects of Information Technology on Personal Travel

    Golob, Thomas F.

    2000-01-01

    Accessibility can no longer be measured only in terms of travel time, distance or generalized travel cost. Information technology gives individuals "virtual accessibility" to a rapidly growing range of activities. Each person who shops at home on the Internet, or uses a handheld Internet device to gather information about the transportation system before embarking on a trip might only change his or her overall pattern of travel behavior just a little. But there are millions of people world...

  17. Signals leading to the activation of NF-kappa B transcription factor are stronger in neonatal than adult T lymphocytes.

    Kilpinen, S; Henttinen, T; Lahdenpohja, N; Hulkkonen, J; Hurme, M

    1996-07-01

    The molecular background of the defects in the immune reactivity of human neonates has not been fully elucidated. As the NF-kappa B transcription factor has a central role in the control of transcription of several genes involved in immune and inflammatory responses, the authors have analysed the activation of NF-kappa B in human umbilical cord T lymphocytes. The activity was tested by quantitating the nuclear proteins binding to an oligonucleotide containing the consensus kappa B binding sequence (electrophoretic mobility shift assay). The data obtained demonstrate that phorbol dibutyrate/calcium ionophore A23187 (PDBu/iono) combination induced a clearly higher nuclear translocation of NF-kappa B in neonatal than adult T cells. This higher NF-kappa B activity was restricted to the CD4+ T-cell subset. Analysis of the nuclear extracts with antibodies directed against the major components of NF-kappa B the p50 and RelA (p65) proteins, indicated that the composition of NF-kappa B was similar in neonatal and adult cells. These results suggest that neonatal T cells are exposed to oxidative stress-inducing signals during delivery and/or are inherently more sensitive to NF-kappa B activating signals than adult T cells. PMID:8693296

  18. Does Cardiac Rehabilitation After an Acute Cardiac Syndrome Lead to Changes in Physical Activity Habits? Systematic Review

    ter Hoeve, Nienke; Huisstede, Bionka M. A.; Stam, Henk J.; van Domburg, Ron T.; Sunamura, Madoka; van den Berg-Emons, Rita J. G.

    2015-01-01

    Background. Optimal physical activity levels have health benefits for patients with acute coronary syndrome (ACS) and are an important goal of cardiac rehabilitation (CR). Purpose. The purpose of this study was to systematically review literature regarding short-term effects (= 6 months after comple

  19. Communicating Ocean Sciences to Informal Audiences: A Scientist-Educator Partnership to Prepare the Next Generation of Scientists

    Halversen, Catherine; Tran, Lynn Uyen

    2010-01-01

    Communicating Ocean Sciences to Informal Audiences (COSIA) is a college course that creates and develops partnerships between science educators in informal science education institutions, such as museums, science centers and aquariums, and ocean scientists in colleges and universities. For the course, a scientist and educator team-teach…

  20. Deficient activation by a human cell strain leads to mitomycin resistance under aerobic but not hypoxic conditions.

    Marshall, R S; Paterson, M C; Rauth, A M

    1989-03-01

    Two non-transformed human skin fibroblast strains, GM38 and 3437T, were found to be more sensitive to the bioreductive alkylating agents mitomycin C (MMC) and porfiromycin (PM) under hypoxic compared to aerobic conditions. One of these strains, 3437T, was 6-7 times more resistant to these agents under aerobic exposure conditions, but was identical in sensitivity to the normal strain, GM38, under hypoxic conditions. Aerobic 3437T cells demonstrated no increased resistance to cisplatin compared to the normal strain, arguing against enhanced ability to repair DNA interstrand cross-links as the underlying explanation for the mitomycin resistance. The aerobic resistance of 3437T was not altered by dicumarol, an inhibitor of the enzyme DT-diaphorase which is believed to be involved in aerobic activation of MMC and PM. Dicumarol did increase the resistance of GM38, but not to the same level of resistance demonstrated by 3437T. These results suggest that the aerobic MMC and PM resistance of 3437T may arise, in part, from a deficiency in DT-diaphorase activity. The identical sensitivities under hypoxic conditions indicate that drug activation pathways operative in the absence of oxygen are similar in both the normal and 3437T cells. PMID:2467684

  1. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis

    Rasmussen, Kasper D.; Jia, Guangshuai; Johansen, Jens V.; Pedersen, Marianne T.; Rapin, Nicolas; Bagger, Frederik O.; Porse, Bo T; Bernard, Olivier A; Christensen, Jesper; Helin, Kristian

    2015-01-01

    The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CpG islands and promoters from aberrant DNA methylation. Rasmussen et al. used a novel Tet2-dependent leukemia mouse model to show that the primary effect of Tet2 loss in preleukemic hematopoietic cells is progressive and widespread DNA hypermethylation affecting up to 25% of active enhancer elements.

  2. Mixed disulfide formation at Cys141 leads to apparent unidirectional attenuation of Aspergillus niger NADP-glutamate dehydrogenase activity.

    Adhish S Walvekar

    Full Text Available NADP-Glutamate dehydrogenase from Aspergillus niger (AnGDH exhibits sigmoid 2-oxoglutarate saturation. Incubation with 2-hydroxyethyl disulfide (2-HED, the disulfide of 2-mercaptoethanol resulted in preferential attenuation of AnGDH reductive amination (forward activity but with a negligible effect on oxidative deamination (reverse activity, when monitored in the described standard assay. Such a disulfide modified AnGDH displaying less than 1.0% forward reaction rate could be isolated after 2-HED treatment. This unique forward inhibited GDH form (FIGDH, resembling a hypothetical 'one-way' active enzyme, was characterized. Kinetics of 2-HED mediated inhibition and protein thiol titrations suggested that a single thiol group is modified in FIGDH. Two site-directed cysteine mutants, C141S and C415S, were constructed to identify the relevant thiol in FIGDH. The forward activity of C141S alone was insensitive to 2-HED, implicating Cys141 in FIGDH formation. It was observed that FIGDH displayed maximal reaction rate only after a pre-incubation with 2-oxoglutarate and NADPH. In addition, compared to the native enzyme, FIGDH showed a four fold increase in K0.5 for 2-oxoglutarate and a two fold increase in the Michaelis constants for ammonium and NADPH. With no change in the GDH reaction equilibrium constant, the FIGDH catalyzed rate of approach to equilibrium from reductive amination side was sluggish. Altered kinetic properties of FIGDH at least partly account for the observed apparent loss of forward activity when monitored under defined assay conditions. In sum, although Cys141 is catalytically not essential, its covalent modification provides a striking example of converting the biosynthetic AnGDH into a catabolic enzyme.

  3. Research on Activators for Lead-Acid Batteries

    Sugawara, Michio; Kozawa, Akiya

    2008-01-01

    Abstract : The ITE Battery Research group has developed a new organic battery activator for new and used lead-acid batteries. Ten years of investigation have established the validity of the ITE activator that prolongs the useful life of lead-acid batteries. It has been shown that the specific gravity of spent batteries can be restored to the original level in automotive, motive power; uninterruptible power supplies (UPS) and stationary energy storage batteries. Our results show that the disca...

  4. 78 FR 51276 - Proposed Information Collection (Access to Care Dialysis Pilot Survey and Interview); Activity...

    2013-08-20

    ... Questionnaire, VA Form 10-10067. b. Access to Care Semi-Structured Interview Guide. OMB Control Number: 2900-NEW... AFFAIRS Proposed Information Collection (Access to Care Dialysis Pilot Survey and Interview); Activity... refer to ``OMB Control No. 2900-NEW (Access to Care Dialysis Pilot Survey and Interview)'' in...

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

    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.

  6. Salt stress response triggers activation of the jasmonate signaling pathway leading to inhibition of cell elongation in Arabidopsis primary root.

    Valenzuela, Camilo E; Acevedo-Acevedo, Orlando; Miranda, Giovanna S; Vergara-Barros, Pablo; Holuigue, Loreto; Figueroa, Carlos R; Figueroa, Pablo M

    2016-07-01

    Salinity is a severe abiotic stress that affects irrigated croplands. Jasmonate (JA) is an essential hormone involved in plant defense against herbivory and in responses to abiotic stress. However, the relationship between the salt stress response and the JA pathway in Arabidopsis thaliana is not well understood at molecular and cellular levels. In this work we investigated the activation of JA signaling by NaCl and its effect on primary root growth. We found that JA-responsive JAZ genes were up-regulated by salt stress in a COI1-dependent manner in the roots. Using a JA-Ile sensor we demonstrated that activation of JA signaling by salt stress occurs in the meristematic zone and stele of the differentiation zone and that this activation was dependent on JAR1 and proteasome functions. Another finding is that the elongation zone (EZ) and its cortical cells were significantly longer in JA-related mutants (AOS, COI1, JAZ3 and MYC2/3/4 genes) compared with wild-type plants under salt stress, revealing the participation of the canonical JA signaling pathway. Noteworthy, osmotic stress - a component of salt stress - inhibited cell elongation in the EZ in a COI1-dependent manner. We propose that salt stress triggers activation of the JA signaling pathway followed by inhibition of cell elongation in the EZ. We have shown that salt-inhibited root growth partially involves the jasmonate signaling pathway in Arabidopsis. PMID:27217545

  7. Decreased glycolate oxidase activity leads to altered carbon allocation and leaf senescence after a transfer from high CO2 to ambient air in Arabidopsis thaliana.

    Dellero, Younès; Jossier, Mathieu; Glab, Nathalie; Oury, Céline; Tcherkez, Guillaume; Hodges, Michael

    2016-05-01

    Metabolic and physiological analyses of Arabidopsis thaliana glycolate oxidase (GOX) mutant leaves were performed to understand the development of the photorespiratory phenotype after transfer from high CO2 to air. We show that two Arabidopsis genes, GOX1 and GOX2, share a redundant photorespiratory role. Air-grown single gox1 and gox2 mutants grew normally and no significant differences in leaf metabolic levels and photosynthetic activities were found when compared with wild-type plants. To study the impact of a highly reduced GOX activity on plant metabolism, both GOX1 and GOX2 expression was knocked-down using an artificial miRNA strategy. Air-grown amiRgox1/2 plants with a residual 5% GOX activity exhibited a severe growth phenotype. When high-CO2-grown adult plants were transferred to air, the photosynthetic activity of amiRgox1/2 was rapidly reduced to 50% of control levels, and a high non-photochemical chlorophyll fluorescence quenching was maintained. (13)C-labeling revealed that daily assimilated carbon accumulated in glycolate, leading to reduced carbon allocation to sugars, organic acids, and amino acids. Such changes were not always mirrored in leaf total metabolite levels, since many soluble amino acids increased after transfer, while total soluble protein, RuBisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase), and chlorophyll amounts decreased in amiRgox1/2 plants. The senescence marker, SAG12, was induced only in amiRgox1/2 rosettes after transfer to air. The expression of maize photorespiratory GOX in amiRgox1/2 abolished all observed phenotypes. The results indicate that the inhibition of the photorespiratory cycle negatively impacts photosynthesis, alters carbon allocation, and leads to early senescence in old rosette leaves. PMID:26896850

  8. Renal ischemia-reperfusion leads to long term infiltration of activated and effector-memory T lymphocytes

    Ascon, Miguel; Ascon, Dolores B.; Liu, Manchang; Cheadle, Chris; Sarkar, Chaitali; Racusen, Lorraine; Hassoun, Heitham T.; Rabb, Hamid

    2008-01-01

    It is well-established that significant ischemia-reperfusion injury during kidney transplantation results in increased incidence of long-term fibrosis and rejection. To test for a role of T cell infiltration and activation following ischemic injury, we induced both bilateral and unilateral renal ischemia in mice, followed by reperfusion, and then isolated mononuclear cells. Analysis of these cells by flow cytometry showed that 2 weeks after bilateral ischemia there was a significant increase ...

  9. Depletion of RNase HI activity in Escherichia coli lacking DNA topoisomerase I leads to defects in DNA supercoiling and segregation.

    Usongo, Valentine; Nolent, Flora; Sanscartier, Patrick; Tanguay, Cynthia; Broccoli, Sonia; Baaklini, Imad; Drlica, Karl; Drolet, Marc

    2008-08-01

    Gyrase-mediated hypernegative supercoiling is one manifestation of R-loop formation, a phenomenon that is normally suppressed by topoisomerase I (topA) in Escherichia coli. Overproduction of RNase HI (rnhA), an enzyme that removes the RNA moiety of R-loops, prevents hypernegative supercoiling and allows growth of topA null mutants. We previously showed that topA and rnhA null mutations are incompatible. We now report that such mutants were viable when RNase HI or topoisomerase III was expressed from a plasmid-borne gene. Surprisingly, DNA of topA null mutants became relaxed rather than hypernegatively supercoiled following depletion of RNase HI activity. This result failed to correlate with the cellular concentration of gyrase or topoisomerase IV (the other relaxing enzyme in the cell) or with transcription-induced supercoiling. Rather, intracellular DNA relaxation in the absence of RNase HI was related to inhibition of gyrase activity both in vivo and in extracts. Cells lacking topA and rnhA also exhibited properties consistent with segregation defects. Overproduction of topoisomerase III, an enzyme that can carry out DNA decatenation, corrected the segregation defects without restoring supercoiling activity. Collectively these data reveal (i) the existence of a cellular response to loss of RNase HI that counters the supercoiling activity of gyrase, and (ii) supercoiling-independent segregation defects due to loss of RNase HI from topA null mutants. Thus RNase HI plays a more central role in DNA topology than previously thought. PMID:18554330

  10. Rational Improvement of Simvastatin Synthase Solubility in Escherichia coli Leads to Higher Whole-cell Biocatalytic Activity

    Xie, Xinkai; Pashkov, Inna; Gao, Xue; Guerrero, Jennifer L.; Yeates, Todd O; Tang, Yi

    2009-01-01

    Simvastatin is the active pharmaceutical ingredient of the blockbuster cholesterol lowering drug Zocor. We have previously developed an Escherichia coli based whole-cell biocatalytic platform towards the synthesis of simvastatin sodium salt (SS) starting from the precursor monacolin J sodium salt (MJSS). The centerpiece of the biocatalytic approach is the simvastatin synthase LovD, which is highly prone to misfolding and aggregation when overexpressed from E. coli. Increasing the solubility o...