Homology-guided mutational analysis reveals the functional requirements for antinociceptive specificity of collapsin response mediator protein 2-derived peptides.

Science.gov (United States)

Moutal, Aubin; Li, Wennan; Wang, Yue; Ju, Weina; Luo, Shizhen; Cai, Song; François-Moutal, Liberty; Perez-Miller, Samantha; Hu, Jackie; Dustrude, Erik T; Vanderah, Todd W; Gokhale, Vijay; Khanna, May; Khanna, Rajesh

2017-02-05

N-type voltage-gated calcium (Ca v 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Ca v 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and often exhibit numerous side effects. Collapsin response mediator protein 2 (CRMP2) targets Ca v 2.2 channels to the sensory neuron membrane and allosterically modulates their function. A 15-amino-acid peptide (CBD3), derived from CRMP2, disrupts the functional protein-protein interaction between CRMP2 and Ca v 2.2 channels to inhibit calcium influx, transmitter release and acute, inflammatory and neuropathic pain. Here, we have mapped the minimal domain of CBD3 necessary for its antinociceptive potential. Truncated as well as homology-guided mutant versions of CBD3 were generated and assessed using depolarization-evoked calcium influx in rat dorsal root ganglion neurons, binding between CRMP2 and Ca v 2.2 channels, whole-cell voltage clamp electrophysiology and behavioural effects in two models of experimental pain: post-surgical pain and HIV-induced sensory neuropathy induced by the viral glycoprotein 120. The first six amino acids within CBD3 accounted for all in vitro activity and antinociception. Spinal administration of a prototypical peptide (TAT-CBD3-L5M) reversed pain behaviours. Homology-guided mutational analyses of these six amino acids identified at least two residues, Ala1 and Arg4, as being critical for antinociception in two pain models. These results identify an antinociceptive scaffold core in CBD3 that can be used for development of low MW mimetics of CBD3. © 2017 The British Pharmacological Society.

A novel integrated process of coal pyrolysis and methane CO{sub 2} reforming

Energy Technology Data Exchange (ETDEWEB)

Jing Wang; Pengfei Wang; Lijun Jin; Haoquan Hu [Dalian University of Technology, Dalian (China)

2007-07-01

In the paper, a novel pyrolysis method, namely coal pyrolysis coupling with CO{sub 2} reforming of methane (CRMP) or catalytic pyrolysis of coal coupling with CO{sub 2} reforming of methane (CRMCP), for improving the tar yield of coal pyrolysis was introduced. The behaviours of YM coal in both processes were investigated and compared with pyrolysis under N{sub 2} and H{sub 2}. The results show that the tar yield of coal pyrolysis in both processes obviously increase compared with that in N{sub 2} or H{sub 2}. When YM coal pyrolysis was carried out in stream of mixture gas CH{sub 4}/CO{sub 2} (1:1) with the existence of the catalyst at 0.1 MPa and 800{sup o}C, the tar yield is 2.8 times for CRMP and 4.3 times for CRMCP as that of pyrolysis under N{sub 2} and 1.7 and 2.6 times as that of hydropyrolysis at the same conditions, respectively. Sulfur content of char obtained from CRMP and CRMCP process are lower, especially in CRMP process, than that from N{sub 2} or H{sub 2}. 16 refs., 4 figs., 1 tab.

CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

Directory of Open Access Journals (Sweden)

Piekarz Andrew D

2012-07-01

Full Text Available Abstract Background The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2 to bind to N-type voltage-activated calcium channels (CaV2.2 [Brittain et al. Nature Medicine 17:822–829 (2011]. Results and discussion Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP release compared to vehicle control. Conclusions Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of

Sphingosine-1-Phosphate and the S1P3 Receptor Initiate Neuronal Retraction via RhoA/ROCK Associated with CRMP2 Phosphorylation

Science.gov (United States)

Quarta, Serena; Camprubí-Robles, Maria; Schweigreiter, Rüdiger; Matusica, Dusan; Haberberger, Rainer V.; Proia, Richard L.; Bandtlow, Christine E.; Ferrer-Montiel, Antonio; Kress, Michaela

2017-01-01

The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in the nervous system. Here, we explored the role of S1P and its receptors in vitro and in preclinical models of peripheral nerve regeneration. Adult sensory neurons and motor neuron-like cells were exposed to S1P in an in vitro assay, and virtually all neurons responded with a rapid retraction of neurites and growth cone collapse which were associated with RhoA and ROCK activation. The S1P1 receptor agonist SEW2871 neither activated RhoA or neurite retraction, nor was S1P-induced neurite retraction mitigated in S1P1-deficient neurons. Depletion of S1P3 receptors however resulted in a dramatic inhibition of S1P-induced neurite retraction and was on the contrary associated with a significant elongation of neuronal processes in response to S1P. Opposing responses to S1P could be observed in the same neuron population, where S1P could activate S1P1 receptors to stimulate elongation or S1P3 receptors and retraction. S1P was, for the first time in sensory neurons, linked to the phosphorylation of collapsin response-mediated protein-2 (CRMP2), which was inhibited by ROCK inhibition. The improved sensory recovery after crush injury further supported the relevance of a critical role for S1P and receptors in fine-tuning axonal outgrowth in peripheral neurons. PMID:29066950

Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis.

Science.gov (United States)

Grant, Nicola J; Coates, Philip J; Woods, Yvonne L; Bray, Susan E; Morrice, Nicholas A; Hastie, C James; Lamont, Douglas J; Carey, Francis A; Sutherland, Calum

2015-11-10

Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. For the first time this data associates altered CDK5 substrate phosphorylation with

Effect of specialized combined strains on reconstituted milk reduced ...

African Journals Online (AJOL)

On the other hand, results of the main flavor compounds in CRMP indicated that combination of the EPS-producing S. thermophilus TM11 and an adjunct Lactococcus lactis ssp. lactis could provide CRMP with novel and proper flavor properties while improving the textural characteristics. Key words: Reconstituted milk, ...

Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis

International Nuclear Information System (INIS)

Grant, Nicola J.; Coates, Philip J.; Woods, Yvonne L.; Bray, Susan E.; Morrice, Nicholas A.; Hastie, C. James; Lamont, Douglas J.; Carey, Francis A.; Sutherland, Calum

2015-01-01

Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. For the first time this data associates altered CDK5 substrate phosphorylation with

Identifying key genes associated with acute myocardial infarction.

Science.gov (United States)

Cheng, Ming; An, Shoukuan; Li, Junquan

2017-10-01

This study aimed to identify key genes associated with acute myocardial infarction (AMI) by reanalyzing microarray data. Three gene expression profile datasets GSE66360, GSE34198, and GSE48060 were downloaded from GEO database. After data preprocessing, genes without heterogeneity across different platforms were subjected to differential expression analysis between the AMI group and the control group using metaDE package. P FI) network. Then, DEGs in each module were subjected to pathway enrichment analysis using DAVID. MiRNAs and transcription factors predicted to regulate target DEGs were identified. Quantitative real-time polymerase chain reaction (RT-PCR) was applied to verify the expression of genes. A total of 913 upregulated genes and 1060 downregulated genes were identified in the AMI group. A FI network consists of 21 modules and DEGs in 12 modules were significantly enriched in pathways. The transcription factor-miRNA-gene network contains 2 transcription factors FOXO3 and MYBL2, and 2 miRNAs hsa-miR-21-5p and hsa-miR-30c-5p. RT-PCR validations showed that expression levels of FOXO3 and MYBL2 were significantly increased in AMI, and expression levels of hsa-miR-21-5p and hsa-miR-30c-5p were obviously decreased in AMI. A total of 41 DEGs, such as SOCS3, VAPA, and COL5A2, are speculated to have roles in the pathogenesis of AMI; 2 transcription factors FOXO3 and MYBL2, and 2 miRNAs hsa-miR-21-5p and hsa-miR-30c-5p may be involved in the regulation of the expression of these DEGs.

Identifying key factors and strategies for reducing industrial CO2 emissions from a non-Kyoto protocol member's (Taiwan) perspective

International Nuclear Information System (INIS)

Lin, Sue J.; Lu, I.J.; Lewis, Charles

2006-01-01

In this study we use Divisia index approach to identify key factors affecting CO 2 emission changes of industrial sectors in Taiwan. The changes of CO 2 emission are decomposed into emission coefficient, energy intensity, industrial structure and economic growth. Furthermore, comparisons with USA, Japan, Germany, the Netherlands and South Korea are made to have a better understanding of emission tendency in these countries and to help formulate our CO 2 reduction strategies for responding to the international calls for CO 2 cuts. The results show that economic growth and high energy intensity were two key factors for the rapid increase of industrial CO 2 emission in Taiwan, while adjustment of industrial structure was the main component for the decrease. Although economic development is important, Taiwan must keep pace with the international trends for CO 2 reduction. Among the most important strategies are continuous efforts to improve energy intensity, fuel mix toward lower carbon, setting targets for industrial CO 2 cuts, and advancing green technology through technology transfer. Also, the clean development mechanism (CDM) is expected to play an important role in the future

Research Note Identifying key grazing indicators to monitor trends in ...

African Journals Online (AJOL)

Research Note Identifying key grazing indicators to monitor trends in the veld condition of Lambert's Bay Strandveld, South Africa. ... from which a minimum number of species necessary to monitor trends in the condition of the veld were determined, making it user-friendly for land-users, extension officers and others. The key ...

Social Network Analysis Identifies Key Participants in Conservation Development.

Science.gov (United States)

Farr, Cooper M; Reed, Sarah E; Pejchar, Liba

2018-05-01

Understanding patterns of participation in private lands conservation, which is often implemented voluntarily by individual citizens and private organizations, could improve its effectiveness at combating biodiversity loss. We used social network analysis (SNA) to examine participation in conservation development (CD), a private land conservation strategy that clusters houses in a small portion of a property while preserving the remaining land as protected open space. Using data from public records for six counties in Colorado, USA, we compared CD participation patterns among counties and identified actors that most often work with others to implement CDs. We found that social network characteristics differed among counties. The network density, or proportion of connections in the network, varied from fewer than 2 to nearly 15%, and was higher in counties with smaller populations and fewer CDs. Centralization, or the degree to which connections are held disproportionately by a few key actors, was not correlated strongly with any county characteristics. Network characteristics were not correlated with the prevalence of wildlife-friendly design features in CDs. The most highly connected actors were biological and geological consultants, surveyors, and engineers. Our work demonstrates a new application of SNA to land-use planning, in which CD network patterns are examined and key actors are identified. For better conservation outcomes of CD, we recommend using network patterns to guide strategies for outreach and information dissemination, and engaging with highly connected actor types to encourage widespread adoption of best practices for CD design and stewardship.

CULTURAL RESOURCE MANAGEMENT PLAN FOR BROOKHAVEN NATIONAL LABORATORY.

Energy Technology Data Exchange (ETDEWEB)

DAVIS, M.

2005-04-01

The Cultural Resource Management Plan (CRMP) for Brookhaven National Laboratory (BNL) provides an organized guide that describes or references all facets and interrelationships of cultural resources at BNL. This document specifically follows, where applicable, the format of the U.S. Department of Energy (DOE) Environmental Guidelines for Development of Cultural Resource Management Plans, DOE G 450.1-3 (9-22-04[m1]). Management strategies included within this CRMP are designed to adequately identify the cultural resources that BNL and DOE consider significant and to acknowledge associated management actions. A principal objective of the CRMP is to reduce the need for additional regulatory documents and to serve as the basis for a formal agreement between the DOE and the New York State Historic Preservation Officer (NYSHPO). The BNL CRMP is designed to be a ''living document.'' Each section includes identified gaps in the management plan, with proposed goals and actions for addressing each gap. The plan will be periodically revised to incorporate new documentation.

Tamper-proof secret image-sharing scheme for identifying cheated secret keys and shared images

Science.gov (United States)

Chen, Chien-Chang; Liu, Chong-An

2013-01-01

A (t,n) secret image-sharing scheme shares a secret image to n participants, and the t users recover the image. During the recovery procedure of a conventional secret image-sharing scheme, cheaters may use counterfeit secret keys or modified shared images to cheat other users' secret keys and shared images. A cheated secret key or shared image leads to an incorrect secret image. Unfortunately, the cheater cannot be identified. We present an exponent and modulus-based scheme to provide a tamper-proof secret image-sharing scheme for identifying cheaters on secret keys or shared images. The proposed scheme allows users to securely select their secret key. This assignment can be performed over networks. Modulus results of each shared image is calculated to recognize cheaters of a shared image. Experimental results indicate that the proposed scheme is excellent at identifying cheated secret keys and shared images.

Methods of Developing User-Friendly Keys to Identify Green Sea Turtles (Chelonia mydas L. from Photographs

Directory of Open Access Journals (Sweden)

Jane R. Lloyd

2012-01-01

Full Text Available Identifying individual animals is important in understanding their ecology and behaviour, as well as providing estimates of population sizes for conservation efforts. We produce identification keys from photographs of green sea turtles to identify them while foraging in Akumal Bay, Mexico. We create three keys, which (a minimise the length of the key, (b present the most obvious differential characteristics first, and (c remove the strict dichotomy from key b. Keys were capable of identifying >99% of turtles in >2500 photographs during the six-month study period. The keys differed significantly in success rate for students to identify individual turtles, with key (c being the best with >70% success and correctly being followed further than other keys before making a mistake. User-friendly keys are, therefore, a suitable method for the photographic identification of turtles and could be used for other large marine vertebrates in conservation or behavioural studies.

BENCHMARKING - PRACTICAL TOOLS IDENTIFY KEY SUCCESS FACTORS

Directory of Open Access Journals (Sweden)

Olga Ju. Malinina

2016-01-01

Full Text Available The article gives a practical example of the application of benchmarking techniques. The object of study selected fashion store Company «HLB & M Hennes & Mauritz», located in the shopping center «Gallery», Krasnodar. Hennes & Mauritz. The purpose of this article is to identify the best ways to develop a fashionable brand clothing store Hennes & Mauritz on the basis of benchmarking techniques. On the basis of conducted market research is a comparative analysis of the data from different perspectives. The result of the author’s study is a generalization of the ndings, the development of the key success factors that will allow to plan a successful trading activities in the future, based on the best experience of competitors.

Identifying Key Attributes for Protein Beverages.

Science.gov (United States)

Oltman, A E; Lopetcharat, K; Bastian, E; Drake, M A

2015-06-01

This study identified key attributes of protein beverages and evaluated effects of priming on liking of protein beverages. An adaptive choice-based conjoint study was conducted along with Kano analysis to gain insight on protein beverage consumers (n = 432). Attributes evaluated included label claim, protein type, amount of protein, carbohydrates, sweeteners, and metabolic benefits. Utility scores for levels and importance scores for attributes were determined. Subsequently, two pairs of clear acidic whey protein beverages were manufactured that differed by age of protein source or the amount of whey protein per serving. Beverages were evaluated by 151 consumers on two occasions with or without priming statements. One priming statement declared "great flavor," the other priming statement declared 20 g protein per serving. A two way analysis of variance was applied to discern the role of each priming statement. The most important attribute for protein beverages was sweetener type, followed by amount of protein, followed by type of protein followed by label claim. Beverages with whey protein, naturally sweetened, reduced sugar and ≥15 g protein per serving were most desired. Three consumer clusters were identified, differentiated by their preferences for protein type, sweetener and amount of protein. Priming statements positively impacted concept liking (P 0.05). Consistent with trained panel profiles of increased cardboard flavor with higher protein content, consumers liked beverages with 10 g protein more than beverages with 20 g protein (6.8 compared with 5.7, P appeal. © 2015 Institute of Food Technologists®

A User Centered Innovation Approach Identifying Key User Values for the E-Newspaper

OpenAIRE

Carina Ihlström Eriksson; Jesper Svensson

2009-01-01

We have studied the pre-adoption phase of the e-newspaper, i.e. a newspaper published with e-paper technology. The research question of this article is: In what way can a user centered innovation process contribute to identifying key values in mobile innovations? The aim of this article is threefold: firstly, to identify key values for the e-newspaper, secondly, to examine the intention to adopt a new possible innovation and thirdly, to explore user centered design processes ability to captur...

Identifying Regional Key Eco-Space to Maintain Ecological Security Using GIS

Directory of Open Access Journals (Sweden)

Hualin Xie

2014-02-01

Full Text Available Ecological security and environmental sustainability are the foundations of sustainable development. With the acceleration of urbanization, increasing human activities have promoted greater impacts on the eco-spaces that maintain ecological security. Regional key eco-space has become the primary need to maintain environmental sustainability and can offer society with continued ecosystem services. In this paper, considering the security of water resources, biodiversity conservation, disaster avoidance and protection and natural recreation, an integrated index of eco-space importance was established and a method for identifying key eco-space was created using GIS, with Lanzhou City, China as a case study. The results show that the area of core eco-space in the Lanzhou City is approximately 50,908.7 hm2, accounting for 40% of the region’s total area. These areas mainly consist of geological hazard protection zones and the core zones of regional river systems, wetlands, nature reserves, forest parks and scenic spots. The results of this study provide some guidance for the management of ecological security, ecological restoration and environmental sustainability.

Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition

Directory of Open Access Journals (Sweden)

Naoya eYamashita

2013-12-01

Full Text Available Collapsin response mediator protein 1 (CRMP1 is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1-/- mice exhibited behavioral abnormalities related to schizophrenia. The crmp1-/- mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1-/- mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1-/- mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1-/- mouse may model endophenotypes present in this neuropsychiatric disorder.

Framework for Identifying Key Environmental Concerns in Marine Renewable Energy Projects- Appendices

Energy Technology Data Exchange (ETDEWEB)

Kramer, Sharon; Previsic, Mirko; Nelson, Peter; Woo, Sheri

2010-06-17

) 3 project sizes: pilot, small commercial, and large commercial The possible combinations total 24 wave technology scenarios and 9 tidal technology scenarios. We evaluated 3 of the 33 scenarios in detail: 1. A small commercial OPT Power Buoy project off the Humboldt County, California coast 2. A small commercial Pelamis Wave Power P-2 project off Makapu’u Point, Oahu, Hawaii 3. A pilot MCT SeaGen tidal project, sited in the Tacoma Narrows, Washington. This framework document used information available from permitting documents that were written to support actual wave or tidal energy projects, but the results obtained here should not be confused with those of the permitting documents1. The main difference between this framework document and permitting documents of currently proposed pilot projects is that this framework identifies key environmental concerns and describes the next steps in addressing those concerns; permitting documents must identify effects, find or declare thresholds of significance, evaluate the effects against the thresholds, and find mitigation measures that will minimize or avoid the effects so they can be considered less-than-significant. Two methodologies, 1) an environmental effects analysis and 2) Raptools, were developed and tested to identify potential environmental effects associated with wave or tidal energy conversion projects. For the environmental effects analysis, we developed a framework based on standard risk assessment techniques. The framework was applied to the three scenarios listed above. The environmental effects analysis addressed questions such as: What is the temporal and spatial exposure of a species at a site? What are the specific potential project effects on that species? What measures could minimize, mitigate, or eliminate negative effects? Are there potential effects of the project, or species’ response to the effect, that are highly uncertain and warrant additional study? The second methodology, Raptools, is a

Key Issues in Empirically Identifying Chronically Low-Performing and Turnaround Schools

Science.gov (United States)

Hansen, Michael

2012-01-01

One of the US Department of Education's key priorities is turning around the nation's persistently low-achieving schools, yet exactly how to identify low-performing schools is a task left to state policy makers, and a myriad of definitions have been utilized. In addition, exactly how to recognize when a school begins to turn around is not well…

Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

Science.gov (United States)

Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

2015-12-01

Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

Energy Technology Data Exchange (ETDEWEB)

Toba, Junya; Nikkuni, Miyu [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ishizeki, Masato [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Yoshii, Aya; Watamura, Naoto [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Inoue, Takafumi [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ohshima, Toshio, E-mail: ohshima@waseda.jp [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan)

2016-05-13

Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

International Nuclear Information System (INIS)

Toba, Junya; Nikkuni, Miyu; Ishizeki, Masato; Yoshii, Aya; Watamura, Naoto; Inoue, Takafumi; Ohshima, Toshio

2016-01-01

Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

Identifying key performance indicators for nursing and midwifery care using a consensus approach.

Science.gov (United States)

McCance, Tanya; Telford, Lorna; Wilson, Julie; Macleod, Olive; Dowd, Audrey

2012-04-01

The aim of this study was to gain consensus on key performance indicators that are appropriate and relevant for nursing and midwifery practice in the current policy context. There is continuing demand to demonstrate effectiveness and efficiency in health and social care and to communicate this at boardroom level. Whilst there is substantial literature on the use of clinical indicators and nursing metrics, there is less evidence relating to indicators that reflect the patient experience. A consensus approach was used to identify relevant key performance indicators. A nominal group technique was used comprising two stages: a workshop involving all grades of nursing and midwifery staff in two HSC trusts in Northern Ireland (n = 50); followed by a regional Consensus Conference (n = 80). During the workshop, potential key performance indicators were identified. This was used as the basis for the Consensus Conference, which involved two rounds of consensus. Analysis was based on aggregated scores that were then ranked. Stage one identified 38 potential indicators and stage two prioritised the eight top-ranked indicators as a core set for nursing and midwifery. The relevance and appropriateness of these indicators were confirmed with nurses and midwives working in a range of settings and from the perspective of service users. The eight indicators identified do not conform to the majority of other nursing metrics generally reported in the literature. Furthermore, they are strategically aligned to work on the patient experience and are reflective of the fundamentals of nursing and midwifery practice, with the focus on person-centred care. Nurses and midwives have a significant contribution to make in determining the extent to which these indicators are achieved in practice. Furthermore, measurement of such indicators provides an opportunity to evidence of the unique impact of nursing/midwifery care on the patient experience. © 2011 Blackwell Publishing Ltd.

Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph.

Directory of Open Access Journals (Sweden)

Shuai Zhao

Full Text Available In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks' price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds.

Identifying key hospital service quality factors in online health communities.

Science.gov (United States)

Jung, Yuchul; Hur, Cinyoung; Jung, Dain; Kim, Minki

2015-04-07

The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. We defined social media-based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea's two biggest online portals were used to test the effectiveness of detection of social media-based key quality factors for hospitals. To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is 78% on average. Extraction and

Structural study of U1-xAmxO2±δ oxide microspheres dedicated to the production of americium bearing blankets

International Nuclear Information System (INIS)

Caisso, Marie

2016-01-01

One of the studied routes to reduce nuclear waste amount, is, after plutonium recycling, americium (Am) heterogeneous transmutation in fast neutron reactors, through the generation of short-lives and inert elements. Am irradiation requires the fabrication of U 1-x Am x O 2±δ pellets and the CRMP (Calcined Resin Microsphere Pelletization) process is currently considered as one the most promising candidate among other fabrication routes. It is based, before pellet sintering, on the compaction of U 1-x Am x O 2±δ oxide microspheres, synthesized through the thermal conversion of ion exchange resin microspheres, loaded with UO 2 2+ and Am 3+ cations. Compared to standard methods using powder metallurgy, CRMP process favours pressing step (easy microsphere flow) while limiting generation of highly radioactive Am-based fine particles. In this context, this PhD work was focused on the exhaustive characterization of CRMP process different steps, from a mechanistic and structural point of view. The cation molecular complex used in the resin was thus determined, highlighting carboxylic bidentate ligand binding around U and Am elements. Thermal conversion was also in-situ followed, and the structures of the different synthesized compounds evidenced and accurately characterized, i.e. (U 1-x Am x ) 3 O 8 et U 1-x Am x O 2±δ . Am substitution in each of them was explained, revealing related distortions around U and Am cations. Finally, sintering of U 1-x Am x O 2±δ microspheres shaped into pellets was studied, showing a two-step densification. This unusual behavior corresponds to multi-scale reorganization into the material during sintering thermal treatment, associated to the presence of nanoparticles in the green pellet that sinter at low temperature. (author) [fr

A matter of definition--key elements identified in a discourse analysis of definitions of palliative care.

Science.gov (United States)

Pastrana, T; Jünger, S; Ostgathe, C; Elsner, F; Radbruch, L

2008-04-01

For more than 30 years, the term "palliative care" has been used. From the outset, the term has undergone a series of transformations in its definitions and consequently in its tasks and goals. There remains a lack of consensus on a definition. The aim of this article is to analyse the definitions of palliative care in the specialist literature and to identify the key elements of palliative care using discourse analysis: a qualitative methodology. The literature search focused on definitions of the term 'palliative medicine' and 'palliative care' in the World Wide Web and medical reference books in English and German. A total of 37 English and 26 German definitions were identified and analysed. Our study confirmed the lack of a consistent meaning concerning the investigated terms, reflecting on-going discussion about the nature of the field among palliative care practitioners. Several common key elements were identified. Four main categories emerged from the discourse analysis of the definition of palliative care: target groups, structure, tasks and expertise. In addition, the theoretical principles and goals of palliative care were discussed and found to be key elements, with relief and prevention of suffering and improvement of quality of life as main goals. The identified key elements can contribute to the definition of the concept 'palliative care'. Our study confirms the importance of semantic and ethical influences on palliative care that should be considered in future research on semantics in different languages.

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

International Nuclear Information System (INIS)

Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

2016-01-01

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

Dilatometric Study Of U1-xAmxO2±δ Transmutation Fuels

International Nuclear Information System (INIS)

Lebreton, Florent; Horlait, Denis; Delahaye, Thibaud; Blanchart, P.

2013-01-01

Conclusions - Dilatometric study results: • Reactive sintering: competition between solidsolution formation and densification process → the latter is slowed down and final density limited; • Conventional sintering: avoids this competition → higher densities are reached. - New homogeneous U 1-x Am x O 2±δ precursors: • Powders synthesized by oxalate co-conversion; • Microspheres formed using the CRMP (WAR-like) process

Key clinical features to identify girls with CDKL5 mutations.

Science.gov (United States)

Bahi-Buisson, Nadia; Nectoux, Juliette; Rosas-Vargas, Haydeé; Milh, Mathieu; Boddaert, Nathalie; Girard, Benoit; Cances, Claude; Ville, Dorothée; Afenjar, Alexandra; Rio, Marlène; Héron, Delphine; N'guyen Morel, Marie Ange; Arzimanoglou, Alexis; Philippe, Christophe; Jonveaux, Philippe; Chelly, Jamel; Bienvenu, Thierry

2008-10-01

Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome (RTT)-like phenotype. To date, less than 25 different mutations have been reported. So far, there are still little data on the key clinical diagnosis criteria and on the natural history of CDKL5-associated encephalopathy. We screened the entire coding region of CDKL5 for mutations in 183 females with encephalopathy with early seizures by denaturing high liquid performance chromatography and direct sequencing, and we identified in 20 unrelated girls, 18 different mutations including 7 novel mutations. These mutations were identified in eight patients with encephalopathy with RTT-like features, five with infantile spasms and seven with encephalopathy with refractory epilepsy. Early epilepsy with normal interictal EEG and severe hypotonia are the key clinical features in identifying patients likely to have CDKL5 mutations. Our study also indicates that these patients clearly exhibit some RTT features such as deceleration of head growth, stereotypies and hand apraxia and that these RTT features become more evident in older and ambulatory patients. However, some RTT signs are clearly absent such as the so called RTT disease profile (period of nearly normal development followed by regression with loss of acquired fine finger skill in early childhood and characteristic intensive eye communication) and the characteristic evolution of the RTT electroencephalogram. Interestingly, in addition to the overall stereotypical symptomatology (age of onset and evolution of the disease) resulting from CDKL5 mutations, atypical forms of CDKL5-related conditions have also been observed. Our data suggest that phenotypic heterogeneity does not correlate with the nature or the position of the mutations or with the pattern of X-chromosome inactivation, but most probably with the functional transcriptional and/or translational consequences of CDKL5

Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

Science.gov (United States)

Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

2014-01-01

Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

Predictive model identifies key network regulators of cardiomyocyte mechano-signaling.

Directory of Open Access Journals (Sweden)

Philip M Tan

2017-11-01

Full Text Available Mechanical strain is a potent stimulus for growth and remodeling in cells. Although many pathways have been implicated in stretch-induced remodeling, the control structures by which signals from distinct mechano-sensors are integrated to modulate hypertrophy and gene expression in cardiomyocytes remain unclear. Here, we constructed and validated a predictive computational model of the cardiac mechano-signaling network in order to elucidate the mechanisms underlying signal integration. The model identifies calcium, actin, Ras, Raf1, PI3K, and JAK as key regulators of cardiac mechano-signaling and characterizes crosstalk logic imparting differential control of transcription by AT1R, integrins, and calcium channels. We find that while these regulators maintain mostly independent control over distinct groups of transcription factors, synergy between multiple pathways is necessary to activate all the transcription factors necessary for gene transcription and hypertrophy. We also identify a PKG-dependent mechanism by which valsartan/sacubitril, a combination drug recently approved for treating heart failure, inhibits stretch-induced hypertrophy, and predict further efficacious pairs of drug targets in the network through a network-wide combinatorial search.

Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal – a case study from health science [version 2; referees: 1 approved, 2 approved with reservations

Directory of Open Access Journals (Sweden)

Heidi Holst Madsen

2016-09-01

Full Text Available Unique identifiers (UID are seen as an effective key to match identical publications across databases or identify duplicates in a database. The objective of the present study is to investigate how well UIDs work as match keys in the integration between Pure and SciVal, based on a case with publications from the health sciences. We evaluate the matching process based on information about coverage, precision, and characteristics of publications matched versus not matched with UIDs as the match keys. We analyze this information to detect errors, if any, in the matching process. As an example we also briefly discuss how publication sets formed by using UIDs as the match keys may affect the bibliometric indicators number of publications, number of citations, and the average number of citations per publication.  The objective is addressed in a literature review and a case study. The literature review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (DOI, incorrect DOIs in reference lists and databases, DOIs not registered by the database where a bibliometric analysis is performed, and erroneous optical or special character recognition. The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character recognition in our publication sets. In particular the duplicate DOIs constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation of average number of citations per publication. The use of UIDs as a match key in citation linking is implemented in many settings, and the availability of

Evaluation of unique identifiers used as keys to match identical publications in Pure and SciVal

DEFF Research Database (Denmark)

Madsen, Heidi Holst; Madsen, Dicte; Gauffriau, Marianne

2016-01-01

, and erroneous optical or special character recognition. The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character......Unique identifiers (UID) are seen as an effective key to match identical publications across databases or identify duplicates in a database. The objective of the present study is to investigate how well UIDs work as match keys in the integration between Pure and SciVal, based on a case...... also briefly discuss how publication sets formed by using UIDs as the match keys may affect the bibliometric indicators number of publications, number of citations, and the average number of citations per publication. The objective is addressed in a literature review and a case study. The literature...

Iterative key-residues interrogation of a phytase with thermostability increasing substitutions identified in directed evolution.

Science.gov (United States)

Shivange, Amol V; Roccatano, Danilo; Schwaneberg, Ulrich

2016-01-01

Bacterial phytases have attracted industrial interest as animal feed supplement due to their high activity and sufficient thermostability (required for feed pelleting). We devised an approach named KeySIDE,  an iterative Key-residues interrogation of the wild type with Substitutions Identified in Directed Evolution for improving Yersinia mollaretii phytase (Ymphytase) thermostability by combining key beneficial substitutions and elucidating their individual roles. Directed evolution yielded in a discovery of nine positions in Ymphytase and combined iteratively to identify key positions. The "best" combination (M6: T77K, Q154H, G187S, and K289Q) resulted in significantly improved thermal resistance; the residual activity improved from 35 % (wild type) to 89 % (M6) at 58 °C and 20-min incubation. Melting temperature increased by 3 °C in M6 without a loss of specific activity. Molecular dynamics simulation studies revealed reduced flexibility in the loops located next to helices (B, F, and K) which possess substitutions (Helix-B: T77K, Helix-F: G187S, and Helix-K: K289E/Q). Reduced flexibility in the loops might be caused by strengthened hydrogen bonding network (e.g., G187S and K289E/K289Q) and a salt bridge (T77K). Our results demonstrate a promising approach to design phytases in food research, and we hope that the KeySIDE might become an attractive approach for understanding of structure-function relationships of enzymes.

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

Energy Technology Data Exchange (ETDEWEB)

Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Uehara, Takeki; Kato, Yuki [Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka (Japan); Kono, Hiroshi [First Department of Surgery, University of Yamanashi, Yamanashi (Japan); Bataller, Ramon [Division of Gastroenterology & Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC (United States); Rusyn, Ivan, E-mail: irusyn@tamu.edu [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States)

2016-11-01

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.

Identifying Key Stakeholder Groups for Implementing a Place Branding Policy in Saint Petersburg

Directory of Open Access Journals (Sweden)

Kulibanova V. V.

2017-10-01

Full Text Available Regional brands have become a valuable intangible asset and a crucial competitive resource for forging partnerships. An effective place branding policy is impossible without a precise understanding of the interests of stakeholder groups. It is essential to realize that each region is unique in its own way. Territories differ in the structure of stakeholders, their influence on regional development, and the range of leverages over regional decision-makers. This study aims to give a more precise definition of key groups of stakeholders in Saint Petersburg place branding, and to identify them. The authors employ the method of theoretical and empirical typology of a territory’s stakeholders within a theoretical framework proposed by E. Freeman, P. Kotler, S. Zenker, and E. Brown. The article defines the concept of key regional stakeholders and identifies them. The proposed target audience (stakeholder group model for a place branding policy is tested on the case of Saint Petersburg. The authors show that each target audience of place marketing requires an individual policy. This is explained by the fact that each group enjoys its unique features that should be taken into account when creating and transmitting messages.

Identifying and characterizing key nodes among communities based on electrical-circuit networks.

Science.gov (United States)

Zhu, Fenghui; Wang, Wenxu; Di, Zengru; Fan, Ying

2014-01-01

Complex networks with community structures are ubiquitous in the real world. Despite many approaches developed for detecting communities, we continue to lack tools for identifying overlapping and bridging nodes that play crucial roles in the interactions and communications among communities in complex networks. Here we develop an algorithm based on the local flow conservation to effectively and efficiently identify and distinguish the two types of nodes. Our method is applicable in both undirected and directed networks without a priori knowledge of the community structure. Our method bypasses the extremely challenging problem of partitioning communities in the presence of overlapping nodes that may belong to multiple communities. Due to the fact that overlapping and bridging nodes are of paramount importance in maintaining the function of many social and biological networks, our tools open new avenues towards understanding and controlling real complex networks with communities accompanied with the key nodes.

Modelling Creativity: Identifying Key Components through a Corpus-Based Approach.

Science.gov (United States)

Jordanous, Anna; Keller, Bill

2016-01-01

Creativity is a complex, multi-faceted concept encompassing a variety of related aspects, abilities, properties and behaviours. If we wish to study creativity scientifically, then a tractable and well-articulated model of creativity is required. Such a model would be of great value to researchers investigating the nature of creativity and in particular, those concerned with the evaluation of creative practice. This paper describes a unique approach to developing a suitable model of how creative behaviour emerges that is based on the words people use to describe the concept. Using techniques from the field of statistical natural language processing, we identify a collection of fourteen key components of creativity through an analysis of a corpus of academic papers on the topic. Words are identified which appear significantly often in connection with discussions of the concept. Using a measure of lexical similarity to help cluster these words, a number of distinct themes emerge, which collectively contribute to a comprehensive and multi-perspective model of creativity. The components provide an ontology of creativity: a set of building blocks which can be used to model creative practice in a variety of domains. The components have been employed in two case studies to evaluate the creativity of computational systems and have proven useful in articulating achievements of this work and directions for further research.

Identifying Key Performance Indicators for Holistic Hospital Management with a Modified DEMATEL Approach.

Science.gov (United States)

Si, Sheng-Li; You, Xiao-Yue; Liu, Hu-Chen; Huang, Jia

2017-08-19

Performance analysis is an important way for hospitals to achieve higher efficiency and effectiveness in providing services to their customers. The performance of the healthcare system can be measured by many indicators, but it is difficult to improve them simultaneously due to the limited resources. A feasible way is to identify the central and influential indicators to improve healthcare performance in a stepwise manner. In this paper, we propose a hybrid multiple criteria decision making (MCDM) approach to identify key performance indicators (KPIs) for holistic hospital management. First, through integrating evidential reasoning approach and interval 2-tuple linguistic variables, various assessments of performance indicators provided by healthcare experts are modeled. Then, the decision making trial and evaluation laboratory (DEMATEL) technique is adopted to build an interactive network and visualize the causal relationships between the performance indicators. Finally, an empirical case study is provided to demonstrate the proposed approach for improving the efficiency of healthcare management. The results show that "accidents/adverse events", "nosocomial infection", ''incidents/errors", "number of operations/procedures" are significant influential indicators. Also, the indicators of "length of stay", "bed occupancy" and "financial measures" play important roles in performance evaluation of the healthcare organization. The proposed decision making approach could be considered as a reference for healthcare administrators to enhance the performance of their healthcare institutions.

Identifying key areas for active interprofessional learning partnerships: A facilitated dialogue.

Science.gov (United States)

Steven, Kathryn; Angus, Allyson; Breckenridge, Jenna; Davey, Peter; Tully, Vicki; Muir, Fiona

2016-11-01

Student and service user involvement is recognised as an important factor in creating interprofessional education (IPE) opportunities. We used a team-based learning approach to bring together undergraduate health professional students, early career professionals (ECPs), public partners, volunteers, and carers to explore learning partnerships. Influenced by evaluative inquiry, this qualitative study used a free text response to allow participants to give their own opinion. A total of 153 participants (50 public partners and 103 students and professionals representing 11 healthcare professions) took part. Participants were divided into mixed groups of six (n = 25) and asked to identify areas where students, professionals, and public could work together to improve health professional education. Each group documented their discussions by summarising agreed areas and next steps. Responses were collected and transcribed for inductive content analysis. Seven key themes (areas for joint working) were identified: communication, public as partners, standards of conduct, IPE, quality improvement, education, and learning environments. The team-based learning format enabled undergraduate and postgraduate health professionals to achieve consensus with public partners on areas for IPE and collaboration. Some of our results may be context-specific but the approach is generalisable to other areas.

Identifying key drivers of greenhouse gas emissions from biomass feedstocks for energy production

International Nuclear Information System (INIS)

Johnson, David R.; Curtright, Aimee E.; Willis, Henry H.

2013-01-01

Highlights: • Production emissions dominate transportation and processing emissions. • Choice of feedstock, geographic location and prior land use drive emissions profile. • Within scenarios, emissions variability is driven by uncertainty in yields. • Favorable scenarios maximize carbon storage from direct land-use change. • Similarly, biomass production should attempt to minimize indirect land-use change. -- Abstract: Many policies in the United States, at both the federal and state levels, encourage the adoption of renewable energy from biomass. Though largely motivated by a desire to reduce greenhouse gas emissions, these policies do not explicitly identify scenarios in which the use of biomass will produce the greatest benefits. We have modeled “farm-to-hopper” emissions associated with seven biomass feedstocks, under a wide variety of scenarios and production choices, to characterize the uncertainty in emissions. We demonstrate that only a handful of factors have a significant impact on life cycle emissions: choice of feedstock, geographic location, prior land use, and time dynamics. Within a given production scenario, the remaining variability in emissions is driven by uncertainty in feedstock yields and the release rate of N 2 O into the atmosphere from nitrogen fertilizers. With few exceptions, transport and processing choices have relatively little impact on total emissions. These results illustrate the key decisions that will determine the success of biomass programs in reducing the emissions profile of energy production, and our publicly available model provides a useful tool for identifying the most beneficial production scenarios. While model data and results are restricted to biomass production in the contiguous United States, we provide qualitative guidance for identifying favorable production scenarios that should be applicable in other regions

Identification of Key Issues in Adopting a Web 2.0 E-Portfolio Strategy

Science.gov (United States)

McKenna, Gary F.; Stansfield, Mark H.

2013-01-01

The purpose of the paper is to identify key issues relating to best practice and sustainability in Web 2.0 as an e-Learning strategy for supporting e-portfolios in Higher Education. A practical guidelines framework was developed for best practices, which can be justified by the lack of available frameworks in the e-Learning literature. A…

Peripheral neuropathies associated with antibodies directed to intracellular neural antigens.

Science.gov (United States)

Antoine, J-C

2014-10-01

Antibodies directed to intracellular neural antigens have been mainly described in paraneoplastic peripheral neuropathies and mostly includes anti-Hu and anti-CV2/CRMP5 antibodies. These antibodies occur with different patterns of neuropathy. With anti-Hu antibody, the most frequent manifestation is sensory neuronopathy with frequent autonomic involvement. With anti-CV2/CRMP5 the neuropathy is more frequently sensory and motor with an axonal or mixed demyelinating and axonal electrophysiological pattern. The clinical pattern of these neuropathies is in keeping with the cellular distribution of HuD and CRMP5 in the peripheral nervous system. Although present in high titer, these antibodies are probably not directly responsible for the neuropathy. Pathological and experimental studies indicate that cytotoxic T-cells are probably the main effectors of the immune response. These disorders contrast with those in which antibodies recognize a cell surface antigen and are probably responsible for the disease. The neuronal cell death and axonal degeneration which result from T-cell mediated immunity explains why treating these disorders remains challenging. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Identifying the key personnel in a nurse-initiated hospital waste reduction program.

Science.gov (United States)

McDermott-Levy, Ruth; Fazzini, Carol

2010-01-01

Hospitals in the United States generate more than 6600 tons of trash a day and approximately 85% of the waste is nonhazardous solid waste such as food, cardboard, and plastic. Treatment and management of hospital waste can lead to environmental problems for the communities that receive the waste. One health system's shared governance model provided the foundation to develop a nurse-led hospital waste reduction program that focused on point-of-care waste management. Waste reduction program development required working with a variety of departments within and external to the health system. The interdisciplinary approach informed the development of the waste reduction program. This article identifies the key departments that were necessary to include when developing a hospital waste reduction program.

GuiaTreeKey, a multi-access electronic key to identify tree genera in French Guiana.

Science.gov (United States)

Engel, Julien; Brousseau, Louise; Baraloto, Christopher

2016-01-01

The tropical rainforest of Amazonia is one of the most species-rich ecosystems on earth, with an estimated 16000 tree species. Due to this high diversity, botanical identification of trees in the Amazon is difficult, even to genus, often requiring the assistance of parataxonomists or taxonomic specialists. Advances in informatics tools offer a promising opportunity to develop user-friendly electronic keys to improve Amazonian tree identification. Here, we introduce an original multi-access electronic key for the identification of 389 tree genera occurring in French Guiana terra-firme forests, based on a set of 79 morphological characters related to vegetative, floral and fruit characters. Its purpose is to help Amazonian tree identification and to support the dissemination of botanical knowledge to non-specialists, including forest workers, students and researchers from other scientific disciplines. The electronic key is accessible with the free access software Xper ², and the database is publicly available on figshare: https://figshare.com/s/75d890b7d707e0ffc9bf (doi: 10.6084/m9.figshare.2682550).

Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

Directory of Open Access Journals (Sweden)

Eric Baranowski

Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

Directory of Open Access Journals (Sweden)

Xi Yu

2014-01-01

Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

Modified Principal Component Analysis for Identifying Key Environmental Indicators and Application to a Large-Scale Tidal Flat Reclamation

Directory of Open Access Journals (Sweden)

Kejian Chu

2018-01-01

Full Text Available Identification of the key environmental indicators (KEIs from a large number of environmental variables is important for environmental management in tidal flat reclamation areas. In this study, a modified principal component analysis approach (MPCA has been developed for determining the KEIs. The MPCA accounts for the two important attributes of the environmental variables: pollution status and temporal variation, in addition to the commonly considered numerical divergence attribute. It also incorporates the distance correlation (dCor to replace the Pearson’s correlation to measure the nonlinear interrelationship between the variables. The proposed method was applied to the Tiaozini sand shoal, a large-scale tidal flat reclamation region in China. Five KEIs were identified as dissolved inorganic nitrogen, Cd, petroleum in the water column, Hg, and total organic carbon in the sediment. The identified KEIs were shown to respond well to the biodiversity of phytoplankton. This demonstrated that the identified KEIs adequately represent the environmental condition in the coastal marine system. Therefore, the MPCA is a practicable method for extracting effective indicators that have key roles in the coastal and marine environment.

A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice.

Science.gov (United States)

Abulizi, Abudukadier; Perry, Rachel J; Camporez, João Paulo G; Jurczak, Michael J; Petersen, Kitt Falk; Aspichueta, Patricia; Shulman, Gerald I

2017-07-01

Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes. After 4 wk of oral CRMP (2 mg/kg body weight per day) or vehicle treatment, mice underwent hyperinsulinemic-euglycemic clamps combined with radiolabeled glucose to assess liver and muscle insulin responsiveness and tissue lipid measurements. CRMP treatment reversed hypertriglyceridemia and insulin resistance in liver and skeletal muscle. Reversal of insulin resistance could be attributed to reductions in diacylglycerol content and reduced PKC-ε and PKC-θ activity in liver and muscle respectively. CRMP treatment also reversed NASH as reflected by reductions in plasma aspartate aminotransferase and alanine aminotransferase concentrations; hepatic steatosis; and hepatic expression of IL-1α, -β, -2, -4, -6, -10, -12, CD69, and caspase 3 and attenuated activation of the IRE-1α branch of the unfolded protein response. Taken together, these results provide proof of concept for the development of liver-targeted mitochondrial uncoupling agents as a potential novel therapy for lipodystrophy-associated hypertriglyceridemia, NASH and diabetes.-Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., Shulman, G. I. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. © FASEB.

Protocol for a thematic synthesis to identify key themes and messages from a palliative care research network.

LENUS (Irish Health Repository)

Nicholson, Emma

2016-10-21

Research networks that facilitate collaborative research are increasing both regionally and globally and such collaborations contribute greatly to knowledge transfer particularly in health research. The Palliative Care Research Network is an Irish-based network that seeks to create opportunities and engender a collaborative environment to encourage innovative research that is relevant for policy and practice. The current review outlines a methodology to identify cross-cutting messages to identify how dissemination outputs can be optimized to ensure that key messages from this research reaches all knowledge users.

Risk and Performance Technologies: Identifying the Keys to Successful Implementation

International Nuclear Information System (INIS)

McClain, Lynn; Smith, Art; O'Regan, Patrick

2002-01-01

The nuclear power industry has been utilizing risk and performance based technologies for over thirty years. Applications of these technologies have included risk assessment (e.g. Individual Plant Examinations), burden reduction (e.g. Risk-Informed Inservice Inspection, RI-ISI) and risk management (Maintenance Rule, 10CFR50.65). Over the last five to ten years the number of risk-informed (RI) burden reduction initiatives has increased. Unfortunately, the efficiencies of some of these applications have been questionable. This paper investigates those attributes necessary to support successful, cost-effective RI-applications. The premise to this paper is that by understanding the key attributes that support one successful application, insights can be gleaned that will streamline/coordinate future RI-applications. This paper is an extension to a paper presented at the Pressure Vessel and Piping (PVP-2001) Conference. In that paper, a number issues and opportunities were identified that needed to be assessed in order to support future (and efficient) RI-applications. It was noted in the paper that a proper understanding and resolution of these issues will facilitate implementation of risk and performance technology in the operation, maintenance and design disciplines. In addition, it will provide the foundation necessary to support regulatory review and approval. (authors)

78 FR 16528 - Notice of Intent To Prepare a Cultural Resources Management Plan/Environmental Impact Statement...

Science.gov (United States)

2013-03-15

....C. 1131-36) and other laws and policies, will frame the decision-making for the CRMP/EIS. The CRMP...-action and a preferred alternative. The potential environmental effects of each alternative will be... decisions related to this project are invited to participate in the scoping process and, if eligible, may...

MicroRNA-301a mediated regulation of Kv4.2 in diabetes: identification of key modulators.

Directory of Open Access Journals (Sweden)

Siva K Panguluri

Full Text Available Diabetes is a metabolic disorder that ultimately results in major pathophysiological complications in the cardiovascular system. Diabetics are predisposed to higher incidences of sudden cardiac deaths (SCD. Several studies have associated diabetes as a major underlying risk for heart diseases and its complications. The diabetic heart undergoes remodeling to cope up with the underlying changes, however ultimately fails. In the present study we investigated the changes associated with a key ion channel and transcriptional factors in a diabetic heart model. In the mouse db/db model, we identified key transcriptional regulators and mediators that play important roles in the regulation of ion channel expression. Voltage-gated potassium channel (Kv4.2 is modulated in diabetes and is down regulated. We hypothesized that Kv4.2 expression is altered by potassium channel interacting protein-2 (KChIP2 which is regulated upstream by NFkB and miR-301a. We utilized qRT-PCR analysis and identified the genes that are affected in diabetes in a regional specific manner in the heart. At protein level we identified and validated differential expression of Kv4.2 and KChIP2 along with NFkB in both ventricles of diabetic hearts. In addition, we identified up-regulation of miR-301a in diabetic ventricles. We utilized loss and gain of function approaches to identify and validate the role of miR-301a in regulating Kv4.2. Based on in vivo and in vitro studies we conclude that miR-301a may be a central regulator for the expression of Kv4.2 in diabetes. This miR-301 mediated regulation of Kv4.2 is independent of NFkB and Irx5 and modulates Kv4.2 by direct binding on Kv4.2 3'untranslated region (3'-UTR. Therefore targeting miR-301a may offer new potential for developing therapeutic approaches.

Postsecondary Students With Psychiatric Disabilities Identify Core Services and Key Ingredients to Supporting Education Goals.

Science.gov (United States)

Biebel, Kathleen; Mizrahi, Raphael; Ringeisen, Heather

2017-10-26

Accessing and successfully completing postsecondary educational opportunities may be challenging for those living with psychiatric disabilities. This exploratory study highlights the experiences of individuals with psychiatric disabilities participating in postsecondary educational support initiatives. Investigators conducted case studies with 3 education support initiatives across the United States. Focus groups revealed what concrete supported education services were helpful and key ingredients in delivering education supports. Access to specialists, mindfulness techniques, help with time management and procrastination, and facilitating classroom accommodations were identified as critical. Developing authentic relationships with supported education staff, flexibility in service delivery and access to student peers living with psychiatric disabilities were noted as key ingredients in service delivery. Incorporating the voice of students with psychiatric disabilities into supported education services can increase access, involvement, and retention, therein providing more supports to students with psychiatric disabilities achieving their postsecondary education goals. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.

Science.gov (United States)

Ali, Yousuf O; Bradley, Gillian; Lu, Hui-Chen

2017-03-07

Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.

Identifying the key concerns of Irish persons with intellectual disability.

Science.gov (United States)

García Iriarte, Edurne; O'Brien, Patricia; McConkey, Roy; Wolfe, Marie; O'Doherty, Siobhain

2014-11-01

Internationally, people with intellectual disability are socially marginalized, and their rights under the United Nations Convention for the Rights of Persons with Disabilities (CRPD) are often ignored. This paper aims to define the key concerns of adults with an intellectual disability in relation to their participation in society using an inclusive research strategy for both data gathering and data analysis. A national study involving 23 focus groups and 168 persons was conducted on the island of Ireland with people with intellectual disability as co-facilitators. A thematic content analysis was undertaken of the verbatim transcripts initially by university co-researchers, and 19 themes were identified. Co-researchers with intellectual disability joined in identifying the eight core themes. These were as follows: living options, employment, relationships, citizenship, leisure time, money management, self-advocacy, and communication. The concerns are discussed within the framework of the CRPD, and implications for transforming service policy are drawn. Why we did the research In many countries, people with intellectual disability have difficulties doing things other people without disabilities do, for example to study, to get a job or to live independently. They also find that their rights are not respected under the Convention on the Rights of Persons with Disabilities (the Convention). We did this study to Learn what are the main issues for adults with intellectual disability in Ireland. Do research with people with intellectual disability. How we did the research People with intellectual disability and their supporters worked with university researchers to plan and do the research. We met with people in groups and 168 people told us about things important to them. What we found out We found that there were very important things that people talked about in the groups. We chose the most important: living options, employment, relationships, rights, leisure, money

Identifying key radiogenomic associations between DCE-MRI and micro-RNA expressions for breast cancer

Science.gov (United States)

Samala, Ravi K.; Chan, Heang-Ping; Hadjiiski, Lubomir; Helvie, Mark A.; Kim, Renaid

2017-03-01

Understanding the key radiogenomic associations for breast cancer between DCE-MRI and micro-RNA expressions is the foundation for the discovery of radiomic features as biomarkers for assessing tumor progression and prognosis. We conducted a study to analyze the radiogenomic associations for breast cancer using the TCGA-TCIA data set. The core idea that tumor etiology is a function of the behavior of miRNAs is used to build the regression models. The associations based on regression are analyzed for three study outcomes: diagnosis, prognosis, and treatment. The diagnosis group consists of miRNAs associated with clinicopathologic features of breast cancer and significant aberration of expression in breast cancer patients. The prognosis group consists of miRNAs which are closely associated with tumor suppression and regulation of cell proliferation and differentiation. The treatment group consists of miRNAs that contribute significantly to the regulation of metastasis thereby having the potential to be part of therapeutic mechanisms. As a first step, important miRNA expressions were identified and their ability to classify the clinical phenotypes based on the study outcomes was evaluated using the area under the ROC curve (AUC) as a figure-of-merit. The key mapping between the selected miRNAs and radiomic features were determined using least absolute shrinkage and selection operator (LASSO) regression analysis within a two-loop leave-one-out cross-validation strategy. These key associations indicated a number of radiomic features from DCE-MRI to be potential biomarkers for the three study outcomes.

CRMPs colocalize and interact with cytoskeleton in hippocampal neurons

Science.gov (United States)

Yang, Yuhao; Zhao, Bo; Ji, Zhisheng; Zhang, Guowei; Zhang, Jifeng; Li, Sumei; Guo, Guoqing; Lin, Hongsheng

2015-01-01

CRMP family proteins (CRMPs) are widely expressed in the developing neurons, mediating a variety of fundamental functions such as growth cone guidance, neuronal polarity and axon elongation. However, whether all the CRMP proteins interact with cytoskeleton remains unknown. In this study, we found that in cultured hippocampal neurons, CRMPs mainly colocalized with tubulin and actin network in neurites. In growth cones, CRMPs colocalized with tubulinmainly in the central (C-) domain and transition zone (T-zone), less in the peripheral (P-) domain and colocalized with actin in all the C-domain, T-zone and P-domain. The correlation efficiency of CRMPs between actin was significantly higher than that between tubulin, especially in growth cones. We successfully constructed GST-CRMPs plasmids, expressed and purified the GST-CRMP proteins. By GST-pulldown assay, all the CRMP family proteins were found to beinteracted with cytoskeleton proteins. Taken together, we revealed that CRMPs were colocalized with cytoskeleton in hippocampal neurons, especially in growth cones. CRMPs can interact with both tubulin and actin, thus mediating neuronal development. PMID:26885211

Integrated microarray and ChIP analysis identifies multiple Foxa2 dependent target genes in the notochord.

Science.gov (United States)

Tamplin, Owen J; Cox, Brian J; Rossant, Janet

2011-12-15

The node and notochord are key tissues required for patterning of the vertebrate body plan. Understanding the gene regulatory network that drives their formation and function is therefore important. Foxa2 is a key transcription factor at the top of this genetic hierarchy and finding its targets will help us to better understand node and notochord development. We performed an extensive microarray-based gene expression screen using sorted embryonic notochord cells to identify early notochord-enriched genes. We validated their specificity to the node and notochord by whole mount in situ hybridization. This provides the largest available resource of notochord-expressed genes, and therefore candidate Foxa2 target genes in the notochord. Using existing Foxa2 ChIP-seq data from adult liver, we were able to identify a set of genes expressed in the notochord that had associated regions of Foxa2-bound chromatin. Given that Foxa2 is a pioneer transcription factor, we reasoned that these sites might represent notochord-specific enhancers. Candidate Foxa2-bound regions were tested for notochord specific enhancer function in a zebrafish reporter assay and 7 novel notochord enhancers were identified. Importantly, sequence conservation or predictive models could not have readily identified these regions. Mutation of putative Foxa2 binding elements in two of these novel enhancers abrogated reporter expression and confirmed their Foxa2 dependence. The combination of highly specific gene expression profiling and genome-wide ChIP analysis is a powerful means of understanding developmental pathways, even for small cell populations such as the notochord. Copyright © 2011 Elsevier Inc. All rights reserved.

Identifying extensions required by RUP (Rational Unified Process) to comply with CMM (Capability Maturity Model) levels 2 and 3

OpenAIRE

Manzoni, Lisandra Vielmo; Price, Roberto Tom

2003-01-01

This paper describes an assessment of the Rational Unified Process (RUP) based on the Capability Maturity Model (CMM). For each key practice (KP) identified in each key process area (KPA) of CMM levels 2 and 3, the Rational Unified Process was assessed to determine whether it satisfied the KP or not. For each KPA, the percentage of the key practices supported was calculated, and the results were tabulated. The report includes considerations about the coverage of each key process area, describ...

Exploring the effects of spatial autocorrelation when identifying key drivers of wildlife crop-raiding.

Science.gov (United States)

Songhurst, Anna; Coulson, Tim

2014-03-01

Few universal trends in spatial patterns of wildlife crop-raiding have been found. Variations in wildlife ecology and movements, and human spatial use have been identified as causes of this apparent unpredictability. However, varying spatial patterns of spatial autocorrelation (SA) in human-wildlife conflict (HWC) data could also contribute. We explicitly explore the effects of SA on wildlife crop-raiding data in order to facilitate the design of future HWC studies. We conducted a comparative survey of raided and nonraided fields to determine key drivers of crop-raiding. Data were subsampled at different spatial scales to select independent raiding data points. The model derived from all data was fitted to subsample data sets. Model parameters from these models were compared to determine the effect of SA. Most methods used to account for SA in data attempt to correct for the change in P-values; yet, by subsampling data at broader spatial scales, we identified changes in regression estimates. We consequently advocate reporting both model parameters across a range of spatial scales to help biological interpretation. Patterns of SA vary spatially in our crop-raiding data. Spatial distribution of fields should therefore be considered when choosing the spatial scale for analyses of HWC studies. Robust key drivers of elephant crop-raiding included raiding history of a field and distance of field to a main elephant pathway. Understanding spatial patterns and determining reliable socio-ecological drivers of wildlife crop-raiding is paramount for designing mitigation and land-use planning strategies to reduce HWC. Spatial patterns of HWC are complex, determined by multiple factors acting at more than one scale; therefore, studies need to be designed with an understanding of the effects of SA. Our methods are accessible to a variety of practitioners to assess the effects of SA, thereby improving the reliability of conservation management actions.

Eight Key Facets of Small Business Management.

Science.gov (United States)

Scott, James Calvert

1980-01-01

Identifies eight key facets of small business management and suggests activities that may be used to assist in their development. The key facets are (1) product or service, (2) competition, (3) marketing strategies, (4) personnel needs, (5) equipment and facility needs, (6) finances, (7) planning, and (8) entrepreneurship. (JOW)

Human-automation collaboration in manufacturing: identifying key implementation factors

OpenAIRE

Charalambous, George; Fletcher, Sarah; Webb, Philip

2013-01-01

Human-automation collaboration refers to the concept of human operators and intelligent automation working together interactively within the same workspace without conventional physical separation. This concept has commanded significant attention in manufacturing because of the potential applications, such as the installation of large sub-assemblies. However, the key human factors relevant to human-automation collaboration have not yet been fully investigated. To maximise effective implement...

The Use of Key Informant Method for Identifying Children with Blindness and Severe Visual Impairment in Developing Countries.

Science.gov (United States)

du Toit, Rènée; Courtright, Paul; Lewallen, Susan

2017-06-01

An estimated 19 million children are visually impaired; of these, 1.4 million are irreversibly blind. A key challenge is to identify them early in life to benefit maximally from visual rehabilitation, and/or treatment. This aggregative review and structured literature analysis summarizes evidence of what it is about the key informant (KI) approach that works to identify children with blindness or severe visual impairment (B/SVI) in the community (for whom, to what extent, in what circumstances, in what respect, how and why). Peer-reviewed (PubMed, hand search) and grey literature (Google, World Health Organization website, academic theses, direct requests) were included, and methods and criteria used for identification, productivity (number of children referred per KI), accuracy of referrals (positive predictive value, PPV), age of children with B/SVI, KI definition, sex, information about cost and comparisons aggregated. We included 31 documents describing 22 unique KI programs. Mostly KIs identified children with B/SVI in 1-3 weeks, i.e. "campaign mode." In 60%, KIs were community volunteers, others formal health sector workers (FHSW). Around 0.02-1.56 children per KI (median = 0.25) were successfully recruited. PPV ranged from 12 to 66%. In two studies comparing FHSWs and community KIs, the latter were 8 and 10 times more productive. KIs working in campaign mode may provide an effective approach to identifying children with B/SVI in communities. Including identification of ocular problems and/or other impairments has been recommended. Research on factors that influence effectiveness and on whether KIs continue to contribute could inform programs.

Identifying Determinants of Organizational Development as the Key Developers of Employee Soft Skill

Directory of Open Access Journals (Sweden)

Shahjahan Laghari

2016-10-01

Full Text Available The purpose of this article is to identify the determinants of organizational development as the key developers of employee soft skills. Various studies have been taken where determinants of organizational development defining soft skills in employees are discussed. However, the current study is different in Pakistani industry context as the link was missing about the determinants of organizational development which in synchronized way help in developing soft skills in employees of firm. This research uses explanatory approach; incorporating secondary data extracted under the light of existing school of thoughts paired with quantification through data collected from respondents in Pakistani corporate sector. Hypotheses are tested using structural equation model (SEM technique. Results This research showed an affirmative link between determinants of organizational development and development of soft skills in employees. Finally, the study proposes enriching insights on few missing links that can be researched and triggered achieving maximized outcomes.

Setting objectives for managing Key deer

Science.gov (United States)

Diefenbach, Duane R.; Wagner, Tyler; Stauffer, Glenn E.

2014-01-01

of available habitat. The identified management approach must balance relevant social and economic concerns, Federal (e.g., Endangered Species Act, Wilderness Act, Refuge Act) and state regulations, and the conservation of biodiversity (e.g., Endangered/Threatened species, native habitat) in the Lower Keys.”The stakeholder group identified four fundamental objectives that are essential to addressing the problem: 1) Maximize a sustainable, viable, and healthy Key deer population, 2) Maximize value of Key deer to the People, 3) Minimize deer-related negative impacts to biodiversity, and 4) Minimize costs. In addition, the group identified 25 additional objectives that, if met, would help meet the fundamental objectives. The objectives network and measurable attributes identified by the stakeholder group can be used in the future to develop and evaluate potential management alternatives.

GuiaTreeKey, a multi-access electronic key to identify tree genera in French Guiana

OpenAIRE

Brousseau, Louise; Baraloto, Christopher

2016-01-01

The tropical rainforest of Amazonia is one of the most species-rich ecosystems on earth, with an estimated 16000 tree species. Due to this high diversity, botanical identification of trees in the Amazon is difficult, even to genus, often requiring the assistance of parataxonomists or taxonomic specialists. Advances in informatics tools offer a promising opportunity to develop user-friendly electronic keys to improve Amazonian tree identification. Here, we introduce an original mult...

Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex.

Science.gov (United States)

Li, Shih-Wen; Chen, Yu-Chieh; Sheen, Jiunn-Ming; Hsu, Mei-Hsin; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung

2017-07-01

Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively. We used 2D/LC-MS/MS to analyze for affected proteins in the prefrontal cortex of young BDL rats. Results were verified with Western blotting, immunohistochemistry, and quantitative real-time PCR. The effect of minocycline in BDL rats was assessed. BDL induced spatial deficits, while minocycline rescued it. Collapsin response mediator protein 2 (CRMP2) and manganese-dependent superoxide dismutase (MnSOD) were upregulated and nucleoside diphosphate kinase B (NME2) was downregulated in young BDL rats. BDL rats exhibited decreased levels of brain-derived neurotrophic factor (BDNF) mRNA as compared with those by the control. However, minocycline treatment restored CRMP2 and NME2 protein expression, BDNF mRNA level, and MnSOD activity to control levels. We demonstrated that BDL altered the expression of CRMP2, NME2, MnSOD, and BDNF in the prefrontal cortex of young BDL rats. However, minocycline treatment restored the expression of the affected mediators that are implicated in cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Simple Web-based interactive key development software (WEBiKEY) and an example key for Kuruna (Poaceae: Bambusoideae).

Science.gov (United States)

Attigala, Lakshmi; De Silva, Nuwan I; Clark, Lynn G

2016-04-01

Programs that are user-friendly and freely available for developing Web-based interactive keys are scarce and most of the well-structured applications are relatively expensive. WEBiKEY was developed to enable researchers to easily develop their own Web-based interactive keys with fewer resources. A Web-based multiaccess identification tool (WEBiKEY) was developed that uses freely available Microsoft ASP.NET technologies and an SQL Server database for Windows-based hosting environments. WEBiKEY was tested for its usability with a sample data set, the temperate woody bamboo genus Kuruna (Poaceae). WEBiKEY is freely available to the public and can be used to develop Web-based interactive keys for any group of species. The interactive key we developed for Kuruna using WEBiKEY enables users to visually inspect characteristics of Kuruna and identify an unknown specimen as one of seven possible species in the genus.

Identifying Key Stakeholders in Blended Tertiary Environments: Experts' Perspectives

Science.gov (United States)

Tuapawa, Kimberley

2017-01-01

Although key stakeholders in blended tertiary environments (BTEs) fulfil an extraordinary role in higher education, significant gaps in knowledge about their identities may be impeding the provision of stakeholder support, limiting their ability to promote effective learning and teaching. As online growth intensifies, it is critical that tertiary…

Protein: MPB4 [TP Atlas

Lifescience Database Archive (English)

Full Text Available MPB4 Sema3A signaling molecules DPYSL2 CRMP2, ULIP2 DPYSL2 Dihydropyrimidinase-related pr...otein 2 Collapsin response mediator protein 2, N2A3, Unc-33-like phosphoprotein 2 9606 Homo sapiens Q16555 1808 2VM8, 2GSE 1808 Q16555 ...

A Simple Key for Identifying the Sibling Species of the Malaria Vector Anopheles gambiae (Giles Complex by Polytene Chromosome Cytogenetics

Directory of Open Access Journals (Sweden)

Music Temitope OBEMBE

2018-03-01

Full Text Available It has been established that Anopheles gambiae complex sibling species are the major Plasmodium malaria vectors in Africa; however, not all the sibling species transmit the infection. Easier molecular methods, PCR-based assays, have been developed to distinguish the several members of the A. gambiae complex. However, malaria vector research in less developed countries, particularly sub-Saharan Africa, is being hampered by the lack of PCR facilities in laboratories and the cost of carrying out the assay within lack of funding. Hence, the present study was designed to develop a simple identification key, based on an affordable method of polytene chromosome cytotaxonomy, for identifying the major P. falciparum vectors. The Identification Key was successfully used to identify two members of the A. gambiae complex, A. gambiae sensu stricto and A. arabiensis, which are the most potent malaria vectors in Africa; even so, it could not be used to establish the infective and the refractory strains.

Identifying key research objectives to make European forests greener for bats

Directory of Open Access Journals (Sweden)

Danilo Russo

2016-07-01

Full Text Available Bats are a biodiverse mammal order providing key ecosystem services such as pest suppression, pollination and seed dispersal. Bats are also very sensitive to human actions, and significant declines in many bat populations have been recorded consequently. Many bat species find crucial roosting and foraging opportunities in European forests. Such forests have historically been exploited by humans and are still influenced by harvesting. One of the consequences of this pressure is the loss of key habitat resources, often making forests inhospitable to bats. Despite the legal protection granted to bats across Europe, the impacts of forestry on bats are still often neglected. Because forest exploitation influences forest structure at several spatial scales, economically viable forestry could become more sustainable and even favour bats. We highlight that a positive future for bat conservation that simultaneously benefits forestry is foreseeable, although more applied research is needed to develop sound management. Key future research topics include the detection of factors influencing the carrying capacity of forests, and determining the impacts of forest management and the economic importance of bats in forests. Predictive tools to inform forest managers are much needed, together with greater synergies between forest managers and bat conservationists.

Key Clinical Features to Identify Girls with "CDKL5" Mutations

Science.gov (United States)

Bahi-Buisson, Nadia; Nectoux, Juliette; Rosas-Vargas, Haydee; Milh, Mathieu; Boddaert, Nathalie; Girard, Benoit; Cances, Claude; Ville, Dorothee; Afenjar, Alexandra; Rio, Marlene; Heron, Delphine; Morel, Marie Ange N'Guyen; Arzimanoglou, Alexis; Philippe, Christophe; Jonveaux, Philippe; Chelly, Jamel; Bienvenu, Thierry

2008-01-01

Mutations in the human X-linked cyclin-dependent kinase-like 5 ("CDKL5") gene have been shown to cause infantile spasms as well as Rett syndrome (RTT)-like phenotype. To date, less than 25 different mutations have been reported. So far, there are still little data on the key clinical diagnosis criteria and on the natural history of…

Identification of the Key Fields and Their Key Technical Points of Oncology by Patent Analysis.

Science.gov (United States)

Zhang, Ting; Chen, Juan; Jia, Xiaofeng

2015-01-01

This paper aims to identify the key fields and their key technical points of oncology by patent analysis. Patents of oncology applied from 2006 to 2012 were searched in the Thomson Innovation database. The key fields and their key technical points were determined by analyzing the Derwent Classification (DC) and the International Patent Classification (IPC), respectively. Patent applications in the top ten DC occupied 80% of all the patent applications of oncology, which were the ten fields of oncology to be analyzed. The number of patent applications in these ten fields of oncology was standardized based on patent applications of oncology from 2006 to 2012. For each field, standardization was conducted separately for each of the seven years (2006-2012) and the mean of the seven standardized values was calculated to reflect the relative amount of patent applications in that field; meanwhile, regression analysis using time (year) and the standardized values of patent applications in seven years (2006-2012) was conducted so as to evaluate the trend of patent applications in each field. Two-dimensional quadrant analysis, together with the professional knowledge of oncology, was taken into consideration in determining the key fields of oncology. The fields located in the quadrant with high relative amount or increasing trend of patent applications are identified as key ones. By using the same method, the key technical points in each key field were identified. Altogether 116,820 patents of oncology applied from 2006 to 2012 were retrieved, and four key fields with twenty-nine key technical points were identified, including "natural products and polymers" with nine key technical points, "fermentation industry" with twelve ones, "electrical medical equipment" with four ones, and "diagnosis, surgery" with four ones. The results of this study could provide guidance on the development direction of oncology, and also help researchers broaden innovative ideas and discover new

On the Security of a Simple Three-Party Key Exchange Protocol without Server’s Public Keys

Directory of Open Access Journals (Sweden)

Junghyun Nam

2014-01-01

Full Text Available Authenticated key exchange protocols are of fundamental importance in securing communications and are now extensively deployed for use in various real-world network applications. In this work, we reveal major previously unpublished security vulnerabilities in the password-based authenticated three-party key exchange protocol according to Lee and Hwang (2010: (1 the Lee-Hwang protocol is susceptible to a man-in-the-middle attack and thus fails to achieve implicit key authentication; (2 the protocol cannot protect clients’ passwords against an offline dictionary attack; and (3 the indistinguishability-based security of the protocol can be easily broken even in the presence of a passive adversary. We also propose an improved password-based authenticated three-party key exchange protocol that addresses the security vulnerabilities identified in the Lee-Hwang protocol.

Quantum key management

Energy Technology Data Exchange (ETDEWEB)

Hughes, Richard John; Thrasher, James Thomas; Nordholt, Jane Elizabeth

2016-11-29

Innovations for quantum key management harness quantum communications to form a cryptography system within a public key infrastructure framework. In example implementations, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a Merkle signature scheme (using Winternitz one-time digital signatures or other one-time digital signatures, and Merkle hash trees) to constitute a cryptography system. More generally, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a hash-based signature scheme. This provides a secure way to identify, authenticate, verify, and exchange secret cryptographic keys. Features of the quantum key management innovations further include secure enrollment of users with a registration authority, as well as credential checking and revocation with a certificate authority, where the registration authority and/or certificate authority can be part of the same system as a trusted authority for quantum key distribution.

[Key effect genes responding to nerve injury identified by gene ontology and computer pattern recognition].

Science.gov (United States)

Pan, Qian; Peng, Jin; Zhou, Xue; Yang, Hao; Zhang, Wei

2012-07-01

In order to screen out important genes from large gene data of gene microarray after nerve injury, we combine gene ontology (GO) method and computer pattern recognition technology to find key genes responding to nerve injury, and then verify one of these screened-out genes. Data mining and gene ontology analysis of gene chip data GSE26350 was carried out through MATLAB software. Cd44 was selected from screened-out key gene molecular spectrum by comparing genes' different GO terms and positions on score map of principal component. Function interferences were employed to influence the normal binding of Cd44 and one of its ligands, chondroitin sulfate C (CSC), to observe neurite extension. Gene ontology analysis showed that the first genes on score map (marked by red *) mainly distributed in molecular transducer activity, receptor activity, protein binding et al molecular function GO terms. Cd44 is one of six effector protein genes, and attracted us with its function diversity. After adding different reagents into the medium to interfere the normal binding of CSC and Cd44, varying-degree remissions of CSC's inhibition on neurite extension were observed. CSC can inhibit neurite extension through binding Cd44 on the neuron membrane. This verifies that important genes in given physiological processes can be identified by gene ontology analysis of gene chip data.

Breaking chaotic shift key communication via adaptive key identification

International Nuclear Information System (INIS)

Ren Haipeng; Han Chongzhao; Liu Ding

2008-01-01

This paper proposes an adaptive parameter identification method for breaking chaotic shift key communication from the transmitted signal in public channel. The sensitive dependence property of chaos on parameter mismatch is used for chaos adaptive synchronization and parameter identification. An index function about the synchronization error is defined and conjugate gradient method is used to minimize the index function and to search the transmitter's parameter (key). By using proposed method, secure key is recovered from transmitted signal generated by low dimensional chaos and hyper chaos switching communication. Multi-parameters can also be identified from the transmitted signal with noise

Partitioned key-value store with atomic memory operations

Energy Technology Data Exchange (ETDEWEB)

Bent, John M.; Faibish, Sorin; Grider, Gary

2017-02-07

A partitioned key-value store is provided that supports atomic memory operations. A server performs a memory operation in a partitioned key-value store by receiving a request from an application for at least one atomic memory operation, the atomic memory operation comprising a memory address identifier; and, in response to the atomic memory operation, performing one or more of (i) reading a client-side memory location identified by the memory address identifier and storing one or more key-value pairs from the client-side memory location in a local key-value store of the server; and (ii) obtaining one or more key-value pairs from the local key-value store of the server and writing the obtained one or more key-value pairs into the client-side memory location identified by the memory address identifier. The server can perform functions obtained from a client-side memory location and return a result to the client using one or more of the atomic memory operations.

Key identifiers and spelling conventions in MXit-lingo as found in conversations with Dr Math

Directory of Open Access Journals (Sweden)

Laurie Butgereit

2012-07-01

Full Text Available Different human languages look different from other human languages. To use a term from the computer industry, each human language has its own “look and feel”. European English speakers can easily recognise a phrase such as “Comment allez-vous?” as being written in French while the phrase “¿Habla usted español?” is written in Spanish. Each language has its own letter frequencies, word frequencies and other identifiers. This paper describes key identifiers in MXit lingo as found in Dr Math conversations. MXit is a mobile instant messaging system which originated in South Africa and is expanding to other countries. Dr Math is a mobile tutoring system which uses MXit as a communication protocol. Primary and secondary school pupils can receive help with the mathematics homework using the Dr Math tutoring system. The pupils use MXit on their cell phones and the tutors use traditional Internet workstations. After exploring how MXit lingo is written, this paper will briefly explore why MXit lingo is written the way it is. By identifying and describing the orthographic conventions visible in the spelling of MXit lingo, although with some theoretical support, insight into the purposeful and functional nature of written, mobile communication will be revealed. In highlighting spelling that is influenced by Black South African English, an attempt will be made to contribute to the empirical development of a field of study that explores the construction of words used in South African mobile communication. Keywords: MXit, Math, letters, writing, orthography Disciplines: Linguistics, mathematics, information technology

Genome-wide expression profiling analysis to identify key genes in the anti-HIV mechanism of CD4+ and CD8+ T cells.

Science.gov (United States)

Gao, Lijie; Wang, Yunqi; Li, Yi; Dong, Ya; Yang, Aimin; Zhang, Jie; Li, Fengying; Zhang, Rongqiang

2018-07-01

Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4 + and CD8 + T cells. The numbers of CD4 + and CD8 + T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for differentially expressed genes (DEGs) in HIV infected CD4 + and CD8 + T cells. Gene Ontology enrichment, KEGG pathway analyses, and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4 + and CD8 + T cells. Finally, we analyzed the expressions of key proteins in HIV-infected T cells (GSE6740 dataset) and peripheral blood mononuclear cells(PBMCs) (GSE511 dataset). 1) CD4 + T cells counts and ratio of CD4 + /CD8 + T cells decreased while CD8 + T cells counts increased in HIV positive individuals; 2) 517 DEGs were found in HIV infected CD4 + and CD8 + T cells at acute and chronic stage with the criterial of P-value T cells. The main biological processes of the DEGs were response to virus and defense response to virus. At chronic stage, ISG15 protein, in conjunction with IFN-1 pathway might play key roles in anti-HIV responses of CD4 + T cells; and 4) The expression of ISG15 increased in both T cells and PBMCs after HIV infection. Gene expression profile of CD4 + and CD8 + T cells changed significantly in HIV infection, in which ISG15 gene may play a central role in activating the natural antiviral process of immune cells. © 2018 Wiley Periodicals, Inc.

Attacking 44 Rounds of the SHACAL-2 Block Cipher Using Related-Key Rectangle Cryptanalysis

Science.gov (United States)

Lu, Jiqiang; Kim, Jongsung

SHACAL-2 is a 64-round block cipher with a 256-bit block size and a variable length key of up to 512 bits. It is a NESSIE selected block cipher algorithm. In this paper, we observe that, when checking whether a candidate quartet is useful in a (related-key) rectangle attack, we can check the two pairs from the quartet one after the other, instead of checking them simultaneously; if the first pair does not meet the expected conditions, we can discard the quartet immediately. We next exploit a 35-round related-key rectangle distinguisher with probability 2-460 for the first 35 rounds of SHACAL-2, which is built on an existing 24-round related-key differential and a new 10-round differential. Finally, taking advantage of the above observation, we use the distinguisher to mount a related-key rectangle attack on the first 44 rounds of SHACAL-2. The attack requires 2233 related-key chosen plaintexts, and has a time complexity of 2497.2 computations. This is better than any previously published cryptanalytic results on SHACAL-2 in terms of the numbers of attacked rounds.

Elucidating Key Motifs Required for Arp2/3-Dependent and Independent Actin Nucleation by Las17/WASP

Science.gov (United States)

Urbanek, Agnieszka N.; Smaczynska-de Rooij, Iwona I.

2016-01-01

Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. Arp2/3 is a well-characterised protein complex that can promote nucleation of new filaments, though its activity requires additional nucleation promotion factors (NPFs). The best recognized of these factors are the WASP family of proteins that contain binding motifs for both monomeric actin and for Arp2/3. Previously we demonstrated that the yeast WASP homologue, Las17, in addition to activating Arp2/3 can also nucleate actin filaments de novo, independently of Arp2/3. This activity is dependent on its polyproline rich region. Through biochemical and in vivo analysis we have now identified key motifs within the polyproline region that are required for nucleation and elongation of actin filaments, and have addressed the role of the WH2 domain in the context of actin nucleation without Arp2/3. We have also demonstrated that full length Las17 is able to bind liposomes giving rise to the possibility of direct linkage of nascent actin filaments to specific membrane sites to which Las17 has been recruited. Overall, we propose that Las17 functions as the key initiator of de novo actin filament formation at endocytic sites by nucleating, elongating and tethering nascent filaments which then serve as a platform for Arp2/3 recruitment and function. PMID:27637067

Use of a scenario-neutral approach to identify the key hydro-meteorological attributes that impact runoff from a natural catchment

Science.gov (United States)

Guo, Danlu; Westra, Seth; Maier, Holger R.

2017-11-01

Scenario-neutral approaches are being used increasingly for assessing the potential impact of climate change on water resource systems, as these approaches allow the performance of these systems to be evaluated independently of climate change projections. However, practical implementations of these approaches are still scarce, with a key limitation being the difficulty of generating a range of plausible future time series of hydro-meteorological data. In this study we apply a recently developed inverse stochastic generation approach to support the scenario-neutral analysis, and thus identify the key hydro-meteorological variables to which the system is most sensitive. The stochastic generator simulates synthetic hydro-meteorological time series that represent plausible future changes in (1) the average, extremes and seasonal patterns of rainfall; and (2) the average values of temperature (Ta), relative humidity (RH) and wind speed (uz) as variables that drive PET. These hydro-meteorological time series are then fed through a conceptual rainfall-runoff model to simulate the potential changes in runoff as a function of changes in the hydro-meteorological variables, and runoff sensitivity is assessed with both correlation and Sobol' sensitivity analyses. The method was applied to a case study catchment in South Australia, and the results showed that the most important hydro-meteorological attributes for runoff were winter rainfall followed by the annual average rainfall, while the PET-related meteorological variables had comparatively little impact. The high importance of winter rainfall can be related to the winter-dominated nature of both the rainfall and runoff regimes in this catchment. The approach illustrated in this study can greatly enhance our understanding of the key hydro-meteorological attributes and processes that are likely to drive catchment runoff under a changing climate, thus enabling the design of tailored climate impact assessments to specific

Non-metastatic 2 (NME2)-mediated suppression of lung cancer metastasis involves transcriptional regulation of key cell adhesion factor vinculin

Science.gov (United States)

Thakur, Ram Krishna; Yadav, Vinod Kumar; Kumar, Akinchan; Singh, Ankita; Pal, Krishnendu; Hoeppner, Luke; Saha, Dhurjhoti; Purohit, Gunjan; Basundra, Richa; Kar, Anirban; Halder, Rashi; Kumar, Pankaj; Baral, Aradhita; Kumar, MJ Mahesh; Baldi, Alfonso; Vincenzi, Bruno; Lorenzon, Laura; Banerjee, Rajkumar; Kumar, Praveen; Shridhar, Viji; Mukhopadhyay, Debabrata; Chowdhury, Shantanu

2014-01-01

Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n = 382), survival data (n = 530) and lymph node metastases (n = 100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis. PMID:25249619

A semi-automatic 2D-to-3D video conversion with adaptive key-frame selection

Science.gov (United States)

Ju, Kuanyu; Xiong, Hongkai

2014-11-01

To compensate the deficit of 3D content, 2D to 3D video conversion (2D-to-3D) has recently attracted more attention from both industrial and academic communities. The semi-automatic 2D-to-3D conversion which estimates corresponding depth of non-key-frames through key-frames is more desirable owing to its advantage of balancing labor cost and 3D effects. The location of key-frames plays a role on quality of depth propagation. This paper proposes a semi-automatic 2D-to-3D scheme with adaptive key-frame selection to keep temporal continuity more reliable and reduce the depth propagation errors caused by occlusion. The potential key-frames would be localized in terms of clustered color variation and motion intensity. The distance of key-frame interval is also taken into account to keep the accumulated propagation errors under control and guarantee minimal user interaction. Once their depth maps are aligned with user interaction, the non-key-frames depth maps would be automatically propagated by shifted bilateral filtering. Considering that depth of objects may change due to the objects motion or camera zoom in/out effect, a bi-directional depth propagation scheme is adopted where a non-key frame is interpolated from two adjacent key frames. The experimental results show that the proposed scheme has better performance than existing 2D-to-3D scheme with fixed key-frame interval.

ClinicalKey 2.0: Upgrades in a Point-of-Care Search Engine.

Science.gov (United States)

Huslig, Mary Ann; Vardell, Emily

2015-01-01

ClinicalKey 2.0, launched September 23, 2014, offers a mobile-friendly design with a search history feature for targeting point-of-care resources for health care professionals. Browsing is improved with searchable, filterable listings of sources highlighting new resources. ClinicalKey 2.0 improvements include more than 1,400 new Topic Pages for quick access to point-of-care content. A sample search details some of the upgrades and content options.

Energy efficiency and CO2: is electricity the key factor?

Energy Technology Data Exchange (ETDEWEB)

Bamberger, Y.

2007-07-01

Europe must face soon to the depletion of fossil energy resources. Efficiency in end energy uses is a key to prepare this challenge. First, the report shows that significant energy efficiency capacities remain in the main economy sectors in France and Europe: buildings, industry, transportation. The key technologies, mainly electricity-driven, are briefly presented, together with the related main tracks for R and D: heat pumps, thermal insulation, induction and mechanical vapour compression for industry, plugged hybrid vehicle, LED sources for lighting. Their ability to decrease CO2 emissions is shown. Control equipment and users behaviour are pointed out, mainly with the key role of price energy with recent French experience : load shifting, peak shaving. Finally, the report shows that a firm policy, based on high performance equipments, could lead to a significant decrease of energy needs in France around 2030.

Analysis of Transcription Factors Key for Mouse Pancreatic Development Establishes NKX2-2 and MNX1 Mutations as Causes of Neonatal Diabetes in Man

Science.gov (United States)

Flanagan, Sarah E.; De Franco, Elisa; Lango Allen, Hana; Zerah, Michele; Abdul-Rasoul, Majedah M.; Edge, Julie A.; Stewart, Helen; Alamiri, Elham; Hussain, Khalid; Wallis, Sam; de Vries, Liat; Rubio-Cabezas, Oscar; Houghton, Jayne A.L.; Edghill, Emma L.; Patch, Ann-Marie; Ellard, Sian; Hattersley, Andrew T.

2014-01-01

Summary Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development. PMID:24411943

Using Range-Wide Abundance Modeling to Identify Key Conservation Areas for the Micro-Endemic Bolson Tortoise (Gopherus flavomarginatus.

Directory of Open Access Journals (Sweden)

Cinthya A Ureña-Aranda

Full Text Available A widespread biogeographic pattern in nature is that population abundance is not uniform across the geographic range of species: most occurrence sites have relatively low numbers, whereas a few places contain orders of magnitude more individuals. The Bolson tortoise Gopherus flavomarginatus is endemic to a small region of the Chihuahuan Desert in Mexico, where habitat deterioration threatens this species with extinction. In this study we combined field burrows counts and the approach for modeling species abundance based on calculating the distance to the niche centroid to obtain range-wide abundance estimates. For the Bolson tortoise, we found a robust, negative relationship between observed burrows abundance and distance to the niche centroid, with a predictive capacity of 71%. Based on these results we identified four priority areas for the conservation of this microendemic and threatened tortoise. We conclude that this approach may be a useful approximation for identifying key areas for sampling and conservation efforts in elusive and rare species.

An ELMO2-RhoG-ILK network modulates microtubule dynamics.

Science.gov (United States)

Jackson, Bradley C; Ivanova, Iordanka A; Dagnino, Lina

2015-07-15

ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG, forming tripartite ERI complexes. These complexes are involved in promoting β1 integrin-dependent directional migration in undifferentiated epidermal keratinocytes. ELMO2 and ILK have also separately been implicated in microtubule regulation at integrin-containing focal adhesions. During differentiation, epidermal keratinocytes cease to express integrins, but ERI complexes persist. Here we show an integrin-independent role of ERI complexes in modulation of microtubule dynamics in differentiated keratinocytes. Depletion of ERI complexes by inactivating the Ilk gene in these cells reduces microtubule growth and increases the frequency of catastrophe. Reciprocally, exogenous expression of ELMO2 or RhoG stabilizes microtubules, but only if ILK is also present. Mechanistically, activation of Rac1 downstream from ERI complexes mediates their effects on microtubule stability. In this pathway, Rac1 serves as a hub to modulate microtubule dynamics through two different routes: 1) phosphorylation and inactivation of the microtubule-destabilizing protein stathmin and 2) phosphorylation and inactivation of GSK-3β, which leads to the activation of CRMP2, promoting microtubule growth. At the cellular level, the absence of ERI species impairs Ca(2+)-mediated formation of adherens junctions, critical to maintaining mechanical integrity in the epidermis. Our findings support a key role for ERI species in integrin-independent stabilization of the microtubule network in differentiated keratinocytes. © 2015 Jackson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A systems toxicology approach identifies Lyn as a key signaling phosphoprotein modulated by mercury in a B lymphocyte cell model

Energy Technology Data Exchange (ETDEWEB)

Caruso, Joseph A.; Stemmer, Paul M. [Institute of Environmental Health Sciences, Wayne State University, Detroit, MI (United States); Dombkowski, Alan [Department of Pediatrics, Wayne State University, Detroit, MI (United States); Caruthers, Nicholas J. [Institute of Environmental Health Sciences, Wayne State University, Detroit, MI (United States); Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit, MI (United States); Rosenspire, Allen J., E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit, MI (United States)

2014-04-01

Network and protein–protein interaction analyses of proteins undergoing Hg{sup 2+}-induced phosphorylation and dephosphorylation in Hg{sup 2+}-intoxicated mouse WEHI-231 B cells identified Lyn as the most interconnected node. Lyn is a Src family protein tyrosine kinase known to be intimately involved in the B cell receptor (BCR) signaling pathway. Under normal signaling conditions the tyrosine kinase activity of Lyn is controlled by phosphorylation, primarily of two well known canonical regulatory tyrosine sites, Y-397 and Y-508. However, Lyn has several tyrosine residues that have not yet been determined to play a major role under normal signaling conditions, but are potentially important sites for phosphorylation following mercury exposure. In order to determine how Hg{sup 2+} exposure modulates the phosphorylation of additional residues in Lyn, a targeted MS assay was developed. Initial mass spectrometric surveys of purified Lyn identified 7 phosphorylated tyrosine residues. A quantitative assay was developed from these results using the multiple reaction monitoring (MRM) strategy. WEHI-231 cells were treated with Hg{sup 2+}, pervanadate (a phosphatase inhibitor), or anti-Ig antibody (to stimulate the BCR). Results from these studies showed that the phosphoproteomic profile of Lyn after exposure of the WEHI-231 cells to a low concentration of Hg{sup 2+} closely resembled that of anti-Ig antibody stimulation, whereas exposure to higher concentrations of Hg{sup 2+} led to increases in the phosphorylation of Y-193/Y-194, Y-501 and Y-508 residues. These data indicate that mercury can disrupt a key regulatory signal transduction pathway in B cells and point to phospho-Lyn as a potential biomarker for mercury exposure. - Highlights: • Inorganic mercury (Hg{sup 2+}) induces changes in the WEHI-231 B cell phosphoproteome. • The B cell receptor (BCR) signaling pathway was the pathway most affected by Hg{sup 2+}. • The Src family phosphoprotein kinase Lyn was the

Identifying Key Flavors in Strawberries Driving Liking via Internal and External Preference Mapping.

Science.gov (United States)

Oliver, Penelope; Cicerale, Sara; Pang, Edwin; Keast, Russell

2018-04-01

Australian consumers desire the development of a more flavorsome Australian strawberry cultivar. To aid in the development of well-liked strawberries, the attributes driving liking need to be identified. The objective of this research is to apply Preference Mapping (PM) techniques to the descriptive profile of commercial and newly bred strawberry cultivars, together with consumer preference data to determine the flavors contributing to liking. A trained sensory panel (n = 12) used Quantitative Descriptive Analysis (QDA®) methodology to evaluate two appearance, seven aroma, five texture, 10 flavor and 10 aftertaste attributes of three commercial strawberry cultivars and six elite breeding lines grown in Victoria, Australia. Strawberry consumers (n = 150) assessed their liking of the same strawberry cultivars. QDA® significantly discriminated strawberries on 28 of the 34 sensory attributes. There were significant differences in hedonic ratings of strawberries (F(8,714) = 11.5, P = 0.0001), with Hierarchical Cluster Analysis (HCA) identifying three consumer clusters each displaying differing patterns of preference. Internal and external PM techniques were applied to the data to identify the attributes driving consumer acceptability. Sweet, berry, caramel, fruity and floral attributes were identified as most contributing to liking. Sour, citrus, green, astringent, firm and gritty attributes were conversely associated with a reduction in consumer liking. Elite Lines 2 and 6 have been identified as having the broadest appeal, satisfying between 60% and 70% of consumers in the population assessed, thus the introduction of these cultivars should satisfy the largest group of consumers in the Australian market. The results of this research could be applied to breeding programs, to ensure newly bred cultivars express characteristics that were identified as well-liked amongst consumers. In addition, this research provides evidence for marketing strawberries by

Key figures for the regional- and distribution grid

International Nuclear Information System (INIS)

Vikingstad, S.

1996-02-01

In Norway, improving the efficiency of the hydroelectric grid operation is a stated goal of the Energy Act. Several studies have identified potential profits of such improvement. This publication focuses on costs and improvement potentials. Publication of key figures may stimulate grid owners, boards and administrations to improve the operating efficiency of their grids. The publication shows key figures for the regional- and distribution grid and is based on accounting data for 1994. The key figures are divided into: (1) Cost structure: The key figures express the relative contributions of each cost component to the total income of the grid, (2) Costs and physical quantities: The key figures show the cost of delivering the transport services, (3) Physical quantities: The key figures describe the working conditions of the energy utility. It appears that the cost structure of the sector varies considerably. The same is true of the cost related to the delivery of grid services. 30 figs., 6 tabs

Identifying the Key Weaknesses in Network Security at Colleges.

Science.gov (United States)

Olsen, Florence

2000-01-01

A new study identifies and ranks the 10 security gaps responsible for most outsider attacks on college computer networks. The list is intended to help campus system administrators establish priorities as they work to increase security. One network security expert urges that institutions utilize multiple security layers. (DB)

Using sensitivity analysis to identify key factors for the propagation of a plant epidemic.

Science.gov (United States)

Rimbaud, Loup; Bruchou, Claude; Dallot, Sylvie; Pleydell, David R J; Jacquot, Emmanuel; Soubeyrand, Samuel; Thébaud, Gaël

2018-01-01

Identifying the key factors underlying the spread of a disease is an essential but challenging prerequisite to design management strategies. To tackle this issue, we propose an approach based on sensitivity analyses of a spatiotemporal stochastic model simulating the spread of a plant epidemic. This work is motivated by the spread of sharka, caused by plum pox virus , in a real landscape. We first carried out a broad-range sensitivity analysis, ignoring any prior information on six epidemiological parameters, to assess their intrinsic influence on model behaviour. A second analysis benefited from the available knowledge on sharka epidemiology and was thus restricted to more realistic values. The broad-range analysis revealed that the mean duration of the latent period is the most influential parameter of the model, whereas the sharka-specific analysis uncovered the strong impact of the connectivity of the first infected orchard. In addition to demonstrating the interest of sensitivity analyses for a stochastic model, this study highlights the impact of variation ranges of target parameters on the outcome of a sensitivity analysis. With regard to sharka management, our results suggest that sharka surveillance may benefit from paying closer attention to highly connected patches whose infection could trigger serious epidemics.

A General Construction of IND-CCA2 Secure Public Key Encryption

DEFF Research Database (Denmark)

Kiltz, Eike; Malone-Lee, John

2003-01-01

We propose a general construction for public key encryption schemes that are IND-CCA2 secure in the random oracle model. We show that the scheme proposed in [1, 2] fits our general framework and moreover that our method of analysis leads to a more efficient security reduction....

Almost-sure identifiability of multidimensional harmonic retrieval

NARCIS (Netherlands)

Jiang, T; Sidiropoulos, ND; ten Berge, JMF

Two-dimensional (2-D) and, more generally, multidimensional harmonic retrieval is of interest in a variety of applications, including transmitter localization and joint time and frequency offset estimation in wireless communications. The associated identifiability problem is key in understanding the

Key attributes of expert NRL referees.

Science.gov (United States)

Morris, Gavin; O'Connor, Donna

2017-05-01

Experiential knowledge of elite National Rugby League (NRL) referees was investigated to determine the key attributes contributing to expert officiating performance. Fourteen current first-grade NRL referees were asked to identify the key attributes they believed contributed to their expert refereeing performance. The modified Delphi method involved a 3-round process of an initial semi-structured interview followed by 2 questionnaires to reach consensus of opinion. The data revealed 25 attributes that were rated as most important that underpin expert NRL refereeing performance. Results illustrate the significance of the cognitive category, with the top 6 ranked attributes all cognitive skills. Of these, the referees ranked decision-making accuracy as the most important attribute, followed by reading the game, communication, game understanding, game management and knowledge of the rules. Player rapport, positioning and teamwork were the top ranked game skill attributes underpinning performance excellence. Expert referees also highlighted a number of psychological attributes (e.g., concentration, composure and mental toughness) that were significant to performance. There were only 2 physiological attributes (fitness, aerobic endurance) that were identified as significant to elite officiating performance. In summary, expert consensus was attained which successfully provided a hierarchy of the most significant attributes of expert NRL refereeing performance.

SARS: Key factors in crisis management.

Science.gov (United States)

Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

2005-03-01

This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

Identifying ELIXIR Core Data Resources [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Christine Durinx

2017-03-01

Full Text Available The core mission of ELIXIR is to build a stable and sustainable infrastructure for biological information across Europe. At the heart of this are the data resources, tools and services that ELIXIR offers to the life-sciences community, providing stable and sustainable access to biological data. ELIXIR aims to ensure that these resources are available long-term and that the life-cycles of these resources are managed such that they support the scientific needs of the life-sciences, including biological research. ELIXIR Core Data Resources are defined as a set of European data resources that are of fundamental importance to the wider life-science community and the long-term preservation of biological data. They are complete collections of generic value to life-science, are considered an authority in their field with respect to one or more characteristics, and show high levels of scientific quality and service. Thus, ELIXIR Core Data Resources are of wide applicability and usage. This paper describes the structures, governance and processes that support the identification and evaluation of ELIXIR Core Data Resources. It identifies key indicators which reflect the essence of the definition of an ELIXIR Core Data Resource and support the promotion of excellence in resource development and operation. It describes the specific indicators in more detail and explains their application within ELIXIR’s sustainability strategy and science policy actions, and in capacity building, life-cycle management and technical actions. The identification process is currently being implemented and tested for the first time. The findings and outcome will be evaluated by the ELIXIR Scientific Advisory Board in March 2017. Establishing the portfolio of ELIXIR Core Data Resources and ELIXIR Services is a key priority for ELIXIR and publicly marks the transition towards a cohesive infrastructure.

Image encryption using fingerprint as key based on phase retrieval algorithm and public key cryptography

Science.gov (United States)

Zhao, Tieyu; Ran, Qiwen; Yuan, Lin; Chi, Yingying; Ma, Jing

2015-09-01

In this paper, a novel image encryption system with fingerprint used as a secret key is proposed based on the phase retrieval algorithm and RSA public key algorithm. In the system, the encryption keys include the fingerprint and the public key of RSA algorithm, while the decryption keys are the fingerprint and the private key of RSA algorithm. If the users share the fingerprint, then the system will meet the basic agreement of asymmetric cryptography. The system is also applicable for the information authentication. The fingerprint as secret key is used in both the encryption and decryption processes so that the receiver can identify the authenticity of the ciphertext by using the fingerprint in decryption process. Finally, the simulation results show the validity of the encryption scheme and the high robustness against attacks based on the phase retrieval technique.

Simulation-based Assessment to Reliably Identify Key Resident Performance Attributes.

Science.gov (United States)

Blum, Richard H; Muret-Wagstaff, Sharon L; Boulet, John R; Cooper, Jeffrey B; Petrusa, Emil R; Baker, Keith H; Davidyuk, Galina; Dearden, Jennifer L; Feinstein, David M; Jones, Stephanie B; Kimball, William R; Mitchell, John D; Nadelberg, Robert L; Wiser, Sarah H; Albrecht, Meredith A; Anastasi, Amanda K; Bose, Ruma R; Chang, Laura Y; Culley, Deborah J; Fisher, Lauren J; Grover, Meera; Klainer, Suzanne B; Kveraga, Rikante; Martel, Jeffrey P; McKenna, Shannon S; Minehart, Rebecca D; Mitchell, John D; Mountjoy, Jeremi R; Pawlowski, John B; Pilon, Robert N; Shook, Douglas C; Silver, David A; Warfield, Carol A; Zaleski, Katherine L

2018-04-01

Obtaining reliable and valid information on resident performance is critical to patient safety and training program improvement. The goals were to characterize important anesthesia resident performance gaps that are not typically evaluated, and to further validate scores from a multiscenario simulation-based assessment. Seven high-fidelity scenarios reflecting core anesthesiology skills were administered to 51 first-year residents (CA-1s) and 16 third-year residents (CA-3s) from three residency programs. Twenty trained attending anesthesiologists rated resident performances using a seven-point behaviorally anchored rating scale for five domains: (1) formulate a clear plan, (2) modify the plan under changing conditions, (3) communicate effectively, (4) identify performance improvement opportunities, and (5) recognize limits. A second rater assessed 10% of encounters. Scores and variances for each domain, each scenario, and the total were compared. Low domain ratings (1, 2) were examined in detail. Interrater agreement was 0.76; reliability of the seven-scenario assessment was r = 0.70. CA-3s had a significantly higher average total score (4.9 ± 1.1 vs. 4.6 ± 1.1, P = 0.01, effect size = 0.33). CA-3s significantly outscored CA-1s for five of seven scenarios and domains 1, 2, and 3. CA-1s had a significantly higher proportion of worrisome ratings than CA-3s (chi-square = 24.1, P < 0.01, effect size = 1.50). Ninety-eight percent of residents rated the simulations more educational than an average day in the operating room. Sensitivity of the assessment to CA-1 versus CA-3 performance differences for most scenarios and domains supports validity. No differences, by experience level, were detected for two domains associated with reflective practice. Smaller score variances for CA-3s likely reflect a training effect; however, worrisome performance scores for both CA-1s and CA-3s suggest room for improvement.

Identifying Opportunities for Vertical Integration of Biochemistry and Clinical Medicine.

Science.gov (United States)

Wendelberger, Karen J.; Burke, Rebecca; Haas, Arthur L.; Harenwattananon, Marisa; Simpson, Deborah

1998-01-01

Objectives: Retention of basic science knowledge, as judged by National Board of Medical Examiners' (NBME) data, suffers due to lack of apparent relevance and isolation of instruction from clinical application, especially in biochemistry. However, the literature reveals no systematic process for identifying key biochemical concepts and associated clinical conditions. This study systematically identified difficult biochemical concepts and their common clinical conditions as a critical step towards enhancing relevance and retention of biochemistry.Methods: A multi-step/ multiple stakeholder process was used to: (1) identify important biochemistry concepts; (2) determine students' perceptions of concept difficulty; (3) assess biochemistry faculty, student, and clinical teaching scholars' perceived relevance of identified concepts; and (4) identify associated common clinical conditions for relevant and difficult concepts. Surveys and a modified Delphi process were used to gather data, subsequently analyzed using SPSS for Windows.Results: Sixteen key biochemical concepts were identified. Second year medical students rated 14/16 concepts as extremely difficult while fourth year students rated nine concepts as moderately to extremely difficult. On average, each teaching scholar generated common clinical conditions for 6.2 of the 16 concepts, yielding a set of seven critical concepts and associated clinical conditions.Conclusions: Key stakeholders in the instructional process struggle to identify biochemistry concepts that are critical, difficult to learn and associated with common clinical conditions. However, through a systematic process beginning with identification of concepts and associated clinical conditions, relevance of basic science instruction can be enhanced.

Production of Volatile Compounds in Reconstituted Milk Reduced-Fat Cheese and the Physicochemical Properties as Affected by Exopolysaccharide-Producing Strain

Directory of Open Access Journals (Sweden)

Weijun Wang

2012-12-01

Full Text Available The application of the exopolysaccharide-producing strains for improving the texture and technical properties of reduced-fat cheese looks very promising. Streptococcus thermophilus TM11 was evaluated for production of reduced-fat cheese using reconstituted milk powder (CRMP. The physicochemical analysis of fresh and stored cheeses showed that this strain slightly increased moisture content resulting in cheese with higher yield and lower protein content compared to the direct acidified cheese. The volatiles of cheese were determined by SPME and GC equipped with a mass spectrometer. The results indicated that the major compounds included aldehydes, ketones and acids, whereas, alcohols and branched-chain aldehydes that contribute to exciting and harsh flavors were not found in CRMP. By the textural profile analysis, we found the cheese made with S. thermophilus TM11 had lower cohesiveness, resilience and higher adhesiveness than the direct acidified cheese, and had similar hardness. Further, S. thermophilus TM11 greatly changed the protein matrix with more opened cavities according to observation by scanning electron microscopy. Consequently, use of S. thermophilus TM11 could endow CRMP with the novel and suitable flavor properties and improved texture quality.

Identifying key nodes in multilayer networks based on tensor decomposition.

Science.gov (United States)

Wang, Dingjie; Wang, Haitao; Zou, Xiufen

2017-06-01

The identification of essential agents in multilayer networks characterized by different types of interactions is a crucial and challenging topic, one that is essential for understanding the topological structure and dynamic processes of multilayer networks. In this paper, we use the fourth-order tensor to represent multilayer networks and propose a novel method to identify essential nodes based on CANDECOMP/PARAFAC (CP) tensor decomposition, referred to as the EDCPTD centrality. This method is based on the perspective of multilayer networked structures, which integrate the information of edges among nodes and links between different layers to quantify the importance of nodes in multilayer networks. Three real-world multilayer biological networks are used to evaluate the performance of the EDCPTD centrality. The bar chart and ROC curves of these multilayer networks indicate that the proposed approach is a good alternative index to identify real important nodes. Meanwhile, by comparing the behavior of both the proposed method and the aggregated single-layer methods, we demonstrate that neglecting the multiple relationships between nodes may lead to incorrect identification of the most versatile nodes. Furthermore, the Gene Ontology functional annotation demonstrates that the identified top nodes based on the proposed approach play a significant role in many vital biological processes. Finally, we have implemented many centrality methods of multilayer networks (including our method and the published methods) and created a visual software based on the MATLAB GUI, called ENMNFinder, which can be used by other researchers.

Key Management Infrastructure Increment 2 (KMI Inc 2)

Science.gov (United States)

2016-03-01

Infrastructure (KMI) is a unified, scalable, interoperable, and trusted infrastructure that provides net-centric key management services to systems that rely ...products to human users and devices (hereinafter referred to as "supported" or "security-enabled") to enable secure communications. The objectives for...Threshold met during Spiral 1 IOT &E and FOT&E. Connected Networks: Network Identification KMI products and services shall be provided to KMI clients via

Identifying key performance indicators in food technology contract R&D

NARCIS (Netherlands)

Flipse, S.M.; Sanden, van der M.C.A.; Velden, van der T.; Fortuin, F.T.J.M.; Omta, S.W.F.; Osseweijer, P.

2013-01-01

Innovating companies increasingly rely on outsourcing to Contract Research Organisations (CROs) for their Research and Development (R&D), which are largely understudied. This paper presents the outcome of a case study in the field of food technology contract research, identifying context

Identification of the key bitter compounds in our daily diet is a prerequisite for the understanding of the hTAS2R gene polymorphisms affecting food choice.

Science.gov (United States)

Hofmann, Thomas

2009-07-01

In order to decode genetic variations affecting food choice and to determine whether to accept or to reject certain food products, it is a necessary prerequisite to deorphanize the hTAS2R/ligand pairs using the key bitter compounds in foods as stimuli rather than doing this either by using artificial molcules, to which the normal consumer had never been exposed, or by using food-born molecules which do not at all contribute to the overall bitterness. Therefore, the chemical structure of the most active bitter molecules in foods needs to be unequivocally determined in order to be sure that hTAS2R polymorphisms are related to the key molecules which really contribute to the overall bitterness perception of food products. As most studies focused primarily on quantitatively predominating compounds, rather than selecting the target compounds to be identified with regard to taste-activity, it seems that yet unknown components play a key role in evoking the bitter taste of food products. Driven by the need to discover the key players inducing the food taste, the research area "sensomics" made tremendous efforts in recent years to map the sensometabolome and to identify the most intense taste-active metabolites in fresh and processed foods. The present article summarizes recent studies on the identification of orphan key bitter stimuli in fresh, fermented, and thermally processed foods using carrots, cheese, and roasted coffee as examples.

In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer

Science.gov (United States)

Colaprico, Antonio; Bontempi, Gianluca; Castiglioni, Isabella

2018-01-01

Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have an important role in PC development. Despite efforts to profile PC, the alterations (gene, CNA, and miRNA) and biological processes that correlate with disease development and progression remain partially elusive. Many gene signatures proposed as diagnostic or prognostic tools in cancer poorly overlap. The identification of co-expressed genes, that are functionally related, can identify a core network of genes associated with PC with a better reproducibility. By combining different approaches, including the integration of mRNA expression profiles, CNAs, and miRNA expression levels, we identified a gene signature of four genes overlapping with other published gene signatures and able to distinguish, in silico, high Gleason-scored PC from normal human tissue, which was further enriched to 19 genes by gene co-expression analysis. From the analysis of miRNAs possibly regulating this network, we found that hsa-miR-153 was highly connected to the genes in the network. Our results identify a four-gene signature with diagnostic and prognostic value in PC and suggest an interesting gene network that could play a key regulatory role in PC development and progression. Furthermore, hsa-miR-153, controlling this network, could be a potential biomarker for theranostics in high Gleason-scored PC. PMID:29562723

Evaluation of unique identifiers used for citation linking [version 1; referees: 1 approved, 2 approved with reservations

Directory of Open Access Journals (Sweden)

Heidi Holst Madsen

2016-06-01

Full Text Available Unique identifiers (UID are seen as an effective tool to create links between identical publications in databases or identify duplicates in a database. The purpose of the present study is to investigate how well UIDs work for citation linking. We have two objectives: Explore the coverage, precision, and characteristics of publications matched versus not matched with UIDs as the match key.   Illustrate how publication sets formed by using UIDs as the match key may affect the bibliometric indicators: Number of publications, number of citations and the average number of citations per publication.   The objectives are addressed in a literature review and a case study. The literature review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (DOI, incorrect DOIs in reference lists and databases, DOIs not registered by the database where a bibliometric analysis is performed, and erroneous optical or special character recognition.   The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character recognition in our publication sets. In particular the duplicate DOIs constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation of average number of citations per publication.   The use of UIDs as a match key in citation linking is implemented in many settings, and the availability of UIDs may become critical for the inclusion of a publication or a database in a bibliometric analysis.

Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes

Science.gov (United States)

McNay, Ewan C.; Recknagel, Andrew K.

2011-01-01

Understanding of the role of insulin in the brain has gradually expanded, from initial conceptions of the brain as insulin-insensitive through identification of a role in regulation of feeding to recent demonstration of insulin as a key component of hippocampal memory processes. Conversely, systemic insulin resistance such as that seen in type 2 diabetes is associated with a range of cogntive and neural deficits. Here we review the evidence for insulin as a cognitive and neural modulator, including potential effector mechanisms, and examine the impact that type 2 diabetes has on these mechanisms in order to identify likely bases for the cognitive impairments seen in type 2 diabetic patients. PMID:21907815

Key Drivers for Cooperation toward Sustainable Development and the Management of CO2 Emissions: Comparative Analysis of Six Northeast Asian Countries

Directory of Open Access Journals (Sweden)

Andrew Chapman

2018-01-01

Full Text Available This study analyzes the key drivers of the relationship between economic growth and carbon emissions in six Northeast Asian countries (China, Japan, Republic of Korea, Democratic People’s Republic of Korea, Mongolia, and Russia from 1991 to 2015. We apply a decomposition analysis approach using Logarithmic Mean Divisia Index to identify the main contributing factors toward CO2 emission changes. To discuss the decomposition results in more in detail, we explain the energy portfolio change in each country to understand the energy and resource utilization strategy. From the results, we find that the key driving factors of CO2 emissions change and energy portfolio trends are different among Northeast Asian countries, driven by economic growth in China and Korea, reduced by energy efficiency improvements in Russia and the DPRK, while being relatively benign in Japan and Mongolia due to a combination of these factors. This result implies that we can better understand the regional cooperation policy for improving each driving factor to achieve sustainable development and management of CO2 emissions considering the characteristics of each country.

A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress

DEFF Research Database (Denmark)

Surma, Michal A; Klose, Christian; Peng, Debby

2013-01-01

Biological membranes are complex, and the mechanisms underlying their homeostasis are incompletely understood. Here, we present a quantitative genetic interaction map (E-MAP) focused on various aspects of lipid biology, including lipid metabolism, sorting, and trafficking. This E-MAP contains ∼250......,000 negative and positive genetic interaction scores and identifies a molecular crosstalk of protein quality control pathways with lipid bilayer homeostasis. Ubx2p, a component of the endoplasmic-reticulum-associated degradation pathway, surfaces as a key upstream regulator of the essential fatty acid (FA...

Identification of Key Indicators for Sustainable Construction Materials

Directory of Open Access Journals (Sweden)

Humphrey Danso

2018-01-01

Full Text Available Studies on sustainable construction materials are on the rise with their environmental, social, and economic benefits. This study identifies the key indicators for measuring sustainable construction materials. The design used for the study was that of a survey which relied on a questionnaire with five-point Likert scale to generate data for the analysis. For this purpose, 25 indicators from the three dimensions (environmental, social, and economic identified from the literature were presented to the respondents in a structured questionnaire, and responses were collected and analysed using SPSS. The study identified three key environmental indicators for measuring sustainable construction materials, and these indicators are human toxicity, climate change, and solid waste. Furthermore, adaptability, thermal comfort, local resources, and housing for all were identified as the four key social indicators for sustainable construction materials. In addition, maintenance cost, operational cost, initial cost, long-term savings, and life span were found to be the five key economic indicators for measuring sustainable construction materials. The study therefore suggests that these twelve indicators should be considered in future studies that seek to measure sustainable construction materials.

Superfund TIO videos. Set A. Identifying PRPS. Removal process: Removal site evaluation. Part 2. Audio-Visual

International Nuclear Information System (INIS)

1990-01-01

The videotape is divided into three sections. Section 1 details the liability of Potentially Responsible Parties (PRPs) and describes the four classes of PRPs: current owners and operators, former owners and operators, generators, and transporters (if they selected the site). Section 2 lists the goals of the Potentially Responsible Party (PRP) search and explains how to identify key players during the PRP search. How to plan and conduct the PRP search is also outlined. Section 3 outlines the steps involved in conducting a removal site evaluation. A discussion of when to conduct a removal preliminary assessment, a removal site inspection, and an Engineering Evaluation/Cost Analysis (EE/AC) also is covered

Digest of Key Science and Engineering Indicators, 2008. NSB-08-2

Science.gov (United States)

National Science Foundation, 2008

2008-01-01

This digest of key science and engineering indicators draws primarily from the National Science Board's two-volume "Science and Engineering Indicators, 2008" report. The digest serves two purposes: (1) to draw attention to important trends and data points from across the chapters and volumes of "Science and Engineering Indicators, 2008," and (2)…

Nuclear import of human MLH1, PMS2, and MutLalpha: redundancy is the key.

Science.gov (United States)

Leong, Vivian; Lorenowicz, Jessica; Kozij, Natalie; Guarné, Alba

2009-08-01

DNA mismatch repair maintains genomic stability by correcting errors that have escaped polymerase proofreading. Defects on mismatch repair genes lead to an increased mutation rate, microsatellite instability and predisposition to human non-polyposis colorectal cancer (HNPCC). Human MutLalpha is a heterodimer formed by the interaction of MLH1 and PMS2 that coordinates a series of key events in mismatch repair. It has been proposed that nuclear import of MutLalpha may be the first regulatory step on the activation of the mismatch repair pathway. Using confocal microscopy and mismatch repair deficient cells, we have identified the sequence determinants that drive nuclear import of human MLH1, PMS2, and MutLalpha. Transient transfection of the individual proteins reveals that MLH1 has a bipartite and PMS2 has a single monopartite nuclear localization signal. Although dimerization is not required for nuclear localization, the MutLalpha heterodimer is imported more efficiently than the MLH1 or PMS2 monomers. Interestingly, the bipartite localization signal of MLH1 can direct import of MutLalpha even when PMS2 encompasses a mutated localization signal. Hence we conclude that the presence of redundant nuclear localization signals guarantees nuclear transport of MutLalpha and, consequently, efficient mismatch repair.

KDiamend: a package for detecting key drivers in a molecular ecological network of disease.

Science.gov (United States)

Lyu, Mengxuan; Chen, Jiaxing; Jiang, Yiqi; Dong, Wei; Fang, Zhou; Li, Shuaicheng

2018-04-11

Microbial abundance profiles are applied widely to understand diseases from the aspect of microbial communities. By investigating the abundance associations of species or genes, we can construct molecular ecological networks (MENs). The MENs are often constructed by calculating the Pearson correlation coefficient (PCC) between genes. In this work, we also applied multimodal mutual information (MMI) to construct MENs. The members which drive the concerned MENs are referred to as key drivers. We proposed a novel method to detect the key drivers. First, we partitioned the MEN into subnetworks. Then we identified the most pertinent subnetworks to the disease by measuring the correlation between the abundance pattern and the delegated phenotype-the variable representing the disease phenotypes. Last, for each identified subnetwork, we detected the key driver by PageRank. We developed a package named KDiamend and applied it to the gut and oral microbial data to detect key drivers for Type 2 diabetes (T2D) and Rheumatoid Arthritis (RA). We detected six T2D-relevant subnetworks and three key drivers of them are related to the carbohydrate metabolic process. In addition, we detected nine subnetworks related to RA, a disease caused by compromised immune systems. The extracted subnetworks include InterPro matches (IPRs) concerned with immunoglobulin, Sporulation, biofilm, Flaviviruses, bacteriophage, etc., while the development of biofilms is regarded as one of the drivers of persistent infections. KDiamend is feasible to detect key drivers and offers insights to uncover the development of diseases. The package is freely available at http://www.deepomics.org/pipelines/3DCD6955FEF2E64A/ .

Identifying Key Factors Relevant for Base Camp Siting

Science.gov (United States)

2017-12-01

centers. 3.2.6.3 Religious and historical sites Respecting sacred sites helps build rapport with the host nation. 3.2.6.4 Local infrastructure...churches, mosques, national libraries, hospitals, cemeteries, historical ruins, religious sites, cultural areas, and other protected sites...controlled and protected wells. • Electricity: town engineer • Academic: government and religious leaders • Trash: private business (local

Language Learning at Key Stage 2: Findings from a Longitudinal Study

Science.gov (United States)

Cable, Carrie; Driscoll, Patricia; Mitchell, Rosamond; Sing, Sue; Cremin, Teresa; Earl, Justine; Eyres, Ian; Holmes, Bernardette; Martin, Cynthia; Heins, Barbara

2012-01-01

This paper discusses some of the findings from a 3-year longitudinal study of language learning in the upper stage of English primary schools, i.e. at Key Stage 2. This largely qualitative study (commissioned by the then Department for Children, Schools and Families) was designed to explore and document developing provision and practice in a…

Investigating key beliefs guiding mothers' dietary decisions for their 2-3 year old.

Science.gov (United States)

Spinks, Teagan; Hamilton, Kyra

2015-06-01

Currently, there is no research in Australia that systematically investigates the underlying beliefs for mothers' decisions regarding their young child's nutritional needs based on current guidelines. We aimed to determine, using a Theory of Planned Behaviour (TPB) belief-based approach, key beliefs that guide mothers' decisions with regards to: (a) providing their child with a wide range of foods from the five food groups ('healthy eating'); and (b) limiting their child's intake of 'discretionary choices' (e.g. lollies). Mothers (N = 197, M age = 34.39, SD = 5.65) completed a main questionnaire either online or on hard copy (paper-based), with a 1-week phone follow-up of the target behaviours (N = 161). Correlations and multiple regression analyses were conducted, and a number of key behavioural, normative, and control beliefs emerged for both healthy eating and discretionary choice behaviours. For healthy eating, mothers identified behavioural beliefs 'improving my child's health' and 'resistance from my child'; normative beliefs 'other family members' and 'spouse/partner'; and control beliefs 'child's food preferences'. For discretionary choices, behavioural beliefs 'maintain consistent energy levels in my child' for intentions, and 'give my child their required nutritional intake'; normative beliefs 'spouse/partner', 'healthcare professionals' and 'friends'; and control beliefs 'child's food preferences' were identified. These findings can inform the development of future intervention programmes aimed at modifying mothers' child feeding practices to encourage healthy eating and limit discretionary choice intake and, ultimately, increase the life expectancy of the current generation of children. Copyright © 2015 Elsevier Ltd. All rights reserved.

An 8-year old boy with continuous spikes and waves during slow sleep presenting with positive onconeuronal antibodies.

Science.gov (United States)

Hu, Lin-Yan; Shi, Xiu-Yu; Feng, Chen; Wang, Jian-Wen; Yang, Guan; Lammers, Stephen H T; Yang, Xiao Fan; Ebrahimi-Fakhari, Darius; Zou, Li-Ping

2015-03-01

To determine the etiology of epilepsy with continuous spikes and waves during slow sleep (CSWS)/electrical status epilepticus during sleep (ESES) in an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus. A combination of clinical characterization and follow-up, video EEG and laboratory investigations. We report the case of an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus, who presented with intellectual disability, pharmacotherapy-resistant epilepsy and CSWS/ESES. Although the patient's neuroblastoma had been successfully treated 8 years prior to presentation and an extensive workup did not show a tumor reoccurrence, testing for onconeuronal antibodies was positive for anti-Ma2 and anti-CV2/CRMP5 antibodies. High-dose intravenous methylprednisolone and a taper of oral methylprednisolone were given, leading to a significant clinical improvement. During the taper the patient's condition and EEG manifestations deteriorated again necessitating another cycle of steroid therapy, which lead to a stable improvement. During a 6-month follow-up no CSWS/ESES was seen on EEG and anti-Ma2 and anti-CV2/CRMP5 antibodies remained undetectable. This case suggests that onconeuronal antibodies may be involved in the pathogenesis of CSWS/ESES. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The building blocks of a 'Liveable Neighbourhood': Identifying the key performance indicators for walking of an operational planning policy in Perth, Western Australia.

Science.gov (United States)

Hooper, Paula; Knuiman, Matthew; Foster, Sarah; Giles-Corti, Billie

2015-11-01

Planning policy makers are requesting clearer guidance on the key design features required to build neighbourhoods that promote active living. Using a backwards stepwise elimination procedure (logistic regression with generalised estimating equations adjusting for demographic characteristics, self-selection factors, stage of construction and scale of development) this study identified specific design features (n=16) from an operational planning policy ("Liveable Neighbourhoods") that showed the strongest associations with walking behaviours (measured using the Neighbourhood Physical Activity Questionnaire). The interacting effects of design features on walking behaviours were also investigated. The urban design features identified were grouped into the "building blocks of a Liveable Neighbourhood", reflecting the scale, importance and sequencing of the design and implementation phases required to create walkable, pedestrian friendly developments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation of deuteriated adipic [2H2]-, [2H4]-, [2H6]-, and [2H8]-acids by use of Kolbe electrolysis as a key reaction

International Nuclear Information System (INIS)

Tashiro, Masahi; Tsuzuki, Hirohisa; Mataka, Shuntaro; Goto, Hideyuki; Ogasahara, Shoji

1990-01-01

Using Kolbe electrolysis of methyl hydrogen [ 2 H 0 ]-, [ 2 H 2 ]-, and [ 2 H 4 ]-succinates as a key reaction, adipic [2,2- 2 H 2 ]-, [2,3- 2 H 2 ]-, [2,2,3,3- 2 H 4 ]-, [2,3,4,5- 2 H 4 ]-, [2,3,5,5- 2 H 4 ]-, [2,2,3,3,5,5- 2 H 6 ]-, and [2,2,3,3,4,4,5,5- 2 H 8 ]-acids were prepared in high deuterium contents. (author)

75 FR 17463 - Key West Bank, Key West, Florida; Notice of Appointment of Receiver

Science.gov (United States)

2010-04-06

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision Key West Bank, Key West, Florida; Notice... section 5(d)(2) of the Home Owners' Loan Act, the Office of Thrift Supervision has duly appointed the Federal Deposit Insurance Corporation as sole Receiver for Key West Bank, Key West, Florida, (OTS No...

Hillslope characterization: Identifying key controls on local-scale plant communities' distribution using remote sensing and subsurface data fusion.

Science.gov (United States)

Falco, N.; Wainwright, H. M.; Dafflon, B.; Leger, E.; Peterson, J.; Steltzer, H.; Wilmer, C.; Williams, K. H.; Hubbard, S. S.

2017-12-01

Mountainous watershed systems are characterized by extreme heterogeneity in hydrological and pedological properties that influence biotic activities, plant communities and their dynamics. To gain predictive understanding of how ecosystem and watershed system evolve under climate change, it is critical to capture such heterogeneity and to quantify the effect of key environmental variables such as topography, and soil properties. In this study, we exploit advanced geophysical and remote sensing techniques - coupled with machine learning - to better characterize and quantify the interactions between plant communities' distribution and subsurface properties. First, we have developed a remote sensing data fusion framework based on the random forest (RF) classification algorithm to estimate the spatial distribution of plant communities. The framework allows the integration of both plant spectral and structural information, which are derived from multispectral satellite images and airborne LiDAR data. We then use the RF method to evaluate the estimated plant community map, exploiting the subsurface properties (such as bedrock depth, soil moisture and other properties) and geomorphological parameters (such as slope, curvature) as predictors. Datasets include high-resolution geophysical data (electrical resistivity tomography) and LiDAR digital elevation maps. We demonstrate our approach on a mountain hillslope and meadow within the East River watershed in Colorado, which is considered to be a representative headwater catchment in the Upper Colorado Basin. The obtained results show the existence of co-evolution between above and below-ground processes; in particular, dominant shrub communities in wet and flat areas. We show that successful integration of remote sensing data with geophysical measurements allows identifying and quantifying the key environmental controls on plant communities' distribution, and provides insights into their potential changes in the future

End-to-End Key Exchange through Disjoint Paths in P2P Networks

Directory of Open Access Journals (Sweden)

Daouda Ahmat

2015-01-01

Full Text Available Due to their inherent features, P2P networks have proven to be effective in the exchange of data between autonomous peers. Unfortunately, these networks are subject to various security threats that cannot be addressed readily since traditional security infrastructures, which are centralized, cannot be applied to them. Furthermore, communication reliability across the Internet is threatened by various attacks, including usurpation of identity, eavesdropping or traffic modification. Thus, in order to overcome these security issues and allow peers to securely exchange data, we propose a new key management scheme over P2P networks. Our approach introduces a new method that enables a secret key exchange through disjoint paths in the absence of a trusted central coordination point which would be required in traditional centralized security systems.

Invertase SUC2 Is the Key Hydrolase for Inulin Degradation in Saccharomyces cerevisiae

OpenAIRE

Wang, Shi-An; Li, Fu-Li

2013-01-01

Specific Saccharomyces cerevisiae strains were recently found to be capable of efficiently utilizing inulin, but genetic mechanisms of inulin hydrolysis in yeast remain unknown. Here we report functional characteristics of invertase SUC2 from strain JZ1C and demonstrate that SUC2 is the key enzyme responsible for inulin metabolism in S. cerevisiae.

Identification of okadaic acid-induced phosphorylation events by a mass spectrometry approach

International Nuclear Information System (INIS)

Hill, Jennifer J.; Callaghan, Deborah A.; Ding Wen; Kelly, John F.; Chakravarthy, Balu R.

2006-01-01

Okadaic acid (OA) is a widely used small-molecule phosphatase inhibitor that is thought to selectively inhibit protein phosphatase 2A (PP2A). Multiple studies have demonstrated that PP2A activity is compromised in Brains of Alzheimer's disease patients. Thus, we set out to determine changes in phosphorylation that occur upon OA treatment of neuronal cells. Utilizing isotope-coded affinity tags and mass spectrometry analysis, we determined the relative abundance of proteins in a phosphoprotein enriched fraction from control and OA-treated primary cortical neurons. We identified many proteins whose phosphorylation state is regulated by OA, including glycogen synthase kinase 3β, collapsin-response mediator proteins (DRP-2, DPYSL-5, and CRMP-4), and the B subunit of PP2A itself. Most interestingly, we have found that complexin 2, an important regulator of neurotransmitter release and synaptic plasticity, is phosphorylated at serine 93 upon OA treatment of neurons. This is First report of a phosphorylation site on complexin 2

Labont? Identifies Key Issues for Health Promoters in the New World Order

OpenAIRE

Raphael, Dennis

2016-01-01

For over 35 years Ronald Labonté has been critically analyzing the state of health promotion in Canada and the world. In 1981, he identified the shortcomings of the groundbreaking Lalonde Report by warning of the seductive appeal of so-called lifestyle approaches to health. Since then, he has left a trail of critical work identifying the barriers to — and opportunities for —health promotion work. More recently, he has shown how the rise of economic globalization and acceptance of neo-liberal ...

Characteristics of evolving models of care for arthritis: A key informant study

Directory of Open Access Journals (Sweden)

Veinot Paula

2008-07-01

Full Text Available Abstract Background The burden of arthritis is increasing in the face of diminishing health human resources to deliver care. In response, innovative models of care delivery are developing to facilitate access to quality care. Most models have developed in response to local needs with limited evaluation. The primary objective of this study is to a examine the range of models of care that deliver specialist services using a medical/surgical specialist and at least one other health care provider and b document the strengths and challenges of the identified models. A secondary objective is to identify key elements of best practice models of care for arthritis. Methods Semi-structured interviews were conducted with a sample of key informants with expertise in arthritis from jurisdictions with primarily publicly-funded health care systems. Qualitative data were analyzed using a constant comparative approach to identify common types of models of care, strengths and challenges of models, and key components of arthritis care. Results Seventy-four key informants were interviewed from six countries. Five main types of models of care emerged. 1 Specialized arthritis programs deliver comprehensive, multidisciplinary team care for arthritis. Two models were identified using health care providers (e.g. nurses or physiotherapists in expanded clinical roles: 2 triage of patients with musculoskeletal conditions to the appropriate services including specialists; and 3 ongoing management in collaboration with a specialist. Two models promoting rural access were 4 rural consultation support and 5 telemedicine. Key informants described important components of models of care including knowledgeable health professionals and patients. Conclusion A range of models of care for arthritis have been developed. This classification can be used as a framework for discussing care delivery. Areas for development include integration of care across the continuum, including primary

Maintained activity of glycogen synthase kinase-3β despite of its phosphorylation at serine-9 in okadaic acid-induced neurodegenerative model

International Nuclear Information System (INIS)

Lim, Yong-Whan; Yoon, Seung-Yong; Choi, Jung-Eun; Kim, Sang-Min; Lee, Hui-Sun; Choe, Han; Lee, Seung-Chul; Kim, Dong-Hou

2010-01-01

Glycogen synthase kinase-3β (GSK3β) is recognized as one of major kinases to phosphorylate tau in Alzheimer's disease (AD), thus lots of AD drug discoveries target GSK3β. However, the inactive form of GSK3β which is phosphorylated at serine-9 is increased in AD brains. This is also inconsistent with phosphorylation status of other GSK3β substrates, such as β-catenin and collapsin response mediator protein-2 (CRMP2) since their phosphorylation is all increased in AD brains. Thus, we addressed this paradoxical condition of AD in rat neurons treated with okadaic acid (OA) which inhibits protein phosphatase-2A (PP2A) and induces tau hyperphosphorylation and cell death. Interestingly, OA also induces phosphorylation of GSK3β at serine-9 and other substrates including tau, β-catenin and CRMP2 like in AD brains. In this context, we observed that GSK3β inhibitors such as lithium chloride and 6-bromoindirubin-3'-monoxime (6-BIO) reversed those phosphorylation events and protected neurons. These data suggest that GSK3β may still have its kinase activity despite increase of its phosphorylation at serine-9 in AD brains at least in PP2A-compromised conditions and that GSK3β inhibitors could be a valuable drug candidate in AD.

Identifying key conservation threats to Alpine birds through expert knowledge

Science.gov (United States)

Pedrini, Paolo; Brambilla, Mattia; Rolando, Antonio; Girardello, Marco

2016-01-01

Alpine biodiversity is subject to a range of increasing threats, but the scarcity of data for many taxa means that it is difficult to assess the level and likely future impact of a given threat. Expert opinion can be a useful tool to address knowledge gaps in the absence of adequate data. Experts with experience in Alpine ecology were approached to rank threat levels for 69 Alpine bird species over the next 50 years for the whole European Alps in relation to ten categories: land abandonment, climate change, renewable energy, fire, forestry practices, grazing practices, hunting, leisure, mining and urbanization. There was a high degree of concordance in ranking of perceived threats among experts for most threat categories. The major overall perceived threats to Alpine birds identified through expert knowledge were land abandonment, urbanization, leisure and forestry, although other perceived threats were ranked highly for particular species groups (renewable energy and hunting for raptors, hunting for gamebirds). For groups of species defined according to their breeding habitat, open habitat species and treeline species were perceived as the most threatened. A spatial risk assessment tool based on summed scores for the whole community showed threat levels were highest for bird communities of the northern and western Alps. Development of the approaches given in this paper, including addressing biases in the selection of experts and adopting a more detailed ranking procedure, could prove useful in the future in identifying future threats, and in carrying out risk assessments based on levels of threat to the whole bird community. PMID:26966659

Identifying key conservation threats to Alpine birds through expert knowledge

Directory of Open Access Journals (Sweden)

Dan E. Chamberlain

2016-02-01

Full Text Available Alpine biodiversity is subject to a range of increasing threats, but the scarcity of data for many taxa means that it is difficult to assess the level and likely future impact of a given threat. Expert opinion can be a useful tool to address knowledge gaps in the absence of adequate data. Experts with experience in Alpine ecology were approached to rank threat levels for 69 Alpine bird species over the next 50 years for the whole European Alps in relation to ten categories: land abandonment, climate change, renewable energy, fire, forestry practices, grazing practices, hunting, leisure, mining and urbanization. There was a high degree of concordance in ranking of perceived threats among experts for most threat categories. The major overall perceived threats to Alpine birds identified through expert knowledge were land abandonment, urbanization, leisure and forestry, although other perceived threats were ranked highly for particular species groups (renewable energy and hunting for raptors, hunting for gamebirds. For groups of species defined according to their breeding habitat, open habitat species and treeline species were perceived as the most threatened. A spatial risk assessment tool based on summed scores for the whole community showed threat levels were highest for bird communities of the northern and western Alps. Development of the approaches given in this paper, including addressing biases in the selection of experts and adopting a more detailed ranking procedure, could prove useful in the future in identifying future threats, and in carrying out risk assessments based on levels of threat to the whole bird community.

The contributing factors of business process strategy on customer ...

African Journals Online (AJOL)

Journal Home > Vol 10, No 5S (2018) > ... The tremendous of customer relationship management performance are frolicking a progressively ... factors that donate to the CRMP subjected to operative, resourceful and advanced execution.

Setting Organizational Key Performance Indicators in the Precision Machine Industry

Directory of Open Access Journals (Sweden)

Mei-Hsiu Hong

2015-11-01

Full Text Available The aim of this research is to define (or set organizational key performance indicators (KPIs in the precision machine industry using the concept of core competence and the supply chain operations reference (SCOR model. The research is conducted in three steps. In the first step, a benchmarking study is conducted to collect major items of core competence and to group them into main categories in order to form a foundation for the research. In the second step, a case company questionnaire and interviews are conducted to identify the key factors of core competence in the precision machine industry. The analysis is conducted based on four dimensions and hence several analysis rounds are completed. Questionnaire data is analyzed with grey relational analysis (GRA and resulted in 5–6 key factors in each dimension or sub-dimension. Based on the conducted interviews, 13 of these identified key factors are separated into one organization objective, five key factors of core competence and seven key factors of core ability. In the final step, organizational KPIs are defined (or set for the five identified key factors of core competence. The most competitive core abilities for each of the five key factors are established. After that, organizational KPIs are set based on the core abilities within 3 main categories of KPIs (departmental, office grade and hierarchal for each key factor. The developed KPI system based on organizational objectives, core competences, and core abilities allow enterprises to handle dynamic market demand and business environments, as well as changes in overall corporate objectives.

Use of gas chromatography-olfactometry to identify key odorant compounds in dark chocolate. Comparison of samples before and after conching.

Science.gov (United States)

Counet, Christine; Callemien, Delphine; Ouwerx, Caroline; Collin, Sonia

2002-04-10

After vacuum distillation and liquid-liquid extraction, the volatile fractions of dark chocolates were analyzed by gas chromatography-olfactometry and gas chromatography-mass spectrometry. Aroma extract dilution analysis revealed the presence of 33 potent odorants in the neutral/basic fraction. Three of these had a strong chocolate flavor: 2-methylpropanal, 2-methylbutanal, and 3-methylbutanal. Many others were characterized by cocoa/praline-flavored/nutty/coffee notes: 2,3-dimethylpyrazine, trimethylpyrazine, tetramethylpyrazine, 3(or 2),5-dimethyl-2(or 3)-ethylpyrazine, 3,5(or 6)-diethyl-2-methylpyrazine, and furfurylpyrrole. Comparisons carried out before and after conching indicate that although no new key odorant is synthesized during the heating process, levels of 2-phenyl-5-methyl-2-hexenal, Furaneol, and branched pyrazines are significantly increased while most Strecker aldehydes are lost by evaporation.

The Geo-strategies and Global Peace of Technology on Customer Relationship Management Performance: A Pilot Study among SME’s Logistic Operators

Directory of Open Access Journals (Sweden)

Muhamad Fairos Mohamad Shah

2017-12-01

Full Text Available Small and medium enterprises (SMEs are playing an increasingly important role in sustaining geo strategies and global peace economic growth and logistic system in Malaysia. SMEs also play a very crucial role in customer relationship as they may serve the roles of customer, distributor producer and supplier. However, adaption of customer relationship in Malaysian SMEs has not been fully explored. CRMP model for logistic service presents the combination of technology strategy in term of geo strategies and global peace. The goal of this study is to investigate customer relationship management performance and technology strategy. The dimensions for technology factors are Support information system, information sharing, Usefulness, care/help, ease of use, service portfolio, security and Update System. The populations of study were customers from a logistic company located in Pulau Pinang. Simple random sampling was selected from the target populations. Data collection resulted in 100 respondents to answers questionnaire from the customers of logistic company. Based on the finding, the result showed that, technology strategies are anchor factors in determining geo strategies and global peace on customer relationship management performance. Further study has important managerial implications as the findings will enable management of SMEs to understand progressive and highly varied CRMP practices and contextual factors that contribute to the CRMP as well as geo strategies and global peace and innovative implementation.

SUPPLY CHAIN MANAGEMENT – KEY FACTORS

Directory of Open Access Journals (Sweden)

Magdalena Daniela DINU

2014-06-01

Full Text Available This paper exposes Supply Chain Management by its key factors. Briefly, where the Supply Chain Management is treated as strategic part of a company then maintaining both control and influence throughout the entire supply chain are key factors and critical to success. On the other hand, finding the right partner to manage the non-strategic Supply Chains would be another key factor too. To define the most important key factors within Supply Chain Management means a deeply understanding of both Supply Chain’ s components, procedures, workflow, processes and the importance of Supply Chain Management into maximizing company's value. SCORE model able to provide solid information about measuring performance and identifying priorities within Supply Chain Management will help us to understand the key factors by analyzing its elements: Plan, Source, Make, Deliver,Return, Enable. These elements covers all the challenging areas from first to third tier of Supply Chain Management.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Science.gov (United States)

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; van der Veen, JP Wietze; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W.; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R.; Santorico, Stephanie A; Spritz, Richard A

2016-01-01

Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes1, with epidemiologic association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment. PMID:27723757

Key drivers of airline loyalty.

Science.gov (United States)

Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

2011-10-01

This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty.

LOCKS AND KEYS SERVICE

CERN Multimedia

Locks and Keys Service

2002-01-01

The Locks and Keys service (ST/FM) will move from building 55 to building 570 from the 2nd August to the 9th August 2002 included. During this period the service will be closed. Only in case of extreme urgency please call the 164550. Starting from Monday, 12th August, the Locks and Keys Service will continue to follow the activities related to office keys (keys and locks) and will provide the keys for furniture. The service is open from 8h30 to 12h00 and from 13h00 to 17h30. We remind you that your divisional correspondents can help you in the execution of the procedures. We thank you for your comprehension and we remain at your service to help you in solving all the matters related to keys for offices and furniture. Locks and Keys Service - ST Division - FM Group

The E2F transcription factors: key regulators of cell proliferation

DEFF Research Database (Denmark)

Müller, H; Helin, K

2000-01-01

Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression....... It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has...

Key Research Issues in Clostridium difficile

Directory of Open Access Journals (Sweden)

George Zhanel

2005-01-01

Full Text Available Clostridium difficile is an emerging pathogen that causes C difficile-associated diarrhea, an important nosocomial infection. Control of this infection remains a challenge, and much needs to be determined about the antimicrobial resistance of the organism, antibiotic stewardship, contamination of the patient environment, and various host factors that determine susceptibility or resistance to infection. A national symposium focusing on C difficile infections, the Clostridium difficile Symposium on Emerging Issues and Research, was hosted on November 23, 2004, by the Department of Medical Microbiology and Infectious Diseases at the University of Manitoba, Winnipeg, Manitoba, in partnership with the Canadian Institutes of Health Research. This symposium, which aimed to summarize key research issues regarding C difficile infections in Canada, had the following objectives: to provide a forum for learning and discussion about C difficile and its impact on the health of Canadians; to identify the key research issues that should be addressed; and to explore potential research funding opportunities and collaboration. The present report summarizes key research issues identified for C difficile infections in Canada by addressing four major themes: diagnosis and surveillance, infection prevention and control, antibiotic stewardship, and clinical management.

Soil fauna: key to new carbon models

OpenAIRE

Filser, Juliane; Faber, Jack H.; Tiunov, Alexei V.; Brussaard, Lijbert; Frouz, Jan; Deyn, Gerlinde; Uvarov, Alexei V.; Berg, Matty P.; Lavelle, Patrick; Loreau, Michel; Wall, Diana H.; Querner, Pascal; Eijsackers, Herman; Jiménez, Juan José

2016-01-01

Soil organic matter (SOM) is key to maintaining soil fertility, mitigating climate change, combatting land degradation, and conserving above- and below-ground biodiversity and associated soil processes and ecosystem services. In order to derive management options for maintaining these essential services provided by soils, policy makers depend on robust, predictive models identifying key drivers of SOM dynamics. Existing SOM models and suggested guidelines for future SOM modelling are defined ...

Evaluating predictive models for solar energy growth in the US states and identifying the key drivers

Science.gov (United States)

Chakraborty, Joheen; Banerji, Sugata

2018-03-01

Driven by a desire to control climate change and reduce the dependence on fossil fuels, governments around the world are increasing the adoption of renewable energy sources. However, among the US states, we observe a wide disparity in renewable penetration. In this study, we have identified and cleaned over a dozen datasets representing solar energy penetration in each US state, and the potentially relevant socioeconomic and other factors that may be driving the growth in solar. We have applied a number of predictive modeling approaches - including machine learning and regression - on these datasets over a 17-year period and evaluated the relative performance of the models. Our goals were: (1) identify the most important factors that are driving the growth in solar, (2) choose the most effective predictive modeling technique for solar growth, and (3) develop a model for predicting next year’s solar growth using this year’s data. We obtained very promising results with random forests (about 90% efficacy) and varying degrees of success with support vector machines and regression techniques (linear, polynomial, ridge). We also identified states with solar growth slower than expected and representing a potential for stronger growth in future.

Identification of key residues for protein conformational transition using elastic network model.

Science.gov (United States)

Su, Ji Guo; Xu, Xian Jin; Li, Chun Hua; Chen, Wei Zu; Wang, Cun Xin

2011-11-07

Proteins usually undergo conformational transitions between structurally disparate states to fulfill their functions. The large-scale allosteric conformational transitions are believed to involve some key residues that mediate the conformational movements between different regions of the protein. In the present work, a thermodynamic method based on the elastic network model is proposed to predict the key residues involved in protein conformational transitions. In our method, the key functional sites are identified as the residues whose perturbations largely influence the free energy difference between the protein states before and after transition. Two proteins, nucleotide binding domain of the heat shock protein 70 and human/rat DNA polymerase β, are used as case studies to identify the critical residues responsible for their open-closed conformational transitions. The results show that the functionally important residues mainly locate at the following regions for these two proteins: (1) the bridging point at the interface between the subdomains that control the opening and closure of the binding cleft; (2) the hinge region between different subdomains, which mediates the cooperative motions between the corresponding subdomains; and (3) the substrate binding sites. The similarity in the positions of the key residues for these two proteins may indicate a common mechanism in their conformational transitions.

Security of Color Image Data Designed by Public-Key Cryptosystem Associated with 2D-DWT

Science.gov (United States)

Mishra, D. C.; Sharma, R. K.; Kumar, Manish; Kumar, Kuldeep

2014-08-01

In present times the security of image data is a major issue. So, we have proposed a novel technique for security of color image data by public-key cryptosystem or asymmetric cryptosystem. In this technique, we have developed security of color image data using RSA (Rivest-Shamir-Adleman) cryptosystem with two-dimensional discrete wavelet transform (2D-DWT). Earlier proposed schemes for security of color images designed on the basis of keys, but this approach provides security of color images with the help of keys and correct arrangement of RSA parameters. If the attacker knows about exact keys, but has no information of exact arrangement of RSA parameters, then the original information cannot be recovered from the encrypted data. Computer simulation based on standard example is critically examining the behavior of the proposed technique. Security analysis and a detailed comparison between earlier developed schemes for security of color images and proposed technique are also mentioned for the robustness of the cryptosystem.

Identifying Key Features of Student Performance in Educational Video Games and Simulations through Cluster Analysis

Science.gov (United States)

Kerr, Deirdre; Chung, Gregory K. W. K.

2012-01-01

The assessment cycle of "evidence-centered design" (ECD) provides a framework for treating an educational video game or simulation as an assessment. One of the main steps in the assessment cycle of ECD is the identification of the key features of student performance. While this process is relatively simple for multiple choice tests, when…

An Integrated Strategy to Identify Key Genes in Almond Adventitious Shoot Regeneration

Science.gov (United States)

Plant genetic transformation usually depends on efficient adventitious regeneration systems. In almond (Prunus dulcis Mill.), regeneration of transgenic adventitious shoots was achieved but with low efficiency. Histological studies identified two main stages of organogenesis in almond explants that ...

Improving the key biodiversity areas approach for effective conservation planning

CSIR Research Space (South Africa)

Knight, AT

2007-03-01

Full Text Available The key biodiversity areas (KBA) approach aims to identify globally important areas for species conservation. Although a similar methodology has been used successfully to identify important Bird Areas, the authors have identified five limitations...

Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

Directory of Open Access Journals (Sweden)

Gaora Peadar Ó

2010-10-01

Full Text Available Abstract Background Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of

Identification of the key ecological factors influencing vegetation degradation in semi-arid agro-pastoral ecotone considering spatial scales

Science.gov (United States)

Peng, Yu; Wang, Qinghui; Fan, Min

2017-11-01

When assessing re-vegetation project performance and optimizing land management, identification of the key ecological factors inducing vegetation degradation has crucial implications. Rainfall, temperature, elevation, slope, aspect, land use type, and human disturbance are ecological factors affecting the status of vegetation index. However, at different spatial scales, the key factors may vary. Using Helin County, Inner-Mongolia, China as the study site and combining remote sensing image interpretation, field surveying, and mathematical methods, this study assesses key ecological factors affecting vegetation degradation under different spatial scales in a semi-arid agro-pastoral ecotone. It indicates that the key factors are different at various spatial scales. Elevation, rainfall, and temperature are identified as crucial for all spatial extents. Elevation, rainfall and human disturbance are key factors for small-scale quadrats of 300 m × 300 m and 600 m × 600 m, temperature and land use type are key factors for a medium-scale quadrat of 1 km × 1 km, and rainfall, temperature, and land use are key factors for large-scale quadrats of 2 km × 2 km and 5 km × 5 km. For this region, human disturbance is not the key factor for vegetation degradation across spatial scales. It is necessary to consider spatial scale for the identification of key factors determining vegetation characteristics. The eco-restoration programs at various spatial scales should identify key influencing factors according their scales so as to take effective measurements. The new understanding obtained in this study may help to explore the forces which driving vegetation degradation in the degraded regions in the world.

Water dynamics clue to key residues in protein folding

International Nuclear Information System (INIS)

Gao, Meng; Zhu, Huaiqiu; Yao, Xin-Qiu; She, Zhen-Su

2010-01-01

A computational method independent of experimental protein structure information is proposed to recognize key residues in protein folding, from the study of hydration water dynamics. Based on all-atom molecular dynamics simulation, two key residues are recognized with distinct water dynamical behavior in a folding process of the Trp-cage protein. The identified key residues are shown to play an essential role in both 3D structure and hydrophobic-induced collapse. With observations on hydration water dynamics around key residues, a dynamical pathway of folding can be interpreted.

Identify and Quantify the Mechanistic Sources of Sensor Performance Variation Between Individual Sensors SN1 and SN2

Energy Technology Data Exchange (ETDEWEB)

Diaz, Aaron A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baldwin, David L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Cinson, Anthony D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Jones, Anthony M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Larche, Michael R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mathews, Royce [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mullen, Crystal A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Pardini, Allan F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Posakony, Gerald J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Prowant, Matthew S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hartman, Trenton S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Edwards, Matthew K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2014-08-06

This Technical Letter Report satisfies the M3AR-14PN2301022 milestone, and is focused on identifying and quantifying the mechanistic sources of sensor performance variation between individual 22-element, linear phased-array sensor prototypes, SN1 and SN2. This effort constitutes an iterative evolution that supports the longer term goal of producing and demonstrating a pre-manufacturing prototype ultrasonic probe that possesses the fundamental performance characteristics necessary to enable the development of a high-temperature sodium-cooled fast reactor inspection system. The scope of the work for this portion of the PNNL effort conducted in FY14 includes performing a comparative evaluation and assessment of the performance characteristics of the SN1 and SN2 22 element PA-UT probes manufactured at PNNL. Key transducer performance parameters, such as sound field dimensions, resolution capabilities, frequency response, and bandwidth are used as a metric for the comparative evaluation and assessment of the SN1 and SN2 engineering test units.

Identifying ELIXIR Core Data Resources [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Christine Durinx

2016-09-01

Full Text Available The core mission of ELIXIR is to build a stable and sustainable infrastructure for biological information across Europe. At the heart of this are the data resources, tools and services that ELIXIR offers to the life-sciences community, providing stable and sustainable access to biological data. ELIXIR aims to ensure that these resources are available long-term and that the life-cycles of these resources are managed such that they support the scientific needs of the life-sciences, including biological research. ELIXIR Core Data Resources are defined as a set of European data resources that are of fundamental importance to the wider life-science community and the long-term preservation of biological data. They are complete collections of generic value to life-science, are considered an authority in their field with respect to one or more characteristics, and show high levels of scientific quality and service. Thus, ELIXIR Core Data Resources are of wide applicability and usage. This paper describes the structures, governance and processes that support the identification and evaluation of ELIXIR Core Data Resources. It identifies key indicators which reflect the essence of the definition of an ELIXIR Core Data Resource and support the promotion of excellence in resource development and operation. It describes the specific indicators in more detail and explains their application within ELIXIR’s sustainability strategy and science policy actions, and in capacity building, life-cycle management and technical actions. Establishing the portfolio of ELIXIR Core Data Resources and ELIXIR Services is a key priority for ELIXIR and publicly marks the transition towards a cohesive infrastructure.

25 CFR 502.14 - Key employee.

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Key employee. 502.14 Section 502.14 Indians NATIONAL....14 Key employee. Key employee means: (a) A person who performs one or more of the following functions... gaming operation. (d) Any other person designated by the tribe as a key employee. [57 FR 12392, Apr. 9...

Identifying key controls on the behavior of an acidic-U(VI) plume in the Savannah River Site using reactive transport modeling.

Science.gov (United States)

Bea, Sergio A; Wainwright, Haruko; Spycher, Nicolas; Faybishenko, Boris; Hubbard, Susan S; Denham, Miles E

2013-08-01

Acidic low-level waste radioactive waste solutions were discharged to three unlined seepage basins at the F-Area of the Department of Energy (DOE) Savannah River Site (SRS), South Carolina, USA, from 1955 through 1989. Despite many years of active remediation, the groundwater remains acidic and contaminated with significant levels of U(VI) and other radionuclides. Monitored Natural Attenuation (MNA) is a desired closure strategy for the site, based on the premise that regional flow of clean background groundwater will eventually neutralize the groundwater acidity, immobilizing U(VI) through adsorption. An in situ treatment system is currently in place to accelerate this in the downgradient portion of the plume and similar measures could be taken upgradient if necessary. Understanding the long-term pH and U(VI) adsorption behavior at the site is critical to assess feasibility of MNA along with the in-situ remediation treatments. This paper presents a reactive transport (RT) model and uncertainty quantification (UQ) analyses to explore key controls on the U(VI)-plume evolution and long-term mobility at this site. Two-dimensional numerical RT simulations are run including the saturated and unsaturated (vadose) zones, U(VI) and H(+) adsorption (surface complexation) onto sediments, dissolution and precipitation of Al and Fe minerals, and key hydrodynamic processes are considered. UQ techniques are applied using a new open-source tool that is part of the developing ASCEM reactive transport modeling and analysis framework to: (1) identify the complex physical and geochemical processes that control the U(VI) plume migration in the pH range where the plume is highly mobile, (2) evaluate those physical and geochemical parameters that are most controlling, and (3) predict the future plume evolution constrained by historical, chemical and hydrological data. The RT simulation results show a good agreement with the observed historical pH and concentrations of U(VI), nitrates

The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

Science.gov (United States)

Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

2006-01-01

Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

Targeting the CRMP2-Ca2+ Channel Complex for Abortive Treatment of Migraine and Posttraumatic Headache

Science.gov (United States)

2017-09-01

LCM prevents nitric oxide (NO) donor -induced CA and blood CGRP elevation in rats with triptan-induced latent sensitization. • Aim 3 (PORRECA Lab...the development of cephalic and extracephalic allodynia induced by nitric oxide (NO) donor given at 30 min prior to the NO donor injections in...cranial cup, inflammatory mediators, nitric oxide donor , sodium channels, calcium channels, excitability, constellation pharmacology constellation

Targeting the CRMP2-Ca2+ Channel Complex for Abortive Treatment of Migraine and Posttraumatic Headache

Science.gov (United States)

2017-09-01

Cat# P6407, Sigma) coated glass coverslips (Cat# 72196-15, electron microscopy sciences ) as a drop of 20 µl on the center of each coverslip, then...transfer? Nothing to Report. o What was the impact on society beyond science and technology? Nothing to Report. 5. CHANGES/PROBLEMS: o Changes...GVIA and MVIIA block. The Journal of biological chemistry 2001;276(19):15728-15735. [4] Kane MJ, Angoa-Perez M, Briggs DI, Viano DC, Kreipke CW, Kuhn

Key acceptability attributes of orodispersible films.

Science.gov (United States)

Scarpa, Mariagiovanna; Paudel, Amrit; Kloprogge, Frank; Hsiao, Wen Kai; Bresciani, Massimo; Gaisford, Simon; Orlu, Mine

2018-04-01

The features rendering orodispersible films (ODFs) patient-centric formulations are widely discussed in the scientific literature. However there is a lack of research studies exploring ODF characteristics with a potential impact on end-user acceptability. The aim of this study was to identify the key ODF characteristics affecting end-user acceptability by developing in vitro test methods for the prediction of ODFs acceptability and correlate these formulation characteristics with the data obtained from a human panel study. Four drug-free single-polymer films were prepared by solvent casting. Solutions of poly(vinyl) alcohol (PVOH) 39 KDa (P1), PVOH 197 KDa (P2), carboxymethylcellulose (CMC) 395 KDa (C1), and CMC 725 KDa (C2) were prepared. Texture analysis and Dynamic Mechanical Analysis (DMA) were used to assess film tack. Petri dish and drop methods were used to assess disintegration time. A human panel of 24 healthy young adults was employed to identify end-user acceptability criteria of the four study film samples. Texture analysis data of ODF tack were not found to be in agreement with the in vivo perceived stickiness in the mouth. However, measurement of the area under the adhesive force curve obtained by DMA correlated with in vivo perceived stickiness data for all samples. The disintegration times obtained by drop method were more comparable to human panel data than the petri dish method. Hence DMA and drop methods proved to be promising methodologies for the prediction of the end-user acceptability. The type and molecular weight of the film-forming polymer had a strong influence on stickiness perception, whereas only polymeric molecular weight influenced perceived disintegration time. The human panel study showed that Participant Reported Outcomes (PROs) for the perceived stickiness in the mouth and disintegration time of test films received significantly different scores between samples, and thus were identified as the key attributes with the

Identifying key factors for mobilising under-utilised low carbon land resources : A case study on Kalimantan

NARCIS (Netherlands)

Goh, Chun Sheng; Junginger, Martin; Potter, Lesley; Faaij, André; Wicke, Birka

2018-01-01

Mobilising under-utilised low carbon (ULC) land for future agricultural expansion helps minimising further carbon stock loss. This study examined the regency cases in Kalimantan, a carbon loss hotspot, to understand the key factors for mobilising ULC land via narrative interviews with a range of

Identifying the impacts of climate change on key pests and diseases of plant and animal industries

International Nuclear Information System (INIS)

Luck, Jo; Aurambout, Jean-Philippe; Finlay, Kyla; Azuloas, Joe; Constable, Fiona; Rijswijk, Bonny Rowles-Van

2007-01-01

Full text: Full text: Climate change is increasingly recognised as a major threat to natural and agricultural systems. Understanding these threats will enable government and primary industries to better prepare and adapt to climate change. While observations of climate change are well documented, the potential effects on pests, pathogens and their hosts are not clearly understood. To address this, a review of the potential impacts on plant biosecurity was undertaken to determine the effects of climate change on the behaviour and distribution of emergent plant pests and pathogens. The review identified increasing C02 and temperature, decreasing frost events, heavy and unseasonal rains, increased humidity, drought, cyclones and hurricanes, and warmer winter temperatures as influencing the behaviour of plant pests and pathogens. To study the effects of these changes in detail, three key plant biosecurity threats were analysed in case studies; wheat stripe rust, silver leaf whitefly and citrus canker. The predicted distribution of citrus canker was examined with increasing temperature scenarios using the bioclimatic model CLIMEX. The model predicted a southerly shift in the geographic range of the causal organism which would threaten the major southern citrus growing regions in future climates. A similar study on Bluetongue disease of sheep, spread by the Culicoides midge, also predicted a southerly shift in the vector's geographic range. Significant limitations were identified with bioclimatic modelling when examining the effects of climate change on pests and diseases. The model was unable to assess the plant and animal response to increasing temperature in conjunction with the pest. Also the influence of temperature on the life cycle of the organism, pathogenicity of strains, competition with other species, host coverage and the general effect on the biology of the organism could not be assessed. To begin to address this, a dynamic model was constructed using daily

Development of key indicators to quantify the health impacts of climate change on Canadians.

Science.gov (United States)

Cheng, June J; Berry, Peter

2013-10-01

This study aimed at developing a list of key human health indicators for quantifying the health impacts of climate change in Canada. A literature review was conducted in OVID Medline to identify health morbidity and mortality indicators currently used to quantify climate change impacts. Public health frameworks and other studies of climate change indicators were reviewed to identify criteria with which to evaluate the list of proposed key indicators and a rating scale was developed. Total scores for each indicator were calculated based on the rating scale. A total of 77 health indicators were identified from the literature. After evaluation using the chosen criteria, 8 indicators were identified as the best for use. They include excess daily all-cause mortality due to heat, premature deaths due to air pollution (ozone and particulate matter 2.5), preventable deaths from climate change, disability-adjusted life years lost from climate change, daily all-cause mortality, daily non-accidental mortality, West Nile Disease incidence, and Lyme borreliosis incidence. There is need for further data and research related to health effect quantification in the area of climate change.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

Science.gov (United States)

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; Wietze van der Veen, J P; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R; Santorico, Stephanie A; Spritz, Richard A

2016-11-01

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

Key-value store with internal key-value storage interface

Science.gov (United States)

Bent, John M.; Faibish, Sorin; Ting, Dennis P. J.; Tzelnic, Percy; Gupta, Uday; Grider, Gary; Bonnie, David J.

2018-01-16

A key-value store is provided having one or more key-value storage interfaces. A key-value store on at least one compute node comprises a memory for storing a plurality of key-value pairs; and an abstract storage interface comprising a software interface module that communicates with at least one persistent storage device providing a key-value interface for persistent storage of one or more of the plurality of key-value pairs, wherein the software interface module provides the one or more key-value pairs to the at least one persistent storage device in a key-value format. The abstract storage interface optionally processes one or more batch operations on the plurality of key-value pairs. A distributed embodiment for a partitioned key-value store is also provided.

Interleukin-18 alters protein expressions of neurodegenerative diseases-linked proteins in human SH-SY5Y neuron-like cells

Directory of Open Access Journals (Sweden)

Elina M Sutinen

2014-08-01

Full Text Available Chronic inflammation and oxidative stress (OS are present in Alzheimer´s disease (AD brains in addition to neuronal loss, Amyloid-β (Aβ plaques and hyperphosphorylated tau-protein neurofibrillary tangles. Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18, are elevated in post-mortem AD brains. IL-18 can modulate the tau kinases, Cdk5 and GSK3β, as well as Aβ-production. IL-18 levels are also increased in AD risk diseases, including type-2 diabetes and obesity. Here, we explored other IL-18 regulated proteins in neuron-like SH-SY5Y cells. Differentiated SH-SY5Y cells, incubated with IL-18 for 24, 48 or 72h, were analyzed by two-dimensional gel electrophoresis (2D-DIGE. Specific altered protein spots were chosen and identified with mass spectrometry and verified by western immunoblotting. IL-18 had time-dependent effects on the SH-SY5Y proteome, modulating numerous protein levels/modifications. We concentrated on those related to OS (DDAH2, peroxiredoxins 2, 3 and 6, DJ-1, BLVRA, Aβ-degradation (MMP14, TIMP2, Aβ-aggregation (Septin-2 and modifications of axon growth and guidance associated, collapsing response mediator protein 2 (CRMP2. IL-18 significantly increased antioxidative enzymes, indicative of OS, and altered levels of glycolytic α- and γ-enolase and multifunctional 14-3-3γ and -ε, commonly affected in neurodegenerative diseases. MMP14, TIMP2, α-enolase and 14-3-3ε, indirectly involved in Aβ metabolism, as well as Septin-2 showed changes that increase Aβ levels. Increased 14-3-3γ may contribute to GSK3β driven tau hyperphosphorylation and CRMP2 Thr514 and Ser522 phosphorylation with the Thr555-site, a target for Rho kinase, showing time-dependent changes. IL-18 also increased caspase-1 levels and vacuolization of the cells. Although our SH-SY5Y cells were not aged, as neurons in AD, our work suggests that heightened or prolonged IL-18 levels can drive protein changes of known

Mapping key antecedents of employee-driven innovations

DEFF Research Database (Denmark)

Smith, Pernille; Ulhøi, John Parm; Kesting, Peter

2012-01-01

Research on employee-driven innovation (EDI) is still in its infancy, and as yet there is no independent body of literature on the topic. The aim of this paper is to review existing insights into the key antecedents of EDI in other research contexts. In particular, we focus on: leader support......, autonomy, collaboration, and organisational norms of exploration. The main contribution of this paper is to discuss how these key antecedents apply to the specific case of EDI and to identify an agenda for new research....

Dustless fabrication process for minor actinide bearing blankets: first applications to (Ce,Gd)O2 and (U,Am)O2

International Nuclear Information System (INIS)

Caisso, M.; Lebreton, F.; Horlait, D.; Delahaye, T.; Picart, S.; Gauthe, A.; Renard, C.; Roussel, P.; Martin, P.; Neuville, D.R.; Ayral, A.

2014-01-01

Minor actinides (MA) are generated in UOX and MOX fuels during irradiation in nuclear reactors. In the framework of their recycling, transmutation of americium in fast neutron reactors through MABB (Minor Actinide-Bearing Blanket) irradiation represents a major research focus. However, MABB fabrication requires special attention due to the high radiotoxicity of MA. Currently, the fabrication of these mixed-oxide pellets follows a powder metallurgy route which generates fine particles. Dustless processes which can avoid the use of such fine, thus highly contaminant, powder in the fabrication line are recommended. In this aim, the development of a spherule route called the calcined resin microsphere pelletizing (CRMP) process has been initiated. The general approach consists of elaborating micrometric spherical mixed-oxide precursors through an adaptation of the weak acid resin (WAR) process, and their compaction into pellets before sintering. The spherule synthesis is based on the fixation of americium and uranium ions into the beads composed of an ion exchange resin, and their mineralization leading to the formation of oxide microspheres. Our study is a first step in the elaboration of mixed-oxide pellets by the CRMP process, using cerium and gadolinium as lanthanide surrogates for uranium and americium, respectively. In a first part, the resin loading with a selected Ce/Gd ratio of 80/20 is described, with the use of actinide nitrates dissolved in aqueous solution. In a second part, characterizations by TGA (thermogravimetric analysis), HT-XRD (high-temperature X-ray diffraction), HT-Raman spectroscopy and HT-XAS (high temperature X-ray absorption spectroscopy) of the loaded resin were performed to study the departure of carbon from the initial structure and the oxide formation. Key temperatures were identified, corresponding to the important steps of the formation of a gadolinium doped ceria solid solution. The organic matter departure happens around 400 K and

Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors

Directory of Open Access Journals (Sweden)

Polonsky WH

2016-07-01

Full Text Available William H Polonsky,1,2 Robert R Henry2,3 1Behavioral Diabetes Institute, San Diego, 2University of California, San Diego, 3Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA, USA Abstract: At least 45% of patients with type 2 diabetes (T2D fail to achieve adequate glycemic control (HbA1c <7%. One of the major contributing factors is poor medication adherence. Poor medication adherence in T2D is well documented to be very common and is associated with inadequate glycemic control; increased morbidity and mortality; and increased costs of outpatient care, emergency room visits, hospitalization, and managing complications of diabetes. Poor medication adherence is linked to key nonpatient factors (eg, lack of integrated care in many health care systems and clinical inertia among health care professionals, patient demographic factors (eg, young age, low education level, and low income level, critical patient beliefs about their medications (eg, perceived treatment inefficacy, and perceived patient burden regarding obtaining and taking their medications (eg, treatment complexity, out-of-pocket costs, and hypoglycemia. Specific barriers to medication adherence in T2D, especially those that are potentially modifiable, need to be more clearly identified; strategies that target poor adherence should focus on reducing medication burden and addressing negative medication beliefs of patients. Solutions to these problems would require behavioral innovations as well as new methods and modes of drug delivery. Keywords: glycemic control, HbA1c, hypoglycemia, medication adherence, psychosocial, type 2 diabetes

Identifying key components for an effective case report poster: an observational study.

Science.gov (United States)

Willett, Lisa L; Paranjape, Anuradha; Estrada, Carlos

2009-03-01

Residents demonstrate scholarly activity by presenting posters at academic meetings. Although recommendations from national organizations are available, evidence identifying which components are most important is not. To develop and test an evaluation tool to measure the quality of case report posters and identify the specific components most in need of improvement. Faculty evaluators reviewed case report posters and provided on-site feedback to presenters at poster sessions of four annual academic general internal medicine meetings. A newly developed ten-item evaluation form measured poster quality for specific components of content, discussion, and format (5-point Likert scale, 1 = lowest, 5 = highest). Evaluation tool performance, including Cronbach alpha and inter-rater reliability, overall poster scores, differences across meetings and evaluators and specific components of the posters most in need of improvement. Forty-five evaluators from 20 medical institutions reviewed 347 posters. Cronbach's alpha of the evaluation form was 0.84 and inter-rater reliability, Spearman's rho 0.49 (p words. Our evaluation tool provides empirical data to guide trainees as they prepare posters for presentation which may improve poster quality and enhance their scholarly productivity.

SNP interaction pattern identifier (SIPI)

DEFF Research Database (Denmark)

Lin, Hui Yi; Chen, Dung Tsa; Huang, Po Yu

2017-01-01

Motivation: Testing SNP-SNP interactions is considered as a key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped. Results: We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45...

76 FR 18801 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Science.gov (United States)

2011-04-05

... request: The proposed change would revise the application of Risk-Managed Technical Specifications (RMTS) to Technical Specification (TS) 3.7.7, ``Control Room Makeup and Cleanup Filtration System.'' This... change allows the Configuration Risk Management Program (CRMP) to be applied to Technical Specification...

Physician Appraisals: Key Challenges

Directory of Open Access Journals (Sweden)

Klich Jacek

2017-06-01

Full Text Available The main purpose of the article is to identify key criteria being used for physician appraisals and to find how communication skills of physicians are valued in those appraisals. ScienceDirect and EBSCOhost databases were used for this search. The results show that a physician appraisal is underestimated both theoretically and empirically. The particular gap exists with respect to the communication skills of physicians, which are rarely present in medical training syllabi and physician assessments. The article contributes to the theoretical discourse on physician appraisals and points out at the inconsistency between the high status of physicians as a key hospital resource on the one hand and, on the other hand, at inadequate and poorly researched assessment of their performance with a special emphasis on communication skills. The article may inspire health managers to develop and implement up-to-date assessment forms for physicians and good managerial practices in this respect in hospitals and other health care units.

[Key to chironomid pupal exuviae (Diptera: Chironomidae) of tropical high Andean streams].

Science.gov (United States)

Pratt, Narcís; González-Trujillo, Juan David; Ospina-Torres, Rodulfo

2014-12-01

The Chironomidae is a cosmopolitan family of Nematoceran flies with more than 20,000 species described. However the diversity of genera and species of the family in the Andean region beyond the 2,000 m.a.s.l are scarcely known. We conducted faunal surveys and biomonitoring research in different streams of Colombia, Ecuador and Peru from May 2005 to October 2011. Based on specimens collections, a taxonomic key was developed to identify pupae and pupal exuviae of 46 genera of midges (Diptera, Chironomidae) collected from streams at high altitude areas on the Andean tropical mountains. We included illustrations and brief taxonomic descriptions for all genera, of which several ones have not yet been formally described; in this latter case we used the nomenclature of Roback & Coffman (1983). For two genera, Cricotopus and Genus 1, keys to the most com- mon morphospecies were provided. Results showed that in this area the chironomid assemblages are dominated by the members of the subfamily Orthocladiinae (22 genera) followed by the Chironominae (13). Six genera of Tanypodinae were identified, while only three and two genera were present from subfamilies Podonominae and Diamesinae. This key may be very useful for both studies about drift in streams, and for biomonitoring purposes.

Identification of novel key amino acids at the interface of the transmembrane domains of human BST-2 and HIV-1 Vpu.

Science.gov (United States)

Pang, Xiaojing; Hu, Siqi; Li, Jian; Xu, Fengwen; Mei, Shan; Zhou, Jinming; Cen, Shan; Jin, Qi; Guo, Fei

2013-08-06

BST-2 (bone marrow stromal cell antigen 2) is an interferon-inducible protein that inhibits virus release by tethering viral particles to the cell surface. This antiviral activity of BST-2 is antagonized by HIV-1 accessory protein Vpu. Vpu physically interacts with BST-2 through their mutual transmembrane (TM) domains. In this study, we utilized the BRET assay and molecular dynamics (MD) simulation method to further characterize the interaction of BST-2 and Vpu. Amino acids I34, L37, P40 and L41 in the TM domain of BST-2, and L11, A18 and W22 in the TM domain of Vpu were identified to be critical for the interaction between BST-2 and Vpu. The residues P40 in the TM domain of BST-2 and L11 in the TM domain of Vpu were shown, for the first time, to be important for their interaction. Furthermore, triple-amino-acid substitutions, 14-16 (AII to VAA) and 26-28 (IIE to AAA) in Vpu TM, not the single-residue mutation, profoundly disrupted BST-2/Vpu interaction. The results of MD simulation revealed significant conformational changes of the BST-2/Vpu complex as a result of mutating P40 of BST-2 and L11, 14-16 (AII to VAA) and 26-28 (IIE to AAA) of Vpu. In addition, disrupting the interaction between BST-2 and Vpu rendered BST-2 resistant to Vpu antagonization. Through use of the BRET assay, we identified novel key residues P40 in the TM domain of BST-2 and L11 in the TM domain of Vpu that are important for their interaction. These results add new insights into the molecular mechanism behind BST-2 antagonization by HIV-1 Vpu.

Key Distribution and Changing Key Cryptosystem Based on Phase Retrieval Algorithm and RSA Public-Key Algorithm

Directory of Open Access Journals (Sweden)

Tieyu Zhao

2015-01-01

Full Text Available The optical image encryption has attracted more and more researchers’ attention, and the various encryption schemes have been proposed. In existing optical cryptosystem, the phase functions or images are usually used as the encryption keys, and it is difficult that the traditional public-key algorithm (such as RSA, ECC, etc. is used to complete large numerical key transfer. In this paper, we propose a key distribution scheme based on the phase retrieval algorithm and the RSA public-key algorithm, which solves the problem for the key distribution in optical image encryption system. Furthermore, we also propose a novel image encryption system based on the key distribution principle. In the system, the different keys can be used in every encryption process, which greatly improves the security of the system.

Recombinant yeast screen for new inhibitors of human acetyl-CoA carboxylase 2 identifies potential drugs to treat obesity

Science.gov (United States)

Marjanovic, Jasmina; Chalupska, Dominika; Patenode, Caroline; Coster, Adam; Arnold, Evan; Ye, Alice; Anesi, George; Lu, Ying; Okun, Ilya; Tkachenko, Sergey; Haselkorn, Robert; Gornicki, Piotr

2010-01-01

Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism with multiple isozymes often expressed in different eukaryotic cellular compartments. ACC-made malonyl-CoA serves as a precursor for fatty acids; it also regulates fatty acid oxidation and feeding behavior in animals. ACC provides an important target for new drugs to treat human diseases. We have developed an inexpensive nonradioactive high-throughput screening system to identify new ACC inhibitors. The screen uses yeast gene-replacement strains depending for growth on cloned human ACC1 and ACC2. In “proof of concept” experiments, growth of such strains was inhibited by compounds known to target human ACCs. The screen is sensitive and robust. Medium-size chemical libraries yielded new specific inhibitors of human ACC2. The target of the best of these inhibitors was confirmed with in vitro enzymatic assays. This compound is a new drug chemotype inhibiting human ACC2 with 2.8 μM IC50 and having no effect on human ACC1 at 100 μM. PMID:20439761

Key to marine arthropod larvae

Directory of Open Access Journals (Sweden)

John A. Fornshell

2012-03-01

Full Text Available The scope of this key is restricted to the larvae of marine arthropods. The key is based solely on their morphology, patterns of body segmentation, numbers of appendages, and mode of locomotion. An effort has been made to treat all traditionally named larval forms, both planktonic and benthic. It is intended that this key be useful for a researcher working with archived museum specimens and therefore, does not include habitat information as a identifying trait, even though this information is usually available in the archived records. Within the phylum Arthropoda there are two sub-phyla and eleven classes having larval stages in the marineenvironment. Where feasible the original names of the various larval types have been used. Because this nomenclature is less commonly used today compared to the past, the more recent taxonomic affinities are included in parentheses after the original larval name. The key includes the following thirty-four larvae: Branchhiopoda nauplii; Cephalocarida nauplii; Mystacocarida nauplii; trilobite larva; protonymphon; hexapod larvae; Remipedia nauplii; nauplius - Y larvae; Cirripedia nauplii; Ascothoracida nauplii; Ostracoda nauplii; Euphausiacea nauplii; Penaeidea nauplii; Cyclopoida nauplii; Calanoida nauplii; Harpacticoida nauplii;Polyarthra nauplii; cypris larva; eryonecius larva; cypris-Y larva; elapthocaris larvae; mysis larvae; lucifer zoea; acetes zoea; acanthosoma larva; phyllosoma; antizoea larva; anomuran zoea; brachyuran zoea; calyptopis larvae; furcilia larva; crytopia larva; puerulus larva; alima larva.

Key Questions in Building Defect Prediction Models in Practice

Science.gov (United States)

Ramler, Rudolf; Wolfmaier, Klaus; Stauder, Erwin; Kossak, Felix; Natschläger, Thomas

The information about which modules of a future version of a software system are defect-prone is a valuable planning aid for quality managers and testers. Defect prediction promises to indicate these defect-prone modules. However, constructing effective defect prediction models in an industrial setting involves a number of key questions. In this paper we discuss ten key questions identified in context of establishing defect prediction in a large software development project. Seven consecutive versions of the software system have been used to construct and validate defect prediction models for system test planning. Furthermore, the paper presents initial empirical results from the studied project and, by this means, contributes answers to the identified questions.

Key principles for a national clinical decision support knowledge sharing framework: synthesis of insights from leading subject matter experts.

Science.gov (United States)

Kawamoto, Kensaku; Hongsermeier, Tonya; Wright, Adam; Lewis, Janet; Bell, Douglas S; Middleton, Blackford

2013-01-01

To identify key principles for establishing a national clinical decision support (CDS) knowledge sharing framework. As part of an initiative by the US Office of the National Coordinator for Health IT (ONC) to establish a framework for national CDS knowledge sharing, key stakeholders were identified. Stakeholders' viewpoints were obtained through surveys and in-depth interviews, and findings and relevant insights were summarized. Based on these insights, key principles were formulated for establishing a national CDS knowledge sharing framework. Nineteen key stakeholders were recruited, including six executives from electronic health record system vendors, seven executives from knowledge content producers, three executives from healthcare provider organizations, and three additional experts in clinical informatics. Based on these stakeholders' insights, five key principles were identified for effectively sharing CDS knowledge nationally. These principles are (1) prioritize and support the creation and maintenance of a national CDS knowledge sharing framework; (2) facilitate the development of high-value content and tooling, preferably in an open-source manner; (3) accelerate the development or licensing of required, pragmatic standards; (4) acknowledge and address medicolegal liability concerns; and (5) establish a self-sustaining business model. Based on the principles identified, a roadmap for national CDS knowledge sharing was developed through the ONC's Advancing CDS initiative. The study findings may serve as a useful guide for ongoing activities by the ONC and others to establish a national framework for sharing CDS knowledge and improving clinical care.

Community Advisory Boards Guiding Engaged Research Efforts within a Clinical Translational Sciences Award: Key Contextual Factors Explored.

Science.gov (United States)

Halladay, Jacqueline R; Donahue, Katrina E; Sleath, Betsy; Reuland, Dan; Black, Adina; Mitchell, C Madeline; Breland, Carol E; Coyne-Beasley, Tamera; Mottus, Kathleen; Watson, Sable Noelle; Lewis, Virginia; Wynn, Mysha; Corbie-Smith, Giselle

2017-01-01

Engaging stakeholders in research carries the promise of enhancing the research relevance, transparency, and speed of getting findings into practice. By describing the context and functional aspects of stakeholder groups, like those working as community advisory boards (CABs), others can learn from these experiences and operationalize their own CABs. Our objective is to describe our experiences with diverse CABs affiliated with our community engagement group within our institution's Clinical Translational Sciences Award (CTSA). We identify key contextual elements that are important to administering CABs. A group of investigators, staff, and community members engaged in a 6-month collaboration to describe their experiences of working with six research CABs. We identified the key contextual domains that illustrate how CABS are developed and sustained. Two lead authors, with experience with CABs and identifying contextual domains in other work, led a team of 13 through the process. Additionally, we devised a list of key tips to consider when devising CABs. The final domains include (1) aligned missions among stakeholders (2) resources/support, (3) defined operational processes/shared power, (4) well-described member roles, and (5) understanding and mitigating challenges. The tips are a set of actions that support the domains. Identifying key contextual domains was relatively easy, despite differences in the respective CAB's condition of focus, overall mission, or patient demographics represented. By contextualizing these five domains, other research and community partners can take an informed approach to move forward with CAB planning and engaged research.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

NARCIS (Netherlands)

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M.; Ben, Songtao; Brownson, Kelly M.; Holland, Paulene J.; Birlea, Stanca A.; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M.; Wolkerstorfer, Albert; Wietze van der Veen, J. P.; Bennett, Dorothy C.; Taïeb, Alain; Ezzedine, Khaled; Kemp, E. Helen; Gawkrodger, David J.; Weetman, Anthony P.; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R.; McCormack, Wayne T.; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B.; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W.; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R.; Santorico, Stephanie A.; Spritz, Richard A.

2016-01-01

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in

Ecological Understanding 2: Transformation--A Key to Ecological Understanding.

Science.gov (United States)

Carlsson, Britta

2002-01-01

Describes the structure and general features of the phenomenon of ecological understanding. Presents qualitatively different ways of experiencing cycling of matter and the flow of energy in the context of ecosystems. The idea of transformation is key to the development of ecological understanding. (Contains 17 references.) (Author/YDS)

Biomechanical loading on the upper extremity increases from single key tapping to directional tapping.

Science.gov (United States)

Qin, Jin; Trudeau, Matthieu; Katz, Jeffrey N; Buchholz, Bryan; Dennerlein, Jack T

2011-08-01

Musculoskeletal disorders associated with computer use span the joints of the upper extremity. Computing typically involves tapping in multiple directions. Thus, we sought to describe the loading on the finger, wrist, elbow and shoulder joints in terms of kinematic and kinetic difference across single key switch tapping to directional tapping on multiple keys. An experiment with repeated measures design was conducted. Six subjects tapped with their right index finger on a stand-alone number keypad placed horizontally in three conditions: (1) on single key switch (the number key 5); (2) left and right on number key 4 and 6; (3) top and bottom on number key 8 and 2. A force-torque transducer underneath the keypad measured the fingertip force. An active-marker infrared motion analysis system measured the kinematics of the fingertip, hand, forearm, upper arm and torso. Joint moments for the metacarpophalangeal, wrist, elbow, and shoulder joints were estimated using inverse dynamics. Tapping in the top-bottom orientation introduced the largest biomechanical loading on the upper extremity especially for the proximal joint, followed by tapping in the left-right orientation, and the lowest loading was observed during single key switch tapping. Directional tapping on average increased the fingertip force, joint excursion, and peak-to-peak joint torque by 45%, 190% and 55%, respectively. Identifying the biomechanical loading patterns associated with these fundamental movements of keying improves the understanding of the risks of upper extremity musculoskeletal disorders for computer keyboard users. Copyright © 2010 Elsevier Ltd. All rights reserved.

Conceptualizing childhood health problems using survey data: a comparison of key indicators

Directory of Open Access Journals (Sweden)

Miller Anton R

2007-12-01

Full Text Available Abstract Background Many definitions are being used to conceptualize child health problems. With survey data, commonly used indicators for identifying children with health problems have included chronic condition checklists, measures of activity limitations, elevated service use, and health utility thresholds. This study compares these different indicators in terms of the prevalence rates elicited, and in terms of how the subgroups identified differ. Methods Secondary data analyses used data from the National Longitudinal Survey of Children and Youth, which surveyed a nationally representative sample of Canadian children (n = 13,790. Descriptive analyses compared healthy children to those with health problems, as classified by any of the key indicators. Additional analyses examined differences between subgroups of children captured by a single indicator and those described as having health problems by multiple indicators. Results This study demonstrates that children captured by any of the indicators had poorer health than healthy children, despite the fact that over half the sample (52.2% was characterized as having a health problem by at least one indicator. Rates of child ill health differed by indicator; 5.6% had an activity limitation, 9.2% exhibited a severe health difficulty, 31.7% reported a chronic condition, and 36.6% had elevated service use. Further, the four key indicators captured different types of children. Indicator groupings differed on child and socio-demographic factors. Compared to children identified by more than one indicator, those identified only by the severe health difficulty indicator displayed more cognitive problems (p Conclusion We provide information useful to researchers when selecting indicators from survey data to identify children with health problems. Researchers and policy makers need to be aware of the impact of such definitions on prevalence rates as well as on the composition of children classified as

Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

Science.gov (United States)

Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

2016-02-29

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

RNA sequencing of Populus x canadensis roots identifies key molecular mechanisms underlying physiological adaption to excess zinc.

Directory of Open Access Journals (Sweden)

Andrea Ariani

Full Text Available Populus x canadensis clone I-214 exhibits a general indicator phenotype in response to excess Zn, and a higher metal uptake in roots than in shoots with a reduced translocation to aerial parts under hydroponic conditions. This physiological adaptation seems mainly regulated by roots, although the molecular mechanisms that underlie these processes are still poorly understood. Here, differential expression analysis using RNA-sequencing technology was used to identify the molecular mechanisms involved in the response to excess Zn in root. In order to maximize specificity of detection of differentially expressed (DE genes, we consider the intersection of genes identified by three distinct statistical approaches (61 up- and 19 down-regulated and validate them by RT-qPCR, yielding an agreement of 93% between the two experimental techniques. Gene Ontology (GO terms related to oxidation-reduction processes, transport and cellular iron ion homeostasis were enriched among DE genes, highlighting the importance of metal homeostasis in adaptation to excess Zn by P. x canadensis clone I-214. We identified the up-regulation of two Populus metal transporters (ZIP2 and NRAMP1 probably involved in metal uptake, and the down-regulation of a NAS4 gene involved in metal translocation. We identified also four Fe-homeostasis transcription factors (two bHLH38 genes, FIT and BTS that were differentially expressed, probably for reducing Zn-induced Fe-deficiency. In particular, we suggest that the down-regulation of FIT transcription factor could be a mechanism to cope with Zn-induced Fe-deficiency in Populus. These results provide insight into the molecular mechanisms involved in adaption to excess Zn in Populus spp., but could also constitute a starting point for the identification and characterization of molecular markers or biotechnological targets for possible improvement of phytoremediation performances of poplar trees.

Identifying Key Actors in Heterogeneous Networks

Science.gov (United States)

2017-11-29

Department of Defense (DOD) present social situations that are outside the scope and violate the assumptions of existing formal social science models. SNA by...assumptions of these existing social science models. SNA by its very construction focuses on dyadic relations and standard SNA metrics are focused only on...problematic for our purposes of determining relative valuations among vertices, but it is in contrast to the behavior of valuations like the Shapley value

Food Safety Is a Key Determinant of Fruit and Vegetable Consumption in Urban Beninese Adolescents

Science.gov (United States)

Nago, Eunice S.; Verstraeten, Roosmarijn; Lachat, Carl K.; Dossa, Romain A.; Kolsteren, Patrick W.

2012-01-01

Objective: To identify the determinants of fruit and vegetable consumption in urban Beninese adolescents and elements to develop a school-based fruit and vegetable program. Design: Sixteen focus groups conducted with a key word guide. Setting and Participants: Two private and 2 public secondary schools in Cotonou, Benin. One hundred fifty-three…

Scalable Multi-group Key Management for Advanced Metering Infrastructure

OpenAIRE

Benmalek , Mourad; Challal , Yacine; Bouabdallah , Abdelmadjid

2015-01-01

International audience; Advanced Metering Infrastructure (AMI) is composed of systems and networks to incorporate changes for modernizing the electricity grid, reduce peak loads, and meet energy efficiency targets. AMI is a privileged target for security attacks with potentially great damage against infrastructures and privacy. For this reason, Key Management has been identified as one of the most challenging topics in AMI development. In this paper, we propose a new Scalable multi-group key ...

First- and third-party ground truth for key frame extraction from consumer video clips

Science.gov (United States)

Costello, Kathleen; Luo, Jiebo

2007-02-01

Extracting key frames (KF) from video is of great interest in many applications, such as video summary, video organization, video compression, and prints from video. KF extraction is not a new problem. However, current literature has been focused mainly on sports or news video. In the consumer video space, the biggest challenges for key frame selection from consumer videos are the unconstrained content and lack of any preimposed structure. In this study, we conduct ground truth collection of key frames from video clips taken by digital cameras (as opposed to camcorders) using both first- and third-party judges. The goals of this study are: (1) to create a reference database of video clips reasonably representative of the consumer video space; (2) to identify associated key frames by which automated algorithms can be compared and judged for effectiveness; and (3) to uncover the criteria used by both first- and thirdparty human judges so these criteria can influence algorithm design. The findings from these ground truths will be discussed.

Internal transcribed spacer 2 barcode: A good tool for identifying Acanthopanacis cortex

Directory of Open Access Journals (Sweden)

Sha eZhao

2015-10-01

Full Text Available Acanthopanacis cortex has been used in clinical applications for a long time. Considering some historical and geographical factors, Acanthopanacis cortex is easily confused with other herbs in medicine markets, thereby causing potential safety issues. In this study, we used the internal transcribed spacer 2 (ITS2 barcode to identify 69 samples belonging to six species, including Acanthopanacis cortex and its adulterants. The nearest distance, single-nucleotide polymorphisms (SNPs, and neighbor-joining (NJ tree methods were used to evaluate the identification ability of the ITS2 barcode. According to the kimura-2-parameter model, the intraspecific distance of Eleutherococcus nodiflorus ITS2 sequences ranged from 0 to 0.0132. The minimum interspecific distance between E. nodiflorus and E. giraldii was 0.0221, which was larger than the maximum intraspecific distance of E. nodiflorus. Three stable SNPs in ITS2 can be used to distinguish Acanthopanacis cortex and its closely related species. The NJ tree indicated that the Acanthopanacis cortex samples clustered into one clade, which can be distinguished clearly from the adulterants of this herb. A secondary structure of ITS2 provided another dimensionality to identify species. In conclusion, the ITS2 barcode effectively identifies Acanthopanacis cortex, and DNA barcoding is a convenient tool for medicine market supervision.

Manet key management via Mobile Ficlke Key protocol (MFK ...

African Journals Online (AJOL)

Manet key management via Mobile Ficlke Key protocol (MFK) ... Journal of Fundamental and Applied Sciences. Journal Home · ABOUT THIS JOURNAL ... No Abstract. Keywords: MANET; key management scheme; simulation environment ...

Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.

Science.gov (United States)

Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin

2017-08-01

This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Diagnosing climate change impacts and identifying adaptation strategies by involving key stakeholder organisations and farmers in Sikkim, India: Challenges and opportunities.

Science.gov (United States)

Azhoni, Adani; Goyal, Manish Kumar

2018-06-01

Narrowing the gap between research, policy making and implementing adaptation remains a challenge in many parts of the world where climate change is likely to severely impact water security. This research aims to narrow this gap by matching the adaptation strategies being framed by policy makers to that of the perspectives of development agencies, researchers and farmers in the Himalayan state of Sikkim in India. Our case study examined the perspectives of various stakeholders for climate change impacts, current adaptation strategies, knowledge gaps and adaptation barriers, particularly in the context of implementing the Sikkim State Action Plan on Climate Change through semi-structured interviews carried out with decision makers in the Sikkim State Government, researchers, consultants, local academia, development agencies and farmers. Using Stakeholders Network Analysis tools, this research unravels the complexities of perceiving climate change impacts, identifying strategies, and implementing adaptation. While farmers are less aware about the global phenomenon of climate change impacts for water security, their knowledge of the local conditions and their close interaction with the State Government Agriculture Department provides them opportunities. Although important steps are being initiated through the Sikkim State Action Plan on Climate Change it is yet to deliver effective means of adaptation implementation and hence, strengthening the networks of close coordination between the various implementing agencies will pay dividends. Knowledge gaps and the need for capacity building identified in this research, based on the understandings of key stakeholders are highly relevant to both the research community and for informing policy. Copyright © 2018 Elsevier B.V. All rights reserved.

Whole transcriptome profiling of taste bud cells.

Science.gov (United States)

Sukumaran, Sunil K; Lewandowski, Brian C; Qin, Yumei; Kotha, Ramana; Bachmanov, Alexander A; Margolskee, Robert F

2017-08-08

Analysis of single-cell RNA-Seq data can provide insights into the specific functions of individual cell types that compose complex tissues. Here, we examined gene expression in two distinct subpopulations of mouse taste cells: Tas1r3-expressing type II cells and physiologically identified type III cells. Our RNA-Seq libraries met high quality control standards and accurately captured differential expression of marker genes for type II (e.g. the Tas1r genes, Plcb2, Trpm5) and type III (e.g. Pkd2l1, Ncam, Snap25) taste cells. Bioinformatics analysis showed that genes regulating responses to stimuli were up-regulated in type II cells, while pathways related to neuronal function were up-regulated in type III cells. We also identified highly expressed genes and pathways associated with chemotaxis and axon guidance, providing new insights into the mechanisms underlying integration of new taste cells into the taste bud. We validated our results by immunohistochemically confirming expression of selected genes encoding synaptic (Cplx2 and Pclo) and semaphorin signalling pathway (Crmp2, PlexinB1, Fes and Sema4a) components. The approach described here could provide a comprehensive map of gene expression for all taste cell subpopulations and will be particularly relevant for cell types in taste buds and other tissues that can be identified only by physiological methods.

Community landscapes: an integrative approach to determine overlapping network module hierarchy, identify key nodes and predict network dynamics.

Directory of Open Access Journals (Sweden)

István A Kovács

Full Text Available BACKGROUND: Network communities help the functional organization and evolution of complex networks. However, the development of a method, which is both fast and accurate, provides modular overlaps and partitions of a heterogeneous network, has proven to be rather difficult. METHODOLOGY/PRINCIPAL FINDINGS: Here we introduce the novel concept of ModuLand, an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1 determine persvasively overlapping modules with high resolution; (2 uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3 allow the determination of key network nodes and (4 help to predict network dynamics. CONCLUSIONS/SIGNIFICANCE: The concept opens a wide range of possibilities to develop new approaches and applications including network routing, classification, comparison and prediction.

Using the Theory of Planned Behavior to identify key beliefs underlying chlamydia testing intentions in a sample of young people living in deprived areas.

Science.gov (United States)

Booth, Amy R; Norman, Paul; Harris, Peter R; Goyder, Elizabeth

2015-09-01

The Theory of Planned Behavior was used to identify the key behavioural, normative and control beliefs underlying intentions to test regularly for chlamydia among young people living in socially and economically deprived areas - a high-risk group for infection. Participants (N = 278, 53% male; mean age 17 years) were recruited from a vocational college situated in an area in the most deprived national quintile (England). Participants completed measures of behavioural, normative and control beliefs, plus intention to test regularly for chlamydia. The behavioural, normative and control beliefs most strongly correlated with intentions to test regularly for chlamydia were beliefs about stopping the spread of infection, partners' behaviour and the availability of testing. These beliefs represent potential targets for interventions to increase chlamydia testing among young people living in deprived areas. © The Author(s) 2013.

Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Neeraja Krishnan

2015-11-01

Full Text Available Oral tongue squamous cell carcinomas (OTSCC are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs, indels, regions with loss of heterozygosity (LOH, and copy number variations (CNVs from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence.

Co-extinction in a host-parasite network: identifying key hosts for network stability.

Science.gov (United States)

Dallas, Tad; Cornelius, Emily

2015-08-17

Parasites comprise a substantial portion of total biodiversity. Ultimately, this means that host extinction could result in many secondary extinctions of obligate parasites and potentially alter host-parasite network structure. Here, we examined a highly resolved fish-parasite network to determine key hosts responsible for maintaining parasite diversity and network structure (quantified here as nestedness and modularity). We evaluated four possible host extinction orders and compared the resulting co-extinction dynamics to random extinction simulations; including host removal based on estimated extinction risk, parasite species richness and host level contributions to nestedness and modularity. We found that all extinction orders, except the one based on realistic extinction risk, resulted in faster declines in parasite diversity and network structure relative to random biodiversity loss. Further, we determined species-level contributions to network structure were best predicted by parasite species richness and host family. Taken together, we demonstrate that a small proportion of hosts contribute substantially to network structure and that removal of these hosts results in rapid declines in parasite diversity and network structure. As network stability can potentially be inferred through measures of network structure, our findings may provide insight into species traits that confer stability.

Fundamental quantitative security in quantum key generation

International Nuclear Information System (INIS)

Yuen, Horace P.

2010-01-01

We analyze the fundamental security significance of the quantitative criteria on the final generated key K in quantum key generation including the quantum criterion d, the attacker's mutual information on K, and the statistical distance between her distribution on K and the uniform distribution. For operational significance a criterion has to produce a guarantee on the attacker's probability of correctly estimating some portions of K from her measurement, in particular her maximum probability of identifying the whole K. We distinguish between the raw security of K when the attacker just gets at K before it is used in a cryptographic context and its composition security when the attacker may gain further information during its actual use to help get at K. We compare both of these securities of K to those obtainable from conventional key expansion with a symmetric key cipher. It is pointed out that a common belief in the superior security of a quantum generated K is based on an incorrect interpretation of d which cannot be true, and the security significance of d is uncertain. Generally, the quantum key distribution key K has no composition security guarantee and its raw security guarantee from concrete protocols is worse than that of conventional ciphers. Furthermore, for both raw and composition security there is an exponential catch-up problem that would make it difficult to quantitatively improve the security of K in a realistic protocol. Some possible ways to deal with the situation are suggested.

Novel high-throughput screening system for identifying STAT3-SH2 antagonists

International Nuclear Information System (INIS)

Uehara, Yutaka; Mochizuki, Masato; Matsuno, Kenji; Haino, Takeharu; Asai, Akira

2009-01-01

Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in either expression or phosphorylation level of STAT3 was observed. Thus, the HTS assay system represented herein may be useful for identifying novel STAT3-SH2 antagonists.

Gene expression profiling following NRF2 and KEAP1 siRNA knockdown in human lung fibroblasts identifies CCL11/Eotaxin-1 as a novel NRF2 regulated gene

Science.gov (United States)

2012-01-01

Background Oxidative Stress contributes to the pathogenesis of many diseases. The NRF2/KEAP1 axis is a key transcriptional regulator of the anti-oxidant response in cells. Nrf2 knockout mice have implicated this pathway in regulating inflammatory airway diseases such as asthma and COPD. To better understand the role the NRF2 pathway has on respiratory disease we have taken a novel approach to define NRF2 dependent gene expression in a relevant lung system. Methods Normal human lung fibroblasts were transfected with siRNA specific for NRF2 or KEAP1. Gene expression changes were measured at 30 and 48 hours using a custom Affymetrix Gene array. Changes in Eotaxin-1 gene expression and protein secretion were further measured under various inflammatory conditions with siRNAs and pharmacological tools. Results An anti-correlated gene set (inversely regulated by NRF2 and KEAP1 RNAi) that reflects specific NRF2 regulated genes was identified. Gene annotations show that NRF2-mediated oxidative stress response is the most significantly regulated pathway, followed by heme metabolism, metabolism of xenobiotics by Cytochrome P450 and O-glycan biosynthesis. Unexpectedly the key eosinophil chemokine Eotaxin-1/CCL11 was found to be up-regulated when NRF2 was inhibited and down-regulated when KEAP1 was inhibited. This transcriptional regulation leads to modulation of Eotaxin-1 secretion from human lung fibroblasts under basal and inflammatory conditions, and is specific to Eotaxin-1 as NRF2 or KEAP1 knockdown had no effect on the secretion of a set of other chemokines and cytokines. Furthermore, the known NRF2 small molecule activators CDDO and Sulphoraphane can also dose dependently inhibit Eotaxin-1 release from human lung fibroblasts. Conclusions These data uncover a previously unknown role for NRF2 in regulating Eotaxin-1 expression and further the mechanistic understanding of this pathway in modulating inflammatory lung disease. PMID:23061798

Mining key elements for severe convection prediction based on CNN

Science.gov (United States)

Liu, Ming; Pan, Ning; Zhang, Changan; Sha, Hongzhou; Zhang, Bolei; Liu, Liang; Zhang, Meng

2017-04-01

Severe convective weather is a kind of weather disasters accompanied by heavy rainfall, gust wind, hail, etc. Along with recent developments on remote sensing and numerical modeling, there are high-volume and long-term observational and modeling data accumulated to capture massive severe convective events over particular areas and time periods. With those high-volume and high-variety weather data, most of the existing studies and methods carry out the dynamical laws, cause analysis, potential rule study, and prediction enhancement by utilizing the governing equations from fluid dynamics and thermodynamics. In this study, a key-element mining method is proposed for severe convection prediction based on convolution neural network (CNN). It aims to identify the key areas and key elements from huge amounts of historical weather data including conventional measurements, weather radar, satellite, so as numerical modeling and/or reanalysis data. Under this manner, the machine-learning based method could help the human forecasters on their decision-making on operational weather forecasts on severe convective weathers by extracting key information from the real-time and historical weather big data. In this paper, it first utilizes computer vision technology to complete the data preprocessing work of the meteorological variables. Then, it utilizes the information such as radar map and expert knowledge to annotate all images automatically. And finally, by using CNN model, it cloud analyze and evaluate each weather elements (e.g., particular variables, patterns, features, etc.), and identify key areas of those critical weather elements, then help forecasters quickly screen out the key elements from huge amounts of observation data by current weather conditions. Based on the rich weather measurement and model data (up to 10 years) over Fujian province in China, where the severe convective weathers are very active during the summer months, experimental tests are conducted with

A functional, genome-wide evaluation of liposensitive yeast identifies the "ARE2 required for viability" (ARV1) gene product as a major component of eukaryotic fatty acid resistance.

Science.gov (United States)

Ruggles, Kelly V; Garbarino, Jeanne; Liu, Ying; Moon, James; Schneider, Kerry; Henneberry, Annette; Billheimer, Jeff; Millar, John S; Marchadier, Dawn; Valasek, Mark A; Joblin-Mills, Aidan; Gulati, Sonia; Munkacsi, Andrew B; Repa, Joyce J; Rader, Dan; Sturley, Stephen L

2014-02-14

The toxic subcellular accumulation of lipids predisposes several human metabolic syndromes, including obesity, type 2 diabetes, and some forms of neurodegeneration. To identify pathways that prevent lipid-induced cell death, we performed a genome-wide fatty acid sensitivity screen in Saccharomyces cerevisiae. We identified 167 yeast mutants as sensitive to 0.5 mm palmitoleate, 45% of which define pathways that were conserved in humans. 63 lesions also impacted the status of the lipid droplet; however, this was not correlated to the degree of fatty acid sensitivity. The most liposensitive yeast strain arose due to deletion of the "ARE2 required for viability" (ARV1) gene, encoding an evolutionarily conserved, potential lipid transporter that localizes to the endoplasmic reticulum membrane. Down-regulation of mammalian ARV1 in MIN6 pancreatic β-cells or HEK293 cells resulted in decreased neutral lipid synthesis, increased fatty acid sensitivity, and lipoapoptosis. Conversely, elevated expression of human ARV1 in HEK293 cells or mouse liver significantly increased triglyceride mass and lipid droplet number. The ARV1-induced hepatic triglyceride accumulation was accompanied by up-regulation of DGAT1, a triglyceride synthesis gene, and the fatty acid transporter, CD36. Furthermore, ARV1 was identified as a transcriptional of the protein peroxisome proliferator-activated receptor α (PPARα), a key regulator of lipid homeostasis whose transcriptional targets include DGAT1 and CD36. These results implicate ARV1 as a protective factor in lipotoxic diseases due to modulation of fatty acid metabolism. In conclusion, a lipotoxicity-based genetic screen in a model microorganism has identified 75 human genes that may play key roles in neutral lipid metabolism and disease.

Application of the key characteristics of carcinogens in cancer hazard identification

Science.gov (United States)

Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David C; Beland, Frederick A; Smith, Martyn T

2018-01-01

Abstract Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as ‘is genotoxic,’ ‘is immunosuppressive’ or ‘modulates receptor-mediated effects,’ and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification. PMID:29562322

Robust de novo pathway enrichment with KeyPathwayMiner 5 [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Nicolas Alcaraz

2016-06-01

Full Text Available Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks that are enriched for differentially active entities from a series of molecular profiles encoded as binary indicator matrices. Since interaction networks constantly evolve, an important question is how robust the extracted results are when the network is modified. We enable users to study this effect through several network perturbation techniques and over a range of perturbation degrees. In addition, users may now provide a gold-standard set to determine how enriched extracted pathways are with relevant genes compared to randomized versions of the original network.

Identification of Key Residues for Enzymatic Carboxylate Reduction

Directory of Open Access Journals (Sweden)

Holly Stolterfoht

2018-02-01

Full Text Available Carboxylate reductases (CARs, E.C. 1.2.1.30 generate aldehydes from their corresponding carboxylic acid with high selectivity. Little is known about the structure of CARs and their catalytically important amino acid residues. The identification of key residues for carboxylate reduction provides a starting point to gain deeper understanding of enzymatic carboxylate reduction. A multiple sequence alignment of CARs with confirmed activity recently identified in our lab and from the literature revealed a fingerprint of conserved amino acids. We studied the function of conserved residues by multiple sequence alignments and mutational replacements of these residues. In this study, single-site alanine variants of Neurospora crassa CAR were investigated to determine the contribution of conserved residues to the function, expressability or stability of the enzyme. The effect of amino acid replacements was investigated by analyzing enzymatic activity of the variants in vivo and in vitro. Supported by molecular modeling, we interpreted that five of these residues are essential for catalytic activity, or substrate and co-substrate binding. We identified amino acid residues having significant impact on CAR activity. Replacement of His 237, Glu 433, Ser 595, Tyr 844, and Lys 848 by Ala abolish CAR activity, indicating their key role in acid reduction. These results may assist in the functional annotation of CAR coding genes in genomic databases. While some other conserved residues decreased activity or had no significant impact, four residues increased the specific activity of NcCAR variants when replaced by alanine. Finally, we showed that NcCAR wild-type and mutants efficiently reduce aliphatic acids.

Genetic and Pharmacological Screens Converge in Identifying FLIP, BCL2, and IAP Proteins as Key Regulators of Sensitivity to the TRAIL-Inducing Anticancer Agent ONC201/TIC10.

Science.gov (United States)

Allen, Joshua E; Prabhu, Varun V; Talekar, Mala; van den Heuvel, A Pieter J; Lim, Bora; Dicker, David T; Fritz, Jennifer L; Beck, Adam; El-Deiry, Wafik S

2015-04-15

ONC201/TIC10 is a small-molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway-inducer KSR1. Unexpectedly, KSR1 silencing did not affect MAPK signaling in the presence or absence of ONC201, but instead reduced expression of the antiapoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin. In parallel to this work, we also conducted a synergy screen in which ONC201 was combined with approved small-molecule anticancer drugs. In multiple cancer cell populations, ONC201 synergized with diverse drug classes, including the multikinase inhibitor sorafenib. Notably, combining ONC201 and sorafenib led to synergistic induction of TRAIL and its receptor DR5 along with a potent induction of cell death. In a mouse xenograft model of hepatocellular carcinoma, we demonstrated that ONC201 and sorafenib cooperatively and safely triggered tumor regressions. Overall, our results established a set of determinants for ONC201 sensitivity that may predict therapeutic response, particularly in settings of sorafenib cotreatment to enhance anticancer responses. ©2015 American Association for Cancer Research.

How to identify the key factors that affect driver perception of accident risk. A comparison between Italian and Spanish driver behavior.

Science.gov (United States)

de Oña, Juan; de Oña, Rocio; Eboli, Laura; Forciniti, Carmen; Mazzulla, Gabriella

2014-12-01

Road crashes can be caused by different factors, including infrastructure, vehicles, and human variables. Many research studies have focused solely on identifying the key factors that cause road crashes. From these studies, it emerged that human factors have the most relevant impact on accident severity. More specifically, accident severity depends on several factors related directly to the driver, i.e., driving experience, driver's socio-economic characteristics, and driving behavior and attitudes. In this paper, we investigate driver behaviors and attitudes while driving and specifically focus on different methods for identifying the factors that most affect the driver's perception of accident risk. To this end, we designed and conducted a survey in two different European contexts: the city of Cosenza, which is located in the south of Italy, and the city of Granada, which is located in the south of Spain. Samples of drivers were contacted for their opinions on certain aspects of driving rules and attitudes while driving, and different types of questions were addressed to the drivers to assess their judgments of these aspects. Consequently, different methods of data analysis were applied to determine the aspects that heavily influence driver perception of accident risk. An experiment based on the stated preferences (SP) was carried out with the drivers, and the SP data were analyzed using an ordered probit (OP) model. Interesting findings emerged from different analyses of the data and from the comparisons among the data collected in the two different territorial contexts. We found that both Italian and Spanish drivers consider driving in an altered psychophysical state and violating the overtaking rules to be the most risky behaviors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lifelong Learning Key Competence Levels of Graduate Students

Science.gov (United States)

Adabas, Abdurrahman; Kaygin, Hüseyin

2016-01-01

The European Union defines lifelong learning as all activities aimed at improving an individual's knowledge, skills and competences individually, socially or vocationally throughout his/her life. In 2007, eight key competences necessary for lifelong learning were identified by the European Union Education and Culture Commission. These competences…

E-Commerce Performance. Shopping Cart Key Performance Indicators

Directory of Open Access Journals (Sweden)

Mihaela I. MUNTEAN

2016-01-01

Full Text Available In an e-commerce performance framework is important to identify the key performance indicators that measure success and together provide the greatest context into the business perfor-mance. Shopping carts are an essential part of ecommerce, a minimal set of key performance indicators being the subject of our debate. The theoretical approach is sustained by a case study, an e-shop implemented using PHP and MySQL, for simulating main business processes within the considered performance framework. Our approach opens a perspective for future research using additional indicators in order to properly evaluate the global performance of any e-shop.

Detailed Report on the Behaviour of the User Entrepreneur as a Key 'System Changer' in Future Scenarios

DEFF Research Database (Denmark)

Varga, Liz; Adams, Gemma; Verbong, Geert

This document synthesizes the outputs of work packages 1, 2, 5 and 6 relating to the behaviour of the user entrepreneur. It identifies the key roles of the user entrepreneur in user innovation which have an impact on system change and how these changes are relevant in future scenarios....

Technical note: Characterization of key volatile odorants in rabbit meat using gas chromatography mass spectrometry with simultaneous distillation extraction

Directory of Open Access Journals (Sweden)

Y.J. Xie

2016-12-01

Full Text Available This study explored the key volatile compounds in both male and female rabbit meat. Simultaneous distillation extraction with dichloromethane was adopted to extract the volatile compounds in Hyla rabbit meat. A total of 35 volatile compounds were identified by gas chromatography–mass spectrometry and quantified with 2, 4, 6-thimethylpyridine as internal standard. Seventeen volatile aldehydes, 4 alcohols, 2 ketones, 2 acids, 1 heterocyclic compound, 2 alkanes and 7 esters were detected. Hexanal, heptanal, octanal, nonanal, (E, E-2, 4-decadienal, 1-octen-3-ol and (Z-2-decenal were the key odorant compounds, with high relative odour activity value. Furthermore, the concentration of volatile compounds in male rabbit meat was higher than that in female rabbit meat.

Energy conservation in China: Key provincial sectors at two-digit level

International Nuclear Information System (INIS)

Liao, Hua; Du, Jian; Wei, Yi-Ming

2013-01-01

Highlights: ► We identify the keys for energy conversation across China’s 31 provinces × 65 sectors. ► The results are visualized in map and matrix tables, and easy for use. ► 39 Industrial sectors by province are classified into three categories for conservation. ► There is large energy wasting in the public management sector. ► There are both urban–rural gap and provincial inequality on electricity consumption. - Abstract: In March 2011, China’s central government set a new challenging target of reducing its energy intensity by 16% during 2011–2015, after it had achieved a reduction of 19.1% during 2006–2010. And this new target was assigned to provincial authorities in August 2011. However, China’s provincial energy-economic developments are unbalanced and different provinces have different key sectors for energy conservation. Most previous studies focused on provincial energy efficiency at the aggregate level, or the three-industry level (or one-digit level). However, whether for policy decision or academic research, it is necessary to further subdivide the sectors. In this paper, we use three indicators (Gini Coefficient, energy consumption share and energy intensity) to compare provincial energy conservation potentials at the two-digit sector level. To our knowledge, this paper is the first one to identify the keys for energy conversation across the 31 provinces × 65 sectors. And the results are shown in visualized maps and matrix tables to help identify the key province × sectors for energy conservation easier. This also helps the central and provincial governments to distinguish key sectors when they monitor the energy conservation progress

Decommissioning: Regulatory activities and identification of key organizational and human factors safety issues

International Nuclear Information System (INIS)

Durbin, N.E.; Melber, B.D.; Lekberg, A.

2001-12-01

In the late 1990's the Swedish government decided to shut down Unit 1 of the Barsebaeck nuclear power plant. This report documents some of the efforts made by the Swedish Nuclear Power Inspectorate (SKI) to address human factors and organizational issues in nuclear safety during decommissioning of a nuclear facility. This report gives a brief review of the background to the decommissioning of Barsebaeck 1 and points out key safety issues that can arise during decommissioning. The main regulatory activities that were undertaken were requirements that the plant provide special safety reports on decommissioning focusing on first, the operation of both units until closure of Unit 1 and second, the operation of Unit 2 when Unit 1 was closed. In addition, SKI identified areas that might be affected by decommissioning and called these areas out for special attention. With regard to these areas of special attention, SKI required that the plant provide monthly reports on changing and emerging issues as well as self-assessments of the areas to be addressed in the special safety reports. Ten key safety issues were identified and evaluated with regard to different stages of decommissioning and with regard to the actions taken by Barsebaeck. Some key conclusions from SKI's experience in regulating a decommissioning nuclear power plant conclude the report

Fate of key odorants in Sauternes wines through aging.

Science.gov (United States)

Bailly, Sabine; Jerkovic, Vesna; Meurée, Ariane; Timmermans, Aurore; Collin, Sonia

2009-09-23

Recent work has revealed the importance of polyfunctional thiols in young Sauternes wines, but very little is yet known about the fate of such compounds during aging in the bottle. In this study, two Sauternes wines were investigated by gas chromatography-olfactometry (GC-O) aroma extract dilution analysis (AEDA), gas chromatography-mass spectrometry (GC-MS), and gas chromatography-pulsed flame photometric detector (GC-PFPD) after XAD 2 and thiol-specific extractions. Most polyfunctional thiols (3-sulfanylpropyl acetate, 2-sulfanylethyl acetate, 3-methyl-3-sulfanylbutanal, etc.) proved to be completely degraded after 2 years of bottle aging in a cellar. Only 3-sulfanylhexan-1-ol was still found in aged samples at concentrations above its threshold value. Most other key odorants found in the young noble rot wine were still detected 5-6 years after harvest: varietal aroma (alpha-terpineol), sotolon, fermentation alcohols (3-methylbutan-1-ol and 2-phenylethanol) and esters (ethyl butyrate, isobutyrate, hexanoate, and isovalerate), and oak maturation-related compounds (guaiacol, vanillin, eugenol, beta-damascenone, trans-non-2-enal, beta-methyl-gamma-octalactone, gamma-nonalactone, and furaneol), as well as three newly identified aromas exhibiting interesting cake, honey-like, and dried apricot odors: homofuraneol, theaspirane, and gamma-decalactone. Interestingly, abhexon, never mentioned in sweet wines before, was found to be synthesized during bottle aging. An optimized extraction method allowed us to quantify this honey/spicy compound at levels close to its threshold value (up to 7 microg/L after 5-6 years), thus suggesting a key role of this strong odorant in old Sauternes wines.

Key Features of the Manufacturing Vision Development Process

DEFF Research Database (Denmark)

Dukovska-Popovska, Iskra; Riis, Jens Ove; Boer, Harry

2005-01-01

of action research. The methodology recommends wide participation of people from different hierarchical and functional positions, who engage in a relatively short, playful and creative process and come up with a vision (concept) for the future manufacturing system in the company. Based on three case studies......This paper discusses the key features of the process of Manufacturing Vision Development, a process that enables companies to develop their future manufacturing concept. The basis for the process is a generic five-phase methodology (Riis and Johansen 2003) developed as a result of ten years...... of companies going through the initial phases of the methodology, this research identified the key features of the Manufacturing Vision Development process. The paper elaborates the key features by defining them, discussing how and when they can appear, and how they influence the process....

75 FR 20364 - Public Buildings Service; Key Largo Beacon Annex Site; Key Largo, FL; Transfer of Property

Science.gov (United States)

2010-04-19

... GENERAL SERVICES ADMINISTRATION [Wildlife Order 187; 4-D-FL-1218] Public Buildings Service; Key Largo Beacon Annex Site; Key Largo, FL; Transfer of Property Pursuant to section 2 of Public Law 537, 80th Congress, approved May 19, 1948 (16 U.S.C. 667c), notice is hereby given that: 1. The General...

Characterization of key aroma-active compounds in lychee (Litchi chinensis Sonn.).

Science.gov (United States)

Feng, Shi; Huang, Mingyang; Crane, Jonathan Henry; Wang, Yu

2018-04-01

Volatile compounds in 'Sweetheart' lychee were examined using gas chromatography-olfactometry/mass spectrometry (GC-O/MS). Solvent assisted flavor evaporation (SAFE) technique was used to identify the aroma-active compounds in lychee. Further characterization of the most important odorants in 'Sweetheart' lychee was achieved using aroma extract dilution analysis (AEDA). Thirty-one key aroma-active odorants were identified in the flavor dilution (FD) factor range of 2-1024. Methional (cooked potato) and geraniol (sweet, floral) exhibited the highest FD factors of 1024 and 512, respectively, these were followed by furaneol (sweet, caramel), nerol (floral, sweet), dimethyl trisulfide (DMTS) (preserved vegetable, sulfury), linalool (floral), (E,Z)-2,6 nonadienal (cucumber) and nerolidol (metalic, sesame oil). Furthermore, the flavor profile of 'Sweetheart' lychee was described by sensory analysis. Floral, tropical fruit, peach/apricot and honey were scored with relatively high scores for each aroma attribute. The sweetness rating was the highest score among all the attributes. Copyright © 2017. Published by Elsevier B.V.

KEY COMPARISON: Final report on CCQM-K9.2: Subsequent key comparison on pH determination of phosphate buffer by Harned cell measurements

Science.gov (United States)

Spitzer, Petra; Giera, Janine; Fraga, Isabel C.; Tønnes Jakobsen, Pia; Jensen, Hans D.; Hyllested, Peter; Karpov, Oleg; Kutovoy, Viatcheslav; Nakamura, Susumu; Vospelova, Alena; Zvezdina, Valentina

2008-01-01

CCQM-K9.2 was performed supplementary to the key comparison CCQM-K9 on the pH determination of a phosphate buffer with nominal pH ~ 6.9 (at 25 °C). The sample composition was very similar in both comparisons. Only the source of the starting material used for sample preparation was different. The comparison was restricted to the use of the primary method for pH (Harned cell measurement) as defined in the IUPAC Recommendations [2]. The measurement temperatures were 15 °C, 25 °C, 37 °C. CCQM-K9.2, CCQM-K.9 and the first supplementary comparison CCQM-K9.1 [5] are activities of the Electrochemical Working Group (EAWG) of the CCQM. All three comparisons were coordinated by the PTB, Germany. The Danish Primary Laboratory (DPL) successfully took part in the CCQM-K9. Meanwhile the primary set-up for pH in Denmark moved from DPL affiliated to Radiometer Medical to DFM, Denmark. The subsequent comparison allows assessing the degree of equivalence for the measurement of pH at DFM after the move. Due to the interest of other laboratories in demonstrating their progress in pH measurements on the primary level the CCQM-K9.2 supplementary comparison was extended to other participants than DFM, namely NMIJ, VNIIFTRI, INMETRO and CMI. The reported quantity for CCQM-K9.2 was not the pH of the sample but the acidity function at zero chloride molality (see chapter 12). To calculate the pH value from the acidity function it is necessary to know the ionic strength of the sample buffer solution, which was undisclosed by the coordinator. With the exception of the Czech Metrology Institute, CMI, good agreement in the determined acidity function is found between the participants. The results reported by DFM and by PTB agree within their measurement uncertainty at all measurement temperatures. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report

Designing key-dependent chaotic S-box with larger key space

International Nuclear Information System (INIS)

Yin Ruming; Yuan Jian; Wang Jian; Shan Xiuming; Wang Xiqin

2009-01-01

The construction of cryptographically strong substitution boxes (S-boxes) is an important concern in designing secure cryptosystems. The key-dependent S-boxes designed using chaotic maps have received increasing attention in recent years. However, the key space of such S-boxes does not seem to be sufficiently large due to the limited parameter range of discretized chaotic maps. In this paper, we propose a new key-dependent S-box based on the iteration of continuous chaotic maps. We explore the continuous-valued state space of chaotic systems, and devise the discrete mapping between the input and the output of the S-box. A key-dependent S-box is constructed with the logistic map in this paper. We show that its key space could be much larger than the current key-dependent chaotic S-boxes.

Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury (Addendum)

Science.gov (United States)

2016-03-01

terminus amino acids of amyloid precursor protein (cAPP). cAPP had been found in our publication in Gene Therapy (2013) to be the most effective known axon...Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. NatRevMolCell Biol. 2011;12:21-35. 8. Morita T, Sobue K...Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S6K pathway. JBiolChem. 2009;284:27734-45. 9. Yan

A Functional, Genome-wide Evaluation of Liposensitive Yeast Identifies the “ARE2 Required for Viability” (ARV1) Gene Product as a Major Component of Eukaryotic Fatty Acid Resistance*

Science.gov (United States)

Ruggles, Kelly V.; Garbarino, Jeanne; Liu, Ying; Moon, James; Schneider, Kerry; Henneberry, Annette; Billheimer, Jeff; Millar, John S.; Marchadier, Dawn; Valasek, Mark A.; Joblin-Mills, Aidan; Gulati, Sonia; Munkacsi, Andrew B.; Repa, Joyce J.; Rader, Dan; Sturley, Stephen L.

2014-01-01

The toxic subcellular accumulation of lipids predisposes several human metabolic syndromes, including obesity, type 2 diabetes, and some forms of neurodegeneration. To identify pathways that prevent lipid-induced cell death, we performed a genome-wide fatty acid sensitivity screen in Saccharomyces cerevisiae. We identified 167 yeast mutants as sensitive to 0.5 mm palmitoleate, 45% of which define pathways that were conserved in humans. 63 lesions also impacted the status of the lipid droplet; however, this was not correlated to the degree of fatty acid sensitivity. The most liposensitive yeast strain arose due to deletion of the “ARE2 required for viability” (ARV1) gene, encoding an evolutionarily conserved, potential lipid transporter that localizes to the endoplasmic reticulum membrane. Down-regulation of mammalian ARV1 in MIN6 pancreatic β-cells or HEK293 cells resulted in decreased neutral lipid synthesis, increased fatty acid sensitivity, and lipoapoptosis. Conversely, elevated expression of human ARV1 in HEK293 cells or mouse liver significantly increased triglyceride mass and lipid droplet number. The ARV1-induced hepatic triglyceride accumulation was accompanied by up-regulation of DGAT1, a triglyceride synthesis gene, and the fatty acid transporter, CD36. Furthermore, ARV1 was identified as a transcriptional of the protein peroxisome proliferator-activated receptor α (PPARα), a key regulator of lipid homeostasis whose transcriptional targets include DGAT1 and CD36. These results implicate ARV1 as a protective factor in lipotoxic diseases due to modulation of fatty acid metabolism. In conclusion, a lipotoxicity-based genetic screen in a model microorganism has identified 75 human genes that may play key roles in neutral lipid metabolism and disease. PMID:24273168

A Key Establishment Protocol for RFID User in IPTV Environment

Science.gov (United States)

Jeong, Yoon-Su; Kim, Yong-Tae; Sohn, Jae-Min; Park, Gil-Cheol; Lee, Sang-Ho

In recent years, the usage of IPTV (Internet Protocol Television) has been increased. The reason is a technological convergence of broadcasting and telecommunication delivering interactive applications and multimedia content through high speed Internet connections. The main critical point of IPTV security requirements is subscriber authentication. That is, IPTV service should have the capability to identify the subscribers to prohibit illegal access. Currently, IPTV service does not provide a sound authentication mechanism to verify the identity of its wireless users (or devices). This paper focuses on a lightweight authentication and key establishment protocol based on the use of hash functions. The proposed approach provides effective authentication for a mobile user with a RFID tag whose authentication information is communicated back and forth with the IPTV authentication server via IPTV set-top box (STB). That is, the proposed protocol generates user's authentication information that is a bundle of two public keys derived from hashing user's private keys and RFID tag's session identifier, and adds 1bit to this bundled information for subscriber's information confidentiality before passing it to the authentication server.

Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.

Science.gov (United States)

Zanotto-Filho, Alfeu; Dashnamoorthy, Ravi; Loranc, Eva; de Souza, Luis H T; Moreira, José C F; Suresh, Uthra; Chen, Yidong; Bishop, Alexander J R

2016-01-01

Alkylating agents are a key component of cancer chemotherapy. Several cellular mechanisms are known to be important for its survival, particularly DNA repair and xenobiotic detoxification, yet genomic screens indicate that additional cellular components may be involved. Elucidating these components has value in either identifying key processes that can be modulated to improve chemotherapeutic efficacy or may be altered in some cancers to confer chemoresistance. We therefore set out to reevaluate our prior Drosophila RNAi screening data by comparison to gene expression arrays in order to determine if we could identify any novel processes in alkylation damage survival. We noted a consistent conservation of alkylation survival pathways across platforms and species when the analysis was conducted on a pathway/process level rather than at an individual gene level. Better results were obtained when combining gene lists from two datasets (RNAi screen plus microarray) prior to analysis. In addition to previously identified DNA damage responses (p53 signaling and Nucleotide Excision Repair), DNA-mRNA-protein metabolism (transcription/translation) and proteasome machinery, we also noted a highly conserved cross-species requirement for NRF2, glutathione (GSH)-mediated drug detoxification and Endoplasmic Reticulum stress (ER stress)/Unfolded Protein Responses (UPR) in cells exposed to alkylation. The requirement for GSH, NRF2 and UPR in alkylation survival was validated by metabolomics, protein studies and functional cell assays. From this we conclude that RNAi/gene expression fusion is a valid strategy to rapidly identify key processes that may be extendable to other contexts beyond damage survival.

Combined Gene Expression and RNAi Screening to Identify Alkylation Damage Survival Pathways from Fly to Human.

Directory of Open Access Journals (Sweden)

Alfeu Zanotto-Filho

Full Text Available Alkylating agents are a key component of cancer chemotherapy. Several cellular mechanisms are known to be important for its survival, particularly DNA repair and xenobiotic detoxification, yet genomic screens indicate that additional cellular components may be involved. Elucidating these components has value in either identifying key processes that can be modulated to improve chemotherapeutic efficacy or may be altered in some cancers to confer chemoresistance. We therefore set out to reevaluate our prior Drosophila RNAi screening data by comparison to gene expression arrays in order to determine if we could identify any novel processes in alkylation damage survival. We noted a consistent conservation of alkylation survival pathways across platforms and species when the analysis was conducted on a pathway/process level rather than at an individual gene level. Better results were obtained when combining gene lists from two datasets (RNAi screen plus microarray prior to analysis. In addition to previously identified DNA damage responses (p53 signaling and Nucleotide Excision Repair, DNA-mRNA-protein metabolism (transcription/translation and proteasome machinery, we also noted a highly conserved cross-species requirement for NRF2, glutathione (GSH-mediated drug detoxification and Endoplasmic Reticulum stress (ER stress/Unfolded Protein Responses (UPR in cells exposed to alkylation. The requirement for GSH, NRF2 and UPR in alkylation survival was validated by metabolomics, protein studies and functional cell assays. From this we conclude that RNAi/gene expression fusion is a valid strategy to rapidly identify key processes that may be extendable to other contexts beyond damage survival.

Habitat Restoration as a Key Conservation Lever for Woodland Caribou: A review of restoration programs and key learnings from Alberta

Directory of Open Access Journals (Sweden)

Paula Bentham

2015-12-01

Full Text Available The Recovery Strategy for the Woodland Caribou (Rangifer tarandus caribou, Boreal Population in Canada (EC, 2012, identifies coordinated actions to reclaim woodland caribou habitat as a key step to meeting current and future caribou population objectives. Actions include restoring industrial landscape features such as roads, seismic lines, pipelines, cut-lines, and cleared areas in an effort to reduce landscape fragmentation and the changes in caribou population dynamics associated with changing predator-prey dynamics in highly fragmented landscapes. Reliance on habitat restoration as a recovery action within the federal recovery strategy is high, considering all Alberta populations have less than 65% undisturbed habitat, which is identified in the recovery strategy as a threshold providing a 60% chance that a local population will be self-sustaining. Alberta’s Provincial Woodland Caribou Policy also identifies habitat restoration as a critical component of long-term caribou habitat management. We review and discuss the history of caribou habitat restoration programs in Alberta and present outcomes and highlights of a caribou habitat restoration workshop attended by over 80 representatives from oil and gas, forestry, provincial and federal regulators, academia and consulting who have worked on restoration programs. Restoration initiatives in Alberta began in 2001 and have generally focused on construction methods, revegetation treatments, access control programs, and limiting plant species favourable to alternate prey. Specific treatments include tree planting initiatives, coarse woody debris management along linear features, and efforts for multi-company and multi-stakeholder coordinated habitat restoration on caribou range. Lessons learned from these programs have been incorporated into large scale habitat restoration projects near Grande Prairie, Cold Lake, and Fort McMurray. A key outcome of our review is the opportunity to provide a

Genetic and pharmacological screens converge in identifying FLIP, BCL2 and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anti-cancer agent ONC201/TIC10

Science.gov (United States)

Allen, Joshua E.; Prabhu, Varun V.; Talekar, Mala; van den Heuvel, AP; Lim, Bora; Dicker, David T.; Fritz, Jennifer L.; Beck, Adam; El-Deiry, Wafik S.

2015-01-01

ONC201/TIC10 is a small molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway inducer KSR1. Unexpectedly, KSR1 silencing did not affect MAPK signaling in the presence or absence of ONC201, but instead reduced expression of the anti-apoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin. In parallel to this work, we also conducted a synergy screen in which ONC201 was combined with approved small molecule anticancer drugs. In multiple cancer cell populations, ONC201 synergized with diverse drug classes including the multi-kinase inhibitor sorafenib. Notably, combining ONC201 and sorafenib led to synergistic induction of TRAIL and its receptor DR5 along with a potent induction of cell death. In a mouse xenograft model of hepatocellular carcinoma, we demonstrated that ONC201 and sorafenib cooperatively and safely triggered tumor regressions. Overall, our results established a set of determinants for ONC201 sensitivity that may predict therapeutic response, particularly in settings of sorafenib co-treatment to enhance anticancer responses. PMID:25681273

Group key management

Energy Technology Data Exchange (ETDEWEB)

Dunigan, T.; Cao, C.

1997-08-01

This report describes an architecture and implementation for doing group key management over a data communications network. The architecture describes a protocol for establishing a shared encryption key among an authenticated and authorized collection of network entities. Group access requires one or more authorization certificates. The implementation includes a simple public key and certificate infrastructure. Multicast is used for some of the key management messages. An application programming interface multiplexes key management and user application messages. An implementation using the new IP security protocols is postulated. The architecture is compared with other group key management proposals, and the performance and the limitations of the implementation are described.

Preservation Analysis of Macrophage Gene Coexpression Between Human and Mouse Identifies PARK2 as a Genetically Controlled Master Regulator of Oxidative Phosphorylation in Humans

Directory of Open Access Journals (Sweden)

Veronica Codoni

2016-10-01

Full Text Available Macrophages are key players involved in numerous pathophysiological pathways and an in-depth characterization of their gene regulatory networks can help in better understanding how their dysfunction may impact on human diseases. We here conducted a cross-species network analysis of macrophage gene expression data between human and mouse to identify conserved networks across both species, and assessed whether such networks could reveal new disease-associated regulatory mechanisms. From a sample of 684 individuals processed for genome-wide macrophage gene expression profiling, we identified 27 groups of coexpressed genes (modules. Six modules were found preserved (P < 10−4 in macrophages from 86 mice of the Hybrid Mouse Diversity Panel. One of these modules was significantly [false discovery rate (FDR = 8.9 × 10−11] enriched for genes belonging to the oxidative phosphorylation (OXPHOS pathway. This pathway was also found significantly (FDR < 10−4 enriched in susceptibility genes for Alzheimer, Parkinson, and Huntington diseases. We further conducted an expression quantitative trait loci analysis to identify SNP that could regulate macrophage OXPHOS gene expression in humans. This analysis identified the PARK2 rs192804963 as a trans-acting variant influencing (minimal P-value = 4.3 × 10−8 the expression of most OXPHOS genes in humans. Further experimental work demonstrated that PARK2 knockdown expression was associated with increased OXPHOS gene expression in THP1 human macrophages. This work provided strong new evidence that PARK2 participates to the regulatory networks associated with oxidative phosphorylation and suggested that PARK2 genetic variations could act as a trans regulator of OXPHOS gene macrophage expression in humans.

STIM1 as a key regulator for Ca2+ homeostasis in skeletal-muscle development and function

Directory of Open Access Journals (Sweden)

Kiviluoto Santeri

2011-04-01

Full Text Available Abstract Stromal interaction molecules (STIM were identified as the endoplasmic-reticulum (ER Ca2+ sensor controlling store-operated Ca2+ entry (SOCE and Ca2+-release-activated Ca2+ (CRAC channels in non-excitable cells. STIM proteins target Orai1-3, tetrameric Ca2+-permeable channels in the plasma membrane. Structure-function analysis revealed the molecular determinants and the key steps in the activation process of Orai by STIM. Recently, STIM1 was found to be expressed at high levels in skeletal muscle controlling muscle function and properties. Novel STIM targets besides Orai channels are emerging. Here, we will focus on the role of STIM1 in skeletal-muscle structure, development and function. The molecular mechanism underpinning skeletal-muscle physiology points toward an essential role for STIM1-controlled SOCE to drive Ca2+/calcineurin/nuclear factor of activated T cells (NFAT-dependent morphogenetic remodeling programs and to support adequate sarcoplasmic-reticulum (SR Ca2+-store filling. Also in our hands, STIM1 is transiently up-regulated during the initial phase of in vitro myogenesis of C2C12 cells. The molecular targets of STIM1 in these cells likely involve Orai channels and canonical transient receptor potential (TRPC channels TRPC1 and TRPC3. The fast kinetics of SOCE activation in skeletal muscle seem to depend on the triad-junction formation, favoring a pre-localization and/or pre-formation of STIM1-protein complexes with the plasma-membrane Ca2+-influx channels. Moreover, Orai1-mediated Ca2+ influx seems to be essential for controlling the resting Ca2+ concentration and for proper SR Ca2+ filling. Hence, Ca2+ influx through STIM1-dependent activation of SOCE from the T-tubule system may recycle extracellular Ca2+ losses during muscle stimulation, thereby maintaining proper filling of the SR Ca2+ stores and muscle function. Importantly, mouse models for dystrophic pathologies, like Duchenne muscular dystrophy, point towards an

Identifying and Ranking the Determinants of Tourism Performance

DEFF Research Database (Denmark)

Assaf, A.George; Josiassen, Alexander

2012-01-01

, their tourism industries, and tourism businesses seek to improve the performance of the tourism industry and its constituents by vigorously promoting themselves to international tourists, cutting costs, and identifying synergies in their tourism endeavors. In seeking to improve the tourism industry......, the determinants that affect tourism performance are of key interest to the stakeholders. A key obstacle toward improving performance is the multitude of determinants that can affect tourism performance. The literature has yet to provide concrete insights into the determinants of tourism performance...... and their relative importance. The present study addresses this important gap. We identify and rank the determinants of tourism performance. We also provide performance measures of international tourism destinations. The results are derived using the Data Envelopment Analysis (DEA) and bootstrap truncated regression...

Key determinants of managing the marketing asset of global companies

Directory of Open Access Journals (Sweden)

Tatyana Tsygankova

2016-12-01

Full Text Available As a result of organization and summarization of key concepts of evolution of the marketing tools of global companies, the authors determined the role of the marketing assets in the system of modern marketing management (as a dialectically higher stage of development of the analyzed tools, which will allow overcoming the antagonistic contradiction of “P- and C-vectors” of their development. The article identified the optimal set of key elements of the system of marketing assets, which are the brand, customer loyalty, reputation, network cooperation, marketing strategy, internal marketing, marketing information system and marketing innovation. Due to correlation and regression analysis of the impact of each system elements on performance of global companies, the model of the "marketing asset octagon" was built as an integrative management tool. Also, as a result of construction of the said model, the authors identified the most profitable marketing assets, return on investment and development of competencies in the field of efficient management will bring the highest profit to the company. On the basis of summarizing the regional and branch features of managing the disparate elements of the marketing assets of global companies, the key regional and sectoral priorities of formation, development and improvement of existing concepts of the international marketing management were identified, particularly in terms of building an author’s integrative octagon model.

Robust Public Key Cryptography — A New Cryptosystem Surviving Private Key Compromise

Science.gov (United States)

Shaik, Cheman

A weakness of the present-day public key cryptosystems is that these cryptosystems do not survive private-key compromise attacks resulting from an internal breach of trust. In a competitive business environment, private key compromise is a common incident that voids the strength of public key cryptosystems such as RSA and ECC. Bribing corporate employees to disclose their secret keys and inadvertently disclosing secret information are among a plethora of practical attacks that occur at the implementation level. Once a breach of trust takes place and subsequently the private key is revealed, any public key cryptosystem fails to secure electronic data in Internet communications. The revealed key may be used by an attacker to decipher the intercepted data at an intermediary router. This weakness of public key cryptography calls for an additional security measure that enables encryptions to survive private key compromise attacks.

KEY PERFORMANCE INDICATORS FOR HEALTHCARE RESEARCH ORGANIZATIONS BETWEEN 2011 AND 2015

OpenAIRE

ANISKEVICH A.S.; HALFIN R.A.

2017-01-01

In this work we identify 16 key indicators to evaluate the performance of healthcare research organizations. These indicators comprehensively characterize such aspects of performance as research output and relevance, human resource development, integration into the international scientific community, distribution of scientific knowledge, promotion of the prestige of science, and resource provision. Below, we review the existing classification of medical research institutions and their key fea...

Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment.

Science.gov (United States)

Uddin, Raihan; Singh, Shiva M

2017-01-01

As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in "learning and memory" related functions and pathways. Subsequent differential network analysis of this "learning and memory" module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they

Key Questions in Marine Megafauna Movement Ecology

KAUST Repository

Hays, Graeme C.; Ferreira, Luciana C.; Sequeira, Ana M.M.; Meekan, Mark G.; Duarte, Carlos M.; Bailey, Helen; Bailleul, Fred; Bowen, W. Don; Caley, M. Julian; Costa, Daniel P.; Eguí luz, Victor M.; Fossette, Sabrina; Friedlaender, Ari S.; Gales, Nick; Gleiss, Adrian C.; Gunn, John; Harcourt, Rob; Hazen, Elliott L.; Heithaus, Michael R.; Heupel, Michelle; Holland, Kim; Horning, Markus; Jonsen, Ian; Kooyman, Gerald L.; Lowe, Christopher G.; Madsen, Peter T.; Marsh, Helene; Phillips, Richard A.; Righton, David; Ropert-Coudert, Yan; Sato, Katsufumi; Shaffer, Scott A.; Simpfendorfer, Colin A.; Sims, David W.; Skomal, Gregory; Takahashi, Akinori; Trathan, Philip N.; Wikelski, Martin; Womble, Jamie N.; Thums, Michele

2016-01-01

It is a golden age for animal movement studies and so an opportune time to assess priorities for future work. We assembled 40 experts to identify key questions in this field, focussing on marine megafauna, which include a broad range of birds, mammals, reptiles, and fish. Research on these taxa has both underpinned many of the recent technical developments and led to fundamental discoveries in the field. We show that the questions have broad applicability to other taxa, including terrestrial animals, flying insects, and swimming invertebrates, and, as such, this exercise provides a useful roadmap for targeted deployments and data syntheses that should advance the field of movement ecology. Technical advances make this an exciting time for animal movement studies, with a range of small, reliable data-loggers and transmitters that can record horizontal and vertical movements as well as aspects of physiology and reproductive biology.Forty experts identified key questions in the field of movement ecology.Questions have broad applicability across species, habitats, and spatial scales, and apply to animals in both marine and terrestrial habitats as well as both vertebrates and invertebrates, including birds, mammals, reptiles, fish, insects, and plankton. © 2016 Elsevier Ltd.

Key Questions in Marine Megafauna Movement Ecology

KAUST Repository

Hays, Graeme C.

2016-03-12

It is a golden age for animal movement studies and so an opportune time to assess priorities for future work. We assembled 40 experts to identify key questions in this field, focussing on marine megafauna, which include a broad range of birds, mammals, reptiles, and fish. Research on these taxa has both underpinned many of the recent technical developments and led to fundamental discoveries in the field. We show that the questions have broad applicability to other taxa, including terrestrial animals, flying insects, and swimming invertebrates, and, as such, this exercise provides a useful roadmap for targeted deployments and data syntheses that should advance the field of movement ecology. Technical advances make this an exciting time for animal movement studies, with a range of small, reliable data-loggers and transmitters that can record horizontal and vertical movements as well as aspects of physiology and reproductive biology.Forty experts identified key questions in the field of movement ecology.Questions have broad applicability across species, habitats, and spatial scales, and apply to animals in both marine and terrestrial habitats as well as both vertebrates and invertebrates, including birds, mammals, reptiles, fish, insects, and plankton. © 2016 Elsevier Ltd.

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

DEFF Research Database (Denmark)

Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur

2010-01-01

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals...

A key to the Mexican and Central America Genera of Anthonomini (Curculionidae, Curculioninae)

Science.gov (United States)

Hernández, Macotulio Soto; Jones, Robert W.; Castillo, Pedro Reyes

2013-01-01

Abstract Presently the only keys available for identification of genera of Anthonomini are limited to those of the United States of America and Canada. A dichotomous key is presented to identify all genera of Mexican and Central American Anthonomini. Previous keys do not include the genera Achia, Botanebius, Loncophorus, Loncophorellus and Melexerus. A brief synopsis is given for each genus and photographs of representative species are included. PMID:23717181

ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

Science.gov (United States)

Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

2016-09-15

The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

NARCIS (Netherlands)

B.F. Voight (Benjamin); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.D. Morris (Andrew); C. Dina (Christian); R.P. Welch (Ryan); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); N. Amin (Najaf); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steven); C. Langenberg (Claudia); O.M. Hofmann (Oliver); J. Dupuis (Josée); L. Qi (Lu); A.V. Segrè (Ayellet); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); B. Balkau (Beverley); R. Benediktsson (Rafn); A.J. Bennett (Amanda); R. Blagieva (Roza); E.A. Boerwinkle (Eric); L.L. Bonnycastle (Lori); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); M.R. Erdos (Michael); C.S. Fox (Caroline); C.S. Franklin (Christopher); M. Ganser (Martha); C. Gieger (Christian); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C.J. Groves (Christopher); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); B. Isomaa (Bo); A.U. Jackson (Anne); P.R.V. Johnson (Paul); T. Jørgensen (Torben); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); J. Kuusisto (Johanna); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); C.M. Lindgren (Cecilia); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); N. Narisu (Narisu); P. Nilsson (Peter); K.R. Owen (Katharine); F. Payne (Felicity); J.R.B. Perry (John); A.K. Petersen; C. Platou (Carl); C. Proença (Christine); I. Prokopenko (Inga); W. Rathmann (Wolfgang); N.W. Rayner (Nigel William); N.R. Robertson (Neil); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); G. Sigurdsson (Gunnar); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); A.J. Swift (Amy); B. Thorand (Barbara); J. Tichet (Jean); T. Tuomi (Tiinamaija); R.M. van Dam (Rob); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G.B. Walters (Bragi); M.N. Weedon (Michael); C. Wijmenga (Cisca); J.C.M. Witteman (Jacqueline); R.N. Bergman (Richard); S. Cauchi (Stephane); F.S. Collins (Francis); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (Torben); W.A. Hide (Winston); G.A. Hitman (Graham); A. Hofman (Albert); D. Hunter (David); K. Hveem (Kristian); M. Laakso (Markku); K.L. Mohlke (Karen); C.N.A. Palmer (Colin); P.P. Pramstaller (Peter Paul); I. Rudan (Igor); E.J.G. Sijbrands (Eric); L.D. Stein (Lincoln); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); M. Walker (Mark); N.J. Wareham (Nick); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); H. Campbell (Harry); M.J. Daly (Mark); A.T. Hattersley (Andrew); F.B. Hu (Frank); J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); H.E. Wichmann (Erich); I.E. Barroso (Inês); J.C. Florez (Jose); T.M. Frayling (Timothy); L. Groop (Leif); R. Sladek (Rob); U. Thorsteinsdottir (Unnur); J.F. Wilson (James); T. Illig (Thomas); P. Froguel (Philippe); P. Tikka-Kleemola (Päivi); J-A. Zwart (John-Anker); D. Altshuler (David); M. Boehnke (Michael); M.I. McCarthy (Mark); R.M. Watanabe (Richard)

2010-01-01

textabstractBy combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals

Genome-wide association study identifies three novel loci for type 2 diabetes

DEFF Research Database (Denmark)

Hara, Kazuo; Fujita, Hayato; Johnson, Todd A

2014-01-01

Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly g...

Identifying PHM market and network opportunities.

Science.gov (United States)

Grube, Mark E; Krishnaswamy, Anand; Poziemski, John; York, Robert W

2015-11-01

Two key processes for healthcare organizations seeking to assume a financially sustainable role in population health management (PHM), after laying the groundwork for the effort, are to identify potential PHM market opportunities and determine the scope of the PHM network. Key variables organizations should consider with respect to market opportunities include the patient population, the overall insurance/employer market, and available types of insurance products. Regarding the network's scope, organizations should consider both traditional strategic criteria for a viable network and at least five additional criteria: network essentiality and PHM care continuum, network adequacy, service distribution right-sizing, network growth strategy, and organizational agility.

Public key infrastructure for DOE security research

Energy Technology Data Exchange (ETDEWEB)

Aiken, R.; Foster, I.; Johnston, W.E. [and others

1997-06-01

This document summarizes the Department of Energy`s Second Joint Energy Research/Defence Programs Security Research Workshop. The workshop, built on the results of the first Joint Workshop which reviewed security requirements represented in a range of mission-critical ER and DP applications, discussed commonalties and differences in ER/DP requirements and approaches, and identified an integrated common set of security research priorities. One significant conclusion of the first workshop was that progress in a broad spectrum of DOE-relevant security problems and applications could best be addressed through public-key cryptography based systems, and therefore depended upon the existence of a robust, broadly deployed public-key infrastructure. Hence, public-key infrastructure ({open_quotes}PKI{close_quotes}) was adopted as a primary focus for the second workshop. The Second Joint Workshop covered a range of DOE security research and deployment efforts, as well as summaries of the state of the art in various areas relating to public-key technologies. Key findings were that a broad range of DOE applications can benefit from security architectures and technologies built on a robust, flexible, widely deployed public-key infrastructure; that there exists a collection of specific requirements for missing or undeveloped PKI functionality, together with a preliminary assessment of how these requirements can be met; that, while commercial developments can be expected to provide many relevant security technologies, there are important capabilities that commercial developments will not address, due to the unique scale, performance, diversity, distributed nature, and sensitivity of DOE applications; that DOE should encourage and support research activities intended to increase understanding of security technology requirements, and to develop critical components not forthcoming from other sources in a timely manner.

Predicting Key Events in the Popularity Evolution of Online Information.

Science.gov (United States)

Hu, Ying; Hu, Changjun; Fu, Shushen; Fang, Mingzhe; Xu, Wenwen

2017-01-01

The popularity of online information generally experiences a rising and falling evolution. This paper considers the "burst", "peak", and "fade" key events together as a representative summary of popularity evolution. We propose a novel prediction task-predicting when popularity undergoes these key events. It is of great importance to know when these three key events occur, because doing so helps recommendation systems, online marketing, and containment of rumors. However, it is very challenging to solve this new prediction task due to two issues. First, popularity evolution has high variation and can follow various patterns, so how can we identify "burst", "peak", and "fade" in different patterns of popularity evolution? Second, these events usually occur in a very short time, so how can we accurately yet promptly predict them? In this paper we address these two issues. To handle the first one, we use a simple moving average to smooth variation, and then a universal method is presented for different patterns to identify the key events in popularity evolution. To deal with the second one, we extract different types of features that may have an impact on the key events, and then a correlation analysis is conducted in the feature selection step to remove irrelevant and redundant features. The remaining features are used to train a machine learning model. The feature selection step improves prediction accuracy, and in order to emphasize prediction promptness, we design a new evaluation metric which considers both accuracy and promptness to evaluate our prediction task. Experimental and comparative results show the superiority of our prediction solution.

Predicting Key Events in the Popularity Evolution of Online Information.

Directory of Open Access Journals (Sweden)

Ying Hu

Full Text Available The popularity of online information generally experiences a rising and falling evolution. This paper considers the "burst", "peak", and "fade" key events together as a representative summary of popularity evolution. We propose a novel prediction task-predicting when popularity undergoes these key events. It is of great importance to know when these three key events occur, because doing so helps recommendation systems, online marketing, and containment of rumors. However, it is very challenging to solve this new prediction task due to two issues. First, popularity evolution has high variation and can follow various patterns, so how can we identify "burst", "peak", and "fade" in different patterns of popularity evolution? Second, these events usually occur in a very short time, so how can we accurately yet promptly predict them? In this paper we address these two issues. To handle the first one, we use a simple moving average to smooth variation, and then a universal method is presented for different patterns to identify the key events in popularity evolution. To deal with the second one, we extract different types of features that may have an impact on the key events, and then a correlation analysis is conducted in the feature selection step to remove irrelevant and redundant features. The remaining features are used to train a machine learning model. The feature selection step improves prediction accuracy, and in order to emphasize prediction promptness, we design a new evaluation metric which considers both accuracy and promptness to evaluate our prediction task. Experimental and comparative results show the superiority of our prediction solution.

Multiparty quantum key agreement with single particles

Science.gov (United States)

Liu, Bin; Gao, Fei; Huang, Wei; Wen, Qiao-yan

2013-04-01

Two conditions must be satisfied in a secure quantum key agreement (QKA) protocol: (1) outside eavesdroppers cannot gain the generated key without introducing any error; (2) the generated key cannot be determined by any non-trivial subset of the participants. That is, a secure QKA protocol can not only prevent the outside attackers from stealing the key, but also resist the attack from inside participants, i.e. some dishonest participants determine the key alone by illegal means. How to resist participant attack is an aporia in the design of QKA protocols, especially the multi-party ones. In this paper we present the first secure multiparty QKA protocol against both outside and participant attacks. Further more, we have proved its security in detail.

Identifying Key Issues and Potential Solutions for Integrated Arrival, Departure, Surface Operations by Surveying Stakeholder Preferences

Science.gov (United States)

Aponso, Bimal; Coppenbarger, Richard A.; Jung, Yoon; Quon, Leighton; Lohr, Gary; O’Connor, Neil; Engelland, Shawn

2015-01-01

predictability and suggested several key attributes that were necessary to make the concept successful. The goals and objectives of the planned ATD-2 sub-project will incorporate the results of this stakeholder feedback.

Development of key indicators to quantify the health impacts of climate change on Canadians

OpenAIRE

Cheng, June J.; Berry, Peter

2013-01-01

Objectives This study aimed at developing a list of key human health indicators for quantifying the health impacts of climate change in Canada. Methods A literature review was conducted in OVID Medline to identify health morbidity and mortality indicators currently used to quantify climate change impacts. Public health frameworks and other studies of climate change indicators were reviewed to identify criteria with which to evaluate the list of proposed key indicators and a rating scale was d...

Clinical risk management in hospitals: strategy, central coordination and dialogue as key enablers.

Science.gov (United States)

Briner, Matthias; Manser, Tanja; Kessler, Oliver

2013-04-01

The study aims to identify key enablers fostering clinical risk management (CRM) in hospitals to guide health care in this vital area of patient safety. A cross-sectional survey was conducted at the national level in 324 Swiss hospitals in 2007-2008 to assess the relationship between key elements and systematic CRM. Therefore, a comprehensive monitoring instrument for CRM was used for the first time. Organizational factors (e.g. strategy, coordination, resources) and structural conditions (e.g. hospital size) were tested as key elements. CRM was assessed by evaluating its maturity (i.e. the level of CRM development) by 12 theoretically derived indices joining together essential aspects of CRM at the hospital level and the service level. Chi-square measures were used to analyse the relationships between organizational factors or structural conditions and maturity of CRM. Participation in this voluntary survey was good, with CRM experts of 138 out of 324 hospitals responding (response rate 43%). Three key enablers for CRM were identified: implementing a function for central CRM coordination, assuring dialogue with and between the different hospital services, and developing strategic CRM objectives. This study offers, for the first time, an assessment of the maturity of hospitals' CRM and identifies key enablers related to CRM. This is a feasible first step in guiding hospitals to shape their CRM and presents a basis for future studies, for example, linking CRM to outcome data. © 2012 Blackwell Publishing Ltd.

Genomic analysis identifies masqueraders of full-term cerebral palsy.

Science.gov (United States)

Takezawa, Yusuke; Kikuchi, Atsuo; Haginoya, Kazuhiro; Niihori, Tetsuya; Numata-Uematsu, Yurika; Inui, Takehiko; Yamamura-Suzuki, Saeko; Miyabayashi, Takuya; Anzai, Mai; Suzuki-Muromoto, Sato; Okubo, Yukimune; Endo, Wakaba; Togashi, Noriko; Kobayashi, Yasuko; Onuma, Akira; Funayama, Ryo; Shirota, Matsuyuki; Nakayama, Keiko; Aoki, Yoko; Kure, Shigeo

2018-05-01

Cerebral palsy is a common, heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent studies have suggested genetic diseases can be misdiagnosed as cerebral palsy. We hypothesized that two simple criteria, that is, full-term births and nonspecific brain MRI findings, are keys to extracting masqueraders among cerebral palsy cases due to the following: (1) preterm infants are susceptible to multiple environmental factors and therefore demonstrate an increased risk of cerebral palsy and (2) brain MRI assessment is essential for excluding environmental causes and other particular disorders. A total of 107 patients-all full-term births-without specific findings on brain MRI were identified among 897 patients diagnosed with cerebral palsy who were followed at our center. DNA samples were available for 17 of the 107 cases for trio whole-exome sequencing and array comparative genomic hybridization. We prioritized variants in genes known to be relevant in neurodevelopmental diseases and evaluated their pathogenicity according to the American College of Medical Genetics guidelines. Pathogenic/likely pathogenic candidate variants were identified in 9 of 17 cases (52.9%) within eight genes: CTNNB1 , CYP2U1 , SPAST , GNAO1 , CACNA1A , AMPD2 , STXBP1 , and SCN2A . Five identified variants had previously been reported. No pathogenic copy number variations were identified. The AMPD2 missense variant and the splice-site variants in CTNNB1 and AMPD2 were validated by in vitro functional experiments. The high rate of detecting causative genetic variants (52.9%) suggests that patients diagnosed with cerebral palsy in full-term births without specific MRI findings may include genetic diseases masquerading as cerebral palsy.

New weak keys in simplified IDEA

Science.gov (United States)

Hafman, Sari Agustini; Muhafidzah, Arini

2016-02-01

Simplified IDEA (S-IDEA) is simplified version of International Data Encryption Algorithm (IDEA) and useful teaching tool to help students to understand IDEA. In 2012, Muryanto and Hafman have found a weak key class in the S-IDEA by used differential characteristics in one-round (0, ν, 0, ν) → (0,0, ν, ν) on the first round to produce input difference (0,0, ν, ν) on the fifth round. Because Muryanto and Hafman only use three differential characteristics in one-round, we conducted a research to find new differential characteristics in one-round and used it to produce new weak key classes of S-IDEA. To find new differential characteristics in one-round of S-IDEA, we applied a multiplication mod 216+1 on input difference and combination of active sub key Z1, Z4, Z5, Z6. New classes of weak keys are obtained by combining all of these characteristics and use them to construct two new differential characteristics in full-round of S-IDEA with or without the 4th round sub key. In this research, we found six new differential characteristics in one round and combined them to construct two new differential characteristics in full-round of S-IDEA. When two new differential characteristics in full-round of S-IDEA are used and the 4th round sub key required, we obtain 2 new classes of weak keys, 213 and 28. When two new differential characteristics in full-round of S-IDEA are used, yet the 4th round sub key is not required, the weak key class of 213 will be 221 and 28 will be 210. Membership test can not be applied to recover the key bits in those weak key classes. The recovery of those unknown key bits can only be done by using brute force attack. The simulation result indicates that the bit of the key can be recovered by the longest computation time of 0,031 ms.

Academic Primer Series: Eight Key Papers about Education Theory.

Science.gov (United States)

Gottlieb, Michael; Boysen-Osborn, Megan; Chan, Teresa M; Krzyzaniak, Sara M; Pineda, Nicolas; Spector, Jordan; Sherbino, Jonathan

2017-02-01

Many teachers adopt instructional methods based on assumptions of best practices without attention to or knowledge of supporting education theory. Familiarity with a variety of theories informs education that is efficient, strategic, and evidence-based. As part of the Academic Life in Emergency Medicine Faculty Incubator Program, a list of key education theories for junior faculty was developed. A list of key papers on theories relevant to medical education was generated using an expert panel, a virtual community of practice synthetic discussion, and a social media call for resources. A three-round, Delphi-informed voting methodology including novice and expert educators produced a rank order of the top papers. These educators identified 34 unique papers. Eleven papers described the general use of education theory, while 23 papers focused on a specific theory. The top three papers on general education theories and top five papers on specific education theory were selected and summarized. The relevance of each paper for junior faculty and faculty developers is also presented. This paper presents a reading list of key papers for junior faculty in medical education roles. Three papers about general education theories and five papers about specific educational theories are identified and annotated. These papers may help provide foundational knowledge in education theory to inform junior faculty teaching practice.

The key role of CYC2 during meiosis in Tetrahymena thermophila.

Science.gov (United States)

Xu, Qianlan; Wang, Ruoyu; Ghanam, A R; Yan, Guanxiong; Miao, Wei; Song, Xiaoyuan

2016-04-01

Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks (DSBs) made by the Spo11 protein. The present study shed light on the functional role of cyclin, CYC2, in Tetrahymena thermophila which has transcriptionally high expression level during meiosis process. Knocking out the CYC2 gene results in arrest of meiotic conjugation process at 2.5-3.5 h after conjugation initiation, before the meiosis division starts, and in company with the absence of DSBs. To investigate the underlying mechanism of this phenomenon, a complete transcriptome profile was performed between wild-type strain and CYC2 knock-out strain. Functional analysis of RNA-Seq results identifies related differentially expressed genes (DEGs) including SPO11 and these DEGs are enriched in DNA repair/mismatch repair (MMR) terms in homologous recombination (HR), which indicates that CYC2 could play a crucial role in meiosis by regulating SPO11 and participating in HR.

A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

DEFF Research Database (Denmark)

Taneera, Jalal; Lang, Stefan; Sharma, Amitabh

2012-01-01

Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified ...

Key determinants of managing the marketing asset of global companies

OpenAIRE

Tatyana Tsygankova; Roman Ponomarenko

2016-01-01

As a result of organization and summarization of key concepts of evolution of the marketing tools of global companies, the authors determined the role of the marketing assets in the system of modern marketing management (as a dialectically higher stage of development of the analyzed tools, which will allow overcoming the antagonistic contradiction of “P- and C-vectors” of their development). The article identified the optimal set of key elements of the system of marketing assets, which are th...

Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration.

Science.gov (United States)

Arneson, Douglas; Bhattacharya, Anindya; Shu, Le; Mäkinen, Ville-Petteri; Yang, Xia

2016-09-09

Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development. To make the Mergeomics pipeline available to a wider research community, we have implemented an online, user-friendly web server ( http://mergeomics. idre.ucla.edu/ ). The web server features a modular implementation of the Mergeomics pipeline with detailed tutorials. Additionally, it provides curated genomic resources including tissue-specific expression quantitative trait loci, ENCODE functional annotations, biological pathways, and molecular networks, and offers interactive visualization of analytical results. Multiple computational tools including Marker Dependency Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted Key Driver Analysis (wKDA) can be used separately or in flexible combinations. User-defined summary-level genomic association datasets (e.g., genetic, transcriptomic, epigenomic) related to a particular disease or phenotype can be uploaded and computed real-time to yield biologically interpretable results, which can be viewed online and downloaded for later use. Our Mergeomics web server offers researchers flexible and user-friendly tools to facilitate integration of multidimensional data into holistic views of disease mechanisms in the form of tissue-specific key regulators

A structured elicitation method to identify key direct risk factors for the management of natural resources

Directory of Open Access Journals (Sweden)

Michael Smith

2015-11-01

Full Text Available The high level of uncertainty inherent in natural resource management requires planners to apply comprehensive risk analyses, often in situations where there are few resources. In this paper, we demonstrate a broadly applicable, novel and structured elicitation approach to identify important direct risk factors. This new approach combines expert calibration and fuzzy based mathematics to capture and aggregate subjective expert estimates of the likelihood that a set of direct risk factors will cause management failure. A specific case study is used to demonstrate the approach; however, the described methods are widely applicable in risk analysis. For the case study, the management target was to retain all species that characterise a set of natural biological elements. The analysis was bounded by the spatial distribution of the biological elements under consideration and a 20-year time frame. Fourteen biological elements were expected to be at risk. Eleven important direct risk factors were identified that related to surrounding land use practices, climate change, problem species (e.g., feral predators, fire and hydrological change. In terms of their overall influence, the two most important risk factors were salinisation and a lack of water which together pose a considerable threat to the survival of nine biological elements. The described approach successfully overcame two concerns arising from previous risk analysis work: (1 the lack of an intuitive, yet comprehensive scoring method enabling the detection and clarification of expert agreement and associated levels of uncertainty; and (2 the ease with which results can be interpreted and communicated while preserving a rich level of detail essential for informed decision making.

41 CFR Appendix A to Subpart C of... - 3-Key Points and Principles

Science.gov (United States)

2010-07-01

... Principles A Appendix A to Subpart C of Part 102 Public Contracts and Property Management Federal Property... 102-3—Key Points and Principles This appendix provides additional guidance in the form of answers to frequently asked questions and identifies key points and principles that may be applied to situations not...

Key Future Engineering Capabilities for Human Capital Retention

Science.gov (United States)

Sivich, Lorrie

Projected record retirements of Baby Boomer generation engineers have been predicted to result in significant losses of mission-critical knowledge in space, national security, and future scientific ventures vital to high-technology corporations. No comprehensive review or analysis of engineering capabilities has been performed to identify threats related to the specific loss of mission-critical knowledge posed by the increasing retirement of tenured engineers. Archival data from a single diversified Fortune 500 aerospace manufacturing engineering company's engineering career database were analyzed to ascertain whether relationships linking future engineering capabilities, engineering disciplines, and years of engineering experience could be identified to define critical knowledge transfer models. Chi square, logistic, and linear regression analyses were used to map patterns of discipline-specific, mission-critical knowledge using archival data of engineers' perceptions of engineering capabilities, key developmental experiences, and knowledge learned from their engineering careers. The results from the study were used to document key engineering future capabilities. The results were then used to develop a proposed human capital retention plan to address specific key knowledge gaps of younger engineers as veteran engineers retire. The potential for social change from this study involves informing leaders of aerospace engineering corporations on how to build better quality mentoring or succession plans to fill the void of lost knowledge from retiring engineers. This plan can secure mission-critical knowledge for younger engineers for current and future product development and increased global competitiveness in the technology market.

Turboelectric Aircraft Drive Key Performance Parameters and Functional Requirements

Science.gov (United States)

Jansen, Ralph H.; Brown, Gerald V.; Felder, James L.; Duffy, Kirsten P.

2016-01-01

The purpose of this paper is to propose specific power and efficiency as the key performance parameters for a turboelectric aircraft power system and investigate their impact on the overall aircraft. Key functional requirements are identified that impact the power system design. Breguet range equations for a base aircraft and a turboelectric aircraft are found. The benefits and costs that may result from the turboelectric system are enumerated. A break-even analysis is conducted to find the minimum allowable electric drive specific power and efficiency that can preserve the range, initial weight, operating empty weight, and payload weight of the base aircraft.

41 CFR Appendix A to Subpart D of... - 3-Key Points and Principles

Science.gov (United States)

2010-07-01

... Principles A Appendix A to Subpart D of Part 102 Public Contracts and Property Management Federal Property... Subpart D of Part 102-3—Key Points and Principles This appendix provides additional guidance in the form of answers to frequently asked questions and identifies key points and principles that may be applied...

Network-Guided Key Gene Discovery for a Given Cellular Process

DEFF Research Database (Denmark)

He, Feng Q; Ollert, Markus

2018-01-01

Identification of key genes for a given physiological or pathological process is an essential but still very challenging task for the entire biomedical research community. Statistics-based approaches, such as genome-wide association study (GWAS)- or quantitative trait locus (QTL)-related analysis...... have already made enormous contributions to identifying key genes associated with a given disease or phenotype, the success of which is however very much dependent on a huge number of samples. Recent advances in network biology, especially network inference directly from genome-scale data...

Genomics and relative expression analysis identifies key genes associated with high female to male flower ratio in Jatropha curcas L.

Science.gov (United States)

Gangwar, Manali; Sood, Hemant; Chauhan, Rajinder Singh

2016-04-01

Jatropha curcas, has been projected as a major source of biodiesel due to high seed oil content (42 %). A major roadblock for commercialization of Jatropha-based biodiesel is low seed yield per inflorescence, which is affected by low female to male flower ratio (1:25-30). Molecular dissection of female flower development by analyzing genes involved in phase transitions and floral organ development is, therefore, crucial for increasing seed yield. Expression analysis of 42 genes implicated in floral organ development and sex determination was done at six floral developmental stages of a J. curcas genotype (IC561235) with inherently higher female to male flower ratio (1:8-10). Relative expression analysis of these genes was done on low ratio genotype. Genes TFL1, SUP, AP1, CRY2, CUC2, CKX1, TAA1 and PIN1 were associated with reproductive phase transition. Further, genes CUC2, TAA1, CKX1 and PIN1 were associated with female flowering while SUP and CRY2 in female flower transition. Relative expression of these genes with respect to low female flower ratio genotype showed up to ~7 folds increase in transcript abundance of SUP, TAA1, CRY2 and CKX1 genes in intermediate buds but not a significant increase (~1.25 folds) in female flowers, thereby suggesting that these genes possibly play a significant role in increased transition towards female flowering by promoting abortion of male flower primordia. The outcome of study has implications in feedstock improvement of J. curcas through functional validation and eventual utilization of key genes associated with female flowering.

Two-Dimensional Key Table-Based Group Key Distribution in Advanced Metering Infrastructure

Directory of Open Access Journals (Sweden)

Woong Go

2014-01-01

Full Text Available A smart grid provides two-way communication by using the information and communication technology. In order to establish two-way communication, the advanced metering infrastructure (AMI is used in the smart grid as the core infrastructure. This infrastructure consists of smart meters, data collection units, maintenance data management systems, and so on. However, potential security problems of the AMI increase owing to the application of the public network. This is because the transmitted information is electricity consumption data for charging. Thus, in order to establish a secure connection to transmit electricity consumption data, encryption is necessary, for which key distribution is required. Further, a group key is more efficient than a pairwise key in the hierarchical structure of the AMI. Therefore, we propose a group key distribution scheme using a two-dimensional key table through the analysis result of the sensor network group key distribution scheme. The proposed scheme has three phases: group key predistribution, selection of group key generation element, and generation of group key.

EZID: Long term identifiers made easy (Invited)

Science.gov (United States)

Starr, J.

2013-12-01

Scholarly research is producing ever increasing amounts of digital research data, and this data should be managed throughout the research life cycle both as part of good scientific practice, but also to comply with funder mandates, such as the 2013 OSTP Public Access Memo (http://www.whitehouse.gov/sites/default/files/microsites/ostp/ostp_public_access_memo_2013.pdf). By assigning unique and persistent identifiers to data objects, data managers can gain control and flexibility over what can be a daunting task. This is due to the fact that the objects can be moved to new locations without disruption to links, as long as the identifier target is maintained. EZID is a tool that makes assigning and maintaining unique, persistent identifiers easy. It was designed and built by California Digital Library (CDL) and has both a user interface and a RESTful API. EZID currently offers services for two globally unique, persistent identifier schemes: Digital Object Identifiers (DOIs) and Archival Resource Keys (ARKs). DOIs are identifiers originating from the publishing world and are in widespread use for journal articles. CDL is able to offer DOIs because of being a founding member of DataCite (http://www.datacite.org/), an international consortium established to provide easier access to scientific research data on the Internet. ARKs are identifiers originating from the library, archive and museum community. Like DOIs, they become persistent when the objects and identifier forwarding information is maintained. DOIs and ARKs have a key role in data management and, therefore, in data management plans. DOIs are the recommended identifier for use in data citation, and ARKs provide the maximum flexibility needed for data documentation and management throughout the early phases of a project. The two identifier schemes are able to be used together, and EZID is made to work with both. EZID clients, coming from education, research, government, and the private sector, are utilizing the

Investigation of the key determinants of Asian nurses' quality of life.

Science.gov (United States)

Makabe, Sachiko; Kowitlawakul, Yanika; Nurumal, Mohd Said; Takagai, Junko; Wichaikhum, Orn-Anong; Wangmo, Neyzang; Yap, Suk Foon; Kunaviktikul, Wipada; Komatsu, Junko; Shirakawa, Hideko; Kimura, Yutaka; Asanuma, Yoshihiro

2018-06-01

The study aimed to compare nurses' quality of life and investigate key determinants among Asian countries with different economic status. A cross-sectional survey was conducted across five Asian countries (Japan, Singapore, Malaysia, Thailand, and Bhutan). Quality of life (WHOQOL-BREF), job stress (National Institute of Occupational Safety and Health questionnaire), and demographic data were assessed. Stepwise multivariate linear regression analysis was performed to identify the key determinants of quality of life. Participants were 3,829 nurses (response rate: 82%) with a mean age of 33 ± 10 yr and majority were women (92%). Regarding quality of life, Bhutan yielded the highest scores, followed by Malaysia, Thailand, Singapore, and Japan, and these results were statistically significant. The key determinants that were significantly related to quality of life were "stress coping ability," "life satisfaction," "Japan," "social support," "job stress," and "Singapore" (adjusted R 2 =0.46). In conclusion, nurses' quality of life differs across Asian countries and is not linked to the country's economic development. To maintain a good quality of life for nurses, an international exchange program like international nursing conferences for work environment and staff coping strategies is recommended to broaden institution' minds and share experiences and exchange views to be able to realize their own problems and discover global solutions to them.

Key management of the double random-phase-encoding method using public-key encryption

Science.gov (United States)

Saini, Nirmala; Sinha, Aloka

2010-03-01

Public-key encryption has been used to encode the key of the encryption process. In the proposed technique, an input image has been encrypted by using the double random-phase-encoding method using extended fractional Fourier transform. The key of the encryption process have been encoded by using the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. The encoded key has then been transmitted to the receiver side along with the encrypted image. In the decryption process, first the encoded key has been decrypted using the secret key and then the encrypted image has been decrypted by using the retrieved key parameters. The proposed technique has advantage over double random-phase-encoding method because the problem associated with the transmission of the key has been eliminated by using public-key encryption. Computer simulation has been carried out to validate the proposed technique.

Isolation and Characterization of Well-Defined Silica-Supported Azametallacyclopentane: A Key Intermediate in Catalytic Hydroaminoalkylation Reactions

KAUST Repository

Hamzaoui, Bilel

2015-09-25

Intermolecular catalytic hydroaminoalkylation of unactivated alkene occurs with silica-supported azazirconacyclopropane [[TRIPLE BOND]Si[BOND]O[BOND]Zr(HNMe2)(η2-NMeCH2)(NMe2)]. Mechanistic studies were conducted using surface organometallic chemistry (SOMC) concepts to identify the key surface intermediates. The azametallacyclopentene intermediate {[TRIPLE BOND]Si[BOND]O[BOND]Zr(HNMe2)[η2-NMeCH2CH(Me)CH2](NMe2)} was isolated after treating with 1-propylene and characterized by FT-IR spectroscopy, elemental analysis, 1H 13C HETCOR, DARR SS-NMR and DQ TQ SS-NMR. The regeneration of the catalyst was conducted by dimethylamine protonolysis to yield the pure amine.

Isolation and Characterization of Well-Defined Silica-Supported Azametallacyclopentane: A Key Intermediate in Catalytic Hydroaminoalkylation Reactions

KAUST Repository

Hamzaoui, Bilel; Pelletier, Jé ré mie D. A.; El Eter, Mohamad; Chen, Yin; Abou-Hamad, Edy; Basset, Jean-Marie

2015-01-01

Intermolecular catalytic hydroaminoalkylation of unactivated alkene occurs with silica-supported azazirconacyclopropane [[TRIPLE BOND]Si[BOND]O[BOND]Zr(HNMe2)(η2-NMeCH2)(NMe2)]. Mechanistic studies were conducted using surface organometallic chemistry (SOMC) concepts to identify the key surface intermediates. The azametallacyclopentene intermediate {[TRIPLE BOND]Si[BOND]O[BOND]Zr(HNMe2)[η2-NMeCH2CH(Me)CH2](NMe2)} was isolated after treating with 1-propylene and characterized by FT-IR spectroscopy, elemental analysis, 1H 13C HETCOR, DARR SS-NMR and DQ TQ SS-NMR. The regeneration of the catalyst was conducted by dimethylamine protonolysis to yield the pure amine.

Characterization of key aroma-active compounds in lychee (Litchi chinensis Sonn.

Directory of Open Access Journals (Sweden)

Shi Feng

2018-04-01

Full Text Available Volatile compounds in ‘Sweetheart’ lychee were examined using gas chromatography-olfactometry/mass spectrometry (GC-O/MS. Solvent assisted flavor evaporation (SAFE technique was used to identify the aroma-active compounds in lychee. Further characterization of the most important odorants in ‘Sweetheart’ lychee was achieved using aroma extract dilution analysis (AEDA. Thirty-one key aroma-active odorants were identified in the flavor dilution (FD factor range of 2–1024. Methional (cooked potato and geraniol (sweet, floral exhibited the highest FD factors of 1024 and 512, respectively, these were followed by furaneol (sweet, caramel, nerol (floral, sweet, dimethyl trisulfide (DMTS (preserved vegetable, sulfury, linalool (floral, (E,Z-2,6 nonadienal (cucumber and nerolidol (metalic, sesame oil. Furthermore, the flavor profile of ‘Sweetheart’ lychee was described by sensory analysis. Floral, tropical fruit, peach/apricot and honey were scored with relatively high scores for each aroma attribute. The sweetness rating was the highest score among all the attributes. Keywords: AEDA, Aroma-active compounds, GC-MS/O, SAFE, Sensory analysis

Key Biodiversity Areas in the Philippines: Priorities for Conservation

Directory of Open Access Journals (Sweden)

R.G.R. Ambal

2012-08-01

Full Text Available A process for identifying Key Biodiversity Areas (KBAs for the Philippines was undertaken in two phases. The 128 terrestrial and freshwater KBAs were identified in 2006 and the 123 marine KBAs were identified in 2009. A total of 228 KBAs resulted from the integration of the terrestrial, freshwater and marine KBAs. These KBAs represent the known habitat of 855 globally important species of plants, corals, molluscs, elasmobranchs, fishes, amphibians, reptiles, birds and mammals in the country. Inclusion of these KBAs in the country’s protected area system will be a significant step towards ensuring the conservation of the full scope of the country’s natural heritage.

Book Review: The Communicating Leader: The key to strategic alignment (2nd Ed

Directory of Open Access Journals (Sweden)

X. C. Birkenbach

2003-10-01

Full Text Available Title: The Communicating Leader: The key to strategic alignment (2nd Ed Author: Gustav Puth Publisher: Van Schaik Publishers Reviewer: XC Birkenbach The aim of the book according to the author, is "meant to be a usable tool, an instrument in the toolbox of the real leader and leadership student". The book is written in conversational style (as intended by the author and the 219 pages of the 10 chapters are logically packaged into three parts. While the main emphasis is naturally on leadership and communication, the coverage includes topics typically encountered in Organisational Behaviour or Management texts, e.g., organizational culture, managing change, motivation, conflict management and strategic management.

Assessment of Biotechnology Policies and International Trade in Key Markets for U.S. Agriculture

OpenAIRE

Marchant, Mary A.; Song, Baohui

2005-01-01

The United States leads the world in agricultural biotechnology research, adoption, commercialization, and exports. Our biotech commodities are highly dependent on international markets. Thus, any biotech policy changes by key importing countries may affect U.S. agricultural biotech product exports. This article identifies key markets for U.S. agricultural exports including biotech commodities and discusses current and proposed biotech policies in key markets for U.S. agricultural exports foc...

Key components of financial-analysis education for clinical nurses.

Science.gov (United States)

Lim, Ji Young; Noh, Wonjung

2015-09-01

In this study, we identified key components of financial-analysis education for clinical nurses. We used a literature review, focus group discussions, and a content validity index survey to develop key components of financial-analysis education. First, a wide range of references were reviewed, and 55 financial-analysis education components were gathered. Second, two focus group discussions were performed; the participants were 11 nurses who had worked for more than 3 years in a hospital, and nine components were agreed upon. Third, 12 professionals, including professors, nurse executive, nurse managers, and an accountant, participated in the content validity index. Finally, six key components of financial-analysis education were selected. These key components were as follows: understanding the need for financial analysis, introduction to financial analysis, reading and implementing balance sheets, reading and implementing income statements, understanding the concepts of financial ratios, and interpretation and practice of financial ratio analysis. The results of this study will be used to develop an education program to increase financial-management competency among clinical nurses. © 2015 Wiley Publishing Asia Pty Ltd.

Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma

Directory of Open Access Journals (Sweden)

Ning X

2017-03-01

Full Text Available Xin Ning, Yaoliang Deng Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, People’s Republic of China Background: Genomic profiling can be used to identify the predictive effect of genomic subsets for determining prognosis in bladder urothelial carcinoma (BUC after radical cystectomy. This study aimed to investigate potential gene and pathway markers associated with prognosis in BUC.Methods: A microarray dataset of BUC was obtained from The Cancer Genome Atlas database. Differentially expressed genes (DEGs were identified by DESeq of the R platform. Kaplan–Meier analysis was applied for prognostic markers. Key pathways and genes were identified using bioinformatics tools, such as gene set enrichment analysis, gene ontology, the Kyoto Encyclopedia of Genes and Genomes, gene multiple association network integration algorithm (GeneMANIA, Search Tool for the Retrieval of Interacting Genes/Proteins, and Molecular Complex Detection.Results: A comparative gene set enrichment analysis of tumor and adjacent normal tissues suggested BUC tumorigenesis resulted mainly from enrichment of cell cycle and DNA damage and repair-related biological processes and pathways, including TP53 and mitotic recombination. Two hundred and fifty-six genes were identified as potential prognosis-related DEGs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the potential prognosis-related DEGs were enriched in angiogenesis, including the cyclic adenosine monophosphate biosynthetic process, cyclic guanosine monophosphate-protein kinase G, mitogen-activated protein kinase, Rap1, and phosphoinositide-3-kinase-AKT signaling pathway. Nine hub genes, TAGLN, ACTA2, MYH11, CALD1, MYLK, GEM, PRELP, TPM2, and OGN, were identified from the intersection of protein–protein interaction and GeneMANIA networks. Module analysis of protein–protein interaction and GeneMANIA networks mainly showed

Decoy State Quantum Key Distribution

Science.gov (United States)

Lo, Hoi-Kwong

2005-10-01

Quantum key distribution (QKD) allows two parties to communicate in absolute security based on the fundamental laws of physics. Up till now, it is widely believed that unconditionally secure QKD based on standard Bennett-Brassard (BB84) protocol is limited in both key generation rate and distance because of imperfect devices. Here, we solve these two problems directly by presenting new protocols that are feasible with only current technology. Surprisingly, our new protocols can make fiber-based QKD unconditionally secure at distances over 100km (for some experiments, such as GYS) and increase the key generation rate from O(η2) in prior art to O(η) where η is the overall transmittance. Our method is to develop the decoy state idea (first proposed by W.-Y. Hwang in "Quantum Key Distribution with High Loss: Toward Global Secure Communication", Phys. Rev. Lett. 91, 057901 (2003)) and consider simple extensions of the BB84 protocol. This part of work is published in "Decoy State Quantum Key Distribution", . We present a general theory of the decoy state protocol and propose a decoy method based on only one signal state and two decoy states. We perform optimization on the choice of intensities of the signal state and the two decoy states. Our result shows that a decoy state protocol with only two types of decoy states--a vacuum and a weak decoy state--asymptotically approaches the theoretical limit of the most general type of decoy state protocols (with an infinite number of decoy states). We also present a one-decoy-state protocol as a special case of Vacuum+Weak decoy method. Moreover, we provide estimations on the effects of statistical fluctuations and suggest that, even for long distance (larger than 100km) QKD, our two-decoy-state protocol can be implemented with only a few hours of experimental data. In conclusion, decoy state quantum key distribution is highly practical. This part of work is published in "Practical Decoy State for Quantum Key Distribution

Identifying groups of nonparticipants in type 2 diabetes mellitus education.

Science.gov (United States)

Schäfer, Ingmar; Küver, Claudia; Wiese, Birgitt; Pawels, Marc; van den Bussche, Hendrik; Kaduszkiewicz, Hannah

2013-06-01

Patient education is a compulsory element of the nationwide disease management program (DMP) for type 2 diabetes mellitus in Germany. However, a considerable proportion of patients do not attend diabetes self-management education courses. Therefore, the purpose of this study was to describe patient-reported reasons for nonparticipation and to identify typical subgroups of nonparticipants in order to improve recruitment strategies. The authors performed a cross-sectional observational study on 165 participants and 132 nonparticipants in diabetes education using a postal survey and chart review. Participants and nonparticipants were compared using 2-sided t tests and χ2 tests. Nonparticipants were grouped by cluster analysis based on the reasons for nonparticipation. A total of 95% of participants and 36% of nonparticipants reported to have received a recommendation for diabetes education from their physician. The authors identified 4 typical subgroups of nonparticipants: the "informed and responsible," the "unconcerned without desire for more information," the "uninformed but responsible," and the "anxious and burdened with psychosocial problems and functional limitations." The physician's recommendation seems to influence participation in diabetes education and should be used intentionally to increase participation rates. Also, differentiating barriers of nonparticipants can be determined by the degree of feeling informed and responsible for diabetes management. Physicians should more clearly explore patients' perception of their knowledge of diabetes and their attribution of responsibility for diabetes management. Starting from this patient perspective might help physicians motivate patients to participate in diabetes education.

Preparedness for physiotherapy in private practice: Novices identify key factors in an interpretive description study.

Science.gov (United States)

Atkinson, Robyn; McElroy, Theresa

2016-04-01

Physiotherapists in Australia deliver services to a diverse range of clients, across many settings, however little research exists examining graduate preparedness for practice, even in the populous field of private practice. To explore novice physiotherapist perspectives on preparedness for work in private practice. The qualitative approach of interpretive description was used to guide in-depth interviews with 8 novice physiotherapists from 3 universities working in 5 private practices in Melbourne. All interviews were digitally recorded, transcribed verbatim and analyzed thematically. Four main themes influencing graduate preparedness for work in private practice were identified: 1) non-curricular experiences (e.g. sports training) 2) elective curricular: practicum experiences; 3) curricular: attainment of skills specific to private practice; and 4) the private practice setting: supportive colleagues. This combination of non-curricular, curricular, and practice setting factors offered the necessary scaffolding for the graduates to report feeling prepared for work in private practice. Non-curricular activities, radiological instruction, clinical placements, building supportive colleague relations and professional development in private practice are recommended as potential means of building preparedness in novice therapists. Findings have implications for physiotherapy students, educators and private practice clinics looking to recruit new graduates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stego Keys Performance on Feature Based Coding Method in Text Domain

Directory of Open Access Journals (Sweden)

Din Roshidi

2017-01-01

Full Text Available A main critical factor on embedding process in any text steganography method is a key used known as stego key. This factor will be influenced the success of the embedding process of text steganography method to hide a message from third party or any adversary. One of the important aspects on embedding process in text steganography method is the fitness performance of the stego key. Three parameters of the fitness performance of the stego key have been identified such as capacity ratio, embedded fitness ratio and saving space ratio. It is because a better as capacity ratio, embedded fitness ratio and saving space ratio offers of any stego key; a more message can be hidden. Therefore, main objective of this paper is to analyze three features coding based namely CALP, VERT and QUAD of stego keys in text steganography on their capacity ratio, embedded fitness ratio and saving space ratio. It is found that CALP method give a good effort performance compared to VERT and QUAD methods.

Field Keys to Common Hawaiian Marine Animals and Plants.

Science.gov (United States)

Hawaii State Dept. of Education, Honolulu. Office of Instructional Services.

Presented are keys for identifying common Hawaiian marine algae, beach plants, reef corals, sea urchins, tidepool fishes, and sea cucumbers. Nearly all species considered can be distinguished by characteristics visible to the naked eye. Line drawings illustrate most plants and animals included, and a list of suggested readings follows each…

Use of participant focus groups to identify barriers and facilitators to worksite exercise therapy adherence in randomized controlled trials involving firefighters

Directory of Open Access Journals (Sweden)

Mayer JM

2013-03-01

Full Text Available John M Mayer,1 James L Nuzzo,1 Simon Dagenais2 1School of Physical Therapy and Rehabilitation Sciences, College of Medicine, University of South Florida, Tampa, FL, 2Palladian Health, West Seneca, NY, USA Background: Firefighters are at increased risk for back injuries, which may be mitigated through exercise therapy to increase trunk muscle endurance. However, long-term adherence to exercise therapy is generally poor, limiting its potential benefits. Focus groups can be used to identify key barriers and facilitators to exercise adherence among study participants. Objective: To explore barriers and facilitators to worksite exercise therapy adherence among firefighters to inform future randomized controlled trials (RCTs. Methods: Participants enrolled in a previous RCT requiring twice-weekly worksite exercise therapy for 24 weeks were asked to take part in moderated focus group discussions centered on eight open-ended questions related to exercise adherence. Responses were analyzed qualitatively using a social ecological framework to identify key intrapersonal, interpersonal, and institutional barriers and potential facilitators to exercise adherence. Results: A total of 27 participants were included in the four focus group discussions, representing 50% of those assigned to a worksite exercise therapy group in the previous RCT, in which only 67% of scheduled exercise therapy sessions were completed. Lack of self-motivation was cited as the key intrapersonal barrier to adherence, while lack of peer support was the key interpersonal barrier reported, and lack of time to exercise during work shifts was the key institutional barrier identified. Conclusion: Focus group discussions identified both key barriers and potential facilitators to increase worksite exercise therapy adherence among firefighters. Future studies should consider educating and reminding participants about the benefits of exercise, providing individual and group incentives based on

Which Doctor to Trust: A Recommender System for Identifying the Right Doctors.

Science.gov (United States)

Guo, Li; Jin, Bo; Yao, Cuili; Yang, Haoyu; Huang, Degen; Wang, Fei

2016-07-07

Key opinion leaders (KOLs) are people who can influence public opinion on a certain subject matter. In the field of medical and health informatics, it is critical to identify KOLs on various disease conditions. However, there have been very few studies on this topic. We aimed to develop a recommender system for identifying KOLs for any specific disease with health care data mining. We exploited an unsupervised aggregation approach for integrating various ranking features to identify doctors who have the potential to be KOLs on a range of diseases. We introduce the design, implementation, and deployment details of the recommender system. This system collects the professional footprints of doctors, such as papers in scientific journals, presentation activities, patient advocacy, and media exposure, and uses them as ranking features to identify KOLs. We collected the information of 2,381,750 doctors in China from 3,657,797 medical journal papers they published, together with their profiles, academic publications, and funding. The empirical results demonstrated that our system outperformed several benchmark systems by a significant margin. Moreover, we conducted a case study in a real-world system to verify the applicability of our proposed method. Our results show that doctors' profiles and their academic publications are key data sources for identifying KOLs in the field of medical and health informatics. Moreover, we deployed the recommender system and applied the data service to a recommender system of the China-based Internet technology company NetEase. Patients can obtain authority ranking lists of doctors with this system on any given disease.

The Key Pieces of the Career Survival and Success Puzzle.

Science.gov (United States)

Simonetti, Jack L.

1999-01-01

Analysis of career-success factors identified by 5,000 managers yielded 10 key pieces: excellent performance record, communication skills, interpersonal skills, personality, skill currency, significant work experiences, power, ability to withstand pressure, ability to make difficult decisions, and having a mentor. (SK)

Identifying Key Features of Effective Active Learning: The Effects of Writing and Peer Discussion

Science.gov (United States)

Pangle, Wiline M.; Wyatt, Kevin H.; Powell, Karli N.; Sherwood, Rachel E.

2014-01-01

We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between three sections taught by three different instructors in a full factorial design. The data set was analyzed by generalized linear mixed-effect models with three independent variables: student aptitude, treatment, and instructor, and three dependent (assessment) variables: change in score on pre- and postactivity clicker questions, and coding scores on in-class writing and exam essays. All independent variables had significant effects on student performance for at least one of the dependent variables. Students with higher aptitude scored higher on all assessments. Student scores were higher on exam essay questions when the activity was implemented with a writing component compared with peer discussion only. There was a significant effect of instructor, with instructors showing different degrees of effectiveness with active-learning techniques. We suggest that individual writing should be implemented as part of active learning whenever possible and that instructors may need training and practice to become effective with active learning. PMID:25185230

Monoclonal antibody OKB7, which identifies the 14OKd complement receptor type 2 (CR2), also identifies a 72Kd secreted fragment of CR2 that contains the C3d-binding site

International Nuclear Information System (INIS)

Myones, B.L.; Ross, G.D.

1986-01-01

CR 2 is a 140-145Kd glycoprotein expressed on B lymphocytes which binds both C3d and Epstein-Barr virus (EBV). OKB7, an IgG/sub 2a/ monoclonal antibody to CR 2 , blocks C3d and EBV binding, while HB-5, another monoclonal IgG/sub 2a/ anti-CR 2 , does not. A 72Kd C3d-binding glycoprotein (gp72), isolated from Raji cell media, was previously thought to be CR 2 because a polyclonal rabbit anti-gp72 inhibited EC3d rosettes. ELISA assay demonstrated that OKB7, but not HB-5, bound to purified gp72 fixed to microtiter wells. Insoluble and soluble gp72 blocked Raji cell uptake of 125 I-labeled OKB7, but not labeled anti-B2 or HB-5. Rabbit anti-gp72 immunoprecipitated bands at 140Kd and 72Kd from 125 I-labelled and solubilized B cell membranes. Culture media from Raji cells grown in the presence 3 H-labeled amino acids was sequentially immunoprecipitated by irrelevant antibody, OKB7, and HB-5. A single 72Kd radiolabeled band was demonstrated only with OKB7, and this was identical to that produced by the immunoprecipitation of 125 I-labeled gp72 with rabbit anti-gp72. Thus, OKB7, which identifies the 140Kd CR 2 molecule, also identifies a 72Kd shed fragment of CR 2 isolated from Raji cell media, which contains the C3d-binding site

Identifying continuous quality improvement publications: what makes an improvement intervention 'CQI'?

Science.gov (United States)

O'Neill, Sean M; Hempel, Susanne; Lim, Yee-Wei; Danz, Marjorie S; Foy, Robbie; Suttorp, Marika J; Shekelle, Paul G; Rubenstein, Lisa V

2011-12-01

The term continuous quality improvement (CQI) is often used to refer to a method for improving care, but no consensus statement exists on the definition of CQI. Evidence reviews are critical for advancing science, and depend on reliable definitions for article selection. As a preliminary step towards improving CQI evidence reviews, this study aimed to use expert panel methods to identify key CQI definitional features and develop and test a screening instrument for reliably identifying articles with the key features. We used a previously published method to identify 106 articles meeting the general definition of a quality improvement intervention (QII) from 9427 electronically identified articles from PubMed. Two raters then applied a six-item CQI screen to the 106 articles. Per cent agreement ranged from 55.7% to 75.5% for the six items, and reviewer-adjusted intra-class correlation ranged from 0.43 to 0.62. 'Feedback of systematically collected data' was the most common feature (64%), followed by being at least 'somewhat' adapted to local conditions (61%), feedback at meetings involving participant leaders (46%), using an iterative development process (40%), being at least 'somewhat' data driven (34%), and using a recognised change method (28%). All six features were present in 14.2% of QII articles. We conclude that CQI features can be extracted from QII articles with reasonable reliability, but only a small proportion of QII articles include all features. Further consensus development is needed to support meaningful use of the term CQI for scientific communication.

Final report on CCM key comparison CCM.D-K2: Comparison of liquid density standards

Science.gov (United States)

Bettin, Horst; Jacques, Claude; Zelenka, Zoltán; Fujii, Ken-ichi; Kuramoto, Naoki; Chang, Kyung-Ho; Lee, Yong Jae; Becerra, Luis Omar; Domostroeva, Natalia

2013-01-01

The results are presented of the key comparison CCM.D-K2 that covered the density measurements of four liquids: the density of water at 20 °C, of pentadecane at 15 °C, 20 °C, 40 °C and 60°C, of tetrachloroethlyene at 5 °C and 20 °C and of a viscous oil at 20 °C. Seven national metrology institutes measured the densities at atmospheric pressure by hydrostatic weighing of solid density standards in the time interval from 27 April 2004 to 28 June 2004. Since the participants were asked not to include components for a possible drift or inhomogeneity of the liquid in their uncertainty budget, these uncertainty contributions are investigated for the final evaluation of the data. For this purpose, results of stability and homogeneity measurements of the pilot laboratory are used. The participants decided not to include a possible drift of the liquid's density since no significant drift could be detected, and the influence of the drift and its uncertainty are negligible. Similarly, the inhomogeneity of the water and pentadecane samples is not significant and has no influence on the evaluation. Thus, it was neglected. Only the inhomogeneities of tetrachloroethylene and of the viscous oil were significant. Consequently, they were included in the evaluation. With one or two exceptions, the results show good agreement among the participants. Only in the case of water are the results clearly discrepant. The key comparison reference values were calculated by the weighted mean (taking into account a small correlation between two participants) in the case of consistent results. Otherwise the Procedure B of Cox was used. The expanded uncertainties of all reference densities are below 1 × 10-5 in relative terms. This satisfies the needs of all customers who wish to calibrate or check liquid density measuring instruments such as oscillation-type density meters. The comparison fully supports the calibration measurement capabilities table in the BIPM key comparison database

Data analytics identify glycated haemoglobin co-markers for type 2 diabetes mellitus diagnosis.

Science.gov (United States)

Jelinek, Herbert F; Stranieri, Andrew; Yatsko, Andrew; Venkatraman, Sitalakshmi

2016-08-01

Glycated haemoglobin (HbA1c) is being more commonly used as an alternative test for the identification of type 2 diabetes mellitus (T2DM) or to add to fasting blood glucose level and oral glucose tolerance test results, because it is easily obtained using point-of-care technology and represents long-term blood sugar levels. HbA1c cut-off values of 6.5% or above have been recommended for clinical use based on the presence of diabetic comorbidities from population studies. However, outcomes of large trials with a HbA1c of 6.5% as a cut-off have been inconsistent for a diagnosis of T2DM. This suggests that a HbA1c cut-off of 6.5% as a single marker may not be sensitive enough or be too simple and miss individuals at risk or with already overt, undiagnosed diabetes. In this study, data mining algorithms have been applied on a large clinical dataset to identify an optimal cut-off value for HbA1c and to identify whether additional biomarkers can be used together with HbA1c to enhance diagnostic accuracy of T2DM. T2DM classification accuracy increased if 8-hydroxy-2-deoxyguanosine (8-OhdG), an oxidative stress marker, was included in the algorithm from 78.71% for HbA1c at 6.5% to 86.64%. A similar result was obtained when interleukin-6 (IL-6) was included (accuracy=85.63%) but with a lower optimal HbA1c range between 5.73 and 6.22%. The application of data analytics to medical records from the Diabetes Screening programme demonstrates that data analytics, combined with large clinical datasets can be used to identify clinically appropriate cut-off values and identify novel biomarkers that when included improve the accuracy of T2DM diagnosis even when HbA1c levels are below or equal to the current cut-off of 6.5%. Copyright © 2016 Elsevier Ltd. All rights reserved.

Autoshaping of key pecking in pigeons with negative reinforcement.

Science.gov (United States)

Rachlin, H

1969-07-01

Pigeons exposed to gradually increasing intensities of pulsing electric shock pecked a key and thereby reduced the intensity of shock to zero for 2 min. Acquisition of key pecking was brought about through an autoshaping process in which periodic brief keylight presentations immediately preceded automatic reduction of the shock. On the occasions of such automatic reduction of shock preceding the first measured key peck, little or no orientation to the key was observed. Observations of pigeons with autoshaping of positive reinforcement also revealed little evidence of orientation toward the key.

Integrated network analysis identifies fight-club nodes as a class of hubs encompassing key putative switch genes that induce major transcriptome reprogramming during grapevine development.

Science.gov (United States)

Palumbo, Maria Concetta; Zenoni, Sara; Fasoli, Marianna; Massonnet, Mélanie; Farina, Lorenzo; Castiglione, Filippo; Pezzotti, Mario; Paci, Paola

2014-12-01

We developed an approach that integrates different network-based methods to analyze the correlation network arising from large-scale gene expression data. By studying grapevine (Vitis vinifera) and tomato (Solanum lycopersicum) gene expression atlases and a grapevine berry transcriptomic data set during the transition from immature to mature growth, we identified a category named "fight-club hubs" characterized by a marked negative correlation with the expression profiles of neighboring genes in the network. A special subset named "switch genes" was identified, with the additional property of many significant negative correlations outside their own group in the network. Switch genes are involved in multiple processes and include transcription factors that may be considered master regulators of the previously reported transcriptome remodeling that marks the developmental shift from immature to mature growth. All switch genes, expressed at low levels in vegetative/green tissues, showed a significant increase in mature/woody organs, suggesting a potential regulatory role during the developmental transition. Finally, our analysis of tomato gene expression data sets showed that wild-type switch genes are downregulated in ripening-deficient mutants. The identification of known master regulators of tomato fruit maturation suggests our method is suitable for the detection of key regulators of organ development in different fleshy fruit crops. © 2014 American Society of Plant Biologists. All rights reserved.

Coherent one-way quantum key distribution

Science.gov (United States)

Stucki, Damien; Fasel, Sylvain; Gisin, Nicolas; Thoma, Yann; Zbinden, Hugo

2007-05-01

Quantum Key Distribution (QKD) consists in the exchange of a secrete key between two distant points [1]. Even if quantum key distribution systems exist and commercial systems are reaching the market [2], there are still improvements to be made: simplify the construction of the system; increase the secret key rate. To this end, we present a new protocol for QKD tailored to work with weak coherent pulses and at high bit rates [3]. The advantages of this system are that the setup is experimentally simple and it is tolerant to reduced interference visibility and to photon number splitting attacks, thus resulting in a high efficiency in terms of distilled secret bits per qubit. After having successfully tested the feasibility of the system [3], we are currently developing a fully integrated and automated prototype within the SECOQC project [4]. We present the latest results using the prototype. We also discuss the issue of the photon detection, which still remains the bottleneck for QKD.

Modular Connector Keying Concept

Science.gov (United States)

Ishman, Scott; Dukes, Scott; Warnica, Gary; Conrad, Guy; Senigla, Steven

2013-01-01

For panel-mount-type connectors, keying is usually "built-in" to the connector body, necessitating different part numbers for each key arrangement. This is costly for jobs that require small quantities. This invention was driven to provide a cost savings and to reduce documentation of individual parts. The keys are removable and configurable in up to 16 combinations. Since the key parts are separate from the connector body, a common design can be used for the plug, receptacle, and key parts. The keying can then be set at the next higher assembly.

An approach to identify issues affecting ERP implementation in Indian SMEs

Directory of Open Access Journals (Sweden)

Rana Basu

2012-06-01

Full Text Available Purpose: The purpose of this paper is to present the findings of a study which is based on the results of a comprehensive compilation of literature and subsequent analysis of ERP implementation success issues in context to Indian Small and Medium scale Enterprises (SME’s. This paper attempts to explore the existing literature and highlight those issues on ERP implementation and further to this the researchers applied TOPSIS (Technique for order preference by similarity to ideal solution method to prioritize issues affecting successful implementation of ERP. Design/methodology/approach: Based on the literature review certain issues leading to successful ERP implementation have been identified and to identify key issues Pareto Analysis (80-20 Rule have been applied. Further to extraction of key issues a survey based on TOPSIS was carried out in Indian small and medium scale enterprises. Findings: Based on review of literature 25 issues have been identified and further Pareto analysis has been done to extract key issues which is further prioritized by applying Topsis method. Research limitations/implications: Beside those identified issues there may be other issues that need to be explored. There is scope to enhance this study by taking into consideration different type of industries and by extending number of respondents. Practical implications: By identifying key issues for SMEs, managers can better prioritize issues to make implementation process smooth without disruption. ERP vendors can take inputs from this study to change their implementation approach while targeting small scale enterprises. Originality/value: There is no published literature available which followed a similar approach in identification of the critical issues affecting ERP in small and mid-sized companies in India or in any developing economy.

A quantitative metric to identify critical elements within seafood supply networks.

Directory of Open Access Journals (Sweden)

Éva E Plagányi

Full Text Available A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical.

A Quantitative Metric to Identify Critical Elements within Seafood Supply Networks

Science.gov (United States)

Plagányi, Éva E.; van Putten, Ingrid; Thébaud, Olivier; Hobday, Alistair J.; Innes, James; Lim-Camacho, Lilly; Norman-López, Ana; Bustamante, Rodrigo H.; Farmery, Anna; Fleming, Aysha; Frusher, Stewart; Green, Bridget; Hoshino, Eriko; Jennings, Sarah; Pecl, Gretta; Pascoe, Sean; Schrobback, Peggy; Thomas, Linda

2014-01-01

A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical. PMID:24633147

A quantitative metric to identify critical elements within seafood supply networks.

Science.gov (United States)

Plagányi, Éva E; van Putten, Ingrid; Thébaud, Olivier; Hobday, Alistair J; Innes, James; Lim-Camacho, Lilly; Norman-López, Ana; Bustamante, Rodrigo H; Farmery, Anna; Fleming, Aysha; Frusher, Stewart; Green, Bridget; Hoshino, Eriko; Jennings, Sarah; Pecl, Gretta; Pascoe, Sean; Schrobback, Peggy; Thomas, Linda

2014-01-01

A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical.

Measuring social inclusion--a key outcome in global mental health.

Science.gov (United States)

Baumgartner, Joy Noel; Burns, Jonathan K

2014-04-01

Social inclusion is increasingly recognized as a key outcome for evaluating global mental health programmes and interventions. Whereas social inclusion as an outcome is not a new concept in the field of mental health, its measurement has been hampered by varying definitions, concepts and instruments. To move the field forward, this paper reviews the currently available instruments which measure social inclusion and are reported in the literature, realizing that no single measure will be appropriate for all studies or contexts. A systematic literature search of English language peer-reviewed articles published through February 2013 was undertaken to identify scales specifically developed to measure social inclusion or social/community integration among populations with mental disorders. Five instruments were identified through the search criteria. The scales are discussed in terms of their theoretical underpinnings, domains and/or key items and their potential for use in global settings. Whereas numerous reviewed abstracts discussed mental health and social inclusion or social integration, very few were concerned with direct measurement of the construct. All identified scales were developed in high-income countries with limited attention paid to how the scale could be adapted for cross-cultural use. Social inclusion is increasingly highlighted as a key outcome for global mental health policies and programmes, yet its measurement is underdeveloped. There is need for a global cross-cultural measure that has been developed and tested in diverse settings. However, until that need is met, some of the scales presented here may be amenable to adaptation.

Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases

Directory of Open Access Journals (Sweden)

Giorgia Pierelli

2017-01-01

Full Text Available Uncoupling protein 2 (UCP2 is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension. The deletion of the UCP2 gene contributes to atherosclerosis lesion development in the knockout mice, also showing significantly shorter lifespan. The UCP2 gene downregulation is a key determinant of higher predisposition to renal and cerebrovascular damage in an animal model of spontaneous hypertension and stroke. In contrast, UCP2 overexpression improves both hyperglycemia- and high-salt diet-induced endothelial dysfunction and ameliorates hypertensive target organ damage in SHRSP. Moreover, drugs (fenofibrate and sitagliptin and several vegetable compounds (extracts from Brassicaceae, berberine, curcumin, and capsaicin are able to induce UCP2 expression level and to exert beneficial effects on the occurrence of vascular damage. As a consequence, UCP2 becomes an interesting therapeutic target for the treatment of common human vascular diseases.

Identify and rank key factors influencing the adoption of cloud computing for a healthy Electronics

Directory of Open Access Journals (Sweden)

Javad Shukuhy

2015-02-01

Full Text Available Cloud computing as a new technology with Internet infrastructure and new approaches can be significant benefits in providing medical services electronically. Aplying this technology in E-Health requires consideration of various factors. The main objective of this study is to identify and rank the factors influencing the adoption of e-health cloud. Based on the Technology-Organization-Environment (TOE framework and Human-Organization-Technology fit (HOT-fit model, 16 sub-factors were identified in four major factors. With survey of 60 experts, academics and experts in health information technology and with the help of fuzzy analytic hierarchy process had ranked these sub-factors and factors. In the literature, considering newness this study, no internal or external study, have not alluded these number of criteria. The results show that when deciding to adopt cloud computing in E-Health, respectively, must be considered technological, human, organizational and environmental factors.

Backward compatibility as a key measure for smooth upgrades to the LHC control system

International Nuclear Information System (INIS)

Baggiolini, V.; Csikos, D.; Tarasenko, P.; Zaharieva, Z.; Arruat, M.; Gorbosonov, R.

2012-01-01

It is a big challenge to smoothly upgrade the control system of a large operational accelerator such as the LHC without causing unnecessary downtime. We have identified backward compatibility as a key measure to achieve this, because a backward compatible component can be easily upgraded. This document describes the work the CERN Accelerator Controls group does to provide methods and tools supporting backward compatibility. We have identified four areas for which we want to provide tools: (1) dependency analysis to identify incoming dependencies, (2) backward compatibility validation to verify that API (Application Program Interface) changes are really backward compatible, (3) version upgrading with rules to clearly inform the dependent clients if a modification is backward compatible, and (4) API consolidation to clearly specify classes and methods belonging to the API and to enforce their appropriate usage

Key events and their effects on cycling behaviour in Dar-es-Salaam : abstract + powerpoint

NARCIS (Netherlands)

Nkurunziza, A.; Zuidgeest, M.H.P.; Brussel, M.J.G.; van Maarseveen, M.F.A.M.

2012-01-01

The paper explores key events and investigates their effects on cycling behaviour in the city of Dar-es-Salaam, Tanzania. The objective of the study is to identify specific key events during a person’s life course with a significant effect on change of travel behaviour towards cycling in relation to

Ppargamma2 is a key driver of longevity in the mouse.

Directory of Open Access Journals (Sweden)

Carmen Argmann

2009-12-01

Full Text Available Aging involves a progressive physiological remodeling that is controlled by both genetic and environmental factors. Many of these factors impact also on white adipose tissue (WAT, which has been shown to be a determinant of lifespan. Interrogating a transcriptional network for predicted causal regulatory interactions in a collection of mouse WAT from F2 crosses with a seed set of 60 known longevity genes, we identified a novel transcriptional subnetwork of 742 genes which represent thus-far-unknown longevity genes. Within this subnetwork, one gene was Pparg (Nr1c3, an adipose-enriched nuclear receptor previously not associated with longevity. In silico, both the PPAR signaling pathway and the transcriptional signature of Ppargamma agonist rosiglitazone overlapped with the longevity subnetwork, while in vivo, lowered expression of Pparg reduced lifespan in both the lipodystrophic Pparg1/2-hypomorphic and the Pparg2-deficient mice. These results establish Ppargamma2 as one of the determinants of longevity and suggest that lifespan may be rather determined by a purposeful genetic program than a random process.

Flow hydrodynamics near inlet key of Piano Key Weir (PKW)

Indian Academy of Sciences (India)

Department of Water Resources Development and Management, Indian Institute ... on the hydrodynamic performance near inlet key of Piano Key Weir (PKW). ... nature of flows is clearly understood with the help of advanced instrumentation.

High-Rate Field Demonstration of Large-Alphabet Quantum Key Distribution

Science.gov (United States)

2016-10-12

count rate of Bob’s detectors. In this detector-limited regime , it is advantageous to increase M to encode as much information as possible in each...High- rate field demonstration of large-alphabet quantum key distribution Catherine Lee,1, 2 Darius Bunandar,1 Zheshen Zhang,1 Gregory R. Steinbrecher...October 12, 2016) 2 Quantum key distribution (QKD) enables secure symmetric key exchange for information-theoretically secure com- munication via one-time

Definition of Smart Energy City and State of the art of 6 Transform cities using Key Performance Indicators. Deliverable 1.2

Energy Technology Data Exchange (ETDEWEB)

Sieverts Nielsen, P.; Amer, S.B.; Halsnaes, K.

2013-08-15

This report summarises the work undertaken under the EU-FP7 TRANSFORM project for Work Package 1 (part 1): Becoming a Smart Energy City, state of the Art and Ambition. Part 1 starts with a clear outline of each of the participating cities. The work describes the context in terms of climate, energy assets, ambitions, targets and main possibilities in terms of energy efficiency, flows and energy production. After this first step, the work focuses on the description of what a smart energy city is (this report), what the main Key Performance Indicators (KPIs) are that should be met and how this relates to where the current cities and the living labs are. It describes at the same time the current status of city planning, energy planning tools, and existing energy data. The outline should also include information on energy production, energy flows and energy efficiency, where possible. The work will draw largely on existing Strategic Energy Action Plans, Climate Action Plans and planning documents. This report establishes a definition of smart cities, develops Key Elements, Key Performance Indicators and reports on the state of the art regarding the KPIs for the 6 Transform cities. As specified in the Transform proposal, the objective of the evaluation is to identify previous and existing initiatives as a sort of stocktaking on the way to establishing a smart city transformation pathway for each of the participating cities in the Transform project. The definition of a smart energy city and the key performance indicators will be used throughout Transform the guide the work. (Author)

Quantum cryptography to satellites for global secure key distribution

Science.gov (United States)

Rarity, John G.; Gorman, Philip M.; Knight, Paul; Wallace, Kotska; Tapster, Paul R.

2017-11-01

We have designed and built a free space secure key exchange system using weak laser pulses with polarisation modulation by acousto-optic switching. We have used this system to exchange keys over a 1.2km ground range with absolute security. Building from this initial result we analyse the feasibility of exchanging keys to a low earth orbit satellite.

Key factors in the successful implementation of enterprise resource planning system

Directory of Open Access Journals (Sweden)

Farajollah Rahnavard

2014-04-01

Full Text Available Enterprise Resource Planning Systems (ERP are considered as the newest and most effective tools of enterprise resource planning and include an interconnected information, management and engineering system that meets all the needs of an organization. ERP implementation is costly and time-consuming and makes fundamental change in the process, if not implemented correctly it will cause challenges in most parts of the organization and will certainly fail. Therefore, the identification of key success factors in implementing ERP helps organizations avoid the loss of the project. This research aims to identify key success factors for ERP by examining 185 managers, professionals, experts of the Information and Communication Technology Institute associated with the Ministry of Communications and Information Technology of Iran. A questionnaire was used to collect data. Findings from exploratory factor analysis indicate that five factors: 1 user friendliness, flexible and consistency 2 establishment of project management; 3 alignment with user needs; 4 Management of organizational changes, and 5 observing the principles of successful implementation of ERP affect the institute and the corresponding suggestions are proposed consistent with these findings.

The MycoKey 3.1 DVD. Included in Knudsen, H. & Vesterholt, J. (eds.). Funga Nordica

DEFF Research Database (Denmark)

2008-01-01

. It is, of course, also possible to do a direct search on a name in MycoKey in order to find a genus or a particular species. MycoKey gives access to more than 4,000 illustrations of fungi and more than 17,000 links to references. From within the genera you can also open the Funga Nordica keys in a a pdf-viwer......MycoKey enables the user to identify fungal genera (fruitbody forming Basidiomycota and discomycetes) by means of a digital, synoptical key. This key offers a very different way of choosing between genera than the traditional analytical key and the the two approaches complete each other nicely...

Key to good fit: body measurement problems specific to key ...

African Journals Online (AJOL)

Key to good fit: body measurement problems specific to key dimensions. ... to explore and describe the problems that the South African Clothing Industry currently ... A postal survey was conducted among South African apparel and footwear ...

Determining the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant: a cross-sectional survey.

Science.gov (United States)

Fernandez, Ritin S; Sheppard-Law, Suzanne; Manning, Vicki

2017-06-01

Globally, many nurses and midwives are working at an advanced practice level. The role of a Nurse and/or Midwife Consultant encompasses a diverse and complex interaction between five specified domains namely Clinical Service and Consultancy, Clinical Leadership, Research, Education, and Clinical Services Planning and Management. The objective of this replication study was to identify the key drivers and mitigating factors that impact the role of Australian Nurse and/or Midwife Consultants. Cross-sectional survey. The study was conducted in a large metropolitan health district in Sydney, Australia. Participants for this study consisted of all Nurse and/or Midwife Consultants working within a health district in New South Wales (NSW). Data were collected by an anonymous online survey. Key drivers and mitigating factors perceived to influence their role were identified using previously implemented instruments. Data were analysed using SPSS version 21. Responses were obtained from 122 Nurse and/or Midwife Consultants. The number of years of experience as a Nurse and/or Midwife Consultant ranged from 6 months to 25.5 years. Personal attributes which included personal motivation and own communication skills were identified as key drivers to role performance with a mean score of 7.7±0.6. Other key drivers included peer support, organisational culture, personal attributes, professional learning, Nurse and/or Midwife Consultant experience, and collaborative relationships. Of the 14 mitigating factors to the role, the most common factors were lack of resources to set up and develop the role (2.6 ± 0.9), lack of secretarial support (2.6 ± 1.1), lack of managerial support (2.45 ± 1.1), and lack of understanding of the role by other health professionals (2.40 ± 0.8). Understanding the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant is important for healthcare managers. Given the changing landscape of nursing

Glutamate receptor antagonists and growth factors modulate dentate granule cell neurogenesis in organotypic, rat hippocampal slice cultures

DEFF Research Database (Denmark)

Poulsen, Frantz Rom; Blaabjerg, Morten; Montero, Maria

2005-01-01

facing CA1 and the immediate subgranular zone, exposure for 3 days to the NMDA receptor blocking agents MK-801 (10 microM) or APV (25 microM) in the culture medium, increased the number of TOAD-64/Ulip/CRMP-4 (TUC-4)-positive cells as counted in the slice cultures at the end of the 3-day treatment period...

Predicting suicidal ideation in primary care: An approach to identify easily assessable key variables.

Science.gov (United States)

Jordan, Pascal; Shedden-Mora, Meike C; Löwe, Bernd

To obtain predictors of suicidal ideation, which can also be used for an indirect assessment of suicidal ideation (SI). To create a classifier for SI based on variables of the Patient Health Questionnaire (PHQ) and sociodemographic variables, and to obtain an upper bound on the best possible performance of a predictor based on those variables. From a consecutive sample of 9025 primary care patients, 6805 eligible patients (60% female; mean age = 51.5 years) participated. Advanced methods of machine learning were used to derive the prediction equation. Various classifiers were applied and the area under the curve (AUC) was computed as a performance measure. Classifiers based on methods of machine learning outperformed ordinary regression methods and achieved AUCs around 0.87. The key variables in the prediction equation comprised four items - namely feelings of depression/hopelessness, low self-esteem, worrying, and severe sleep disturbances. The generalized anxiety disorder scale (GAD-7) and the somatic symptom subscale (PHQ-15) did not enhance prediction substantially. In predicting suicidal ideation researchers should refrain from using ordinary regression tools. The relevant information is primarily captured by the depression subscale and should be incorporated in a nonlinear model. For clinical practice, a classification tree using only four items of the whole PHQ may be advocated. Copyright © 2018 Elsevier Inc. All rights reserved.

Positioning and deciding : key factors for talent development in soccer

NARCIS (Netherlands)

Kannekens, R.; Elferink-Gemser, M. T.; Visscher, C.

2011-01-01

Talent identification and development implicate recognizing youth players who will be successful in the future and guiding them to the top. A major determinant of this success is tactical skills. To identify possible key factors that help in predicting success over time, this study assesses the

Key Elements of a Successful Drive toward Marketing Strategy Making

Science.gov (United States)

Cann, Cynthia W.; George, Marie A.

2003-01-01

A conceptual model is presented that depicts the relationship between an internal marketing function and an organization's readiness to learn. Learning and marketing orientations are identified as components to marketing strategy making. Key organizational functions, including communication and decision-making, are utilized in a framework for…

Application of element logging to lithologic identification of key horizons in Sichuan–Chongqing gas provinces

Directory of Open Access Journals (Sweden)

Ping Yin

2018-03-01

Full Text Available With the popularization and application of fast drilling technology in Sichuan–Chongqing gas provinces, the returned cuttings are fine and even powdered, so the traditional cutting lithology identification methods are not applicable any longer. In this paper, qualitative lithology identification and quantitative interpretation based on element logging were conducted on the key oil and gas bearing layers in this area according to the principle of elemental geochemistry. The study results show that: (1 different lithologies can be identified easily because of their different element logging characteristics. For example, basalts have the element characteristics of 0.35 0.55. (2 Clastic rocks, carbonate rocks, sulphate and transition rocks in the category of sedimentary rocks can be identified based on the element combination of (Al + Si + Fe and (Ca + Mg + S. Among them, clastic rocks have (Al + Si + Fe >31%, carbonate rocks have (Al + Si + Fe 36%. (3 Then, based on the element combination of (Si + K + Ca+Si/Al and (Al + Si + Fe + K+(Ca + S/Mg, sandstone, mudstone (shale, gypsum, dolomite, limestone and transition rocks can be identified. Finally, a qualitative identification chart and a set of quantitative interpretation software of element logging on key horizons in Sichuan–Chongqing gas provinces were developed to make this method convenient for field application. This method was applied on site in ten wells (such as Well MX207 in Sichuan–Chongqing gas provinces. It is indicated that the coincidence rate of lithology identification is in the range of 88.75–95.22% (averaging 92.42%. Obviously, it can satisfy the requirements of fast lithology identification while drilling of key oil and gas horizons in Sichuan–Chongqing gas provinces. Keywords: Sichuan–Chongqing gas provinces, Key horizon, Element logging, Lithologic identification while drilling, Quantitative lithologic interpretation, Qualitative

Sulfur Denitrosylation by an Engineered Trx-like DsbG Enzyme Identifies Nucleophilic Cysteine Hydrogen Bonds as Key Functional Determinant.

Science.gov (United States)

Lafaye, Céline; Van Molle, Inge; Tamu Dufe, Veronica; Wahni, Khadija; Boudier, Ariane; Leroy, Pierre; Collet, Jean-François; Messens, Joris

2016-07-15

Exposure of bacteria to NO results in the nitrosylation of cysteine thiols in proteins and low molecular weight thiols such as GSH. The cells possess enzymatic systems that catalyze the denitrosylation of these modified sulfurs. An important player in these systems is thioredoxin (Trx), a ubiquitous, cytoplasmic oxidoreductase that can denitrosylate proteins in vivo and S-nitrosoglutathione (GSNO) in vitro However, a periplasmic or extracellular denitrosylase has not been identified, raising the question of how extracytoplasmic proteins are repaired after nitrosative damage. In this study, we tested whether DsbG and DsbC, two Trx family proteins that function in reducing pathways in the Escherichia coli periplasm, also possess denitrosylating activity. Both DsbG and DsbC are poorly reactive toward GSNO. Moreover, DsbG is unable to denitrosylate its specific substrate protein, YbiS. Remarkably, by borrowing the CGPC active site of E. coli Trx-1 in combination with a T200M point mutation, we transformed DsbG into an enzyme highly reactive toward GSNO and YbiS. The pKa of the nucleophilic cysteine, as well as the redox and thermodynamic properties of the engineered DsbG are dramatically changed and become similar to those of E. coli Trx-1. X-ray structural insights suggest that this results from a loss of two direct hydrogen bonds to the nucleophilic cysteine sulfur in the DsbG mutant. Our results highlight the plasticity of the Trx structural fold and reveal that the subtle change of the number of hydrogen bonds in the active site of Trx-like proteins is the key factor that thermodynamically controls reactivity toward nitrosylated compounds. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer.

Directory of Open Access Journals (Sweden)

Liyan Jiang

2016-04-01

Full Text Available Small cell lung cancer (SCLC is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62% harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1 DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC.

Key Concept Identification: A Comprehensive Analysis of Frequency and Topical Graph-Based Approaches

Directory of Open Access Journals (Sweden)

Muhammad Aman

2018-05-01

Full Text Available Automatic key concept extraction from text is the main challenging task in information extraction, information retrieval and digital libraries, ontology learning, and text analysis. The statistical frequency and topical graph-based ranking are the two kinds of potentially powerful and leading unsupervised approaches in this area, devised to address the problem. To utilize the potential of these approaches and improve key concept identification, a comprehensive performance analysis of these approaches on datasets from different domains is needed. The objective of the study presented in this paper is to perform a comprehensive empirical analysis of selected frequency and topical graph-based algorithms for key concept extraction on three different datasets, to identify the major sources of error in these approaches. For experimental analysis, we have selected TF-IDF, KP-Miner and TopicRank. Three major sources of error, i.e., frequency errors, syntactical errors and semantical errors, and the factors that contribute to these errors are identified. Analysis of the results reveals that performance of the selected approaches is significantly degraded by these errors. These findings can help us develop an intelligent solution for key concept extraction in the future.

Investigation of the key determinants of Asian nurses’ quality of life

Science.gov (United States)

MAKABE, Sachiko; KOWITLAWAKUL, Yanika; NURUMAL, Mohd Said; TAKAGAI, Junko; WICHAIKHUM, Orn-Anong; WANGMO, Neyzang; YAP, Suk Foon; KUNAVIKTIKUL, Wipada; KOMATSU, Junko; SHIRAKAWA, Hideko; KIMURA, Yutaka; ASANUMA, Yoshihiro

2018-01-01

The study aimed to compare nurses’ quality of life and investigate key determinants among Asian countries with different economic status. A cross-sectional survey was conducted across five Asian countries (Japan, Singapore, Malaysia, Thailand, and Bhutan). Quality of life (WHOQOL-BREF), job stress (National Institute of Occupational Safety and Health questionnaire), and demographic data were assessed. Stepwise multivariate linear regression analysis was performed to identify the key determinants of quality of life. Participants were 3,829 nurses (response rate: 82%) with a mean age of 33 ± 10 yr and majority were women (92%). Regarding quality of life, Bhutan yielded the highest scores, followed by Malaysia, Thailand, Singapore, and Japan, and these results were statistically significant. The key determinants that were significantly related to quality of life were “stress coping ability,” “life satisfaction,” “Japan,” “social support,” “job stress,” and “Singapore” (adjusted R2=0.46). In conclusion, nurses’ quality of life differs across Asian countries and is not linked to the country’s economic development. To maintain a good quality of life for nurses, an international exchange program like international nursing conferences for work environment and staff coping strategies is recommended to broaden institution’ minds and share experiences and exchange views to be able to realize their own problems and discover global solutions to them. PMID:29491251

A pilot study using scripted ventilation conditions to identify key factors affecting indoor pollutant concentration and air exchange rate in a residence.

Science.gov (United States)

Johnson, Ted; Myers, Jeffrey; Kelly, Thomas; Wisbith, Anthony; Ollison, Will

2004-01-01

A pilot study was conducted using an occupied, single-family test house in Columbus, OH, to determine whether a script-based protocol could be used to obtain data useful in identifying the key factors affecting air-exchange rate (AER) and the relationship between indoor and outdoor concentrations of selected traffic-related air pollutants. The test script called for hourly changes to elements of the test house considered likely to influence air flow and AER, including the position (open or closed) of each window and door and the operation (on/off) of the furnace, air conditioner, and ceiling fans. The script was implemented over a 3-day period (January 30-February 1, 2002) during which technicians collected hourly-average data for AER, indoor, and outdoor air concentrations for six pollutants (benzene, formaldehyde (HCHO), polycyclic aromatic hydrocarbons (PAH), carbon monoxide (CO), nitric oxide (NO), and nitrogen oxides (NO(x))), and selected meteorological variables. Consistent with expectations, AER tended to increase with the number of open exterior windows and doors. The 39 AER values measured during the study when all exterior doors and windows were closed varied from 0.36 to 2.29 h(-1) with a geometric mean (GM) of 0.77 h(-1) and a geometric standard deviation (GSD) of 1.435. The 27 AER values measured when at least one exterior door or window was opened varied from 0.50 to 15.8 h(-1) with a GM of 1.98 h(-1) and a GSD of 1.902. AER was also affected by temperature and wind speed, most noticeably when exterior windows and doors were closed. Results of a series of stepwise linear regression analyses suggest that (1) outdoor pollutant concentration and (2) indoor pollutant concentration during the preceding hour were the "variables of choice" for predicting indoor pollutant concentration in the test house under the conditions of this study. Depending on the pollutant and ventilation conditions, one or more of the following variables produced a small, but

Key enabling technologies (Kets) observatory. Second report December 2015

OpenAIRE

Velde, Els van de; Pieterjan, Debergh; Wydra, Sven; Som, Oliver; Heide, Marcel de

2015-01-01

Key Enabling Technologies (KETs) provide the basis for innovation in a wide range of products and processes across all industrial sectors (emerging and traditional) and are essential to solve Europe’s major societal challenges. Six KETs have been identified as important for Europe’s future competitiveness: Advanced Manufacturing Technology, Advanced Materials, Nanotechnology, Micro- and Nanoelectronics, Industrial Biotechnology, and Photonics.

An assessment of key health indicators among emergency medical services professionals.

Science.gov (United States)

Studnek, Jonathan R; Bentley, Melissa; Crawford, J Mac; Fernandez, Antonio R

2010-01-01

Ensuring the health and productivity of emergency medical services (EMS) professionals is important. However, there has been no known national baseline assessment of the health and wellness of EMS professionals in the United States. According to Healthy People 2010, top indicators of personal health include physical activity, body mass index (BMI), and smoking prevalence. The objectives of this study included quantifying existing health conditions and describing key health indicators among EMS professionals. It was hypothesized that work-life characteristics were associated with existing health conditions and key health indicators. Data utilized for this analysis were obtained from a 2007 questionnaire included in biennial national recertification packets. This questionnaire utilized validated items from the Behavioral Risk Factor Surveillance System (BRFSS) and the Longitudinal EMT Attributes and Demographics Study (LEADS). Along with common demographic characteristics, items inquired about existing health conditions (diabetes, asthma, hypertension, myocardial infarction, angina, stroke, and/or high blood cholesterol level), general health, physical activity, and smoking status. Descriptive analyses were performed utilizing chi-square tests, and logistic regression was utilized to describe associations between existing health conditions and the key health indicators. There were 58,435 individuals who became recertified in 2007, with 30,560 (52%) returning questionnaires. Individuals with missing data were removed, leaving 19,960 individual records. There were 4,681 (23.5%) individuals who reported at least one existing health condition. The mean BMI for the study participants was 27.69 kg/m(2). There were 5,742 (28.8%) individuals classified as having normal weight and 5,146 (25.8%) who were obese. The overwhelming majority of individuals did not meet the Centers for Disease Control and Prevention (CDC) recommendations for physical activity (15,022, 75.3%). There

Building capacity in Australian interprofessional health education: perspectives from key health and higher education stakeholders.

Science.gov (United States)

Matthews, Lynda R; Pockett, Rosalie B; Nisbet, Gillian; Thistlethwaite, Jill E; Dunston, Roger; Lee, Alison; White, Jill F

2011-05-01

A substantial literature engaging with the directions and experiences of stakeholders involved in interprofessional health education exists at the international level, yet almost nothing has been published that documents and analyses the Australian experience. Accordingly, this study aimed to scope the experiences of key stakeholders in health and higher education in relation to the development of interprofessional practice capabilities in health graduates in Australia. Twenty-seven semi-structured interviews and two focus groups of key stakeholders involved in the development and delivery of interprofessional health education in Australian higher education were undertaken. Interview data were coded to identify categories that were organised into key themes, according to principles of thematic analysis. Three themes were identified: the need for common ground between health and higher education, constraints and enablers in current practice, and the need for research to establish an evidence base. Five directions for national development were also identified. The study identified a range of interconnected changes that will be required to successfully mainstream interprofessional education within Australia, in particular, the importance of addressing issues of culture change and the need for a nationally coordinated and research informed approach. These findings reiterate those found in the international literature.

The applicability of LCA to evaluate the key environmental challenges in food supply chains

DEFF Research Database (Denmark)

Aronsson, Anna K.S.; Landquist, Birgit; Esturo, Aintzane

2014-01-01

System analysis was performed to gain an overview of key environmental challenges and pinpoint hotspots causing environmental impacts in three European food supply chains. An overview was obtained based on a review on LCA studies for beef, dairy, orange juice and aquaculture food supply chains....... Similarities of the main environmental impacts were identified to rationalize and justify the selection of key performance indicators chosen for a simplified web based LCA tool developed within the EC funded project SENSE (FP7). Life Cycle Assessment methodology covered many of the key challenges identified...... but will not be sufficient to address all environmental impacts generated from the food supply chains. Especially for aquaculture impacts that are not taken into account with LCA are i.e. nutrient and organic matter releases, impacts associated with feed provision, diseases introduction, escapes, and changed usage...

Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis)

Science.gov (United States)

Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

2015-01-01

Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants’ growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., ‘Photosynthesis’), GO terms (e.g., ‘response to karrikin’) and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology. PMID:25901577

Key Management Laboratory

Data.gov (United States)

Federal Laboratory Consortium — FUNCTION: Provides a secure environment to research and develop advanced electronic key management and networked key distribution technologies for the Navy and DoD....

Key events and their effects on cycling behaviour in Dar-es-Salaam : abstract + powerpoint

OpenAIRE

Nkurunziza, A.; Zuidgeest, M.H.P.; Brussel, M.J.G.; van Maarseveen, M.F.A.M.

2012-01-01

The paper explores key events and investigates their effects on cycling behaviour in the city of Dar-es-Salaam, Tanzania. The objective of the study is to identify specific key events during a person’s life course with a significant effect on change of travel behaviour towards cycling in relation to stage of change. Stage of change is a key construct of the transtheoretical model of behaviour change that defines behavioural readiness (intentions and actions) into six distinct categories (i.e....

A High-Throughput Cell-Based Screen Identified a 2-[(E)-2-Phenylvinyl]-8-Quinolinol Core Structure That Activates p53.

Science.gov (United States)

Bechill, John; Zhong, Rong; Zhang, Chen; Solomaha, Elena; Spiotto, Michael T

2016-01-01

p53 function is frequently inhibited in cancer either through mutations or by increased degradation via MDM2 and/or E6AP E3-ubiquitin ligases. Most agents that restore p53 expression act by binding MDM2 or E6AP to prevent p53 degradation. However, fewer compounds directly bind to and activate p53. Here, we identified compounds that shared a core structure that bound p53, caused nuclear localization of p53 and caused cell death. To identify these compounds, we developed a novel cell-based screen to redirect p53 degradation to the Skip-Cullin-F-box (SCF) ubiquitin ligase complex in cells expressing high levels of p53. In a multiplexed assay, we coupled p53 targeted degradation with Rb1 targeted degradation in order to identify compounds that prevented p53 degradation while not inhibiting degradation through the SCF complex or other proteolytic machinery. High-throughput screening identified several leads that shared a common 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that stabilized p53. Surface plasmon resonance analysis indicated that these compounds bound p53 with a KD of 200 ± 52 nM. Furthermore, these compounds increased p53 nuclear localization and transcription of the p53 target genes PUMA, BAX, p21 and FAS in cancer cells. Although p53-null cells had a 2.5±0.5-fold greater viability compared to p53 wild type cells after treatment with core compounds, loss of p53 did not completely rescue cell viability suggesting that compounds may target both p53-dependent and p53-independent pathways to inhibit cell proliferation. Thus, we present a novel, cell-based high-throughput screen to identify a 2-[(E)-2-phenylvinyl]-8-quinolinol core structure that bound to p53 and increased p53 activity in cancer cells. These compounds may serve as anti-neoplastic agents in part by targeting p53 as well as other potential pathways.

The Key Lake project

International Nuclear Information System (INIS)

1991-01-01

Key Lake is located in the Athabasca sand stone basin, 640 kilometers north of Saskatoon, Saskatchewan, Canada. The three sources of ore at Key Lake contain 70 100 tonnes of uranium. Features of the Key Lake Project were described under the key headings: work force, mining, mill process, tailings storage, permanent camp, environmental features, worker health and safety, and economic benefits. Appendices covering the historical background, construction projects, comparisons of western world mines, mining statistics, Northern Saskatchewan surface lease, and Key Lake development and regulatory agencies were included

KONJAC1 and 2 Are Key Factors for GDP-Mannose Generation and Affect l-Ascorbic Acid and Glucomannan Biosynthesis in Arabidopsis

Energy Technology Data Exchange (ETDEWEB)

Sawake, Shota [Saitama Univ. (Japan); Tajima, Noriaki [Saitama Univ. (Japan); Mortimer, Jenny C. [Univ. of Cambridge (United Kingdom); RIKEN Center for Sustainable Resource Science, Yokohama (Japan); Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lao, Jeemeng [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Ishikawa, Toshiki [Saitama Univ. (Japan); Yu, Xiaolan [Univ. of Cambridge (United Kingdom); Yamanashi, Yukiko [Saitama Univ. (Japan); Yoshimi, Yoshihisa [Saitama Univ. (Japan); Kawai-Yamada, Maki [Saitama Univ. (Japan); Dupree, Paul [Saitama Univ. (Japan); Tsumuraya, Yoichi [Saitama Univ. (Japan); Kotake, Toshihisa [Saitama Univ. (Japan); Univ. of Cambridge (United Kingdom)

2015-12-01

Humans are unable to synthesize L-ascorbic acid (AsA), yet it is required as a cofactor in many critical biochemical reactions. The majority of human dietary AsA is obtained from plants. In Arabidopsis thaliana, a GDP-mannose pyrophosphorylase (GMPP), VITAMIN C DEFECTIVE1 (VTC1), catalyzes a rate-limiting step in AsA synthesis: the formation of GDP-Man. In this study, we identified two nucleotide sugar pyrophosphorylase-like proteins, KONJAC1 (KJC1) and KJC2, which stimulate the activity of VTC1. The kjc1kjc2 double mutant exhibited severe dwarfism, indicating that KJC proteins are important for growth and development. The kjc1 mutation reduced GMPP activity to 10% of wild-type levels, leading to a 60% reduction in AsA levels. On the contrary, overexpression of KJC1 significantly increased GMPP activity. The kjc1 and kjc1kjc2 mutants also exhibited significantly reduced levels of glucomannan, which is also synthesized from GDP-Man. Recombinant KJC1 and KJC2 enhanced the GMPP activity of recombinant VTC1 in vitro, while KJCs did not show GMPP activity. Yeast two-hybrid assays suggested that the stimulation of GMPP activity occurs via interaction of KJCs with VTC1. These results suggest that KJCs are key factors for the generation of GDP-Man and affect AsA level and glucomannan accumulation through the stimulation of VTC1 GMPP activity.

KONJAC1 and 2 Are Key Factors for GDP-Mannose Generation and Affect l-Ascorbic Acid and Glucomannan Biosynthesis in Arabidopsis.

Science.gov (United States)

Sawake, Shota; Tajima, Noriaki; Mortimer, Jenny C; Lao, Jeemeng; Ishikawa, Toshiki; Yu, Xiaolan; Yamanashi, Yukiko; Yoshimi, Yoshihisa; Kawai-Yamada, Maki; Dupree, Paul; Tsumuraya, Yoichi; Kotake, Toshihisa

2015-12-01

Humans are unable to synthesize l-ascorbic acid (AsA), yet it is required as a cofactor in many critical biochemical reactions. The majority of human dietary AsA is obtained from plants. In Arabidopsis thaliana, a GDP-mannose pyrophosphorylase (GMPP), VITAMIN C DEFECTIVE1 (VTC1), catalyzes a rate-limiting step in AsA synthesis: the formation of GDP-Man. In this study, we identified two nucleotide sugar pyrophosphorylase-like proteins, KONJAC1 (KJC1) and KJC2, which stimulate the activity of VTC1. The kjc1kjc2 double mutant exhibited severe dwarfism, indicating that KJC proteins are important for growth and development. The kjc1 mutation reduced GMPP activity to 10% of wild-type levels, leading to a 60% reduction in AsA levels. On the contrary, overexpression of KJC1 significantly increased GMPP activity. The kjc1 and kjc1kjc2 mutants also exhibited significantly reduced levels of glucomannan, which is also synthesized from GDP-Man. Recombinant KJC1 and KJC2 enhanced the GMPP activity of recombinant VTC1 in vitro, while KJCs did not show GMPP activity. Yeast two-hybrid assays suggested that the stimulation of GMPP activity occurs via interaction of KJCs with VTC1. These results suggest that KJCs are key factors for the generation of GDP-Man and affect AsA level and glucomannan accumulation through the stimulation of VTC1 GMPP activity. © 2015 American Society of Plant Biologists. All rights reserved.

Good Research and Faculty Buy-in: 2 Keys to Effective Marketing

Science.gov (United States)

Blumenstyk, Goldie

2008-01-01

Effective marketing requires more than a sleek new logo. This article presents excerpts of an online discussion on the dos and don'ts of college marketing with Mary R. Stagaman, associate vice president for external relations at the University of Cincinnati. In this discussion, she noted that good research and faculty buy-in are the two keys to…

Identifying Key Proteins in Hg Methylation Pathways of Desulfovibrio by Global Proteomics, Final Technical Report

Energy Technology Data Exchange (ETDEWEB)

Summers, Anne O. [Univ. of Georgia, Athens, GA (United States). Dept. of Microbiology; Miller, Susan M. [Univ. of California, San Francisco, CA (United States). Dept. of Pharmaceutical Chemistry; Wall, Judy [Univ. of Missouri, Columbia, MO (United States). Dept. of Biochemistry; Lipton, Mary [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2016-06-18

Elemental mercury, Hg(0) is a contaminant at many DOE sites, especially at Oak Ridge National Laboratory (ORNL) where the spread of spilled Hg and its effects on microbial populations have been monitored for decades. To explore the microbial interactions with Hg, we have devised a global proteomic approach capable of directly detecting Hg-adducts of proteins. This technique developed in the facultative anaerobe, Escherichia coli, allows us to identify the proteins most vulnerable to acute exposure to organomercurials phenyl- and ethyl-mercury (as surrogates for the highly neurotoxic methyl-Hg) (Polacco, et al, 2011). We have found >300 such proteins in all metabolic functional groups and cellular compartments; most are highly conserved and can serve as markers for acute Hg exposure (Zink, et al. 2016, in preparation). We have also discovered that acute Hg exposure severely disrupts thiol, iron and redox homeostases, and electrolyte balance (LaVoie, et al., 2015) Thus, we proposed to bring these techniques to bear on the central problem of identifying the cellular proteins involved in bacterial uptake and methylation of mercury and its release from the cell.

Identification key to species of the flying lizard genus Draco Linnaeus, 1758 (Squamata: Agamidae in Thailand

Directory of Open Access Journals (Sweden)

Nattawut Srichairat

2017-02-01

Full Text Available A species identification key of flying lizards in the genus Draco from Thailand was constructed based on 521 preserved specimens from collections during 1967–2012 in the Natural History Museum (THNHM, National Science Museum, Technopolis, Pathum Thani, Thailand. Regardless of sexual characters, four characters were used to identify Draco spp. lizards: 1 nostril direction; 2 type of tympanum; 3 pattern of patagium; and 4 snout with or without a series of scales forming a Y-shaped figure. The specimens were identified into nine species—Draco blanfordii, Draco fimbriatus, Draco maculatus, Draco maximus, Draco melanopogon, Draco obscurus, Draco quinquefasciatus, Draco taeniopterus and Draco volans.

Diversity of key players in the microbial ecosystems of the human body.

Science.gov (United States)

Jordán, Ferenc; Lauria, Mario; Scotti, Marco; Nguyen, Thanh-Phuong; Praveen, Paurush; Morine, Melissa; Priami, Corrado

2015-10-30

Coexisting bacteria form various microbial communities in human body parts. In these ecosystems they interact in various ways and the properties of the interaction network can be related to the stability and functional diversity of the local bacterial community. In this study, we analyze the interaction network among bacterial OTUs in 11 locations of the human body. These belong to two major groups. One is the digestive system and the other is the female genital tract. In each local ecosystem we determine the key species, both the ones being in key positions in the interaction network and the ones that dominate by frequency. Beyond identifying the key players and discussing their biological relevance, we also quantify and compare the properties of the 11 networks. The interaction networks of the female genital system and the digestive system show totally different architecture. Both the topological properties and the identity of the key groups differ. Key groups represent four phyla of prokaryotes. Some groups appear in key positions in several locations, while others are assigned only to a single body part. The key groups of the digestive and the genital tracts are totally different.

The Efficacy of Key Performance Indicators in Ontario Universities as Perceived by Key Informants

Science.gov (United States)

Chan, Vivian

2015-01-01

The Ontario Ministry of Education and Training's Task Force on University Accountability first proposed key performance indicators (KPIs) for colleges and universities in Ontario in the early 1990s. The three main KPIs for Ontario universities are the rates of (1) graduation, (2) employment, and (3) Ontario Student Assistance Program loan default.…

Key Supplier Relationship Management: The Case of Croatian Medium-Sized and Large Manufacturing Companies

Directory of Open Access Journals (Sweden)

Dario Miočević

2011-06-01

Full Text Available The key supplier relationship management represents a vital organizational process. Companies should pay attention not only to managing customer relationships but also to managing relationships with suppliers in order to perform well. They should identify the extent to which a certain supplier adds value through the procurement process. In this line of reasoning, both theory and practice make a distinction between strategic (key and non-strategic (transactional suppliers. By employing the segmentation of the supply market, companies balance their supplier portfolio and are capable of identifying the key suppliers. They can also develop specific programs and initiatives that are aimed at preserving these relationships. In the empirical part of the paper, a survey was conducted on a sample of 123 medium-sized and large Croatian manufacturing companies. The structural model involving the relationship between the key supplier relationship management and value-oriented purchasing was tested. The results indicate that there is a statistically direct, positive and significant relationship between these two constructs. Likewise, the results stress that a theoretical conceptualization and operationalization of the key supplier relationship management construct is both valid and justified. Finally, the theoretical and practical implications and limitations of this study are offered.

Identifying suitable sites for Florida panther reintroduction

Science.gov (United States)

Thatcher, Cindy A.; van Manen, Frank T.; Clark, Joseph D.

2006-01-01

A major objective of the 1995 Florida Panther (Puma concolor cory) Recovery Plan is the establishment of 2 additional panther populations within the historic range. Our goal was to identify prospective sites for Florida panther reintroduction within the historic range based on quantitative landscape assessments. First, we delineated 86 panther home ranges using telemetry data collected from 1981 to 2001 in south Florida to develop a Mahalanobis distance (D2) habitat model, using 4 anthropogenic variables and 3 landscape variables mapped at a 500-m resolution. From that analysis, we identified 9 potential reintroduction sites of sufficient size to support a panther population. We then developed a similar D2 model at a higher spatial resolution to quantify the area of favorable panther habitat at each site. To address potential for the population to expand, we calculated the amount of favorable habitat adjacent to each prospective reintroduction site within a range of dispersal distances of female panthers. We then added those totals to the contiguous patches to estimate the total amount of effective panther habitat at each site. Finally, we developed an expert-assisted model to rank and incorporate potentially important habitat variables that were not appropriate for our empirical analysis (e.g., area of public lands, livestock density). Anthropogenic factors heavily influenced both the landscape and the expert-assisted models. Of the 9 areas we identified, the Okefenokee National Wildlife Refuge, Ozark National Forest, and Felsenthal National Wildlife Refuge regions had the highest combination of effective habitat area and expert opinion scores. Sensitivity analyses indicated that variability among key model parameters did not affect the high ranking of those sites. Those sites should be considered as starting points for the field evaluation of potential reintroduction sites.

Dopamine signaling and myopia development: What are the key challenges.

Science.gov (United States)

Zhou, Xiangtian; Pardue, Machelle T; Iuvone, P Michael; Qu, Jia

2017-11-01

In the face of an "epidemic" increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this "myopia booming" and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including retina development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rubella vaccination in India: identifying broad consequences of vaccine introduction and key knowledge gaps.

Science.gov (United States)

Winter, A K; Pramanik, S; Lessler, J; Ferrari, M; Grenfell, B T; Metcalf, C J E

2018-01-01

Rubella virus infection typically presents as a mild illness in children; however, infection during pregnancy may cause the birth of an infant with congenital rubella syndrome (CRS). As of February 2017, India began introducing rubella-containing vaccine (RCV) into the public-sector childhood vaccination programme. Low-level RCV coverage among children over several years can result in an increase in CRS incidence by increasing the average age of infection without sufficiently reducing rubella incidence. We evaluated the impact of RCV introduction on CRS incidence across India's heterogeneous demographic and epidemiological contexts. We used a deterministic age-structured model that reflects Indian states' rural and urban area-specific demography and vaccination coverage levels to simulate rubella dynamics and estimate CRS incidence with and without RCV introduction to the public sector. Our analysis suggests that current low-level private-sector vaccination has already slightly increased the burden of CRS in India. We additionally found that the effect of public-sector RCV introduction depends on the basic reproductive number, R 0, of rubella. If R 0 is five, a value empirically estimated from an array of settings, CRS incidence post-RCV introduction will likely decrease. However, if R 0 is seven or nine, some states may experience short-term or annual increases in CRS, even if a long-term total reduction in cases (30 years) is expected. Investment in population-based serological surveys and India's fever/rash surveillance system will be key to monitoring the success of the vaccination programme.

Identifying continuous quality improvement publications: what makes an improvement intervention ‘CQI’?

Science.gov (United States)

Hempel, Susanne; Lim, Yee-Wei; Danz, Marjorie S; Foy, Robbie; Suttorp, Marika J; Shekelle, Paul G; Rubenstein, Lisa V

2011-01-01

Background The term continuous quality improvement (CQI) is often used to refer to a method for improving care, but no consensus statement exists on the definition of CQI. Evidence reviews are critical for advancing science, and depend on reliable definitions for article selection. Methods As a preliminary step towards improving CQI evidence reviews, this study aimed to use expert panel methods to identify key CQI definitional features and develop and test a screening instrument for reliably identifying articles with the key features. We used a previously published method to identify 106 articles meeting the general definition of a quality improvement intervention (QII) from 9427 electronically identified articles from PubMed. Two raters then applied a six-item CQI screen to the 106 articles. Results Per cent agreement ranged from 55.7% to 75.5% for the six items, and reviewer-adjusted intra-class correlation ranged from 0.43 to 0.62. ‘Feedback of systematically collected data’ was the most common feature (64%), followed by being at least ‘somewhat’ adapted to local conditions (61%), feedback at meetings involving participant leaders (46%), using an iterative development process (40%), being at least ‘somewhat’ data driven (34%), and using a recognised change method (28%). All six features were present in 14.2% of QII articles. Conclusions We conclude that CQI features can be extracted from QII articles with reasonable reliability, but only a small proportion of QII articles include all features. Further consensus development is needed to support meaningful use of the term CQI for scientific communication. PMID:21727199

KEY FACTORS IN MARKETING FOCUSED SERVICES BUSINESSES

Directory of Open Access Journals (Sweden)

Doris Yohanna Martínez Castrillón

2016-07-01

Full Text Available This article aims to identify the key success factors in the marketing area and describe them as managerial allies for companies that wish to position themselves in the market under a good sustainable performance , for it has been consulted theoretical references of Marketing as a management partner with collection and integration of data. Methodologically, it is located within the type of descriptive research field, with a design of transactional non-experimental, with an intentional non-probabilistic stratified sample of four reporting units. The findings established fifteen (15 points of influence called "key success factors (FCE in the area of marketing, and managerial allies of service companies in the security, surveillance and protection sector in industrial, commercial and residential sectors. Finally, it is intended that the actions of marketing service companies should focus to the welfare of both the organization, such as users, both in the environment, and economic, social and technological, characterized by ethics, sustainable development and transparency to respond appropriately.

Key technologies book

International Nuclear Information System (INIS)

1997-01-01

In this book can be found all the useful information on the French industry key technologies of the years 2000-2005. 136 technologies at the junction of the science advances and of the markets expectations are divided into 9 sectors. Among them, only 4 are interesting here: the environment, the transports, the materials and the energy. In 1995, the secretary's office of State for industry has published a first synthesis book on these key technologies. This 1997 new key technologies book extends and completes the initial study. For each key technology, an encyclopedic sheet is given. Each sheet combines thus some exact and practical information on: advance state of the technology, market characteristics, development forecasts, occupation and involved sectors, technology acquisition cost, research programs but also contacts of the main concerned efficiency poles. (O.M.)

Integrated Network Analysis Identifies Fight-Club Nodes as a Class of Hubs Encompassing Key Putative Switch Genes That Induce Major Transcriptome Reprogramming during Grapevine Development[W][OPEN

Science.gov (United States)

Palumbo, Maria Concetta; Zenoni, Sara; Fasoli, Marianna; Massonnet, Mélanie; Farina, Lorenzo; Castiglione, Filippo; Pezzotti, Mario; Paci, Paola

2014-01-01

We developed an approach that integrates different network-based methods to analyze the correlation network arising from large-scale gene expression data. By studying grapevine (Vitis vinifera) and tomato (Solanum lycopersicum) gene expression atlases and a grapevine berry transcriptomic data set during the transition from immature to mature growth, we identified a category named “fight-club hubs” characterized by a marked negative correlation with the expression profiles of neighboring genes in the network. A special subset named “switch genes” was identified, with the additional property of many significant negative correlations outside their own group in the network. Switch genes are involved in multiple processes and include transcription factors that may be considered master regulators of the previously reported transcriptome remodeling that marks the developmental shift from immature to mature growth. All switch genes, expressed at low levels in vegetative/green tissues, showed a significant increase in mature/woody organs, suggesting a potential regulatory role during the developmental transition. Finally, our analysis of tomato gene expression data sets showed that wild-type switch genes are downregulated in ripening-deficient mutants. The identification of known master regulators of tomato fruit maturation suggests our method is suitable for the detection of key regulators of organ development in different fleshy fruit crops. PMID:25490918

Identification of key oil refining technologies for China National Petroleum Co. (CNPC)

International Nuclear Information System (INIS)

Liu Haiyan; Yu Jianning; Xu Jian; Fan Yu; Bao Xiaojun

2007-01-01

This paper summarizes the results from the project 'Vision of the Key Petroleum Refining Technologies for China National Petroleum Co. (CNPC) in the Early 21st Century' undertaken by the Department of R and D Administration, CNPC, and its affiliate key laboratory, The Key Laboratory of Catalysis operated by China University of Petroleum, Beijing. The objective of the project was to identify the challenges and opportunities of CNPC's petroleum refining business given increasing economy globalization and stricter environmental regulations. Using the modified Delphi method, four key technologies for CNPC's oil refining industry were identified. They are: integrated fluid catalytic cracking (FCC), hydroprocessing, residue hydrocracking, and high-grade lubricant production. The most significant technology will be the integrated FCC technology that can economically increase the yield of light fractions as well as upgrade transportation fuels. In China, FCC units produce about 80% and 30% commercial gasoline and diesel, respectively. To ensure compliance with future environmental legislation, hydroprocessing technologies, including those related to petroleum product hydrorefining and distillate hydrocracking, should be developed. By combining residue hydrocracking and FCC technologies, poorer quality residua can be processed. Supplying high-grade lube oils is one of the main tasks for CNPC's oil refining industry. Development of hydrodewaxing technologies to manufacture API group II/III base oil is the main direction for CNPC's lubricant production business

A Large-Scale RNAi Screen Identifies SGK1 as a Key Survival Kinase for GBM Stem Cells.

Science.gov (United States)

Kulkarni, Shreya; Goel-Bhattacharya, Surbhi; Sengupta, Sejuti; Cochran, Brent H

2018-01-01

Glioblastoma multiforme (GBM) is the most common type of primary malignant brain cancer and has a very poor prognosis. A subpopulation of cells known as GBM stem-like cells (GBM-SC) have the capacity to initiate and sustain tumor growth and possess molecular characteristics similar to the parental tumor. GBM-SCs are known to be enriched in hypoxic niches and may contribute to therapeutic resistance. Therefore, to identify genetic determinants important for the proliferation and survival of GBM stem cells, an unbiased pooled shRNA screen of 10,000 genes was conducted under normoxic as well as hypoxic conditions. A number of essential genes were identified that are required for GBM-SC growth, under either or both oxygen conditions, in two different GBM-SC lines. Interestingly, only about a third of the essential genes were common to both cell lines. The oxygen environment significantly impacts the cellular genetic dependencies as 30% of the genes required under hypoxia were not required under normoxic conditions. In addition to identifying essential genes already implicated in GBM such as CDK4, KIF11 , and RAN , the screen also identified new genes that have not been previously implicated in GBM stem cell biology. The importance of the serum and glucocorticoid-regulated kinase 1 (SGK1) for cellular survival was validated in multiple patient-derived GBM stem cell lines using shRNA, CRISPR, and pharmacologic inhibitors. However, SGK1 depletion and inhibition has little effect on traditional serum grown glioma lines and on differentiated GBM-SCs indicating its specific importance in GBM stem cell survival. Implications: This study identifies genes required for the growth and survival of GBM stem cells under both normoxic and hypoxic conditions and finds SGK1 as a novel potential drug target for GBM. Mol Cancer Res; 16(1); 103-14. ©2017 AACR . ©2017 American Association for Cancer Research.

AMNT 2014. Key topic: Reactor operation, safety - report. Pt. 2

International Nuclear Information System (INIS)

Fischer, Klaus-Christian; Willschuetz, Hans-Georg; Wortmann, Birgit

2014-01-01

Summary report on the following sessions of the Annual Conference on Nuclear Technology held in Frankfurt, 6 to 8 May 2014: - Thermo Dynamics and Fluid Dynamics: Experiments and Backfittings for the Improvement of Safety and Efficiency; - Safety of Nuclear Installations - Methods, Analyses, Results: In-Vessel Phenomena; Ex-Vessel Phenomena; - Standards and Regulations; Hazard and Safety Analysis; and Validation and Uncertainty Analysis. The other Sessions of the Key Topics 'Reactor Operation, Safety', 'Competence, Innovation, Regulation' and 'Fuel, Decommissioning and Disposal' have been covered in atw 10 (2014) and will be covered in further issues of atw.

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

OpenAIRE

Voight, Benjamin; Scott, Laura; Steinthorsdottir, Valgerdur; Morris, Andrew; Dina, Christian; Welch, Ryan; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii; Thorleifsson, Gudmar; McCulloch, Laura; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming

2010-01-01

textabstractBy combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P 5 × 10 8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of ov...

Single-cell quantitative HER2 measurement identifies heterogeneity and distinct subgroups within traditionally defined HER2-positive patients.

Science.gov (United States)

Onsum, Matthew D; Geretti, Elena; Paragas, Violette; Kudla, Arthur J; Moulis, Sharon P; Luus, Lia; Wickham, Thomas J; McDonagh, Charlotte F; MacBeath, Gavin; Hendriks, Bart S

2013-11-01

Human epidermal growth factor receptor 2 (HER2) is an important biomarker for breast and gastric cancer prognosis and patient treatment decisions. HER2 positivity, as defined by IHC or fluorescent in situ hybridization testing, remains an imprecise predictor of patient response to HER2-targeted therapies. Challenges to correct HER2 assessment and patient stratification include intratumoral heterogeneity, lack of quantitative and/or objective assays, and differences between measuring HER2 amplification at the protein versus gene level. We developed a novel immunofluorescence method for quantitation of HER2 protein expression at the single-cell level on FFPE patient samples. Our assay uses automated image analysis to identify and classify tumor versus non-tumor cells, as well as quantitate the HER2 staining for each tumor cell. The HER2 staining level is converted to HER2 protein expression using a standard cell pellet array stained in parallel with the tissue sample. This approach allows assessment of HER2 expression and heterogeneity within a tissue section at the single-cell level. By using this assay, we identified distinct subgroups of HER2 heterogeneity within traditional definitions of HER2 positivity in both breast and gastric cancers. Quantitative assessment of intratumoral HER2 heterogeneity may offer an opportunity to improve the identification of patients likely to respond to HER2-targeted therapies. The broad applicability of the assay was demonstrated by measuring HER2 expression profiles on multiple tumor types, and on normal and diseased heart tissues. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Seaworthy Quantum Key Distribution Design and Validation (SEAKEY)

Science.gov (United States)

2015-11-12

polarization control and the CV state and the LO state are separated at a polarizing beam splitter . The CV state is delayed relative to the LO state, and... splitter or loss imperfections. We have identified a number of risks associated with implementing this design . The two most critical risks are: • The...Contractor Address: 10 Moulton Street, Cambridge, MA 02138 Title of the Project: Seaworthy Quantum Key Distribution Design and Validation (SEAKEY

Identifying Two-Dimensional Z 2 Antiferromagnetic Topological Insulators

Science.gov (United States)

Bègue, F.; Pujol, P.; Ramazashvili, R.

2018-01-01

We revisit the question of whether a two-dimensional topological insulator may arise in a commensurate Néel antiferromagnet, where staggered magnetization breaks the symmetry with respect to both elementary translation and time reversal, but retains their product as a symmetry. In contrast to the so-called Z 2 topological insulators, an exhaustive characterization of antiferromagnetic topological phases with the help of topological invariants has been missing. We analyze a simple model of an antiferromagnetic topological insulator and chart its phase diagram, using a recently proposed criterion for centrosymmetric systems [13]. We then adapt two methods, originally designed for paramagnetic systems, and make antiferromagnetic topological phases manifest. The proposed methods apply far beyond the particular examples treated in this work, and admit straightforward generalization. We illustrate this by two examples of non-centrosymmetric systems, where no simple criteria have been known to identify topological phases. We also present, for some cases, an explicit construction of edge states in an antiferromagnetic topological insulator.

Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms.

Science.gov (United States)

Milosevic Feenstra, Jelena D; Nivarthi, Harini; Gisslinger, Heinz; Leroy, Emilie; Rumi, Elisa; Chachoua, Ilyas; Bagienski, Klaudia; Kubesova, Blanka; Pietra, Daniela; Gisslinger, Bettina; Milanesi, Chiara; Jäger, Roland; Chen, Doris; Berg, Tiina; Schalling, Martin; Schuster, Michael; Bock, Christoph; Constantinescu, Stefan N; Cazzola, Mario; Kralovics, Robert

2016-01-21

Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the remaining cases are termed "triple negative." We aimed to identify the disease-causing mutations in the triple-negative cases of ET and PMF by applying whole-exome sequencing (WES) on paired tumor and control samples from 8 patients. We found evidence of clonal hematopoiesis in 5 of 8 studied cases based on clonality analysis and presence of somatic genetic aberrations. WES identified somatic mutations in 3 of 8 cases. We did not detect any novel recurrent somatic mutations. In 3 patients with clonal hematopoiesis analyzed by WES, we identified a somatic MPL-S204P, a germline MPL-V285E mutation, and a germline JAK2-G571S variant. We performed Sanger sequencing of the entire coding region of MPL in 62, and of JAK2 in 49 additional triple-negative cases of ET or PMF. New somatic (T119I, S204F, E230G, Y591D) and 1 germline (R321W) MPL mutation were detected. All of the identified MPL mutations were gain-of-function when analyzed in functional assays. JAK2 variants were identified in 5 of 57 triple-negative cases analyzed by WES and Sanger sequencing combined. We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations. Our results suggest that triple-negative cases of ET and PMF do not represent a homogenous disease entity. Cases with polyclonal hematopoiesis might represent hereditary disorders. © 2016 by The American Society of Hematology.

Public Key Cryptography.

Science.gov (United States)

Tapson, Frank

1996-01-01

Describes public key cryptography, also known as RSA, which is a system using two keys, one used to put a message into cipher and another used to decipher the message. Presents examples using small prime numbers. (MKR)

Monoclonal antibody OKB7, which identifies the 14OKd complement receptor type 2 (CR/sub 2/), also identifies a 72Kd secreted fragment of CR/sub 2/ that contains the C3d-binding site

Energy Technology Data Exchange (ETDEWEB)

Myones, B.L.; Ross, G.D.

1986-03-05

CR/sub 2/ is a 140-145Kd glycoprotein expressed on B lymphocytes which binds both C3d and Epstein-Barr virus (EBV). OKB7, an IgG/sub 2a/ monoclonal antibody to CR/sub 2/, blocks C3d and EBV binding, while HB-5, another monoclonal IgG/sub 2a/ anti-CR/sub 2/, does not. A 72Kd C3d-binding glycoprotein (gp72), isolated from Raji cell media, was previously thought to be CR/sub 2/ because a polyclonal rabbit anti-gp72 inhibited EC3d rosettes. ELISA assay demonstrated that OKB7, but not HB-5, bound to purified gp72 fixed to microtiter wells. Insoluble and soluble gp72 blocked Raji cell uptake of /sup 125/I-labeled OKB7, but not labeled anti-B2 or HB-5. Rabbit anti-gp72 immunoprecipitated bands at 140Kd and 72Kd from /sup 125/I-labelled and solubilized B cell membranes. Culture media from Raji cells grown in the presence /sup 3/H-labeled amino acids was sequentially immunoprecipitated by irrelevant antibody, OKB7, and HB-5. A single 72Kd radiolabeled band was demonstrated only with OKB7, and this was identical to that produced by the immunoprecipitation of /sup 125/I-labeled gp72 with rabbit anti-gp72. Thus, OKB7, which identifies the 140Kd CR/sub 2/ molecule, also identifies a 72Kd shed fragment of CR/sub 2/ isolated from Raji cell media, which contains the C3d-binding site.

Random multiple key streams for encryption with added CBC mode of operation

Directory of Open Access Journals (Sweden)

P. Penchalaiah

2016-09-01

For the first time, in this paper, we present a construction method to generate multiple random keys from a core-key with highest possible immunity to crack. We are with a particular emphasis on novel technique to secure user data, we have designed a secure and cost effective new cryptosystem called Rbits (Random bits cypher. In different directions we identify that Rbits having highest immunity to crack and presenting various analysis tests in support from this viewpoint and the analyzed results are reported.

A QUICK KEY TO THE SUBFAMILIES AND GENERA OF ANTS OF THE SAVANNAH RIVER SITE

Energy Technology Data Exchange (ETDEWEB)

Martin, D

2007-09-04

This taxonomic key was devised to support development of a Rapid Bioassessment Protocol using ants at the Savannah River Site. The emphasis is on 'rapid' and, because the available keys contained a very large number of genera not known to occur at the Savannah River Site, we found that the available keys were unwieldy. Because these keys contained many more genera than we would ever encounter and because this larger number of genera required more couplets in the key and often required examination of characters that are difficult to assess without higher magnifications (60X or higher), more time was required to process samples. In developing this set of keys I emphasized character states that are easier for nonspecialists to recognize. I recognize that the character sets used may lead to some errors but I believe that the error rate will be small and, for the purpose of rapid bioassessment, this error rate will be acceptable provided that overall sample sizes are adequate. Oliver and Beattie (1996a, 1996b) found that for rapid assessment of biodiversity the same results were found when identifications were done to morphospecies by people with minimal expertise as when the same data sets were identified by subject matter experts. Basset et al. (2004) concluded that it was not as important to correctly identify all species as it was to be sure that the study included as many functional groups as possible. If your study requires high levels of accuracy, it is highly recommended that, when you key out a specimen and have any doubts concerning the identification, you should refer to keys in Bolton (1994) or to the other keys used to develop this area specific taxonomic key.

Knowledge, skills, and abilities for key radiation protection positions at DOE facilities

International Nuclear Information System (INIS)

1997-01-01

This document provides detailed qualification criteria for contractor key radiation protection personnel. Although federal key radiation protection positions are also identified, qualification standards for federal positions are provided in DOE O 360.1 and the DOE Technical Qualifications Program. Appendices B and D provide detailed listings for knowledge, skills, and abilities for contractor and DOE federal key radiation protection positions. This information may be used in developing position descriptions and individual development plans. Information provided in Appendix C may be useful in developing performance measures and assessing an individual's performance in his or her specific position. Additionally, Federal personnel may use this information to augment their Office/facility qualification standards under the Technical Qualifications Program

A Recommended Set of Key Arctic Indicators

Science.gov (United States)

Stanitski, D.; Druckenmiller, M.; Fetterer, F. M.; Gerst, M.; Intrieri, J. M.; Kenney, M. A.; Meier, W.; Overland, J. E.; Stroeve, J.; Trainor, S.

2017-12-01

The Arctic is an interconnected and environmentally sensitive system of ice, ocean, land, atmosphere, ecosystems, and people. From local to pan-Arctic scales, the area has already undergone major changes in physical and societal systems and will continue at a pace that is greater than twice the global average. Key Arctic indicators can quantify these changes. Indicators serve as the bridge between complex information and policy makers, stakeholders, and the general public, revealing trends and information people need to make important socioeconomic decisions. This presentation evaluates and compiles more than 70 physical, biological, societal and economic indicators into an approachable summary that defines the changing Arctic. We divided indicators into "existing," "in development," "possible," and "aspirational". In preparing a paper on Arctic Indicators for a special issue of the journal Climatic Change, our group established a set of selection criteria to identify indicators to specifically guide decision-makers in their responses to climate change. A goal of the analysis is to select a manageable composite list of recommended indicators based on sustained, reliable data sources with known user communities. The selected list is also based on the development of a conceptual model that identifies components and processes critical to our understanding of the Arctic region. This list of key indicators is designed to inform the plans and priorities of multiple groups such as the U.S. Global Change Research Program (USGCRP), Interagency Arctic Research Policy Committee (IARPC), and the Arctic Council.

Key principles for adapting South African settlement patterns to climate change

CSIR Research Space (South Africa)

Van Wyk, Llewellyn

2017-06-01

Full Text Available The aim of the paper is to identify key principles for adapting SA settlement patterns to climate change. Section 1 reviews the range of climate-related impacts likely to affect SA settlements using climate change models and scenarios as a context...

Seeking convergence on the key concepts in "no net loss" policy

DEFF Research Database (Denmark)

Bull, Joseph William; Gordon, Ascelin; Watson, James E.M.

2016-01-01

. The recommendations made in this article, on improving clarity and supporting convergence on key no net loss (NNL) concepts, should help eliminate ambiguity in policy documentation. This is crucial if policymakers are to design robust policies that are (i) transparent, (ii) translatable into practice in a consistent......Biodiversity conservation policies incorporating a no net loss (NNL) principle are being implemented in many countries. However, there are linguistic and conceptual inconsistencies in the use of terms underlying these NNL policies. We identify inconsistencies that emerge in the usage of eight key......, reduce ambiguity and improve clarity in communication and policy documentation. However, we also warn of the challenges in achieving convergence, especially given the linguistic inconsistencies in several of these key concepts among countries in which NNL policies are employed. Policy implications...

SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake

NARCIS (Netherlands)

Honrath, Birgit; Matschke, Lina; Meyer, Tammo; Magerhans, Lena; Perocchi, Fabiana; Ganjam, Goutham K; Zischka, Hans; Krasel, Cornelius; Gerding, Albert; Bakker, Barbara M; Bünemann, Moritz; Strack, Stefan; Decher, Niels; Culmsee, Carsten; Dolga, Amalia M

Mitochondrial calcium ([Ca(2+)]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner

Projecting biodiversity and wood production in future forest landscapes: 15 key modeling considerations.

Science.gov (United States)

Felton, Adam; Ranius, Thomas; Roberge, Jean-Michel; Öhman, Karin; Lämås, Tomas; Hynynen, Jari; Juutinen, Artti; Mönkkönen, Mikko; Nilsson, Urban; Lundmark, Tomas; Nordin, Annika

2017-07-15

A variety of modeling approaches can be used to project the future development of forest systems, and help to assess the implications of different management alternatives for biodiversity and ecosystem services. This diversity of approaches does however present both an opportunity and an obstacle for those trying to decide which modeling technique to apply, and interpreting the management implications of model output. Furthermore, the breadth of issues relevant to addressing key questions related to forest ecology, conservation biology, silviculture, economics, requires insights stemming from a number of distinct scientific disciplines. As forest planners, conservation ecologists, ecological economists and silviculturalists, experienced with modeling trade-offs and synergies between biodiversity and wood biomass production, we identified fifteen key considerations relevant to assessing the pros and cons of alternative modeling approaches. Specifically we identified key considerations linked to study question formulation, modeling forest dynamics, forest processes, study landscapes, spatial and temporal aspects, and the key response metrics - biodiversity and wood biomass production, as well as dealing with trade-offs and uncertainties. We also provide illustrative examples from the modeling literature stemming from the key considerations assessed. We use our findings to reiterate the need for explicitly addressing and conveying the limitations and uncertainties of any modeling approach taken, and the need for interdisciplinary research efforts when addressing the conservation of biodiversity and sustainable use of environmental resources. Copyright © 2017 Elsevier Ltd. All rights reserved.

GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

Science.gov (United States)

Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

2011-01-01

Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

Financial Key Ratios

OpenAIRE

Tănase Alin-Eliodor

2014-01-01

This article focuses on computing techniques starting from trial balance data regarding financial key ratios. There are presented activity, liquidity, solvency and profitability financial key ratios. It is presented a computing methodology in three steps based on a trial balance.

Ecological characterization of the lower Everglades, Florida Bay, and the Florida Keys

Energy Technology Data Exchange (ETDEWEB)

Schomer, N.S.; Drew, R.D.

1982-09-01

A conceptual model of the study area identifies four major ecological zones: (1) terrestrial and freshwater wetlands, (2) estuarine and saltwater wetlands, (3) Florida Bay and mangrove islands, and (4) the Florida Keys. These zones are delineated by differences in basic physical-chemical background factors which in turn promote characteristic ecological communities. The terrestrial and freshwater wetlands support pinelands, sawgrass marshes, wet prairies, sloughs and occasional tree islands. The estuarine and saltwater wetlands support mangrove forests, salt marshes and oscillating salinity systems. Florida Bay exhibits oscillating meso- to hypersaline waters over grassbeds on marine lime mud sediments surrounding deeper lake areas. The exposed tips of the mud banks frequently support mangrove or salt prairie vegetation. The Florida Keys support almost all of the above communities to some small degree but are characterized by extensive offshore coral reefs. The productivity of these communities with regard to fish and wildlife reflects (1) the diversity and type of habitats available to species that are potentially capable of exploiting them, (2) the degree of alteration of these habitats by man and natural forces, and (3) historical, biogeographic and random factors that restrict organisms to specific environments or prohibit them from exploiting a potential habitat.

Novel secret key generation techniques using memristor devices

Science.gov (United States)

Abunahla, Heba; Shehada, Dina; Yeun, Chan Yeob; Mohammad, Baker; Jaoude, Maguy Abi

2016-02-01

This paper proposes novel secret key generation techniques using memristor devices. The approach depends on using the initial profile of a memristor as a master key. In addition, session keys are generated using the master key and other specified parameters. In contrast to existing memristor-based security approaches, the proposed development is cost effective and power efficient since the operation can be achieved with a single device rather than a crossbar structure. An algorithm is suggested and demonstrated using physics based Matlab model. It is shown that the generated keys can have dynamic size which provides perfect security. Moreover, the proposed encryption and decryption technique using the memristor based generated keys outperforms Triple Data Encryption Standard (3DES) and Advanced Encryption Standard (AES) in terms of processing time. This paper is enriched by providing characterization results of a fabricated microscale Al/TiO2/Al memristor prototype in order to prove the concept of the proposed approach and study the impacts of process variations. The work proposed in this paper is a milestone towards System On Chip (SOC) memristor based security.

Long non-coding RNA profile in mantle cell lymphoma identifies a functional lncRNA ROR1-AS1 associated with EZH2/PRC2 complex

Science.gov (United States)

Hu, Guangzhen; Gupta, Shiv K.; Troska, Tammy P.; Nair, Asha; Gupta, Mamta

2017-01-01

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed. As a result, several novel lncRNAs were found significantly overexpressed in the MCL samples with lncRNA ROR1-AS1 the most significant one. We cloned the ROR1-AS1 lncRNA in expression vector and ectopically transfected in MCL cell lines. Results showed that overexpression of ROR1-AS1 lncRNA promoted growth of MCL cells while decreased sensitivity to the treatment with drugs ibrutinib and dexamethasone. ROR-AS1 overexpression also decreased the mRNA expression of P16 (P = 0.21), and SOX11 (p = 0.017), without much effect on P53, ATM and P14 mRNA. RNA-immunoprecipitation assays demonstrated high affinity binding of lncRNA ROR1-AS1 with EZH2 and SUZ12 proteins of the polycomb repressive complex-2 (PRC2). Suppressing EZH2 activity with pharmacological inhibitor GSK343 abolished binding of ROR1-AS1 with EZH2. Taken together, this study identified a functional lncRNA ROR-AS1 involved with regulation of gene transcription via associating with PRC2 complex, and may serve as a novel biomarker in MCL patients. PMID:29113297

NAGRADATA. Code key. Geology

International Nuclear Information System (INIS)

Mueller, W.H.; Schneider, B.; Staeuble, J.

1984-01-01

This reference manual provides users of the NAGRADATA system with comprehensive keys to the coding/decoding of geological and technical information to be stored in or retreaved from the databank. Emphasis has been placed on input data coding. When data is retreaved the translation into plain language of stored coded information is done automatically by computer. Three keys each, list the complete set of currently defined codes for the NAGRADATA system, namely codes with appropriate definitions, arranged: 1. according to subject matter (thematically) 2. the codes listed alphabetically and 3. the definitions listed alphabetically. Additional explanation is provided for the proper application of the codes and the logic behind the creation of new codes to be used within the NAGRADATA system. NAGRADATA makes use of codes instead of plain language for data storage; this offers the following advantages: speed of data processing, mainly data retrieval, economies of storage memory requirements, the standardisation of terminology. The nature of this thesaurian type 'key to codes' makes it impossible to either establish a final form or to cover the entire spectrum of requirements. Therefore, this first issue of codes to NAGRADATA must be considered to represent the current state of progress of a living system and future editions will be issued in a loose leave ringbook system which can be updated by an organised (updating) service. (author)

Identifying key features of effective active learning: the effects of writing and peer discussion.

Science.gov (United States)

Linton, Debra L; Pangle, Wiline M; Wyatt, Kevin H; Powell, Karli N; Sherwood, Rachel E

2014-01-01

We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between three sections taught by three different instructors in a full factorial design. The data set was analyzed by generalized linear mixed-effect models with three independent variables: student aptitude, treatment, and instructor, and three dependent (assessment) variables: change in score on pre- and postactivity clicker questions, and coding scores on in-class writing and exam essays. All independent variables had significant effects on student performance for at least one of the dependent variables. Students with higher aptitude scored higher on all assessments. Student scores were higher on exam essay questions when the activity was implemented with a writing component compared with peer discussion only. There was a significant effect of instructor, with instructors showing different degrees of effectiveness with active-learning techniques. We suggest that individual writing should be implemented as part of active learning whenever possible and that instructors may need training and practice to become effective with active learning. © 2014 D. L. Linton et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A Polynomial Subset-Based Efficient Multi-Party Key Management System for Lightweight Device Networks.

Science.gov (United States)

Mahmood, Zahid; Ning, Huansheng; Ghafoor, AtaUllah

2017-03-24

Wireless Sensor Networks (WSNs) consist of lightweight devices to measure sensitive data that are highly vulnerable to security attacks due to their constrained resources. In a similar manner, the internet-based lightweight devices used in the Internet of Things (IoT) are facing severe security and privacy issues because of the direct accessibility of devices due to their connection to the internet. Complex and resource-intensive security schemes are infeasible and reduce the network lifetime. In this regard, we have explored the polynomial distribution-based key establishment schemes and identified an issue that the resultant polynomial value is either storage intensive or infeasible when large values are multiplied. It becomes more costly when these polynomials are regenerated dynamically after each node join or leave operation and whenever key is refreshed. To reduce the computation, we have proposed an Efficient Key Management (EKM) scheme for multiparty communication-based scenarios. The proposed session key management protocol is established by applying a symmetric polynomial for group members, and the group head acts as a responsible node. The polynomial generation method uses security credentials and secure hash function. Symmetric cryptographic parameters are efficient in computation, communication, and the storage required. The security justification of the proposed scheme has been completed by using Rubin logic, which guarantees that the protocol attains mutual validation and session key agreement property strongly among the participating entities. Simulation scenarios are performed using NS 2.35 to validate the results for storage, communication, latency, energy, and polynomial calculation costs during authentication, session key generation, node migration, secure joining, and leaving phases. EKM is efficient regarding storage, computation, and communication overhead and can protect WSN-based IoT infrastructure.

Geotechnics - the key to ground water protection

DEFF Research Database (Denmark)

Baumann, Jens; Foged, Niels; Jørgensen, Peter

2000-01-01

During the past 5 to 10 years research into ground water protection has proved that fractures in clay till may increase the hydraulic conductivity and herby the vulnerability of the ground water considerably. However, research has not identified a non-expensive and efficient method to map...... the fracture conditions of the various clay tills. Tests performed at the Danish Geotechnical Institute with large undisturbed columns of clay till show that there is a relation between the strength of the clay till and the hydraulic conductivity. Geotechnical methods may therefore be the key to determine...

[Key vessels assessment and operation highlights in laparoscopic extended right hemicolectomy].

Science.gov (United States)

Wang, Hao; Zhao, Quanquan

2018-03-25

Laparoscopic radical colectomies have been more widely used gradually, among which laparoscopic extended right hemicolectomy is considered as the most difficult procedure. The difficulty of extended right hemicolectomy lies in the need to dissect lymph nodes along the superior mesenteric vein (SMV) and disconnect numerous and possible aberrant vessels. To address this problem, we emphasize two points in key vessel assessment: getting familiar with the anatomy along the medial-to-lateral approach and having a good understanding about the preoperative imaging presentations. An accurately preoperative imaging assessment by abdominal enhanced CT can help the surgeon understand the relative position of the key vessels to be dealt with during operation and the situation of the possible aberrant vessels so as to guide the procedure more effectively and facilitate the prevention and management of the intraoperative complications. During operation, the operator should pay special attention to the management of the vessels in the ileocolic vessel region, Henle's trunk and middle colon vessels. The operation highlights of the key vessels are as follows: (1) The ileocolic vessels: identifying the Toldt's gap correctly and opening the vascular sheath of the SMV securely; making sure that the duodenum is well protected. (2) Henle's trunk: dissecting along the surface of the Henle's trunk; preserving the anterior superior pancreaticoduodenal vein (ASPDV) and main trunk of the Henle's trunk; disconnecting the roots of the right colic vein (RCV) and right gastroepiploic vein (RGEV), and then dissecting lymph nodes along the surface of the pancreas. (3) The middle colon vessels: identifying the root of the middle colon vessel along the lower edge of the pancreas; avoiding entering behind the pancreas; mobilizing the transverse mesocolon sufficiently along the surface of the pancreas. Finally, we discuss and analyze the disputes currently existing in laparoscopic extended right

Key Health Information Technologies and Related Issues for Iran: A Qualitative Study.

Science.gov (United States)

Hemmat, Morteza; Ayatollahi, Haleh; Maleki, Mohammadreza; Saghafi, Fatemeh

2018-01-01

Planning for the future of Health Information Technology (HIT) requires applying a systematic approach when conducting foresight studies. The aim of this study was to identify key health information technologies and related issues for Iran until 2025. This was a qualitative study and the participants included experts and policy makers in the field of health information technology. In-depth semi-structured interviews were conducted and data were analyzed by using framework analysis and MAXQDA software. The findings revealed that the development of national health information network, electronic health records, patient health records, a cloud-based service center, interoperability standards, patient monitoring technologies, telehealth, mhealth, clinical decision support systems, health information technology and mhealth infrastructure were found to be the key technologies for the future. These technologies could influence the economic, organizational and individual levels. To achieve them, the economic and organizational obstacles need to be overcome. In this study, a number of key technologies and related issues were identified. This approach can help to focus on the most important technologies in the future and to priorities these technologies for better resource allocation and policy making.

Nonmarket economic user values of the Florida Keys/Key West

Science.gov (United States)

Vernon R. Leeworthy; J. Michael Bowker

1997-01-01

This report provides estimates of the nonmarket economic user values for recreating visitors to the Florida Keys/Key West that participated in natural resource-based activities. Results from estimated travel cost models are presented, including visitor’s responses to prices and estimated per person-trip user values. Annual user values are also calculated and presented...

Key aromatic/hydrophobic amino acids controlling a cross-amyloid peptide interaction versus amyloid self-assembly.

Science.gov (United States)

Bakou, Maria; Hille, Kathleen; Kracklauer, Michael; Spanopoulou, Anna; Frost, Christina V; Malideli, Eleni; Yan, Li-Mei; Caporale, Andrea; Zacharias, Martin; Kapurniotu, Aphrodite

2017-09-01

The interaction of the intrinsically disordered polypeptide islet amyloid polypeptide (IAPP), which is associated with type 2 diabetes (T2D), with the Alzheimer's disease amyloid-β (Aβ) peptide modulates their self-assembly into amyloid fibrils and may link the pathogeneses of these two cell-degenerative diseases. However, the molecular determinants of this interaction remain elusive. Using a systematic alanine scan approach, fluorescence spectroscopy, and other biophysical methods, including heterocomplex pulldown assays, far-UV CD spectroscopy, the thioflavin T binding assay, transmission EM, and molecular dynamics simulations, here we identified single aromatic/hydrophobic residues within the amyloid core IAPP region as hot spots or key residues of its cross-interaction with Aβ40(42) peptide. Importantly, we also find that none of these residues in isolation plays a key role in IAPP self-assembly, whereas simultaneous substitution of four aromatic/hydrophobic residues with Ala dramatically impairs both IAPP self-assembly and hetero-assembly with Aβ40(42). Furthermore, our experiments yielded several novel IAPP analogs, whose sequences are highly similar to that of IAPP but have distinct amyloid self- or cross-interaction potentials. The identified similarities and major differences controlling IAPP cross-peptide interaction with Aβ40(42) versus its amyloid self-assembly offer a molecular basis for understanding the underlying mechanisms. We propose that these insights will aid in designing intervention strategies and novel IAPP analogs for the management of type 2 diabetes, Alzheimer's disease, or other diseases related to IAPP dysfunction or cross-amyloid interactions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of the key differential transcriptional responses of human whole blood following TLR2 or TLR4 ligation in-vitro.

Directory of Open Access Journals (Sweden)

Simon Blankley

Full Text Available The use of human whole blood for transcriptomic analysis has potential advantages over the use of isolated immune cells for studying the transcriptional response to pathogens and their products. Whole blood stimulation can be carried out in a laboratory without the expertise or equipment to isolate immune cells from blood, with the added advantage of being able to undertake experiments using very small volumes of blood. Toll like receptors (TLRs are a family of pattern recognition receptors which recognise highly conserved microbial products. Using the TLR2 ligand (Pam3CSK4 and the TLR4 ligand (LPS, human whole blood was stimulated for 0, 1, 3, 6, 12 or 24 hours at which times mRNA was isolated and a comparative microarray was undertaken. A common NFκB transcriptional programme was identified following both TLR2 and TLR4 ligation which peaked at between 3 to 6 hours including upregulation of many of the NFκB family members. In contrast an interferon transcriptional response was observed following TLR4 but not TLR2 ligation as early as 1 hour post stimulation and peaking at 6 hours. These results recapitulate the findings observed in previously published studies using isolated murine and human myeloid cells indicating that in vitro stimulated human whole blood can be used to interrogate the early transcriptional kinetic response of innate cells to TLR ligands. Our study demonstrates that a transcriptomic analysis of mRNA isolated from human whole blood can delineate both the temporal response and the key transcriptional differences following TLR2 and TLR4 ligation.

Fundamental study on the size and inter-key spacing of numeric keys for touch screen.

Science.gov (United States)

Harada, H; Katsuura, T; Kikuchi, Y

1996-12-01

The purpose of this study was to reveal the optimum size and inter-key spacing of numeric square keys for touch screens. Six male students (22-25 years old) and three female students (21-24 years old) volunteered as subjects for this experiment. Each subject took part in data entry tasks using numeric square keys of touch devices. The sizes of keys were 6, 12, 21, 30 and 39 mm and each the inter-key spacing was 0, 3, 6, 12 and 21 mm. Response times with key sizes of 6 and 12 mm were significantly slower than with key sizes of 21 and 30 mm (p touch screens should be more than 21 mm and optimum inter-key spacing should be from 3 to 6 mm. Optimum key size, however, must be selected with regard to the limitation of screen size.

Securing quantum key distribution systems using fewer states

Science.gov (United States)

Islam, Nurul T.; Lim, Charles Ci Wen; Cahall, Clinton; Kim, Jungsang; Gauthier, Daniel J.

2018-04-01

Quantum key distribution (QKD) allows two remote users to establish a secret key in the presence of an eavesdropper. The users share quantum states prepared in two mutually unbiased bases: one to generate the key while the other monitors the presence of the eavesdropper. Here, we show that a general d -dimension QKD system can be secured by transmitting only a subset of the monitoring states. In particular, we find that there is no loss in the secure key rate when dropping one of the monitoring states. Furthermore, it is possible to use only a single monitoring state if the quantum bit error rates are low enough. We apply our formalism to an experimental d =4 time-phase QKD system, where only one monitoring state is transmitted, and obtain a secret key rate of 17.4 ±2.8 Mbits/s at a 4 dB channel loss and with a quantum bit error rate of 0.045 ±0.001 and 0.037 ±0.001 in time and phase bases, respectively, which is 58.4% of the secret key rate that can be achieved with the full setup. This ratio can be increased, potentially up to 100%, if the error rates in time and phase basis are reduced. Our results demonstrate that it is possible to substantially simplify the design of high-dimensional QKD systems, including those that use the spatial or temporal degrees of freedom of the photon, and still outperform qubit-based (d =2 ) protocols.

Autoshaping of key pecking in pigeons with negative reinforcement1

Science.gov (United States)

Rachlin, Howard

1969-01-01

Pigeons exposed to gradually increasing intensities of pulsing electric shock pecked a key and thereby reduced the intensity of shock to zero for 2 min. Acquisition of key pecking was brought about through an autoshaping process in which periodic brief keylight presentations immediately preceded automatic reduction of the shock. On the occasions of such automatic reduction of shock preceding the first measured key peck, little or no orientation to the key was observed. Observations of pigeons with autoshaping of positive reinforcement also revealed little evidence of orientation toward the key. ImagesFig. 3.Fig. 4. PMID:16811371

Exploring key determinants of virtual worlds business success based on users' experience and perception

OpenAIRE

Xu , Xiaobo (Bob)

2010-01-01

Given the growth and popularity of virtual worlds, companies have a strong interest in presenting themselves successfully in virtual worlds. We designed an experimental study to identify the key determinants of virtual worlds business success based on users’ experience and perception. The preliminary results indicate that Starbucks, McDonalds, and Paris are the 3 most favorite sites. Furthermore, 5 key determinants (entertainment, functionality, interactivity, reality, and s...

Enu mutagenesis identifies a novel platelet phenotype in a loss-of-function Jak2 allele.

Directory of Open Access Journals (Sweden)

Nicole M Anderson

Full Text Available Utilizing ENU mutagenesis, we identified a mutant mouse with elevated platelets. Genetic mapping localized the mutation to an interval on chromosome 19 that encodes the Jak2 tyrosine kinase. We identified a A3056T mutation resulting in a premature stop codon within exon 19 of Jak2 (Jak2(K915X, resulting in a protein truncation and functionally inactive enzyme. This novel platelet phenotype was also observed in mice bearing a hemizygous targeted disruption of the Jak2 locus (Jak2(+/-. Timed pregnancy experiments revealed that Jak2(K915X/K915X and Jak2(-/- displayed embryonic lethality; however, Jak2(K915X/K915X embryos were viable an additional two days compared to Jak2(-/- embryos. Our data suggest that perturbing JAK2 activation may have unexpected consequences in elevation of platelet number and correspondingly, important implications for treatment of hematological disorders with constitutive Jak2 activity.

Metropolitan Quantum Key Distribution with Silicon Photonics

Science.gov (United States)

Bunandar, Darius; Lentine, Anthony; Lee, Catherine; Cai, Hong; Long, Christopher M.; Boynton, Nicholas; Martinez, Nicholas; DeRose, Christopher; Chen, Changchen; Grein, Matthew; Trotter, Douglas; Starbuck, Andrew; Pomerene, Andrew; Hamilton, Scott; Wong, Franco N. C.; Camacho, Ryan; Davids, Paul; Urayama, Junji; Englund, Dirk

2018-04-01

Photonic integrated circuits provide a compact and stable platform for quantum photonics. Here we demonstrate a silicon photonics quantum key distribution (QKD) encoder in the first high-speed polarization-based QKD field tests. The systems reach composable secret key rates of 1.039 Mbps in a local test (on a 103.6-m fiber with a total emulated loss of 9.2 dB) and 157 kbps in an intercity metropolitan test (on a 43-km fiber with 16.4 dB loss). Our results represent the highest secret key generation rate for polarization-based QKD experiments at a standard telecom wavelength and demonstrate photonic integrated circuits as a promising, scalable resource for future formation of metropolitan quantum-secure communications networks.

FMRP acts as a key messenger for dopamine modulation in the forebrain.

Science.gov (United States)

Wang, Hansen; Wu, Long-Jun; Kim, Susan S; Lee, Frank J S; Gong, Bo; Toyoda, Hiroki; Ren, Ming; Shang, Yu-Ze; Xu, Hui; Liu, Fang; Zhao, Ming-Gao; Zhuo, Min

2008-08-28

The fragile X mental retardation protein (FMRP) is an RNA-binding protein that controls translational efficiency and regulates synaptic plasticity. Here, we report that FMRP is involved in dopamine (DA) modulation of synaptic potentiation. AMPA glutamate receptor subtype 1 (GluR1) surface expression and phosphorylation in response to D1 receptor stimulation were reduced in cultured Fmr1(-/-) prefrontal cortex (PFC) neurons. Furthermore, D1 receptor signaling was impaired, accompanied by D1 receptor hyperphosphorylation at serine sites and subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2) in both PFC and striatum of Fmr1(-/-) mice. FMRP interacted with GRK2, and pharmacological inhibition of GRK2 rescued D1 receptor signaling in Fmr1(-/-) neurons. Finally, D1 receptor agonist partially rescued hyperactivity and enhanced the motor function of Fmr1(-/-) mice. Our study has identified FMRP as a key messenger for DA modulation in the forebrain and may provide insights into the cellular and molecular mechanisms underlying fragile X syndrome.

Tax and Semaphorin 4D Released from Lymphocytes Infected with Human Lymphotropic Virus Type 1 and Their Effect on Neurite Growth.

Science.gov (United States)

Quintremil, Sebastián; Alberti, Carolina; Rivera, Matías; Medina, Fernando; Puente, Javier; Cartier, Luis; Ramírez, Eugenio; Tanaka, Yuetsu; Valenzuela, M Antonieta

2016-01-01

Human lymphotropic virus type 1 (HTLV-1) is a retrovirus causing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurodegenerative central nervous system (CNS) axonopathy. This virus mainly infects CD4(+) T lymphocytes without evidence of neuronal infection. Viral Tax, secreted from infected lymphocytes infiltrated in the CNS, is proposed to alter intracellular pathways related to axonal cytoskeleton dynamics, producing neurological damage. Previous reports showed a higher proteolytic release of soluble Semaphorin 4D (sSEMA-4D) from CD4(+) T cells infected with HTLV-1. Soluble SEMA-4D binds to its receptor Plexin-B1, activating axonal growth collapse pathways in the CNS. In the current study, an increase was found in both SEMA-4D in CD4(+) T cells and sSEMA-4D released to the culture medium of peripheral blood mononuclear cells (PBMCs) from HAM/TSP patients compared to asymptomatic carriers and healthy donors. After a 16-h culture, infected PBMCs showed significantly higher levels of CRMP-2 phosphorylated at Ser(522). The effect was blocked either with anti-Tax or anti-SEMA-4D antibodies. The interaction of Tax and sSEMA-4D was found in secreted medium of PBMCs in patients, which might be associated with a leading role of Tax with the SEMA-4D-Plexin-B1 signaling pathway. In infected PBMCs, the migratory response after transwell assay showed that sSEMA-4D responding cells were CD4(+)Tax(+) T cells with a high CRMP-2 pSer(522) content. In the present study, the participation of Tax-sSEMA-4D in the reduction in neurite growth in PC12 cells produced by MT2 (HTLV-1-infected cell line) culture medium was observed. These results lead to the participation of plexins in the reported effects of infected lymphocytes on neuronal cells.

Evidentiary requirements to identify potentially acceptable sites (PAS) in crystalline rock

International Nuclear Information System (INIS)

Comella, P.A.; Smith, B.H.

1985-01-01

This report contains information on the evidentiary requirements to identify potentially acceptable sites in crystalline rock for waste disposal. Topics addressed include: chronology, key regulatory assumptions, statutory framework for identifying potentially acceptable sites, application of 10 disqualifiers, consideration of favorable and potentially adverse conditions, a composite favorability analysis, and a proposed outline for PAS identification decision document

Key insights on the structural characterization of textured Er2O3–ZrO2 nano-oxides prepared by a surfactant-free solvothermal route

International Nuclear Information System (INIS)

Julián-López, Beatriz; Luz, Verónica de la; Gonell, Francisco; Cordoncillo, Eloisa; López-Haro, Miguel; Calvino, Jose J.; Escribano, Purificación

2012-01-01

Highlights: ► Structural resolution of fluorite vs. pyrochlore in small nanocrystals. ► Simple template-free solvothermal synthesis of Er 2 O 3 –ZrO 2 nanooxides. ► Good control over size, morphology and surface properties (280 m 2 g −1 ). - Abstract: Zirconia-mixed oxides can exhibit cubic fluorite and pyrochlore structure. Their discrimination is not easy in nanooxides with a crystal size close to that of a few unit cells. In this work, high resolution transmission electron microscopy (HRTEM) has been employed to provide key insights on the structural characterization of a nanometric and porous mixed Er 2 O 3 –ZrO 2 oxide. The material was prepared by a simple template-free solvothermal route that provided nanocrystalline powders at low temperature (170 °C) with spherical morphology, and high surface area (∼280 m 2 g −1 ). The porosity was mainly originated from the assembling of organic complexing agents used in the synthesis to limit the crystal growth and to control hydrolysis and condensation reaction rates. The samples were characterized by thermal analysis, X-ray diffraction, scanning electron microscopy and N 2 adsorption measurements. A detailed study by HRTEM was conducted on microtomed samples. It was observed that the material was made of nanocrystals packed into spherical agglomerates. HRTEM simulations indicated that it is not possible to identify the pyrochlore phase in nanoparticles with diameter below 2 nm. In our samples, the analysis of the HRTEM lattice images by means of fast Fourier transform (FFT) techniques revealed well defined spots that can be assigned to different planes of a cubic fluorite-type phase, even in the raw material. Raman spectroscopy was also a powerful technique to elucidate the crystalline phase of the materials with the smallest nanoparticles. HREM and Raman results evidenced that the material is constituted, irrespective of the temperature of the final calcination step, by an ensemble of randomly

Three state quantum key distribution for small keys

International Nuclear Information System (INIS)

Batuwantudawe, J.; Boileau, J.-C.

2005-01-01

Full text: Quantum key distribution (QKD) protocols allow two parties, Alice and Bob, to establish secure keys. The most well-known protocol is BB84, using four distinct states. Recently, Phoenix et al. proposed a three state protocol. We explain the protocol and discuss its security proof. The three state protocol also has an interesting structure that allows for errors estimation from the inconclusive results (i.e.. where Alice and Bob choose different bases). This eliminates the need for sampling, potentially useful when qubits are limited. We discuss the effectiveness of this approach compared to BB84 for the case where a good error estimate is required. (author)

Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

DEFF Research Database (Denmark)

Imamura, Minako; Takahashi, Atsushi; Yamauchi, Toshimasa

2016-01-01

Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery...... and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P2, rs7107784 near MIR4686 and rs67839313 near INAFM2....... Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P

Key Response Planning Factors for the Aftermath of Nuclear Terrorism

Energy Technology Data Exchange (ETDEWEB)

Buddemeier, B R; Dillon, M B

2009-01-21

appropriate responses by local responders and the general population within the hazard zones, regional planning is essential to success. The remainder of this Executive Summary provides summary guidance for response planning in three areas: (1) Public Protection Strategy details the importance of early, adequate shelter followed by informed evacuation. (2) Responder Priorities identify how to protect response personnel, perform regional situational assessment, and support public safety. (3) Key Planning Considerations refute common myths and provide important information on planning how to respond in the aftermath of nuclear terrorism.

Experimental demonstration of subcarrier multiplexed quantum key distribution system.

Science.gov (United States)

Mora, José; Ruiz-Alba, Antonio; Amaya, Waldimar; Martínez, Alfonso; García-Muñoz, Víctor; Calvo, David; Capmany, José

2012-06-01

We provide, to our knowledge, the first experimental demonstration of the feasibility of sending several parallel keys by exploiting the technique of subcarrier multiplexing (SCM) widely employed in microwave photonics. This approach brings several advantages such as high spectral efficiency compatible with the actual secure key rates, the sharing of the optical fainted pulse by all the quantum multiplexed channels reducing the system complexity, and the possibility of upgrading with wavelength division multiplexing in a two-tier scheme, to increase the number of parallel keys. Two independent quantum SCM channels featuring a sifted key rate of 10 Kb/s/channel over a link with quantum bit error rate <2% is reported.

Bacteria and Archaea in acidic environments and a key to morphological identification

Science.gov (United States)

Robbins, E.I.

2000-01-01

Natural and anthropogenic acidic environments are dominated by bacteria and Archaea. As many as 86 genera or species have been identified or isolated from pH morphological characteristics, habitat information and a key for light microscope identification for the non-microbiologist.

In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target.

Science.gov (United States)

Manguso, Robert T; Pope, Hans W; Zimmer, Margaret D; Brown, Flavian D; Yates, Kathleen B; Miller, Brian C; Collins, Natalie B; Bi, Kevin; LaFleur, Martin W; Juneja, Vikram R; Weiss, Sarah A; Lo, Jennifer; Fisher, David E; Miao, Diana; Van Allen, Eliezer; Root, David E; Sharpe, Arlene H; Doench, John G; Haining, W Nicholas

2017-07-27

Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy. Tumours were sensitized to immunotherapy by deletion of genes involved in several diverse pathways, including NF-κB signalling, antigen presentation and the unfolded protein response. In addition, deletion of the protein tyrosine phosphatase PTPN2 in tumour cells increased the efficacy of immunotherapy by enhancing interferon-γ-mediated effects on antigen presentation and growth suppression. In vivo genetic screens in tumour models can identify new immunotherapy targets in unanticipated pathways.

Novel secret key generation techniques using memristor devices

Directory of Open Access Journals (Sweden)

Heba Abunahla

2016-02-01

Full Text Available This paper proposes novel secret key generation techniques using memristor devices. The approach depends on using the initial profile of a memristor as a master key. In addition, session keys are generated using the master key and other specified parameters. In contrast to existing memristor-based security approaches, the proposed development is cost effective and power efficient since the operation can be achieved with a single device rather than a crossbar structure. An algorithm is suggested and demonstrated using physics based Matlab model. It is shown that the generated keys can have dynamic size which provides perfect security. Moreover, the proposed encryption and decryption technique using the memristor based generated keys outperforms Triple Data Encryption Standard (3DES and Advanced Encryption Standard (AES in terms of processing time. This paper is enriched by providing characterization results of a fabricated microscale Al/TiO2/Al memristor prototype in order to prove the concept of the proposed approach and study the impacts of process variations. The work proposed in this paper is a milestone towards System On Chip (SOC memristor based security.

Independent assessment is key to financial well-being.

Science.gov (United States)

Karling, J; Pyper, T

1999-02-01

Both traditional group practices and IPAs have felt the impact of changes brought about by managed care. Group practices need to ensure that their financial reporting and cost-accounting methods capture information that is key to decision making. An independent assessment of financial procedures helps identify any outstanding issues and maintain financial well-being. This assessment should be conducted at least quarterly so that potential problems can be resolved, income opportunities explored, and cost-saving measures adopted in a timely manner.

Quantum key distribution with finite resources: Secret key rates via Renyi entropies

Energy Technology Data Exchange (ETDEWEB)

Abruzzo, Silvestre; Kampermann, Hermann; Mertz, Markus; Bruss, Dagmar [Institute for Theoretical Physics III, Heinrich-Heine-universitaet Duesseldorf, D-40225 Duesseldorf (Germany)

2011-09-15

A realistic quantum key distribution (QKD) protocol necessarily deals with finite resources, such as the number of signals exchanged by the two parties. We derive a bound on the secret key rate which is expressed as an optimization problem over Renyi entropies. Under the assumption of collective attacks by an eavesdropper, a computable estimate of our bound for the six-state protocol is provided. This bound leads to improved key rates in comparison to previous results.

Quantum key distribution with finite resources: Secret key rates via Renyi entropies

International Nuclear Information System (INIS)

Abruzzo, Silvestre; Kampermann, Hermann; Mertz, Markus; Bruss, Dagmar

2011-01-01

A realistic quantum key distribution (QKD) protocol necessarily deals with finite resources, such as the number of signals exchanged by the two parties. We derive a bound on the secret key rate which is expressed as an optimization problem over Renyi entropies. Under the assumption of collective attacks by an eavesdropper, a computable estimate of our bound for the six-state protocol is provided. This bound leads to improved key rates in comparison to previous results.

Toward sustainable environmental quality: Identifying priority research questions for Latin America

Science.gov (United States)

Furley, Tatiana Heid; Brodeur, Julie; Silva de Assis, Helena C; Carriquiriborde, Pedro; Chagas, Katia R; Corrales, Jone; Denadai, Marina; Fuchs, Julio; Mascarenhas, Renata; Miglioranza, Karina SB; Miguez Caramés, Diana Margarita; Navas, José Maria; Nugegoda, Dayanthi; Planes, Estela; Rodriguez‐Jorquera, Ignacio Alejandro; Orozco‐Medina, Martha; Boxall, Alistair BA; Rudd, Murray A

2018-01-01

ABSTRACT The Global Horizon Scanning Project (GHSP) is an innovative initiative that aims to identify important global environmental quality research needs. Here we report 20 key research questions from Latin America (LA). Members of the Society of Environmental Toxicology and Chemistry (SETAC) LA and other scientists from LA were asked to submit research questions that would represent priority needs to address in the region. One hundred questions were received, then partitioned among categories, examined, and some rearranged during a workshop in Buenos Aires, Argentina. Twenty priority research questions were subsequently identified. These research questions included developing, improving, and harmonizing across LA countries methods for 1) identifying contaminants and degradation products in complex matrices (including biota); 2) advancing prediction of contaminant risks and effects in ecosystems, addressing lab‐to‐field extrapolation challenges, and understanding complexities of multiple stressors (including chemicals and climate change); and 3) improving management and regulatory tools toward achieving sustainable development. Whereas environmental contaminants frequently identified in these key questions were pesticides, pharmaceuticals, endocrine disruptors or modulators, plastics, and nanomaterials, commonly identified environmental challenges were related to agriculture, urban effluents, solid wastes, pulp and paper mills, and natural extraction activities. Several interesting research topics included assessing and preventing pollution impacts on conservation protected areas, integrating environment and health assessments, and developing strategies for identification, substitution, and design of less hazardous chemicals (e.g., green chemistry). Finally, a recurrent research need included developing an understanding of differential sensitivity of regional species and ecosystems to environmental contaminants and other stressors. Addressing these critical

Toward sustainable environmental quality: Identifying priority research questions for Latin America.

Science.gov (United States)

Furley, Tatiana Heid; Brodeur, Julie; Silva de Assis, Helena C; Carriquiriborde, Pedro; Chagas, Katia R; Corrales, Jone; Denadai, Marina; Fuchs, Julio; Mascarenhas, Renata; Miglioranza, Karina Sb; Miguez Caramés, Diana Margarita; Navas, José Maria; Nugegoda, Dayanthi; Planes, Estela; Rodriguez-Jorquera, Ignacio Alejandro; Orozco-Medina, Martha; Boxall, Alistair Ba; Rudd, Murray A; Brooks, Bryan W

2018-05-01

The Global Horizon Scanning Project (GHSP) is an innovative initiative that aims to identify important global environmental quality research needs. Here we report 20 key research questions from Latin America (LA). Members of the Society of Environmental Toxicology and Chemistry (SETAC) LA and other scientists from LA were asked to submit research questions that would represent priority needs to address in the region. One hundred questions were received, then partitioned among categories, examined, and some rearranged during a workshop in Buenos Aires, Argentina. Twenty priority research questions were subsequently identified. These research questions included developing, improving, and harmonizing across LA countries methods for 1) identifying contaminants and degradation products in complex matrices (including biota); 2) advancing prediction of contaminant risks and effects in ecosystems, addressing lab-to-field extrapolation challenges, and understanding complexities of multiple stressors (including chemicals and climate change); and 3) improving management and regulatory tools toward achieving sustainable development. Whereas environmental contaminants frequently identified in these key questions were pesticides, pharmaceuticals, endocrine disruptors or modulators, plastics, and nanomaterials, commonly identified environmental challenges were related to agriculture, urban effluents, solid wastes, pulp and paper mills, and natural extraction activities. Several interesting research topics included assessing and preventing pollution impacts on conservation protected areas, integrating environment and health assessments, and developing strategies for identification, substitution, and design of less hazardous chemicals (e.g., green chemistry). Finally, a recurrent research need included developing an understanding of differential sensitivity of regional species and ecosystems to environmental contaminants and other stressors. Addressing these critical questions will

Metropolitan Quantum Key Distribution with Silicon Photonics

Directory of Open Access Journals (Sweden)

Darius Bunandar

2018-04-01

Full Text Available Photonic integrated circuits provide a compact and stable platform for quantum photonics. Here we demonstrate a silicon photonics quantum key distribution (QKD encoder in the first high-speed polarization-based QKD field tests. The systems reach composable secret key rates of 1.039 Mbps in a local test (on a 103.6-m fiber with a total emulated loss of 9.2 dB and 157 kbps in an intercity metropolitan test (on a 43-km fiber with 16.4 dB loss. Our results represent the highest secret key generation rate for polarization-based QKD experiments at a standard telecom wavelength and demonstrate photonic integrated circuits as a promising, scalable resource for future formation of metropolitan quantum-secure communications networks.

Deletion mutagenesis identifies a haploinsufficient role for gamma-zein in opaque-2 endosperm modification

Science.gov (United States)

Quality Protein Maize (QPM) is a hard kernel variant of the high-lysine mutant, opaque-2. Using gamma irradiation, we created opaque QPM variants to identify opaque-2 modifier genes and to investigate deletion mutagenesis combined with Illumina sequencing as a maize functional genomics tool. A K0326...

Quantum dense key distribution

International Nuclear Information System (INIS)

Degiovanni, I.P.; Ruo Berchera, I.; Castelletto, S.; Rastello, M.L.; Bovino, F.A.; Colla, A.M.; Castagnoli, G.

2004-01-01

This paper proposes a protocol for quantum dense key distribution. This protocol embeds the benefits of a quantum dense coding and a quantum key distribution and is able to generate shared secret keys four times more efficiently than the Bennet-Brassard 1984 protocol. We hereinafter prove the security of this scheme against individual eavesdropping attacks, and we present preliminary experimental results, showing its feasibility

Strategies for Supporting Physician-Scientists in Faculty Roles: A Narrative Review With Key Informant Consultations.

Science.gov (United States)

Lingard, Lorelei; Zhang, Peter; Strong, Michael; Steele, Margaret; Yoo, John; Lewis, James

2017-10-01

Physician-scientists are a population in decline globally. Solutions to reverse this decline often have focused on the training pipeline. Less attention has been paid to reducing attrition post training, when physician-scientists take up faculty roles. However, this period is a known time of vulnerability because of the pressures of clinical duties and the long timeline to securing independent research funding. This narrative review explored existing knowledge regarding how best to support physician-scientists for success in their faculty roles. The authors searched the Medline, Embase, ERIC, and Cochrane Library databases for articles published from 2000 to 2016 on this topic and interviewed key informants in 2015 to solicit their input on the review results. The authors reviewed 78 articles and interviewed 16 key informants. From the literature, they developed a framework of organizational (facilitate mentorship, foster community, value the physician-scientist role, minimize financial barriers) and individual (develop professional and research skills) strategies for supporting physician-scientists. They also outlined key knowledge gaps representing topics either rarely or never addressed in the reviewed articles (percent research time, structural hypocrisy, objective assessment, group metrics, professional identity). The key informants confirmed the identified strategies and discussed how the gaps were particularly important and impactful. This framework offers a basis for assessing an organization's existing support strategies, identifying outstanding needs, and developing targeted programming. The identified gaps require attention, as they threaten to undermine the benefits of existing support strategies.

Key-lock colloids in a nematic liquid crystal.

Science.gov (United States)

Silvestre, Nuno M; Tasinkevych, M

2017-01-01

The Landau-de Gennes free energy is used to study theoretically the effective interaction of spherical "key" and anisotropic "lock" colloidal particles. We assume identical anchoring properties of the surfaces of the key and of the lock particles, and we consider planar degenerate and perpendicular anchoring conditions separately. The lock particle is modeled as a spherical particle with a spherical dimple. When such a particle is introduced into a nematic liquid crystal, it orients its dimple at an oblique angle θ_{eq} with respect to the far field director n_{∞}. This angle depends on the depth of the dimple. Minimization results show that the free energy of a pair of key and lock particles exhibits a global minimum for the configuration when the key particle is facing the dimple of the lock colloidal particle. The preferred orientation ϕ_{eq} of the key-lock composite doublet relative to n_{∞} is robust against thermal fluctuations. The preferred orientation θ_{eq}^{(2)} of the dimple particle in the doublet is different from the isolated situation. This is related to the "direct" interaction of defects accompanying the key particle with the edge of the dimple. We propose that this nematic-amplified key-lock interaction can play an important role in self-organization and clustering of mixtures of colloidal particles with dimple colloids present.

Identifying motivational factors within a multinational company

Directory of Open Access Journals (Sweden)

Daniela Bradutanu

2011-08-01

Full Text Available The aim of the study is to identify the main motivational factors within a multinational company. The first objective is to identify work functions, formulated on Abraham Maslow’s pyramid, following the identification of the key characteristics that motivate an employee at the work place and last, but not least, the type of motivation that employees focus, intrinsic or extrinsic. The research method targeted a questionnaire based survey, including various company employees and an interview with the manager. The results confirmed that in Romania, employees put great emphasis on extrinsic motivation, a certain income and job security being primary. These results have implications for managers that in order to effectively motivate staff, first, must know their needs and expectations. To identify the main needs and motivational factors we had as a starting point Maslow's pyramid.

The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses

DEFF Research Database (Denmark)

Blom, Lars H; Martel, Britta C; Larsen, Lau F

2017-01-01

of this investigation was to identify surface markers associated with type 2 inflammation. METHODS: Naïve human CD4(+) T-cells were short-term activated in the presence or absence of IL-4, and analysed for expression of >300 cell-surface proteins. Ex vivo isolated PBMCs from peanut and non-allergic allergic subjects......, were stimulated (14-16h) with peanut extract to detect peanut-specific CD4(+) CD154(+) T-cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis and psoriasis. RESULTS: Expression analysis of >300 surface proteins...... and ILC2 cells and basophils. In peanut-allergic subjects the peanut-specific Th2 (CD154(+) CRTh2(+) ) cells expressed more CD200R than the non-allergen specific Th2 (CD154(-) CRTh2(+) ) cells. Moreover, co-staining of CD161 and CD200R identified peanut-specific highly differentiated IL-4(+) IL-5(+) Th2...

GTPase activity plays a key role in the pathobiology of LRRK2.

Directory of Open Access Journals (Sweden)

Yulan Xiong

2010-04-01

Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene are associated with late-onset, autosomal-dominant, familial Parkinson's disease (PD and also contribute to sporadic disease. The LRRK2 gene encodes a large protein with multiple domains, including functional Roc GTPase and protein kinase domains. Mutations in LRRK2 most likely cause disease through a toxic gain-of-function mechanism. The expression of human LRRK2 variants in cultured primary neurons induces toxicity that is dependent on intact GTP binding or kinase activities. However, the mechanism(s underlying LRRK2-induced neuronal toxicity is poorly understood, and the contribution of GTPase and/or kinase activity to LRRK2 pathobiology is not well defined. To explore the pathobiology of LRRK2, we have developed a model of LRRK2 cytotoxicity in the baker's yeast Saccharomyces cerevisiae. Protein domain analysis in this model reveals that expression of GTPase domain-containing fragments of human LRRK2 are toxic. LRRK2 toxicity in yeast can be modulated by altering GTPase activity and is closely associated with defects in endocytic vesicular trafficking and autophagy. These truncated LRRK2 variants induce similar toxicity in both yeast and primary neuronal models and cause similar vesicular defects in yeast as full-length LRRK2 causes in primary neurons. The toxicity induced by truncated LRRK2 variants in yeast acts through a mechanism distinct from toxicity induced by human alpha-synuclein. A genome-wide genetic screen identified modifiers of LRRK2-induced toxicity in yeast including components of vesicular trafficking pathways, which can also modulate the trafficking defects caused by expression of truncated LRRK2 variants. Our results provide insight into the basic pathobiology of LRRK2 and suggest that the GTPase domain may contribute to the toxicity of LRRK2. These findings may guide future therapeutic strategies aimed at attenuating LRRK2-mediated neurodegeneration.

A fast and versatile quantum key distribution system with hardware key distillation and wavelength multiplexing

International Nuclear Information System (INIS)

Walenta, N; Gisin, N; Guinnard, O; Houlmann, R; Korzh, B; Lim, C W; Lunghi, T; Portmann, C; Thew, R T; Burg, A; Constantin, J; Caselunghe, D; Kulesza, N; Legré, M; Monat, L; Soucarros, M; Trinkler, P; Junod, P; Trolliet, G; Vannel, F

2014-01-01

We present a compactly integrated, 625 MHz clocked coherent one-way quantum key distribution system which continuously distributes secret keys over an optical fibre link. To support high secret key rates, we implemented a fast hardware key distillation engine which allows for key distillation rates up to 4 Mbps in real time. The system employs wavelength multiplexing in order to run over only a single optical fibre. Using fast gated InGaAs single photon detectors, we reliably distribute secret keys with a rate above 21 kbps over 25 km of optical fibre. We optimized the system considering a security analysis that respects finite-key-size effects, authentication costs and system errors for a security parameter of ε QKD  = 4 × 10 −9 . (paper)