Analyzing and Identifying Teens' Stressful Periods and Stressor Events From a Microblog.

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Li, Qi; Xue, Yuanyuan; Zhao, Liang; Jia, Jia; Feng, Ling

2017-09-01

Increased health problems among adolescents caused by psychological stress have aroused worldwide attention. Long-standing stress without targeted assistance and guidance negatively impacts the healthy growth of adolescents, threatening the future development of our society. So far, research focused on detecting adolescent psychological stress revealed from each individual post on microblogs. However, beyond stressful moments, identifying teens' stressful periods and stressor events that trigger each stressful period is more desirable to understand the stress from appearance to essence. In this paper, we define the problem of identifying teens' stressful periods and stressor events from the open social media microblog. Starting from a case study of adolescents' posting behaviors during stressful school events, we build a Poisson-based probability model for the correlation between stressor events and stressful posting behaviors through a series of posts on Tencent Weibo (referred to as the microblog throughout the paper). With the model, we discover teens' maximal stressful periods and further extract details of possible stressor events that cause the stressful periods. We generalize and present the extracted stressor events in a hierarchy based on common stress dimensions and event types. Taking 122 scheduled stressful study-related events in a high school as the ground truth, we test the approach on 124 students' posts from January 1, 2012 to February 1, 2015 and obtain some promising experimental results: (stressful periods: recall 0.761, precision 0.737, and F 1 -measure 0.734) and (top-3 stressor events: recall 0.763, precision 0.756, and F 1 -measure 0.759). The most prominent stressor events extracted are in the self-cognition domain, followed by the school life domain. This conforms to the adolescent psychological investigation result that problems in school life usually accompanied with teens' inner cognition problems. Compared with the state-of-the-art top

Bringing molecules back into molecular evolution.

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Claus O Wilke

Full Text Available Much molecular-evolution research is concerned with sequence analysis. Yet these sequences represent real, three-dimensional molecules with complex structure and function. Here I highlight a growing trend in the field to incorporate molecular structure and function into computational molecular-evolution work. I consider three focus areas: reconstruction and analysis of past evolutionary events, such as phylogenetic inference or methods to infer selection pressures; development of toy models and simulations to identify fundamental principles of molecular evolution; and atom-level, highly realistic computational modeling of molecular structure and function aimed at making predictions about possible future evolutionary events.

A new index for identifying different types of El Niño Modoki events

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Wang, Xin; Tan, Wei; Wang, Chunzai

2018-04-01

El Niño Modoki events can be further classified into El Niño Modoki I and II in terms of their opposite impacts on southern China rainfall (Wang and Wang, J Clim 26:1322-1338, 2013) and the Indian Ocean dipole mode (Wang and Wang, Clim Dyn 42:991-1005, 2014). The present paper develops an index to identify the types of El Niño events. The El Niño Modoki II (MII) index is defined as the leading principle component of multivariate empirical orthogonal function analysis of the normalized El Niño Modoki index, Niño4 index and 850 hPa relative vorticity anomalies averaged near the Philippine Sea during autumn. The MII index exhibits dominant variations on interannual (2-3 and 4-5 years) and decadal (10-20 years) timescales. El Niño Modoki II events can be well identified by using the MII index value being larger than 1 standard deviation. Further analyses and numerical model experiments confirm that the MII index can portray the major oceanic and atmospheric features of El Niño Modoki II events. The constructed MII index along with previous ENSO indices can be used for classifying and identifying all types of El Niño events. Because of distinct impacts induced by different types of El Niño events, the implication of the present study is that climate prediction and future climate projection under global warming can be improved by using the MII index and other indices to identify the types of El Niño events.

A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease

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Huan, Tianxiao; Zhang, Bin; Wang, Zhi; Joehanes, Roby; Zhu, Jun; Johnson, Andrew D.; Ying, Saixia; Munson, Peter J.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Courchesne, Paul; Hwang, Shih-Jen; Assimes, Themistocles L.; McPherson, Ruth; Samani, Nilesh J.; Schunkert, Heribert; Meng, Qingying; Suver, Christine; O'Donnell, Christopher J.; Derry, Jonathan; Yang, Xia; Levy, Daniel

2013-01-01

Objective Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD. Approach and Results We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age- and sex-matched controls. 24 coexpression modules were identified including one case-specific and one control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with altered gene expression associated SNPs (eSNPs) and with results of GWAS of CHD and its risk factors, the control-specific DM was implicated as CHD-causal based on its significant enrichment for both CHD and lipid eSNPs. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver (KD) genes. Multi-tissue KDs (SPIB and TNFRSF13C) and tissue-specific KDs (e.g. EBF1) were identified. Conclusions Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk. PMID:23539213

Action-Derived Molecular Dynamics in the Study of Rare Events

Energy Technology Data Exchange (ETDEWEB)

Passerone, Daniele; Parrinello, Michele

2001-09-03

We present a practical method to generate classical trajectories with fixed initial and final boundary conditions. Our method is based on the minimization of a suitably defined discretized action. The method finds its most natural application in the study of rare events. Its capabilities are illustrated by nontrivial examples. The algorithm lends itself to straightforward parallelization, and when combined with ab initio molecular dynamics it promises to offer a powerful tool for the study of chemical reactions.

Action-Derived Molecular Dynamics in the Study of Rare Events

International Nuclear Information System (INIS)

Passerone, Daniele; Parrinello, Michele

2001-01-01

We present a practical method to generate classical trajectories with fixed initial and final boundary conditions. Our method is based on the minimization of a suitably defined discretized action. The method finds its most natural application in the study of rare events. Its capabilities are illustrated by nontrivial examples. The algorithm lends itself to straightforward parallelization, and when combined with ab initio molecular dynamics it promises to offer a powerful tool for the study of chemical reactions

Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

International Nuclear Information System (INIS)

Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J.

2016-01-01

Highlights: • Male fathead minnow were exposed to 17alpha ethinylestradiol (EE2). • Both 11-ketotestosterone and testosterone production was decreased relative to controls. • A gene network associated with doublesex and mab-3 related transcription factor 1 were suppressed. • Genes involved in granulosa cell development were increased and sensitive to EE2 exposure. • Molecular initiating events that may be related to the intersex condition were identified. - Abstract: Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15 ng/L) and measured the transcriptome response in the testis after 96 h to identify early molecular initiating events that may proceed the intersex condition. The short-term exposure to EE2 did not affect gonadosomatic index and proportion of gametes within the testes. However, the production of 11-ketotestosterone and testosterone from the testis in vitro was decreased relative to controls. Expression profiling using a 8 × 60 K fathead minnow microarray identified 10 transcripts that were differentially expressed in the testes, the most dramatic change being that of coagulation factor XIII A chain (20-fold increase). Transcripts that included guanine nucleotide binding protein (Beta Polypeptide 2), peroxisome proliferator-activated receptor delta, and WNK lysine deficient protein kinase 1a, were down-regulated by EE2. Subnetwork enrichment analysis revealed that EE2 suppressed transcriptional networks associated with steroid metabolism, hormone biosynthesis, and sperm mobility. Most interesting was that gene networks associated with doublesex and mab-3 related transcription factor 1 (dmrt1) were suppressed in the adult

Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

Energy Technology Data Exchange (ETDEWEB)

Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J., E-mail: cmartyni@yahoo.ca

2016-12-15

Highlights: • Male fathead minnow were exposed to 17alpha ethinylestradiol (EE2). • Both 11-ketotestosterone and testosterone production was decreased relative to controls. • A gene network associated with doublesex and mab-3 related transcription factor 1 were suppressed. • Genes involved in granulosa cell development were increased and sensitive to EE2 exposure. • Molecular initiating events that may be related to the intersex condition were identified. - Abstract: Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15 ng/L) and measured the transcriptome response in the testis after 96 h to identify early molecular initiating events that may proceed the intersex condition. The short-term exposure to EE2 did not affect gonadosomatic index and proportion of gametes within the testes. However, the production of 11-ketotestosterone and testosterone from the testis in vitro was decreased relative to controls. Expression profiling using a 8 × 60 K fathead minnow microarray identified 10 transcripts that were differentially expressed in the testes, the most dramatic change being that of coagulation factor XIII A chain (20-fold increase). Transcripts that included guanine nucleotide binding protein (Beta Polypeptide 2), peroxisome proliferator-activated receptor delta, and WNK lysine deficient protein kinase 1a, were down-regulated by EE2. Subnetwork enrichment analysis revealed that EE2 suppressed transcriptional networks associated with steroid metabolism, hormone biosynthesis, and sperm mobility. Most interesting was that gene networks associated with doublesex and mab-3 related transcription factor 1 (dmrt1) were suppressed in the adult

Identifying Typhoon Tracks based on Event Synchronization derived Spatially Embedded Climate Networks

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Ozturk, Ugur; Marwan, Norbert; Kurths, Jürgen

2017-04-01

Complex networks are commonly used for investigating spatiotemporal dynamics of complex systems, e.g. extreme rainfall. Especially directed networks are very effective tools in identifying climatic patterns on spatially embedded networks. They can capture the network flux, so as the principal dynamics of spreading significant phenomena. Network measures, such as network divergence, bare the source-receptor relation of the directed networks. However, it is still a challenge how to catch fast evolving atmospheric events, i.e. typhoons. In this study, we propose a new technique, namely Radial Ranks, to detect the general pattern of typhoons forward direction based on the strength parameter of the event synchronization over Japan. We suggest to subset a circular zone of high correlation around the selected grid based on the strength parameter. Radial sums of the strength parameter along vectors within this zone, radial ranks are measured for potential directions, which allows us to trace the network flux over long distances. We employed also the delay parameter of event synchronization to identify and separate the frontal storms' and typhoons' individual behaviors.

Molecular Characterization of Transgenic Events Using Next Generation Sequencing Approach.

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Guttikonda, Satish K; Marri, Pradeep; Mammadov, Jafar; Ye, Liang; Soe, Khaing; Richey, Kimberly; Cruse, James; Zhuang, Meibao; Gao, Zhifang; Evans, Clive; Rounsley, Steve; Kumpatla, Siva P

2016-01-01

Demand for the commercial use of genetically modified (GM) crops has been increasing in light of the projected growth of world population to nine billion by 2050. A prerequisite of paramount importance for regulatory submissions is the rigorous safety assessment of GM crops. One of the components of safety assessment is molecular characterization at DNA level which helps to determine the copy number, integrity and stability of a transgene; characterize the integration site within a host genome; and confirm the absence of vector DNA. Historically, molecular characterization has been carried out using Southern blot analysis coupled with Sanger sequencing. While this is a robust approach to characterize the transgenic crops, it is both time- and resource-consuming. The emergence of next-generation sequencing (NGS) technologies has provided highly sensitive and cost- and labor-effective alternative for molecular characterization compared to traditional Southern blot analysis. Herein, we have demonstrated the successful application of both whole genome sequencing and target capture sequencing approaches for the characterization of single and stacked transgenic events and compared the results and inferences with traditional method with respect to key criteria required for regulatory submissions.

Molecular Characterization of Transgenic Events Using Next Generation Sequencing Approach.

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Satish K Guttikonda

Full Text Available Demand for the commercial use of genetically modified (GM crops has been increasing in light of the projected growth of world population to nine billion by 2050. A prerequisite of paramount importance for regulatory submissions is the rigorous safety assessment of GM crops. One of the components of safety assessment is molecular characterization at DNA level which helps to determine the copy number, integrity and stability of a transgene; characterize the integration site within a host genome; and confirm the absence of vector DNA. Historically, molecular characterization has been carried out using Southern blot analysis coupled with Sanger sequencing. While this is a robust approach to characterize the transgenic crops, it is both time- and resource-consuming. The emergence of next-generation sequencing (NGS technologies has provided highly sensitive and cost- and labor-effective alternative for molecular characterization compared to traditional Southern blot analysis. Herein, we have demonstrated the successful application of both whole genome sequencing and target capture sequencing approaches for the characterization of single and stacked transgenic events and compared the results and inferences with traditional method with respect to key criteria required for regulatory submissions.

Positive predictive value of a register-based algorithm using the Danish National Registries to identify suicidal events.

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Gasse, Christiane; Danielsen, Andreas Aalkjaer; Pedersen, Marianne Giørtz; Pedersen, Carsten Bøcker; Mors, Ole; Christensen, Jakob

2018-04-17

It is not possible to fully assess intention of self-harm and suicidal events using information from administrative databases. We conducted a validation study of intention of suicide attempts/self-harm contacts identified by a commonly applied Danish register-based algorithm (DK-algorithm) based on hospital discharge diagnosis and emergency room contacts. Of all 101 530 people identified with an incident suicide attempt/self-harm contact at Danish hospitals between 1995 and 2012 using the DK-algorithm, we selected a random sample of 475 people. We validated the DK-algorithm against medical records applying the definitions and terminology of the Columbia Classification Algorithm of Suicide Assessment of suicidal events, nonsuicidal events, and indeterminate or potentially suicidal events. We calculated positive predictive values (PPVs) of the DK-algorithm to identify suicidal events overall, by gender, age groups, and calendar time. We retrieved medical records for 357 (75%) people. The PPV of the DK-algorithm to identify suicidal events was 51.5% (95% CI: 46.4-56.7) overall, 42.7% (95% CI: 35.2-50.5) in males, and 58.5% (95% CI: 51.6-65.1) in females. The PPV varied further across age groups and calendar time. After excluding cases identified via the DK-algorithm by unspecific codes of intoxications and injury, the PPV improved slightly (56.8% [95% CI: 50.0-63.4]). The DK-algorithm can reliably identify self-harm with suicidal intention in 52% of the identified cases of suicide attempts/self-harm. The PPVs could be used for quantitative bias analysis and implemented as weights in future studies to estimate the proportion of suicidal events among cases identified via the DK-algorithm. Copyright © 2018 John Wiley & Sons, Ltd.

Molecular Events in Primary and Metastatic Colorectal Carcinoma: A Review

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Rani Kanthan

2012-01-01

Full Text Available Colorectal cancer (CRC is a heterogeneous disease, developing through a multipathway sequence of events guided by clonal selections. Pathways included in the development of CRC may be broadly categorized into (a genomic instability, including chromosomal instability (CIN, microsatellite instability (MSI, and CpG island methylator phenotype (CIMP, (b genomic mutations including suppression of tumour suppressor genes and activation of tumour oncogenes, (c microRNA, and (d epigenetic changes. As cancer becomes more advanced, invasion and metastases are facilitated through the epithelial-mesenchymal transition (EMT, with additional genetic alterations. Despite ongoing identification of genetic and epigenetic markers and the understanding of alternative pathways involved in the development and progression of this disease, CRC remains the second highest cause of malignancy-related mortality in Canada. The molecular events that underlie the tumorigenesis of primary and metastatic colorectal carcinoma are detailed in this manuscript.

Defining molecular initiating events in the adverse outcome pathway framework for risk assessment.

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Allen, Timothy E H; Goodman, Jonathan M; Gutsell, Steve; Russell, Paul J

2014-12-15

Consumer and environmental safety decisions are based on exposure and hazard data, interpreted using risk assessment approaches. The adverse outcome pathway (AOP) conceptual framework has been presented as a logical sequence of events or processes within biological systems which can be used to understand adverse effects and refine current risk assessment practices in ecotoxicology. This framework can also be applied to human toxicology and is explored on the basis of investigating the molecular initiating events (MIEs) of compounds. The precise definition of the MIE has yet to reach general acceptance. In this work we present a unified MIE definition: an MIE is the initial interaction between a molecule and a biomolecule or biosystem that can be causally linked to an outcome via a pathway. Case studies are presented, and issues with current definitions are addressed. With the development of a unified MIE definition, the field can look toward defining, classifying, and characterizing more MIEs and using knowledge of the chemistry of these processes to aid AOP research and toxicity risk assessment. We also present the role of MIE research in the development of in vitro and in silico toxicology and suggest how, by using a combination of biological and chemical approaches, MIEs can be identified and characterized despite a lack of detailed reports, even for some of the most studied molecules in toxicology.

Why conventional detection methods fail in identifying the existence of contamination events.

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Liu, Shuming; Li, Ruonan; Smith, Kate; Che, Han

2016-04-15

Early warning systems are widely used to safeguard water security, but their effectiveness has raised many questions. To understand why conventional detection methods fail to identify contamination events, this study evaluates the performance of three contamination detection methods using data from a real contamination accident and two artificial datasets constructed using a widely applied contamination data construction approach. Results show that the Pearson correlation Euclidean distance (PE) based detection method performs better for real contamination incidents, while the Euclidean distance method (MED) and linear prediction filter (LPF) method are more suitable for detecting sudden spike-like variation. This analysis revealed why the conventional MED and LPF methods failed to identify existence of contamination events. The analysis also revealed that the widely used contamination data construction approach is misleading. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of GM events by insert knowledge adapted re-sequencing approaches.

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Yang, Litao; Wang, Congmao; Holst-Jensen, Arne; Morisset, Dany; Lin, Yongjun; Zhang, Dabing

2013-10-03

Detection methods and data from molecular characterization of genetically modified (GM) events are needed by stakeholders of public risk assessors and regulators. Generally, the molecular characteristics of GM events are incomprehensively revealed by current approaches and biased towards detecting transformation vector derived sequences. GM events are classified based on available knowledge of the sequences of vectors and inserts (insert knowledge). Herein we present three insert knowledge-adapted approaches for characterization GM events (TT51-1 and T1c-19 rice as examples) based on paired-end re-sequencing with the advantages of comprehensiveness, accuracy, and automation. The comprehensive molecular characteristics of two rice events were revealed with additional unintended insertions comparing with the results from PCR and Southern blotting. Comprehensive transgene characterization of TT51-1 and T1c-19 is shown to be independent of a priori knowledge of the insert and vector sequences employing the developed approaches. This provides an opportunity to identify and characterize also unknown GM events.

Identifying events that impact self-efficacy in physics learning

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Vashti Sawtelle

2012-09-01

Full Text Available We present a method of analyzing the development of self-efficacy in real time using a framework of self-efficacy opportunities (SEOs. Considerable research has shown a connection between self-efficacy, or the confidence in one’s own ability to perform a task, and success in science fields. Traditional methods of investigating the development of self-efficacy have required participants to recollect past events. This reliance on participant memory makes it difficult to understand what impact particular events may have on developing self-efficacy in the moment. We use video recordings of three undergraduate Modeling Instruction students solving a physics problem to characterize SEOs in a moment-by-moment analysis. We then validate these characterizations of the development of self-efficacy by reviewing the problem-solving session with the participants and find evidence that the SEOs identified are taken up and impact self-efficacy. This characterization and validation of SEOs in the moment represents a first step towards establishing a methodology for analyzing the development of self-efficacy in real time.

Utilization of Satellite Data to Identify and Monitor Changes in Frequency of Meteorological Events

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Mast, J. C.; Dessler, A. E.

2017-12-01

Increases in temperature and climate variability due to human-induced climate change is increasing the frequency and magnitude of extreme heat events (i.e., heatwaves). This will have a detrimental impact on the health of human populations and habitability of certain land locations. Here we seek to utilize satellite data records to identify and monitor extreme heat events. We analyze satellite data sets (MODIS and AIRS land surface temperatures (LST) and water vapor profiles (WV)) due to their global coverage and stable calibration. Heat waves are identified based on the frequency of maximum daily temperatures above a threshold, determined as follows. Land surface temperatures are gridded into uniform latitude/longitude bins. Maximum daily temperatures per bin are determined and probability density functions (PDF) of these maxima are constructed monthly and seasonally. For each bin, a threshold is calculated at the 95th percentile of the PDF of maximum temperatures. Per each bin, an extreme heat event is defined based on the frequency of monthly and seasonal days exceeding the threshold. To account for the decreased ability of the human body to thermoregulate with increasing moisture, and to assess lethality of the heat events, we determine the wet-bulb temperature at the locations of extreme heat events. Preliminary results will be presented.

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

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Farshad Farshidfar

2017-03-01

Full Text Available Cholangiocarcinoma (CCA is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

STRIDE: Species Tree Root Inference from Gene Duplication Events.

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Emms, David M; Kelly, Steven

2017-12-01

The correct interpretation of any phylogenetic tree is dependent on that tree being correctly rooted. We present STRIDE, a fast, effective, and outgroup-free method for identification of gene duplication events and species tree root inference in large-scale molecular phylogenetic analyses. STRIDE identifies sets of well-supported in-group gene duplication events from a set of unrooted gene trees, and analyses these events to infer a probability distribution over an unrooted species tree for the location of its root. We show that STRIDE correctly identifies the root of the species tree in multiple large-scale molecular phylogenetic data sets spanning a wide range of timescales and taxonomic groups. We demonstrate that the novel probability model implemented in STRIDE can accurately represent the ambiguity in species tree root assignment for data sets where information is limited. Furthermore, application of STRIDE to outgroup-free inference of the origin of the eukaryotic tree resulted in a root probability distribution that provides additional support for leading hypotheses for the origin of the eukaryotes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Iterative Calibration: A Novel Approach for Calibrating the Molecular Clock Using Complex Geological Events.

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Loeza-Quintana, Tzitziki; Adamowicz, Sarah J

2018-02-01

During the past 50 years, the molecular clock has become one of the main tools for providing a time scale for the history of life. In the era of robust molecular evolutionary analysis, clock calibration is still one of the most basic steps needing attention. When fossil records are limited, well-dated geological events are the main resource for calibration. However, biogeographic calibrations have often been used in a simplistic manner, for example assuming simultaneous vicariant divergence of multiple sister lineages. Here, we propose a novel iterative calibration approach to define the most appropriate calibration date by seeking congruence between the dates assigned to multiple allopatric divergences and the geological history. Exploring patterns of molecular divergence in 16 trans-Bering sister clades of echinoderms, we demonstrate that the iterative calibration is predominantly advantageous when using complex geological or climatological events-such as the opening/reclosure of the Bering Strait-providing a powerful tool for clock dating that can be applied to other biogeographic calibration systems and further taxa. Using Bayesian analysis, we observed that evolutionary rate variability in the COI-5P gene is generally distributed in a clock-like fashion for Northern echinoderms. The results reveal a large range of genetic divergences, consistent with multiple pulses of trans-Bering migrations. A resulting rate of 2.8% pairwise Kimura-2-parameter sequence divergence per million years is suggested for the COI-5P gene in Northern echinoderms. Given that molecular rates may vary across latitudes and taxa, this study provides a new context for dating the evolutionary history of Arctic marine life.

Development of an online morbidity, mortality, and near-miss reporting system to identify patterns of adverse events in surgical patients.

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Bilimoria, Karl Y; Kmiecik, Thomas E; DaRosa, Debra A; Halverson, Amy; Eskandari, Mark K; Bell, Richard H; Soper, Nathaniel J; Wayne, Jeffrey D

2009-04-01

To design a Web-based system to track adverse and near-miss events, to establish an automated method to identify patterns of events, and to assess the adverse event reporting behavior of physicians. A Web-based system was designed to collect physician-reported adverse events including weekly Morbidity and Mortality (M&M) entries and anonymous adverse/near-miss events. An automated system was set up to help identify event patterns. Adverse event frequency was compared with hospital databases to assess reporting completeness. A metropolitan tertiary care center. Identification of adverse event patterns and completeness of reporting. From September 2005 to August 2007, 15,524 surgical patients were reported including 957 (6.2%) adverse events and 34 (0.2%) anonymous reports. The automated pattern recognition system helped identify 4 event patterns from M&M reports and 3 patterns from anonymous/near-miss reporting. After multidisciplinary meetings and expert reviews, the patterns were addressed with educational initiatives, correction of systems issues, and/or intensive quality monitoring. Only 25% of complications and 42% of inpatient deaths were reported. A total of 75.2% of adverse events resulting in permanent disability or death were attributed to the nature of the disease. Interventions to improve reporting were largely unsuccessful. We have developed a user-friendly Web-based system to track complications and identify patterns of adverse events. Underreporting of adverse events and attributing the complication to the nature of the disease represent a problem in reporting culture among surgeons at our institution. Similar systems should be used by surgery departments, particularly those affiliated with teaching hospitals, to identify quality improvement opportunities.

PASBio: predicate-argument structures for event extraction in molecular biology

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Wattarujeekrit, Tuangthong; Shah, Parantu K; Collier, Nigel

2004-01-01

Background The exploitation of information extraction (IE), a technology aiming to provide instances of structured representations from free-form text, has been rapidly growing within the molecular biology (MB) research community to keep track of the latest results reported in literature. IE systems have traditionally used shallow syntactic patterns for matching facts in sentences but such approaches appear inadequate to achieve high accuracy in MB event extraction due to complex sentence structure. A consensus in the IE community is emerging on the necessity for exploiting deeper knowledge structures such as through the relations between a verb and its arguments shown by predicate-argument structure (PAS). PAS is of interest as structures typically correspond to events of interest and their participating entities. For this to be realized within IE a key knowledge component is the definition of PAS frames. PAS frames for non-technical domains such as newswire are already being constructed in several projects such as PropBank, VerbNet, and FrameNet. Knowledge from PAS should enable more accurate applications in several areas where sentence understanding is required like machine translation and text summarization. In this article, we explore the need to adapt PAS for the MB domain and specify PAS frames to support IE, as well as outlining the major issues that require consideration in their construction. Results We introduce PASBio by extending a model based on PropBank to the MB domain. The hypothesis we explore is that PAS holds the key for understanding relationships describing the roles of genes and gene products in mediating their biological functions. We chose predicates describing gene expression, molecular interactions and signal transduction events with the aim of covering a number of research areas in MB. Analysis was performed on sentences containing a set of verbal predicates from MEDLINE and full text journals. Results confirm the necessity to analyze

Energetic atomic and molecular ions of ionospheric origin observed in distant magnetotail flow-reversal events

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Christon, S. P.; Gloeckler, G.; Williams, D. J.; Mukai, T.; Mcentire, R. W.; Jacquey, C.; Angelopoulos, V.; Lui, A. T. Y.; Kokubun, S.; Fairfield, D. H.

1994-01-01

Energetic atomic (O(+1) and N(+1)) and molecular (O2(+1), NO(+1), and N2(+1)) ions of ionospheric origin were observed in Earth's magnetotail at X approximately -146 R(sub E) during two plasma sheet sunward/tailward flow-reversal events measured by instruments on the GEOTAIL spacecraft. These events were associated with concurrent ground-measured geomagnetic disturbance intensification at auroral-and mid-latitudes (Kp = 7(-)). Energetic ions in the sunward-component and tailward flows were from both the solar wind and ionosphere. Plasma and energetic ions participated in the flows. During tailward flow, ionospheric origin ion abundance ratios at approximately 200-900 km/s in the rest frame were N(+1)/O(+1) = approximately 25-30% and ((O2(+1), NO(+1), and N2(+1))/O(+1) = approximately 1-2%. We argue that tailward flow most likely initiated approximately 80-100 R(sub E) tailward of Earth and molecular ions were in the plasma sheet prior to geomagnetic intensification onset.

Molecular events in matrix protein metabolism in the aging kidney

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Sataranatarajan, Kavithalakshmi; Feliers, Denis; Mariappan, Meenalakshmi M.; Lee, Hak Joo; Lee, Myung Ja; Day, Robert T.; Yalamanchili, Hima Bindu; Choudhury, Goutam G.; Barnes, Jeffrey L.; Van Remmen, Holly; Richardson, Arlan; Kasinath, Balakuntalam S.

2018-01-01

Summary We explored molecular events associated with aging-induced matrix changes in the kidney. C57BL6 mice were studied in youth, middle age, and old age. Albuminuria and serum cystatin C level (an index of glomerular filtration) increased with aging. Renal hypertrophy was evident in middle-aged and old mice and was associated with glomerulomegaly and increase in mesangial fraction occupied by extracellular matrix. Content of collagen types I and III and fibronectin was increased with aging; increment in their mRNA varied with the phase of aging. The content of ZEB1 and ZEB2, collagen type I transcription inhibitors, and their binding to the collagen type Iα2 promoter by ChIP assay also showed age-phase-specific changes. Lack of increase in mRNA and data from polysome assay suggested decreased degradation as a potential mechanism for kidney collagen type I accumulation in the middle-aged mice. These changes occurred with increment in TGFβ mRNA and protein and activation of its SMAD3 pathway; SMAD3 binding to the collagen type Iα2 promoter was also increased. TGFβ-regulated microRNAs (miRs) exhibited selective regulation. The renal cortical content of miR-21 and miR-200c, but not miR-192, miR-200a, or miR-200b, was increased with aging. Increased miR-21 and miR-200c contents were associated with reduced expression of their targets, Sprouty-1 and ZEB2, respectively. These data show that aging is associated with complex molecular events in the kidney that are already evident in the middle age and progress to old age. Agephase-specific regulation of matrix protein synthesis occurs and involves matrix protein-specific transcriptional and post-transcriptional mechanisms. PMID:23020145

Comparing hair-morphology and molecular methods to identify fecal samples from Neotropical felids.

Directory of Open Access Journals (Sweden)

Carlos C Alberts

Full Text Available To avoid certain problems encountered with more-traditional and invasive methods in behavioral-ecology studies of mammalian predators, such as felids, molecular approaches have been employed to identify feces found in the field. However, this method requires a complete molecular biology laboratory, and usually also requires very fresh fecal samples to avoid DNA degradation. Both conditions are normally absent in the field. To address these difficulties, identification based on morphological characters (length, color, banding, scales and medullar patterns of hairs found in feces could be employed as an alternative. In this study we constructed a morphological identification key for guard hairs of eight Neotropical felids (jaguar, oncilla, Geoffroy's cat, margay, ocelot, Pampas cat, puma and jaguarundi and compared its efficiency to that of a molecular identification method, using the ATP6 region as a marker. For this molecular approach, we simulated some field conditions by postponing sample-conservation procedures. A blind test of the identification key obtained a nearly 70% overall success rate, which we considered equivalent to or better than the results of some molecular methods (probably due to DNA degradation found in other studies. The jaguar, puma and jaguarundi could be unequivocally discriminated from any other Neotropical felid. On a scale ranging from inadequate to excellent, the key proved poor only for the margay, with only 30% of its hairs successfully identified using this key; and have intermediate success rates for the remaining species, the oncilla, Geoffroy's cat, ocelot and Pampas cat, were intermediate. Complementary information about the known distributions of felid populations may be necessary to substantially improve the results obtained with the key. Our own molecular results were even better, since all blind-tested samples were correctly identified. Part of these identifications were made from samples kept in suboptimal

Positive predictive value of a register-based algorithm using the Danish National Registries to identify suicidal events

DEFF Research Database (Denmark)

Gasse, Christiane; Danielsen, Andreas Aalkjaer; Pedersen, Marianne Giørtz

2018-01-01

events overall, by gender, age groups, and calendar time. RESULTS: We retrieved medical records for 357 (75%) people. The PPV of the DK-algorithm to identify suicidal events was 51.5% (95% CI: 46.4-56.7) overall, 42.7% (95% CI: 35.2-50.5) in males, and 58.5% (95% CI: 51.6-65.1) in females. The PPV varied...... further across age groups and calendar time. After excluding cases identified via the DK-algorithm by unspecific codes of intoxications and injury, the PPV improved slightly (56.8% [95% CI: 50.0-63.4]). CONCLUSIONS: The DK-algorithm can reliably identify self-harm with suicidal intention in 52......PURPOSE: It is not possible to fully assess intention of self-harm and suicidal events using information from administrative databases. We conducted a validation study of intention of suicide attempts/self-harm contacts identified by a commonly applied Danish register-based algorithm (DK...

Reduced Clostridium difficile Tests and Laboratory-Identified Events With a Computerized Clinical Decision Support Tool and Financial Incentive.

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Madden, Gregory R; German Mesner, Ian; Cox, Heather L; Mathers, Amy J; Lyman, Jason A; Sifri, Costi D; Enfield, Kyle B

2018-06-01

We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.Infect Control Hosp Epidemiol 2018;39:737-740.

A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

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Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

2015-02-01

The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Genomic analyses identify molecular subtypes of pancreatic cancer.

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Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

2016-03-03

Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

Science.gov (United States)

2016-07-01

tsc1 and tsc2 loss of function mutations in Schizosaccharomyces pombe. Northeast Regional Yeast Meeting, June 16-17, University at Buffalo, The State...AWARD NUMBER: W81XWH-14-1-0169 TITLE: Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of...SUBTITLE Using Genetic Buffering Relationships Identified in Fission 5a. CONTRACT NUMBER W81XWH-14-1-0169 Yeast to Elucidate the Molecular Pathology

Identifying Changes in the Probability of High Temperature, High Humidity Heat Wave Events

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Ballard, T.; Diffenbaugh, N. S.

2016-12-01

Understanding how heat waves will respond to climate change is critical for adequate planning and adaptation. While temperature is the primary determinant of heat wave severity, humidity has been shown to play a key role in heat wave intensity with direct links to human health and safety. Here we investigate the individual contributions of temperature and specific humidity to extreme heat wave conditions in recent decades. Using global NCEP-DOE Reanalysis II daily data, we identify regional variability in the joint probability distribution of humidity and temperature. We also identify a statistically significant positive trend in humidity over the eastern U.S. during heat wave events, leading to an increased probability of high humidity, high temperature events. The extent to which we can expect this trend to continue under climate change is complicated due to variability between CMIP5 models, in particular among projections of humidity. However, our results support the notion that heat wave dynamics are characterized by more than high temperatures alone, and understanding and quantifying the various components of the heat wave system is crucial for forecasting future impacts.

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome.

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Burkhart, Keith K; Abernethy, Darrell; Jackson, David

2015-06-01

Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was also analyzed for an internal comparison of the drugs most highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and sodium channel 2 alpha were identified as disproportionately associated with SJS. Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as metabolizing enzymes of the drugs associated with SJS adverse event reports. Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and PEPT2 were also identified and are highly associated with the transport of these drugs. A detailed review of the molecular targets identifies important roles for these targets in immune response. The association with CYP metabolizing enzymes suggests that reactive metabolites and oxidative stress may have a contributory role. Drug transporters may enhance intracellular tissue concentrations and also have vital physiologic roles that impact keratinocyte proliferation and survival. Data mining FAERS may be used to hypothesize mechanisms for adverse drug events by identifying molecular targets that are highly associated with drug-induced adverse events. The information gained may contribute to systems biology disease models.

Genetic plasticity of the Shigella virulence plasmid is mediated by intra- and inter-molecular events between insertion sequences.

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Pilla, Giulia; McVicker, Gareth; Tang, Christoph M

2017-09-01

Acquisition of a single copy, large virulence plasmid, pINV, led to the emergence of Shigella spp. from Escherichia coli. The plasmid encodes a Type III secretion system (T3SS) on a 30 kb pathogenicity island (PAI), and is maintained in a bacterial population through a series of toxin:antitoxin (TA) systems which mediate post-segregational killing (PSK). The T3SS imposes a significant cost on the bacterium, and strains which have lost the plasmid and/or genes encoding the T3SS grow faster than wild-type strains in the laboratory, and fail to bind the indicator dye Congo Red (CR). Our aim was to define the molecular events in Shigella flexneri that cause loss of Type III secretion (T3S), and to examine whether TA systems exert positional effects on pINV. During growth at 37°C, we found that deletions of regions of the plasmid including the PAI lead to the emergence of CR-negative colonies; deletions occur through intra-molecular recombination events between insertion sequences (ISs) flanking the PAI. Furthermore, by repositioning MvpAT (which belongs to the VapBC family of TA systems) near the PAI, we demonstrate that the location of this TA system alters the rearrangements that lead to loss of T3S, indicating that MvpAT acts both globally (by reducing loss of pINV through PSK) as well as locally (by preventing loss of adjacent sequences). During growth at environmental temperatures, we show for the first time that pINV spontaneously integrates into different sites in the chromosome, and this is mediated by inter-molecular events involving IS1294. Integration leads to reduced PAI gene expression and impaired secretion through the T3SS, while excision of pINV from the chromosome restores T3SS function. Therefore, pINV integration provides a reversible mechanism for Shigella to circumvent the metabolic burden imposed by pINV. Intra- and inter-molecular events between ISs, which are abundant in Shigella spp., mediate plasticity of S. flexneri pINV.

Cortical GABA markers identify a molecular subtype of psychotic and bipolar disorders.

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Volk, D W; Sampson, A R; Zhang, Y; Edelson, J R; Lewis, D A

2016-09-01

Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a 'low GABA marker' (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders. Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects. Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype. These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

Systematic procedures for identifying t quarks in p-barp collider events with a muon and jets

International Nuclear Information System (INIS)

Barger, V.; Baer, H.; Martin, A.D.; Phillips, R.J.N.

1984-01-01

Substantial rates are predicted for events containing a muon and jets resulting from W→tb-bar, Z→tt-bar, and tt-bar hadroproduction, with t→μνb decay. We investigate selective cuts to reject backgrounds from bb-bar, cc-bar, and cs-bar production and to identify the t-quark events. For example, from a data sample containing 50 W +- →e +- ν events, we expect that clean samples of approximately 4 tb-bar-(or t-barb-) and conservatively 4 tt-bar-initiated μ +- +jets events can be selected for a t-quark mass below 45 GeV. We suggest methods for distinguishing the contributions and for determining m/sub t/

Cellular and molecular events leading to the development of skin cancer

International Nuclear Information System (INIS)

Melnikova, Vladislava O.; Ananthaswamy, Honnavara N.

2005-01-01

The transition from a normal cell to a neoplastic cell is a complex process and involves both genetic and epigenetic changes. The process of carcinogenesis begins when the DNA is damaged, which then leads to a cascade of events leading to the development of a tumor. Ultraviolet (UV) radiation causes DNA damage, inflammation, erythema, sunburn, immunosuppression, photoaging, gene mutations, and skin cancer. Upon DNA damage, the p53 tumor suppressor protein undergoes phosphorylation and translocation to the nucleus and aids in DNA repair or causes apoptosis. Excessive UV exposure overwhelms DNA repair mechanisms leading to induction of p53 mutations and loss of Fas-FasL interaction. Keratinocytes carrying p53 mutations acquire a growth advantage by virtue of their increased resistance to apoptosis. Thus, resistance to cell death is a key event in photocarcinogenesis and conversely, elimination of cells containing excessive UV-induced DNA damage is a key step in protecting against skin cancer development. Apoptosis-resistant keratinocytes undergo clonal expansion that eventually leads to formation of actinic keratoses and squamous cell carcinomas. In this article, we will review some of the cellular and molecular mechanisms involved in initiation and progression of UV-induced skin cancer

Cellular and molecular events leading to the development of skin cancer

Energy Technology Data Exchange (ETDEWEB)

Melnikova, Vladislava O. [Department of Immunology, University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Unit 902, Houston, TX 77030 (United States); Ananthaswamy, Honnavara N. [Department of Immunology, University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Unit 902, Houston, TX 77030 (United States)]. E-mail: hanantha@mdanderson.org

2005-04-01

The transition from a normal cell to a neoplastic cell is a complex process and involves both genetic and epigenetic changes. The process of carcinogenesis begins when the DNA is damaged, which then leads to a cascade of events leading to the development of a tumor. Ultraviolet (UV) radiation causes DNA damage, inflammation, erythema, sunburn, immunosuppression, photoaging, gene mutations, and skin cancer. Upon DNA damage, the p53 tumor suppressor protein undergoes phosphorylation and translocation to the nucleus and aids in DNA repair or causes apoptosis. Excessive UV exposure overwhelms DNA repair mechanisms leading to induction of p53 mutations and loss of Fas-FasL interaction. Keratinocytes carrying p53 mutations acquire a growth advantage by virtue of their increased resistance to apoptosis. Thus, resistance to cell death is a key event in photocarcinogenesis and conversely, elimination of cells containing excessive UV-induced DNA damage is a key step in protecting against skin cancer development. Apoptosis-resistant keratinocytes undergo clonal expansion that eventually leads to formation of actinic keratoses and squamous cell carcinomas. In this article, we will review some of the cellular and molecular mechanisms involved in initiation and progression of UV-induced skin cancer.

Insights into the Molecular Events That Regulate Heat-Induced Chilling Tolerance in Citrus Fruits.

Science.gov (United States)

Lafuente, María T; Establés-Ortíz, Beatriz; González-Candelas, Luis

2017-01-01

Low non-freezing temperature may cause chilling injury (CI), which is responsible for external quality deterioration in many chilling-sensitive horticultural crops. Exposure of chilling-sensitive citrus cultivars to non-lethal high-temperature conditioning may increase their chilling tolerance. Very little information is available about the molecular events involved in such tolerance. In this work, the molecular events associated with the low temperature tolerance induced by heating Fortune mandarin, which is very sensitive to chilling, for 3 days at 37°C prior to cold storage is presented. A transcriptomic analysis reveals that heat-conditioning has an important impact favoring the repression of genes in cold-stored fruit, and that long-term heat-induced chilling tolerance is an active process that requires activation of transcription factors involved in transcription initiation and of the WRKY family. The analysis also shows that chilling favors degradation processes, which affect lipids and proteins, and that the protective effect of the heat-conditioning treatment is more likely to be related to the repression of the genes involved in lipid degradation than to the modification of fatty acids unsaturation, which affects membrane permeability. Another major factor associated with the beneficial effect of the heat treatment on reducing CI is the regulation of stress-related proteins. Many of the genes that encoded such proteins are involved in secondary metabolism and in oxidative stress-related processes.

Insights into the Molecular Events That Regulate Heat-Induced Chilling Tolerance in Citrus Fruits

Directory of Open Access Journals (Sweden)

María T. Lafuente

2017-06-01

Full Text Available Low non-freezing temperature may cause chilling injury (CI, which is responsible for external quality deterioration in many chilling-sensitive horticultural crops. Exposure of chilling-sensitive citrus cultivars to non-lethal high-temperature conditioning may increase their chilling tolerance. Very little information is available about the molecular events involved in such tolerance. In this work, the molecular events associated with the low temperature tolerance induced by heating Fortune mandarin, which is very sensitive to chilling, for 3 days at 37°C prior to cold storage is presented. A transcriptomic analysis reveals that heat-conditioning has an important impact favoring the repression of genes in cold-stored fruit, and that long-term heat-induced chilling tolerance is an active process that requires activation of transcription factors involved in transcription initiation and of the WRKY family. The analysis also shows that chilling favors degradation processes, which affect lipids and proteins, and that the protective effect of the heat-conditioning treatment is more likely to be related to the repression of the genes involved in lipid degradation than to the modification of fatty acids unsaturation, which affects membrane permeability. Another major factor associated with the beneficial effect of the heat treatment on reducing CI is the regulation of stress-related proteins. Many of the genes that encoded such proteins are involved in secondary metabolism and in oxidative stress-related processes.

Domain-restricted mutation analysis to identify novel driver events in human cancer

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Sanket Desai

2017-10-01

Full Text Available Analysis of mutational spectra across various cancer types has given valuable insights into tumorigenesis. Different approaches have been used to identify novel drivers from the set of somatic mutations, including the methods which use sequence conservation, geometric localization and pathway information. Recent computational methods suggest use of protein domain information for analysis and understanding of the functional consequence of non-synonymous mutations. Similarly, evidence suggests recurrence at specific position in proteins is robust indicators of its functional impact. Building on this, we performed a systematic analysis of TCGA exome derived somatic mutations across 6089 PFAM domains and significantly mutated domains were identified using randomization approach. Multiple alignment of individual domain allowed us to prioritize for conserved residues mutated at analogous positions across different proteins in a statistically disciplined manner. In addition to the known frequently mutated genes, this analysis independently identifies low frequency Meprin and TRAF-Homology (MATH domain in Speckle Type BTB/POZ (SPOP protein, in prostate adenocarcinoma. Results from this analysis will help generate hypotheses about the downstream molecular mechanism resulting in cancer phenotypes.

Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

Science.gov (United States)

Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

2016-01-01

Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat

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Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...

Alternative splicing events identified in human embryonic stem cells and neural progenitors.

Directory of Open Access Journals (Sweden)

Gene W Yeo

2007-10-01

Full Text Available Human embryonic stem cells (hESCs and neural progenitor (NP cells are excellent models for recapitulating early neuronal development in vitro, and are key to establishing strategies for the treatment of degenerative disorders. While much effort had been undertaken to analyze transcriptional and epigenetic differences during the transition of hESC to NP, very little work has been performed to understand post-transcriptional changes during neuronal differentiation. Alternative RNA splicing (AS, a major form of post-transcriptional gene regulation, is important in mammalian development and neuronal function. Human ESC, hESC-derived NP, and human central nervous system stem cells were compared using Affymetrix exon arrays. We introduced an outlier detection approach, REAP (Regression-based Exon Array Protocol, to identify 1,737 internal exons that are predicted to undergo AS in NP compared to hESC. Experimental validation of REAP-predicted AS events indicated a threshold-dependent sensitivity ranging from 56% to 69%, at a specificity of 77% to 96%. REAP predictions significantly overlapped sets of alternative events identified using expressed sequence tags and evolutionarily conserved AS events. Our results also reveal that focusing on differentially expressed genes between hESC and NP will overlook 14% of potential AS genes. In addition, we found that REAP predictions are enriched in genes encoding serine/threonine kinase and helicase activities. An example is a REAP-predicted alternative exon in the SLK (serine/threonine kinase 2 gene that is differentially included in hESC, but skipped in NP as well as in other differentiated tissues. Lastly, comparative sequence analysis revealed conserved intronic cis-regulatory elements such as the FOX1/2 binding site GCAUG as being proximal to candidate AS exons, suggesting that FOX1/2 may participate in the regulation of AS in NP and hESC. In summary, a new methodology for exon array analysis was introduced

Identifying the molecular functions of electron transport proteins using radial basis function networks and biochemical properties.

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Le, Nguyen-Quoc-Khanh; Nguyen, Trinh-Trung-Duong; Ou, Yu-Yen

2017-05-01

The electron transport proteins have an important role in storing and transferring electrons in cellular respiration, which is the most proficient process through which cells gather energy from consumed food. According to the molecular functions, the electron transport chain components could be formed with five complexes with several different electron carriers and functions. Therefore, identifying the molecular functions in the electron transport chain is vital for helping biologists understand the electron transport chain process and energy production in cells. This work includes two phases for discriminating electron transport proteins from transport proteins and classifying categories of five complexes in electron transport proteins. In the first phase, the performances from PSSM with AAIndex feature set were successful in identifying electron transport proteins in transport proteins with achieved sensitivity of 73.2%, specificity of 94.1%, and accuracy of 91.3%, with MCC of 0.64 for independent data set. With the second phase, our method can approach a precise model for identifying of five complexes with different molecular functions in electron transport proteins. The PSSM with AAIndex properties in five complexes achieved MCC of 0.51, 0.47, 0.42, 0.74, and 1.00 for independent data set, respectively. We suggest that our study could be a power model for determining new proteins that belongs into which molecular function of electron transport proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study

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Minsu Ock

2018-01-01

Full Text Available Objectives The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10 Y codes. Methods We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC. We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others. Results Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%, followed by those related to surgery and procedures (1209, 5.8% and those related to vaccines and immunoglobulin (72, 0.3%. Conclusions Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

Genome wide identification of aberrant alternative splicing events in myotonic dystrophy type 2.

Science.gov (United States)

Perfetti, Alessandra; Greco, Simona; Fasanaro, Pasquale; Bugiardini, Enrico; Cardani, Rosanna; Garcia-Manteiga, Jose M; Manteiga, Jose M Garcia; Riba, Michela; Cittaro, Davide; Stupka, Elia; Meola, Giovanni; Martelli, Fabio

2014-01-01

Myotonic dystrophy type 2 (DM2) is a genetic, autosomal dominant disease due to expansion of tetraplet (CCTG) repetitions in the first intron of the ZNF9/CNBP gene. DM2 is a multisystemic disorder affecting the skeletal muscle, the heart, the eye and the endocrine system. According to the proposed pathological mechanism, the expanded tetraplets have an RNA toxic effect, disrupting the splicing of many mRNAs. Thus, the identification of aberrantly spliced transcripts is instrumental for our understanding of the molecular mechanisms underpinning the disease. The aim of this study was the identification of new aberrant alternative splicing events in DM2 patients. By genome wide analysis of 10 DM2 patients and 10 controls (CTR), we identified 273 alternative spliced exons in 218 genes. While many aberrant splicing events were already identified in the past, most were new. A subset of these events was validated by qPCR assays in 19 DM2 and 15 CTR subjects. To gain insight into the molecular pathways involving the identified aberrantly spliced genes, we performed a bioinformatics analysis with Ingenuity system. This analysis indicated a deregulation of development, cell survival, metabolism, calcium signaling and contractility. In conclusion, our genome wide analysis provided a database of aberrant splicing events in the skeletal muscle of DM2 patients. The affected genes are involved in numerous pathways and networks important for muscle physio-pathology, suggesting that the identified variants may contribute to DM2 pathogenesis.

An Event-Driven Hybrid Molecular Dynamics and Direct Simulation Monte Carlo Algorithm

Energy Technology Data Exchange (ETDEWEB)

Donev, A; Garcia, A L; Alder, B J

2007-07-30

A novel algorithm is developed for the simulation of polymer chains suspended in a solvent. The polymers are represented as chains of hard spheres tethered by square wells and interact with the solvent particles with hard core potentials. The algorithm uses event-driven molecular dynamics (MD) for the simulation of the polymer chain and the interactions between the chain beads and the surrounding solvent particles. The interactions between the solvent particles themselves are not treated deterministically as in event-driven algorithms, rather, the momentum and energy exchange in the solvent is determined stochastically using the Direct Simulation Monte Carlo (DSMC) method. The coupling between the solvent and the solute is consistently represented at the particle level, however, unlike full MD simulations of both the solvent and the solute, the spatial structure of the solvent is ignored. The algorithm is described in detail and applied to the study of the dynamics of a polymer chain tethered to a hard wall subjected to uniform shear. The algorithm closely reproduces full MD simulations with two orders of magnitude greater efficiency. Results do not confirm the existence of periodic (cycling) motion of the polymer chain.

Performing drought indices to identify the relationship between agricultural losses and drought events in Spain.

Science.gov (United States)

Peña Gallardo, Marina; Serrano, Sergio Martín Vicente; Portugués Santiago, Beguería; Burguera Miquel, Tomás

2017-04-01

Drought leads to crop failures reducing the productivity. For this reason, the need of appropriate tool for recognize dry periods and evaluate the impact of drought on crop production is important. In this study, we provide an assessment of the relationship between drought episodes and crop failures in Spain as one of the direct consequences of drought is the diminishing of crop yields. First, different drought indices [the Standardized Precipitation and Evapotranspiration Index (SPEI); the Standardized Precipitation Index (SPI); the self-calibrated Palmer Moisture Anomaly Index (Z-Index), the self-calibrated Crop Moisture Index (CMI) and the Standardized Palmer Drought Index (SPDI)] have been calculated at different time scales in order to identify the dry events occurred in Spain and determine the duration and intensity of each event. Second, the drought episodes have been correlated with crop production estimated and final crop production data provided by the Spanish Crop Insurance System for the available period from 1995 to 2014 at the municipal spatial scale, with the purpose of knowing if the characteristics of the drought episodes are reflected on the agricultural losses. The analysis has been carried out in particular for two types of crop, wheat and barley. The results indicate the existence of an agreement between the most important drought events in Spain and the response of the crop productions and the proportion of hectare insurance. Nevertheless, this agreement vary depending on the drought index applied. Authors found a higher competence of the drought indices calculated at different time scales (SPEI, SPI and SPDI) identifying the begging and end of the drought events and the correspondence with the crop failures.

Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

International Nuclear Information System (INIS)

Brinkmann, Markus; Eichbaum, Kathrin; Kammann, Ulrike; Hudjetz, Sebastian; Cofalla, Catrina; Buchinger, Sebastian; Reifferscheid, Georg; Schüttrumpf, Holger; Preuss, Thomas

2014-01-01

Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios

Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

Energy Technology Data Exchange (ETDEWEB)

Brinkmann, Markus; Eichbaum, Kathrin [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Kammann, Ulrike [Thünen-Institute of Fisheries Ecology, Palmaille 9, 22767 Hamburg (Germany); Hudjetz, Sebastian [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Cofalla, Catrina [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Buchinger, Sebastian; Reifferscheid, Georg [Federal Institute of Hydrology (BFG), Department G3: Biochemistry, Ecotoxicology, Am Mainzer Tor 1, 56068 Koblenz (Germany); Schüttrumpf, Holger [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Preuss, Thomas [Department of Environmental Biology and Chemodynamics, Institute for Environmental Research,ABBt- Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); and others

2014-07-01

Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios.

NEWLY IDENTIFIED EXTENDED GREEN OBJECTS (EGOs) FROM THE SPITZER GLIMPSE II SURVEY. II. MOLECULAR CLOUD ENVIRONMENTS

Energy Technology Data Exchange (ETDEWEB)

Chen Xi; Gan Conggui; Shen Zhiqiang [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Chinese Academy of Sciences, Shanghai 200030 (China); Ellingsen, Simon P.; Titmarsh, Anita [School of Mathematics and Physics, University of Tasmania, Hobart, Tasmania (Australia); He Jinhua, E-mail: chenxi@shao.ac.cn [Key Laboratory for the Structure and Evolution of Celestial Objects, Yunnan Astronomical Observatory/National Astronomical Observatory, Chinese Academy of Sciences, P.O. Box 110, Kunming 650011, Yunnan Province (China)

2013-06-01

We have undertaken a survey of molecular lines in the 3 mm band toward 57 young stellar objects using the Australia Telescope National Facility Mopra 22 m radio telescope. The target sources were young stellar objects with active outflows (extended green objects (EGOs)) newly identified from the GLIMPSE II survey. We observe a high detection rate (50%) of broad line wing emission in the HNC and CS thermal lines, which combined with the high detection rate of class I methanol masers toward these sources (reported in Paper I) further demonstrates that the GLIMPSE II EGOs are associated with outflows. The physical and kinematic characteristics derived from the 3 mm molecular lines for these newly identified EGOs are consistent with these sources being massive young stellar objects with ongoing outflow activity and rapid accretion. These findings support our previous investigations of the mid-infrared properties of these sources and their association with other star formation tracers (e.g., infrared dark clouds, methanol masers and millimeter dust sources) presented in Paper I. The high detection rate (64%) of the hot core tracer CH{sub 3}CN reveals that the majority of these new EGOs have evolved to the hot molecular core stage. Comparison of the observed molecular column densities with predictions from hot core chemistry models reveals that the newly identified EGOs from the GLIMPSE II survey are members of the youngest hot core population, with an evolutionary time scale of the order of 10{sup 3} yr.

Diagnostic and molecular evaluation of three iridovirus-associated salamander mortality events

Science.gov (United States)

Docherty, D.E.; Meteyer, C.U.; Wang, Jingyuan; Mao, J.; Case, S.T.; Chinchar, V.G.

2003-01-01

In 1998 viruses were isolated from tiger salamander larvae (Ambystoma tigrinum diaboli and A. tigrinum melanostictum) involved in North Dakota and Utah (USA) mortality events and spotted salamander (A. maculatum) larvae in a third event in Maine (USA). Although sympatric caudates and anurans were present at all three sites only ambystomid larvae appeared to be affected. Mortality at the North Dakota site was in the thousands while at the Utah and Maine sites mortality was in the hundreds. Sick larvae were lethargic and slow moving. They swam in circles with obvious buoyancy problems and were unable to remain upright. On the ventral surface, near the gills and hind limbs, red spots or swollen areas were noted. Necropsy findings included: hemorrhages and ulceration of the skin, subcutaneous and intramuscular edema, swollen and pale livers with multifocal hemorrhage, and distended fluid-filled intestines with areas of hemorrhage. Light microscopy revealed intracytoplasmic inclusions, suggestive of a viral infection, in a variety of organs. Electron microscopy of ultra thin sections of the same tissues revealed iridovirus-like particles within the inclusions. These viruses were isolated from a variety of organs, indicating a systemic infection. Representative viral isolates from the three mortality events were characterized using molecular assays. Characterization confirmed that the viral isolates were iridoviruses and that the two tiger salamander isolates were similar and could be distinguished from the spotted salamander isolate. The spotted salamander isolate was similar to frog virus 3, the type species of the genus Ranavirus, while the tiger salamander isolates were not. These data indicate that different species of salamanders can become infected and die in association with different iridoviruses. Challenge assays are required to determine the fish and amphibian host range of these isolates and to assess the susceptibility of tiger and spotted salamanders to

Tuning and Test of Fragmentation Models Based on Identified Particles and Precision Event Shape Data

CERN Document Server

Abreu, P; Adye, T; Ajinenko, I; Alekseev, G D; Alemany, R; Allport, P P; Almehed, S; Amaldi, Ugo; Amato, S; Andreazza, A; Andrieux, M L; Antilogus, P; Apel, W D; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barate, R; Barbi, M S; Bardin, Dimitri Yuri; Baroncelli, A; Bärring, O; Barrio, J A; Bartl, Walter; Bates, M J; Battaglia, Marco; Baubillier, M; Baudot, J; Becks, K H; Begalli, M; Beillière, P; Belokopytov, Yu A; Belous, K S; Benvenuti, Alberto C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; Bianchi, F; Bigi, M; Bilenky, S M; Billoir, P; Bloch, D; Blume, M; Bolognese, T; Bonesini, M; Bonivento, W; Booth, P S L; Bosio, C; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Bozzo, M; Branchini, P; Brand, K D; Brenke, T; Brenner, R A; Bricman, C; Brown, R C A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschmann, P; Buys, A; Cabrera, S; Caccia, M; Calvi, M; Camacho-Rozas, A J; Camporesi, T; Canale, V; Canepa, M; Cankocak, K; Cao, F; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Chabaud, V; Charpentier, P; Chaussard, L; Checchia, P; Chelkov, G A; Chen, M; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Chudoba, J; Cindro, V; Collins, P; Contreras, J L; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Cowell, J H; Crawley, H B; Crennell, D J; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Dahl-Jensen, Erik; Dahm, J; D'Almagne, B; Dam, M; Damgaard, G; Dauncey, P D; Davenport, Martyn; Da Silva, W; Defoix, C; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Brabandere, S; De Clercq, C; La Vaissière, C de; De Lotto, B; De Min, A; De Paula, L S; De Saint-Jean, C; Dijkstra, H; Di Ciaccio, Lucia; Di Diodato, A; Djama, F; Dolbeau, J; Dönszelmann, M; Doroba, K; Dracos, M; Drees, J; Drees, K A; Dris, M; Durand, J D; Edsall, D M; Ehret, R; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Elsing, M; Engel, J P; Erzen, B; Espirito-Santo, M C; Falk, E; Fassouliotis, D; Feindt, Michael; Ferrer, A; Fichet, S; Filippas-Tassos, A; Firestone, A; Fischer, P A; Föth, H; Fokitis, E; Fontanelli, F; Formenti, F; Franek, B J; Frenkiel, P; Fries, D E C; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gandelman, M; García, C; García, J; Gaspar, C; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Gerber, J P; Gokieli, R; Golob, B; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Graziani, E; Green, C; Grefrath, A; Gris, P; Grosdidier, G; Grzelak, K; Gumenyuk, S A; Gunnarsson, P; Günther, M; Guy, J; Hahn, F; Hahn, S; Hajduk, Z; Hallgren, A; Hamacher, K; Harris, F J; Hedberg, V; Henriques, R P; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Higón, E; Hilke, Hans Jürgen; Hill, T S; Holmgren, S O; Holt, P J; Holthuizen, D J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, L B; Jönsson, P E; Joram, Christian; Juillot, P; Kaiser, M; Kapusta, F; Karafasoulis, K; Karlsson, M; Karvelas, E; Katsanevas, S; Katsoufis, E C; Keränen, R; Khokhlov, Yu A; Khomenko, B A; Khovanskii, N N; King, B J; Kjaer, N J; Klapp, O; Klein, H; Klovning, A; Kluit, P M; Köne, B; Kokkinias, P; Koratzinos, M; Korcyl, K; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Kreuter, C; Kronkvist, I J; Krumshtein, Z; Krupinski, W; Kubinec, P; Kucewicz, W; Kurvinen, K L; Lacasta, C; Laktineh, I; Lamsa, J; Lanceri, L; Lane, D W; Langefeld, P; Lapin, V; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Legan, C K; Leitner, R; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Libby, J; Liko, D; Lindner, R; Lipniacka, A; Lippi, I; Lörstad, B; Loken, J G; López, J M; Loukas, D; Lutz, P; Lyons, L; Naughton, J M; Maehlum, G; Mahon, J R; Maio, A; Malmgren, T G M; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Masik, J; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; Medbo, J; Merk, M; Meroni, C; Meyer, S; Meyer, W T; Myagkov, A; Michelotto, M; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Møller, R; Mönig, K; Monge, M R; Morettini, P; Müller, H; Mulders, M; Mundim, L M; Murray, W J; Muryn, B; Myatt, Gerald; Naraghi, F; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Neumann, W; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nieuwenhuizen, M; Nikolaenko, V; Niss, P; Nomerotski, A; Normand, Ainsley; Oberschulte-Beckmann, W; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Österberg, K; Ouraou, A; Paganini, P; Paganoni, M; Pagès, P; Pain, R; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Passeri, A; Pegoraro, M; Peralta, L; Pernegger, H; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Petrovykh, M; Phillips, H T; Piana, G; Pierre, F; Plaszczynski, S; Podobrin, O; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Rames, J; Ratoff, P N; Read, A L; Reale, M; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Renton, P B; Resvanis, L K; Richard, F; Richardson, J; Rídky, J; Rinaudo, G; Ripp, I; Romero, A; Roncagliolo, I; Ronchese, P; Roos, L; Rosenberg, E I; Rosso, E; Roudeau, Patrick; Rovelli, T; Rückstuhl, W; Ruhlmann-Kleider, V; Ruiz, A; Rybicki, K; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sahr, O; Sajot, G; Salt, J; Sánchez, J; Sannino, M; Schimmelpfennig, M; Schneider, H; Schwickerath, U; Schyns, M A E; Sciolla, G; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Seitz, A; Sekulin, R L; Serbelloni, L; Shellard, R C; Siegrist, P; Silvestre, R; Simonetti, S; Simonetto, F; Sissakian, A N; Sitár, B; Skaali, T B; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Sokolov, A; Sosnowski, R; Souza-Santos, D; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stapnes, Steinar; Stavitski, I; Stevenson, K; Stichelbaut, F; Stocchi, A; Strauss, J; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tavernet, J P; Chikilev, O G; Thomas, J; Tilquin, A; Timmermans, J; Tkatchev, L G; Todorov, T; Todorova, S; Toet, D Z; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Trischuk, W; Tristram, G; Trombini, A; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tyndel, M; Tzamarias, S; Überschär, B; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; van Apeldoorn, G W; van Dam, P; Van Eldik, J; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Vilanova, D; Vincent, P; Vitale, L; Vlasov, E; Vodopyanov, A S; Vrba, V; Wahlen, H; Walck, C; Waldner, F; Weierstall, M; Weilhammer, Peter; Weiser, C; Wetherell, Alan M; Wicke, D; Wickens, J H; Wielers, M; Wilkinson, G R; Williams, W S C; Winter, M; Witek, M; Woschnagg, K; Yip, K; Yushchenko, O P; Zach, F; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zito, M; Zontar, D; Zucchelli, G C; Zumerle, G

1996-01-01

Event shape and charged particle inclusive distributions are measured using 750000 decays of the $Z$ to hadrons from the DELPHI detector at LEP. These precise data allow a decisive confrontation with models of the hadronization process. Improved tunings of the JETSET ARIADNE and HERWIG parton shower models and the JETSET matrix element model are obtained by fitting the models to these DELPHI data as well as to identified particle distributions from all LEP experiments. The description of the data distributions by the models is critically reviewed with special importance attributed to identified particles.

MicroRNA Expression Profiling Identifies Molecular Diagnostic Signatures for Anaplastic Large Cell Lymphoma

DEFF Research Database (Denmark)

Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie

2013-01-01

distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, mi...

Predictive values of diagnostic codes for identifying serious hypocalcemia and dermatologic adverse events among women with postmenopausal osteoporosis in a commercial health plan database.

Science.gov (United States)

Wang, Florence T; Xue, Fei; Ding, Yan; Ng, Eva; Critchlow, Cathy W; Dore, David D

2018-04-10

Post-marketing safety studies of medicines often rely on administrative claims databases to identify adverse outcomes following drug exposure. Valid ascertainment of outcomes is essential for accurate results. We aim to quantify the validity of diagnostic codes for serious hypocalcemia and dermatologic adverse events from insurance claims data among women with postmenopausal osteoporosis (PMO). We identified potential cases of serious hypocalcemia and dermatologic events through ICD-9 diagnosis codes among women with PMO within claims from a large US healthcare insurer (June 2005-May 2010). A physician adjudicated potential hypocalcemic and dermatologic events identified from the primary position on emergency department (ED) or inpatient claims through medical record review. Positive predictive values (PPVs) and 95% confidence intervals (CIs) quantified the fraction of potential cases that were confirmed. Among 165,729 patients with PMO, medical charts were obtained for 40 of 55 (73%) potential hypocalcemia cases; 16 were confirmed (PPV 40%, 95% CI 25-57%). The PPV was higher for ED than inpatient claims (82 vs. 24%). Among 265 potential dermatologic events (primarily urticaria or rash), we obtained 184 (69%) charts and confirmed 128 (PPV 70%, 95% CI 62-76%). The PPV was higher for ED than inpatient claims (77 vs. 39%). Diagnostic codes for hypocalcemia and dermatologic events may be sufficient to identify events giving rise to emergency care, but are less accurate for identifying events within hospitalizations.

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

Science.gov (United States)

Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

2009-01-01

Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

Molecular forensics in avian conservation: a DNA-based approach for identifying mammalian predators of ground-nesting birds and eggs.

Science.gov (United States)

Hopken, Matthew W; Orning, Elizabeth K; Young, Julie K; Piaggio, Antoinette J

2016-01-07

predation can have a high impact on recruitment, predation events are very difficult to observe, and predator species are difficult to identify visually from nest remains, molecular approaches that reduce the need to observe or handle animals offer an additional tool to better understand predator-prey dynamics at nesting sites.

Visions of a Semantic Molecular Future

OpenAIRE

Murray-Rust, Peter; Brooks, Brian; Bolton, Charlotte

2011-01-01

Booklet handout distributed at the VSMF Symposium held at the Unilever Centre on 2011-01-17 The event looks forward. Scholarship (universities, research, teaching, publishing) has been slow to take up the opportunities of this digital century. This is an opportunity to identify and build the future. EPSRC (Pathways to Impact Award). Unilever plc (Unilever Centre for Molecular Science Informatics)

Visions of a Semantic Molecular Future

OpenAIRE

Murray-Rust, Peter

2011-01-01

Additional booklet insert distributed at the VSMF Symposium held at the Unilever Centre on 2011-01-17 The event looks forward. Scholarship (universities, research, teaching, publishing) has been slow to take up the opportunities of this digital century. This is an opportunity to identify and build the future. EPSRC (Pathways to Impact award). Unilever plc (Unilever Centre for Molecular Science Informatics)

Analogies Between Digital Radio and Chemical Orthogonality as a Method for Enhanced Analysis of Molecular Recognition Events

Directory of Open Access Journals (Sweden)

Sang-Hun Lee

2008-02-01

Full Text Available Acoustic wave biosensors are a real-time, label-free biosensor technology, which have been exploited for the detection of proteins and cells. One of the conventional biosensor approaches involves the immobilization of a monolayer of antibodies onto the surface of the acoustic wave device for the detection of a specific analyte. The method described within includes at least two immobilizations of two different antibodies onto the surfaces of two separate acoustic wave devices for the detection of several analogous analytes. The chemical specificity of the molecular recognition event is achieved by virtue of the extremely high (nM to pM binding affinity between the antibody and its antigen. In a standard ELISA (Enzyme-Linked ImmunoSorbent Assay test, there are multiple steps and the end result is a measure of what is bound so tightly that it does not wash away easily. The fact that this “gold standard” is very much not real time, masks the dance that is the molecular recognition event. X-Ray Crystallographer, Ian Wilson, demonstrated more than a decade ago that antibodies undergo conformational change during a binding event[1, 2]. Further, it is known in the arena of immunochemistry that some antibodies exhibit significant cross-reactivity and this is widely termed antibody promiscuity. A third piece of the puzzle that we will exploit in our system of acoustic wave biosensors is the notion of chemical orthogonality. These three biochemical constructs, the dance, antibody promiscuity and chemical orthogonality will be combined in this paper with the notions of Int. J. Mol. Sci. 2008, 9 155 in-phase (I and quadrature (Q signals from digital radio to manifest an approach to molecular recognition that allows a level of discrimination and analysis unobtainable without the aggregate. As an example we present experimental data on the detection of TNT, RDX, C4, ammonium nitrate and musk oil from a system of antibody-coated acoustic

Signal detection to identify serious adverse events (neuropsychiatric events in travelers taking mefloquine for chemoprophylaxis of malaria

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Naing C

2012-08-01

Full Text Available Cho Naing,1,3 Kyan Aung,1 Syed Imran Ahmed,2 Joon Wah Mak31School of Medical Sciences, 2School of Pharmacy and Health Sciences, 3School of Postgraduate Studies and Research, International Medical University, Kuala Lumpur, MalaysiaBackground: For all medications, there is a trade-off between benefits and potential for harm. It is important for patient safety to detect drug-event combinations and analyze by appropriate statistical methods. Mefloquine is used as chemoprophylaxis for travelers going to regions with known chloroquine-resistant Plasmodium falciparum malaria. As such, there is a concern about serious adverse events associated with mefloquine chemoprophylaxis. The objective of the present study was to assess whether any signal would be detected for the serious adverse events of mefloquine, based on data in clinicoepidemiological studies.Materials and methods: We extracted data on adverse events related to mefloquine chemoprophylaxis from the two published datasets. Disproportionality reporting of adverse events such as neuropsychiatric events and other adverse events was presented in the 2 × 2 contingency table. Reporting odds ratio and corresponding 95% confidence interval [CI] data-mining algorithm was applied for the signal detection. The safety signals are considered significant when the ROR estimates and the lower limits of the corresponding 95% CI are ≥2.Results: Two datasets addressing adverse events of mefloquine chemoprophylaxis (one from a published article and one from a Cochrane systematic review were included for analyses. Reporting odds ratio 1.58, 95% CI: 1.49–1.68 based on published data in the selected article, and 1.195, 95% CI: 0.94–1.44 based on data in the selected Cochrane review. Overall, in both datasets, the reporting odds ratio values of lower 95% CI were less than 2.Conclusion: Based on available data, findings suggested that signals for serious adverse events pertinent to neuropsychiatric event were

A new index for identifying socioeconomic drought events under climate change over the East River basin in China

Science.gov (United States)

Shi, H.; Chen, J.; Wang, K.; Niu, J.

2017-12-01

Drought, which means severe water deficiencies, is a complex natural hazard that may have destructive damages on societal properties and lives. Generally, socioeconomic drought occurs when the water resources systems cannot meet the water demands due to a weather-related shortfall in water supply to societies. This paper aims to propose a new index (i.e., socioeconomic drought index (SEDI)) for identifying socioeconomic drought events on different levels (i.e., slight, moderate, severe and extreme) under climate change through considering the gap between water supply and demand. First, the minimum in-stream water requirement (MWR) is determined through comprehensively considering the requirements of water quality, ecology, navigation and water supply. Second, according to the monthly water deficit calculated as the monthly streamflow data minus the MWR, drought month can be identified. Third, according to the cumulative water deficit derived from the monthly water deficit, drought duration (i.e., the number of continuous drought months) can be detected. Fourth, the SEDI of each socioeconomic drought event can be calculated through integrating the impacts of the cumulative water deficit and drought duration. The study area is the East River basin in South China, and the impact of a multi-year reservoir (i.e., the Xinfengjiang Reservoir) on drought is also analyzed. For historical and future drought analysis, it is concluded that the proposed SEDI is feasible to identify socioeconomic drought events. The results show that a number of socioeconomic drought events (including some extreme ones) may occur during 2020-2099, and the appropriate reservoir operation can significantly ease such situation.

A novel computational method identifies intra- and inter-species recombination events in Staphylococcus aureus and Streptococcus pneumoniae.

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Lisa Sanguinetti

Full Text Available Advances in high-throughput DNA sequencing technologies have determined an explosion in the number of sequenced bacterial genomes. Comparative sequence analysis frequently reveals evidences of homologous recombination occurring with different mechanisms and rates in different species, but the large-scale use of computational methods to identify recombination events is hampered by their high computational costs. Here, we propose a new method to identify recombination events in large datasets of whole genome sequences. Using a filtering procedure of the gene conservation profiles of a test genome against a panel of strains, this algorithm identifies sets of contiguous genes acquired by homologous recombination. The locations of the recombination breakpoints are determined using a statistical test that is able to account for the differences in the natural rate of evolution between different genes. The algorithm was tested on a dataset of 75 genomes of Staphylococcus aureus and 50 genomes comprising different streptococcal species, and was able to detect intra-species recombination events in S. aureus and in Streptococcus pneumoniae. Furthermore, we found evidences of an inter-species exchange of genetic material between S. pneumoniae and Streptococcus mitis, a closely related commensal species that colonizes the same ecological niche. The method has been implemented in an R package, Reco, which is freely available from supplementary material, and provides a rapid screening tool to investigate recombination on a genome-wide scale from sequence data.

Local elastic expansion model for viscous-flow activation energies of glass-forming molecular liquids

DEFF Research Database (Denmark)

Dyre, Jeppe; Olsen, Niels Boye; Christensen, Tage Emil

1996-01-01

A model for the viscosity of glass-forming molecular liquids is proposed in which a "flow event" requires a local volume increase. The activation energy for a flow event is identified with the work done in shoving aside the surrounding liquid; this work is proportional to the high-frequency shear...

Ab initio molecular dynamics simulations of low energy recoil events in MgO

International Nuclear Information System (INIS)

Petersen, B. A.; Liu, B.; Weber, W. J.; Oak Ridge National Laboratory; Zhang, Y.; Oak Ridge National Laboratory

2017-01-01

In this paper, low-energy recoil events in MgO are studied using ab initio molecular dynamics simulations to reveal the dynamic displacement processes and final defect configurations. Threshold displacement energies, E_d, are obtained for Mg and O along three low-index crystallographic directions, [100], [110], and [111]. The minimum values for E_d are found along the [110] direction consisting of the same element, either Mg or O atoms. Minimum threshold values of 29.5 eV for Mg and 25.5 eV for O, respectively, are suggested from the calculations. For other directions, the threshold energies are considerably higher, 65.5 and 150.0 eV for O along [111] and [100], and 122.5 eV for Mg along both [111] and [100] directions, respectively. These results show that the recoil events in MgO are partial-charge transfer assisted processes where the charge transfer plays an important role. Finally, there is a similar trend found in other oxide materials, where the threshold displacement energy correlates linearly with the peak partial-charge transfer, suggesting this behavior might be universal in ceramic oxides.

Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data

OpenAIRE

REN, ZHONGLU; WANG, WENHUI; LI, JINMING

2015-01-01

Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristi...

Identifying evidence of climate change impact on extreme events in permeable chalk catchments

Science.gov (United States)

Butler, A. P.; Nubert, S.

2009-12-01

The permeable chalk catchments of southern England are vital for the economy and well being of the UK. Not only important as a water resource, their freely draining soils support intensive agricultural production, and the rolling downs and chalk streams provide important habitants for many protected plant and animal species. Consequently, there are concerns about the potential impact of climate change on such catchments, particularly in relation to groundwater recharge. Of major concern are possible changes in extreme events, such as groundwater floods and droughts, as any increase in the frequency and/or severity of these has important consequences for water resources, ecological systems and local infrastructure. Studies of climate change impact on extreme events for such catchments have indicated that, under medium and high emissions scenarios, droughts are likely to become more severe whilst floods less so. However, given the uncertainties in such predictions and the inherent variability in historic data, producing definitive evidence of changes in flood/drought frequency/severity poses a significant challenge. Thus, there is a need for specific extreme event statistics that can be used as indicators of actual climate change in streamflow and groundwater level observations. Identifying such indicators that are sufficiently robust requires catchments with long historic time series data. One such catchment is the River Lavant, an intermittent chalk stream in West Sussex, UK. Located within this catchment is Chilgrove House, the site of the UK’s longest groundwater monitoring well (with a continuous record of water level observations of varying frequency dating back to 1836). Using a variety of meteorological datasets, the behaviour of the catchment has been modelled, from 1855 to present, using a 'leaky aquifer' conceptual model. Model calibration was based on observed daily streamflow, at a gauging station just outside the town of Chichester, from 1970. Long

Je, a versatile suite to handle multiplexed NGS libraries with unique molecular identifiers

OpenAIRE

Girardot, Charles; Scholtalbers, Jelle; Sauer, Sajoscha; Su, Shu-Yi; Furlong, Eileen E.M.

2016-01-01

Background The yield obtained from next generation sequencers has increased almost exponentially in recent years, making sample multiplexing common practice. While barcodes (known sequences of fixed length) primarily encode the sample identity of sequenced DNA fragments, barcodes made of random sequences (Unique Molecular Identifier or UMIs) are often used to distinguish between PCR duplicates and transcript abundance in, for example, single-cell RNA sequencing (scRNA-seq). In paired-end sequ...

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

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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.

Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach

Science.gov (United States)

Scott, Milcah C.; Sarver, Aaron L.; Gavin, Katherine J.; Thayanithy, Venugopal; Getzy, David M.; Newman, Robert A.; Cutter, Gary R.; Lindblad-Toh, Kerstin; Kisseberth, William C.; Hunter, Lawrence E.; Subramanian, Subbaya; Breen, Matthew; Modiano, Jaime F.

2011-01-01

The heterogeneous and chaotic nature of osteosarcoma has confounded accurate molecular classification, prognosis, and prediction for this tumor. The occurrence of spontaneous osteosarcoma is largely confined to humans and dogs. While the clinical features are remarkably similar in both species, the organization of dogs into defined breeds provides a more homogeneous genetic background that may increase the likelihood to uncover molecular subtypes for this complex disease. We thus hypothesized that molecular profiles derived from canine osteosarcoma would aid in molecular subclassification of this disease when applied to humans. To test the hypothesis, we performed genome wide gene expression profiling in a cohort of dogs with osteosarcoma, primarily from high-risk breeds. To further reduce inter-sample heterogeneity, we assessed tumor-intrinsic properties through use of an extensive panel of osteosarcoma-derived cell lines. We observed strong differential gene expression that segregated samples into two groups with differential survival probabilities. Groupings were characterized by the inversely correlated expression of genes associated with G2/M transition and DNA damage checkpoint and microenvironment-interaction categories. This signature was preserved in data from whole tumor samples of three independent dog osteosarcoma cohorts, with stratification into the two expected groups. Significantly, this restricted signature partially overlapped a previously defined, predictive signature for soft tissue sarcomas, and it unmasked orthologous molecular subtypes and their corresponding natural histories in five independent data sets from human patients with osteosarcoma. Our results indicate that the narrower genetic diversity of dogs can be utilized to group complex human osteosarcoma into biologically and clinically relevant molecular subtypes. This in turn may enhance prognosis and prediction, and identify relevant therapeutic targets. PMID:21621658

An overview of techniques for linking high-dimensional molecular data to time-to-event endpoints by risk prediction models.

Science.gov (United States)

Binder, Harald; Porzelius, Christine; Schumacher, Martin

2011-03-01

Analysis of molecular data promises identification of biomarkers for improving prognostic models, thus potentially enabling better patient management. For identifying such biomarkers, risk prediction models can be employed that link high-dimensional molecular covariate data to a clinical endpoint. In low-dimensional settings, a multitude of statistical techniques already exists for building such models, e.g. allowing for variable selection or for quantifying the added value of a new biomarker. We provide an overview of techniques for regularized estimation that transfer this toward high-dimensional settings, with a focus on models for time-to-event endpoints. Techniques for incorporating specific covariate structure are discussed, as well as techniques for dealing with more complex endpoints. Employing gene expression data from patients with diffuse large B-cell lymphoma, some typical modeling issues from low-dimensional settings are illustrated in a high-dimensional application. First, the performance of classical stepwise regression is compared to stage-wise regression, as implemented by a component-wise likelihood-based boosting approach. A second issues arises, when artificially transforming the response into a binary variable. The effects of the resulting loss of efficiency and potential bias in a high-dimensional setting are illustrated, and a link to competing risks models is provided. Finally, we discuss conditions for adequately quantifying the added value of high-dimensional gene expression measurements, both at the stage of model fitting and when performing evaluation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using molecular tools to identify the geographical origin of a case of human brucellosis.

Science.gov (United States)

Muchowski, J K; Koylass, M S; Dainty, A C; Stack, J A; Perrett, L; Whatmore, A M; Perrier, C; Chircop, S; Demicoli, N; Gatt, A B; Caruana, P A; Gopaul, K K

2015-10-01

Although Malta is historically linked with the zoonosis brucellosis, there had not been a case of the disease in either the human or livestock population for several years. However, in July 2013 a case of human brucellosis was identified on the island. To determine whether this recent case originated in Malta, four isolates from this case were subjected to molecular analysis. Molecular profiles generated using multilocus sequence analysis and multilocus variable number tandem repeat for the recent human case isolates and 11 Brucella melitensis strains of known Maltese origin were compared with others held on in-house and global databases. While the 11 isolates of Maltese origin formed a distinct cluster, the recent human isolation was not associated with these strains but instead clustered with isolates originating from the Horn of Africa. These data was congruent with epidemiological trace-back showed that the individual had travelled to Malta from Eritrea. This work highlights the potential of using molecular typing data to aid in epidemiological trace-back of Brucella isolations and assist in monitoring of the effectiveness of brucellosis control schemes.

Molecular events basic to cellular radiation response

International Nuclear Information System (INIS)

Kolodny, G.M.

The initiation and control of the division process in normal cells is studied to gain insight into changes in these regards caused by x-irradiation and neoplasia. The Primer Hypothesis for eukaryotic gene regulation proposes that small molecular weight RNA acts as primer for new RNA synthesis by hybridizing with DNA and there initiating the transcription of a new RNA chain. The experiments reported here indicate that small molecular weight RNA will induce the production of new proteins. These results are consistent with the Primer Hypothesis, and demonstrate that RNA can be taken up from the media by cells in culture and can induce in vitro the production of differentiated cell products

Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

Science.gov (United States)

San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

2014-12-01

Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

Identify alternative splicing events based on position-specific evolutionary conservation.

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Liang Chen

Full Text Available The evolution of eukaryotes is accompanied by the increased complexity of alternative splicing which greatly expands genome information. One of the greatest challenges in the post-genome era is a complete revelation of human transcriptome with consideration of alternative splicing. Here, we introduce a comparative genomics approach to systemically identify alternative splicing events based on the differential evolutionary conservation between exons and introns and the high-quality annotation of the ENCODE regions. Specifically, we focus on exons that are included in some transcripts but are completely spliced out for others and we call them conditional exons. First, we characterize distinguishing features among conditional exons, constitutive exons and introns. One of the most important features is the position-specific conservation score. There are dramatic differences in conservation scores between conditional exons and constitutive exons. More importantly, the differences are position-specific. For flanking intronic regions, the differences between conditional exons and constitutive exons are also position-specific. Using the Random Forests algorithm, we can classify conditional exons with high specificities (97% for the identification of conditional exons from intron regions and 95% for the classification of known exons and fair sensitivities (64% and 32% respectively. We applied the method to the human genome and identified 39,640 introns that actually contain conditional exons and classified 8,813 conditional exons from the current RefSeq exon list. Among those, 31,673 introns containing conditional exons and 5,294 conditional exons classified from known exons cannot be inferred from RefSeq, UCSC or Ensembl annotations. Some of these de novo predictions were experimentally verified.

A Phylogenomic Census of Molecular Functions Identifies Modern Thermophilic Archaea as the Most Ancient Form of Cellular Life

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Arshan Nasir

2014-01-01

Full Text Available The origins of diversified life remain mysterious despite considerable efforts devoted to untangling the roots of the universal tree of life. Here we reconstructed phylogenies that described the evolution of molecular functions and the evolution of species directly from a genomic census of gene ontology (GO definitions. We sampled 249 free-living genomes spanning organisms in the three superkingdoms of life, Archaea, Bacteria, and Eukarya, and used the abundance of GO terms as molecular characters to produce rooted phylogenetic trees. Results revealed an early thermophilic origin of Archaea that was followed by genome reduction events in microbial superkingdoms. Eukaryal genomes displayed extraordinary functional diversity and were enriched with hundreds of novel molecular activities not detected in the akaryotic microbial cells. Remarkably, the majority of these novel functions appeared quite late in evolution, synchronized with the diversification of the eukaryal superkingdom. The distribution of GO terms in superkingdoms confirms that Archaea appears to be the simplest and most ancient form of cellular life, while Eukarya is the most diverse and recent.

A phylogenomic census of molecular functions identifies modern thermophilic archaea as the most ancient form of cellular life.

Science.gov (United States)

Nasir, Arshan; Kim, Kyung Mo; Caetano-Anollés, Gustavo

2014-01-01

The origins of diversified life remain mysterious despite considerable efforts devoted to untangling the roots of the universal tree of life. Here we reconstructed phylogenies that described the evolution of molecular functions and the evolution of species directly from a genomic census of gene ontology (GO) definitions. We sampled 249 free-living genomes spanning organisms in the three superkingdoms of life, Archaea, Bacteria, and Eukarya, and used the abundance of GO terms as molecular characters to produce rooted phylogenetic trees. Results revealed an early thermophilic origin of Archaea that was followed by genome reduction events in microbial superkingdoms. Eukaryal genomes displayed extraordinary functional diversity and were enriched with hundreds of novel molecular activities not detected in the akaryotic microbial cells. Remarkably, the majority of these novel functions appeared quite late in evolution, synchronized with the diversification of the eukaryal superkingdom. The distribution of GO terms in superkingdoms confirms that Archaea appears to be the simplest and most ancient form of cellular life, while Eukarya is the most diverse and recent.

Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

Directory of Open Access Journals (Sweden)

Byungwoo Ryu

2007-07-01

Full Text Available Gene expression profiling has revolutionized our ability to molecularly classify primary human tumors and significantly enhanced the development of novel tumor markers and therapies; however, progress in the diagnosis and treatment of melanoma over the past 3 decades has been limited, and there is currently no approved therapy that significantly extends lifespan in patients with advanced disease. Profiling studies of melanoma to date have been inconsistent due to the heterogeneous nature of this malignancy and the limited availability of informative tissue specimens from early stages of disease.In order to gain an improved understanding of the molecular basis of melanoma progression, we have compared gene expression profiles from a series of melanoma cell lines representing discrete stages of malignant progression that recapitulate critical characteristics of the primary lesions from which they were derived. Here we describe the unsupervised hierarchical clustering of profiling data from melanoma cell lines and melanocytes. This clustering identifies two distinctive molecular subclasses of melanoma segregating aggressive metastatic tumor cell lines from less-aggressive primary tumor cell lines. Further analysis of expression signatures associated with melanoma progression using functional annotations categorized these transcripts into three classes of genes: 1 Upregulation of activators of cell cycle progression, DNA replication and repair (CDCA2, NCAPH, NCAPG, NCAPG2, PBK, NUSAP1, BIRC5, ESCO2, HELLS, MELK, GINS1, GINS4, RAD54L, TYMS, and DHFR, 2 Loss of genes associated with cellular adhesion and melanocyte differentiation (CDH3, CDH1, c-KIT, PAX3, CITED1/MSG-1, TYR, MELANA, MC1R, and OCA2, 3 Upregulation of genes associated with resistance to apoptosis (BIRC5/survivin. While these broad classes of transcripts have previously been implicated in the progression of melanoma and other malignancies, the specific genes identified within each class

Molecular diagnostics of myeloproliferative neoplasms.

Science.gov (United States)

Langabeer, Stephen E; Andrikovics, Hajnalka; Asp, Julia; Bellosillo, Beatriz; Carillo, Serge; Haslam, Karl; Kjaer, Lasse; Lippert, Eric; Mansier, Olivier; Oppliger Leibundgut, Elisabeth; Percy, Melanie J; Porret, Naomi; Palmqvist, Lars; Schwarz, Jiri; McMullin, Mary F; Schnittger, Susanne; Pallisgaard, Niels; Hermouet, Sylvie

2015-10-01

Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The past and the future of Alzheimer’s disease CSF biomarkers – a journey towards validated biochemical tests covering the whole spectra of molecular events

Directory of Open Access Journals (Sweden)

Kaj eBlennow

2015-09-01

Full Text Available This paper gives a short review on cerebrospinal fluid (CSF biomarkers for Alzheimer’s disease (AD, from early developments to high-precision validated assays on fully automated lab analyzers. We also discuss developments on novel biomarkers, such as synaptic proteins and Aβ oligomers. Our vision for the future is that assaying a set of biomarkers in a single CSF tube can monitor the whole spectra of AD molecular pathogenic events. CSF biomarkers will have a central position not only for clinical diagnosis, but also for the understanding of the sequence of molecular events in the pathogenic process underlying AD and as tools to monitor the effects of novel drug candidates targeting these different mechanisms.

Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

Science.gov (United States)

Ren, Zhonglu; Wang, Wenhui; Li, Jinming

2016-02-01

Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype. Clustering analysis and discriminant analysis were utilized to discover the subtypes in two different molecular levels on 153 colon cancer samples from The Cancer Genome Atlas (TCGA) Data Portal. At gene expression level, we identified two major subtypes, ECL1 (expression cluster 1) and ECL2 (expression cluster 2) and a list of signature genes. Due to the heterogeneity of colon cancer, the subtype ECL1 can be further subdivided into three nested subclasses, and HOTAIR were found upregulated in subclass 2. At DNA methylation level, we uncovered three major subtypes, MCL1 (methylation cluster 1), MCL2 (methylation cluster 2) and MCL3 (methylation cluster 3). We found only three subtypes of CpG island methylator phenotype (CIMP) in colon cancer instead of the four subtypes in the previous reports, and we found no sufficient evidence to subdivide MCL3 into two distinct subgroups.

A suite of molecular markers for identifying species, detecting introgression and describing population structure in spadefoot toads (Spea spp.).

Science.gov (United States)

Pfennig, Karin S; Allenby, Ashley; Martin, Ryan A; Monroy, Anaïs; Jones, Corbin D

2012-09-01

Two congeneric species of spadefoot toad, Spea multiplicata and Spea bombifrons, have been the focus of hybridization studies since the 1970s. Because complex hybrids are not readily distinguished phenotypically, genetic markers are needed to identify introgressed individuals. We therefore developed a set of molecular markers (amplified fragment length polymorphism, polymerase chain reaction-restriction fragment length polymorphism and single nucleotide polymorphism) for identifying pure-species, F1 hybrids and more complex introgressed types. To do so, we tested a series of markers across both species and known hybrids using populations in both allopatry and sympatry. We retained those markers that differentiated the two pure-species and also consistently identified known species hybrids. These markers are well suited for identifying hybrids between these species. Moreover, those markers that show variation within each species can be used in conjunction with existing molecular markers in studies of population structure and gene flow. © 2012 Blackwell Publishing Ltd.

A 6-gene signature identifies four molecular subgroups of neuroblastoma

Science.gov (United States)

2011-01-01

Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p INSS stage 4 and/or dead of disease, p < 0.05, Fisher's exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics. PMID:21492432

A study on method to identify actual causes and conditions of safety rule deviations through analyzing events due to unsafe acts of workers

International Nuclear Information System (INIS)

Hirotsu, Yuko; Takeda, Daisuke

2010-01-01

The purpose of this study is to establish a method to understand actual causes and condition of intentional deviation from safety rules (including norm and written rules that has developed to anticipate, prevent, detect and recover human errors) in an organization by analyzing events due to unsafe acts of workers (human factor events) and to propose effective measures. Firstly, by reviewing literature regarding safety violations, the following two advantages of investigating actual condition of safety rule deviation through human factor event analysis were extracted, such as (a) being able to clarify relationships between deviations, human errors, and events, and (b) being able to identify specific causal factors that influenced the decision to deviate, including acts of people concerned, problems with rules, task demands, environment and management. Next, through the analysis of human factor event data in accordance with existing human error analysis method on the basis of advantages above, the following three requirements for analyzing event data were extracted, such as (a) gathering information such as rules concerning to the work activities related to the human factor events, and whether there are intentional deviations of the rules, (b) gathering information and identify interrelations among causal factors of the intentional deviations, and (c) gathering information on general condition of deviations and the causal factors. (author)

Quantitative proteomics identify molecular targets that are crucial in larval settlement and metamorphosis of bugula neritina

KAUST Repository

Zhang, Huoming

2011-01-07

The marine invertebrate Bugula neritina has a biphasic life cycle that consists of a swimming larval stage and a sessile juvenile and adult stage. The attachment of larvae to the substratum and their subsequent metamorphosis have crucial ecological consequences. Despite many studies on this species, little is known about the molecular mechanism of these processes. Here, we report a comparative study of swimming larvae and metamorphosing individuals at 4 and 24 h postattachment using label-free quantitative proteomics. We identified more than 1100 proteins at each stage, 61 of which were differentially expressed. Specifically, proteins involved in energy metabolism and structural molecules were generally down-regulated, whereas proteins involved in transcription and translation, the extracellular matrix, and calcification were strongly up-regulated during metamorphosis. Many tightly regulated novel proteins were also identified. Subsequent analysis of the temporal and spatial expressions of some of the proteins and an assay of their functions indicated that they may have key roles in metamorphosis of B. neritina. These findings not only provide molecular evidence with which to elucidate the substantial changes in morphology and physiology that occur during larval attachment and metamorphosis but also identify potential targets for antifouling treatment. © 2011 American Chemical Society.

Identifying self-interstitials of bcc and fcc crystals in molecular dynamics

Science.gov (United States)

Bukkuru, S.; Bhardwaj, U.; Warrier, M.; Rao, A. D. P.; Valsakumar, M. C.

2017-02-01

Identification of self-interstitials in molecular dynamics (MD) simulations is of critical importance. There exist several criteria for identifying the self-interstitial. Most of the existing methods use an assumed cut-off value for the displacement of an atom from its lattice position to identify the self-interstitial. The results obtained are affected by the chosen cut-off value. Moreover, these chosen cut-off values are independent of temperature. We have developed a novel unsupervised learning algorithm called Max-Space Clustering (MSC) to identify an appropriate cut-off value and its dependence on temperature. This method is compared with some widely used methods such as effective sphere (ES) method and nearest neighbor sphere (NNS) method. The cut-off radius obtained using our method shows a linear variation with temperature. The value of cut-off radius and its temperature dependence is derived for five bcc (Cr, Fe, Mo, Nb, W) and six fcc (Ag, Au, Cu, Ni, Pd, Pt) crystals. It is seen that the ratio of the cut-off values "r" to the lattice constant "a" lies between 0.23 and 0.3 at 300 K and this ratio is on an average smaller for the fcc crystals. Collision cascade simulations are carried out for Primary knock-on Atom (PKA) energies of 5 keV in Fe (at 300 K and 1000 K) and W (at 300 K and 2500 K) and the results are compared using the various methods.

Dissecting molecular stress networks: identifying nodes of divergence between life-history phenotypes.

Science.gov (United States)

Schwartz, Tonia S; Bronikowski, Anne M

2013-02-01

The complex molecular network that underlies physiological stress response is comprised of nodes (proteins, metabolites, mRNAs, etc.) whose connections span cells, tissues and organs. Variable nodes are points in the network upon which natural selection may act. Thus, identifying variable nodes will reveal how this molecular stress network may evolve among populations in different habitats and how it might impact life-history evolution. Here, we use physiological and genetic assays to test whether laboratory-born juveniles from natural populations of garter snakes (Thamnophis elegans), which have diverged in their life-history phenotypes, vary concomitantly at candidate nodes of the stress response network, (i) under unstressed conditions and (ii) in response to an induced stress. We found that two common measures of stress (plasma corticosterone and liver gene expression of heat shock proteins) increased under stress in both life-history phenotypes. In contrast, the phenotypes diverged at four nodes both under unstressed conditions and in response to stress: circulating levels of reactive oxygen species (superoxide, H(2)O(2)); liver gene expression of GPX1 and erythrocyte DNA damage. Additionally, allele frequencies for SOD2 diverge from neutral markers, suggesting diversifying selection on SOD2 alleles. This study supports the hypothesis that these life-history phenotypes have diverged at the molecular level in how they respond to stress, particularly in nodes regulating oxidative stress. Furthermore, the differences between the life-history phenotypes were more pronounced in females. We discuss the responses to stress in the context of the associated life-history phenotype and the evolutionary pressures thought to be responsible for divergence between the phenotypes. © 2012 Blackwell Publishing Ltd.

Clustering of transcriptional profiles identifies changes to insulin signaling as an early event in a mouse model of Alzheimer's disease.

Science.gov (United States)

Jackson, Harriet M; Soto, Ileana; Graham, Leah C; Carter, Gregory W; Howell, Gareth R

2013-11-25

Alzheimer's disease affects more than 35 million people worldwide but there is no known cure. Age is the strongest risk factor for Alzheimer's disease but it is not clear how age-related changes impact the disease. Here, we used a mouse model of Alzheimer's disease to identify age-specific changes that occur prior to and at the onset of traditional Alzheimer-related phenotypes including amyloid plaque formation. To identify these early events we used transcriptional profiling of mouse brains combined with computational approaches including singular value decomposition and hierarchical clustering. Our study identifies three key events in early stages of Alzheimer's disease. First, the most important drivers of Alzheimer's disease onset in these mice are age-specific changes. These include perturbations of the ribosome and oxidative phosphorylation pathways. Second, the earliest detectable disease-specific changes occur to genes commonly associated with the hypothalamic-adrenal-pituitary (HPA) axis. These include the down-regulation of genes relating to metabolism, depression and appetite. Finally, insulin signaling, in particular the down-regulation of the insulin receptor substrate 4 (Irs4) gene, may be an important event in the transition from age-related changes to Alzheimer's disease specific-changes. A combination of transcriptional profiling combined with computational analyses has uncovered novel features relevant to Alzheimer's disease in a widely used mouse model and offers avenues for further exploration into early stages of AD.

Swarm-Aurora: A web-based tool for quickly identifying multi-instrument auroral events

Science.gov (United States)

Chaddock, D.; Donovan, E.; Spanswick, E.; Knudsen, D. J.; Frey, H. U.; Kauristie, K.; Partamies, N.; Jackel, B. J.; Gillies, M.; Holmdahl Olsen, P. E.

2016-12-01

In recent years there has been a dramatic increase in ground-based auroral imaging systems. These include the continent-wide THEMIS-ASI network, and imagers operated by other programs including GO-Canada, MIRACLE, AGO, OMTI, and more. In the near future, a new Canadian program called TREx will see the deployment of new narrow-band ASIs that will provide multi-wavelength imaging across Western Canada. At the same time, there is an unprecedented fleet of international spacecraft probing geospace at low and high altitudes. We are now in the position to simultaneously observe the magnetospheric drivers of aurora, observe in situ the waves, currents, and particles associated with MI coupling, and the conjugate aurora. Whereas a decade ago, a single magnetic conjunction between one ASI and a low altitude satellite was a relatively rare event, we now have a plethora of triple conjunctions between imagers, low-altitude spacecraft, and near-equatorial magnetospheric probes. But with these riches comes a new level of complexity. It is often difficult to identify the many useful conjunctions for a specific line of inquiry from the multitude of conjunctions where the geospace conditions are often not relevant and/or the imaging is compromised by clouds, moon, or other factors. Swarm-Aurora was designed to facilitate and drive the use of Swarm in situ measurements in auroral science. The project seeks to build a bridge between the Swarm science community, Swarm data, and the complimentary auroral data and community. Swarm-Aurora (http://swarm-aurora.phys.ucalgary.ca) incorporates a web-based tool which provides access to quick-look summary data for a large array of instruments, with Swarm in situ and ground-based ASI data as the primary focus. This web interface allows researchers to quickly and efficiently browse Swarm and ASI data to identify auroral events of interest to them. This allows researchers to be able to easily and quickly identify Swarm overflights of ASIs that

Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

Science.gov (United States)

Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

2009-09-01

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

Molecular defects identified by whole exome sequencing in a child with Fanconi anemia.

Science.gov (United States)

Zheng, Zhaojing; Geng, Juan; Yao, Ru-En; Li, Caihua; Ying, Daming; Shen, Yongnian; Ying, Lei; Yu, Yongguo; Fu, Qihua

2013-11-10

Fanconi anemia is a rare genetic disease characterized by bone marrow failure, multiple congenital malformations, and an increased susceptibility to malignancy. At least 15 genes have been identified that are involved in the pathogenesis of Fanconi anemia. However, it is still a challenge to assign the complementation group and to characterize the molecular defects in patients with Fanconi anemia. In the current study, whole exome sequencing was used to identify the affected gene(s) in a boy with Fanconi anemia. A recurring, non-synonymous mutation was found (c.3971C>T, p.P1324L) as well as a novel frameshift mutation (c.989_995del, p.H330LfsX2) in FANCA gene. Our results indicate that whole exome sequencing may be useful in clinical settings for rapid identification of disease-causing mutations in rare genetic disorders such as Fanconi anemia. © 2013 Elsevier B.V. All rights reserved.

A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling.

Science.gov (United States)

Wieczorek, Dagmar; Bögershausen, Nina; Beleggia, Filippo; Steiner-Haldenstätt, Sabine; Pohl, Esther; Li, Yun; Milz, Esther; Martin, Marcel; Thiele, Holger; Altmüller, Janine; Alanay, Yasemin; Kayserili, Hülya; Klein-Hitpass, Ludger; Böhringer, Stefan; Wollstein, Andreas; Albrecht, Beate; Boduroglu, Koray; Caliebe, Almuth; Chrzanowska, Krystyna; Cogulu, Ozgur; Cristofoli, Francesca; Czeschik, Johanna Christina; Devriendt, Koenraad; Dotti, Maria Teresa; Elcioglu, Nursel; Gener, Blanca; Goecke, Timm O; Krajewska-Walasek, Malgorzata; Guillén-Navarro, Encarnación; Hayek, Joussef; Houge, Gunnar; Kilic, Esra; Simsek-Kiper, Pelin Özlem; López-González, Vanesa; Kuechler, Alma; Lyonnet, Stanislas; Mari, Francesca; Marozza, Annabella; Mathieu Dramard, Michèle; Mikat, Barbara; Morin, Gilles; Morice-Picard, Fanny; Ozkinay, Ferda; Rauch, Anita; Renieri, Alessandra; Tinschert, Sigrid; Utine, G Eda; Vilain, Catheline; Vivarelli, Rossella; Zweier, Christiane; Nürnberg, Peter; Rahmann, Sven; Vermeesch, Joris; Lüdecke, Hermann-Josef; Zeschnigk, Michael; Wollnik, Bernd

2013-12-20

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategies.

Automatically Identifying Fusion Events between GLUT4 Storage Vesicles and the Plasma Membrane in TIRF Microscopy Image Sequences

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Jian Wu

2015-01-01

Full Text Available Quantitative analysis of the dynamic behavior about membrane-bound secretory vesicles has proven to be important in biological research. This paper proposes a novel approach to automatically identify the elusive fusion events between VAMP2-pHluorin labeled GLUT4 storage vesicles (GSVs and the plasma membrane. The differentiation is implemented to detect the initiation of fusion events by modified forward subtraction of consecutive frames in the TIRFM image sequence. Spatially connected pixels in difference images brighter than a specified adaptive threshold are grouped into a distinct fusion spot. The vesicles are located at the intensity-weighted centroid of their fusion spots. To reveal the true in vivo nature of a fusion event, 2D Gaussian fitting for the fusion spot is used to derive the intensity-weighted centroid and the spot size during the fusion process. The fusion event and its termination can be determined according to the change of spot size. The method is evaluated on real experiment data with ground truth annotated by expert cell biologists. The evaluation results show that it can achieve relatively high accuracy comparing favorably to the manual analysis, yet at a small fraction of time.

Identifying self-interstitials of bcc and fcc crystals in molecular dynamics

International Nuclear Information System (INIS)

Bukkuru, S.; Bhardwaj, U.; Warrier, M.; Rao, A.D.P.; Valsakumar, M.C.

2017-01-01

Identification of self-interstitials in molecular dynamics (MD) simulations is of critical importance. There exist several criteria for identifying the self-interstitial. Most of the existing methods use an assumed cut-off value for the displacement of an atom from its lattice position to identify the self-interstitial. The results obtained are affected by the chosen cut-off value. Moreover, these chosen cut-off values are independent of temperature. We have developed a novel unsupervised learning algorithm called Max-Space Clustering (MSC) to identify an appropriate cut-off value and its dependence on temperature. This method is compared with some widely used methods such as effective sphere (ES) method and nearest neighbor sphere (NNS) method. The cut-off radius obtained using our method shows a linear variation with temperature. The value of cut-off radius and its temperature dependence is derived for five bcc (Cr, Fe, Mo, Nb, W) and six fcc (Ag, Au, Cu, Ni, Pd, Pt) crystals. It is seen that the ratio of the cut-off values “r” to the lattice constant “a” lies between 0.23 and 0.3 at 300 K and this ratio is on an average smaller for the fcc crystals. Collision cascade simulations are carried out for Primary knock-on Atom (PKA) energies of 5 keV in Fe (at 300 K and 1000 K) and W (at 300 K and 2500 K) and the results are compared using the various methods. - Highlights: • Max-Space Clustering (MSC) method is developed to identify interstitials in crystals. • MSC provides a structured way to identify the temperature dependent cut-off radius. • It is compared with widely used sphere methods and found to be better. • MSC coupled with graph tree optimization can be used to obtain diffusion trajectory. • Cascade simulations of Fe, W are carried out and results are compared with various methods.

Identifying self-interstitials of bcc and fcc crystals in molecular dynamics

Energy Technology Data Exchange (ETDEWEB)

Bukkuru, S., E-mail: srinivasaraobukkuru@gmail.com [Dept. of Nuclear Physics, Andhra University, Visakhapatnam 530003 (India); Bhardwaj, U., E-mail: haptork@gmail.com [Computational Analysis Division, BARC, Visakhapatnam 530012, Andhra Pradesh (India); Warrier, M., E-mail: manoj.warrier@gmail.com [Computational Analysis Division, BARC, Visakhapatnam 530012, Andhra Pradesh (India); Rao, A.D.P., E-mail: adp_rao_99@yahoo.com [Dept. of Nuclear Physics, Andhra University, Visakhapatnam 530003 (India); Valsakumar, M.C., E-mail: mc.valsakumar@gmail.com [IIT Palakkad, Kozhippara P.O., Palakkad 678557, Kerala (India)

2017-02-15

Identification of self-interstitials in molecular dynamics (MD) simulations is of critical importance. There exist several criteria for identifying the self-interstitial. Most of the existing methods use an assumed cut-off value for the displacement of an atom from its lattice position to identify the self-interstitial. The results obtained are affected by the chosen cut-off value. Moreover, these chosen cut-off values are independent of temperature. We have developed a novel unsupervised learning algorithm called Max-Space Clustering (MSC) to identify an appropriate cut-off value and its dependence on temperature. This method is compared with some widely used methods such as effective sphere (ES) method and nearest neighbor sphere (NNS) method. The cut-off radius obtained using our method shows a linear variation with temperature. The value of cut-off radius and its temperature dependence is derived for five bcc (Cr, Fe, Mo, Nb, W) and six fcc (Ag, Au, Cu, Ni, Pd, Pt) crystals. It is seen that the ratio of the cut-off values “r” to the lattice constant “a” lies between 0.23 and 0.3 at 300 K and this ratio is on an average smaller for the fcc crystals. Collision cascade simulations are carried out for Primary knock-on Atom (PKA) energies of 5 keV in Fe (at 300 K and 1000 K) and W (at 300 K and 2500 K) and the results are compared using the various methods. - Highlights: • Max-Space Clustering (MSC) method is developed to identify interstitials in crystals. • MSC provides a structured way to identify the temperature dependent cut-off radius. • It is compared with widely used sphere methods and found to be better. • MSC coupled with graph tree optimization can be used to obtain diffusion trajectory. • Cascade simulations of Fe, W are carried out and results are compared with various methods.

Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers

OpenAIRE

Taïbi, Khaled; Campo, Antonio D. del; Vilagrosa Carmona, Alberto; Bellés, José M.; López-Gresa, María Pilar; Pla, Davinia; Calvete, Juan J.; López-Nicolás, José M.; Mulet, José M.

2017-01-01

Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of pre...

General perspectives for molecular nuclear imaging

International Nuclear Information System (INIS)

Chung, June Key

2004-01-01

Molecular imaging provides a visualization of normal as well as abnormal cellular processes at a molecular or genetic level rather than at an anatomical level. Conventional medical imaging methods utilize the imaging signals produced by nonspecific physico-chemical interaction. However, molecular imaging methods utilize the imaging signals derived from specific cellular or molecular events. Because molecular and genetic changes precede anatomical change in the course of disease development, molecular imaging can detect early events in disease progression. In the near future, through molecular imaging we can understand basic mechanisms of disease, and diagnose earlier and, subsequently, treat earlier intractable disease such as cancer, neuro-degenerative diseases, and immunologic disorders. In beginning period, nuclear medicine started as a molecular imaging, and has had a leading role in the field of molecular imaging. But recently molecular imaging has been rapidly developed. Besides nuclear imaging, molecular imaging methods such as optical imaging, magnetic resonance imaging are emerging. Each imaging modalities have their advantages and weaknesses. The opportunities from molecular imaging look bright. We should try nuclear medicine continues to have a leading role in molecular imaging

Characterization of GM events by insert knowledge adapted re-sequencing approaches

OpenAIRE

Yang, Litao; Wang, Congmao; Holst-Jensen, Arne; Morisset, Dany; Lin, Yongjun; Zhang, Dabing

2013-01-01

Detection methods and data from molecular characterization of genetically modified (GM) events are needed by stakeholders of public risk assessors and regulators. Generally, the molecular characteristics of GM events are incomprehensively revealed by current approaches and biased towards detecting transformation vector derived sequences. GM events are classified based on available knowledge of the sequences of vectors and inserts (insert knowledge). Herein we present three insert knowledge-ad...

Identifying molecular targets of lifestyle modifications in colon cancer prevention

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Molly Marie Derry

2013-05-01

Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

A 6-gene signature identifies four molecular subgroups of neuroblastoma

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Kogner Per

2011-04-01

Full Text Available Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB; Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples. Four distinct clusters were identified by Principal Components Analysis (PCA in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics.

Can surveillance systems identify and avert adverse drug events? A prospective evaluation of a commercial application.

Science.gov (United States)

Jha, Ashish K; Laguette, Julia; Seger, Andrew; Bates, David W

2008-01-01

Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital. and Measurement We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs. Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily. A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs.

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

OpenAIRE

Burkhart, Keith K.; Abernethy, Darrell; Jackson, David

2015-01-01

Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was al...

MOLECULAR DIAGNOSTICS - ANOTHER PIECE IN THE ENVIRONMENTAL PUZZLE

Science.gov (United States)

Molecular biology offers sensitive and expedient tools for the detection of exposure to environmental stressors. Molecular approaches provide the means for detection of the "first cellular event(s)" in response to environmental changes-specifically, immediate changes in gene expr...

New technique of identifying the hierarchy of dynamic domains in proteins using a method of molecular dynamics simulations

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Yesylevskyy S. O.

2010-04-01

Full Text Available Aim. Despite a large number of existing domain identification techniques there is no universally accepted method, which identifies the hierarchy of dynamic domains using the data of molecular dynamics (MD simulations. The goal of this work is to develop such technique. Methods. The dynamic domains are identified by eliminating systematic motions from MD trajectories recursively in a model-free manner. Results. The technique called the Hierarchical Domain-Wise Alignment (HDWA to identify hierarchically organized dynamic domains in proteins using the MD trajectories has been developed. Conclusion. A new method of domain identification in proteins is proposed

Identifying and Overcoming Barriers to Effective Consideration of Human and Organisational Factors in Event Analysis and Root Cause Analysis. Workshop Proceedings, September 21-22, 2009, Paris, France

International Nuclear Information System (INIS)

2011-01-01

Nuclear licensees must have effective processes for learning from operating experience in order to manage safety, secure continuous improvement and defend against the potential for repeat events. These processes include root cause analysis (RCA) to identify the underlying causes of events and mechanisms to learn from these analyses and to implement improvements. Correctly identifying and correcting the causes of events will allow lessons to be learned and shared with others in the industry. The treatment of Human and Organisational Factors (HOF) in RCA is of special interest to WGHOF. It is estimated that approximately 60-80% of events in the nuclear industry can be attributed to human and organisational factors. Although the importance of correctly identifying the HOF causes is understood, there is still a tendency for the analysis to focus solely on the technical issues of the event. The history of prominent events across the major hazards sector shows that HOF lessons often fail to be learned. A NEA/CSNI special experts meeting entitled 'Identification of Barriers to Analyzing and Identifying Human and Organisational Factors in Root Cause Analysis' was held at the NEA Headquarters in Paris, France on September 21-22, 2009. A total of 17 participants from 10 countries representing licensee organisations, regulators, international organisations and an independent consultant attended the meeting. The meeting was structured to allow for small group discussions during which a number of themes were explored, followed by plenary discussion. There were also four papers presented which complemented the discussion themes. As set out in the objectives of this work, the participants identified barriers to the effective treatment of HOF in RCA and recommendations to mitigate the effects of these barriers. Many of the barriers and recommendations identified relate to the RCA process in general, not specifically to the treatment of HOF in the RCA process. This is logical, for

Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

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Anshuman Dixit

Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE

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Constantinos Yeles

2017-11-01

Full Text Available Ionizing radiation-induced bystander effects (RIBE encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR, something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions.

Transcriptomic Profiling Reveals Complex Molecular Regulation in Cotton Genic Male Sterile Mutant Yu98-8A.

Directory of Open Access Journals (Sweden)

Weiping Fang

Full Text Available Although cotton genic male sterility (GMS plays an important role in the utilization of hybrid vigor, its precise molecular mechanism remains unclear. To characterize the molecular events of pollen abortion, transcriptome analysis, combined with histological observations, was conducted in the cotton GMS line, Yu98-8A. A total of 2,412 genes were identified as significant differentially expressed genes (DEGs before and during the critical pollen abortion stages. Bioinformatics and biochemical analysis showed that the DEGs mainly associated with sugars and starch metabolism, oxidative phosphorylation, and plant endogenous hormones play a critical and complicated role in pollen abortion. These findings extend a better understanding of the molecular events involved in the regulation of pollen abortion in genic male sterile cotton, which may provide a foundation for further research studies on cotton heterosis breeding.

Purchase decision involvement: Event management segments and related event behavior

Science.gov (United States)

Rodney B. Warnick; David C. Bojanic

2012-01-01

The goal of this research was to examine the relationships between different levels of event purchase decision involvement (PDI) segments and their respective event behaviors (e.g., expenditures, travel behavior, event consumption and satisfaction). The specific purpose was to answer two major research questions: 1) Can PDI identify different levels or segments of...

A Network of AOPs for reduced thyroid hormone synthesis derived from inhibition of Thyroperoxidase - A common Molecular Initiating Event Leading to Species-Specific Indices of Adversity.

Science.gov (United States)

This collection of 3 AOPs describe varying outcomes of adversity dependent upon species in response to inhibition of thyroperoxidase (TPO) during development. Chemical inhibition of TPO, the molecular-initiating event (MIE), results in decreased thyroid hormone (TH) synthesis, a...

Impact of Laboratory Cross-Contamination on Molecular Epidemiology Studies of Tuberculosis

Science.gov (United States)

Martínez, Miguel; de Viedma, Darío García; Alonso, María; Andrés, Sandra; Bouza, Emilio; Cabezas, Teresa; Cabeza, Isabel; Reyes, Armando; Sánchez-Yebra, Waldo; Rodríguez, Manuel; Sánchez, M. Isabel; Rogado, M. Cruz; Fernández, Rosa; Peñafiel, Teresa; Martínez, Juan; Barroso, Pilar; Lucerna, M. Ángeles; Diez, L. Felipe; Gutiérrez, Carmelo

2006-01-01

Laboratory cross-contamination by Mycobacterium tuberculosis is known to be responsible for the misdiagnosis of tuberculosis, but its impact on other contexts has not been analyzed. We present the findings of a molecular epidemiology analysis in which the recent transmission events identified by a genotyping reference center were overestimated as a result of unnoticed laboratory cross-contamination in the original diagnostic laboratories. PMID:16891518

Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

Directory of Open Access Journals (Sweden)

Guan-Feng Wang

2015-02-01

Full Text Available Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR. Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC, a nucleotide binding (NB-ARC and a leucine rich repeat (LRR domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

Science.gov (United States)

Wang, Guan-Feng; Ji, Jiabing; El-Kasmi, Farid; Dangl, Jeffery L; Johal, Guri; Balint-Kurti, Peter J

2015-02-01

Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

A 6-gene signature identifies four molecular subgroups of neuroblastoma

LENUS (Irish Health Repository)

Abel, Frida

2011-04-14

Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

Probabilistic analysis of external events with focus on the Fukushima event

International Nuclear Information System (INIS)

Kollasko, Heiko; Jockenhoevel-Barttfeld, Mariana; Klapp, Ulrich

2014-01-01

External hazards are those natural or man-made hazards to a site and facilities that are originated externally to both the site and its processes, i.e. the duty holder may have very little or no control over the hazard. External hazards can have the potential of causing initiating events at the plant, typically transients like e.g., loss of offsite power. Simultaneously, external events may affect safety systems required to control the initiating event and, where applicable, also back-up systems implemented for risk-reduction. The plant safety may especially be threatened when loads from external hazards exceed the load assumptions considered in the design of safety-related systems, structures and components. Another potential threat is given by hazards inducing initiating events not considered in the safety demonstration otherwise. An example is loss of offsite power combined with prolonged plant isolation. Offsite support, e.g., delivery of diesel fuel oil, usually credited in the deterministic safety analysis may not be possible in this case. As the Fukushima events have shown, the biggest threat is likely given by hazards inducing both effects. Such hazards may well be dominant risk contributors even if their return period is very high. In order to identify relevant external hazards for a certain Nuclear Power Plant (NPP) location, a site specific screening analysis is performed, both for single events and for combinations of external events. As a result of the screening analysis, risk significant and therefore relevant (screened-in) single external events and combinations of them are identified for a site. The screened-in events are further considered in a detailed event tree analysis in the frame of the Probabilistic Safety Analysis (PSA) to calculate the core damage/large release frequency resulting from each relevant external event or from each relevant combination. Screening analyses of external events performed at AREVA are based on the approach provided

Nonlinear Methodologies for Identifying Seismic Event and Nuclear Explosion Using Random Forest, Support Vector Machine, and Naive Bayes Classification

Directory of Open Access Journals (Sweden)

Longjun Dong

2014-01-01

Full Text Available The discrimination of seismic event and nuclear explosion is a complex and nonlinear system. The nonlinear methodologies including Random Forests (RF, Support Vector Machines (SVM, and Naïve Bayes Classifier (NBC were applied to discriminant seismic events. Twenty earthquakes and twenty-seven explosions with nine ratios of the energies contained within predetermined “velocity windows” and calculated distance are used in discriminators. Based on the one out cross-validation, ROC curve, calculated accuracy of training and test samples, and discriminating performances of RF, SVM, and NBC were discussed and compared. The result of RF method clearly shows the best predictive power with a maximum area of 0.975 under the ROC among RF, SVM, and NBC. The discriminant accuracies of RF, SVM, and NBC for test samples are 92.86%, 85.71%, and 92.86%, respectively. It has been demonstrated that the presented RF model can not only identify seismic event automatically with high accuracy, but also can sort the discriminant indicators according to calculated values of weights.

MadEvent: automatic event generation with MadGraph

International Nuclear Information System (INIS)

Maltoni, Fabio; Stelzer, Tim

2003-01-01

We present a new multi-channel integration method and its implementation in the multi-purpose event generator MadEvent, which is based on MadGraph. Given a process, MadGraph automatically identifies all the relevant subprocesses, generates both the amplitudes and the mappings needed for an efficient integration over the phase space, and passes them to MadEvent. As a result, a process-specific, stand-alone code is produced that allows the user to calculate cross sections and produce unweighted events in a standard output format. Several examples are given for processes that are relevant for physics studies at present and forthcoming colliders. (author)

Extended Lagrangian Born-Oppenheimer molecular dynamics simulations of the shock-induced chemistry of phenylacetylene

Energy Technology Data Exchange (ETDEWEB)

Cawkwell, M. J., E-mail: cawkwell@lanl.gov; Niklasson, Anders M. N. [Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Dattelbaum, Dana M. [Weapons Experiments Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

2015-02-14

The initial chemical events that occur during the shock compression of liquid phenylacetylene have been investigated using self-consistent tight binding molecular dynamics simulations. The extended Lagrangian Born-Oppenheimer molecular dynamics formalism enabled us to compute microcanonical trajectories with precise conservation of the total energy. Our simulations revealed that the first density-increasing step under shock compression arises from the polymerization of phenylacetylene molecules at the acetylene moiety. The application of electronic structure-based molecular dynamics with long-term conservation of the total energy enabled us to identify electronic signatures of reactivity via monitoring changes in the HOMO-LUMO gap, and to capture directly adiabatic shock heating, transient non-equilibrium states, and changes in temperature arising from exothermic chemistry in classical molecular dynamics trajectories.

Extended Lagrangian Born-Oppenheimer molecular dynamics simulations of the shock-induced chemistry of phenylacetylene.

Science.gov (United States)

Cawkwell, M J; Niklasson, Anders M N; Dattelbaum, Dana M

2015-02-14

The initial chemical events that occur during the shock compression of liquid phenylacetylene have been investigated using self-consistent tight binding molecular dynamics simulations. The extended Lagrangian Born-Oppenheimer molecular dynamics formalism enabled us to compute microcanonical trajectories with precise conservation of the total energy. Our simulations revealed that the first density-increasing step under shock compression arises from the polymerization of phenylacetylene molecules at the acetylene moiety. The application of electronic structure-based molecular dynamics with long-term conservation of the total energy enabled us to identify electronic signatures of reactivity via monitoring changes in the HOMO-LUMO gap, and to capture directly adiabatic shock heating, transient non-equilibrium states, and changes in temperature arising from exothermic chemistry in classical molecular dynamics trajectories.

The Use of Next Generation Sequencing and Junction Sequence Analysis Bioinformatics to Achieve Molecular Characterization of Crops Improved Through Modern Biotechnology

Directory of Open Access Journals (Sweden)

David Kovalic

2012-11-01

Full Text Available The assessment of genetically modified (GM crops for regulatory approval currently requires a detailed molecular characterization of the DNA sequence and integrity of the transgene locus. In addition, molecular characterization is a critical component of event selection and advancement during product development. Typically, molecular characterization has relied on Southern blot analysis to establish locus and copy number along with targeted sequencing of polymerase chain reaction products spanning any inserted DNA to complete the characterization process. Here we describe the use of next generation (NexGen sequencing and junction sequence analysis bioinformatics in a new method for achieving full molecular characterization of a GM event without the need for Southern blot analysis. In this study, we examine a typical GM soybean [ (L. Merr.] line and demonstrate that this new method provides molecular characterization equivalent to the current Southern blot-based method. We also examine an event containing in vivo DNA rearrangement of multiple transfer DNA inserts to demonstrate that the new method is effective at identifying complex cases. Next generation sequencing and bioinformatics offers certain advantages over current approaches, most notably the simplicity, efficiency, and consistency of the method, and provides a viable alternative for efficiently and robustly achieving molecular characterization of GM crops.

Madagascar sheds new light on the molecular systematics and biogeography of grammitid ferns: New unexpected lineages and numerous long-distance dispersal events.

Science.gov (United States)

Bauret, Lucie; Gaudeul, Myriam; Sundue, Michael A; Parris, Barbara S; Ranker, Tom A; Rakotondrainibe, France; Hennequin, Sabine; Ranaivo, Jaona; Selosse, Marc-André; Rouhan, Germinal

2017-06-01

Based on a worldwide phylogenetic framework filling the taxonomic gap of Madagascar and surrounding islands of the Western Indian Ocean (WIO), we revisited the systematics of grammitid fern species (Polypodiaceae). We also investigated the biogeographic origin of the extant diversity in Madagascar and estimated the relative influence of vicariance, long-distance dispersals (LDD) and in situ diversification. Phylogenetic inferences were based on five plastid DNA regions (atpB, rbcL, rps4-trnS, trnG-trnR, trnL-trnF) and the most comprehensive taxonomic sampling ever assembled (224 species belonging to 31 out of 33 recognized grammitids genera). 31 species from Madagascar were included representing 87% of the described diversity and 77% of the endemics. Our results confirmed a Paleotropical clade nested within an amphi-Atlantic grade. In addition, we identified three new major clades involving species currently belonging to Grammitis s.l., Ctenopterella and Enterosora. We resolved for the first time Grammitis s.s. as monophyletic, and Ctenopterella (newly tested here) and Enterosora as polyphyletic. The Neotropical genus Moranopteris was shown to also occur in Madagascar through a newly discovered species. Most importantly, we suggest a >30% inflation of the species number in the WIO due to the hidden diversity in >10 cryptic lineages, best explained by high morphological homoplasy. Molecular dating and ancestral areas reconstruction allowed identifying the Neotropics as the predominant source of LDD to the African-WIO region, with at least 12 colonization events within the last 20Ma. Repeated eastward migrations may be explained by transoceanic westerly winds transporting the dust-like spores. Tropical Asia s.l. would also have played a (minor) role through one dispersal event to Madagascar at the end of the Oligocene. Last, within the complex Malagasy region made of a mosaic of continental and oceanic islands located close to the African continent, we showed that

Identifying biologically meaningful hot-weather events using threshold temperatures that affect life-history.

Directory of Open Access Journals (Sweden)

Susan J Cunningham

Full Text Available Increases in the frequency, duration and intensity of heat waves are frequently evoked in climate change predictions. However, there is no universal definition of a heat wave. Recent, intense hot weather events have caused mass mortalities of birds, bats and even humans, making the definition and prediction of heat wave events that have the potential to impact populations of different species an urgent priority. One possible technique for defining biologically meaningful heat waves is to use threshold temperatures (T(thresh above which known fitness costs are incurred by species of interest. We set out to test the utility of this technique using T(thresh values that, when exceeded, affect aspects of the fitness of two focal southern African bird species: the southern pied babbler Turdiodes bicolor (T(thresh = 35.5 °C and the common fiscal Lanius collaris (T(thresh = 33 °C. We used these T(thresh values to analyse trends in the frequency, duration and intensity of heat waves of magnitude relevant to the focal species, as well as the annual number of hot days (maximum air temperature > T(thresh, in north-western South Africa between 1961 and 2010. Using this technique, we were able to show that, while all heat wave indices increased during the study period, most rapid increases for both species were in the annual number of hot days and in the maximum intensity (and therefore intensity variance of biologically meaningful heat waves. Importantly, we also showed that warming trends were not uniform across the study area and that geographical patterns in warming allowed both areas of high risk and potential climate refugia to be identified. We discuss the implications of the trends we found for our focal species, and the utility of the T(thresh technique as a conservation tool.

Negated bio-events: analysis and identification

Science.gov (United States)

2013-01-01

Background Negation occurs frequently in scientific literature, especially in biomedical literature. It has previously been reported that around 13% of sentences found in biomedical research articles contain negation. Historically, the main motivation for identifying negated events has been to ensure their exclusion from lists of extracted interactions. However, recently, there has been a growing interest in negative results, which has resulted in negation detection being identified as a key challenge in biomedical relation extraction. In this article, we focus on the problem of identifying negated bio-events, given gold standard event annotations. Results We have conducted a detailed analysis of three open access bio-event corpora containing negation information (i.e., GENIA Event, BioInfer and BioNLP’09 ST), and have identified the main types of negated bio-events. We have analysed the key aspects of a machine learning solution to the problem of detecting negated events, including selection of negation cues, feature engineering and the choice of learning algorithm. Combining the best solutions for each aspect of the problem, we propose a novel framework for the identification of negated bio-events. We have evaluated our system on each of the three open access corpora mentioned above. The performance of the system significantly surpasses the best results previously reported on the BioNLP’09 ST corpus, and achieves even better results on the GENIA Event and BioInfer corpora, both of which contain more varied and complex events. Conclusions Recently, in the field of biomedical text mining, the development and enhancement of event-based systems has received significant interest. The ability to identify negated events is a key performance element for these systems. We have conducted the first detailed study on the analysis and identification of negated bio-events. Our proposed framework can be integrated with state-of-the-art event extraction systems. The

Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers.

Science.gov (United States)

Taïbi, Khaled; Del Campo, Antonio D; Vilagrosa, Alberto; Bellés, José M; López-Gresa, María Pilar; Pla, Davinia; Calvete, Juan J; López-Nicolás, José M; Mulet, José M

2017-01-01

Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis . Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas.

Drought Tolerance in Pinus halepensis Seed Sources As Identified by Distinctive Physiological and Molecular Markers

Directory of Open Access Journals (Sweden)

Khaled Taïbi

2017-07-01

Full Text Available Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis. Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas.

Computational exploration of single-protein mechanics by steered molecular dynamics

Energy Technology Data Exchange (ETDEWEB)

Sotomayor, Marcos [Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio (United States)

2015-12-31

Hair cell mechanotransduction happens in tens of microseconds, involves forces of a few picoNewtons, and is mediated by nanometer-scale molecular conformational changes. As proteins involved in this process become identified and their high resolution structures become available, multiple tools are being used to explore their “single-molecule responses” to force. Optical tweezers and atomic force microscopy offer exquisite force and extension resolution, but cannot reach the high loading rates expected for high frequency auditory stimuli. Molecular dynamics (MD) simulations can reach these fast time scales, and also provide a unique view of the molecular events underlying protein mechanics, but its predictions must be experimentally verified. Thus a combination of simulations and experiments might be appropriate to study the molecular mechanics of hearing. Here I review the basics of MD simulations and the different methods used to apply force and study protein mechanics in silico. Simulations of tip link proteins are used to illustrate the advantages and limitations of this method.

A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure.

Science.gov (United States)

Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

2016-05-17

Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

Science.gov (United States)

Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

2016-05-01

Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

The AFFORD clinical decision aid to identify emergency department patients with atrial fibrillation at low risk for 30-day adverse events.

Science.gov (United States)

Barrett, Tyler W; Storrow, Alan B; Jenkins, Cathy A; Abraham, Robert L; Liu, Dandan; Miller, Karen F; Moser, Kelly M; Russ, Stephan; Roden, Dan M; Harrell, Frank E; Darbar, Dawood

2015-03-15

There is wide variation in the management of patients with atrial fibrillation (AF) in the emergency department (ED). We aimed to derive and internally validate the first prospective, ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events. We performed a prospective cohort study at a university-affiliated tertiary-care ED. Patients were enrolled from June 9, 2010, to February 28, 2013, and followed for 30 days. We enrolled a convenience sample of patients in ED presenting with symptomatic AF. Candidate predictors were based on ED data available in the first 2 hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We used an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation. Of 497 patients enrolled, stroke and AF-related death occurred in 13 (3%) and 4 (aid included the following: age, triage vitals (systolic blood pressure, temperature, respiratory rate, oxygen saturation, supplemental oxygen requirement), medical history (heart failure, home sotalol use, previous percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms), and ED data (2 hours heart rate, chest radiograph results, hemoglobin, creatinine, and brain natriuretic peptide). The decision aid's c-statistic in predicting any 30-day adverse event was 0.7 (95% confidence interval 0.65, 0.76). In conclusion, in patients with AF in the ED, Atrial Fibrillation and Flutter Outcome Risk Determination provides the first evidence-based decision aid for identifying patients who are at low risk for 30-day adverse events and candidates for safe discharge. Copyright © 2015 Elsevier Inc. All rights reserved.

An Overview of Biomarkers and Molecular Signatures in HCC

Energy Technology Data Exchange (ETDEWEB)

Yim, Seon-Hee [Integrated Research Center for Genome Polymorphism, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701 (Korea, Republic of); Chung, Yeun-Jun, E-mail: yejun@catholic.ac.kr [Integrated Research Center for Genome Polymorphism, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701 (Korea, Republic of); Department of Microbiology, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701 (Korea, Republic of)

2010-05-07

Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. Although most HCCs seem to originate from the accumulation of genetic abnormalities induced by various risk factors, underlying mechanisms of hepatocarcinogenesis remain unclear. Long-term survival of HCC patients is also poor, partly due to HCC recurrence. Although serum alpha-fetoprotein (AFP) level is a useful marker for the detection and monitoring of HCC, AFP levels may remain normal in the patients even with advanced HCC. To identify useful biomarkers for HCC, many studies have been conducted on molecular events such as genetic and epigenetic alterations, and gene expression. This review summarizes recent studies of potential molecular markers for diagnosis and monitoring metastasis or recurrence of HCC.

Alternative splicing enriched cDNA libraries identify breast cancer-associated transcripts

Science.gov (United States)

2010-01-01

Background Alternative splicing (AS) is a central mechanism in the generation of genomic complexity and is a major contributor to transcriptome and proteome diversity. Alterations of the splicing process can lead to deregulation of crucial cellular processes and have been associated with a large spectrum of human diseases. Cancer-associated transcripts are potential molecular markers and may contribute to the development of more accurate diagnostic and prognostic methods and also serve as therapeutic targets. Alternative splicing-enriched cDNA libraries have been used to explore the variability generated by alternative splicing. In this study, by combining the use of trapping heteroduplexes and RNA amplification, we developed a powerful approach that enables transcriptome-wide exploration of the AS repertoire for identifying AS variants associated with breast tumor cells modulated by ERBB2 (HER-2/neu) oncogene expression. Results The human breast cell line (C5.2) and a pool of 5 ERBB2 over-expressing breast tumor samples were used independently for the construction of two AS-enriched libraries. In total, 2,048 partial cDNA sequences were obtained, revealing 214 alternative splicing sequence-enriched tags (ASSETs). A subset with 79 multiple exon ASSETs was compared to public databases and reported 138 different AS events. A high success rate of RT-PCR validation (94.5%) was obtained, and 2 novel AS events were identified. The influence of ERBB2-mediated expression on AS regulation was evaluated by capillary electrophoresis and probe-ligation approaches in two mammary cell lines (Hb4a and C5.2) expressing different levels of ERBB2. The relative expression balance between AS variants from 3 genes was differentially modulated by ERBB2 in this model system. Conclusions In this study, we presented a method for exploring AS from any RNA source in a transcriptome-wide format, which can be directly easily adapted to next generation sequencers. We identified AS transcripts

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways.

Science.gov (United States)

Michel, L; Reygagne, P; Benech, P; Jean-Louis, F; Scalvino, S; Ly Ka So, S; Hamidou, Z; Bianovici, S; Pouch, J; Ducos, B; Bonnet, M; Bensussan, A; Patatian, A; Lati, E; Wdzieczak-Bakala, J; Choulot, J-C; Loing, E; Hocquaux, M

2017-11-01

Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. To identify biomarkers associated with AGA. Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers. This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/β-catenin and bone morphogenic protein/transforming growth factor-β signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss. This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches. © 2017 British Association of Dermatologists.

Molecular genetics of craniosynostosis

Science.gov (United States)

Caterine; Auerkari, Elza Ibrahim

2018-03-01

Tight regulation process and complex interplay occur along the osteogenic interfaces of the cranial sutures in normal growth and development of the skull. Cranial sutures serve as sites of bone growth while maintaining a state of patency to accommodate the developing brain. Cranial sutures are fibro-cellular structures that separate the rigid plates of the skull bones. Premature fusion of one or more cranial sutures leads to a condition known as craniosynostosis. Craniosynostosis is one of the most common craniofacial anomalies with a prevalence of 1 in 2,500 newborns. Several genes have been identified in the pathogenesis of craniosynostosis. Molecular signaling events and the intracellular signal transduction pathways implicated in the suture pathobiology will provide a useful approach for therapeutic targeting.

Molecular marker to identify radiolarian species -toward establishment of paleo-environmental proxy-

Science.gov (United States)

Ishitani, Y.

2017-12-01

Marine fossilized unicellular plankton are known to have many genetically divergent species (biological species) in the single morphological species and these biological species show the species-specific environments much more precisely than that of morphological species. Among these plankton, Radiolaria are one of the best candidates for time- and environmental-indicators in the modern and past oceans, because radiolarians are the only group which represent entire water column from shallow to deep waters. However, the ecology and evolution of radiolarian were traditionally studied in paleontology and paleoceanography by morphological species. Even Radiolaria has a huge potential for novel proxy of wide and deep environments, there is no criterion to identify the biological species. The motivation for this study is setting the quantitative delimitation to establish the biological species of radiolarians based on molecular data, for leading the future ecological and paleo-environmental study. Identification of the biological species by ribosomal DNA sequences are mainly based on two ways: one is the evolutionary distance of the small subunit (SSU) rDNA, the internal transcribed spacer region of ribosomal DNA (ITS1 and 2), and the large subunit (LSU) rDNA; and the other is the secondary structure of ITS2. In the present study, all four possible genetic markers (SSU, ITS1, ITS2, and LSU rDNA) were amplified from 232 individuals of five radiolarian morphological species and applied to examine the evolutionary distance and secondary structure of rDNA. Comprehensive survey clearly shows that evolutionary distance of ITS1 rDNA and the secondary structure of ITS2 is good to identify the species. Notably, evolutionary distance of ITS1 rDNA is possible to set the common delimitation to identify the biological species, as 0.225 substitution per site. The results show that the ITS1 and ITS 2 rDNA could be the criterion for radiolarian species identification.

Incorporation of unique molecular identifiers in TruSeq adapters improves the accuracy of quantitative sequencing.

Science.gov (United States)

Hong, Jungeui; Gresham, David

2017-11-01

Quantitative analysis of next-generation sequencing (NGS) data requires discriminating duplicate reads generated by PCR from identical molecules that are of unique origin. Typically, PCR duplicates are identified as sequence reads that align to the same genomic coordinates using reference-based alignment. However, identical molecules can be independently generated during library preparation. Misidentification of these molecules as PCR duplicates can introduce unforeseen biases during analyses. Here, we developed a cost-effective sequencing adapter design by modifying Illumina TruSeq adapters to incorporate a unique molecular identifier (UMI) while maintaining the capacity to undertake multiplexed, single-index sequencing. Incorporation of UMIs into TruSeq adapters (TrUMIseq adapters) enables identification of bona fide PCR duplicates as identically mapped reads with identical UMIs. Using TrUMIseq adapters, we show that accurate removal of PCR duplicates results in improved accuracy of both allele frequency (AF) estimation in heterogeneous populations using DNA sequencing and gene expression quantification using RNA-Seq.

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

Using Remote Sensing and High-Resolution Digital Elevation Models to Identify Potential Erosional Hotspots Along River Channels During High Discharge Storm Events

Science.gov (United States)

Orland, E. D.; Amidon, W. H.

2017-12-01

As global warming intensifies, large precipitation events and associated floods are becoming increasingly common. Channel adjustments during floods can occur by both erosion and deposition of sediment, often damaging infrastructure in the process. There is thus a need for predictive models that can help managers identify river reaches that are most prone to adjustment during storms. Because rivers in post-glacial landscapes often flow over a mixture of bedrock and alluvial substrates, the identification of bedrock vs. alluvial channel reaches is an important first step in predicting vulnerability to channel adjustment during flood events, especially because bedrock channels are unlikely to adjust significantly, even during floods. This study develops a semi-automated approach to predicting channel substrate using a high-resolution LiDAR-derived digital elevation model (DEM). The study area is the Middlebury River in Middlebury, VT-a well-studied watershed with a wide variety of channel substrates, including reaches with documented channel adjustments during recent flooding events. Multiple metrics were considered for reference—such as channel width and drainage area—but the study utilized channel slope as a key parameter for identifying morphological variations within the Middlebury River. Using data extracted from the DEM, a power law was fit to selected slope and drainage area values for each branch in order to model idealized slope-drainage area relationships, which were then compared with measured slope-drainage area relationships. Differences in measured slope minus predicted slope (called delta-slope) are shown to help predict river channel substrate. Compared with field observations, higher delta-slope values correlate with more stable, boulder rich channels or bedrock gorges; conversely the lowest delta-slope values correlate with flat, sediment rich alluvial channels. The delta-slope metric thus serves as a reliable first-order predictor of channel

Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

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Victor M. Bii

2016-10-01

Full Text Available Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types.

Identifying treatment effect heterogeneity in clinical trials using subpopulations of events: STEPP.

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Lazar, Ann A; Bonetti, Marco; Cole, Bernard F; Yip, Wai-Ki; Gelber, Richard D

2016-04-01

Investigators conducting randomized clinical trials often explore treatment effect heterogeneity to assess whether treatment efficacy varies according to patient characteristics. Identifying heterogeneity is central to making informed personalized healthcare decisions. Treatment effect heterogeneity can be investigated using subpopulation treatment effect pattern plot (STEPP), a non-parametric graphical approach that constructs overlapping patient subpopulations with varying values of a characteristic. Procedures for statistical testing using subpopulation treatment effect pattern plot when the endpoint of interest is survival remain an area of active investigation. A STEPP analysis was used to explore patterns of absolute and relative treatment effects for varying levels of a breast cancer biomarker, Ki-67, in the phase III Breast International Group 1-98 randomized clinical trial, comparing letrozole to tamoxifen as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer. Absolute treatment effects were measured by differences in 4-year cumulative incidence of breast cancer recurrence, while relative effects were measured by the subdistribution hazard ratio in the presence of competing risks using O-E (observed-minus-expected) methodology, an intuitive non-parametric method. While estimation of hazard ratio values based on O-E methodology has been shown, a similar development for the subdistribution hazard ratio has not. Furthermore, we observed that the subpopulation treatment effect pattern plot analysis may not produce results, even with 100 patients within each subpopulation. After further investigation through simulation studies, we observed inflation of the type I error rate of the traditional test statistic and sometimes singular variance-covariance matrix estimates that may lead to results not being produced. This is due to the lack of sufficient number of events within the subpopulations, which we refer to as instability of

Rational approach to identify newer caspase-1 inhibitors using pharmacophore based virtual screening, docking and molecular dynamic simulation studies.

Science.gov (United States)

Patel, Shivani; Modi, Palmi; Chhabria, Mahesh

2018-05-01

Caspase-1 is a key endoprotease responsible for the post-translational processing of pro-inflammatory cytokines IL-1β, 18 & 33. Excessive secretion of IL-1β leads to numerous inflammatory and autoimmune diseases. Thus caspase-1 inhibition would be considered as an important therapeutic strategy for development of newer anti-inflammatory agents. Here we have employed an integrated virtual screening by combining pharmacophore mapping and docking to identify small molecules as caspase-1 inhibitors. The ligand based 3D pharmacophore model was generated having the essential structural features of (HBA, HY & RA) using a data set of 27 compounds. A validated pharmacophore hypothesis (Hypo 1) was used to screen ZINC and Minimaybridge chemical databases. The retrieved virtual hits were filtered by ADMET properties and molecular docking analysis. Subsequently, the cross-docking study was also carried out using crystal structure of caspase-1, 3, 7 and 8 to identify the key residual interaction for specific caspase-1 inhibition. Finally, the best mapped and top scored (ZINC00885612, ZINC72003647, BTB04175 and BTB04410) molecules were subjected to molecular dynamics simulation for accessing the dynamic structure of protein after ligand binding. This study identifies the most promising hits, which can be leads for the development of novel caspase-1 inhibitors as anti-inflammatory agents. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of satellite imagery to identify vegetation cover changes following the Waldo Canyon Fire event, Colorado, 2012-2013

Science.gov (United States)

Cole, Christopher J.; Friesen, Beverly A.; Wilson, Earl M.

2014-01-01

The Waldo Canyon Fire of 2012 was one of the most destructive wildfire events in Colorado history. The fire burned a total of 18,247 acres, claimed 2 lives, and destroyed 347 homes. The Waldo Canyon Fire continues to pose challenges to nearby communities. In a preliminary emergency assessment conducted in 2012, the U.S. Geological Survey (USGS) concluded that drainage basins within and near the area affected by the Waldo Canyon Fire pose a risk for future debris flow events. Rainfall over burned, formerly vegetated surfaces resulted in multiple flood and debris flow events that affected the cities of Colorado Springs and Manitou Springs in 2013. One fatality resulted from a mudslide near Manitou Springs in August 2013. Federal, State, and local governments continue to monitor these hazards and other post-fire effects, along with the region’s ecological recovery. At the request of the Colorado Springs Office of Emergency Management, the USGS Special Applications Science Center developed a geospatial product to identify vegetation cover changes following the 2012 Waldo Canyon Fire event. Vegetation cover was derived from July 2012 WorldView-2 and September 2013 QuickBird multispectral imagery at a spatial resolution of two meters. The 2012 image was collected after the fire had reached its maximum extent. Per-pixel increases and decreases in vegetation cover were identified by measuring spectral changes that occurred between the 2012 and 2013 image dates. A Normalized Difference Vegetation Index (NDVI), and Green-Near Infrared Index (GRNIR) were computed from each image. These spectral indices are commonly used to characterize vegetation cover and health condition, due to their sensitivity to detect foliar chlorophyll content. Vector polygons identifying surface-cover feature boundaries were derived from the 2013 imagery using image segmentation software. This geographic software groups similar image pixels into vector objects based upon their spatial and spectral

Epigenetics and Shared Molecular Processes in the Regeneration of Complex Structures

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Labib Rouhana

2016-01-01

Full Text Available The ability to regenerate complex structures is broadly represented in both plant and animal kingdoms. Although regenerative abilities vary significantly amongst metazoans, cumulative studies have identified cellular events that are broadly observed during regenerative events. For example, structural damage is recognized and wound healing initiated upon injury, which is followed by programmed cell death in the vicinity of damaged tissue and a burst in proliferation of progenitor cells. Sustained proliferation and localization of progenitor cells to site of injury give rise to an assembly of differentiating cells known as the regeneration blastema, which fosters the development of new tissue. Finally, preexisting tissue rearranges and integrates with newly differentiated cells to restore proportionality and function. While heterogeneity exists in the basic processes displayed during regenerative events in different species—most notably the cellular source contributing to formation of new tissue—activation of conserved molecular pathways is imperative for proper regulation of cells during regeneration. Perhaps the most fundamental of such molecular processes entails chromatin rearrangements, which prime large changes in gene expression required for differentiation and/or dedifferentiation of progenitor cells. This review provides an overview of known contributions to regenerative processes by noncoding RNAs and chromatin-modifying enzymes involved in epigenetic regulation.

PyRETIS: A well-done, medium-sized python library for rare events.

Science.gov (United States)

Lervik, Anders; Riccardi, Enrico; van Erp, Titus S

2017-10-30

Transition path sampling techniques are becoming common approaches in the study of rare events at the molecular scale. More efficient methods, such as transition interface sampling (TIS) and replica exchange transition interface sampling (RETIS), allow the investigation of rare events, for example, chemical reactions and structural/morphological transitions, in a reasonable computational time. Here, we present PyRETIS, a Python library for performing TIS and RETIS simulations. PyRETIS directs molecular dynamics (MD) simulations in order to sample rare events with unbiased dynamics. PyRETIS is designed to be easily interfaced with any molecular simulation package and in the present release, it has been interfaced with GROMACS and CP2K, for classical and ab initio MD simulations, respectively. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.

Tiered High-Throughput Screening Approach to Identify ...

Science.gov (United States)

High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the US EPA ToxCast screening assay portfolio. To fill one critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast Phase I and II chemical libraries, comprised of 1,074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single concentration screen were retested in concentration-response. Due to high false positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed two additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using

Molecular events associated with increased regenerative capacity of the goldfish retinal ganglion cells following X-irradiation: decreased level of axonal growth inhibitors

International Nuclear Information System (INIS)

Rachailovich, I.; Schwartz, M.

1984-01-01

In our previous work we established conditions to study the contribution of non-neuronal cells to the process of goldfish optic nerve regeneration. This issue has been studied successfully by adapting the use of X-irradiation to manipulate division of non-neuronal cells associated with the injured nerve. The regenerative capacity of the goldfish retinal ganglion cells was determined subsequent to the X-ray treatment. The authors present an analysis of the molecular events associated with regeneration and enhanced regenerative capacity which follows X-irradiation. (Auth.)

Molecular events associated with increased regenerative capacity of the goldfish retinal ganglion cells following X-irradiation: decreased level of axonal growth inhibitors

Energy Technology Data Exchange (ETDEWEB)

Rachailovich, I.; Schwartz, M. (Weizmann Inst. of Science, Rehovot (Israel). Dept. of Neurobiology)

1984-07-23

In our previous work we established conditions to study the contribution of non-neuronal cells to the process of goldfish optic nerve regeneration. This issue has been studied successfully by adapting the use of X-irradiation to manipulate division of non-neuronal cells associated with the injured nerve. The regenerative capacity of the goldfish retinal ganglion cells was determined subsequent to the X-ray treatment. The authors present an analysis of the molecular events associated with regeneration and enhanced regenerative capacity which follows X-irradiation.

Molecular analysis of expansion, differentiation, and growth factor treatment of human chondrocytes identifies differentiation markers and growth-related genes.

Science.gov (United States)

Benz, Karin; Breit, Stephen; Lukoschek, Martin; Mau, Hans; Richter, Wiltrud

2002-04-26

This study is intended to optimise expansion and differentiation of cultured human chondrocytes by growth factor application and to identify molecular markers to monitor their differentiation state. We dissected the molecular consequences of matrix release, monolayer, and 3D-alginate culture, growth factor optimised expansion, and re-differentiation protocols by gene expression analysis. Among 19 common cartilage molecules assessed by cDNA array, six proved best to monitor differentiation. Instant down-regulation at release of cells from the matrix was strongest for COL 2A1, fibromodulin, and PRELP while LUM, CHI3L1, and CHI3L2 were expansion-related. Both gene sets reflected the physiologic effects of the most potent growth-inducing (PDGF-BB) and proteoglycan-inducing (BMP-4) factors. Only CRTAC1 expression correlated with 2D/3D switches while the molecular phenotype of native chondrocytes was not restored. The markers and optimised protocols we suggest can help to improve cell therapy of cartilage defects and chondrocyte differentiation from stem cell sources.

Duodenoscope-Related Outbreak of a Carbapenem-Resistant Klebsiella pneumoniae Identified Using Advanced Molecular Diagnostics.

Science.gov (United States)

Humphries, Romney M; Yang, Shuan; Kim, Stephen; Muthusamy, Venkatara Raman; Russell, Dana; Trout, Alisa M; Zaroda, Teresa; Cheng, Quen J; Aldrovandi, Grace; Uslan, Daniel Zachary; Hemarajata, Peera; Rubin, Zachary Aaron

2017-10-01

Carbapenem-resistant Klebsiella pneumoniae infections are increasingly prevalent in North American hospitals. We describe an outbreak of carbapenem-resistant K. pneumoniae containing the blaOXA-232 gene transmitted by contaminated duodenoscopes during endoscopic retrograde cholangiopancreatography (ERCP) procedures. An outbreak investigation was performed when 9 patients with blaOXA-232 carbapenem-resistant K. pneumoniae infections were identified at a tertiary care hospital. The investigation included 2 case-control studies, review of duodenoscope reprocessing procedures, and culture of devices. Carbapenem-resistant Enterobacteriacieae (CRE) isolates were evaluated with polymerase chain reaction analysis for carbapenemase genes, and isolates with the blaOXA-232 gene were subjected to whole-genome sequencing and chromosome single-nucleotide polymorphism analysis. On recognition of ERCP as a key risk factor for infection, targeted patient notification and CRE screening cultures were performed. Molecular testing ultimately identified 17 patients with blaOxa-232 carbapenem-resistant K. pneumoniae isolates, including 9 with infections, 7 asymptomatic carriers who had undergone ERCP, and 1 additional patient who had been hospitalized in India and was probably the initial carrier. Two case-control studies established a point-source outbreak associated with 2 specific duodenoscopes. A field investigation of the use, reprocessing, and storage of deuodenoscopes did not identify deviations from US Food and Drug Administration or manufacturer recommendations for reprocessing. This outbreak demonstrated the previously underappreciated potential for duodenoscopes to transmit disease, even after undergoing high-level disinfection according to manufacturers' guidelines.

Reliable Approximation of Long Relaxation Timescales in Molecular Dynamics

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Wei Zhang

2017-07-01

Full Text Available Many interesting rare events in molecular systems, like ligand association, protein folding or conformational changes, occur on timescales that often are not accessible by direct numerical simulation. Therefore, rare event approximation approaches like interface sampling, Markov state model building, or advanced reaction coordinate-based free energy estimation have attracted huge attention recently. In this article we analyze the reliability of such approaches. How precise is an estimate of long relaxation timescales of molecular systems resulting from various forms of rare event approximation methods? Our results give a theoretical answer to this question by relating it with the transfer operator approach to molecular dynamics. By doing so we also allow for understanding deep connections between the different approaches.

Parameter trajectory analysis to identify treatment effects of pharmacological interventions.

Directory of Open Access Journals (Sweden)

Christian A Tiemann

Full Text Available The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT, to analyze the long-term effects of a pharmacological intervention. A concept of time-dependent evolution of model parameters is introduced to study the dynamics of molecular adaptations. The progression of these adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition between experimental data obtained during different stages of the treatment. The trajectories provide insight in the affected underlying biological systems and identify the molecular events that should be studied in more detail to unravel the mechanistic basis of treatment outcome. Modulating effects caused by interactions with the proteome and transcriptome levels, which are often less well understood, can be captured by the time-dependent descriptions of the parameters. ADAPT was employed to identify metabolic adaptations induced upon pharmacological activation of the liver X receptor (LXR, a potential drug target to treat or prevent atherosclerosis. The trajectories were investigated to study the cascade of adaptations. This provided a counter-intuitive insight concerning the function of scavenger receptor class B1 (SR-B1, a receptor that facilitates the hepatic uptake of cholesterol. Although activation of LXR promotes cholesterol efflux and -excretion, our computational analysis showed that the hepatic capacity to clear cholesterol was reduced upon prolonged treatment. This prediction was confirmed experimentally by immunoblotting measurements of SR-B1

LUMINOSITY FUNCTIONS OF SPITZER-IDENTIFIED PROTOSTARS IN NINE NEARBY MOLECULAR CLOUDS

Energy Technology Data Exchange (ETDEWEB)

Kryukova, E.; Megeath, S. T.; Allen, T. S. [Department of Physics and Astronomy, University of Toledo, Toledo, OH (United States); Gutermuth, R. A. [Department of Astronomy, University of Massachusetts, Amherst, MA (United States); Pipher, J. [Department of Physics and Astronomy, University of Rochester, Rochester, NY (United States); Allen, L. E. [National Optical Astronomy Observatories, Tucson, AZ (United States); Myers, P. C. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA (United States); Muzerolle, J. [Space Telescope Science Institute, Baltimore, MD (United States)

2012-08-15

We identify protostars in Spitzer surveys of nine star-forming (SF) molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. These clouds encompass a variety of SF environments, including both low-mass and high-mass SF regions, as well as dense clusters and regions of sparsely distributed star formation. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine near- and mid-infrared photometry from the Two Micron All Sky Survey and Spitzer to create 1-24 {mu}m spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities, we derive a relationship between bolometric luminosity, mid-IR luminosity (integrated from 1-24 {mu}m), and SED slope. Estimations of the bolometric luminosities for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high-mass SF clouds (Orion, Mon R2, and Cep OB3) peak near 1 L{sub Sun} and show a tail extending toward luminosities above 100 L{sub Sun }. The luminosity functions of the low-mass SF clouds (Serpens, Perseus, Ophiuchus, Taurus, Lupus, and Chamaeleon) do not exhibit a common peak, however the combined luminosity function of these regions peaks below 1 L{sub Sun }. Finally, we examine the luminosity functions as a function of the local surface density of young stellar objects. In the Orion molecular clouds, we find a significant difference between the luminosity functions of protostars in regions of high and low stellar density, the former of which is biased toward more luminous sources. This may be the result of primordial mass segregation, although this interpretation is not unique. We compare our luminosity

LUMINOSITY FUNCTIONS OF SPITZER-IDENTIFIED PROTOSTARS IN NINE NEARBY MOLECULAR CLOUDS

International Nuclear Information System (INIS)

Kryukova, E.; Megeath, S. T.; Allen, T. S.; Gutermuth, R. A.; Pipher, J.; Allen, L. E.; Myers, P. C.; Muzerolle, J.

2012-01-01

We identify protostars in Spitzer surveys of nine star-forming (SF) molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. These clouds encompass a variety of SF environments, including both low-mass and high-mass SF regions, as well as dense clusters and regions of sparsely distributed star formation. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine near- and mid-infrared photometry from the Two Micron All Sky Survey and Spitzer to create 1-24 μm spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities, we derive a relationship between bolometric luminosity, mid-IR luminosity (integrated from 1-24 μm), and SED slope. Estimations of the bolometric luminosities for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high-mass SF clouds (Orion, Mon R2, and Cep OB3) peak near 1 L ☉ and show a tail extending toward luminosities above 100 L ☉ . The luminosity functions of the low-mass SF clouds (Serpens, Perseus, Ophiuchus, Taurus, Lupus, and Chamaeleon) do not exhibit a common peak, however the combined luminosity function of these regions peaks below 1 L ☉ . Finally, we examine the luminosity functions as a function of the local surface density of young stellar objects. In the Orion molecular clouds, we find a significant difference between the luminosity functions of protostars in regions of high and low stellar density, the former of which is biased toward more luminous sources. This may be the result of primordial mass segregation, although this interpretation is not unique. We compare our luminosity functions to those

Gene expression analysis to identify molecular correlates of pre- and post-conditioning derived neuroprotection.

Science.gov (United States)

Prasad, Shiv S; Russell, Marsha; Nowakowska, Margeryta; Williams, Andrew; Yauk, Carole

2012-06-01

Mild ischaemic exposures before or after severe injurious ischaemia that elicit neuroprotective responses are referred to as preconditioning and post-conditioning. The corresponding molecular mechanisms of neuroprotection are not completely understood. Identification of the genes and associated pathways of corresponding neuroprotection would provide insight into neuronal survival, potential therapeutic approaches and assessments of therapies for stroke. The objectives of this study were to use global gene expression approach to infer the molecular mechanisms in pre- and post-conditioning-derived neuroprotection in cortical neurons following oxygen and glucose deprivation (OGD) in vitro and then to apply these findings to predict corresponding functional pathways. To this end, microarray analysis was applied to rat cortical neurons with or without the pre- and post-conditioning treatments at 3-h post-reperfusion, and differentially expressed transcripts were subjected to statistical, hierarchical clustering and pathway analyses. The expression patterns of 3,431 genes altered under all conditions of ischaemia (with and without pre- or post-conditioning). We identified 1,595 genes that were commonly regulated within both the pre- and post-conditioning treatments. Cluster analysis revealed that transcription profiles clustered tightly within controls, non-conditioned OGD and neuroprotected groups. Two clusters defining neuroprotective conditions associated with up- and downregulated genes were evident. The five most upregulated genes within the neuroprotective clusters were Tagln, Nes, Ptrf, Vim and Adamts9, and the five most downregulated genes were Slc7a3, Bex1, Brunol4, Nrxn3 and Cpne4. Pathway analysis revealed that the intracellular and second messenger signalling pathways in addition to cell death were predominantly associated with downregulated pre- and post-conditioning associated genes, suggesting that modulation of cell death and signal transduction pathways

Trending analysis of precursor events

International Nuclear Information System (INIS)

Watanabe, Norio

1998-01-01

The Accident Sequence Precursor (ASP) Program of United States Nuclear Regulatory Commission (U.S.NRC) identifies and categorizes operational events at nuclear power plants in terms of the potential for core damage. The ASP analysis has been performed on yearly basis and the results have been published in the annual reports. This paper describes the trends in initiating events and dominant sequences for 459 precursors identified in the ASP Program during the 1969-94 period and also discusses a comparison with dominant sequences predicted in the past Probabilistic Risk Assessment (PRA) studies. These trends were examined for three time periods, 1969-81, 1984-87 and 1988-94. Although the different models had been used in the ASP analyses for these three periods, the distribution of precursors by dominant sequences show similar trends to each other. For example, the sequences involving loss of both main and auxiliary feedwater were identified in many PWR events and those involving loss of both high and low coolant injection were found in many BWR events. Also, it was found that these dominant sequences were comparable to those determined to be dominant in the predictions by the past PRAs. As well, a list of the 459 precursors identified are provided in Appendix, indicating initiating event types, unavailable systems, dominant sequences, conditional core damage probabilities, and so on. (author)

Evidence for nucleosynthetic enrichment of the protosolar molecular cloud core by multiple supernova events

DEFF Research Database (Denmark)

Schiller, Martin; Paton, Chad; Bizzarro, Martin

2015-01-01

The presence of isotope heterogeneity of nucleosynthetic origin amongst meteorites and their components provides a record of the diverse stars that contributed matter to the protosolar molecular cloud core. Understanding how and when the solar system's nucleosynthetic heterogeneity was established...... and preserved within the solar protoplanetary disk is critical for unraveling the earliest formative stages of the solar system. Here, we report calcium and magnesium isotope measurements of primitive and differentiated meteorites as well as various types of refractory inclusions, including refractory...... and differentiated meteorites along with canonical and FUN-CAIs define correlated, mass-independent variations in 43Ca, 46Ca and 48Ca. Moreover, sequential dissolution experiments of the Ivuna carbonaceous chondrite aimed at identifying the nature and number of presolar carriers of isotope anomalies within primitive...

Event-Based Conceptual Modeling

DEFF Research Database (Denmark)

Bækgaard, Lars

2009-01-01

The purpose of the paper is to obtain insight into and provide practical advice for event-based conceptual modeling. We analyze a set of event concepts and use the results to formulate a conceptual event model that is used to identify guidelines for creation of dynamic process models and static...... information models. We characterize events as short-duration processes that have participants, consequences, and properties, and that may be modeled in terms of information structures. The conceptual event model is used to characterize a variety of event concepts and it is used to illustrate how events can...... be used to integrate dynamic modeling of processes and static modeling of information structures. The results are unique in the sense that no other general event concept has been used to unify a similar broad variety of seemingly incompatible event concepts. The general event concept can be used...

Serious adverse events with infliximab: analysis of spontaneously reported adverse events.

Science.gov (United States)

Hansen, Richard A; Gartlehner, Gerald; Powell, Gregory E; Sandler, Robert S

2007-06-01

Serious adverse events such as bowel obstruction, heart failure, infection, lymphoma, and neuropathy have been reported with infliximab. The aims of this study were to explore adverse event signals with infliximab by using a long period of post-marketing experience, stratifying by indication. The relative reporting of infliximab adverse events to the U.S. Food and Drug Administration (FDA) was assessed with the public release version of the adverse event reporting system (AERS) database from 1968 to third quarter 2005. On the basis of a systematic review of adverse events, Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to predefined categories of adverse events, including death, heart failure, hepatitis, infection, infusion reaction, lymphoma, myelosuppression, neuropathy, and obstruction. Disproportionality analysis was used to calculate the empiric Bayes geometric mean (EBGM) and corresponding 90% confidence intervals (EB05, EB95) for adverse event categories. Infliximab was identified as the suspect medication in 18,220 reports in the FDA AERS database. We identified a signal for lymphoma (EB05 = 6.9), neuropathy (EB05 = 3.8), infection (EB05 = 2.9), and bowel obstruction (EB05 = 2.8). The signal for granulomatous infections was stronger than the signal for non-granulomatous infections (EB05 = 12.6 and 2.4, respectively). The signals for bowel obstruction and infusion reaction were specific to patients with IBD; this suggests potential confounding by indication, especially for bowel obstruction. In light of this additional evidence of risk of lymphoma, neuropathy, and granulomatous infections, clinicians should stress this risk in the shared decision-making process.

Signal transduction by FcεRI: Analysis of the early molecular events

Directory of Open Access Journals (Sweden)

Henry Metzger

1999-01-01

Full Text Available We are analysing the initial molecular events stimulated by the high-affinity receptor for IgE, FcεRI. Earlier studies have shown that the first response when the receptor-bound IgE interacts with a multivalent antigen is a transphosphorylation of receptor tyrosines, induced by the approximation of two or more receptors by a constitutively associated src-family kinase (Lyn. The amount of weakly associated kinase regulates the intensity of the response. Several aspects are being analyzed: (i the sites on Lyn and the receptor that account for the constitutive interaction; (ii how the intrinsic affinity of a ligand for the receptor-bound IgE influences the responses; and (iii the mechanism(s by which low-affinity ligands can act as antagonists. In the latter studies, mast cell responses were followed by monitoring the phosphorylation of tyrosines on several proteins and secretion. At equivalent levels of receptor phosphorylation, a ligand with high affinity stimulated vigorous phosphorylation of downstream components, whereas a low-affinity ligand was unable to stimulate phosphorylation of the same components effectively. Cells stimulated with a mixture of high- and low-affinity ligands, under a protocol where simple displacement of one by the other was prevented, remarkably showed that excess low-affinity ligand inhibited the phosphorylation as well as degranulation by the high-affinity ligand. This antagonism results from a competition for the limiting amount of the constitutive initiating kinase. Related receptors that depend on recruitment of initiating kinases may be subject to similar regulatory mechanisms.

Je, a versatile suite to handle multiplexed NGS libraries with unique molecular identifiers.

Science.gov (United States)

Girardot, Charles; Scholtalbers, Jelle; Sauer, Sajoscha; Su, Shu-Yi; Furlong, Eileen E M

2016-10-08

The yield obtained from next generation sequencers has increased almost exponentially in recent years, making sample multiplexing common practice. While barcodes (known sequences of fixed length) primarily encode the sample identity of sequenced DNA fragments, barcodes made of random sequences (Unique Molecular Identifier or UMIs) are often used to distinguish between PCR duplicates and transcript abundance in, for example, single-cell RNA sequencing (scRNA-seq). In paired-end sequencing, different barcodes can be inserted at each fragment end to either increase the number of multiplexed samples in the library or to use one of the barcodes as UMI. Alternatively, UMIs can be combined with the sample barcodes into composite barcodes, or with standard Illumina® indexing. Subsequent analysis must take read duplicates and sample identity into account, by identifying UMIs. Existing tools do not support these complex barcoding configurations and custom code development is frequently required. Here, we present Je, a suite of tools that accommodates complex barcoding strategies, extracts UMIs and filters read duplicates taking UMIs into account. Using Je on publicly available scRNA-seq and iCLIP data containing UMIs, the number of unique reads increased by up to 36 %, compared to when UMIs are ignored. Je is implemented in JAVA and uses the Picard API. Code, executables and documentation are freely available at http://gbcs.embl.de/Je . Je can also be easily installed in Galaxy through the Galaxy toolshed.

Molecular events in the induction of murine tumors by ionizing radiation

International Nuclear Information System (INIS)

Andrews, K.L.

1993-01-01

A new method is presented to identify and clone novel transforming genes from radiation-induced tumors. It involves the creation of a cDNA expression library from radiation-induced tumors. The library is transfected into non-transformed cells, and the nude mouse tumorigenicity assay functionally defines the acquisition of a transformed phenotype. cDNA clones responsible for transformation are rescued by PCR amplification. This method is applicable to a variety of mammalian systems. The only requirement is a functional assay with which to measure the acquisition of an altered phenotype following transfection of a cDNA library. This method has identified a cDNA for the 16 kD subunit of v-H + -ATPase, which has been associated with cellular transformation. Two protocols were used to generate radiation-induced tumors. One experiment utilizing fractionated doses of ionizing radiation had a much greater tumor yield than the second protocol using a single dose of 11.25 Gy. To determine if the mechanism of gene activation is different in radiation- and chemically-induced tumors, the expression pattern of five tumor-associated genes was analyzed. The expression patterns of mals 1-4 were not significantly different. However, transin, a secreted protease, was overexpressed in radiation-induced papillomas and undetectable in chemically-induced papillomas. Transin degrades basement membrane proteins and may be involved in the progression of benign, encapsulated tumors to malignant, invasive squamous cell carcinomas. Isolation and characterization of genes with dominant transforming activity from radiation-induced tumors will provide information to bridge the gap between the initial ionizing radiation event and the subsequent development of malignant tumors. The function of these genes may also provide information about the development of human malignancies. An understanding the natural biology of cells will help elucidate the pathogenesis cancer and other diseases

Application of the RES methodology for identifying features, events and processes (FEPs) for near-field analysis of copper-steel canister

International Nuclear Information System (INIS)

Vieno, T.; Hautojaervi, A.; Raiko, H.; Ahonen, L.; Salo, J.P.

1994-12-01

Rock Engineering Systems (RES) is an approach to discover the important characteristics and interactions of a complex problem. Recently RES has been applied to identify features, events and processes (FEPs) for performance analysis of nuclear waste repositories. The RES methodology was applied to identify FEPs for the near-field analysis of the copper-steel canister for spent fuel disposal. The aims of the exercise were to learn and test the RES methodology and, secondly, to find out how much the results differ when RES is applied by two different groups on the same problem. A similar exercise was previously carried out by a SKB group. A total of 90 potentially significant FEPs were identified. The exercise showed that the RES methodology is a practicable tool to get a comprehensive and transparent picture of a complex problem. The approach is easy to learn and use. It reveals the important characteristics and interactions and organizes them in a format easy to understand. (9 refs., 5 figs., 3 tabs.)

The Role of Difficulty in Identifying and Describing Feelings in Non-Suicidal Self-Injury Behavior (NSSI): Associations With Perceived Attachment Quality, Stressful Life Events, and Suicidal Ideation.

Science.gov (United States)

Cerutti, Rita; Zuffianò, Antonio; Spensieri, Valentina

2018-01-01

Objective: Core alexithymic features, such as the difficulty in identifying and describing feelings, are associated with poor attachment styles and emotional trauma, which influence the capacity to regulate affect. Additionally, emotional regulation has been found to be the most commonly identified function associated with non-suicidal self-injury behavior (NSSI) in adolescents as they attempt to modulate strong emotions. However, few studies have examined the link between difficulty in identifying and describing feelings (core components of alexithymia), NSSI behaviors, quality of attachment, life stressors and suicidal ideation in healthy early adolescents. Consequently, this study aims to investigate these constructs and the relationship among them in a large non-clinical sample of adolescents. Methods: Seven hundred and nine middle school students (50.4% males), aged 10-15 years ( M = 12.6; SD = 1.06) were involved in this study. In order to investigate the variables considered in the study, the following measures were administered: the Deliberate Self-Harm Inventory exploring non-suicidal self-injurious behaviors; the Alexithymia Questionnaire for Children examining difficulty in identifying and describing feelings; the Inventory of Parent and Peer Attachment assessing the quality of parental and peer attachment; the Life Stressor Checklist-Revised outlining stressful/traumatic events and the Children's Depression Inventory evaluating suicidal ideation. Results: We found significantly positive relationships among difficulty in identifying and describing feelings, NSSI behaviors, stressful events, and suicidal ideation. Data indicated a significant negative association of difficulty in identifying and describing feelings with quality of attachment to parents and peers. Further findings highlighted that difficulty in identifying and describing feelings significantly mediated the effect of quality of attachment (parent and peer) on NSSI and suicidal ideation

Piecing together the puzzle: Improving event content coverage for real-time sub-event detection using adaptive microblog crawling.

Science.gov (United States)

Tokarchuk, Laurissa; Wang, Xinyue; Poslad, Stefan

2017-01-01

In an age when people are predisposed to report real-world events through their social media accounts, many researchers value the benefits of mining user generated content from social media. Compared with the traditional news media, social media services, such as Twitter, can provide more complete and timely information about the real-world events. However events are often like a puzzle and in order to solve the puzzle/understand the event, we must identify all the sub-events or pieces. Existing Twitter event monitoring systems for sub-event detection and summarization currently typically analyse events based on partial data as conventional data collection methodologies are unable to collect comprehensive event data. This results in existing systems often being unable to report sub-events in real-time and often in completely missing sub-events or pieces in the broader event puzzle. This paper proposes a Sub-event detection by real-TIme Microblog monitoring (STRIM) framework that leverages the temporal feature of an expanded set of news-worthy event content. In order to more comprehensively and accurately identify sub-events this framework first proposes the use of adaptive microblog crawling. Our adaptive microblog crawler is capable of increasing the coverage of events while minimizing the amount of non-relevant content. We then propose a stream division methodology that can be accomplished in real time so that the temporal features of the expanded event streams can be analysed by a burst detection algorithm. In the final steps of the framework, the content features are extracted from each divided stream and recombined to provide a final summarization of the sub-events. The proposed framework is evaluated against traditional event detection using event recall and event precision metrics. Results show that improving the quality and coverage of event contents contribute to better event detection by identifying additional valid sub-events. The novel combination of

Piecing together the puzzle: Improving event content coverage for real-time sub-event detection using adaptive microblog crawling.

Directory of Open Access Journals (Sweden)

Laurissa Tokarchuk

Full Text Available In an age when people are predisposed to report real-world events through their social media accounts, many researchers value the benefits of mining user generated content from social media. Compared with the traditional news media, social media services, such as Twitter, can provide more complete and timely information about the real-world events. However events are often like a puzzle and in order to solve the puzzle/understand the event, we must identify all the sub-events or pieces. Existing Twitter event monitoring systems for sub-event detection and summarization currently typically analyse events based on partial data as conventional data collection methodologies are unable to collect comprehensive event data. This results in existing systems often being unable to report sub-events in real-time and often in completely missing sub-events or pieces in the broader event puzzle. This paper proposes a Sub-event detection by real-TIme Microblog monitoring (STRIM framework that leverages the temporal feature of an expanded set of news-worthy event content. In order to more comprehensively and accurately identify sub-events this framework first proposes the use of adaptive microblog crawling. Our adaptive microblog crawler is capable of increasing the coverage of events while minimizing the amount of non-relevant content. We then propose a stream division methodology that can be accomplished in real time so that the temporal features of the expanded event streams can be analysed by a burst detection algorithm. In the final steps of the framework, the content features are extracted from each divided stream and recombined to provide a final summarization of the sub-events. The proposed framework is evaluated against traditional event detection using event recall and event precision metrics. Results show that improving the quality and coverage of event contents contribute to better event detection by identifying additional valid sub-events. The

Event-by-event particle multiplicity fluctuations in Pb-Pb collisions with ALICE

Energy Technology Data Exchange (ETDEWEB)

Arslandok, Mesut [Institut fuer Kernphysik, Goethe-Universitaet Frankfurt (Germany); Collaboration: ALICE-Collaboration

2014-07-01

The study of event-by-event fluctuations of identified hadrons may reveal the degrees of freedom of the strongly interacting mater created in heavy-ion collisions. Particle identification that is based on the measurement of the specific ionization energy loss dE/dx works well on a statistical basis, however, suffers from ambiguities when applied on the event-by-event level. A novel experimental technique called the ''Identity Method'' was recently proposed to overcome such limitations. The method follows a probabilistic approach using the inclusive dE/dx distributions measured in the ALICE TPC, and determines the moments of the multiplicity distributions by an unfolding procedure. In this contribution, the status of an event-by-event fluctuation analysis that applies the Identity Method to Pb-Pb data from ALICE is presented.

Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

Science.gov (United States)

Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

2014-01-01

Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

Identifying cognitive preferences for attractive female faces: an event-related potential experiment using a study-test paradigm.

Science.gov (United States)

Zhang, Yan; Kong, Fanchang; Chen, Hong; Jackson, Todd; Han, Li; Meng, Jing; Yang, Zhou; Gao, Jianguo; Najam ul Hasan, Abbasi

2011-11-01

In this experiment, sensitivity to female facial attractiveness was examined by comparing event-related potentials (ERPs) in response to attractive and unattractive female faces within a study-test paradigm. Fourteen heterosexual participants (age range 18-24 years, mean age 21.67 years) were required to judge 84 attractive and 84 unattractive face images as either "attractive" or "unattractive." They were then asked whether they had previously viewed each face in a recognition task in which 50% of the images were novel. Analyses indicated that attractive faces elicited more enhanced ERP amplitudes than did unattractive faces in judgment (N300 and P350-550 msec) and recognition (P160 and N250-400 msec and P400-700 msec) tasks on anterior locations. Moreover, longer reaction times and higher accuracy rate were observed in identifying attractive faces than unattractive faces. In sum, this research identified neural and behavioral bases related to cognitive preferences for judging and recognizing attractive female faces. Explanations for the results are that attractive female faces arouse more intense positive emotions in participants than do unattractive faces, and they also represent reproductive fitness and mating value from the evolutionary perspective. Copyright © 2011 Wiley-Liss, Inc.

Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma.

Science.gov (United States)

Weiser, Keith C; Liu, Bin; Hansen, Gwenn M; Skapura, Darlene; Hentges, Kathryn E; Yarlagadda, Sujatha; Morse Iii, Herbert C; Justice, Monica J

2007-10-01

AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFkappaB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision .

Molecular signatures associated with HCV-induced hepatocellular carcinoma and liver metastasis.

Directory of Open Access Journals (Sweden)

Valeria De Giorgi

Full Text Available Hepatocellular carcinomas (HCCs are a heterogeneous group of tumors that differ in risk factors and genetic alterations. In Italy, particularly Southern Italy, chronic hepatitis C virus (HCV infection represents the main cause of HCC. Using high-density oligoarrays, we identified consistent differences in gene-expression between HCC and normal liver tissue. Expression patterns in HCC were also readily distinguishable from those associated with liver metastases. To characterize molecular events relevant to hepatocarcinogenesis and identify biomarkers for early HCC detection, gene expression profiling of 71 liver biopsies from HCV-related primary HCC and corresponding HCV-positive non-HCC hepatic tissue, as well as gastrointestinal liver metastases paired with the apparently normal peri-tumoral liver tissue, were compared to 6 liver biopsies from healthy individuals. Characteristic gene signatures were identified when normal tissue was compared with HCV-related primary HCC, corresponding HCV-positive non-HCC as well as gastrointestinal liver metastases. Pathway analysis classified the cellular and biological functions of the genes differentially expressed as related to regulation of gene expression and post-translational modification in HCV-related primary HCC; cellular Growth and Proliferation, and Cell-To-Cell Signaling and Interaction in HCV-related non HCC samples; Cellular Growth and Proliferation and Cell Cycle in metastasis. Also characteristic gene signatures were identified of HCV-HCC progression for early HCC diagnosis.A diagnostic molecular signature complementing conventional pathologic assessment was identified.

Early molecular events involved in Pinus pinaster Ait. somatic embryo development under reduced water availability: transcriptomic and proteomic analyses.

Science.gov (United States)

Morel, Alexandre; Teyssier, Caroline; Trontin, Jean-François; Eliášová, Kateřina; Pešek, Bedřich; Beaufour, Martine; Morabito, Domenico; Boizot, Nathalie; Le Metté, Claire; Belal-Bessai, Leila; Reymond, Isabelle; Harvengt, Luc; Cadene, Martine; Corbineau, Françoise; Vágner, Martin; Label, Philippe; Lelu-Walter, Marie-Anne

2014-09-01

Maritime pine somatic embryos (SEs) require a reduction in water availability (high gellan gum concentration in the maturation medium) to reach the cotyledonary stage. This key switch, reported specifically for pine species, is not yet well understood. To facilitate the use of somatic embryogenesis for mass propagation of conifers, we need a better understanding of embryo development. Comparison of both transcriptome (Illumina RNA sequencing) and proteome [two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with mass spectrometry (MS) identification] of immature SEs, cultured on either high (9G) or low (4G) gellan gum concentration, was performed, together with analysis of water content, fresh and dry mass, endogenous abscisic acid (ABA; gas chromatography-MS), soluble sugars (high-pressure liquid chromatography), starch and confocal laser microscope observations. This multiscale, integrated analysis was used to unravel early molecular and physiological events involved in SE development. Under unfavorable conditions (4G), the glycolytic pathway was enhanced, possibly in relation to cell proliferation that may be antagonistic to SE development. Under favorable conditions (9G), SEs adapted to culture constraint by activating specific protective pathways, and ABA-mediated molecular and physiological responses promoting embryo development. Our results suggest that on 9G, germin-like protein and ubiquitin-protein ligase could be used as predictive markers of SE development, whereas protein phosphatase 2C could be a biomarker for culture adaptive responses. This is the first characterization of early molecular mechanisms involved in the development of pine SEs following an increase in gellan gum concentration in the maturation medium, and it is also the first report on somatic embryogenesis in conifers combining transcriptomic and proteomic datasets. © 2014 Scandinavian Plant Physiology Society.

Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

Science.gov (United States)

van Uitert, Miranda; Moerland, Perry D; Enquobahrie, Daniel A; Laivuori, Hannele; van der Post, Joris A M; Ris-Stalpers, Carrie; Afink, Gijs B

2015-01-01

Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

PRELIMINARY SELECTION OF MGR DESIGN BASIS EVENTS

International Nuclear Information System (INIS)

Kappes, J.A.

1999-01-01

The purpose of this analysis is to identify the preliminary design basis events (DBEs) for consideration in the design of the Monitored Geologic Repository (MGR). For external events and natural phenomena (e.g., earthquake), the objective is to identify those initiating events that the MGR will be designed to withstand. Design criteria will ensure that radiological release scenarios resulting from these initiating events are beyond design basis (i.e., have a scenario frequency less than once per million years). For internal (i.e., human-induced and random equipment failures) events, the objective is to identify credible event sequences that result in bounding radiological releases. These sequences will be used to establish the design basis criteria for MGR structures, systems, and components (SSCs) design basis criteria in order to prevent or mitigate radiological releases. The safety strategy presented in this analysis for preventing or mitigating DBEs is based on the preclosure safety strategy outlined in ''Strategy to Mitigate Preclosure Offsite Exposure'' (CRWMS M andO 1998f). DBE analysis is necessary to provide feedback and requirements to the design process, and also to demonstrate compliance with proposed 10 CFR 63 (Dyer 1999b) requirements. DBE analysis is also required to identify and classify the SSCs that are important to safety (ITS)

PET-based molecular imaging in neuroscience

International Nuclear Information System (INIS)

Jacobs, A.H.; Heiss, W.D.; Li, H.; Knoess, C.; Schaller, B.; Kracht, L.; Monfared, P.; Vollmar, S.; Bauer, B.; Wagner, R.; Graf, R.; Wienhard, K.; Winkeler, A.; Rueger, A.; Klein, M.; Hilker, R.; Galldiks, N.; Herholz, K.; Sobesky, J.

2003-01-01

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and ''phenotyping'' of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed. (orig.)

Life events and escape in conversion disorder.

Science.gov (United States)

Nicholson, T R; Aybek, S; Craig, T; Harris, T; Wojcik, W; David, A S; Kanaan, R A

2016-09-01

Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged. Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel 'escape' rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of 'secondary gain'. CD patients had significantly more severe life events and 'escape' events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients - significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56-13.70] and healthy controls (OR 5.81, 95% CI 1.86-18.2). In the same time period 53% of CD patients had at least one 'high escape' event - again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05-23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events. Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation.

Analysis for Human-related Events during the Overhaul

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Tae; Kim, Min Chull; Choi, Dong Won; Lee, Durk Hun [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2011-10-15

The event frequency due to human error is decreasing among 20 operating Nuclear Power Plants (NPPs) excluding the NPP (Shin-Kori unit-1) in the commissioning stage since 2008. However, the events due to human error during an overhaul (O/H) occur annually (see Table I). An analysis for human-related events during the O/H was performed. Similar problems were identified for each event from the analysis and also, organizational and safety cultural factors were also identified

Accident sequence precursor events with age-related contributors

Energy Technology Data Exchange (ETDEWEB)

Murphy, G.A.; Kohn, W.E.

1995-12-31

The Accident Sequence Precursor (ASP) Program at ORNL analyzed about 14.000 Licensee Event Reports (LERs) filed by US nuclear power plants 1987--1993. There were 193 events identified as precursors to potential severe core accident sequences. These are reported in G/CR-4674. Volumes 7 through 20. Under the NRC Nuclear Plant Aging Research program, the authors evaluated these events to determine the extent to which component aging played a role. Events were selected that involved age-related equipment degradation that initiated an event or contributed to an event sequence. For the 7-year period, ORNL identified 36 events that involved aging degradation as a contributor to an ASP event. Except for 1992, the percentage of age-related events within the total number of ASP events over the 7-year period ({approximately}19%) appears fairly consistent up to 1991. No correlation between plant ape and number of precursor events was found. A summary list of the age-related events is presented in the report.

Molecular profiling of appendiceal epithelial tumors using massively parallel sequencing to identify somatic mutations.

Science.gov (United States)

Liu, Xiaoying; Mody, Kabir; de Abreu, Francine B; Pipas, J Marc; Peterson, Jason D; Gallagher, Torrey L; Suriawinata, Arief A; Ripple, Gregory H; Hourdequin, Kathryn C; Smith, Kerrington D; Barth, Richard J; Colacchio, Thomas A; Tsapakos, Michael J; Zaki, Bassem I; Gardner, Timothy B; Gordon, Stuart R; Amos, Christopher I; Wells, Wendy A; Tsongalis, Gregory J

2014-07-01

Some epithelial neoplasms of the appendix, including low-grade appendiceal mucinous neoplasm and adenocarcinoma, can result in pseudomyxoma peritonei (PMP). Little is known about the mutational spectra of these tumor types and whether mutations may be of clinical significance with respect to therapeutic selection. In this study, we identified somatic mutations using the Ion Torrent AmpliSeq Cancer Hotspot Panel v2. Specimens consisted of 3 nonneoplastic retention cysts/mucocele, 15 low-grade mucinous neoplasms (LAMNs), 8 low-grade/well-differentiated mucinous adenocarcinomas with pseudomyxoma peritonei, and 12 adenocarcinomas with/without goblet cell/signet ring cell features. Barcoded libraries were prepared from up to 10 ng of extracted DNA and multiplexed on single 318 chips for sequencing. Data analysis was performed using Golden Helix SVS. Variants that remained after the analysis pipeline were individually interrogated using the Integrative Genomics Viewer. A single Janus kinase 3 (JAK3) mutation was detected in the mucocele group. Eight mutations were identified in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) genes among LAMN samples. Additional gene mutations were identified in the AKT1 (v-akt murine thymoma viral oncogene homolog 1), APC (adenomatous polyposis coli), JAK3, MET (met proto-oncogene), phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA), RB1 (retinoblastoma 1), STK11 (serine/threonine kinase 11), and tumor protein p53 (TP53) genes. Among the PMPs, 6 mutations were detected in the KRAS gene and also in the GNAS, TP53, and RB1 genes. Appendiceal cancers showed mutations in the APC, ATM (ataxia telangiectasia mutated), KRAS, IDH1 [isocitrate dehydrogenase 1 (NADP+)], NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog], PIK3CA, SMAD4 (SMAD family member 4), and TP53 genes. Our results suggest molecular heterogeneity among epithelial tumors of the appendix. Next generation sequencing efforts

Molecular Characterization of Macrophage-Biomaterial Interactions.

Science.gov (United States)

Moore, Laura Beth; Kyriakides, Themis R

2015-01-01

Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulation. In this review, we discuss the molecular events that contribute to macrophage activation and fusion with a focus on the role of the inflammasome, signaling pathways such as JAK/STAT and NF-κB, and the putative involvement of micro RNAs in the regulation of these processes.

Cardiovascular Molecular Imaging

International Nuclear Information System (INIS)

Lee, Kyung Han

2009-01-01

Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis. Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field

MelanomaDB: a Web Tool for Integrative Analysis of Melanoma Genomic Information to Identify Disease-Associated Molecular Pathways

Directory of Open Access Journals (Sweden)

Alexander Joseph Trevarton

2013-07-01

Full Text Available Despite on-going research, metastatic melanoma survival rates remain low and treatment options are limited. Researchers can now access a rapidly growing amount of molecular and clinical information about melanoma. This information is becoming difficult to assemble and interpret due to its dispersed nature, yet as it grows it becomes increasingly valuable for understanding melanoma. Integration of this information into a comprehensive resource to aid rational experimental design and patient stratification is needed. As an initial step in this direction, we have assembled a web-accessible melanoma database, MelanomaDB, which incorporates clinical and molecular data from publically available sources, which will be regularly updated as new information becomes available. This database allows complex links to be drawn between many different aspects of melanoma biology: genetic changes (e.g. mutations in individual melanomas revealed by DNA sequencing, associations between gene expression and patient survival, data concerning drug targets, biomarkers, druggability and clinical trials, as well as our own statistical analysis of relationships between molecular pathways and clinical parameters that have been produced using these data sets. The database is freely available at http://genesetdb.auckland.ac.nz/melanomadb/about.html . A subset of the information in the database can also be accessed through a freely available web application in the Illumina genomic cloud computing platform BaseSpace at http://www.biomatters.com/apps/melanoma-profiler-for-research . This illustrates dysregulation of specific signalling pathways, both across 310 exome-sequenced melanomas and in individual tumours and identifies novel features about the distribution of somatic variants in melanoma. We suggest that this database can provide a context in which to interpret the tumour molecular profiles of individual melanoma patients relative to biological information and available

Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

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Miranda van Uitert

Full Text Available Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite and protein-protein associations (STRING. This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome. The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300 and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

Development of a new marker system for identifying the complex members of the low-molecular-weight glutenin subunit gene family in bread wheat (Triticum aestivum L.).

Science.gov (United States)

Zhang, Xiaofei; Liu, Dongcheng; Yang, Wenlong; Liu, Kunfan; Sun, Jiazhu; Guo, Xiaoli; Li, Yiwen; Wang, Daowen; Ling, Hongqing; Zhang, Aimin

2011-05-01

Low-molecular-weight glutenin subunits (LMW-GSs) play an important role in determining the bread-making quality of bread wheat. However, LMW-GSs display high polymorphic protein complexes encoded by multiple genes, and elucidating the complex LMW-GS gene family in bread wheat remains challenging. In the present study, using conventional polymerase chain reaction (PCR) with conserved primers and high-resolution capillary electrophoresis, we developed a new molecular marker system for identifying LMW-GS gene family members. Based on sequence alignment of 13 LMW-GS genes previously identified in the Chinese bread wheat variety Xiaoyan 54 and other genes available in GenBank, PCR primers were developed and assigned to conserved sequences spanning the length polymorphism regions of LMW-GS genes. After PCR amplification, 17 DNA fragments in Xiaoyan 54 were detected using capillary electrophoresis. In total, 13 fragments were identical to previously identified LMW-GS genes, and the other 4 were derived from unique LMW-GS genes by sequencing. This marker system was also used to identify LMW-GS genes in Chinese Spring and its group 1 nulli-tetrasomic lines. Among the 17 detected DNA fragments, 4 were located on chromosome 1A, 5 on 1B, and 8 on 1D. The results suggest that this marker system is useful for large-scale identification of LMW-GS genes in bread wheat varieties, and for the selection of desirable LMW-GS genes to improve the bread-making quality in wheat molecular breeding programmes.

Event-by-event fluctuations in the medium-induced jet evolution

International Nuclear Information System (INIS)

Escobedo, Miguel A.; Iancu, Edmond

2016-01-01

We develop the event-by-event picture of the gluon distribution produced via medium-induced gluon branching by an energetic jet which propagates through a dense QCD medium. A typical event is characterized by the production of a large number of soft gluons which propagate at large angles with respect to the jet axis and which collectively carry a substantial amount of energy. By explicitly computing 2-gluon correlations, we demonstrate the existence of large event-by-event fluctuations, which reflect the stochastic nature of the branching process. For the two quantities that we have investigated — the energy loss at large angles and the soft gluon multiplicity —, the dispersion is parametrically as large as the respective expectation value. We identify interesting scaling laws, which suggest that the multiplicity distribution should exhibit KNO (Koba-Nielsen-Olesen) scaling. A similar scaling is known to hold for a jet branching in the vacuum, but the medium-induced distribution is found to be considerably broader. We predict that event-by-event measurements of the di-jet asymmetry in Pb+Pb collisions at the LHC should observe large fluctuations in the number of soft hadrons propagating at large angles and also in the total energy carried by these hadrons.

Novel thrombopoietin mimetic peptides bind c-Mpl receptor: Synthesis, biological evaluation and molecular modeling.

Science.gov (United States)

Liu, Yaquan; Tian, Fang; Zhi, Dejuan; Wang, Haiqing; Zhao, Chunyan; Li, Hongyu

2017-02-01

Thrombopoietin (TPO) acts in promoting the proliferation of hematopoietic stem cells and by initiating specific maturation events in megakaryocytes. Now, TPO-mimetic peptides with amino acid sequences unrelated to TPO are of considerable pharmaceutical interest. In the present paper, four new TPO mimetic peptides that bind and activate c-Mpl receptor have been identified, synthesized and tested by Dual-Luciferase reporter gene assay for biological activities. The molecular modeling research was also approached to understand key molecular mechanisms and structural features responsible for peptide binding with c-Mpl receptor. The results presented that three of four mimetic peptides showed significant activities. In addition, the molecular modeling approaches proved hydrophobic interactions were the driven positive forces for binding behavior between peptides and c-Mpl receptor. TPO peptide residues in P7, P13 and P7' positions were identified by the analysis of hydrogen bonds and energy decompositions as the key ones for benefiting better biological activities. Our data suggested the synthesized peptides have considerable potential for the future development of stable and highly active TPO mimetic peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Integration of molecular biology tools for identifying promoters and genes abundantly expressed in flowers of Oncidium Gower Ramsey

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Tung Shu-Yun

2011-04-01

Full Text Available Abstract Background Orchids comprise one of the largest families of flowering plants and generate commercially important flowers. However, model plants, such as Arabidopsis thaliana do not contain all plant genes, and agronomic and horticulturally important genera and species must be individually studied. Results Several molecular biology tools were used to isolate flower-specific gene promoters from Oncidium 'Gower Ramsey' (Onc. GR. A cDNA library of reproductive tissues was used to construct a microarray in order to compare gene expression in flowers and leaves. Five genes were highly expressed in flower tissues, and the subcellular locations of the corresponding proteins were identified using lip transient transformation with fluorescent protein-fusion constructs. BAC clones of the 5 genes, together with 7 previously published flower- and reproductive growth-specific genes in Onc. GR, were identified for cloning of their promoter regions. Interestingly, 3 of the 5 novel flower-abundant genes were putative trypsin inhibitor (TI genes (OnTI1, OnTI2 and OnTI3, which were tandemly duplicated in the same BAC clone. Their promoters were identified using transient GUS reporter gene transformation and stable A. thaliana transformation analyses. Conclusions By combining cDNA microarray, BAC library, and bombardment assay techniques, we successfully identified flower-directed orchid genes and promoters.

Diet, lifestyle, and molecular alterations that drive colorectal carcinogenesis

NARCIS (Netherlands)

Diergaarde, B.

2004-01-01

Environmental factors have been repeatedly implicated in the etiology of colorectal cancer, and much is known about the molecular events involved in colorectal carcinogenesis. The relationships between environmental risk factors and the molecular alterations that drive colorectal carcinogenesis are

Identifying Preserved Storm Events on Beaches from Trenches and Cores

Science.gov (United States)

Wadman, H. M.; Gallagher, E. L.; McNinch, J.; Reniers, A.; Koktas, M.

2014-12-01

Recent research suggests that even small scale variations in grain size in the shallow stratigraphy of sandy beaches can significantly influence large-scale morphology change. However, few quantitative studies of variations in shallow stratigraphic layers, as differentiated by variations in mean grain size, have been conducted, in no small part due to the difficulty of collecting undisturbed sediment cores in the energetic lower beach and swash zone. Due to this lack of quantitative stratigraphic grain size data, most coastal morphology models assume that uniform grain sizes dominate sandy beaches, allowing for little to no temporal or spatial variations in grain size heterogeneity. In a first-order attempt to quantify small-scale, temporal and spatial variations in beach stratigraphy, thirty-five vibracores were collected at the USACE Field Research Facility (FRF), Duck, NC, in March-April of 2014 using the FRF's Coastal Research and Amphibious Buggy (CRAB). Vibracores were collected at set locations along a cross-shore profile from the toe of the dune to a water depth of ~1m in the surf zone. Vibracores were repeatedly collected from the same locations throughout a tidal cycle, as well as pre- and post a nor'easter event. In addition, two ~1.5m deep trenches were dug in the cross-shore and along-shore directions (each ~14m in length) after coring was completed to allow better interpretation of the stratigraphic sequences observed in the vibracores. The elevations of coherent stratigraphic layers, as revealed in vibracore-based fence diagrams and trench data, are used to relate specific observed stratigraphic sequences to individual storm events observed at the FRF. These data provide a first-order, quantitative examination of the small-scale temporal and spatial variability of shallow grain size along an open, sandy coastline. The data will be used to refine morphological model predictions to include variations in grain size and associated shallow stratigraphy.

Trends of significant operating events in assessing programmatic issues

International Nuclear Information System (INIS)

Lanning, W.D.

1990-01-01

This paper describes one part of the U. S. Nuclear Regulatory Commission's (NRC's) program for evaluating significant events and the process for identifying trends that may be indicative of programmatic weaknesses at operating nuclear power plants. A database management system was developed to permit analyses of significant operating events, events of potential safety significance, and certain reactor scrams. The analyses were based on events and problems reported by telephone to the NRC by licensees within hours of the events and, therefore, provided current operational data trend information. The regulatory requirements for reporting significant events, the screening criteria, and the process for identifying outliers for formal evaluation are described herein. This process contributed to an understanding of the underlying causes for events and problems. Examples are included of operating experience assessments that identified plants with a poor operating experience history that was attributable to procedural inadequacies, operator training deficiencies, inadequate root cause analysis, and inadequate control and planning of activities

Imaging transient blood vessel fusion events in zebrafish by correlative volume electron microscopy.

Directory of Open Access Journals (Sweden)

Hannah E J Armer

Full Text Available The study of biological processes has become increasingly reliant on obtaining high-resolution spatial and temporal data through imaging techniques. As researchers demand molecular resolution of cellular events in the context of whole organisms, correlation of non-invasive live-organism imaging with electron microscopy in complex three-dimensional samples becomes critical. The developing blood vessels of vertebrates form a highly complex network which cannot be imaged at high resolution using traditional methods. Here we show that the point of fusion between growing blood vessels of transgenic zebrafish, identified in live confocal microscopy, can subsequently be traced through the structure of the organism using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM and Serial Block Face/Scanning Electron Microscopy (SBF/SEM. The resulting data give unprecedented microanatomical detail of the zebrafish and, for the first time, allow visualization of the ultrastructure of a time-limited biological event within the context of a whole organism.

Learning and Memory, Part II: Molecular Mechanisms of Synaptic Plasticity

Science.gov (United States)

Lombroso, Paul; Ogren, Marilee

2009-01-01

The molecular events that are responsible for strengthening synaptic connections and how these are linked to memory and learning are discussed. The laboratory preparations that allow the investigation of these events are also described.

Life events in schizoaffective disorder: A systematic review.

Science.gov (United States)

Vardaxi, Chrysoula Ch; Gonda, Xenia; Fountoulakis, Konstantinos N

2018-02-01

Life events play a central role in the development of psychiatric disorders and impact course and outcome. We present a systematic review of the literature on the relationship of life events with the onset and long-term course of schizoaffective disorder. MEDLINE was searched with the combination of the key words: 'life events' plus 'schizoaffective'. The PRISMA method was followed in the review process. From the identified 66 papers only 12 were considered to be of relevance to the current study and 6 more papers were identified by inspecting the reference lists of the identified papers. There are very few studies focusing on the role of life events in schizoaffective disorder indicating insufficient data concerning the relationship of life events with onset and long-term course of schizoaffective disorder. Reported effects are not generic but concern specific events like the loss of mother, and females seem to be more vulnerable. Patients with schizoaffective disorder manifest high rates of PTSD. The literature on life events with the development and course of schizoaffective disorder is limited and precludes solid conclusions. Copyright © 2017 Elsevier B.V. All rights reserved.

Kinetic modelling of hydrocracking catalytic reactions by the single events theory; Modelisation cinetique des reactions catalytiques d`hydrocraquage par la theorie des evenements constitutifs

Energy Technology Data Exchange (ETDEWEB)

Schweitzer, J.M.

1998-11-23

Kinetic modelling of petroleum hydrocracking is particularly difficult given the complexity of the feedstocks. There are two distinct classes of kinetics models: lumped empirical models and detailed molecular models. The productivity of lumped empirical models is generally not very accurate, and the number of kinetic parameters increases rapidly with the number of lumps. A promising new methodology is the use of kinetic modelling based on the single events theory. Due to the molecular approach, a finite and limited number of kinetic parameters can describe the kinetic behaviour of the hydrocracking of heavy feedstock. The parameters are independent of the feedstock. However, the available analytical methods are not able to identify the products on the molecular level. This can be accounted for by means of an posteriori lamping technique, which incorporates the detailed knowledge of the elementary step network. Thus, the lumped kinetic parameters are directly calculated from the fundamental kinetic coefficients and the single event model is reduced to a re-lumped molecular model. Until now, the ability of the method to extrapolate to higher carbon numbers had not been demonstrated. In addition, no study had been published for three phase (gas-liquid-solid) systems and a complex feedstock. The objective of this work is to validate the `single events` method using a paraffinic feedstock. First of all, a series of experiments was conducted on a model compound (hexadecane) in order to estimate the fundamental kinetic parameters for acyclic molecules. To validate the single event approach, these estimated kinetic coefficients were used to simulate hydrocracking of a paraffinic mixture ranging from C11 to C18. The simulation results were then compared to the results obtained from the hydrocracking experiments. The comparison allowed to validate the model for acyclic molecules and to demonstrate that the model is applicable to compounds with higher carbon numbers. (author

Review of licensee event reports, 1976 to 1978

International Nuclear Information System (INIS)

1979-09-01

This report was prepared in response to a request by the Chairman of the US Nuclear Regulatory Commission for the Advisory Committee on Reactor Safeguards to review, with specific objectives, the Licensee Event Reports (LERs) issued fom 1976 through 1978. A principal objective of the present study was to identify those events which have implications for improved reactor safety. Approximately 8,700 LERs were filed during the three-year period under review. These described events ranging from the trivial to those of major safety significance. This study has confirmed that LERs represent a source of valuable data and information. However, it must be recognized that a detailed review of LERs will not identify all safety problems likely to be encountered in the operation of nuclear power plants. As a result of this review, a number of classes of events were identified. These classes were subsequently categorized into three groups: (a) those having potentially serious safety implications, (b) events that must be regarded as matters of concern, and (c) events of lower safety significance but with excessive frequency

Uncovering molecular processes in crystal nucleation and growth by using molecular simulation.

Science.gov (United States)

Anwar, Jamshed; Zahn, Dirk

2011-02-25

Exploring nucleation processes by molecular simulation provides a mechanistic understanding at the atomic level and also enables kinetic and thermodynamic quantities to be estimated. However, whilst the potential for modeling crystal nucleation and growth processes is immense, there are specific technical challenges to modeling. In general, rare events, such as nucleation cannot be simulated using a direct "brute force" molecular dynamics approach. The limited time and length scales that are accessible by conventional molecular dynamics simulations have inspired a number of advances to tackle problems that were considered outside the scope of molecular simulation. While general insights and features could be explored from efficient generic models, new methods paved the way to realistic crystal nucleation scenarios. The association of single ions in solvent environments, the mechanisms of motif formation, ripening reactions, and the self-organization of nanocrystals can now be investigated at the molecular level. The analysis of interactions with growth-controlling additives gives a new understanding of functionalized nanocrystals and the precipitation of composite materials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New molecular probes of vascular inflammation

International Nuclear Information System (INIS)

Molecular Cardiovascular Imaging, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (Department of Nuclear Medicine, University Hospital Münster, Münster, and DFG CRC 656 Molecular Cardiovascular Imaging, Westfälische Wilhelms University Münster, Münster, (Germany))" >VRACHIMIS, Alexis; HONOLD, Lisa; Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (European Institute of Molecular Imaging, Westfälische Wilhelms University Münster, Münster, and DFG EXC 1003 Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" >FAUST, Andreas; Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (European Institute of Molecular Imaging, Westfälische Wilhelms University Münster, Münster, and DFG EXC 1003 Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" >HERMANN, Sven; SCHÄFERS, Michael

2016-01-01

New molecular imaging approaches featuring the assessment of inflammatory processes in the vascular wall on top of existing anatomic and functional vessel imaging procedures could emerge as decisive tools for the understanding and prevention of cardiovascular events. In this respect imaging approaches addressing specific molecular and cellular targets in atherosclerosis are of high interest. This review summarizes the rationale and current status of nuclear imaging probes which possess high translational potential.

Molecular ion photofragment spectroscopy

International Nuclear Information System (INIS)

Bustamente, S.W.

1983-11-01

A new molecular ion photofragment spectrometer is described which features a supersonic molecular beam ion source and a radio frequency octapole ion trap interaction region. This unique combination allows several techniques to be applied to the problem of detecting a photon absorption event of a molecular ion. In particular, it may be possible to obtain low resolution survey spectra of exotic molecular ions by using a direct vibrational predissociation process, or by using other more indirect detection methods. The use of the spectrometer is demonstrated by measuring the lifetime of the O 2 + ( 4 π/sub u/) metastable state which is found to consist of two main components: the 4 π/sub 5/2/ and 4 π/sub -1/2/ spin components having a long lifetime (approx. 129 ms) and the 4 π/sub 3/2/ and 4 π/sub 1/2/ spin components having a short lifetime (approx. 6 ms)

Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders.

Science.gov (United States)

Bukalo, Olena; Pinard, Courtney R; Holmes, Andrew

2014-10-01

The burden of anxiety disorders is growing, but the efficacy of available anxiolytic treatments remains inadequate. Cognitive behavioural therapy for anxiety disorders focuses on identifying and modifying maladaptive patterns of thinking and behaving, and has a testable analogue in rodents in the form of fear extinction. A large preclinical literature has amassed in recent years describing the neural and molecular basis of fear extinction in rodents. In this review, we discuss how this work is being harnessed to foster translational research on anxiety disorders and facilitate the search for new anxiolytic treatments. We begin by summarizing the anatomical and functional connectivity of a medial prefrontal cortex (mPFC)-amygdala circuit that subserves fear extinction, including new insights from optogenetics. We then cover some of the approaches that have been taken to model impaired fear extinction and associated impairments with mPFC-amygdala dysfunction. The principal goal of the review is to evaluate evidence that various neurotransmitter and neuromodulator systems mediate fear extinction by modulating the mPFC-amygdala circuitry. To that end, we describe studies that have tested how fear extinction is impaired or facilitated by pharmacological manipulations of dopamine, noradrenaline, 5-HT, GABA, glutamate, neuropeptides, endocannabinoids and various other systems, which either directly target the mPFC-amygdala circuit, or produce behavioural effects that are coincident with functional changes in the circuit. We conclude that there are good grounds to be optimistic that the progress in defining the molecular substrates of mPFC-amygdala circuit function can be effectively leveraged to identify plausible candidates for extinction-promoting therapies for anxiety disorders. © 2014 The British Pharmacological Society.

Computational challenges in modeling gene regulatory events.

Science.gov (United States)

Pataskar, Abhijeet; Tiwari, Vijay K

2016-10-19

Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology.

Adrenocortical carcinoma: the dawn of a new era of genomic and molecular biology analysis.

Science.gov (United States)

Armignacco, R; Cantini, G; Canu, L; Poli, G; Ercolino, T; Mannelli, M; Luconi, M

2018-05-01

Over the last decade, the development of novel and high penetrance genomic approaches to analyze biological samples has provided very new insights in the comprehension of the molecular biology and genetics of tumors. The use of these techniques, consisting of exome sequencing, transcriptome, miRNome, chromosome alteration, genome, and epigenome analysis, has also been successfully applied to adrenocortical carcinoma (ACC). In fact, the analysis of large cohorts of patients allowed the stratification of ACC with different patterns of molecular alterations, associated with different outcomes, thus providing a novel molecular classification of the malignancy to be associated with the classical pathological analysis. Improving our knowledge about ACC molecular features will result not only in a better diagnostic and prognostic accuracy, but also in the identification of more specific therapeutic targets for the development of more effective pharmacological anti-cancer approaches. In particular, the specific molecular alteration profiles identified in ACC may represent targetable events by the use of already developed or newly designed drugs enabling a better and more efficacious management of the ACC patient in the context of new frontiers of personalized precision medicine.

Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels

Directory of Open Access Journals (Sweden)

Tomoko Miyata

2015-01-01

Full Text Available Uterine leiomyosarcoma (LMS is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM, a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions only by ultrasound and pelvic MRI. While histopathological diagnosis is currently the main approach used to distinguish them postoperatively, unusual histologic variants of LM tend to be misdiagnosed as LMS. Therefore, development of molecular diagnosis as an alternative or confirmatory means will help to diagnose LMS more accurately. We adopted omics-based technologies to identify genome-wide features to distinguish LMS from LM and revealed that copy number, gene expression, and DNA methylation profiles successfully distinguished these tumors. LMS was found to possess features typically observed in malignant solid tumors, such as extensive chromosomal abnormalities, overexpression of cell cycle-related genes, hypomethylation spreading through large genomic regions, and frequent hypermethylation at the polycomb group target genes and protocadherin genes. We also identified candidate expression and DNA methylation markers, which will facilitate establishing postoperative molecular diagnostic tests based on conventional quantitative assays. Our results demonstrate the feasibility of establishing such tests and the possibility of developing preoperative and noninvasive methods.

Molecular markers for identifying a new selected variety of Pacific white shrimp Litopenaeus vannamei

Science.gov (United States)

Yu, Yang; Zhang, Xiaojun; Liu, Jingwen; Li, Fuhua; Huang, Hao; Li, Yijun; Liu, Xiaolin; Xiang, Jianhai

2015-01-01

Selective breeding of the Pacific white shrimp Litopenaeus vannamei during the last decade has produced new varieties exhibiting high growth rates and disease resistance. However, the identification of new varieties of shrimps from their phenotypic characters is difficult. This study introduces a new approach for identifying varieties of shrimps using molecular markers of microsatellites and mitochondrial control region sequences. The method was employed to identify a new selected variety, Kehai No. 1 (KH-1), from three representative stocks (control group): Zhengda; Tongwei; and a stock collected from Fujian Province, which is now cultured in mainland China. By pooled genotyping of KH-1 and the control group, five microsatellites showing differences between KH-1 and the control group were screened out. Individual genotyping data confirmed the results from pooled genotyping. The genotyping data for the five microsatellites were applied to the assignment analysis of the KH-1 group and the control group using the partial Bayesian assignment method in GENECLASS2. By sequencing the mitochondrial control regions of individuals from the KH-1 and control group, four haplotypes were observed in the KH-1 group, whereas 14 haplotypes were obtained in the control group. By combining the microsatellite assignment analysis with mitochondrial control region analysis, the average accuracy of identification of individuals in the KH-1 group and control group reached 89%. The five selected microsatellite loci and mitochondrial control region sequences were highly polymorphic and could be used to distinguish new selected varieties of L. vannamei from other populations cultured in China.

Molecular profiling of short-term and long-term surviving patients identifies CD34 mRNA level as prognostic for glioblastoma survival

DEFF Research Database (Denmark)

Michaelsen, Signe Regner; Urup, Thomas; Olsen, Lars Rønn

2018-01-01

Despite extensive treatment, overall survival (OS) for glioblastoma (GBM) remains poor. A small proportion of patients present long survival over 3 years, but the underlying molecular background separating these long-term survivors (LTS) from short-term survivors (STS) are insufficiently understood....... Accordingly, study aim was to identify independent prognostic biomarkers for survival. Study cohort consisted of 93 primary GBM patients treated with radiation-, chemo- and bevacizumab therapy, among which 14 STS (OS ≤ 12 months) and 6 LTS (OS ≥ 36 months) were identified, all confirmed being IDH wild......-type. RNA expression levels in diagnostic tumor specimen for 792 genes were analyzed by NanoString technology. While no differences were found with regard to GBM subtype between LTS versus STS, comparative analysis of individual genes identified 14 significantly differently expressed candidate genes...

Screening and evaluation of First Half 1980 licensee event reports

International Nuclear Information System (INIS)

Waage, J.M.

1981-05-01

This program was established to identify those events which contain important operating experience and to communicate the insights gained from evaluation of such events to other plant owners and operators. This report represents a summary of that work for the LERs produced during roughly the first half of 1980. It discusses events of major significance reported during that period and summarizes those events which were identified as important. Several generic problem areas are discussed. Six major significant events took place during this period

Global transcriptomic profiling of aspen trees under elevated [CO2] to identify potential molecular mechanisms responsible for enhanced radial growth.

Science.gov (United States)

Wei, Hairong; Gou, Jiqing; Yordanov, Yordan; Zhang, Huaxin; Thakur, Ramesh; Jones, Wendy; Burton, Andrew

2013-03-01

Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)].

Molecular genetic studies in Saudi population; identified variants from GWAS and meta-analysis in stroke.

Science.gov (United States)

Alharbi, Khalid Khalaf; Ali Khan, Imran; Alotaibi, Mohammad Abdullah; Saud Aloyaid, Abdullah; Al-Basheer, Haifa Abdulaziz; Alghamdi, Naelah Abdullah; Al-Baradie, Raid Saleem; Al-Sulaiman, A M

2018-01-01

Stroke is a multifactorial and heterogeneous disorder, correlates with heritability and considered as one of the major diseases. The prior reports performed the variable models such as genome-wide association studies (GWAS), replication, case-control, cross-sectional and meta-analysis studies and still, we lack diagnostic marker in the global world. There are limited studies were carried out in Saudi population, and we aim to investigate the molecular association of single nucleotide polymorphisms (SNPs) identified through GWAS and meta-analysis studies in stroke patients in the Saudi population. In this case-control study, we have opted gender equality of 207 cases and 207 controls from the capital city of Saudi Arabia in King Saud University Hospital. The peripheral blood (5 ml) sample will be collected in two different vacutainers, and three mL of the coagulated blood will be used for lipid analysis (biochemical tests) and two mL will be used for DNA analysis (molecular tests). Genomic DNA will be extracted with the collected blood samples, and specific primers will be designed for the opted SNPs ( SORT1 -rs646218 and OLR1 -rs11053646 polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be carried out to cross check the results. The rs646218 and rs11053646 polymorphisms were significantly associated with allele, genotype and dominant models with and without crude odds ratios (OR's) and Multiple logistic regression analysis (p Saudi population. The current results were in the association with the prior study results documented through GWAS and meta-analysis association. However, other ethnic population studies should be performed to rule out in the human hereditary diseases.

Identifying Population Vulnerable to Extreme Heat Events in San Jose, California.

Science.gov (United States)

Rivera, A. L.

2016-12-01

The extreme heat days not only make cities less comfortable for living but also they are associated with increased morbidity and mortality. Mapping studies have demonstrated spatial variability in heat vulnerability. A study conducted between 2000 and 2011 in New York City shows that deaths during heat waves was more likely to occur in black individuals, at home in census tracts which received greater public assistance. This map project intends to portray areas in San Jose California that are vulnerable to extreme heat events. The variables considered to build a vulnerability index are: land surface temperature, vegetated areas (NDVI), and people exposed to these area (population density).

Phylogenetic estimates of diversification rate are affected by molecular rate variation.

Science.gov (United States)

Duchêne, D A; Hua, X; Bromham, L

2017-10-01

Molecular phylogenies are increasingly being used to investigate the patterns and mechanisms of macroevolution. In particular, node heights in a phylogeny can be used to detect changes in rates of diversification over time. Such analyses rest on the assumption that node heights in a phylogeny represent the timing of diversification events, which in turn rests on the assumption that evolutionary time can be accurately predicted from DNA sequence divergence. But there are many influences on the rate of molecular evolution, which might also influence node heights in molecular phylogenies, and thus affect estimates of diversification rate. In particular, a growing number of studies have revealed an association between the net diversification rate estimated from phylogenies and the rate of molecular evolution. Such an association might, by influencing the relative position of node heights, systematically bias estimates of diversification time. We simulated the evolution of DNA sequences under several scenarios where rates of diversification and molecular evolution vary through time, including models where diversification and molecular evolutionary rates are linked. We show that commonly used methods, including metric-based, likelihood and Bayesian approaches, can have a low power to identify changes in diversification rate when molecular substitution rates vary. Furthermore, the association between the rates of speciation and molecular evolution rate can cause the signature of a slowdown or speedup in speciation rates to be lost or misidentified. These results suggest that the multiple sources of variation in molecular evolutionary rates need to be considered when inferring macroevolutionary processes from phylogenies. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Identifying recombinants in human and primate immunodeficiency virus sequence alignments using quartet scanning

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Martin Darren P

2009-04-01

Full Text Available Abstract Background Recombination has a profound impact on the evolution of viruses, but characterizing recombination patterns in molecular sequences remains a challenging endeavor. Despite its importance in molecular evolutionary studies, identifying the sequences that exhibit such patterns has received comparatively less attention in the recombination detection framework. Here, we extend a quartet-mapping based recombination detection method to enable identification of recombinant sequences without prior specifications of either query and reference sequences. Through simulations we evaluate different recombinant identification statistics and significance tests. We compare the quartet approach with triplet-based methods that employ additional heuristic tests to identify parental and recombinant sequences. Results Analysis of phylogenetic simulations reveal that identifying the descendents of relatively old recombination events is a challenging task for all methods available, and that quartet scanning performs relatively well compared to the triplet based methods. The use of quartet scanning is further demonstrated by analyzing both well-established and putative HIV-1 recombinant strains. In agreement with recent findings, we provide evidence that the presumed circulating recombinant CRF02_AG is a 'pure' lineage, whereas the presumed parental lineage subtype G has a recombinant origin. We also demonstrate HIV-1 intrasubtype recombination, confirm the hybrid origin of SIV in chimpanzees and further disentangle the recombinant history of SIV lineages in a primate immunodeficiency virus data set. Conclusion Quartet scanning makes a valuable addition to triplet-based methods for identifying recombinant sequences without prior specifications of either query and reference sequences. The new method is available in the VisRD v.3.0 package http://www.cmp.uea.ac.uk/~vlm/visrd.

The threshold bootstrap clustering: a new approach to find families or transmission clusters within molecular quasispecies.

Directory of Open Access Journals (Sweden)

Mattia C F Prosperi

2010-10-01

Full Text Available Phylogenetic methods produce hierarchies of molecular species, inferring knowledge about taxonomy and evolution. However, there is not yet a consensus methodology that provides a crisp partition of taxa, desirable when considering the problem of intra/inter-patient quasispecies classification or infection transmission event identification. We introduce the threshold bootstrap clustering (TBC, a new methodology for partitioning molecular sequences, that does not require a phylogenetic tree estimation.The TBC is an incremental partition algorithm, inspired by the stochastic Chinese restaurant process, and takes advantage of resampling techniques and models of sequence evolution. TBC uses as input a multiple alignment of molecular sequences and its output is a crisp partition of the taxa into an automatically determined number of clusters. By varying initial conditions, the algorithm can produce different partitions. We describe a procedure that selects a prime partition among a set of candidate ones and calculates a measure of cluster reliability. TBC was successfully tested for the identification of type-1 human immunodeficiency and hepatitis C virus subtypes, and compared with previously established methodologies. It was also evaluated in the problem of HIV-1 intra-patient quasispecies clustering, and for transmission cluster identification, using a set of sequences from patients with known transmission event histories.TBC has been shown to be effective for the subtyping of HIV and HCV, and for identifying intra-patient quasispecies. To some extent, the algorithm was able also to infer clusters corresponding to events of infection transmission. The computational complexity of TBC is quadratic in the number of taxa, lower than other established methods; in addition, TBC has been enhanced with a measure of cluster reliability. The TBC can be useful to characterise molecular quasipecies in a broad context.

The threshold bootstrap clustering: a new approach to find families or transmission clusters within molecular quasispecies.

Science.gov (United States)

Prosperi, Mattia C F; De Luca, Andrea; Di Giambenedetto, Simona; Bracciale, Laura; Fabbiani, Massimiliano; Cauda, Roberto; Salemi, Marco

2010-10-25

Phylogenetic methods produce hierarchies of molecular species, inferring knowledge about taxonomy and evolution. However, there is not yet a consensus methodology that provides a crisp partition of taxa, desirable when considering the problem of intra/inter-patient quasispecies classification or infection transmission event identification. We introduce the threshold bootstrap clustering (TBC), a new methodology for partitioning molecular sequences, that does not require a phylogenetic tree estimation. The TBC is an incremental partition algorithm, inspired by the stochastic Chinese restaurant process, and takes advantage of resampling techniques and models of sequence evolution. TBC uses as input a multiple alignment of molecular sequences and its output is a crisp partition of the taxa into an automatically determined number of clusters. By varying initial conditions, the algorithm can produce different partitions. We describe a procedure that selects a prime partition among a set of candidate ones and calculates a measure of cluster reliability. TBC was successfully tested for the identification of type-1 human immunodeficiency and hepatitis C virus subtypes, and compared with previously established methodologies. It was also evaluated in the problem of HIV-1 intra-patient quasispecies clustering, and for transmission cluster identification, using a set of sequences from patients with known transmission event histories. TBC has been shown to be effective for the subtyping of HIV and HCV, and for identifying intra-patient quasispecies. To some extent, the algorithm was able also to infer clusters corresponding to events of infection transmission. The computational complexity of TBC is quadratic in the number of taxa, lower than other established methods; in addition, TBC has been enhanced with a measure of cluster reliability. The TBC can be useful to characterise molecular quasipecies in a broad context.

Global mapping of protein phosphorylation events identifies novel signalling hubs mediating fatty acid starvation responses in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Pultz, Dennis; Bennetzen, Martin; Rødkær, Steven Vestergaard

2011-01-01

Dietary restriction (DR) extends the life span of multiple species, ranging from single-celled organisms like yeast to mammals. This increase in longevity by dietary restriction is coupled to profound beneficial effects on age-related pathology. Despite the number of studies on DR...... and the physiological changes DR induces, only little is known about the genetics and signalling networks, which regulate the DR response. We have recently shown that inhibition of fatty acid synthesis in Saccharomyces cerevisiae induces autophagy mediated by TORC1 signalling and affects life span. In the present study...... in a temporal manner in response to inhibition of fatty acid synthesis by cerulenin. By in silico analysis of these phosphorylation events, we have identified the major downstream regulated processes and signalling networks mediating the cellular response to fatty acid starvation. The analysis further...

HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.

Directory of Open Access Journals (Sweden)

Stéphane Buhler

2011-02-01

Full Text Available Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model. However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used

Deciphering the molecular events necessary for synergistic tumor cell apoptosis mediated by the histone deacetylase inhibitor vorinostat and the BH3 mimetic ABT-737

NARCIS (Netherlands)

Wiegmans, Adrian P.; Alsop, Amber E.; Bots, Michael; Cluse, Leonie A.; Williams, Steven P.; Banks, Kellie-Marie; Ralli, Rachael; Scott, Clare L.; Frenzel, Anna; Villunger, Andreas; Johnstone, Ricky W.

2011-01-01

The concept of personalized anticancer therapy is based on the use of targeted therapeutics through in-depth knowledge of the molecular mechanisms of action of these agents when used alone and in combination. We have identified the apoptotic proteins and pathways necessary for synergistic tumor cell

Introduction to Molecular Dynamics and Accelerated Molecular Dynamics

International Nuclear Information System (INIS)

Perez, Danny

2012-01-01

We first introduce classical molecular dynamics (MD) simulations. We discuss their main constituents - the interatomic potentials, the boundary conditions, and the integrators - and the discuss the various ensembles that can be sampled. We discuss the strengths and weaknesses of MD, specifically in terms of time and length-scales. We then move on to discuss accelerated MD (AMD) methods, techniques that were designed to circumvent the timescale limitations of MD for rare event systems. The different methods are introduced and examples of use given.

Energy dependence of identified hadron spectra and event-by-event fluctuations in p+p interactions from NA61/SHINE at the CERN SPS

CERN Document Server

Rybczynski, Maciej; Aduszkiewicz, A.; Ali, Y.; Anticic, T.; Antoniou, N.; Argyriades, J.; Baatar, B.; Blondel, A.; Blumer, J.; Bogomilov, M.; Bravar, A.; Brooks, W.; Brzychczyk, J.; Bubak, A.; Bunyatov, S.A.; Busygina, O.; Christakoglou, P.; Czopowicz, T.; Davis, N.; Debieux, S.; Dembinski, H.; Diakonos, F.; Di Luise, S.; Dominik, W.; Drozhzhova, T.; Dumarchez, J.; Dynowski, K.; Engel, R.; Ereditato, A.; Esposito, L.S.; Feofilov, G.A.; Fodor, Z.; Ferrero, A.; Fulop, A.; Gazdzicki, M.; Golubeva, M.; Grabez, B.; Grebieszkow, K.; Grzeszczuk, A.; Guber, F.; Hakobyan, H.; Hasegawa, T.; Hierholzer, M.; Idczak, R.; Igolkin, S.; Ivanov, Y.; Ivashkin, A.; Jakovic, D.; Kadija, K.; Kapoyannis, A.; Katrynska, N.; Kaptur, E.; Kielczewska, D.; Kikola, D.; Kirejczyk, M.; Kisiel, J.; Kiss, T.; Kleinfelder, S.; Kobayashi, T.; Kolesnikov, V.I.; Kolev, D.; Kondratiev, V.P.; Korzenev, A.; Kowalski, S.; Krasnoperov, A.; Kuleshov, S.; Kurepin, A.; Larsen, D.; Laszlo, A.; Lyubushkin, V.V.; Mackowiak-Pawlowska, M.; Majka, Z.; Maksiak, B.; Malakhov, A.I.; Maletic, D.; Marchionni, A.; Marcinek, A.; Marin, V.; Marton, K.; Mathes, H.J.; Matulewicz, T.; Matveev, V.; Melkumov, G.L.; Mrowczynski, St.; Murphy, S.; Nakadaira, T.; Nirkko, M.; Nishikawa, K.; Palczewski, T.; Palla, G.; Panagiotou, A.D.; Paul, T.; Pistillo, C.; Redij, A.; Peryt, W.; Petukhov, O.; Planeta, R.; Pluta, J.; Popov, B.A.; Posiadala, M.; Pulawski, S.; Puzovic, J.; Rauch, W.; Ravonel, M.; Renfordt, R.; Robert, A.; Röhrich, D.; Rondio, E.; Roth, M.; Rubbia, A.; Rustamov, A.; Rybczynski, M.; Sadovsky, A.; Sakashita, K.; Savic, M.; Sekiguchi, T.; Seyboth, P.; Shibata, M.; Sipos, M.; Skrzypczak, E.; Slodkowski, M.; Staszel, P.; Stefanek, G.; Stepaniak, J.; Stroebele, H.; Susa, T.; Szuba, M.; Tada, M.; Tereshchenko, V.; Tolyhi, T.; Tsenov, R.; Turko, L.; Ulrich, R.; Unger, M.; Vassiliou, M.; Veberic, D.; Vechernin, V.V.; Vesztergombi, G.; Vinogradov, L.; Wilczek, A.; Wlodarczyk, Z.; Wojtaszek, A.; Wyszynski, O.; Zambelli, L.; Zipper, W.

2013-01-01

NA61/SHINE at the CERN SPS is a fixed-target experiment pursuing a rich physics program including measurements for heavy ion, neutrino and cosmic ray physics. The main goal of the ion program is to explore the most interesting $T, mu_{B}$ region of the phase diagram of strongly interacting matter. We plan to study the properties of the onset of deconfinement and to search for the signatures of the critical point. The search is performed by varying collision energy (13A-158A GeV/c) and system size (p+p, Be+Be, Ar+Ca, Xe+La). Thanks to its large acceptance and excellent particle identification capability NA61/SHINE is well suited for performing high-precision particle production measurements as well as for studying event-by-event fluctuations in p+p, p+nucleus and nucleus+nucleus collisions. Preliminary results on p+p interactions at 20, 31, 40, 80 and 158 GeV/c are presented. They include inclusive spectra of pi+, pi-, K- and protons as a function of transverse momentum/mass and rapidity as well as event-by-ev...

Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders

Science.gov (United States)

Bukalo, Olena; Pinard, Courtney R; Holmes, Andrew

2014-01-01

The burden of anxiety disorders is growing, but the efficacy of available anxiolytic treatments remains inadequate. Cognitive behavioural therapy for anxiety disorders focuses on identifying and modifying maladaptive patterns of thinking and behaving, and has a testable analogue in rodents in the form of fear extinction. A large preclinical literature has amassed in recent years describing the neural and molecular basis of fear extinction in rodents. In this review, we discuss how this work is being harnessed to foster translational research on anxiety disorders and facilitate the search for new anxiolytic treatments. We begin by summarizing the anatomical and functional connectivity of a medial prefrontal cortex (mPFC)–amygdala circuit that subserves fear extinction, including new insights from optogenetics. We then cover some of the approaches that have been taken to model impaired fear extinction and associated impairments with mPFC–amygdala dysfunction. The principal goal of the review is to evaluate evidence that various neurotransmitter and neuromodulator systems mediate fear extinction by modulating the mPFC–amygdala circuitry. To that end, we describe studies that have tested how fear extinction is impaired or facilitated by pharmacological manipulations of dopamine, noradrenaline, 5-HT, GABA, glutamate, neuropeptides, endocannabinoids and various other systems, which either directly target the mPFC–amygdala circuit, or produce behavioural effects that are coincident with functional changes in the circuit. We conclude that there are good grounds to be optimistic that the progress in defining the molecular substrates of mPFC–amygdala circuit function can be effectively leveraged to identify plausible candidates for extinction-promoting therapies for anxiety disorders. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014

Molecular sieving through a graphene nanopore: non-equilibrium molecular dynamics simulation

Institute of Scientific and Technical Information of China (English)

Chengzhen Sun; Bofeng Bai

2017-01-01

Two-dimensional graphene nanopores have shown great promise as ultra-permeable molecular sieves based on their size-sieving effects.We design a nitrogen/hydrogen modified graphene nanopore and conduct a transient non-equilibrium molecular dynamics simulation on its molecular sieving effects.The distinct time-varying molecular crossing numbers show that this special nanopore can efficiently sieve CO2 and H2S molecules from CH4 molecules with high selectivity.By analyzing the molecular structure and pore functionalization-related molecular orientation and permeable zone in the nanopore,density distribution in the molecular adsorption layer on the graphene surface,as well as other features,the molecular sieving mechanisms of graphene nanopores are revealed.Finally,several implications on the design of highly-efficient graphene nanopores,especially for determining the porosity and chemical functionalization,as gas separation membranes are summarized based on the identified phenomena and mechanisms.

Identification of coronal heating events in 3D simulations

Science.gov (United States)

Kanella, Charalambos; Gudiksen, Boris V.

2017-07-01

Context. The solar coronal heating problem has been an open question in the science community since 1939. One of the proposed models for the transport and release of mechanical energy generated in the sub-photospheric layers and photosphere is the magnetic reconnection model that incorporates Ohmic heating, which releases a part of the energy stored in the magnetic field. In this model many unresolved flaring events occur in the solar corona, releasing enough energy to heat the corona. Aims: The problem with the verification and quantification of this model is that we cannot resolve small scale events due to limitations of the current observational instrumentation. Flaring events have scaling behavior extending from large X-class flares down to the so far unobserved nanoflares. Histograms of observable characteristics of flares show powerlaw behavior for energy release rate, size, and total energy. Depending on the powerlaw index of the energy release, nanoflares might be an important candidate for coronal heating; we seek to find that index. Methods: In this paper we employ a numerical three-dimensional (3D)-magnetohydrodynamic (MHD) simulation produced by the numerical code Bifrost, which enables us to look into smaller structures, and a new technique to identify the 3D heating events at a specific instant. The quantity we explore is the Joule heating, a term calculated directly by the code, which is explicitly correlated with the magnetic reconnection because it depends on the curl of the magnetic field. Results: We are able to identify 4136 events in a volume 24 × 24 × 9.5 Mm3 (I.e., 768 × 786 × 331 grid cells) of a specific snapshot. We find a powerlaw slope of the released energy per second equal to αP = 1.5 ± 0.02, and two powerlaw slopes of the identified volume equal to αV = 1.53 ± 0.03 and αV = 2.53 ± 0.22. The identified energy events do not represent all the released energy, but of the identified events, the total energy of the largest events

Molecular and cytogenetic characterization of radon-induced lung tumors in the rat

International Nuclear Information System (INIS)

Dano, Laurent

2000-01-01

Radon is a natural radioactive gas. This radioelement, which is an α-particle emitter, is omnipresent in the environment. Inhalation of atmospheric radon is the major exposure route in man of natural radioactivity which results in respiratory tract contamination. An increased lung cancer risk associated with radon inhalation has been shown both in humans and animals by epidemiological and experimental studies, respectively. In rats, characterization of dose-effect relationships has led to the construction of statistical models that may help theoretically in the prediction of human health involvements of both occupational and domestic chronic exposure to radon. However, little is known about the cellular and molecular mechanisms of radon-induced lung carcinogenesis. In the laboratory, a model of lung cancers induced in rats after radon inhalation is available. This model represents a good tool to identify and characterize the genetic events contributing to the development of radon-induced lung tumors. Carrying out a global approach based on the combined use of classical and molecular cytogenetic methods, the analysis of 17 neoplasms allowed the identification of chromosomal regions frequently altered in these tumors. Numerous similarities have been found between our results and the cytogenetic data for human lung cancers, suggesting common underlying genetic molecular mechanisms for lung cancer development in both species. Moreover, our study has allowed to point to tumor suppressor genes and proto-oncogenes potentially involved in radon-induced lung carcinogenesis. Thus, our results may aid further molecular studies aimed either at confirming the role of these candidate genes or at demonstrating the involvement of yet to be identified genes. (author) [fr

Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy

Science.gov (United States)

There is increasing interest in using live-cell imaging to monitor not just individual intracellular endpoints, but to investigate the interplay between multiple molecular events as they unfold in real time within the cell. A major impediment to simultaneous acquisition of multip...

Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

International Nuclear Information System (INIS)

Lambros, Maria Polikandritou; Parsa, Cyrus; Mulamalla, HariChandana; Orlando, Robert; Lau, Bernard; Huang, Ying; Pon, Doreen; Chow, Moses

2011-01-01

Research highlights: → We irradiated a 3-D human oral cell culture of keratinocytes and fibroblasts with 12 and 2 Gy. → 6 h after irradiation the histopathology and apoptosis of the 3-D culture were evaluated. Microarrays were used to assess the gene expression in the irradiated 3-D tissue. → 12 Gy induced significant histopathologic changes and cellular apoptosis. → 12 Gy significantly affected genes of the NF-kB pathway, inflammatory cytokines and DAMPs. -- Abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this is an important first

Molecular confirmation of Bacillus Calmette Guerin vaccine related adverse events among Saudi Arabian children.

Directory of Open Access Journals (Sweden)

Sahal Al-Hajoj

Full Text Available Bacillus Calmette Guerin (BCG is the only available vaccine for tuberculosis (TB. Low grade complications in healthy recipients and disseminated vaccine associated complications among immuno-suppressed individuals were noticed globally after administration. Recently a series of clinically suspected BCG associated suppurative and non-suppurative lymphadenitis cases were reported from different regions of Saudi Arabia. However a molecular confirmative analysis was lacking to prove these claims.During 2009-2010, 42 Mycobacterium bovis BCG suspected clinical isolates from children diagnosed with suppurative lymphadenitis from different provinces of the country were collected and subjected to 24 loci based MIRU-VNTR typing, spoligotyping and first line anti-TB drugs susceptibility testing.Of the total 42 cases, 41 (97.6% were Saudi nationals and particularly male (64.3%. Majority of the cases were aged below 6 months (83.3% with a median of age 4 months. All the enrolled subjects showed left axillary mass which suppurated in a median of 4 months after vaccination. Among the study subjects, 1 (2.4% case was reactive to HIV antigen and 2 (4.8% case had severe combined immunodeficiency. Genotyping results showed that, 41 (97.6% isolates were identical to the vaccine strain Danish 1331 and one to Tokyo 172-1. Phylogenetic analysis revealed all the Danish 1331 isolates in a single cluster.Elevated proportion of suppurative lymphadenitis caused by M. bovis BCG reported in the country recently is majorly related to the vaccine strain Danish 1331. However lack of nationwide data on real magnitude of BCG related adverse events warrants population centric, long term future studies.

Lessons-Learned from an Event during Overhaul

Energy Technology Data Exchange (ETDEWEB)

Kim, Jitae [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2013-05-15

The event frequency, also including portion of human errors, has been decreasing compared to last ten years. However, events due to human errors during overhaul occur every year. From analyzed results for human-related events during overhaul, similar problems were identified. And organizational and safety cultural factors were also identified. On the other hand, another event during overhaul is analyzed and Lessons-Learned is drawn in an aspect of the operators' situation awareness. There was an event during overhaul and the analyzed results drawn Lessons-Learned in the aspect of the operators' situation awareness. From the analysis, several alarms and variation of plant parameters during overhaul can occur due to various maintenance works and tests. And in the aspect of the situation awareness, operators can miss, neglect, or not recognize the abnormal situation due to other maintenance activities occurring simultaneously. Therefore, countermeasures such as operator education or training, development of operator support systems, and further researches should be necessary to cope with these problems.

Lessons-Learned from an Event during Overhaul

International Nuclear Information System (INIS)

Kim, Jitae

2013-01-01

The event frequency, also including portion of human errors, has been decreasing compared to last ten years. However, events due to human errors during overhaul occur every year. From analyzed results for human-related events during overhaul, similar problems were identified. And organizational and safety cultural factors were also identified. On the other hand, another event during overhaul is analyzed and Lessons-Learned is drawn in an aspect of the operators' situation awareness. There was an event during overhaul and the analyzed results drawn Lessons-Learned in the aspect of the operators' situation awareness. From the analysis, several alarms and variation of plant parameters during overhaul can occur due to various maintenance works and tests. And in the aspect of the situation awareness, operators can miss, neglect, or not recognize the abnormal situation due to other maintenance activities occurring simultaneously. Therefore, countermeasures such as operator education or training, development of operator support systems, and further researches should be necessary to cope with these problems

Visual search of cyclic spatio-temporal events

Science.gov (United States)

Gautier, Jacques; Davoine, Paule-Annick; Cunty, Claire

2018-05-01

The analysis of spatio-temporal events, and especially of relationships between their different dimensions (space-time-thematic attributes), can be done with geovisualization interfaces. But few geovisualization tools integrate the cyclic dimension of spatio-temporal event series (natural events or social events). Time Coil and Time Wave diagrams represent both the linear time and the cyclic time. By introducing a cyclic temporal scale, these diagrams may highlight the cyclic characteristics of spatio-temporal events. However, the settable cyclic temporal scales are limited to usual durations like days or months. Because of that, these diagrams cannot be used to visualize cyclic events, which reappear with an unusual period, and don't allow to make a visual search of cyclic events. Also, they don't give the possibility to identify the relationships between the cyclic behavior of the events and their spatial features, and more especially to identify localised cyclic events. The lack of possibilities to represent the cyclic time, outside of the temporal diagram of multi-view geovisualization interfaces, limits the analysis of relationships between the cyclic reappearance of events and their other dimensions. In this paper, we propose a method and a geovisualization tool, based on the extension of Time Coil and Time Wave, to provide a visual search of cyclic events, by allowing to set any possible duration to the diagram's cyclic temporal scale. We also propose a symbology approach to push the representation of the cyclic time into the map, in order to improve the analysis of relationships between space and the cyclic behavior of events.

Integration of molecular typing results into tuberculosis surveillance in Germany-A pilot study.

Science.gov (United States)

Andrés, Marta; Göhring-Zwacka, Elke; Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

2017-01-01

An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age Germany (OR = 2.01, 95% CI: 1.44-2.80) were associated with clustering. At cluster level, molecular typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48-98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the

Slow Earthquake Hunters: A New Citizen Science Project to Identify and Catalog Slow Slip Events in Geodetic Data

Science.gov (United States)

Bartlow, N. M.

2017-12-01

Slow Earthquake Hunters is a new citizen science project to detect, catalog, and monitor slow slip events. Slow slip events, also called "slow earthquakes", occur when faults slip too slowly to generate significant seismic radiation. They typically take between a few days and over a year to occur, and are most often found on subduction zone plate interfaces. While not dangerous in and of themselves, recent evidence suggests that monitoring slow slip events is important for earthquake hazards, as slow slip events have been known to trigger damaging "regular" earthquakes. Slow slip events, because they do not radiate seismically, are detected with a variety of methods, most commonly continuous geodetic Global Positioning System (GPS) stations. There is now a wealth of GPS data in some regions that experience slow slip events, but a reliable automated method to detect them in GPS data remains elusive. This project aims to recruit human users to view GPS time series data, with some post-processing to highlight slow slip signals, and flag slow slip events for further analysis by the scientific team. Slow Earthquake Hunters will begin with data from the Cascadia subduction zone, where geodetically detectable slow slip events with a duration of at least a few days recur at regular intervals. The project will then expand to other areas with slow slip events or other transient geodetic signals, including other subduction zones, and areas with strike-slip faults. This project has not yet rolled out to the public, and is in a beta testing phase. This presentation will show results from an initial pilot group of student participants at the University of Missouri, and solicit feedback for the future of Slow Earthquake Hunters.

Galleria mellonella model identifies highly virulent strains among all major molecular types of Cryptococcus gattii.

Directory of Open Access Journals (Sweden)

Carolina Firacative

Full Text Available Cryptococcosis is mainly caused by Cryptococcus neoformans. However, the number of cases due to C. gattii is increasing, affecting mainly immunocompetent hosts. C. gattii is divided into four major molecular types, VGI to VGIV, which differ in their host range, epidemiology, antifungal susceptibility and geographic distribution. Besides studies on the Vancouver Island outbreak strains, which showed that the subtype VGIIa is highly virulent compared to the subtype VGIIb, little is known about the virulence of the other major molecular types. To elucidate the virulence potential of the major molecular types of C. gattii, Galleria mellonella larvae were inoculated with ten globally selected strains per molecular type. Survival rates were recorded and known virulence factors were studied. One VGII, one VGIII and one VGIV strain were more virulent (p 0.05, 21 (five VGI, five VGII, four VGIII and seven VGIV were less virulent (p <0.05 while one strain of each molecular type were avirulent. Cell and capsule size of all strains increased markedly during larvae infection (p <0.001. No differences in growth rate at 37°C were observed. Melanin synthesis was directly related with the level of virulence: more virulent strains produced more melanin than less virulent strains (p <0.05. The results indicate that all C. gattii major molecular types exhibit a range of virulence, with some strains having the potential to be more virulent. The study highlights the necessity to further investigate the genetic background of more and less virulent strains in order to recognize critical features, other than the known virulence factors (capsule, melanin and growth at mammalian body temperature, that maybe crucial for the development and progression of cryptococcosis.

Analysis of loss of offsite power events reported in nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Volkanovski, Andrija, E-mail: Andrija.VOLKANOVSKI@ec.europa.eu [European Commission, Joint Research Centre, Institute for Energy and Transport, P.O. Box 2, NL-1755 ZG Petten (Netherlands); Ballesteros Avila, Antonio; Peinador Veira, Miguel [European Commission, Joint Research Centre, Institute for Energy and Transport, P.O. Box 2, NL-1755 ZG Petten (Netherlands); Kančev, Duško [Kernkraftwerk Goesgen-Daeniken AG, CH-4658 Daeniken (Switzerland); Maqua, Michael [Gesellschaft für Anlagen-und-Reaktorsicherheit (GRS) gGmbH, Schwertnergasse 1, 50667 Köln (Germany); Stephan, Jean-Luc [Institut de Radioprotection et de Sûreté Nucléaire (IRSN), BP 17 – 92262 Fontenay-aux-Roses Cedex (France)

2016-10-15

Highlights: • Loss of offsite power events were identified in four databases. • Engineering analysis of relevant events was done. • The dominant root cause for LOOP are human failures. • Improved maintenance procedures can decrease the number of LOOP events. - Abstract: This paper presents the results of analysis of the loss of offsite power events (LOOP) in four databases of operational events. The screened databases include: the Gesellschaft für Anlagen und Reaktorsicherheit mbH (GRS) and Institut de Radioprotection et de Sûreté Nucléaire (IRSN) databases, the IAEA International Reporting System for Operating Experience (IRS) and the U.S. Licensee Event Reports (LER). In total 228 relevant loss of offsite power events were identified in the IRSN database, 190 in the GRS database, 120 in U.S. LER and 52 in IRS database. Identified events were classified in predefined categories. Obtained results show that the largest percentage of LOOP events is registered during On power operational mode and lasted for two minutes or more. The plant centered events is the main contributor to LOOP events identified in IRSN, GRS and IAEA IRS database. The switchyard centered events are the main contributor in events registered in the NRC LER database. The main type of failed equipment is switchyard failures in IRSN and IAEA IRS, main or secondary lines in NRC LER and busbar failures in GRS database. The dominant root cause for the LOOP events are human failures during test, inspection and maintenance followed by human failures due to the insufficient or wrong procedures. The largest number of LOOP events resulted in reactor trip followed by EDG start. The actions that can result in reduction of the number of LOOP events and minimize consequences on plant safety are identified and presented.

EpiGeNet: A Graph Database of Interdependencies Between Genetic and Epigenetic Events in Colorectal Cancer.

Science.gov (United States)

Balaur, Irina; Saqi, Mansoor; Barat, Ana; Lysenko, Artem; Mazein, Alexander; Rawlings, Christopher J; Ruskin, Heather J; Auffray, Charles

2017-10-01

The development of colorectal cancer (CRC)-the third most common cancer type-has been associated with deregulations of cellular mechanisms stimulated by both genetic and epigenetic events. StatEpigen is a manually curated and annotated database, containing information on interdependencies between genetic and epigenetic signals, and specialized currently for CRC research. Although StatEpigen provides a well-developed graphical user interface for information retrieval, advanced queries involving associations between multiple concepts can benefit from more detailed graph representation of the integrated data. This can be achieved by using a graph database (NoSQL) approach. Data were extracted from StatEpigen and imported to our newly developed EpiGeNet, a graph database for storage and querying of conditional relationships between molecular (genetic and epigenetic) events observed at different stages of colorectal oncogenesis. We illustrate the enhanced capability of EpiGeNet for exploration of different queries related to colorectal tumor progression; specifically, we demonstrate the query process for (i) stage-specific molecular events, (ii) most frequently observed genetic and epigenetic interdependencies in colon adenoma, and (iii) paths connecting key genes reported in CRC and associated events. The EpiGeNet framework offers improved capability for management and visualization of data on molecular events specific to CRC initiation and progression.

ATLAS event at 13 TeV - JPsi candidate - run: 265545, lb: 68, event: 1020606

CERN Multimedia

ATLAS Collaboration

2015-01-01

Display of a proton-proton collision event recorded by ATLAS on 21 May 2015 at a collision energy of 13 TeV. Tracks reconstructed from hits in the inner tracking detector are shown as arcs curving in the solenoidal magnetic field and the green bars indicate hits in the Muon spectrometer. In this event two muons are identified, and their invariant mass is consistent with that of a J/Psi meson.

Expert panel evaluation of health information technology effects on adverse events.

Science.gov (United States)

Abramson, Erika L; Kern, Lisa M; Brenner, Samantha; Hufstader, Meghan; Patel, Vaishali; Kaushal, Rainu

2014-08-01

Adverse events (AEs) among hospitalized patients occur frequently and result in significant sequelae. Federal policy is incentivizing health information technology (HIT) use, although research demonstrating safety benefits from HIT is mixed. Our objective was to evaluate the potential effects of HIT on reducing 21 different inpatient AEs. Identifying AEs most likely to be reduced by HIT can inform the design of future studies evaluating its effectiveness. We conducted a modified Delphi panel of national experts in HIT and safety. We conducted a focused literature review to inform the experts. Using a novel framework, experts rated each AE as 'definitely reduced by health IT,' 'possibly reduced by health IT' and 'not likely to be reduced by health IT'. From our panel discussion, experts identified six AEs as 'definitely reduced by health IT': (1) adverse drug events (ADEs) associated with digoxin; (2) ADE associated with IV heparin; (3) ADE associated with hypoglycaemic agents; (4) ADE associated with low molecular weight heparin and factor Xa inhibitor; (5) contrast nephropathy associated with catheter angiography; and (6) ADE hospital-acquired antibiotic-associated Clostridium difficile. Understanding the effects of HIT on patient outcomes will be essential to ensuring that the significant federal investment results in anticipated improvements. This study serves as an important early step in helping with the design of future work evaluating level of HIT infrastructure and rates of inpatient AEs. © 2014 John Wiley & Sons, Ltd.

Metabolic and Molecular Events Occurring during Chromoplast Biogenesis

Directory of Open Access Journals (Sweden)

Wanping Bian

2011-01-01

Full Text Available Chromoplasts are nonphotosynthetic plastids that accumulate carotenoids. They derive from other plastid forms, mostly chloroplasts. The biochemical events responsible for the interconversion of one plastid form into another are poorly documented. However, thanks to transcriptomics and proteomics approaches, novel information is now available. Data of proteomic and biochemical analysis revealed the importance of lipid metabolism and carotenoids biosynthetic activities. The loss of photosynthetic activity was associated with the absence of the chlorophyll biosynthesis branch and the presence of proteins involved in chlorophyll degradation. Surprisingly, the entire set of Calvin cycle and of the oxidative pentose phosphate pathway persisted after the transition from chloroplast to chromoplast. The role of plastoglobules in the formation and organisation of carotenoid-containing structures and that of the Or gene in the control of chromoplastogenesis are reviewed. Finally, using transcriptomic data, an overview is given the expression pattern of a number of genes encoding plastid-located proteins during tomato fruit ripening.

Molecular mechanisms of lipoapoptosis and metformin protection in GLP-1 secreting cells

DEFF Research Database (Denmark)

Kappe, Camilla; Holst, Jens Juul; Zhang, Qimin

2012-01-01

Evidence is emerging that elevated serum free fatty acids (hyperlipidemia) contribute to the pathogenesis of type-2-diabetes, and lipotoxicity is observed in many cell types. We recently published data indicating lipotoxic effects of simulated hyperlipidemia also in GLP-1-secreting cells, where...... the antidiabetic drug metformin conferred protection from lipoapoptosis. The aim of the present study was to identify mechanisms involved in mediating lipotoxicity and metformin lipoprotection in GLP-1 secreting cells. These signaling events triggered by simulated hyperlipidemia may underlie reduced GLP-1...... secretion in diabetic subjects, and metformin lipoprotection by metformin could explain elevated plasma GLP-1 levels in diabetic patients on chronic metformin therapy. The present study may thus identify potential molecular targets for increasing endogenous GLP-1 secretion through enhanced viability of GLP...

Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010-2012.

Science.gov (United States)

Baldeviano, G Christian; Okoth, Sheila Akinyi; Arrospide, Nancy; Gonzalez, Rommell V; Sánchez, Juan F; Macedo, Silvia; Conde, Silvia; Tapia, L Lorena; Salas, Carola; Gamboa, Dionicia; Herrera, Yeni; Edgel, Kimberly A; Udhayakumar, Venkatachalam; Lescano, Andrés G

2015-05-01

During 2010-2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998-2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events.

Detection of anomalous events

Science.gov (United States)

Ferragut, Erik M.; Laska, Jason A.; Bridges, Robert A.

2016-06-07

A system is described for receiving a stream of events and scoring the events based on anomalousness and maliciousness (or other classification). The system can include a plurality of anomaly detectors that together implement an algorithm to identify low-probability events and detect atypical traffic patterns. The anomaly detector provides for comparability of disparate sources of data (e.g., network flow data and firewall logs.) Additionally, the anomaly detector allows for regulatability, meaning that the algorithm can be user configurable to adjust a number of false alerts. The anomaly detector can be used for a variety of probability density functions, including normal Gaussian distributions, irregular distributions, as well as functions associated with continuous or discrete variables.

Identifying the null subject: evidence from event-related brain potentials.

Science.gov (United States)

Demestre, J; Meltzer, S; García-Albea, J E; Vigil, A

1999-05-01

Event-related brain potentials (ERPs) were recorded during spoken language comprehension to study the on-line effects of gender agreement violations in controlled infinitival complements. Spanish sentences were constructed in which the complement clause contained a predicate adjective marked for syntactic gender. By manipulating the gender of the antecedent (i.e., the controller) of the implicit subject while holding constant the gender of the adjective, pairs of grammatical and ungrammatical sentences were created. The detection of such a gender agreement violation would indicate that the parser had established the coreference relation between the null subject and its antecedent. The results showed a complex biphasic ERP (i.e., an early negativity with prominence at anterior and central sites, followed by a centroparietal positivity) in the violating condition as compared to the non-violating conditions. The brain reacts to NP-adjective gender agreement violations within a few hundred milliseconds of their occurrence. The data imply that the parser has properly coindexed the null subject of an infinitive clause with its antecedent.

Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna.

Directory of Open Access Journals (Sweden)

Haritha Bollinedi

Full Text Available Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis.

Molecular imaging of cancer using PET and SPECT

DEFF Research Database (Denmark)

Kjaer, Andreas

2006-01-01

for molecular imaging of cancer. Especially the possibility of a quick transfer of methods developed in animals to patients (translational research) is an important strength. This article will briefly discuss the newest applications and their importance and perspective in relation to the shift in paradigm......Molecular imaging allows for the study of molecular and cellular events in the living intact organism. The nuclear medicine methodologies of positron emission tomography (PET) and single photon emission computer tomography (SPECT) posses several advantages, which make them particularly suited...

Expression Profiling of Differentiating Emerin-Null Myogenic Progenitor Identifies Molecular Pathways Implicated in Their Impaired Differentiation

Directory of Open Access Journals (Sweden)

Ashvin Iyer

2017-10-01

Full Text Available Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD, a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons. RNA sequencing was performed on differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in EDMD, 340 genes were uniquely differentially expressed during the transition from day 0 to day 1 in wildtype cells. 1605 genes were uniquely expressed in emerin-null cells; 1706 genes were shared among both wildtype and emerin-null cells. One thousand and forty-seven transcripts showed differential expression during the transition from day 1 to day 2. Four hundred and thirty-one transcripts showed altered expression in both wildtype and emerin-null cells. Two hundred and ninety-five transcripts were differentially expressed only in emerin-null cells and 321 transcripts were differentially expressed only in wildtype cells. DAVID, STRING and Ingenuity Pathway Analysis identified pathways implicated in impaired emerin-null differentiation, including cell signaling, cell cycle checkpoints, integrin signaling, YAP/TAZ signaling, stem cell differentiation, and multiple muscle development and myogenic differentiation pathways. Functional enrichment analysis showed biological functions associated with the growth of muscle tissue and myogenesis of skeletal muscle were inhibited. The large number of differentially expressed transcripts upon differentiation induction suggests emerin functions during transcriptional reprograming of progenitors to committed myoblasts.

Identification of events with a secondary vertex in the experiment EXCHARM

International Nuclear Information System (INIS)

Bonyushkina, A.Yu.; Ivanov, V.V.; Potrebenikov, Yu.K.; Progulova, T.B.; Tatishvili, G.T.

1996-01-01

A simple algorithm for identifying events with secondary vertices (signal events) is suggested. The differences R x , R y between the largest and the smallest impact parameters D i of the tracks belonging to each of the events analyzed are used in establishing the identification criteria for signal and background events. An effective method for identifying the tracks associated with a particular secondary vertex in an event is developed. The method is based on the differences between the asymmetries exhibited by the sets D i for individual signal events and background events. The algorithm has been tested using simulated data. 12 refs., 7 figs

Probabilistic Cross-Identification of Cosmic Events

OpenAIRE

Budavari, Tamas

2011-01-01

We discuss a novel approach to identifying cosmic events in separate and independent observations. In our focus are the true events, such as supernova explosions, that happen once, hence, whose measurements are not repeatable. Their classification and analysis have to make the best use of all the available data. Bayesian hypothesis testing is used to associate streams of events in space and time. Probabilities are assigned to the matches by studying their rates of occurrence. A case study of ...

Contingency Analysis of Cascading Line Outage Events

Energy Technology Data Exchange (ETDEWEB)

Thomas L Baldwin; Magdy S Tawfik; Miles McQueen

2011-03-01

As the US power systems continue to increase in size and complexity, including the growth of smart grids, larger blackouts due to cascading outages become more likely. Grid congestion is often associated with a cascading collapse leading to a major blackout. Such a collapse is characterized by a self-sustaining sequence of line outages followed by a topology breakup of the network. This paper addresses the implementation and testing of a process for N-k contingency analysis and sequential cascading outage simulation in order to identify potential cascading modes. A modeling approach described in this paper offers a unique capability to identify initiating events that may lead to cascading outages. It predicts the development of cascading events by identifying and visualizing potential cascading tiers. The proposed approach was implemented using a 328-bus simplified SERC power system network. The results of the study indicate that initiating events and possible cascading chains may be identified, ranked and visualized. This approach may be used to improve the reliability of a transmission grid and reduce its vulnerability to cascading outages.

Identifying high-risk medication

DEFF Research Database (Denmark)

Sædder, Eva; Brock, Birgitte; Nielsen, Lars Peter

2014-01-01

salicylic acid, and beta-blockers; 30 drugs or drug classes caused 82 % of all serious MEs. The top ten drugs involved in fatal events accounted for 73 % of all drugs identified. CONCLUSION: Increasing focus on seven drugs/drug classes can potentially reduce hospitalizations, extended hospitalizations...

Full-length genomic and molecular characterization of Canine parvovirus in dogs from North of Brazil.

Science.gov (United States)

Silva, S P; Silva, L N P P; Rodrigues, E D L; Cardoso, J F; Tavares, F N; Souza, W M; Santos, C M P; Martins, F M S; Jesus, I S; Brito, T C; Moura, T P C; Nunes, M R T; Casseb, L M N; Silva Filho, E; Casseb, A R

2017-09-21

With the objective of characterizing Canine parvovirus (CPV) from some suspected fecal samples of dogs collected from the Veterinarian Hospital in Belém city, five positive samples were found by PCR assay and an update molecular characterization was provided of the CPV-2 circulation in Belém. Through sequencing of the complete DNA sequences (NS1, NS2, VP1, and VP2 genes), the CPV-2 strain was identified as CPV-2b (Asn426Asp) circulating in Belém. The CPV-2b strain with a different change at the position Tyr324Leu was detected in all samples assessed and thus reported for the first time for the scientific community. Phylogenetic analysis indicated that Belém CPV-2b and CPV-2a strains would be related to a cluster with samples after the 1990s, suggesting that CPV-2b in Belém originated from CPV-2a circulating in Brazil after the 1990s. Potential recombination events were analyzed using RDP4 and SplitsTree4; therefore, results suggest that CPV-2 sequences here described were not potentially recombination events. Continuous monitoring and molecular characterization of CPV-2 samples are needed not only to identify possible genetic and antigenic changes that may interfere with the effectiveness of vaccines but also to bring a better understanding of the mechanisms that drive the evolution of CPV-2 in Brazil.

Intra-event correlations and the statistical moments of the identified particle multiplicity distributions in the RHIC beam energy scan data collected by STAR

Science.gov (United States)

Llope, W. J.; STAR Collaboration

2013-10-01

Specific products of the statistical moments of the multiplicity distributions of identified particles can be directly compared to susceptibility ratios obtained from lattice QCD calculations. They may also diverge for nuclear systems formed close to a possible QCD critical point due to the phenomenon of critical opalescence. Of particular interest are the moments products for net-protons, net-kaons, and net-charge, as these are considered proxies for conserved quantum numbers. The moments products have been measured by the STAR experiment for Au+Au collisions at seven beam energies ranging from 7.7 to 200 GeV. In this presentation, the experimental results are compared to data-based calculations in which the intra-event correlations of the numbers of positive and negative particles are broken by construction. The importance of intra-event correlations to the moments products values for net-protons, net-kaons, and net-charge can thus be evaluated. Work supported by the U.S. Dept of Energy under grant DE-PS02-09ER09.

A review for identification of initiating events in event tree development process on nuclear power plants

International Nuclear Information System (INIS)

Riyadi, Eko H.

2014-01-01

Initiating event is defined as any event either internal or external to the nuclear power plants (NPPs) that perturbs the steady state operation of the plant, if operating, thereby initiating an abnormal event such as transient or loss of coolant accident (LOCA) within the NPPs. These initiating events trigger sequences of events that challenge plant control and safety systems whose failure could potentially lead to core damage or large early release. Selection for initiating events consists of two steps i.e. first step, definition of possible events, such as by evaluating a comprehensive engineering, and by constructing a top level logic model. Then the second step, grouping of identified initiating event's by the safety function to be performed or combinations of systems responses. Therefore, the purpose of this paper is to discuss initiating events identification in event tree development process and to reviews other probabilistic safety assessments (PSA). The identification of initiating events also involves the past operating experience, review of other PSA, failure mode and effect analysis (FMEA), feedback from system modeling, and master logic diagram (special type of fault tree). By using the method of study for the condition of the traditional US PSA categorization in detail, could be obtained the important initiating events that are categorized into LOCA, transients and external events

Molecular Evolution and Expansion Analysis of the NAC Transcription Factor in Zea mays

Science.gov (United States)

Fan, Kai; Wang, Ming; Miao, Ying; Ni, Mi; Bibi, Noreen; Yuan, Shuna; Li, Feng; Wang, Xuede

2014-01-01

NAC (NAM, ATAF1, 2 and CUC2) family is a plant-specific transcription factor and it controls various plant developmental processes. In the current study, 124 NAC members were identified in Zea mays and were phylogenetically clustered into 13 distinct subfamilies. The whole genome duplication (WGD), especially an additional WGD event, may lead to expanding ZmNAC members. Different subfamily has different expansion rate, and NAC subfamily preference was found during the expansion in maize. Moreover, the duplication events might occur after the divergence of the lineages of Z. mays and S. italica, and segmental duplication seemed to be the dominant pattern for the gene duplication in maize. Furthermore, the expansion of ZmNAC members may be also related to gain and loss of introns. Besides, the restriction of functional divergence was discovered after most of the gene duplication events. These results could provide novel insights into molecular evolution and expansion analysis of NAC family in maize, and advance the NAC researches in other plants, especially polyploid plants. PMID:25369196

Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles

Directory of Open Access Journals (Sweden)

Yanara Marincevic-Zuniga

2017-08-01

Full Text Available Abstract Background Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL. In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. Methods We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. Results We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Conclusion Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.

Molecular evolution of rbcL in three gymnosperm families: identifying adaptive and coevolutionary patterns

LENUS (Irish Health Repository)

Sen, Lin

2011-06-03

Abstract Background The chloroplast-localized ribulose-1, 5-biphosphate carboxylase\\/oxygenase (Rubisco), the primary enzyme responsible for autotrophy, is instrumental in the continual adaptation of plants to variations in the concentrations of CO2. The large subunit (LSU) of Rubisco is encoded by the chloroplast rbcL gene. Although adaptive processes have been previously identified at this gene, characterizing the relationships between the mutational dynamics at the protein level may yield clues on the biological meaning of such adaptive processes. The role of such coevolutionary dynamics in the continual fine-tuning of RbcL remains obscure. Results We used the timescale and phylogenetic analyses to investigate and search for processes of adaptive evolution in rbcL gene in three gymnosperm families, namely Podocarpaceae, Taxaceae and Cephalotaxaceae. To understand the relationships between regions identified as having evolved under adaptive evolution, we performed coevolutionary analyses using the software CAPS. Importantly, adaptive processes were identified at amino acid sites located on the contact regions among the Rubisco subunits and on the interface between Rubisco and its activase. Adaptive amino acid replacements at these regions may have optimized the holoenzyme activity. This hypothesis was pinpointed by evidence originated from our analysis of coevolution that supported the correlated evolution between Rubisco and its activase. Interestingly, the correlated adaptive processes between both these proteins have paralleled the geological variation history of the concentration of atmospheric CO2. Conclusions The gene rbcL has experienced bursts of adaptations in response to the changing concentration of CO2 in the atmosphere. These adaptations have emerged as a result of a continuous dynamic of mutations, many of which may have involved innovation of functional Rubisco features. Analysis of the protein structure and the functional implications of such

Foundations for Streaming Model Transformations by Complex Event Processing.

Science.gov (United States)

Dávid, István; Ráth, István; Varró, Dániel

2018-01-01

Streaming model transformations represent a novel class of transformations to manipulate models whose elements are continuously produced or modified in high volume and with rapid rate of change. Executing streaming transformations requires efficient techniques to recognize activated transformation rules over a live model and a potentially infinite stream of events. In this paper, we propose foundations of streaming model transformations by innovatively integrating incremental model query, complex event processing (CEP) and reactive (event-driven) transformation techniques. Complex event processing allows to identify relevant patterns and sequences of events over an event stream. Our approach enables event streams to include model change events which are automatically and continuously populated by incremental model queries. Furthermore, a reactive rule engine carries out transformations on identified complex event patterns. We provide an integrated domain-specific language with precise semantics for capturing complex event patterns and streaming transformations together with an execution engine, all of which is now part of the Viatra reactive transformation framework. We demonstrate the feasibility of our approach with two case studies: one in an advanced model engineering workflow; and one in the context of on-the-fly gesture recognition.

Molecular photoionization studies of nucleobases and correlated systems

Energy Technology Data Exchange (ETDEWEB)

Poliakoff, Erwin D. [Louisiana State Univ., Baton Rouge, LA (United States)

2015-03-11

We proposed molecular photoionization studies in order to probe correlated events in fundamental scattering phenomena. In particular, we suggested that joint theoretical-experimental studies would provide a window into the microscopic aspects that are of central importance in AMO and chemical physics generally, and would generate useful data for wide array of important DOE topics, such as ultrafast dynamics, high harmonic generation, and probes of nonadiabatic processes. The unifying theme is that correlations between electron scattering dynamics and molecular geometry highlight inherently molecular aspects of the photoelectron behavior.

Inferring phylogenetic trees from the knowledge of rare evolutionary events.

Science.gov (United States)

Hellmuth, Marc; Hernandez-Rosales, Maribel; Long, Yangjing; Stadler, Peter F

2018-06-01

Rare events have played an increasing role in molecular phylogenetics as potentially homoplasy-poor characters. In this contribution we analyze the phylogenetic information content from a combinatorial point of view by considering the binary relation on the set of taxa defined by the existence of a single event separating two taxa. We show that the graph-representation of this relation must be a tree. Moreover, we characterize completely the relationship between the tree of such relations and the underlying phylogenetic tree. With directed operations such as tandem-duplication-random-loss events in mind we demonstrate how non-symmetric information constrains the position of the root in the partially reconstructed phylogeny.

Molecular mechanisms in lithium-associated renal disease: a systematic review.

Science.gov (United States)

Rej, Soham; Pira, Shamira; Marshe, Victoria; Do, André; Elie, Dominique; Looper, Karl J; Herrmann, Nathan; Müller, Daniel J

2016-11-01

Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium-associated renal disease. We conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium's effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers. From a total of 3510 records, 71 pre-clinical studies and two relevant clinical studies were identified. Molecular alterations were reported in calcium signaling, inositol monophosphate, extracellular-regulated, prostaglandin, sodium/solute transport, G-protein-coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation-related pathways in lithium-associated renal disease. The majority of studies found that these mechanisms were implicated in NDI, while few studies had examined CKD. Future studies will have to focus on (1) validating the present findings in human subjects and (2) examining CKD, which is the most clinically relevant lithium-associated renal effect. This will improve our understanding of lithium's biological effects, as well as inform a personalized medicine approach, which could lead to safer lithium prescribing and less renal adverse events.

An analysis of hydrated proton diffusion in ab initio molecular dynamics

Energy Technology Data Exchange (ETDEWEB)

Tse, Ying-Lung Steve; Voth, Gregory A., E-mail: gavoth@uchicago.edu [Department of Chemistry, James Franck Institute, and Computation Institute, University of Chicago, Chicago, Illinois 60637 (United States); Knight, Chris [Leadership Computing Facility, Argonne National Laboratory, Argonne, Illinois 60439 (United States)

2015-01-07

A detailed understanding of the inherently multiscale proton transport process raises a number of scientifically challenging questions. For example, there remain many (partially addressed) questions on the molecular mechanism for long-range proton migration and the potential for the formation of long-lived traps giving rise to burst-and-rest proton dynamics. Using results from a sizeable collection of ab initio molecular dynamics (AIMD) simulations (totaling ∼2.7 ns) with various density functional approximations (Becke-Lee-Yang-Parr (BLYP), BLYP–D3, Hamprecht-Cohen-Tozer-Handy, B3LYP) and temperatures (300–330 K), equilibrium and dynamical properties of one excess proton and 128 water molecules are studied. Two features in particular (concerted hops and weak hydrogen-bond donors) are investigated to identify modes in the system that are strongly correlated with the onset of periods of burst-and-rest dynamics. The question of concerted hops seeks to identify those time scales over which long-range proton transport can be classified as a series of sequential water hopping events or as a near-simultaneous concerted process along compressed water wires. The coupling of the observed burst-and-rest dynamics with motions of a fourth neighboring water molecule (a weak hydrogen-bond donor) solvating the protonated water molecule is also investigated. The presence (absence) of hydrogen bonds involving this fourth water molecule before and after successful proton hopping events is found to be strongly correlated with periods of burst (rest) dynamics (and consistent with pre-solvation concepts). By analyzing several realizations of the AIMD trajectories on the 100-ps time scale, convergence of statistics can be assessed. For instance, it was observed that the probability for a fourth water molecule to approach the hydronium, if not already proximal at the beginning of the lifetime of the hydronium, is very low, indicative of the formation of stable void regions

Proceedings of the workshop on how to prevent recurring events more effectively

International Nuclear Information System (INIS)

2003-01-01

papers were presented at the workshop in the presence of 38 participants. These papers discussed recent current events, processes and systems used to identify and investigate recurring events, and actions being taken or planned to reduce the likelihood for recurrence of events. The workshop also included two breakout sessions. This was to allow working groups to explore causes for recurring events and to discuss possible actions that can be taken by NPP, regulatory, and research staff to better identify and respond in a focused manner when an event with actual or potential safety significance recurs. Summaries from each breakout session along with breakout session facilitators guides are included below. Important points identified by the workshop participants concerning recurring events include the following: - Specific definition of 'what is a recurring event' is an important foundation needed for responding to recurring events. Definition of the term is necessary to be able to identify when a recurring event occurs. Additionally, a widely accepted definition across all NPPs and regulatory bodies is desirable such that consistent identification of recurring events are made from country to country. It was generally agreed that a widely accepted definition of a recurring event could then be further revised at a local NPP or regulatory body level to more restrictive criteria to meet local requirements. - NPPs should be expected to review events from other NPPs, both domestically and internationally, to identify and implement lessons learned from others. The definition of a recurring event at any one NPP should encompass domestic or international events at other NPPs. Here, one has to take into account if it is reasonable to expect that the NPP was aware of the event at another installation that is the event was shared via IRS or WANO event reporting systems. - Normal event investigation procedures and processes currently used by some NPPs and regulatory bodies may not

[Molecular imaging; current status and future prospects in USA].

Science.gov (United States)

Kobayashi, Hisataka

2007-02-01

The goal of this review is to introduce the definition, current status, and future prospects of the molecular imaging, which has recently been a hot topic in medicine and the biological science in USA. In vivo imaging methods to visualize the molecular events and functions in organs or animals/humans are overviewed and discussed especially in combinations of imaging modalities (machines) and contrast agents(chemicals) used in the molecular imaging. Next, the close relationship between the molecular imaging and the nanotechnology, an important part of nanomedicine, is stressed from the aspect of united multidisciplinary sciences such as physics, chemistry, biology, and medicine.

Strategies and Exemplars for Public Outreach Events: Planning, Implementation, Evaluation

Science.gov (United States)

Cobb, W. H.; Buxner, S.; Shipp, S. S.; Shebby, S.

2015-12-01

IntroductionEach year the National Aeronautics and Space Administration (NASA) sponsors a variety of public outreach events to share information with educators, students, and the general public. These events are designed to increase interest in and awareness of the mission and goals of NASA. Planning and implementation best practices gleaned from the NASA SMD Education's review of large-scale events, "Best Practices in Outreach Events" will be shared. Outcomes from an event, i C Ceres, celebrating the Dawn mission's arrival at dwarf planet Ceres that utilized these strategies will be shared. Best practices included can be pertinent for all event organizers and evaluators regardless of event size. BackgroundThe literature review focused on identifying evaluations of large-scale public outreach events—and, within these evaluations, identifying best practices. The following criteria for identifying journal articles and reports to potentially include: Public, science-related events open to adults and children. Events with more than 1,000 attendees. Events that occurred during the last 5 years. Evaluations that included information on data collected from visitors and/or volunteers. Evaluations that specified the type of data collected, methodology, and associated results. Planning and Implementation Best PracticesThe literature review revealed key considerations for planning and of large-scale events implementing events. A summary of related best practices is presented below. 1) Advertise the event 2) Use and advertise access to scientists 3) Recruit scientists using these findings 4) Ensure that the event is group and particularly child friendly 5) Target specific event outcomes Best Practices Informing Real-world Planning, Implementation and EvaluationDawn mission's collaborative design of a series of events, i C Ceres, including in-person, interactive events geared to families and live presentations will be shared. Outcomes and lessons learned will be imparted

Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model.

Science.gov (United States)

van Koppen, Arianne; Verschuren, Lars; van den Hoek, Anita M; Verheij, Joanne; Morrison, Martine C; Li, Kelvin; Nagabukuro, Hiroshi; Costessi, Adalberto; Caspers, Martien P M; van den Broek, Tim J; Sagartz, John; Kluft, Cornelis; Beysen, Carine; Emson, Claire; van Gool, Alain J; Goldschmeding, Roel; Stoop, Reinout; Bobeldijk-Pastorova, Ivana; Turner, Scott M; Hanauer, Guido; Hanemaaijer, Roeland

2018-01-01

The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. A time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis. An integrative systems biology approach was used to elucidate candidate markers linked to the active fibrosis process by combining transcriptomics, dynamic proteomics, and histopathology. The translational value of these findings were confirmed using human NASH data sets. High-fat-diet feeding resulted in obesity, hyperlipidemia, insulin resistance, and NASH with fibrosis in a time-dependent manner. Temporal dynamics of key molecular processes involved in the development of NASH were identified, including lipid metabolism, inflammation, oxidative stress, and fibrosis. A data-integrative approach enabled identification of the active fibrotic process preceding histopathologic detection using a novel molecular fibrosis signature. Human studies were used to identify overlap of genes and processes and to perform a network biology-based prioritization to rank top candidate markers representing the early manifestation of fibrosis. An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (pre)clinical experimental time frames.

Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010–2012

Science.gov (United States)

Okoth, Sheila Akinyi; Arrospide, Nancy; Gonzalez, Rommell V.; Sánchez, Juan F.; Macedo, Silvia; Conde, Silvia; Tapia, L. Lorena; Salas, Carola; Gamboa, Dionicia; Herrera, Yeni; Edgel, Kimberly A.; Udhayakumar, Venkatachalam; Lescano, Andrés G.

2015-01-01

During 2010–2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998–2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events. PMID:25897626

A review for identification of initiating events in event tree development process on nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Riyadi, Eko H., E-mail: e.riyadi@bapeten.go.id [Center for Regulatory Assessment of Nuclear Installation and Materials, Nuclear Energy Regulatory Agency (BAPETEN), Jl. Gajah Mada 8 Jakarta 10120 (Indonesia)

2014-09-30

Initiating event is defined as any event either internal or external to the nuclear power plants (NPPs) that perturbs the steady state operation of the plant, if operating, thereby initiating an abnormal event such as transient or loss of coolant accident (LOCA) within the NPPs. These initiating events trigger sequences of events that challenge plant control and safety systems whose failure could potentially lead to core damage or large early release. Selection for initiating events consists of two steps i.e. first step, definition of possible events, such as by evaluating a comprehensive engineering, and by constructing a top level logic model. Then the second step, grouping of identified initiating event's by the safety function to be performed or combinations of systems responses. Therefore, the purpose of this paper is to discuss initiating events identification in event tree development process and to reviews other probabilistic safety assessments (PSA). The identification of initiating events also involves the past operating experience, review of other PSA, failure mode and effect analysis (FMEA), feedback from system modeling, and master logic diagram (special type of fault tree). By using the method of study for the condition of the traditional US PSA categorization in detail, could be obtained the important initiating events that are categorized into LOCA, transients and external events.

Massive expansion of marine archaea during a mid-Cretaceous oceanic anoxic event

DEFF Research Database (Denmark)

Kuypers, M.M.M.; Blokker, P.; Erbacher, J.

2001-01-01

molecular fossils indicates that these archaea were living chemoautotrophically. Their massive expansion may have been a response to the strong stratification of the ocean during this anoxic event. Indeed, the sedimentary record of archaeal membrane lipids suggests that this anoxic event marks a time......Biogeochemical and stable carbon isotopic analysis of black-shale sequences deposited during an Albian oceanic anoxic event (∼112 million years ago) indicate that up to 80 weight percent of sedimentary organic carbon is derived from marine, nonthermophilic archaea. The carbon-13 content of archaeal...

Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

Science.gov (United States)

Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

2017-06-01

The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Southern-by-Sequencing: A Robust Screening Approach for Molecular Characterization of Genetically Modified Crops

Directory of Open Access Journals (Sweden)

Gina M. Zastrow-Hayes

2015-03-01

Full Text Available Molecular characterization of events is an integral part of the advancement process during genetically modified (GM crop product development. Assessment of these events is traditionally accomplished by polymerase chain reaction (PCR and Southern blot analyses. Southern blot analysis can be time-consuming and comparatively expensive and does not provide sequence-level detail. We have developed a sequence-based application, Southern-by-Sequencing (SbS, utilizing sequence capture coupled with next-generation sequencing (NGS technology to replace Southern blot analysis for event selection in a high-throughput molecular characterization environment. SbS is accomplished by hybridizing indexed and pooled whole-genome DNA libraries from GM plants to biotinylated probes designed to target the sequence of transformation plasmids used to generate events within the pool. This sequence capture process enriches the sequence data obtained for targeted regions of interest (transformation plasmid DNA. Taking advantage of the DNA adjacent to the targeted bases (referred to as next-to-target sequence that accompanies the targeted transformation plasmid sequence, the data analysis detects plasmid-to-genome and plasmid-to-plasmid junctions introduced during insertion into the plant genome. Analysis of these junction sequences provides sequence-level information as to the following: the number of insertion loci including detection of unlinked, independently segregating, small DNA fragments; copy number; rearrangements, truncations, or deletions of the intended insertion DNA; and the presence of transformation plasmid backbone sequences. This molecular evidence from SbS analysis is used to characterize and select GM plants meeting optimal molecular characterization criteria. SbS technology has proven to be a robust event screening tool for use in a high-throughput molecular characterization environment.

Integration of molecular typing results into tuberculosis surveillance in Germany—A pilot study

Science.gov (United States)

Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

2017-01-01

An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48–98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the communication between local public health offices in different counties to enhance TB control

Event Reconstruction Algorithms for the ATLAS Trigger

Energy Technology Data Exchange (ETDEWEB)

Fonseca-Martin, T.; /CERN; Abolins, M.; /Michigan State U.; Adragna, P.; /Queen Mary, U. of London; Aleksandrov, E.; /Dubna, JINR; Aleksandrov, I.; /Dubna, JINR; Amorim, A.; /Lisbon, LIFEP; Anderson, K.; /Chicago U., EFI; Anduaga, X.; /La Plata U.; Aracena, I.; /SLAC; Asquith, L.; /University Coll. London; Avolio, G.; /CERN; Backlund, S.; /CERN; Badescu, E.; /Bucharest, IFIN-HH; Baines, J.; /Rutherford; Barria, P.; /Rome U. /INFN, Rome; Bartoldus, R.; /SLAC; Batreanu, S.; /Bucharest, IFIN-HH /CERN; Beck, H.P.; /Bern U.; Bee, C.; /Marseille, CPPM; Bell, P.; /Manchester U.; Bell, W.H.; /Glasgow U. /Pavia U. /INFN, Pavia /Regina U. /CERN /Annecy, LAPP /Paris, IN2P3 /Royal Holloway, U. of London /Napoli Seconda U. /INFN, Naples /Argonne /CERN /UC, Irvine /Barcelona, IFAE /Barcelona, Autonoma U. /CERN /Montreal U. /CERN /Glasgow U. /Michigan State U. /Bucharest, IFIN-HH /Napoli Seconda U. /INFN, Naples /New York U. /Barcelona, IFAE /Barcelona, Autonoma U. /Salento U. /INFN, Lecce /Pisa U. /INFN, Pisa /Bucharest, IFIN-HH /UC, Irvine /CERN /Glasgow U. /INFN, Genoa /Genoa U. /Lisbon, LIFEP /Napoli Seconda U. /INFN, Naples /UC, Irvine /Valencia U. /Rio de Janeiro Federal U. /University Coll. London /New York U.; /more authors..

2011-11-09

The ATLAS experiment under construction at CERN is due to begin operation at the end of 2007. The detector will record the results of proton-proton collisions at a center-of-mass energy of 14 TeV. The trigger is a three-tier system designed to identify in real-time potentially interesting events that are then saved for detailed offline analysis. The trigger system will select approximately 200 Hz of potentially interesting events out of the 40 MHz bunch-crossing rate (with 10{sup 9} interactions per second at the nominal luminosity). Algorithms used in the trigger system to identify different event features of interest will be described, as well as their expected performance in terms of selection efficiency, background rejection and computation time per event. The talk will concentrate on recent improvements and on performance studies, using a very detailed simulation of the ATLAS detector and electronics chain that emulates the raw data as it will appear at the input to the trigger system.

Event reconstruction algorithms for the ATLAS trigger

Energy Technology Data Exchange (ETDEWEB)

F-Martin, T; Avolio, G; Backlund, S [European Laboratory for Particle Physics (CERN), Geneva (Switzerland); Abolins, M [Michigan State University, Department of Physics and Astronomy, East Lansing, Michigan (United States); Adragna, P [Department of Physics, Queen Mary and Westfield College, University of London, London (United Kingdom); Aleksandrov, E; Aleksandrov, I [Joint Institute for Nuclear Research, Dubna (Russian Federation); Amorim, A [Laboratorio de Instrumentacao e Fisica Experimental, Lisboa (Portugal); Anderson, K [University of Chicago, Enrico Fermi Institute, Chicago, Illinois (United States); Anduaga, X [National University of La Plata, La Plata (United States); Aracena, I; Bartoldus, R [Stanford Linear Accelerator Center (SLAC), Stanford (United States); Asquith, L [Department of Physics and Astronomy, University College London, London (United Kingdom); Badescu, E [National Institute for Physics and Nuclear Engineering, Institute of Atomic Physics, Bucharest (Romania); Baines, J [Rutherford Appleton Laboratory, Chilton, Didcot (United Kingdom); Beck, H P [Laboratory for High Energy Physics, University of Bern, Bern (Switzerland); Bee, C [Centre de Physique des Particules de Marseille, IN2P3-CNRS, Marseille (France); Bell, P [Department of Physics and Astronomy, University of Manchester, Manchester (United Kingdom); Barria, P; Batreanu, S [and others

2008-07-01

The ATLAS experiment under construction at CERN is due to begin operation at the end of 2007. The detector will record the results of proton-proton collisions at a center-of-mass energy of 14 TeV. The trigger is a three-tier system designed to identify in real-time potentially interesting events that are then saved for detailed offline analysis. The trigger system will select approximately 200 Hz of potentially interesting events out of the 40 MHz bunch-crossing rate (with 10{sup 9} interactions per second at the nominal luminosity). Algorithms used in the trigger system to identify different event features of interest will be described, as well as their expected performance in terms of selection efficiency, background rejection and computation time per event. The talk will concentrate on recent improvements and on performance studies, using a very detailed simulation of the ATLAS detector and electronics chain that emulates the raw data as it will appear at the input to the trigger system.

Event reconstruction algorithms for the ATLAS trigger

International Nuclear Information System (INIS)

F-Martin, T; Avolio, G; Backlund, S; Abolins, M; Adragna, P; Aleksandrov, E; Aleksandrov, I; Amorim, A; Anderson, K; Anduaga, X; Aracena, I; Bartoldus, R; Asquith, L; Badescu, E; Baines, J; Beck, H P; Bee, C; Bell, P; Barria, P; Batreanu, S

2008-01-01

The ATLAS experiment under construction at CERN is due to begin operation at the end of 2007. The detector will record the results of proton-proton collisions at a center-of-mass energy of 14 TeV. The trigger is a three-tier system designed to identify in real-time potentially interesting events that are then saved for detailed offline analysis. The trigger system will select approximately 200 Hz of potentially interesting events out of the 40 MHz bunch-crossing rate (with 10 9 interactions per second at the nominal luminosity). Algorithms used in the trigger system to identify different event features of interest will be described, as well as their expected performance in terms of selection efficiency, background rejection and computation time per event. The talk will concentrate on recent improvements and on performance studies, using a very detailed simulation of the ATLAS detector and electronics chain that emulates the raw data as it will appear at the input to the trigger system

Molecular Pharmacology of VEGF-A Isoforms: Binding and Signalling at VEGFR2.

Science.gov (United States)

Peach, Chloe J; Mignone, Viviane W; Arruda, Maria Augusta; Alcobia, Diana C; Hill, Stephen J; Kilpatrick, Laura E; Woolard, Jeanette

2018-04-23

Vascular endothelial growth factor-A (VEGF-A) is a key mediator of angiogenesis, signalling via the class IV tyrosine kinase receptor family of VEGF Receptors (VEGFRs). Although VEGF-A ligands bind to both VEGFR1 and VEGFR2, they primarily signal via VEGFR2 leading to endothelial cell proliferation, survival, migration and vascular permeability. Distinct VEGF-A isoforms result from alternative splicing of the Vegfa gene at exon 8, resulting in VEGF xxx a or VEGF xxx b isoforms. Alternative splicing events at exons 5⁻7, in addition to recently identified posttranslational read-through events, produce VEGF-A isoforms that differ in their bioavailability and interaction with the co-receptor Neuropilin-1. This review explores the molecular pharmacology of VEGF-A isoforms at VEGFR2 in respect to ligand binding and downstream signalling. To understand how VEGF-A isoforms have distinct signalling despite similar affinities for VEGFR2, this review re-evaluates the typical classification of these isoforms relative to the prototypical, “pro-angiogenic” VEGF 165 a. We also examine the molecular mechanisms underpinning the regulation of VEGF-A isoform signalling and the importance of interactions with other membrane and extracellular matrix proteins. As approved therapeutics targeting the VEGF-A/VEGFR signalling axis largely lack long-term efficacy, understanding these isoform-specific mechanisms could aid future drug discovery efforts targeting VEGF receptor pharmacology.

Towards 'selection rules' in the radiation chemistry of molecular materials

International Nuclear Information System (INIS)

Feldman, V.I.; Inst. of Synthetic Polymetric Materials, Moscow; Moscow State Univ.

2002-01-01

Complete text of publication follows. There are a lot of experimental evidences suggesting that the primary radiation-induced events in organic solids and polymers are highly selective and sensitive to conformation, molecular packing, matrix environment, etc. Nevertheless, specific 'selection rules' in the radiation chemistry of molecules in solids are still not established. This contribution presents a review of our recent studies of the radiation damage in organic molecules in low-temperature matrices and polymers aimed at elucidation of basic physical factors controlling selectivity of the primary chemical events. The following aspects will be analyzed: 1. 'Fine tuning' effects in positive hole trapping in rigid systems containing molecular 'traps' with close ionization energy. 2. Selective chemical bond weakening in ionized molecules: experimental and theoretical results. 3. Matrix-assisted and matrix-controlled chemical reactions of ionized molecules in solid media (including the effect of 'matrix-catalysis'). 4. Effect of excess energy on the fate of ionized molecules in solid matrices: the role of intramolecular and intermolecular relaxation. Finally, the problem of experimental and theoretical simulation of the distribution of the radiation-induced events in complex molecular systems and polymers will be addressed

Forecast of icing events at a wind farm in Sweden

DEFF Research Database (Denmark)

Davis, Neil; Hahmann, Andrea N.; Clausen, Niels-Erik

2014-01-01

This paper introduces a method for identifying icing events using a physical icing model, driven by atmospheric data from the Weather Research and Forecasting (WRF) model, and applies it to a wind park in Sweden. Observed wind park icing events were identified by deviation from an idealized power...

The CBM first-level event selector

Energy Technology Data Exchange (ETDEWEB)

Cuveland, Jan de; Lindenstruth, Volker [Frankfurt Institute for Advanced Studies, Goethe University, Frankfurt (Germany)

2015-07-01

The CBM experiment currently under construction at GSI/FAIR is designed to study QCD predictions at high baryon densities. The CBM First-Level Event Selector (FLES) is the central event selection system of the experiment. Designed as a high-performance computer cluster, its task is an online analysis of the physics data including full event reconstruction at an incoming data rate exceeding 1 TByte/s. The CBM detector systems are free-running and self-triggered, delivering time-stamped data streams. As there is no inherent event separation, traditional approaches for global event building and event selection are not directly applicable. Instead of event building, the FLES combines the data from approximately 1000 input links to self-contained, overlapping processing intervals and distributes them to compute nodes. It employs a high-bandwidth InfiniBand network as well as dedicated custom FPGA input boards providing time-addressed access to buffered data. Subsequently, specialized event selection algorithms analyze these processing intervals in 4-D, identify events, and select those relevant for storage depending on the chosen CBM setup and selection scenario. This presentation outlines the design of the CBM First-level Event Selector and summarizes the results from first prototype systems.

Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques

Science.gov (United States)

Calfon, Marcella A.; Vinegoni, Claudio; Ntziachristos, Vasilis; Jaffer, Farouc A.

2010-01-01

New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics.

Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

Science.gov (United States)

Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

2016-11-01

Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Identifying Witness Accounts from Social Media Using Imagery

Directory of Open Access Journals (Sweden)

Marie Truelove

2017-04-01

Full Text Available This research investigates the use of image category classification to distinguish images posted to social media that are Witness Accounts of an event. Only images depicting observations of the event, captured by micro-bloggers at the event, are considered Witness Accounts. Identifying Witness Accounts from social media is important for services such as news, marketing and emergency response. Automated image category classification is essential due to the large number of images on social media and interest in identifying witnesses in near real time. This paper begins research of this emerging problem with an established procedure, using a bag-of-words method to create a vocabulary of visual words and classifier trained to categorize the encoded images. In order to test the procedure, a set of images were collected for case study events, Australian Football League matches, from Twitter. Evaluation shows an overall accuracy of 90% and precision and recall for both classes exceeding 83%.

Evidence of molecular evolution driven by recombination events influencing tropism in a novel human adenovirus that causes epidemic keratoconjunctivitis.

Directory of Open Access Journals (Sweden)

Michael P Walsh

2009-06-01

the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus.

Identification and analysis of external event combinations for Hanhikivi 1PRA

Energy Technology Data Exchange (ETDEWEB)

Helander, Juho [Fennovoima Oy, Helsinki (Finland)

2017-03-15

Fennovoima's nuclear power plant, Hanhikivi 1, Pyhäjoki, Finland, is currently in design phase, and its construction is scheduled to begin in 2018 and electricity production in 2024. The objective of this paper is to produce a preliminary list of safety-significant external event combinations including preliminary probability estimates, to be used in the probabilistic risk assessment of Hanhikivi 1 plant. Starting from the list of relevant single events, the relevant event combinations are identified based on seasonal variation, preconditions related to different events, and dependencies (fundamental and cascade type) between events. Using this method yields 30 relevant event combinations of two events for the Hanhikivi site. The preliminary probability of each combination is evaluated, and event combinations with extremely low probability are excluded from further analysis. Event combinations of three or more events are identified by adding possible events to the remaining combinations of two events. Finally, 10 relevant combinations of two events and three relevant combinations of three events remain. The results shall be considered preliminary and will be updated after evaluating more detailed effects of different events on plant safety.

Survey of operating experience from LERs to identify aging trends

International Nuclear Information System (INIS)

Murphy, G.A.

1985-01-01

The results of a study using the Oak Ridge National Laboratory's Nuclear Operations Analysis Center computer files of operating experience reports [licensee event reports (LERs), abnormal occurrences, etc.] are summarized in this study, specific time-related degradation mechanisms are identified as possible causes of a reportable occurrence. Data collected on domestic commercial nuclear power plants covering 1969 to 1982 yielded over 5800 events attributable to possible age related failures. Of these events, 2795 were attributable to instrument drift and are addressed separately in the report. The remaining events (3098) were reviewed, and data were collected for each event, which identified the specific system, component, and subpart: the information included the age-related mechanism, severity of the failure, and method of detection of the failure. About two-thirds of the failures were judged to be degraded, with one-third listed as catastrophic

Identification of Initiating Events for PGSFR

International Nuclear Information System (INIS)

Kim, Jintae; Jae, Moosung

2016-01-01

The Sodium-cooled Fast Reactor (SFR) is by far the most advanced reactor of the six Generation IV reactors. The SFR uses liquid sodium as the reactor coolant, which has superior heat transport characteristics. It also allows high power density with low coolant volume fraction and operation at low pressure. In Korea, KAERI has been developing Prototype Generation-IV Sodium-cooled Fast Reactor (PGSFR) that employs passive safety systems and inherent reactivity feedback effects. In order to prepare for the licensing, it is necessary to assess the safety of the reactor. Thus, the objective of this study is to conduct accident sequence analysis that can contribute to risk assessment. The analysis embraces identification of initiating events and accident sequences development. PGSFR is to test and demonstrate the performance of transuranic (TRU)-containing metal fuel required for a commercial SFR, and to demonstrate the TRU transmutation capability of a burner reactor as a part of an advanced fuel cycle system. Initiating events that can happen in PGSFR were identified through the MLD method. This method presents a model of a plant in terms of individual events and their combinations in a systematic and logical way. The 11 identified initiating events in this study include the events considered in the past analysis that was conducted for PRISM-150

Identification of Initiating Events for PGSFR

Energy Technology Data Exchange (ETDEWEB)

Kim, Jintae; Jae, Moosung [Hanyang University, Seoul (Korea, Republic of)

2016-10-15

The Sodium-cooled Fast Reactor (SFR) is by far the most advanced reactor of the six Generation IV reactors. The SFR uses liquid sodium as the reactor coolant, which has superior heat transport characteristics. It also allows high power density with low coolant volume fraction and operation at low pressure. In Korea, KAERI has been developing Prototype Generation-IV Sodium-cooled Fast Reactor (PGSFR) that employs passive safety systems and inherent reactivity feedback effects. In order to prepare for the licensing, it is necessary to assess the safety of the reactor. Thus, the objective of this study is to conduct accident sequence analysis that can contribute to risk assessment. The analysis embraces identification of initiating events and accident sequences development. PGSFR is to test and demonstrate the performance of transuranic (TRU)-containing metal fuel required for a commercial SFR, and to demonstrate the TRU transmutation capability of a burner reactor as a part of an advanced fuel cycle system. Initiating events that can happen in PGSFR were identified through the MLD method. This method presents a model of a plant in terms of individual events and their combinations in a systematic and logical way. The 11 identified initiating events in this study include the events considered in the past analysis that was conducted for PRISM-150.

Experience feedback from event reports: the human contribution

International Nuclear Information System (INIS)

Swaton, E.; Tolstykh, V.

1990-01-01

Analysis of reported events reveals that in a large number of areas human intervention contributed to the initiation and/or development of these events. Since an accident at any nuclear power plant can have a world-wide effect on public acceptance, the need for attentive and reliable human behavior assumes an even greater significance. The identification of areas where human interaction can have an impact on safe operation is mainly relying on the analysis of events reported to the nuclear community. Any substantial compilation of safety significant operational events such as contained in the IAEA-IRS (Incident Reporting System) is bound to provide valuable and factual insights into problem areas, their origin, development, impact and some remedial actions. Thus a systematic analysis has been carried out on over 200 events where a human contribution could be identified. Some events of particular interest will be discussed and furthermore generic lessons will be presented. In addition the Assessment of Safety Significant Event Technique (ASSET) developed within IAEA which provides a structured methodology to identify not only the direct cause explaining why an individual failed but more important, insights on the root causes explaining why this latent deficiency was not detected earlier through the plant surveillance programme was applied. (author)

Recurring events - Volume 2

International Nuclear Information System (INIS)

2003-04-01

known, thus the actions taken were not effective in preventing recurrence of an event, - The contributing factors or causes of the event were not taken into account in defining the actions to be taken. Several good practices were identified to prevent recurring events. These practices are part of related guides provided by national and international bodies. Some of these are: - NPPs should analyse recurring events in-depth, in order to identify root causes and contributing factors to prevent further recurrence. The specific factors that failed to prevent recurrence should be investigated and identified (that is, why prior operating experience was not effectively applied). - For minor events, trend analyses should be performed to monitor the frequency of component failures (which may be unavoidable) or the frequency of minor human performance problems (which may indicate weaknesses in error prevention processes and programs). - Analysis of external operating experiences from other NPPs should be strengthened to broaden the basis for preventive measures; - Actions taken after events should be assessed regarding their effectiveness in preventing recurrence of similar events. Subsequent to the workshop, a more detailed search of reports of operating experience, including IRS and other reports from national sources, resulted in the determination of a number of recurring categories: - Loss of RHR at mid-loop (in the 1999 report also); - BWR instability (in the 1999 report also); - PWR vessel corrosion due to boric acid effects; - Hydrogen detonation in BWR piping; - Steam Generator Tube Rupture; - Multiple valve failures in ECCS; - Service Water Failure due to Marine Biofouling (in the 1999 report also); - System Level Failures with Human Factors Considerations; - Strainer Clogging (sources of emergency injection or recirculation). Five conclusions were established on the basis of the workshop and the recurring event analysis: Conclusion 1: Recurring events continue to be

Molecular networks of human muscle adaptation to exercise and age.

Directory of Open Access Journals (Sweden)

Bethan E Phillips

2013-03-01

Full Text Available Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44 who then undertook 20 weeks of supervised resistance-exercise training (RET. Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%, and when applying Ingenuity Pathway Analysis (IPA up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR signaling associating with growth (P = 1.4 × 10(-30. Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6 × 10(-13 and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = -2.3; P = 3 × 10(-7 with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET, they appear to represent "generic" physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52, with a continuum of subject ages (18-78 y, the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1 × 10(-6 and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to

Licensee Event Report (LER) compilation, March 1992

International Nuclear Information System (INIS)

1992-05-01

This monthly report contains Licensee Event Report (LER) operational information that was processed into the LER data file of the Nuclear Operations Analysis Center (NOAC) during the one month period identified on the cover of the document. The LERs, from which this information is derived, are submitted to the Nuclear Regulatory Commission (NRC) by nuclear power plant licensees in accordance with federal regulations. Procedures for LER reporting for revisions to those events occurring prior to 1984 are described in NRC Regulatory Guide 1.16 and NUREG-0161, Instructions for Preparation of Data Entry Sheets for Licensee Event Reports. For those events occurring on and after January 1, 1984, LERs are being submitted in accordance with the revised rule contained in Title 10 Part 50.73 of the Code of Federal Regulations (10 CFR 50.73 -- Licensee Event Report System) which was published in the Federal Register (Vol. 48, No. 144) on July 26, 1983. NUREG-1022, Licensee Event Report System -- Description of Systems and Guidelines for Reporting, provides supporting guidance and information on the revised LER rule. The LER summaries in this report are arranged alphabetically by facility name and then chronologically by event date for each facility. Component, system, keyword, and component vendor indexes follow the summaries. Vendors are those identified by the utility when the LER form is initiated; the keywords for the component, system, and general keyword indexes are assigned by the computer using correlation tables from the Sequence Coding and Search System

Licensee Event Report (LER) compilation, April 1991

International Nuclear Information System (INIS)

1991-05-01

This monthly report contains Licensee Event Report (LER) operational information that was processed into the LER data file of the Nuclear Safety Information Center (NSIC) during the one month period identified on the cover of the document. The LERs, from which this information is derived, are submitted to the Nuclear Regulatory Commission (NRC) by nuclear power plant licensees in accordance with federal regulations. Procedures for LER reporting for revisions to those events occurring prior to 1984 are described in NRC Regulatory Guide 1.16 and NUREG-0161, Instructions for Preparation of Data Entry Sheets for Licensee Event Reports. For those events occurring on and after January 1, 1984, LERs are being submitted in accordance with the revised rule contained in Title 10 Part 50.73 of the Code of Federal Regulations (10 CFR 50.73 -- Licensee Event Report System) which was published in the Federal Register (Vol. 48, No. 144) on July 26, 1983. NUREG-1022, Licensee Event Report System -- Description of Systems and Guidelines for Reporting, provides supporting guidance and information on the revised LER rule. The LER summaries in this report are arranged alphabetically by facility name and then chronologically by event date for each facility. Component, system, keyword, and component vendor indexes follow the summaries. Vendors are those identified by the utility when the LER form is initiated; the keywords for the component, system, and general keyword indexes are assigned by the computer using correlation tables from the Sequence Coding and Search System

Tool for Automated Retrieval of Generic Event Tracks (TARGET)

Science.gov (United States)

Clune, Thomas; Freeman, Shawn; Cruz, Carlos; Burns, Robert; Kuo, Kwo-Sen; Kouatchou, Jules

2013-01-01

Methods have been developed to identify and track tornado-producing mesoscale convective systems (MCSs) automatically over the continental United States, in order to facilitate systematic studies of these powerful and often destructive events. Several data sources were combined to ensure event identification accuracy. Records of watches and warnings issued by National Weather Service (NWS), and tornado locations and tracks from the Tornado History Project (THP) were used to locate MCSs in high-resolution precipitation observations and GOES infrared (11-micron) Rapid Scan Operation (RSO) imagery. Thresholds are then applied to the latter two data sets to define MCS events and track their developments. MCSs produce a broad range of severe convective weather events that are significantly affecting the living conditions of the populations exposed to them. Understanding how MCSs grow and develop could help scientists improve their weather prediction models, and also provide tools to decision-makers whose goals are to protect populations and their property. Associating storm cells across frames of remotely sensed images poses a difficult problem because storms evolve, split, and merge. Any storm-tracking method should include the following processes: storm identification, storm tracking, and quantification of storm intensity and activity. The spatiotemporal coordinates of the tracks will enable researchers to obtain other coincident observations to conduct more thorough studies of these events. In addition to their tracked locations, their areal extents, precipitation intensities, and accumulations all as functions of their evolutions in time were also obtained and recorded for these events. All parameters so derived can be catalogued into a moving object database (MODB) for custom queries. The purpose of this software is to provide a generalized, cross-platform, pluggable tool for identifying events within a set of scientific data based upon specified criteria with the

Life Events, Sibling Warmth, and Youths' Adjustment

Science.gov (United States)

Waite, Evelyn B.; Shanahan, Lilly; Calkins, Susan D.; Keane, Susan P.; O'Brien, Marion

2011-01-01

Sibling warmth has been identified as a protective factor from life events, but stressor-support match-mismatch and social domains perspectives suggest that sibling warmth may not efficiently protect youths from all types of life events. We tested whether sibling warmth moderated the association between each of family-wide, youths' personal, and…

Traumatic Childhood Events and Autism Spectrum Disorder

Science.gov (United States)

Kerns, Connor Morrow; Newschaffer, Craig J.; Berkowitz, Steven J.

2015-01-01

Traumatic childhood events are associated with a wide range of negative physical, psychological and adaptive outcomes over the life course and are one of the few identifiable causes of psychiatric illness. Children with autism spectrum disorder (ASD) may be at increased risk for both encountering traumatic events and developing traumatic sequelae;…

Molecular analysis of precursor lesions in familial pancreatic cancer.

Directory of Open Access Journals (Sweden)

Tatjana Crnogorac-Jurcevic

Full Text Available With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical.We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses.Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic

ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

Directory of Open Access Journals (Sweden)

Benfeard Williams

2015-10-01

Full Text Available The increased risk of developing Alzheimer's disease (AD is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

Trends in swimming training for individual medley events

OpenAIRE

Brtník, Tomáš

2013-01-01

Title: Trends in swimming training for individual medley events Objectives: The aim of our study was to analyze performance and training for 200 and 400 m individual medley events and describe new trends in training for these swimming events Methods: Our research design was a case study. We were interested in training of three swimmers of elite performance in the 200 and 400 m individual medley events. To identify cases, we used the analysis of documents and literature, to a limited extent, t...

Whole genome sequencing identifies circulating Beijing-lineage Mycobacterium tuberculosis strains in Guatemala and an associated urban outbreak.

Science.gov (United States)

Saelens, Joseph W; Lau-Bonilla, Dalia; Moller, Anneliese; Medina, Narda; Guzmán, Brenda; Calderón, Maylena; Herrera, Raúl; Sisk, Dana M; Xet-Mull, Ana M; Stout, Jason E; Arathoon, Eduardo; Samayoa, Blanca; Tobin, David M

2015-12-01

Limited data are available regarding the molecular epidemiology of Mycobacterium tuberculosis (Mtb) strains circulating in Guatemala. Beijing-lineage Mtb strains have gained prevalence worldwide and are associated with increased virulence and drug resistance, but there have been only a few cases reported in Central America. Here we report the first whole genome sequencing of Central American Beijing-lineage strains of Mtb. We find that multiple Beijing-lineage strains, derived from independent founding events, are currently circulating in Guatemala, but overall still represent a relatively small proportion of disease burden. Finally, we identify a specific Beijing-lineage outbreak centered on a poor neighborhood in Guatemala City. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Molecular outflows in the L1641 region of Orion

International Nuclear Information System (INIS)

Morgan, J.A.

1990-01-01

Little is known about the interaction between molecular outflows associated with young stellar objects and the parent molecular cloud that produced them. This is because molecular outflows are a recently discovered phenomenon and, so, have not had their global properties studied in great detail and molecular clouds were not mapped to sufficiently high spatial resolution to resolve the interaction. The interaction between molecular outflows and the L1641 molecular cloud is addressed by both identifying and mapping all the molecular outflows as well as the detailed structure of the cloud. Candidate molecular outflows were found from single point 12-CO observations of young stellar objects identified from the IRAS survey data. The candidate sources were then mapped to confirm their molecular outflow nature. From these maps, molecular outflow characteristics such as their morphology, orientation, and energetics were determined. In addition, the Orion molecular cloud was mapped to compare directly with the molecular outflows. The molecular outflows identified were found to have rising infrared spectra, radio continuum emission that suggests a stellar wind or optically thick H II region, and molecular line strengths that indicate that they are embedded within a very dense environment. The lack of an optical counterpart for many molecular outflows suggests that they occur at the earliest stages of stellar evolution. The lack of an optical counterpart for many molecular outflows suggest that they occur at the earliest stages of stellar evolution. The orientations of the molecular outflows appear to lie in no preferred direction and they have shapes that indicate that the molecular cloud is responsible for determining their direction and collimation

Microaerophilic conditions permit to mimic in vitro events occurring during in vivo Helicobacter pylori infection and to identify Rho/Ras-associated proteins in cellular signaling.

Science.gov (United States)

Cottet, Sandra; Corthésy-Theulaz, Irène; Spertini, François; Corthésy, Blaise

2002-09-13

Molecular dissection of the mechanisms underlying Helicobacter pylori infection suffers from the lack of in vitro systems mimicking in vivo observations. A system was developed whereby human epithelial cells (Caco-2) grown as polarized monolayers and bacteria can communicate with each other under culture conditions optimal for each partner. Caco-2 cells grown on filter supports were inserted in a vertical position into diffusion chambers equilibrated with air and 5% CO(2) at their basolateral surface (aerophilic conditions) and 5% CO(2), 5% O(2), 90% N(2) (microaerophilic conditions) in the apical compartment. Remarkably, the epithelial polarized layer was stable under these asymmetric culture conditions for at least 24 h, and the presence of Caco-2 cells was necessary to maintain H. pylori growth. In contrast to previous studies conducted with non-polarized Caco-2 cells and other cell lines kept under aerophilic conditions, we found H. pylori-dependent stimulation of cytokine secretion (MCP-1 (monocyte chemoattractant protein-1), GRO-alpha (growth-regulated oncogene-alpha), RANTES (regulated on activation normal T cell expressed and secreted)). This correlated with nuclear translocation of NF-kappaB p50 and p65 subunits. Tyrosine phosphorylation of nine cellular proteins was induced or enhanced; we identified p120(RasGAP), p190(RhoGAP), p62dok (downstream of tyrosine kinases), and cortactin as H. pylori-inducible targets. Moreover, reduction of H. pylori urease expression was observed in adherent bacteria as compared with bacteria in suspension. In addition to mimicking several observations seen in the inflamed gastric mucosa, the novel in vitro system was allowed to underscore complex cellular events not seen in classical in vitro analyses of microaerophilic bacteria-epithelial cell cross-talk.

Disease management research using event graphs.

Science.gov (United States)

Allore, H G; Schruben, L W

2000-08-01

Event Graphs, conditional representations of stochastic relationships between discrete events, simulate disease dynamics. In this paper, we demonstrate how Event Graphs, at an appropriate abstraction level, also extend and organize scientific knowledge about diseases. They can identify promising treatment strategies and directions for further research and provide enough detail for testing combinations of new medicines and interventions. Event Graphs can be enriched to incorporate and validate data and test new theories to reflect an expanding dynamic scientific knowledge base and establish performance criteria for the economic viability of new treatments. To illustrate, an Event Graph is developed for mastitis, a costly dairy cattle disease, for which extensive scientific literature exists. With only a modest amount of imagination, the methodology presented here can be seen to apply modeling to any disease, human, plant, or animal. The Event Graph simulation presented here is currently being used in research and in a new veterinary epidemiology course. Copyright 2000 Academic Press.

Automated Testing of Event-Driven Applications

DEFF Research Database (Denmark)

Jensen, Casper Svenning

may be tested by selecting an interesting input (i.e. a sequence of events), and deciding if a failure occurs when the selected input is applied to the event-driven application under test. Automated testing promises to reduce the workload for developers by automatically selecting interesting inputs...... and detect failures. However, it is non-trivial to conduct automated testing of event-driven applications because of, for example, infinite input spaces and the absence of specifications of correct application behavior. In this PhD dissertation, we identify a number of specific challenges when conducting...... automated testing of event-driven applications, and we present novel techniques for solving these challenges. First, we present an algorithm for stateless model-checking of event-driven applications with partial-order reduction, and we show how this algorithm may be used to systematically test web...

Molecular collision theory

CERN Document Server

Child, M S

2010-01-01

This high-level monograph offers an excellent introduction to the theory required for interpretation of an increasingly sophisticated range of molecular scattering experiments. There are five helpful appendixes dealing with continuum wavefunctions, Green's functions, semi-classical connection formulae, curve-crossing in the momentum representation, and elements of classical mechanics.The contents of this volume have been chosen to emphasize the quantum mechanical and semi-classical nature of collision events, with little attention given to purely classical behavior. The treatment is essentiall

Molecular Imaging to Identify Tumor Recurrence following Chemoradiation in a Hostile Surgical Environment

Directory of Open Access Journals (Sweden)

Olugbenga T. Okusanya

2015-01-01

Full Text Available Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a “hostile” field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

A controlled vocabulary for pathway entities and events.

Science.gov (United States)

Jupe, Steve; Jassal, Bijay; Williams, Mark; Wu, Guanming

2014-01-01

Entities involved in pathways and the events they participate in require descriptive and unambiguous names that are often not available in the literature or elsewhere. Reactome is a manually curated open-source resource of human pathways. It is accessible via a website, available as downloads in standard reusable formats and via Representational State Transfer (REST)-ful and Simple Object Access Protocol (SOAP) application programming interfaces (APIs). We have devised a controlled vocabulary (CV) that creates concise, unambiguous and unique names for reactions (pathway events) and all the molecular entities they involve. The CV could be reapplied in any situation where names are used for pathway entities and events. Adoption of this CV would significantly improve naming consistency and readability, with consequent benefits for searching and data mining within and between databases. Database URL: http://www.reactome.org. © The Author(s) 2014. Published by Oxford University Press.

Identify Dynamic Network Modules with Temporal and Spatial Constraints

Energy Technology Data Exchange (ETDEWEB)

Jin, R; McCallen, S; Liu, C; Almaas, E; Zhou, X J

2007-09-24

Despite the rapid accumulation of systems-level biological data, understanding the dynamic nature of cellular activity remains a difficult task. The reason is that most biological data are static, or only correspond to snapshots of cellular activity. In this study, we explicitly attempt to detangle the temporal complexity of biological networks by using compilations of time-series gene expression profiling data.We define a dynamic network module to be a set of proteins satisfying two conditions: (1) they form a connected component in the protein-protein interaction (PPI) network; and (2) their expression profiles form certain structures in the temporal domain. We develop the first efficient mining algorithm to discover dynamic modules in a temporal network, as well as frequently occurring dynamic modules across many temporal networks. Using yeast as a model system, we demonstrate that the majority of the identified dynamic modules are functionally homogeneous. Additionally, many of them provide insight into the sequential ordering of molecular events in cellular systems. We further demonstrate that identifying frequent dynamic network modules can significantly increase the signal to noise separation, despite the fact that most dynamic network modules are highly condition-specific. Finally, we note that the applicability of our algorithm is not limited to the study of PPI systems, instead it is generally applicable to the combination of any type of network and time-series data.

Mechanical and mechanobiological influences on bone fracture repair : identifying important cellular characteristics

NARCIS (Netherlands)

Isaksson, H.E.

2007-01-01

Fracture repair is a complex and multifactorial process, which involves a well-programmed series of cellular and molecular events that result in a combination of intramembranous and endochondral bone formation. The vast majority of fractures is treated successfully. They heal through ‘secondary

Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

Directory of Open Access Journals (Sweden)

Deodutta Roy

2015-10-01

Full Text Available We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs, bisphenols (BPs, and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

Distinct Molecular Signature of Murine Fetal Liver and Adult Hematopoietic Stem Cells Identify Novel Regulators of Hematopoietic Stem Cell Function.

Science.gov (United States)

Manesia, Javed K; Franch, Monica; Tabas-Madrid, Daniel; Nogales-Cadenas, Ruben; Vanwelden, Thomas; Van Den Bosch, Elisa; Xu, Zhuofei; Pascual-Montano, Alberto; Khurana, Satish; Verfaillie, Catherine M

2017-04-15

During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs. We reanalyzed these data to identify key transcriptional regulators that play important roles in the expansion of HSCs during development. The comparison of FL E14.5 with ABM HSCs identified more than 1,400 differentially expressed genes. More than 200 genes were shortlisted based on the gene ontology (GO) annotation term "transcription." By morpholino-based knockdown studies in zebrafish, we assessed the function of 18 of these regulators, previously not associated with HSC proliferation. Our studies identified a previously unknown role for tdg, uhrf1, uchl5, and ncoa1 in the emergence of definitive hematopoiesis in zebrafish. In conclusion, we demonstrate that identification of genes involved in transcriptional regulation differentially expressed between expanding FL HSCs and quiescent ABM HSCs, uncovers novel regulators of HSC function.

Korea Microlensing Telescope Network Microlensing Events from 2015: Event-finding Algorithm, Vetting, and Photometry

Science.gov (United States)

Kim, D.-J.; Kim, H.-W.; Hwang, K.-H.; Albrow, M. D.; Chung, S.-J.; Gould, A.; Han, C.; Jung, Y. K.; Ryu, Y.-H.; Shin, I.-G.; Yee, J. C.; Zhu, W.; Cha, S.-M.; Kim, S.-L.; Lee, C.-U.; Lee, D.-J.; Lee, Y.; Park, B.-G.; Pogge, R. W.; The KMTNet Collaboration

2018-02-01

We present microlensing events in the 2015 Korea Microlensing Telescope Network (KMTNet) data and our procedure for identifying these events. In particular, candidates were detected with a novel “completed-event” microlensing event-finder algorithm. The algorithm works by making linear fits to a ({t}0,{t}{eff},{u}0) grid of point-lens microlensing models. This approach is rendered computationally efficient by restricting u 0 to just two values (0 and 1), which we show is quite adequate. The implementation presented here is specifically tailored to the commission-year character of the 2015 data, but the algorithm is quite general and has already been applied to a completely different (non-KMTNet) data set. We outline expected improvements for 2016 and future KMTNet data. The light curves of the 660 “clear microlensing” and 182 “possible microlensing” events that were found in 2015 are presented along with our policy for their public release.

Using Lead Concentrations and Stable Lead Isotope Ratios to Identify Contamination Events in Alluvial Soils

International Nuclear Information System (INIS)

Saint-Laurent, D.; St-Laurent, J.; Hahni, M.; Chapados, C.; Ghaleb, B.

2010-01-01

Soils contaminated with hydrocarbons (C10,C50), polycyclic aromatic hydrocarbons (PAHs), and other contaminants (e.g., As, Cd, Cu, Pb) were recently discovered on the banks of the Saint-Francois and Massawippi rivers. Alluvial soils are contaminated over a distance of 100 kilometers, and the level of the contaminated-hydrocarbon layer in the soil profiles is among the highest at the Windsor and Richmond sites. Concentrations of lead and stable lead isotope ratios ( 204 Pb/ 206 Pb, 206 Pb/ 207 Pb, 208 Pb/ 20 '6Pb) are also used to identify contamination events. The maximum and minimum values detected in soil profiles for arsenic, cadmium, and lead vary from 3.01 to 37.88?mg kg -1 (As), 0.11 to 0.81?mg kg-1 (Cd) 12.32 to 149.13?mg kg -1 (Pb), respectively, while the 207 Pb/ 206 Pb isotopic ratio values are between 0.8545 and 0.8724 for all the profiles. The highest values of trace elements (As, Pb and Zn) were detected in the hydrocarbon layer (C10,C50), most often located at the bottom of the profiles (160, 200, and 220 cm in depth). The various peaks recorded in the soils and the position of the profiles suggest that various contaminants were transported by the river on several occasions and infiltrated the soil matrix or deposited on flood plains during successive floods. Atmospheric particles which entered the river or deposited on riverbanks must also be considered as another source of pollution recorded in soils

Using Lead Concentrations and Stable Lead Isotope Ratios to Identify Contamination Events in Alluvial Soils

Directory of Open Access Journals (Sweden)

Diane Saint-Laurent

2010-01-01

Full Text Available Soils contaminated with hydrocarbons (C10–C50, polycyclic aromatic hydrocarbons (PAHs, and other contaminants (e.g., As, Cd, Cu, Pb were recently discovered on the banks of the Saint-François and Massawippi rivers. Alluvial soils are contaminated over a distance of 100 kilometers, and the level of the contaminated-hydrocarbon layer in the soil profiles is among the highest at the Windsor and Richmond sites. Concentrations of lead and stable lead isotope ratios (204Pb/206Pb, 207Pb/206Pb, 208Pb/206Pb are also used to identify contamination events. The maximum and minimum values detected in soil profiles for arsenic, cadmium, and lead vary from 3.01 to 37.88 mg kg-1 (As, 0.11 to 0.81 mg kg-1 (Cd 12.32 to 149.13 mg kg-1 (Pb, respectively, while the 207Pb/206Pb isotopic ratio values are between 0.8545 and 0.8724 for all the profiles. The highest values of trace elements (As, Pb and Zn were detected in the hydrocarbon layer (C10–C50, most often located at the bottom of the profiles (160, 200, and 220 cm in depth. The various peaks recorded in the soils and the position of the profiles suggest that various contaminants were transported by the river on several occasions and infiltrated the soil matrix or deposited on floodplains during successive floods. Atmospheric particles which entered the river or deposited on riverbanks must also be considered as another source of pollution recorded in soils.

Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity

Science.gov (United States)

Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.

2015-01-01

Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

Science.gov (United States)

Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

2015-08-01

Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

Evaluation of serological and molecular tests used to identify Toxoplasma gondii infection in pregnant women attended in a public health service in São Paulo state, Brazil.

Science.gov (United States)

Murata, Fernando Henrique Antunes; Ferreira, Marina Neves; Pereira-Chioccola, Vera Lucia; Spegiorin, Lígia Cosentino Junqueira Franco; Meira-Strejevitch, Cristina da Silva; Gava, Ricardo; Silveira-Carvalho, Aparecida Perpétuo; de Mattos, Luiz Carlos; Brandão de Mattos, Cinara Cássia

2017-09-01

Toxoplasmosis during pregnancy can have severe consequences. The use of sensitive and specific serological and molecular methods is extremely important for the correct diagnosis of the disease. We compared the ELISA and ELFA serological methods, conventional PCR (cPCR), Nested PCR and quantitative PCR (qPCR) in the diagnosis of Toxoplasma gondii infection in pregnant women without clinical suspicion of toxoplasmosis (G1=94) and with clinical suspicion of toxoplasmosis (G2=53). The results were compared using the Kappa index, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. The results of the serological methods showed concordance between the ELISA and ELFA methods even though ELFA identified more positive cases than ELISA. Molecular methods were discrepant with cPCR using B22/23 primers having greater sensitivity and lower specificity compared to the other molecular methods. Copyright © 2017 Elsevier Inc. All rights reserved.

Extreme inflow events and synoptic forcing in Sydney catchments

International Nuclear Information System (INIS)

Pepler, Acacia S; Rakich, Clinton S

2010-01-01

The Sydney catchment region encompasses over 16,000km 2 , supplying water to over 4 million inhabitants. However, few studies have investigated the synoptic and climatic influences on inflow in this region, which are crucial for understanding the vulnerability of water supply in a changing climate. This study identifies extremely high and low inflow events between 1960 and 2008 based on catchment averages. The focus of the study is an analysis of the synoptic cause/s of each extreme inflow event. The events are evaluated to identify any trends and also to determine the concurrent significant climatic influences on rainfall over the catchments. Relationships between catchment inflow, rainfall, tropical SST indices, and other influencing factors such as observed wind and temperatures are investigated. Our results show that East Coast Lows and anomalously easterly flow are the drivers of high inflow events, with low inflow events dominated by westerly wind patterns and the El Nino-Southern Oscillation.

Molecular aspects of tumor cell migration and invasion

Directory of Open Access Journals (Sweden)

Giuseppina Bozzuto

2010-03-01

Full Text Available Cell migration and invasion are crucial steps in many physiological events. However, they are also implicated in the physiopathology of many diseases, such as cancer. To spread through the tissues, tumor cells use mechanisms that involve several molecular actors: adhesion receptor families, receptor tyrosine kinases, cytoskeleton proteins, adapter and signalling proteins interplay in a complex scenario. The balance of cellular signals for proliferation and survival responses also regulates migratory behaviours of tumor cells. To complicate the scene of crime drug resistance players can interfere thus worsening this delicate situation. The complete understanding of this molecular jungle is an impossible mission: some molecular aspects are reviewed in this paper.

Molecular imaging: current status and emerging strategies

International Nuclear Information System (INIS)

Pysz, M.A.; Gambhir, S.S.; Willmann, J.K.

2010-01-01

In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (SPECT)-based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly-targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future.

Therapeutic molecules for multiple human diseases identified from pigeon pea (Cajanus cajan L. Millsp. through GC–MS and molecular docking

Directory of Open Access Journals (Sweden)

Deepu Mathew

2017-12-01

Full Text Available Molecular mechanism behind the therapeutic potential of pigeon pea over the human diseases such as rheumatoid arthritis, breast cancer, type II diabetes, malaria, measles and sickle cell disease were revealed through docking of GC–MS identified phyto-compound ligands with candidate disease proteins. Of the 242 ligands, three dimensional structures of 47 compounds had to be drawn using ChemSketch and the remaining structures were retrieved from PubChem and docked with the active sites of candidate proteins. The molecules identified through docking were further subjected to ADMET analysis and promising drug candidates were identified for each disease. This paper presents a precise account of the chemoprofile of pigeon pea leaves, stems and seeds, interaction of these molecules with target proteins and suggests 26 highly potential molecules which are drug candidates for multiple human diseases. Pigeon pea seeds are especially proven as invaluable source for therapeutic molecules. Keywords: Breast cancer, Drug discovery, Herbal medicine, In silico, Malaria, Measles, Phyto-compounds, Rheumatoid arthritis, Sickle cell disease, Type II diabetes

Molecular, phylogenetic and comparative genomic analysis of the cytokinin oxidase/dehydrogenase gene family in the Poaceae.

Science.gov (United States)

Mameaux, Sabine; Cockram, James; Thiel, Thomas; Steuernagel, Burkhard; Stein, Nils; Taudien, Stefan; Jack, Peter; Werner, Peter; Gray, John C; Greenland, Andy J; Powell, Wayne

2012-01-01

The genomes of cereals such as wheat (Triticum aestivum) and barley (Hordeum vulgare) are large and therefore problematic for the map-based cloning of agronomicaly important traits. However, comparative approaches within the Poaceae permit transfer of molecular knowledge between species, despite their divergence from a common ancestor sixty million years ago. The finding that null variants of the rice gene cytokinin oxidase/dehydrogenase 2 (OsCKX2) result in large yield increases provides an opportunity to explore whether similar gains could be achieved in other Poaceae members. Here, phylogenetic, molecular and comparative analyses of CKX families in the sequenced grass species rice, brachypodium, sorghum, maize and foxtail millet, as well as members identified from the transcriptomes/genomes of wheat and barley, are presented. Phylogenetic analyses define four Poaceae CKX clades. Comparative analyses showed that CKX phylogenetic groupings can largely be explained by a combination of local gene duplication, and the whole-genome duplication event that predates their speciation. Full-length OsCKX2 homologues in barley (HvCKX2.1, HvCKX2.2) and wheat (TaCKX2.3, TaCKX2.4, TaCKX2.5) are characterized, with comparative analysis at the DNA, protein and genetic/physical map levels suggesting that true CKX2 orthologs have been identified. Furthermore, our analysis shows CKX2 genes in barley and wheat have undergone a Triticeae-specific gene-duplication event. Finally, by identifying ten of the eleven CKX genes predicted to be present in barley by comparative analyses, we show that next-generation sequencing approaches can efficiently determine the gene space of large-genome crops. Together, this work provides the foundation for future functional investigation of CKX family members within the Poaceae. © 2011 National Institute of Agricultural Botany (NIAB). Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell

ATLAS proton-proton event containing four muons

CERN Multimedia

ATLAS Collaboration

2011-01-01

An event with four identified muons from a proton-proton collision in ATLAS. This event is consistent with coming from two Z particles decaying: both Z particles decay to two muons each. Such events are produced by Standard Model processes without Higgs particles. They are also a possible signature for Higgs particle production, but many events must be analysed together in order to tell if there is a Higgs signal. This view is a zoom into the central part of the detector. The four muons are picked out as red tracks. Other tracks and deposits of energy in the calorimeters are shown in yellow.

Proceedings of II Molecular Imaging Symposium Cuba - Japan

International Nuclear Information System (INIS)

2016-01-01

In the Central Theater, University Hospital 'General Calixto Garcia' took place the II Symposium on Molecular Imaging Cuba Japan in the framework of the Scientific Convention for the 120th anniversary of the hospital. The event was organized by the hospital itself with the support of the Society of Medical Physics (medical physics section), CEADEN, the Embassy of Japan and the Theragnostic Compounds R&D Center Neuroscience Research Institute Gachon University, Incheon Korea. It was attended by 80 national scientific leaders and with the invaluable presence of Dr. Tatsuo IDO, Emeritus professor of Tohoku University (Sendai, Japan) who presented the results of the scientific papers presented this year in national and international events , referring to the new technologies of molecular imaging and the importance of medical physics in its development. During the meeting the importance of the new technologies of molecular imaging, its undisputed diagnosis intake and medical treatment and the value of human capital struggled to deal with the new technologies, the view that these are only used best when it is understood that they are multidisciplinary systems where each specialist and technical personnel plays an indispensable role. The challenge has medical physics to address these new technologies and the need for changes in the theoretical and practical training in the specialty. These analyzes will be given continuity in the next symposia molecular imaging. (author)

Assessing the association between omalizumab and arteriothrombotic events through spontaneous adverse event reporting.

Science.gov (United States)

Ali, Ayad K; Hartzema, Abraham G

2012-01-01

Omalizumab is a monoclonal antibody, indicated for the treatment of severe allergic asthma. In Europe, there have been concerns about the cardiovascular safety of omalizumab. The objective of this study was to analyze the association between omalizumab and arterial thrombotic events in a spontaneous adverse drug reaction reporting database in the US. Reports of arterial thrombotic events submitted to the US Food and Drug Administration's Adverse Event Reporting System (AERS) between 2004 and 2011 were retrieved and analyzed by the reporting odds ratio data mining algorithm. The reporting odds ratio of arterial thrombotic events for omalizumab was compared with specific asthma medications and all drugs in the AERS. Values ≥2 were considered significant safety signals. The Medical Dictionary for Regulatory Activities Preferred Terms were used to identify arterial thrombotic events (eg, stroke, myocardial infarction). In total, 293,783 reports of arterial thrombotic events were retrieved (about 2% of all adverse drug reaction reports), corresponding to 2274 asthma drug-arterial thrombotic events pairs (omalizumab, 222; inhaled corticosteroids [ICS], 131; long-acting beta-agonists [LABA], 102; single-device combination ICS-LABA, 506; inhaled short-acting beta-agonists [SABA], 475; oral SABA, 6; inhaled antimuscarinics [AMC], 477; single-device combination AMC-SABA, 127; xanthines, 50; leukotriene modifiers, 174; and mast cell stabilizers, 4). Reporting odds ratio and 95% confidence interval values for omalizumab compared with other asthma drugs and all drugs in AERS were 2.75 (2.39-316) and 1.09 (0.95-1.24), respectively. Omalizumab ranked second after ICS in the risk of arterial thrombotic events, followed by AMC, AMC-SABA, and ICS-LABA. Omalizumab is associated with higher than expected reporting of arterial thrombotic events in asthmatic patients. This hypothesis needs further testing in robust epidemiological studies.

Assessing the association between omalizumab and arteriothrombotic events through spontaneous adverse event reporting

Directory of Open Access Journals (Sweden)

Ali AK

2012-05-01

Full Text Available Ayad K Ali, Abraham G HartzemaDepartment of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USABackground: Omalizumab is a monoclonal antibody, indicated for the treatment of severe allergic asthma. In Europe, there have been concerns about the cardiovascular safety of omalizumab. The objective of this study was to analyze the association between omalizumab and arterial thrombotic events in a spontaneous adverse drug reaction reporting database in the US.Methods and materials: Reports of arterial thrombotic events submitted to the US Food and Drug Administration's Adverse Event Reporting System (AERS between 2004 and 2011 were retrieved and analyzed by the reporting odds ratio data mining algorithm. The reporting odds ratio of arterial thrombotic events for omalizumab was compared with specific asthma medications and all drugs in the AERS. Values ≥2 were considered significant safety signals. The Medical Dictionary for Regulatory Activities Preferred Terms were used to identify arterial thrombotic events (eg, stroke, myocardial infarction.Results: In total, 293,783 reports of arterial thrombotic events were retrieved (about 2% of all adverse drug reaction reports, corresponding to 2274 asthma drug-arterial thrombotic events pairs (omalizumab, 222; inhaled corticosteroids [ICS], 131; long-acting beta-agonists [LABA], 102; single-device combination ICS-LABA, 506; inhaled short-acting beta-agonists [SABA], 475; oral SABA, 6; inhaled antimuscarinics [AMC], 477; single-device combination AMC-SABA, 127; xanthines, 50; leukotriene modifiers, 174; and mast cell stabilizers, 4. Reporting odds ratio and 95% confidence interval values for omalizumab compared with other asthma drugs and all drugs in AERS were 2.75 (2.39–316 and 1.09 (0.95–1.24, respectively. Omalizumab ranked second after ICS in the risk of arterial thrombotic events, followed by AMC, AMC-SABA, and ICS-LABA.Conclusion: Omalizumab is

Molecular profiling of intrahepatic cholangiocarcinoma

DEFF Research Database (Denmark)

Oliveira, Douglas V N P; Zhang, Shanshan; Chen, Xin

2017-01-01

. Areas covered: The present review article outlines the main studies and resulting discoveries on the molecular profiling of iCCA, with a special emphasis on the different techniques used for this purpose, the diagnostic and prognostic markers identified, as well as the genes and pathways that could......INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary tumor of the liver and a highly lethal disease. Therapeutic options for advanced iCCA are limited and ineffective due to the largely incomplete understanding of the molecular pathogenesis of this deadly tumor...... be potentially targeted with innovative therapies. Expert commentary: Molecular profiling has led to the identification of distinct iCCA subtypes, characterized by peculiar genetic alterations and transcriptomic features. Targeted therapies against some of the identified genes are ongoing and hold great promise...

Sensor-Generated Time Series Events: A Definition Language

Science.gov (United States)

Anguera, Aurea; Lara, Juan A.; Lizcano, David; Martínez, Maria Aurora; Pazos, Juan

2012-01-01

There are now a great many domains where information is recorded by sensors over a limited time period or on a permanent basis. This data flow leads to sequences of data known as time series. In many domains, like seismography or medicine, time series analysis focuses on particular regions of interest, known as events, whereas the remainder of the time series contains hardly any useful information. In these domains, there is a need for mechanisms to identify and locate such events. In this paper, we propose an events definition language that is general enough to be used to easily and naturally define events in time series recorded by sensors in any domain. The proposed language has been applied to the definition of time series events generated within the branch of medicine dealing with balance-related functions in human beings. A device, called posturograph, is used to study balance-related functions. The platform has four sensors that record the pressure intensity being exerted on the platform, generating four interrelated time series. As opposed to the existing ad hoc proposals, the results confirm that the proposed language is valid, that is generally applicable and accurate, for identifying the events contained in the time series.

Intentions and actions in molecular self-assembly: perspectives on students' language use

Science.gov (United States)

Höst, Gunnar E.; Anward, Jan

2017-04-01

Learning to talk science is an important aspect of learning to do science. Given that scientists' language frequently includes intentions and purposes in explanations of unobservable objects and events, teachers must interpret whether learners' use of such language reflects a scientific understanding or inaccurate anthropomorphism and teleology. In the present study, a framework consisting of three 'stances' (Dennett, 1987) - intentional, design and physical - is presented as a powerful tool for analysing students' language use. The aim was to investigate how the framework can be differentiated and used analytically for interpreting students' talk about a molecular process. Semi-structured group discussions and individual interviews about the molecular self-assembly process were conducted with engineering biology/chemistry (n = 15) and biology/chemistry teacher students (n = 6). Qualitative content analysis of transcripts showed that all three stances were employed by students. The analysis also identified subcategories for each stance, and revealed that intentional language with respect to molecular movement and assumptions about design requirements may be potentially problematic areas. Students' exclusion of physical stance explanations may indicate literal anthropomorphic interpretations. Implications for practice include providing teachers with a tool for scaffolding their use of metaphorical language and for supporting students' metacognitive development as scientific language users.

Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

Directory of Open Access Journals (Sweden)

Philip Stegmaier

Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

Molecular pathology of bone tumours: diagnostic implications.

Science.gov (United States)

Puls, Florian; Niblett, Angela J; Mangham, D Chas

2014-03-01

Alongside histomorphology and immunohistochemistry, molecular pathology is now established as one of the cornerstones in the tissue diagnosis of bone tumours. We describe the principal molecular pathological techniques employed, and each of the bone tumour entities where their identified characteristic molecular pathological changes can be detected to support and confirm the suspected histological diagnosis. Tumours discussed include fibrous dysplasia, classical and subtype osteosarcomas, central and surface cartilaginous tumours, Ewing's sarcoma, vascular tumours, aneurysmal bone cyst, chordoma, myoepithelioma, and angiomatoid fibrous histiocytoma. This is a rapidly evolving field with discoveries occurring every few months, and some of the newer entities (the Ewing's-like sarcomas), which are principally identified by their molecular pathology characteristics, are discussed. © 2013 John Wiley & Sons Ltd.

Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice.

Science.gov (United States)

Caudell, David; Harper, David P; Novak, Rachel L; Pierce, Rachel M; Slape, Christopher; Wolff, Linda; Aplan, Peter D

2010-02-11

The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.

Fast transient current response to switching events in short chains of molecular islands

Czech Academy of Sciences Publication Activity Database

Kalvová, Anděla; Špička, Václav; Velický, B.

2013-01-01

Roč. 26, č. 4 (2013), s. 773-777 ISSN 1557-1939 R&D Projects: GA ČR GAP204/12/0897 Institutional support: RVO:68378271 Keywords : nonequilibrium * molecular islands * initial correlations * transient currents Subject RIV: BE - Theoretical Physics Impact factor: 0.930, year: 2013

Events as Power Source: Wireless Sustainable Corrosion Monitoring

OpenAIRE

Sun, Guodong; Qiao, Guofu; Zhao, Lin; Chen, Zhibo

2013-01-01

This study presents and implements a corrosion-monitoring wireless sensor platform, EPS (Events as Power Source), which monitors the corrosion events in reinforced concrete (RC) structures, while being powered by the micro-energy released from the corrosion process. In EPS, the proposed corrosion-sensing device serves both as the signal source for identifying corrosion and as the power source for driving the sensor mote, because the corrosion process (event) releases electric energy; this is ...

Unusual event report from Oskarshamn

International Nuclear Information System (INIS)

1996-01-01

The title of the report was intended to reflect the cause of the shutdown and the report to be regarded as a summary of the deficiencies that had been revealed and remedied. No single deficiency was regarded as reportable as an unusual event, but taken together the identified deficiencies deviated from the assumed safety level to the extent that it should be reported. The unusual event report refers to two main documents presenting measures taken to return to reported safety level, one concerning technical and one organizational measures

Alternative measures of risk of extreme events in decision trees

International Nuclear Information System (INIS)

Frohwein, H.I.; Lambert, J.H.; Haimes, Y.Y.

1999-01-01

A need for a methodology to control the extreme events, defined as low-probability, high-consequence incidents, in sequential decisions is identified. A variety of alternative and complementary measures of the risk of extreme events are examined for their usability as objective functions in sequential decisions, represented as single- or multiple-objective decision trees. Earlier work had addressed difficulties, related to non-separability, with the minimization of some measures of the risk of extreme events in sequential decisions. In an extension of these results, it is shown how some non-separable measures of the risk of extreme events can be interpreted in terms of separable constituents of risk, thereby enabling a wider class of measures of the risk of extreme events to be handled in a straightforward manner in a decision tree. Also for extreme events, results are given to enable minimax- and Hurwicz-criterion analyses in decision trees. An example demonstrates the incorporation of different measures of the risk of extreme events in a multi-objective decision tree. Conceptual formulations for optimizing non-separable measures of the risk of extreme events are identified as an important area for future investigation

MGR External Events Hazards Analysis

International Nuclear Information System (INIS)

Booth, L.

1999-01-01

The purpose and objective of this analysis is to apply an external events Hazards Analysis (HA) to the License Application Design Selection Enhanced Design Alternative 11 [(LADS EDA II design (Reference 8.32))]. The output of the HA is called a Hazards List (HL). This analysis supersedes the external hazards portion of Rev. 00 of the PHA (Reference 8.1). The PHA for internal events will also be updated to the LADS EDA II design but under a separate analysis. Like the PHA methodology, the HA methodology provides a systematic method to identify potential hazards during the 100-year Monitored Geologic Repository (MGR) operating period updated to reflect the EDA II design. The resulting events on the HL are candidates that may have potential radiological consequences as determined during Design Basis Events (DBEs) analyses. Therefore, the HL that results from this analysis will undergo further screening and analysis based on the criteria that apply during the performance of DBE analyses

Consequence Prioritization Process for Potential High Consequence Events (HCE)

Energy Technology Data Exchange (ETDEWEB)

Freeman, Sarah G. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-10-31

This document describes the process for Consequence Prioritization, the first phase of the Consequence-Driven Cyber-Informed Engineering (CCE) framework. The primary goal of Consequence Prioritization is to identify potential disruptive events that would significantly inhibit an organization’s ability to provide the critical services and functions deemed fundamental to their business mission. These disruptive events, defined as High Consequence Events (HCE), include both events that have occurred or could be realized through an attack of critical infrastructure owner assets. While other efforts have been initiated to identify and mitigate disruptive events at the national security level, such as Presidential Policy Directive 41 (PPD-41), this process is intended to be used by individual organizations to evaluate events that fall below the threshold for a national security. Described another way, Consequence Prioritization considers threats greater than those addressable by standard cyber-hygiene and includes the consideration of events that go beyond a traditional continuity of operations (COOP) perspective. Finally, Consequence Prioritization is most successful when organizations adopt a multi-disciplinary approach, engaging both cyber security and engineering expertise, as in-depth engineering perspectives are required to recognize and characterize and mitigate HCEs. Figure 1 provides a high-level overview of the prioritization process.

Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens

DEFF Research Database (Denmark)

Skjøt, R L; Oettinger, T; Rosenkrands, I

2000-01-01

Culture filtrate from Mycobacterium tuberculosis contains protective antigens of relevance for the generation of a new antituberculosis vaccine. We have identified two previously uncharacterized M. tuberculosis proteins (TB7.3 and TB10.4) from the highly active low-mass fraction of culture filtrate....... The molecules were characterized, mapped in a two-dimensional electrophoresis reference map of short-term culture filtrate, and compared with another recently identified low-mass protein, CFP10 (F. X. Berthet, P. B. Rasmussen, I. Rosenkrands, P. Andersen, and B. Gicquel. Microbiology 144:3195-3203, 1998......), and the well-described ESAT-6 antigen. Genetic analyses demonstrated that TB10.4 as well as CFP10 belongs to the ESAT-6 family of low-mass proteins, whereas TB7.3 is a low-molecular-mass protein outside this family. The proteins were expressed in Escherichia coli, and their immunogenicity was tested...

Report on Fukushima Daiichi NPP precursor events

International Nuclear Information System (INIS)

2014-01-01

The main questions to be answered by this report were: The Fukushima Daiichi NPP accident, could it have been prevented? If there is a next severe accident, may it be prevented? To answer the first question, the report addressed several aspects. First, the report investigated whether precursors to the Fukushima Daiichi NPP accident existed in the operating experience; second, the reasons why these precursors did not evolve into a severe accident. Third, whether lessons learned from these precursor events were adequately considered by member countries; and finally, if the operating experience feedback system needs to be improved, based on the previous analysis. To address the second question which is much more challenging, the report considered precursor events identified through a search and analysis of the IRS database and also precursors events based on risk significance. Both methods can point out areas where further work may be needed, even if it depends heavily on design and site-specific factors. From the operating experience side, more efforts are needed to ensure timely and full implementation of lessons learnt from precursor events. Concerning risk considerations, a combined use of risk precursors and operating experience may drive to effective changes to plants to reduce risk. The report also contains a short description and evaluation of selected precursors that are related to the course of the Fukushima Daiichi NPP accident. The report addresses the question whether operating experience feedback can be effectively used to identify plant vulnerabilities and minimize potential for severe core damage accidents. Based on several of the precursor events national or international in-depth evaluations were started. The vulnerability of NPPs due to external and internal flooding has clearly been addressed. In addition to the IRS based investigation, the WGRISK was asked to identify important precursor events based on risk significance. These precursors have

Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens

DEFF Research Database (Denmark)

Skjøt, Rikke L. V.; Oettinger, Thomas; Rosenkrands, Ida

2000-01-01

. The molecules were characterized, mapped in a two-dimensional electrophoresis reference map of short-term culture filtrate, and compared with another recently identified low-mass protein, CFP10 (F. X. Berthet, P, B. Rasmussen, I. Rosenkrands, P. Andersen, and B. Gicquel. Microbiology 144:3195-3203, 1998......), and the well-described ESAT-6 antigen. Genetic analyses demonstrated that TB10.4 as well as CFP10 belongs to the ESAT-6 family of low-mass proteins, whereas TB7.3 is a low-molecular-mass protein outside this family. The proteins were expressed in Escherichia coli, and their immunogenicity was tested...

Financial market response to extreme events indicating climatic change

Science.gov (United States)

Anttila-Hughes, J. K.

2016-05-01

A variety of recent extreme climatic events are considered to be strong evidence that the climate is warming, but these incremental advances in certainty often seem ignored by non-scientists. I identify two unusual types of events that are considered to be evidence of climate change, announcements by NASA that the global annual average temperature has set a new record, and the sudden collapse of major polar ice shelves, and then conduct an event study to test whether news of these events changes investors' valuation of energy companies, a subset of firms whose future performance is closely tied to climate change. I find evidence that both classes of events have influenced energy stock prices since the 1990s, with record temperature announcements on average associated with negative returns and ice shelf collapses associated with positive returns. I identify a variety of plausible mechanisms that may be driving these differential responses, discuss implications for energy markets' views on long-term regulatory risk, and conclude that investors not only pay attention to scientifically significant climate events, but discriminate between signals carrying different information about the nature of climatic change.

Adverse event reporting in cancer clinical trial publications.

Science.gov (United States)

Sivendran, Shanthi; Latif, Asma; McBride, Russell B; Stensland, Kristian D; Wisnivesky, Juan; Haines, Lindsay; Oh, William K; Galsky, Matthew D

2014-01-10

Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated. A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness. A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores. Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.

Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

Directory of Open Access Journals (Sweden)

Michelle R Jones

2015-08-01

Full Text Available Genome wide association studies (GWAS have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS, a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

Serial killers: ordering caspase activation events in apoptosis.

Science.gov (United States)

Slee, E A; Adrain, C; Martin, S J

1999-11-01

Caspases participate in the molecular control of apoptosis in several guises; as triggers of the death machinery, as regulatory elements within it, and ultimately as a subset of the effector elements of the machinery itself. The mammalian caspase family is steadily growing and currently contains 14 members. At present, it is unclear whether all of these proteases participate in apoptosis. Thus, current research in this area is focused upon establishing the repertoire and order of caspase activation events that occur during the signalling and demolition phases of cell death. Evidence is accumulating to suggest that proximal caspase activation events are typically initiated by molecules that promote caspase aggregation. As expected, distal caspase activation events are likely to be controlled by caspases activated earlier in the cascade. However, recent data has cast doubt upon the functional demarcation of caspases into signalling (upstream) and effector (downstream) roles based upon their prodomain lengths. In particular, caspase-3 may perform an important role in propagating the caspase cascade, in addition to its role as an effector caspase within the death programme. Here, we discuss the apoptosis-associated caspase cascade and the hierarchy of caspase activation events within it.

First-in-Human Ultrasound Molecular Imaging With a VEGFR2-Specific Ultrasound Molecular Contrast Agent (BR55) in Prostate Cancer: A Safety and Feasibility Pilot Study.

Science.gov (United States)

Smeenge, Martijn; Tranquart, François; Mannaerts, Christophe K; de Reijke, Theo M; van de Vijver, Marc J; Laguna, M Pilar; Pochon, Sibylle; de la Rosette, Jean J M C H; Wijkstra, Hessel

2017-07-01

BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-specific ultrasound molecular contrast agent (MCA), has shown promising results in multiple preclinical models regarding cancer imaging. In this first-in-human, phase 0, exploratory study, we investigated the feasibility and safety of the MCA for the detection of prostate cancer (PCa) in men using clinical standard technology. Imaging with the MCA was performed in 24 patients with biopsy-proven PCa scheduled for radical prostatectomy using a clinical ultrasound scanner at low acoustic power. Safety monitoring was done by physical examination, blood pressure and heart rate measurements, electrocardiogram, and blood sampling. As first-in-human study, MCA dosing and imaging protocol were necessarily fine-tuned along the enrollment to improve visualization. Imaging data were correlated with radical prostatectomy histopathology to analyze the detection rate of ultrasound molecular imaging with the MCA. Imaging with MCA doses of 0.03 and 0.05 mL/kg was adequate to obtain contrast enhancement images up to 30 minutes after administration. No serious adverse events or clinically meaningful changes in safety monitoring data were identified during or after administration. BR55 dosing and imaging were fine-tuned in the first 12 patients leading to 12 subsequent patients with an improved MCA dosing and imaging protocol. Twenty-three patients underwent radical prostatectomy. A total of 52 lesions were determined to be malignant by histopathology with 26 (50%) of them seen during BR55 imaging. In the 11 patients that were scanned with the improved protocol and underwent radical prostatectomy, a total of 28 malignant lesions were determined: 19 (68%) were seen during BR55 ultrasound molecular imaging, whereas 9 (32%) were not identified. Ultrasound molecular imaging with BR55 is feasible with clinical standard technology and demonstrated a good safety profile. Detectable levels of the MCA can be reached in patients

Molecular Foundry

Science.gov (United States)

. New Study Indicates Greater Capacity for Carbon Storage in the Earth's Subsurface A team of Foundry minerals which make up the dominant clays in the Earth's deep subsurface. Doubling Down on Energy Storage identify molecular components within small volumes of biological samples, such as blood or urine. Industry

Significant events in psychotherapy: An update of research findings.

Science.gov (United States)

Timulak, Ladislav

2010-11-01

Significant events research represents a specific approach to studying client-identified important moments in the therapy process. The current study provides an overview of the significant events research conducted, the methodology used together with findings and implications. PsychInfo database was searched with keywords such as significant events, important events, significant moments, important moments, and counselling or psychotherapy. The references of the selected studies were also searched. This process led to the identification of 41 primary studies that used client-identified significant event(s) as a main or secondary focus of the study. These were consequently reviewed with regard to their methodology and findings. The findings are presented according to type of study conducted. The impacts of helpful events reported by clients are focused on contributions to therapeutic relationship and to in-session outcomes. Hindering events focus on some client disappointment with the therapist or therapy. The group therapy modality highlighted additional helpful impacts (like learning from others). Perspectives on what is significant in therapy differ between clients and therapists. The intensive qualitative studies reviewed confirm that the processes involved in significant events are complex and ambiguous. Studies show that the helpful events may also contain many hindering elements and that specific events are deeply contextually embedded in the preceding events of therapy. Some studies suggest that helpful significant events are therapeutically productive although this may need to be established further. Specific intensive studies show that the clients' perceptions in therapy may differ dramatically from that of the therapist. Furthermore, the relational and emotional aspects of significant moments may be more important for the clients than the cognitive aspects of therapy which are frequently stressed by therapists. 2010 The British Psychological Society.

Fungal peroxidases : molecular aspects and applications

NARCIS (Netherlands)

Conesa, A.; Punt, P.J.; Hondel, C.A.M.J.J.

2002-01-01

Peroxidases are oxidoreductases that utilize hydrogen peroxide to catalyze oxidative reactions. A large number of peroxidases have been identified in fungal species and are being characterized at the molecular level. In this manuscript we review the current knowledge on the molecular aspects of this

Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.

Directory of Open Access Journals (Sweden)

Xianxin Li

Full Text Available Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of 'key' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or

Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.

Directory of Open Access Journals (Sweden)

Jiangan Xie

Full Text Available M. bovis strain Bacillus Calmette-Guérin (BCG has been the only licensed live attenuated vaccine against tuberculosis (TB for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis, skin (e.g., skin ulceration and cyanosis, and respiratory system (e.g., cough and pneumonia; in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria. With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG

Survival under stress: molecular mechanisms of metabolic rate ...

African Journals Online (AJOL)

Studies in my laboratory are analysing the molecular mechanisms and regulatory events that underlie transitions to and from hypometabolic states In systems including anoxia-tolerant turtles and molluscs, estivating snails and toads, hibernating small mammals, and freeze tolerant frogs and insects. Our newest research ...

An Examination of Three Spatial Event Cluster Detection Methods

Directory of Open Access Journals (Sweden)

Hensley H. Mariathas

2015-03-01

Full Text Available In spatial disease surveillance, geographic areas with large numbers of disease cases are to be identified, so that targeted investigations can be pursued. Geographic areas with high disease rates are called disease clusters and statistical cluster detection tests are used to identify geographic areas with higher disease rates than expected by chance alone. In some situations, disease-related events rather than individuals are of interest for geographical surveillance, and methods to detect clusters of disease-related events are called event cluster detection methods. In this paper, we examine three distributional assumptions for the events in cluster detection: compound Poisson, approximate normal and multiple hypergeometric (exact. The methods differ on the choice of distributional assumption for the potentially multiple correlated events per individual. The methods are illustrated on emergency department (ED presentations by children and youth (age < 18 years because of substance use in the province of Alberta, Canada, during 1 April 2007, to 31 March 2008. Simulation studies are conducted to investigate Type I error and the power of the clustering methods.

Event-by-event jet quenching

Energy Technology Data Exchange (ETDEWEB)

Fries, R.J.; Rodriguez, R.; Ramirez, E.

2010-08-14

High momentum jets and hadrons can be used as probes for the quark gluon plasma (QGP) formed in nuclear collisions at high energies. We investigate the influence of fluctuations in the fireball on jet quenching observables by comparing propagation of light quarks and gluons through averaged, smooth QGP fireballs with event-by-event jet quenching using realistic inhomogeneous fireballs. We find that the transverse momentum and impact parameter dependence of the nuclear modification factor R{sub AA} can be fit well in an event-by-event quenching scenario within experimental errors. However the transport coefficient {cflx q} extracted from fits to the measured nuclear modification factor R{sub AA} in averaged fireballs underestimates the value from event-by-event calculations by up to 50%. On the other hand, after adjusting {cflx q} to fit R{sub AA} in the event-by-event analysis we find residual deviations in the azimuthal asymmetry v{sub 2} and in two-particle correlations, that provide a possible faint signature for a spatial tomography of the fireball. We discuss a correlation function that is a measure for spatial inhomogeneities in a collision and can be constrained from data.

Event-by-event jet quenching

Energy Technology Data Exchange (ETDEWEB)

Rodriguez, R. [Cyclotron Institute and Physics Department, Texas A and M University, College Station, TX 77843 (United States); Fries, R.J., E-mail: rjfries@comp.tamu.ed [Cyclotron Institute and Physics Department, Texas A and M University, College Station, TX 77843 (United States); RIKEN/BNL Research Center, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ramirez, E. [Physics Department, University of Texas El Paso, El Paso, TX 79968 (United States)

2010-09-27

High momentum jets and hadrons can be used as probes for the quark gluon plasma (QGP) formed in nuclear collisions at high energies. We investigate the influence of fluctuations in the fireball on jet quenching observables by comparing propagation of light quarks and gluons through averaged, smooth QGP fireballs with event-by-event jet quenching using realistic inhomogeneous fireballs. We find that the transverse momentum and impact parameter dependence of the nuclear modification factor R{sub AA} can be fit well in an event-by-event quenching scenario within experimental errors. However the transport coefficient q extracted from fits to the measured nuclear modification factor R{sub AA} in averaged fireballs underestimates the value from event-by-event calculations by up to 50%. On the other hand, after adjusting q to fit R{sub AA} in the event-by-event analysis we find residual deviations in the azimuthal asymmetry v{sub 2} and in two-particle correlations, that provide a possible faint signature for a spatial tomography of the fireball. We discuss a correlation function that is a measure for spatial inhomogeneities in a collision and can be constrained from data.

Molecular evolution of the polyamine oxidase gene family in Metazoa

Directory of Open Access Journals (Sweden)

Polticelli Fabio

2012-06-01

Full Text Available Abstract Background Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi. Polyamine oxidases (PAOs from yeast can oxidize spermine, N1-acetylspermine, and N1-acetylspermidine, however, in vertebrates two different enzymes, namely spermine oxidase (SMO and acetylpolyamine oxidase (APAO, specifically catalyze the oxidation of spermine, and N1-acetylspermine/N1-acetylspermidine, respectively. Little is known about the molecular evolutionary history of these enzymes. However, since the yeast PAO is able to catalyze the oxidation of both acetylated and non acetylated polyamines, and in vertebrates these functions are addressed by two specialized polyamine oxidase subfamilies (APAO and SMO, it can be hypothesized an ancestral reference for the former enzyme from which the latter would have been derived. Results We analysed 36 SMO, 26 APAO, and 14 PAO homologue protein sequences from 54 taxa including various vertebrates and invertebrates. The analysis of the full-length sequences and the principal domains of vertebrate and invertebrate PAOs yielded consensus primary protein sequences for vertebrate SMOs and APAOs, and invertebrate PAOs. This analysis, coupled to molecular modeling techniques, also unveiled sequence regions that confer specific structural and functional properties, including substrate specificity, by the different PAO subfamilies. Molecular phylogenetic trees revealed a basal position of all the invertebrates PAO enzymes relative to vertebrate SMOs and APAOs. PAOs from insects constitute a monophyletic clade. Two PAO variants sampled in the amphioxus are basal to the dichotomy between two well supported

Tracing the Spatial-Temporal Evolution of Events Based on Social Media Data

Directory of Open Access Journals (Sweden)

Xiaolu Zhou

2017-03-01

Full Text Available Social media data provide a great opportunity to investigate event flow in cities. Despite the advantages of social media data in these investigations, the data heterogeneity and big data size pose challenges to researchers seeking to identify useful information about events from the raw data. In addition, few studies have used social media posts to capture how events develop in space and time. This paper demonstrates an efficient approach based on machine learning and geovisualization to identify events and trace the development of these events in real-time. We conducted an empirical study to delineate the temporal and spatial evolution of a natural event (heavy precipitation and a social event (Pope Francis’ visit to the US in the New York City—Washington, DC regions. By investigating multiple features of Twitter data (message, author, time, and geographic location information, this paper demonstrates how voluntary local knowledge from tweets can be used to depict city dynamics, discover spatiotemporal characteristics of events, and convey real-time information.

First evidence for a massive extinction event affecting bees close to the K-T boundary.

Directory of Open Access Journals (Sweden)

Sandra M Rehan

Full Text Available Bees and eudicot plants both arose in the mid-late Cretaceous, and their co-evolutionary relationships have often been assumed as an important element in the rise of flowering plants. Given the near-complete dependence of bees on eudicots we would expect that major extinction events affecting the latter would have also impacted bees. However, given the very patchy distribution of bees in the fossil record, identifying any such extinctions using fossils is very problematic. Here we use molecular phylogenetic analyses to show that one bee group, the Xylocopinae, originated in the mid-Cretaceous, coinciding with the early radiation of the eudicots. Lineage through time analyses for this bee subfamily show very early diversification, followed by a long period of seemingly no radiation and then followed by rapid diversification in each of the four constituent tribes. These patterns are consistent with both a long-fuse model of radiation and a massive extinction event close to the K-T boundary. We argue that massive extinction is much more plausible than a long fuse, given the historical biogeography of these bees and the diversity of ecological niches that they occupy. Our results suggest that events near the K-T boundary would have disrupted many plant-bee relationships, with major consequences for the subsequent evolution of eudicots and their pollinators.

First evidence for a massive extinction event affecting bees close to the K-T boundary.

Science.gov (United States)

Rehan, Sandra M; Leys, Remko; Schwarz, Michael P

2013-01-01

Bees and eudicot plants both arose in the mid-late Cretaceous, and their co-evolutionary relationships have often been assumed as an important element in the rise of flowering plants. Given the near-complete dependence of bees on eudicots we would expect that major extinction events affecting the latter would have also impacted bees. However, given the very patchy distribution of bees in the fossil record, identifying any such extinctions using fossils is very problematic. Here we use molecular phylogenetic analyses to show that one bee group, the Xylocopinae, originated in the mid-Cretaceous, coinciding with the early radiation of the eudicots. Lineage through time analyses for this bee subfamily show very early diversification, followed by a long period of seemingly no radiation and then followed by rapid diversification in each of the four constituent tribes. These patterns are consistent with both a long-fuse model of radiation and a massive extinction event close to the K-T boundary. We argue that massive extinction is much more plausible than a long fuse, given the historical biogeography of these bees and the diversity of ecological niches that they occupy. Our results suggest that events near the K-T boundary would have disrupted many plant-bee relationships, with major consequences for the subsequent evolution of eudicots and their pollinators.

Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

NARCIS (Netherlands)

Wang, Kai; Yuen, Siu Tsan; Xu, Jiangchun; Lee, Siu Po; Yan, Helen H N; Shi, Stephanie T; Siu, Hoi Cheong; Deng, Shibing; Chu, Kent Man; Law, Simon; Chan, Kok Hoe; Chan, Annie S Y; Tsui, Wai Yin; Ho, Siu Lun; Chan, Anthony K W; Man, Jonathan L K; Foglizzo, Valentina; Ng, Man Kin; Chan, April S; Ching, Yick Pang; Cheng, Grace H W; Xie, Tao; Fernandez, Julio; Li, Vivian S W; Clevers, Hans; Rejto, Paul A; Mao, Mao; Leung, Suet Yi

Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and

Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient.

Science.gov (United States)

Talbott, Vanessa A; Yeo, Charles J; Brody, Jonathan R; Witkiewicz, Agnieszka K

2012-07-01

Pancreatic ductal adenocarcinoma (PDA) is rarely a survivable disease. In rare cases, separate synchronous tumors are discovered at the time of resection, while in others, patients present with a metachronous cancer after prior surgical resection. Studying molecular markers of synchronous and metachronous lesions may aid to clarify the biology of this often deadly disease. Two patients presented with synchronous tumors (each one with a tumor in the pancreatic head/neck and the other in the tail, designated patients A and B). An additional patient (patient C) underwent an R0 resection for PDA of the head and recurred 1.5 y later with PDA in the tail. Genomic DNA was laser capture microdissected (LCM) from the tumor and molecular analysis was performed. K-ras status and loss of heterozygosity (LOH) were determined from multiple specimens for each case. All samples from each patient harbored identical K-ras mutations. In patient A, the tumor at the head of the pancreas had more clonal genetic instability as reflected by LOH analysis over multiple LCM samples. Patient B had more genetic instability in the tail lesion compared with the neck. Patient C had virtually the identical molecular profile in both tumors, supporting the notion that both tumors were related. We conclude that the synchronous and metachronous tumors likely are initiated from identical precursor lesions and/or events (i.e., K-ras mutations). Future studies will need to investigate if these tumors will respond similarly to adjuvant therapies targeted against the clonal molecular events in the tumor. Copyright © 2012 Elsevier Inc. All rights reserved.

Evolutionary molecular medicine.

Science.gov (United States)

Nesse, Randolph M; Ganten, Detlev; Gregory, T Ryan; Omenn, Gilbert S

2012-05-01

Evolution has long provided a foundation for population genetics, but some major advances in evolutionary biology from the twentieth century that provide foundations for evolutionary medicine are only now being applied in molecular medicine. They include the need for both proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, competition between alleles, co-evolution, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are transforming evolutionary biology in ways that create even more opportunities for progress at its interfaces with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and related principles to speed the development of evolutionary molecular medicine.

Applications of Location Similarity Measures and Conceptual Spaces to Event Coreference and Classification

Science.gov (United States)

McConky, Katie Theresa

2013-01-01

This work covers topics in event coreference and event classification from spoken conversation. Event coreference is the process of identifying descriptions of the same event across sentences, documents, or structured databases. Existing event coreference work focuses on sentence similarity models or feature based similarity models requiring slot…

Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life

Directory of Open Access Journals (Sweden)

Reusch Thorsten BH

2011-01-01

Full Text Available Abstract Background Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L. Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. Results In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. Conclusions These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life.

Science.gov (United States)

Wissler, Lothar; Codoñer, Francisco M; Gu, Jenny; Reusch, Thorsten B H; Olsen, Jeanine L; Procaccini, Gabriele; Bornberg-Bauer, Erich

2011-01-12

Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs) of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L.) Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica) and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

Genome characterization of Turkey Rotavirus G strains from the United States identifies potential recombination events with human Rotavirus B strains.

Science.gov (United States)

Chen, Fangzhou; Knutson, Todd P; Porter, Robert E; Ciarlet, Max; Mor, Sunil Kumar; Marthaler, Douglas G

2017-12-01

Rotavirus G (RVG) strains have been detected in a variety of avian species, but RVG genomes have been published from only a single pigeon and two chicken strains. Two turkey RVG strains were identified and characterized, one in a hatchery with no reported health issues and the other in a hatchery with high embryo/poult mortality. The two turkey RVG strains shared only an 85.3 % nucleotide sequence identity in the VP7 gene while the other genes possessed high nucleotide identity among them (96.3-99.9 %). Low nucleotide percentage identities (31.6-87.3 %) occurred among the pigeon and chicken RVG strains. Interestingly, potential recombination events were detected between our RVG strains and a human RVB strain, in the VP6 and NSP3 segments. The epidemiology of RVG in avian flocks and the pathogenicity of the two different RVG strains should be further investigated to understand the ecology and impact of RVG in commercial poultry flocks.

Linguistic Legitimation of Political Events in Newspaper Discourse

Directory of Open Access Journals (Sweden)

Marwah Kareem Ali

2016-08-01

Full Text Available This paper examines the discursive structures employed in legitimizing the event of U.S. forces withdrawal from Iraq and identifies them in relation to linguistic features. It attempts to describe the relation between language use and legitimation discursive structures in depicting political events. The paper focuses on the political event of U.S. forces’ withdrawal from Iraq in the English newspaper issued in Iraq. The study shows the way in which journalists express their values and attitudes concerning this critical event. Consequently, this requires a critical discourse analysis (henceforth, CDA to analyse news articles in the Iraqi English newspaper: The Kurdish Globe (henceforth, KG newspaper. Accordingly, the study presents a qualitative content analysis of newspaper articles to identify the legitimation discursive structures and their linguistic features. It is found that the main discursive structures of legitimation employed in the KG newspaper are: authorization, rationalization, and moral evaluation. Besides, there were five verb processes used to represent this legitimation, including material, verbal, relational, mental, and existential. Keywords: Critical discourse analysis, legitimation discursive structures, linguistic features, newspaper discourse, systemic functional linguistics

Tipping the Balance: Hepatotoxicity and the Four Apical Key Events of Hepatic Steatosis

Science.gov (United States)

Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk r...

OAE: The Ontology of Adverse Events.

Science.gov (United States)

He, Yongqun; Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Guo, Abra; Zhang, Shelley; Jagannathan, Desikan; Toldo, Luca; Tao, Cui; Smith, Barry

2014-01-01

A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term 'adverse event' denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

Science.gov (United States)

Lupo, Giuseppe; Nisi, Paola S; Esteve, Pilar; Paul, Yu-Lee; Novo, Clara Lopes; Sidders, Ben; Khan, Muhammad A; Biagioni, Stefano; Liu, Hai-Kun; Bovolenta, Paola; Cacci, Emanuele; Rugg-Gunn, Peter J

2018-06-01

Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Omics analysis of human bone to identify genes and molecular networks regulating skeletal remodeling in health and disease.

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Reppe, Sjur; Datta, Harish K; Gautvik, Kaare M

2017-08-01

The skeleton is a metabolically active organ throughout life where specific bone cell activity and paracrine/endocrine factors regulate its morphogenesis and remodeling. In recent years, an increasing number of reports have used multi-omics technologies to characterize subsets of bone biological molecular networks. The skeleton is affected by primary and secondary disease, lifestyle and many drugs. Therefore, to obtain relevant and reliable data from well characterized patient and control cohorts are vital. Here we provide a brief overview of omics studies performed on human bone, of which our own studies performed on trans-iliacal bone biopsies from postmenopausal women with osteoporosis (OP) and healthy controls are among the first and largest. Most other studies have been performed on smaller groups of patients, undergoing hip replacement for osteoarthritis (OA) or fracture, and without healthy controls. The major findings emerging from the combined studies are: 1. Unstressed and stressed bone show profoundly different gene expression reflecting differences in bone turnover and remodeling and 2. Omics analyses comparing healthy/OP and control/OA cohorts reveal characteristic changes in transcriptomics, epigenomics (DNA methylation), proteomics and metabolomics. These studies, together with genome-wide association studies, in vitro observations and transgenic animal models have identified a number of genes and gene products that act via Wnt and other signaling systems and are highly associated to bone density and fracture. Future challenge is to understand the functional interactions between bone-related molecular networks and their significance in OP and OA pathogenesis, and also how the genomic architecture is affected in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Search for charged Higgs bosons and measurement of |V sub c sub s | in quark and lepton flavour identified events at LEP2

CERN Document Server

Kiiskinen, A P

1999-01-01

A search for pair produced charged Higgs bosons was performed on the high energy data collected by DELPHI at LEP2. All three major final states, tau nu tau nu, cs tau nu and cscs were searched for. The analyses used a combination of event shape variables, di-jet masses and jet flavour tagging. The jet flavours were identified by using life time tagging and particle identification based on the RICH detector complemented by ionisation energy loss measurements. A similar type of jet flavour tagging was also used in extracting the |V sub c sub s | element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix in hadronic decays of the W sup+- boson.

Accident and Off-Normal Response and Recovery from Multi-Canister Overpack (MCO) Processing Events

International Nuclear Information System (INIS)

ALDERMAN, C.A.

2000-01-01

In the process of removing spent nuclear fuel (SNF) from the K Basins through its subsequent packaging, drymg, transportation and storage steps, the SNF Project must be able to respond to all anticipated or foreseeable off-normal and accident events that may occur. Response procedures and recovery plans need to be in place, personnel training established and implemented to ensure the project will be capable of appropriate actions. To establish suitable project planning, these events must first be identified and analyzed for their expected impact to the project. This document assesses all off-normal and accident events for their potential cross-facility or Multi-Canister Overpack (MCO) process reversal impact. Table 1 provides the methodology for establishing the event planning level and these events are provided in Table 2 along with the general response and recovery planning. Accidents and off-normal events of the SNF Project have been evaluated and are identified in the appropriate facility Safety Analysis Report (SAR) or in the transportation Safety Analysis Report for Packaging (SARP). Hazards and accidents are summarized from these safety analyses and listed in separate tables for each facility and the transportation system in Appendix A, along with identified off-normal events. The tables identify the general response time required to ensure a stable state after the event, governing response documents, and the events with potential cross-facility or SNF process reversal impacts. The event closure is predicated on stable state response time, impact to operations and the mitigated annual occurrence frequency of the event as developed in the hazard analysis process

Interpreting closed-loop learning control of molecular fragmentation in terms of wave-packet dynamics and enhanced molecular ionization

International Nuclear Information System (INIS)

Cardoza, David; Baertschy, Mark; Weinacht, Thomas

2005-01-01

We interpret a molecular fragmentation experiment using shaped, ultrafast laser pulses in terms of enhanced molecular ionization during dissociation. A closed-loop learning control experiment was performed to maximize the CF 3 + /CH 3 + production ratio in the dissociative ionization of CH 3 COCF 3 . Using ab inito molecular structure calculations and quasistatic molecular ionization calculations along with data from pump-probe experiments, we identify the primary control mechanism which is quite general and should be applicable to a broad class of molecules

Event Shape Analysis in ALICE

CERN Document Server

AUTHOR|(CDS)2073367; Paic, Guy

2009-01-01

The jets are the final state manifestation of the hard parton scattering. Since at LHC energies the production of hard processes in proton-proton collisions will be copious and varied, it is important to develop methods to identify them through the study of their final states. In the present work we describe a method based on the use of some shape variables to discriminate events according their topologies. A very attractive feature of this analysis is the possibility of using the tracking information of the TPC+ITS in order to identify specific events like jets. Through the correlation between the quantities: thrust and recoil, calculated in minimum bias simulations of proton-proton collisions at 10 TeV, we show the sensitivity of the method to select specific topologies and high multiplicity. The presented results were obtained both at level generator and after reconstruction. It remains that with any kind of jet reconstruction algorithm one will confronted in general with overlapping jets. The present meth...

Molecular packing in 1-hexanol-DMPC bilayers studied by molecular dynamics simulation

DEFF Research Database (Denmark)

Pedersen, U.R.; Peters, Günther H.j.; Westh, P.

2007-01-01

The structure and molecular packing density of a “mismatched” solute, 1-hexanol, in lipid membranes of dimyristoyl phosphatidylcholine (DMPC) was studied by molecular dynamics simulations. We found that the average location and orientation of the hexanol molecules matched earlier experimental data...... on comparable systems. The local density or molecular packing in DMPC–hexanol was elucidated through the average Voronoi volumes of all heavy (non-hydrogen) atoms. Analogous analysis was conducted on trajectories from simulations of pure 1-hexanol and pure (hydrated) DMPC bilayers. The results suggested...... of the alcohol upon partitioning and an even stronger loosening in the packing of the lipid. Furthermore, analysis of Voronoi volumes along the membrane normal identifies a distinctive depth dependence of the changes in molecular packing. The outer (interfacial) part of the lipid acyl chains (up to C8...

Molecular characterization of occult hepatitis B virus infection in patients with end-stage liver disease in Colombia.

Directory of Open Access Journals (Sweden)

Julio Cesar Rendon

Full Text Available Hepatitis B virus (HBV occult infection (OBI is a risk factor to be taken into account in transfusion, hemodialysis and organ transplantation. The aim of this study was to identify and characterize at the molecular level OBI cases in patients with end-stage liver disease.Sixty-six liver samples were obtained from patients with diagnosis of end-stage liver disease submitted to liver transplantation in Medellin (North West, Colombia. Samples obtained from patients who were negative for the surface antigen of HBV (n = 50 were tested for viral DNA detection by nested PCR for ORFs S, C, and X and confirmed by Southern-Blot. OBI cases were analyzed by sequencing the viral genome to determine the genotype and mutations; additionally, viral genome integration events were examined by the Alu-PCR technique.In five cases out of 50 patients (10% the criteria for OBI was confirmed. HBV genotype F (subgenotypes F1 and F3, genotype A and genotype D were characterized in liver samples. Three integration events in chromosomes 5q14.1, 16p13 and 20q12 affecting Receptor-type tyrosine-protein phosphatase T, Ras Protein Specific Guanine Nucleotide Releasing Factor 2, and the zinc finger 263 genes were identified in two OBI cases. Sequence analysis of the viral genome of the 5 OBI cases showed several punctual missense and nonsense mutations affecting ORFs S, P, Core and X.This is the first characterization of OBI in patients with end-stage liver disease in Colombia. The OBI cases were identified in patients with HCV infection or cryptogenic cirrhosis. The integration events (5q14.1, 16p13 and 20q12 described in this study have not been previously reported. Further studies are required to validate the role of mutations and integration events in OBI pathogenesis.

Best Practices in Pulic Outreach Events

Science.gov (United States)

Cobb, Whitney; Buxner, Sanlyn; Shipp, Stephanie

2015-11-01

IntroductionEach year the National Aeronautics and Space Administration (NASA) sponsors public outreach events designed to increase student, educator, and general public engagement in its missions and goals. NASA SMD Education’s review of large-scale events, “Best Practices in Outreach Events,” highlighted planning and implementation best practices, which were used by the Dawn mission to strategize and implement its Ceres arrival celebration event, i C Ceres.BackgroundThe literature review focused on best identifying practices rising from evaluations of large-scale public outreach events. The following criteria guided the study:* Public, science-related events open to adults and children* Events that occurred during the last 5 years* Evaluations that included information on data collected from visitors and/or volunteers* Evaluations that specified the type of data collected, methodology, and associated resultsBest Practices: Planning and ImplementationThe literature review revealed key considerations for planning implement large-scale events. Best practices included can be pertinent for all event organizers and evaluators regardless of event size. A summary of related best practices is presented below.1) Advertise the event2) Use and advertise access to scientists* Attendees who reported an interaction with a science professional were 15% to 19% more likely to report positive learning impacts, (SFA, 2012, p. 24).3) Recruit scientists using findings such as:* High percentages of scientists (85% to 96%) from most events were interested in participating again (SFA, 2012).4) Ensure that the event is group and, particularly, child friendly5) Target specific event outcomesBest Practices Informing Real-world Planning, Implementation and EvaluationDawn mission’s collaborative design of a series of events, i C Ceres, including in-person, interactive events geared to families and live presentations, will be shared, with focus on the family event, and the evidence

Quasi-molecular states in sd-shell nuclei

International Nuclear Information System (INIS)

Kubono, S.; Ikeda, N.; Nomura, T.

1988-08-01

Quasi-molecular states near and below the threshold of the molecular configuration in sd-shell nuclei are discussed using recent experimental data with particle-gamma coincidence method and particle-particle coincidence method. Possible quasi-molecular states have been identified in 24 Mg as well as in 28 Si and 32 S. The important role of quasi-molecular states are discussed, specifically for the shape evolution of nuclei as a function of excitation energy and angular momentum. (author)

CRITICAL EVENTS IN CONSTRUCTION PROCESS

DEFF Research Database (Denmark)

Jørgensen, Kirsten; Rasmussen, Grane Mikael Gregaard

2009-01-01

cause-effects of failures and defects in the construction industry by using an analytical approach (The bowtie model) which is developed in the accident research. Using this model clarifies the relationships within the chain of failures that causes critical events with undesirable consequences......Function failures, defects and poor communication are major problems in the construction industry. These failures and defects are caused by a row of critical events in the construction process. The purpose of this paper is to define “critical events” in the construction process and to investigate....... In this way the causes of failures and the relationships between various failures are rendered visible. A large construction site was observed from start to finish as the empirical element in the research. The research focuses on all kinds of critical events identified throughout every phase during...

Heterologous microarray experiments allow the identification of the early events associated with potato tuber cold sweetening

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Vitulli Federico

2008-04-01

Full Text Available Abstract Background Since its discovery more than 100 years ago, potato (Solanum tuberosum tuber cold-induced sweetening (CIS has been extensively investigated. Several carbohydrate-associated genes would seem to be involved in the process. However, many uncertainties still exist, as the relative contribution of each gene to the process is often unclear, possibly as the consequence of the heterogeneity of experimental systems. Some enzymes associated with CIS, such as β-amylases and invertases, have still to be identified at a sequence level. In addition, little is known about the early events that trigger CIS and on the involvement/association with CIS of genes different from carbohydrate-associated genes. Many of these uncertainties could be resolved by profiling experiments, but no GeneChip is available for the potato, and the production of the potato cDNA spotted array (TIGR has recently been discontinued. In order to obtain an overall picture of early transcriptional events associated with CIS, we investigated whether the commercially-available tomato Affymetrix GeneChip could be used to identify which potato cold-responsive gene family members should be further studied in detail by Real-Time (RT-PCR (qPCR. Results A tomato-potato Global Match File was generated for the interpretation of various aspects of the heterologous dataset, including the retrieval of best matching potato counterparts and annotation, and the establishment of a core set of highly homologous genes. Several cold-responsive genes were identified, and their expression pattern was studied in detail by qPCR over 26 days. We detected biphasic behaviour of mRNA accumulation for carbohydrate-associated genes and our combined GeneChip-qPCR data identified, at a sequence level, enzymatic activities such as β-amylases and invertases previously reported as being involved in CIS. The GeneChip data also unveiled important processes accompanying CIS, such as the induction of redox

Structure of proton-proton events at high center-of-mass energy with an identified particle of large transverse momentum

International Nuclear Information System (INIS)

Hanke, P.

1977-01-01

At the CERN-ISR events of pp-collisions, in which particles of large transverse momentum psub(T) are produced, were studied at √S = 52 GeV center-of-mass energy, using the 'Split-Field'-magnetspectrometer. The lorentz-invariant production cross-section of positive particles with high psub(T) was measured in the fragmentation region (average* approximately 20 0 ). In the same kinematical region the pion-fraction of produced particles for both charges was determined. In these events the effect of 'strangeness'-conservation on the dynamics of additionally produced particles was investigated. The comparison of events with negative pions and events with heavier particles - mainly kaons - at high psub(T) indicates, that the compensation of transverse momentum does not depend on the 'strangeness' of the particle at high psub(T). The quantum-number conservation rather influences the particle-content from the hadronic rest inside longitudinal phase-space. This was shown by reconstruction of decay-vertices of neutral kaons. The results obtained can be interpreted by 'constituent'-models of the proton-structure. (orig.) [de

Germanium cryogenic detectors: Alpha surface events rejection capabilities

International Nuclear Information System (INIS)

Fiorucci, S.; Broniatowski, A.; Chardin, G.; Censier, B.; Lesquen, A. de; Deschamps, H.; Fesquet, M.; Jin, Y.

2006-01-01

Alpha surface events and multiple compton gamma interactions are the two major background components in Ge detectors for double-beta decay investigations. Two different methods have been studied to identify such type of events, using cryogenic Ge detectors developed primarily for dark matter search: (i) combined heat and ionization measurements, and (ii) pulse-shape analysis of the charge collection signals. Both methods show strong separation between electron recoil events and surface alphas. Cryogenic heat-ionization detectors therefore appear able to reject virtually all surface alpha interactions

Cancer as a stressful life event: Perceptions of children with cancer and their peers.

Science.gov (United States)

Sharp, Katianne M Howard; Lindwall, Jennifer J; Willard, Victoria W; Long, Alanna M; Martin-Elbahesh, Karen M; Phipps, Sean

2017-09-01

The medical traumatic stress model is commonly applied to childhood cancer, assuming that the diagnosis of cancer is a traumatic event. However, to the authors' knowledge, little is known regarding what specifically children perceive as stressful about cancer or how it compares with other stressful events more often experienced by children. Children with cancer (254 children) and demographically similar peers without a history of serious illness (202 children) identified their most stressful life event as part of a diagnostic interview assessing for symptoms of posttraumatic stress disorder (PTSD). The events identified as most stressful were categorized thematically, with categories established separately for cancer-related and non-cancer-related events. Events also were examined to assess whether they met Diagnostic and Statistical Manual of Mental Disorders (DSM) A criteria for PTSD. In the group of children with cancer, 54% described a cancer-related event as the most stressful event they had experienced. Six distinct categories of cancer-related events and 10 categories of non-cancer-related events were identified. The same noncancer events were identified by children in both groups, and occurred at similar frequencies. The percentage of cancer-related events that met DSM A criteria for PTSD differed dramatically depending on which version of the DSM was applied. Children do not necessarily view their cancer experience as their most stressful life event. The findings of the current study suggest that the diagnosis of cancer might be better viewed as a manageable stressor rather than a major trauma, and are consistent with the change in the fifth edition of the DSM to eliminate the diagnosis of a life-threatening illness as a qualifying trauma for PTSD. Cancer 2017;123:3385-93. © 2017 American Cancer Society. © 2017 American Cancer Society.

Molecular dissection of Norrie disease.

Science.gov (United States)

Berger, W

1998-01-01

Norrie disease (ND) is a severe form of congenital blindness accompanied by mental retardation and/or deafness in at least one third of the patients. This article summarizes advances in the molecular genetic analysis of this disease during the last 13 years, including mapping and cloning of the human gene and the generation and characterization of a mouse model. Genetic linkage studies and physical mapping strategies have assigned the ND locus to the proximal short arm of the human X chromosome. The identification of chromosomal rearrangements in several patients, such as microdeletions, enabled the isolation of the ND gene by a positional cloning approach. Numerous point mutations in this gene have been identified in three distinct clinical entities: (1) ND, (2) familial and sporadic exudative vitreoretinopathy, and (3) retinopathy of prematurity. The gene encodes a relatively small protein, consisting of 133 amino acids. The function of the gene product is yet unknown, although homologies with known proteins and molecular modelling data suggest a role in the regulation of cell interaction or differentiation processes. A mouse model has been generated to shed more light on early pathogenic events involved in ND and allelic disorders. The mouse homologous protein is highly identical (94%) to the human polypeptide. The gene is expressed in the neuronal layers of the mouse retina, the cerebellum and olfactory epithelium. Mutant mice show snowflake-like opacities within the vitreous, dysgenesis of the ganglion cell layer and occasionally degeneration of photoreceptor cells. The mouse phenotype does not include phthisis bulbi and, overall, resembles a mild form of ND. Electrophysiological studies revealed a severely altered electroretinogram b-wave. These results suggest a primary defect in the inner neuronal layers of the retina. Defects in the vitreous and photoreceptor cell layer are most likely secondary effects. Further histological, functional and molecular

Molecular helpers wanted... Call for volunteers!

CERN Multimedia

2008-01-01

The Task Force in charge of the organization of the LHC Inauguration is looking for 40 volunteers to support the team of molecular cooks directed by international chef Ettore Bocchia. The "molecular" volunteers will help in the preparation of liquid nitrogen ice-cream. Your help is requested from 12h to 18h on October 21st. Your participation in a general rehearsal on October 20th is also required - (the time of the rehearsal will be communicated at a later moment). Dress code: black pants and shoes, long sleeved white shirt. Do not miss this opportunity to take part in an extraordinary event! For further information and to enrol, contact: mailto:Catherine.Brandt@cern.ch

Event Index - a LHCb Event Search System

CERN Document Server

INSPIRE-00392208; Kazeev, Nikita; Redkin, Artem

2015-12-23

LHC experiments generate up to $10^{12}$ events per year. This paper describes Event Index - an event search system. Event Index's primary function is quickly selecting subsets of events from a combination of conditions, such as the estimated decay channel or stripping lines output. Event Index is essentially Apache Lucene optimized for read-only indexes distributed over independent shards on independent nodes.

Identifying salt stress-responsive transcripts from Roselle ( Hibiscus ...

African Journals Online (AJOL)

Hibiscus sabdariffa L.). Identifying the potentially novel transcripts responsible for salt stress tolerance in roselle will increase knowledge of the molecular mechanism underlying salt stress responses. In this study, differential display reverse ...

Leisure and Pleasure: Science events in unusual locations

Science.gov (United States)

Bultitude, Karen; Margarida Sardo, Ana

2012-12-01

Building on concepts relating to informal science education, this work compares science-related activities which successfully engaged public audiences at three different 'generic' locations: a garden festival, a public park, and a music festival. The purpose was to identify what factors contribute to the perceived success of science communication activities occurring within leisure spaces. This article reports the results of 71 short (2-3 min) structured interviews with public participants at the events, and 18 structured observations sessions, demonstrating that the events were considered both novel and interesting by the participants. Audience members were found to perceive both educational and affective purposes from the events. Three key elements were identified as contributing to the success of the activities across the three 'generic venues': the informality of the surroundings, the involvement of 'real' scientists, and the opportunity to re-engage participants with scientific concepts outside formal education.

PROBABILISTIC CROSS-IDENTIFICATION OF COSMIC EVENTS

International Nuclear Information System (INIS)

Budavari, Tamas

2011-01-01

I discuss a novel approach to identifying cosmic events in separate and independent observations. The focus is on the true events, such as supernova explosions, that happen once and, hence, whose measurements are not repeatable. Their classification and analysis must make the best use of all available data. Bayesian hypothesis testing is used to associate streams of events in space and time. Probabilities are assigned to the matches by studying their rates of occurrence. A case study of Type Ia supernovae illustrates how to use light curves in the cross-identification process. Constraints from realistic light curves happen to be well approximated by Gaussians in time, which makes the matching process very efficient. Model-dependent associations are computationally more demanding but can further boost one's confidence.

Event-related brain potentials that distinguish false memory for events that occurred only seconds in the past.

Science.gov (United States)

Chen, Hong; Voss, Joel L; Guo, Chunyan

2012-07-30

False memory often involves retrieving events from the distant past that did not actually happen. However, recent evidence obtained using the Deese/Roediger-McDermott (DRM) paradigm for eliciting false memory experiences suggests that individuals can falsely believe that events occurred mere seconds in the past when they in fact did not. Subjects in these experiments endorsed unstudied critical lure words as having been studied, despite the fact that word lists were studied just moments before. We identified event-related brain potential (ERP) correlates of this experience, and included a repetition priming manipulation to better assess the functional significance of these ERPs. Behavioral and ERP data were collected from 21 Capital Normal University students using a short-term DRM task. Two categories of effects were identified that distinguished true from false short-term memory: (1) early semantic priming effects from 300 to 500 ms and (2) later retrieval and retrieval-monitoring effects after 500 ms. The repetition priming manipulation had distinct influences on these effects, consistent with their differential associations with semantic priming versus episodic retrieval. Characterization of ERPs related to semantic priming and episodic retrieval provides important information regarding the mechanisms of short-term false memory. In contrast, most studies examining false memory in standard long-delay DRM paradigms identify ERP effects related only to retrieval monitoring. These findings highlight the neural processing involved in illusions of memory after very brief delays and highlight the role of semantic processing in short-term false memory.

Transcriptomic profiling of diverse Aedes aegypti strains reveals increased basal-level immune activation in dengue virus-refractory populations and identifies novel virus-vector molecular interactions.

Directory of Open Access Journals (Sweden)

Shuzhen Sim

Full Text Available Genetic variation among Aedes aegypti populations can greatly influence their vector competence for human pathogens such as the dengue virus (DENV. While intra-species transcriptome differences remain relatively unstudied when compared to coding sequence polymorphisms, they also affect numerous aspects of mosquito biology. Comparative molecular profiling of mosquito strain transcriptomes can therefore provide valuable insight into the regulation of vector competence. We established a panel of A. aegypti strains with varying levels of susceptibility to DENV, comprising both laboratory-maintained strains and field-derived colonies collected from geographically distinct dengue-endemic regions spanning South America, the Caribbean, and Southeast Asia. A comparative genome-wide gene expression microarray-based analysis revealed higher basal levels of numerous immunity-related gene transcripts in DENV-refractory mosquito strains than in susceptible strains, and RNA interference assays further showed different degrees of immune pathway contribution to refractoriness in different strains. By correlating transcript abundance patterns with DENV susceptibility across our panel, we also identified new candidate modulators of DENV infection in the mosquito, and we provide functional evidence for two potential DENV host factors and one potential restriction factor. Our comparative transcriptome dataset thus not only provides valuable information about immune gene regulation and usage in natural refractoriness of mosquito populations to dengue virus but also allows us to identify new molecular interactions between the virus and its mosquito vector.

Event segmentation ability uniquely predicts event memory.

Science.gov (United States)

Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

2013-11-01

Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.

SPEED : a semantics-based pipeline for economic event detection

NARCIS (Netherlands)

Hogenboom, F.P.; Hogenboom, A.C.; Frasincar, F.; Kaymak, U.; Meer, van der O.; Schouten, K.; Vandic, D.; Parsons, J.; Motoshi, S.; Shoval, P.; Woo, C.; Wand, Y.

2010-01-01

Nowadays, emerging news on economic events such as acquisitions has a substantial impact on the financial markets. Therefore, it is important to be able to automatically and accurately identify events in news items in a timely manner. For this, one has to be able to process a large amount of

Licensee Event Report (LER) compilation, December 1991

International Nuclear Information System (INIS)

1992-01-01

This monthly report contains licensee event report (LER) operational information that was processed into the LER data file of the Nuclear Safety Information Center (NSIC) during the one month period identified on the cover of the document. The LERs, from which this information is derived, are submitted to the Nuclear Regulatory Commission (NRC) by nuclear power plant licensees in accordance with federal regulations. Procedures for LER reporting for revisions to those events occurring prior to 1984 are described in NRC Regulatory Guide 1.16 and NUREG-0161, Instructions for Preparation of Data Entry Sheets for Licensee Event Reports. For those events occurring on and after January 1, 1984, LERs are being submitted in accordance with the revised rule contained in Title 10 Part 50.73 of the Code of Federal Regulations (10 CFR 50.73 - Licensee Event Report System) which was published in the Federal Register (Vol. 48, No. 144) on July 26, 1983. NUREG-1022, Licensee Event Report System - Description of Systems and Guidelines for Reporting, provides supporting guidance and information on the revised LER rule

A review of molecular biomarkers for bladder cancer | Miakhil ...

African Journals Online (AJOL)

Background: Numerous molecular markers for bladder cancer have been identified and investigated with various laboratory techniques. Molecular markers are isolated from tissue, serum and urine. They fall into proteomic, genetic and epigenetic categories. Some of molecular markers show promising results in terms of ...

Extreme Weather Events and Climate Change Attribution

Energy Technology Data Exchange (ETDEWEB)

Thomas, Katherine [National Academy of Sciences, Washington, DC (United States)

2016-03-31

A report from the National Academies of Sciences, Engineering, and Medicine concludes it is now possible to estimate the influence of climate change on some types of extreme events. The science of extreme event attribution has advanced rapidly in recent years, giving new insight to the ways that human-caused climate change can influence the magnitude or frequency of some extreme weather events. This report examines the current state of science of extreme weather attribution, and identifies ways to move the science forward to improve attribution capabilities. Confidence is strongest in attributing types of extreme events that are influenced by climate change through a well-understood physical mechanism, such as, the more frequent heat waves that are closely connected to human-caused global temperature increases, the report finds. Confidence is lower for other types of events, such as hurricanes, whose relationship to climate change is more complex and less understood at present. For any extreme event, the results of attribution studies hinge on how questions about the event's causes are posed, and on the data, modeling approaches, and statistical tools chosen for the analysis.

ATLAS proton-proton event containing two electrons and two muons

CERN Multimedia

ATLAS Collaboration

2011-01-01

An event with two identified muons and two identified electrons from a proton- proton collision in ATLAS. This event is consistent with coming from two Z particles decaying: one Z decays to two muons, the other to two electrons. Such events are produced by Standard Model processes without Higgs particles. They are also a possible signature for Higgs particle production, but many events must be analysed together in order to tell if there is a Higgs signal. The two muons are picked out as red tracks penetrating right through the detector. The two electrons are picked out as green tracks in the central, inner detector, matching narrow green clusters of energy in the barrel part of the calorimeters. The inset at the bottom right shows a map of the energy seen in the detector: the two big yellow spikes correspond to the two electrons.

Array-based molecular karyotyping in 115 VATER/VACTERL and VATER/VACTERL-like patients identifies disease-causing copy number variations.

Science.gov (United States)

Zhang, Rong; Marsch, Florian; Kause, Franziska; Degenhardt, Franziska; Schmiedeke, Eeberhard; Märzheuser, Stefanie; Hoppe, Bernd; Bachour, Haitham; Boemers, Thomas M; Schäfer, Matthias; Spychalski, Nicole; Neser, Jörg; Leonhardt, Johannes; Kosch, Ferdinand; Ure, Benno; Gómez, Barbara; Lacher, Martin; Deffaa, Oliver J; Palta, Markus; Wittekindt, Boris; Kleine, Katharina; Schmedding, Andrea; Grasshoff-Derr, Sabine; Ven, Amelie van der; Heilmann-Heimbach, Stefanie; Zwink, Nadine; Jenetzky, Ekkehart; Ludwig, Michael; Reutter, Heiko

2017-07-17

The acronym VATER/VACTERL refers to the rare nonrandom association of the following component features (CF): vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia, renal malformations (R), and limb defects (L). Patients presenting with at least three CFs are diagnosed as having VATER/VACTERL association while patients presenting with only two CFs are diagnosed as having VATER/VACTERL-like phenotypes. Recently, rare causative copy number variations (CNVs) have been identified in patients with VATER/VACTERL association and VATER/VACTERL-like phenotypes. To detect further causative CNVs we performed array based molecular karyotyping in 75 VATER/VACTERL and 40 VATER/VACTERL-like patients. Following the application of stringent filter criteria, we identified 13 microdeletions and seven microduplications in 20 unrelated patients all of which were absent in 1,307 healthy inhouse controls (n microdeletion at 17q12 was confirmed to be de novo. Three microdeletions at 5q23.1, 16q23.3, 22q11.21, and one microduplication at 10q11.21 were all absent in the available parent. Microdeletion of chromosomal region 22q11.21 was previously found in VATER/VACTERL patients rendering it to be causative in our patient. The remaining 15 CNVs were inherited from a healthy parent. In two of 115 patients' causative CNVs were found (2%). The remaining identified rare CNVs represent candidates for further evaluation. Rare inherited CNVs may constitute modifiers of, or contributors to, multifactorial VATER/VACTERL or VATER/VACTERL-like phenotypes. Birth Defects Research 109:1063-1069, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Event-based criteria in GT-STAF information indices: theory, exploratory diversity analysis and QSPR applications.

Science.gov (United States)

Barigye, S J; Marrero-Ponce, Y; Martínez López, Y; Martínez Santiago, O; Torrens, F; García Domenech, R; Galvez, J

2013-01-01

Versatile event-based approaches for the definition of novel information theory-based indices (IFIs) are presented. An event in this context is the criterion followed in the "discovery" of molecular substructures, which in turn serve as basis for the construction of the generalized incidence and relations frequency matrices, Q and F, respectively. From the resultant F, Shannon's, mutual, conditional and joint entropy-based IFIs are computed. In previous reports, an event named connected subgraphs was presented. The present study is an extension of this notion, in which we introduce other events, namely: terminal paths, vertex path incidence, quantum subgraphs, walks of length k, Sach's subgraphs, MACCs, E-state and substructure fingerprints and, finally, Ghose and Crippen atom-types for hydrophobicity and refractivity. Moreover, we define magnitude-based IFIs, introducing the use of the magnitude criterion in the definition of mutual, conditional and joint entropy-based IFIs. We also discuss the use of information-theoretic parameters as a measure of the dissimilarity of codified structural information of molecules. Finally, a comparison of the statistics for QSPR models obtained with the proposed IFIs and DRAGON's molecular descriptors for two physicochemical properties log P and log K of 34 derivatives of 2-furylethylenes demonstrates similar to better predictive ability than the latter.

Adverse events while awaiting myocardial revascularization

DEFF Research Database (Denmark)

Head, Stuart J.; da Costa, Bruno R.; Beumer, Berend

2017-01-01

OBJECTIVES: The aim of the current study was to estimate adverse event rates while awaiting myocardial revascularization and review criteria for prioritizing patients. METHODS: A PubMed search was performed on 19 January 2015, to identify English-language, original, observational studies reportin...

Initial Chemical Events in CL-20 Under Extreme Conditions: An Ab Initio Molecular Dynamics Study

National Research Council Canada - National Science Library

Isaev, Olexandr; Kholod, Yana; Gorb, Leonid; Qasim, Mohammad; Fredrickson, Herb; Leszczynski, Jerzy

2006-01-01

.... In the present study molecular structure, electrostatic potential, vibrational spectrum and dynamics of thermal decomposition of CL-20 have been investigated by static and dynamic methods of ab...

Messina: a novel analysis tool to identify biologically relevant molecules in disease.

Directory of Open Access Journals (Sweden)

Mark Pinese

Full Text Available BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package.

Molecular signatures define two main classes of meningiomas

Directory of Open Access Journals (Sweden)

Costello Joseph F

2007-10-01

Full Text Available Abstract Background Meningiomas are common brain tumors that are classified into three World Health Organization grades (benign, atypical and malignant and are molecularly ill-defined tumors. The purpose of this study was identify molecular signatures unique to the different grades of meningiomas and to unravel underlying molecular mechanisms driving meningioma tumorigenesis. Results We have used a combination of gene expression microarrays and array comparative genomic hybridization (aCGH to show that meningiomas of all three grades fall into two main molecular groups designated 'low-proliferative' and 'high-proliferative' meningiomas. While all benign meningiomas fall into the low-proliferative group and all malignant meningiomas fall into the high-proliferative group, atypical meningiomas distribute into either one of these groups. High-proliferative atypical meningiomas had an elevated median MIB-1 labeling index and a greater frequency of copy number aberrations (CNAs compared to low-proliferative atypical meningiomas. Additionally, losses on chromosome 6q, 9p, 13 and 14 were found exclusively in the high-proliferative meningiomas. We have identified genes that distinguish benign low-proliferative meningiomas from malignant high-proliferative meningiomas and have found that gain of cell-proliferation markers and loss of components of the transforming growth factor-beta signaling pathway were the major molecular mechanisms that distinguish these two groups. Conclusion Collectively, our data suggests that atypical meningiomas are not a molecularly distinct group but are similar to either benign or malignant meningiomas. It is anticipated that identified molecular and CNA markers will potentially be more accurate prognostic markers of meningiomas.

Molecular genetic approaches to the study of cellular senescence.

Science.gov (United States)

Goletz, T J; Smith, J R; Pereira-Smith, O M

1994-01-01

Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

[Molecular heterogeneity of malignant pleural mesotheliomas].

Science.gov (United States)

Tranchant, Robin; Montagne, François; Jaurand, Marie-Claude; Jean, Didier

2018-01-01

Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2 LN tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2 LN subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Proarrhythmic potential of dronedarone: emerging evidence from spontaneous adverse event reporting.

Science.gov (United States)

Kao, David P; Hiatt, William R; Krantz, Mori J

2012-08-01

To characterize the frequency and type of cardiac events, including torsade de pointes, associated with dronedarone and its structural analog, amiodarone, outside of the clinical trial setting. Retrospective analysis. Spontaneous reports in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database generated between July 1, 2009, and June 30, 2011. All reports of adverse events during the study period were reviewed to identify cardiac events associated with any approved drug in the United States. The type and number of cardiac events associated with dronedarone and amiodarone were determined. Active ingredients were identified using the Drugs@FDA database, and the Medical Dictionary for Regulatory Activities (MedDRA) was used to aggregate related adverse events. To avoid redundant reporting, all statistics were generated in reference to unique case identifiers. Dronedarone was associated with more adverse cardiovascular event reports than amiodarone (810 vs 493 reports) during the study period. Dronedarone was also associated with the most reports of torsade de pointes of any approved drug in the United States (37 reports), followed by amiodarone (29 reports). Reports of ventricular arrhythmias and cardiac arrest (138 vs 113 reports) as well as heart failure (179 vs 126 reports) were more common with dronedarone than amiodarone. Dronedarone was associated with reports of ventricular arrhythmia, cardiac arrest, and torsade de pointes in clinical practice. Whether this observation accounts for the increased risk of fatal arrhythmia observed in a recent prospective trial requires further investigation. © 2012 Pharmacotherapy Publications, Inc. All rights reserved.

Molecular radio-oncology

International Nuclear Information System (INIS)

Baumann, Michael; Krause, Mechthild; Cordes, Nils

2016-01-01

This book concisely reviews our current understanding of hypoxia, molecular targeting, DNA repair, cancer stem cells, and tumor pathophysiology, while also discussing novel strategies for putting these findings into practice in daily clinical routine. Radiotherapy is an important part of modern multimodal cancer treatment, and the past several years have witnessed not only substantial improvements in radiation techniques and the use of new beam qualities, but also major strides in our understanding of molecular tumor biology and tumor radiation response. Against this backdrop, the book highlights recent efforts to identify reasonable and clinically applicable biomarkers using broad-spectrum tissue microarrays and high-throughput systems biology approaches like genomics and epigenomics. In particular, it describes in detail how such molecular information is now being exploited for diagnostic imaging and imaging throughout treatment using the example of positron emission tomography. By discussing all these issues in the context of modern radiation oncology, the book provides a broad, up-to-date overview of the molecular aspects of radiation oncology that will hopefully foster its further optimization.

Molecular radio-oncology

Energy Technology Data Exchange (ETDEWEB)

Baumann, Michael; Krause, Mechthild; Cordes, Nils (eds.) [Technische Univ. Dresden (Germany). Faculty of Medicine and University Hospital

2016-07-01

This book concisely reviews our current understanding of hypoxia, molecular targeting, DNA repair, cancer stem cells, and tumor pathophysiology, while also discussing novel strategies for putting these findings into practice in daily clinical routine. Radiotherapy is an important part of modern multimodal cancer treatment, and the past several years have witnessed not only substantial improvements in radiation techniques and the use of new beam qualities, but also major strides in our understanding of molecular tumor biology and tumor radiation response. Against this backdrop, the book highlights recent efforts to identify reasonable and clinically applicable biomarkers using broad-spectrum tissue microarrays and high-throughput systems biology approaches like genomics and epigenomics. In particular, it describes in detail how such molecular information is now being exploited for diagnostic imaging and imaging throughout treatment using the example of positron emission tomography. By discussing all these issues in the context of modern radiation oncology, the book provides a broad, up-to-date overview of the molecular aspects of radiation oncology that will hopefully foster its further optimization.

Storm loads of culturable and molecular fecal indicators in an inland urban stream.

Science.gov (United States)

Liao, Hehuan; Krometis, Leigh-Anne H; Cully Hession, W; Benitez, Romina; Sawyer, Richard; Schaberg, Erin; von Wagoner, Emily; Badgley, Brian D

2015-10-15

Elevated concentrations of fecal indicator bacteria in receiving waters during wet-weather flows are a considerable public health concern that is likely to be exacerbated by future climate change and urbanization. Knowledge of factors driving the fate and transport of fecal indicator bacteria in stormwater is limited, and even less is known about molecular fecal indicators, which may eventually supplant traditional culturable indicators. In this study, concentrations and loading rates of both culturable and molecular fecal indicators were quantified throughout six storm events in an instrumented inland urban stream. While both concentrations and loading rates of each fecal indicator increased rapidly during the rising limb of the storm hydrographs, it is the loading rates rather than instantaneous concentrations that provide a better estimate of transport through the stream during the entire storm. Concentrations of general fecal indicators (both culturable and molecular) correlated most highly with each other during storm events but not with the human-associated HF183 Bacteroides marker. Event loads of general fecal indicators most strongly correlated with total runoff volume, maximum discharge, and maximum turbidity, while event loads of HF183 most strongly correlated with the time to peak flow in a hydrograph. These observations suggest that collection of multiple samples during a storm event is critical for accurate predictions of fecal indicator loading rates and total loads during wet-weather flows, which are required for effective watershed management. In addition, existing predictive models based on general fecal indicators may not be sufficient to predict source-specific genetic markers of fecal contamination. Copyright © 2015 Elsevier B.V. All rights reserved.

Nanomedicine for the molecular diagnosis of cardiovascular pathologies

Energy Technology Data Exchange (ETDEWEB)

Juenet, Maya; Varna, Mariana; Aid-Launais, Rachida [Inserm, U1148, Cardiovascular Bio-Engineering, X. Bichat Hospital, 75018, Paris (France); Université Paris 13, Institut Galilée, Sorbonne Paris Cité, 75018, Paris (France); Chauvierre, Cédric, E-mail: cedric.chauvierre@inserm.fr [Inserm, U1148, Cardiovascular Bio-Engineering, X. Bichat Hospital, 75018, Paris (France); Université Paris 13, Institut Galilée, Sorbonne Paris Cité, 75018, Paris (France); Letourneur, Didier [Inserm, U1148, Cardiovascular Bio-Engineering, X. Bichat Hospital, 75018, Paris (France); Université Paris 13, Institut Galilée, Sorbonne Paris Cité, 75018, Paris (France)

2015-12-18

Predicting acute clinical events caused by atherosclerotic plaque rupture remains a clinical challenge. Anatomic mapping of the vascular tree provided by standard imaging technologies is not always sufficient for a robust diagnosis. Yet biological mechanisms leading to unstable plaques have been identified and corresponding biomarkers have been described. Nanosystems charged with contrast agents and targeted towards these specific biomarkers have been developed for several types of imaging modalities. The first systems that have reached the clinic are ultrasmall superparamagnetic iron oxides for Magnetic Resonance Imaging. Their potential relies on their passive accumulation by predominant physiological mechanisms in rupture-prone plaques. Active targeting strategies are under development to improve their specificity and set up other types of nanoplatforms. Preclinical results show a huge potential of nanomedicine for cardiovascular diagnosis, as long as the safety of these nanosystems in the body is studied in depth. - Highlights: • Ischemic stroke and myocardial infarction are the main causes of death in the world. • Their prevalence is related to late detection of high-risk atherosclerotic plaques. • Biomarkers of atherosclerosis evolution and potential ligands have been identified. • Nanosystems based on these ligands appear promising for early molecular diagnosis. • Preclinical and clinical nanosystems for common imaging modalities are described.

Nanomedicine for the molecular diagnosis of cardiovascular pathologies

International Nuclear Information System (INIS)

Juenet, Maya; Varna, Mariana; Aid-Launais, Rachida; Chauvierre, Cédric; Letourneur, Didier

2015-01-01

Predicting acute clinical events caused by atherosclerotic plaque rupture remains a clinical challenge. Anatomic mapping of the vascular tree provided by standard imaging technologies is not always sufficient for a robust diagnosis. Yet biological mechanisms leading to unstable plaques have been identified and corresponding biomarkers have been described. Nanosystems charged with contrast agents and targeted towards these specific biomarkers have been developed for several types of imaging modalities. The first systems that have reached the clinic are ultrasmall superparamagnetic iron oxides for Magnetic Resonance Imaging. Their potential relies on their passive accumulation by predominant physiological mechanisms in rupture-prone plaques. Active targeting strategies are under development to improve their specificity and set up other types of nanoplatforms. Preclinical results show a huge potential of nanomedicine for cardiovascular diagnosis, as long as the safety of these nanosystems in the body is studied in depth. - Highlights: • Ischemic stroke and myocardial infarction are the main causes of death in the world. • Their prevalence is related to late detection of high-risk atherosclerotic plaques. • Biomarkers of atherosclerosis evolution and potential ligands have been identified. • Nanosystems based on these ligands appear promising for early molecular diagnosis. • Preclinical and clinical nanosystems for common imaging modalities are described.

[Advance in molecular biology of Dendrobium (Orchidaceae)].

Science.gov (United States)

Li, Qing; Li, Biao; Guo, Shun-Xing

2016-08-01

With the development of molecular biology, the process in molecular biology research of Dendrobium is going fast. Not only did it provide new ways to identify Dendrobium quickly, reveal the genetic diversity and relationship of Dendrobium, but also lay the vital foundation for explaining the mechanism of Dendrobium growth and metabolism. The present paper reviews the recent process in molecular biology research of Dendrobium from three aspects, including molecular identification, genetic diversity and functional genes. And this review will facilitate the development of this research area and Dendrobium. Copyright© by the Chinese Pharmaceutical Association.

Molecular pathology and thyroid FNA.

Science.gov (United States)

Poller, D N; Glaysher, S

2017-12-01

This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule-in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven-gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next-generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule-out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non-invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies. This review describes practical examples of molecular techniques as applied to thyroid FNA in routine clinical practice and the value of molecular diagnostics in thyroid FNA. It describes the range of molecular abnormalities identified in thyroid nodules and thyroid cancers with some practical applications of molecular methods to diagnosis and prognosis of thyroid nodules and thyroid cancer. © 2017 John Wiley & Sons Ltd.

Multiscale Molecular Dynamics Simulations of Beta-Amyloid Interactions with Neurons

Science.gov (United States)

Qiu, Liming; Vaughn, Mark; Cheng, Kelvin

2012-10-01

Early events of human beta-amyloid protein interactions with cholesterol-containing membranes are critical to understanding the pathogenesis of Alzheimer's disease (AD) and to exploring new therapeutic interventions of AD. Atomistic molecular dynamics (AMD) simulations have been extensively used to study the protein-lipid interaction at high atomic resolutions. However, traditional MD simulations are not efficient in sampling the phase space of complex lipid/protein systems with rugged free energy landscapes. Meanwhile, coarse-grained MD (CGD) simulations are efficient in the phase space sampling but suffered from low spatial resolutions and from the fact that the energy landscapes are not identical to those of the AMD. Here, a multiscale approach was employed to simulate the protein-lipid interactions of beta-amyloid upon its release from proteolysis residing in the neuronal membranes. We utilized a forward (AMD to CGD) and reverse (CGD-AMD) strategy to explore new transmembrane and surface protein configuration and evaluate the stabilization mechanisms by measuring the residue-specific protein-lipid or protein conformations. The detailed molecular interactions revealed in this multiscale MD approach will provide new insights into understanding the early molecular events leading to the pathogenesis of AD.

Adverse events associated with pediatric exposures to dextromethorphan.

Science.gov (United States)

Paul, Ian M; Reynolds, Kate M; Kauffman, Ralph E; Banner, William; Bond, G Randall; Palmer, Robert B; Burnham, Randy I; Green, Jody L

2017-01-01

Dextromethorphan is the most common over-the-counter (OTC) antitussive medication. We sought to characterize adverse events associated with dextromethorphan in children dextromethorphan with ≥1 adverse event from multiple U.S. sources (National Poison Data System, FDA Adverse Event Reporting System, manufacturer safety reports, news/media, medical literature) reported between 2008 and 2014. An expert panel determined the relationship between exposure and adverse events, estimated dose ingested, intent of exposure, and identified contributing factors to exposure. 1716 cases contained ≥1 adverse event deemed at least potentially related to dextromethorphan; 1417 were single product exposures. 773/1417 (55%) involved only one single-ingredient dextromethorphan product (dextromethorphan-only). Among dextromethorphan-only cases, 3% followed ingestion of a therapeutic dose; 78% followed an overdose. 69% involved unsupervised self-administration and 60% occurred in children dextromethorphan-only ingestion. Adverse events were predominantly associated with overdose, most commonly affecting the central nervous and autonomic systems.

Event storm detection and identification in communication systems

International Nuclear Information System (INIS)

Albaghdadi, Mouayad; Briley, Bruce; Evens, Martha

2006-01-01

Event storms are the manifestation of an important class of abnormal behaviors in communication systems. They occur when a large number of nodes throughout the system generate a set of events within a small period of time. It is essential for network management systems to detect every event storm and identify its cause, in order to prevent and repair potential system faults. This paper presents a set of techniques for the effective detection and identification of event storms in communication systems. First, we introduce a new algorithm to synchronize events to a single node in the system. Second, the system's event log is modeled as a normally distributed random process. This is achieved by using data analysis techniques to explore and then model the statistical behavior of the event log. Third, event storm detection is proposed using a simple test statistic combined with an exponential smoothing technique to overcome the non-stationary behavior of event logs. Fourth, the system is divided into non-overlapping regions to locate the main contributing regions of a storm. We show that this technique provides us with a method for event storm identification. Finally, experimental results from a commercially deployed multimedia communication system that uses these techniques demonstrate their effectiveness

Elucidation of molecular kinetic schemes from macroscopic traces using system identification.

Directory of Open Access Journals (Sweden)

Miguel Fribourg

2017-02-01

Full Text Available Overall cellular responses to biologically-relevant stimuli are mediated by networks of simpler lower-level processes. Although information about some of these processes can now be obtained by visualizing and recording events at the molecular level, this is still possible only in especially favorable cases. Therefore the development of methods to extract the dynamics and relationships between the different lower-level (microscopic processes from the overall (macroscopic response remains a crucial challenge in the understanding of many aspects of physiology. Here we have devised a hybrid computational-analytical method to accomplish this task, the SYStems-based MOLecular kinetic scheme Extractor (SYSMOLE. SYSMOLE utilizes system-identification input-output analysis to obtain a transfer function between the stimulus and the overall cellular response in the Laplace-transformed domain. It then derives a Markov-chain state molecular kinetic scheme uniquely associated with the transfer function by means of a classification procedure and an analytical step that imposes general biological constraints. We first tested SYSMOLE with synthetic data and evaluated its performance in terms of its rate of convergence to the correct molecular kinetic scheme and its robustness to noise. We then examined its performance on real experimental traces by analyzing macroscopic calcium-current traces elicited by membrane depolarization. SYSMOLE derived the correct, previously known molecular kinetic scheme describing the activation and inactivation of the underlying calcium channels and correctly identified the accepted mechanism of action of nifedipine, a calcium-channel blocker clinically used in patients with cardiovascular disease. Finally, we applied SYSMOLE to study the pharmacology of a new class of glutamate antipsychotic drugs and their crosstalk mechanism through a heteromeric complex of G protein-coupled receptors. Our results indicate that our methodology

External Events PSA for the Paks NPP

International Nuclear Information System (INIS)

Bareith, Attila; Karsa, Zoltan; Siklossy, Tamas; Vida, Zoltan

2014-01-01

quantification and interpretation of results. The risk of core damage induced by natural external hazards was quantified to the extent seen feasible. In addition to risk quantification, unresolved issues and necessary follow-on analyses were identified and proposed. At present an action plan is being developed for these analyses. Core damage risk has been assessed quantitatively for wind, snow and frost hazards. Detailed importance, sensitivity and uncertainty analyses were conducted. Moreover the main risk contributors induced by these external events were also identified. Additional follow-on analyses were proposed to enable an improved risk quantification by means of reducing uncertainties, establishing a better technical basis for the applied analytical assumptions, or decreasing unnecessarily high conservatism. Based on the findings of hazard assessment and plant response analysis, the core damage risk induced by extreme rainfall and lightning was found to be insignificant. However, some follow-on analyses were proposed and safety enhancement measures were conceptualised to fully underpin this conclusion. Due to lack of appropriate data and supporting analysis on the capacity of plant systems and components no PSA model has been developed yet for extreme temperatures. Follow-on analyses necessary for quantifying the risk of core damage induced by extreme temperatures have been identified. (authors)

Molecular Simulation of Reacting Systems; TOPICAL

International Nuclear Information System (INIS)

THOMPSON, AIDAN P.