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Sample records for identify potential regulatory

  1. iTRAQ-Based Quantitative Proteomics Identifies Potential Regulatory Proteins Involved in Chicken Eggshell Brownness.

    Directory of Open Access Journals (Sweden)

    Guangqi Li

    Full Text Available Brown eggs are popular in many countries and consumers regard eggshell brownness as an important indicator of egg quality. However, the potential regulatory proteins and detailed molecular mechanisms regulating eggshell brownness have yet to be clearly defined. In the present study, we performed quantitative proteomics analysis with iTRAQ technology in the shell gland epithelium of hens laying dark and light brown eggs to investigate the candidate proteins and molecular mechanisms underlying variation in chicken eggshell brownness. The results indicated 147 differentially expressed proteins between these two groups, among which 65 and 82 proteins were significantly up-regulated in the light and dark groups, respectively. Functional analysis indicated that in the light group, the down-regulated iron-sulfur cluster assembly protein (Iba57 would decrease the synthesis of protoporphyrin IX; furthermore, the up-regulated protein solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator, member 5 (SLC25A5 and down-regulated translocator protein (TSPO would lead to increased amounts of protoporphyrin IX transported into the mitochondria matrix to form heme with iron, which is supplied by ovotransferrin protein (TF. In other words, chickens from the light group produce less protoporphyrin IX, which is mainly used for heme synthesis. Therefore, the exported protoporphyrin IX available for eggshell deposition and brownness is reduced in the light group. The current study provides valuable information to elucidate variation of chicken eggshell brownness, and demonstrates the feasibility and sensitivity of iTRAQ-based quantitative proteomics analysis in providing useful insights into the molecular mechanisms underlying brown eggshell pigmentation.

  2. Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene

    DEFF Research Database (Denmark)

    Phylactides, M.; Rowntree, R.; Nuthall, H.

    2002-01-01

    hypersensitive sites (DHS) within the locus. We previously identified at least 12 clusters of DHS across the CFTR gene and here further evaluate DHS in introns 2,3,10,16,17a, 18, 20 and 21 to assess their functional importance in regulation of CFTR gene expression. Transient transfections of enhancer/reporter...

  3. IBT-based quantitative proteomics identifies potential regulatory proteins involved in pigmentation of purple sea cucumber, Apostichopus japonicus.

    Science.gov (United States)

    Xing, Lili; Sun, Lina; Liu, Shilin; Li, Xiaoni; Zhang, Libin; Yang, Hongsheng

    2017-09-01

    Sea cucumbers are an important economic species and exhibit high yield value among aquaculture animals. Purple sea cucumbers are very rare and beautiful and have stable hereditary patterns. In this study, isobaric tags (IBT) were first used to reveal the molecular mechanism of pigmentation in the body wall of the purple sea cucumber. We analyzed the proteomes of purple sea cucumber in early pigmentation stage (Pa), mid pigmentation stage (Pb) and late pigmentation stage (Pc), resulting in the identification of 5580 proteins, including 1099 differentially expressed proteins in Pb: Pa and 339 differentially expressed proteins in Pc: Pb. GO and KEGG analyses revealed possible differentially expressed proteins, including"melanogenesis", "melanosome", "melanoma", "pigment-biosynthetic process", "Epidermis development", "Ras-signaling pathway", "Wnt-signaling pathway", "response to UV light", and "tyrosine metabolism", involved in pigment synthesis and regulation in purple sea cucumbers. The large number of differentially expressed proteins identified here should be highly useful in further elucidating the mechanisms underlying pigmentation in sea cucumbers. Furthermore, these results may also provide the base for further identification of proteins involved in resistance mechanisms against melanoma, albinism, UV damage, and other diseases in sea cucumbers. Copyright © 2017. Published by Elsevier Inc.

  4. Clinical trial regulation in Argentina: overview and analysis of regulatory framework, use of existing tools, and researchers' perspectives to identify potential barriers.

    Science.gov (United States)

    White, Lauren; Ortiz, Zulma; Cuervo, Luis G; Reveiz, Ludovic

    2011-11-01

    To review and analyze the regulatory framework of clinical trial registration, use of existing tools (publicly accessible national/international registration databases), and users' perspectives to identify possible barriers to registration compliance by sponsors and researchers in Argentina. Internationally registered trials recruiting patients in Argentina were found through clincialtrials.gov and the International Clinical Trial Registration Platform (ICTRP) and compared with publically available clinical trials registered through the National Administration of Drugs, Foods, and Medical Devices (ANMAT). A questionnaire addressing hypothesized attitudinal, knowledge-related, idiomatic, technical, economic, and regulatory barriers that could discourage or impede registration of clinical trials was developed, and semi-structured, in-depth interviews were conducted with a purposively selected sample of researchers (investigators, sponsors, and monitors) in Argentina. A response rate of 74.3% (n = 29) was achieved, and 27 interviews were ultimately used for analysis. Results suggested that the high proportion of foreign-sponsored or multinational trials (64.8% of all protocols approved by ANMAT from 1994-2006) may contribute to a communication gap between locally based investigators and foreign-based administrative officials. A lack of knowledge about available international registration tools and limited awareness of the importance of registration were also identified as limiting factors for local investigators and sponsors. To increase compliance and promote clinical trial registration in Argentina, national health authorities, sponsors, and local investigators could take the following steps: implement a grassroots educational campaign to improve clinical trial regulation, support local investigator-sponsor-initiated clinical trials, and/or encourage local and regional scientific journal compliance with standards from the International Committee of Medical Journal

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

    Science.gov (United States)

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

    2015-12-01

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

  6. Regulatory Monitoring of Fortified Foods: Identifying Barriers and Good Practices

    Science.gov (United States)

    Rowe, Laura A; Vossenaar, Marieke; Garrett, Greg S

    2015-01-01

    While fortification of staple foods and condiments has gained enormous global traction, poor performance persists throughout many aspects of implementation, most notably around the critical element of regulatory monitoring, which is essential for ensuring foods meet national fortification standards. Where coverage of fortified foods is high, limited nutritional impact of fortification programs largely exists due to regulatory monitoring that insufficiently identifies and holds producers accountable for underfortified products. Based on quality assurance data from 20 national fortification programs in 12 countries, we estimate that less than half of the samples are adequately fortified against relevant national standards. In this paper, we outline key findings from a literature review, key informant interviews with 11 fortification experts, and semi-quantitative surveys with 39 individuals from regulatory agencies and the food fortification industry in 17 countries on the perceived effectiveness of regulatory monitoring systems and barriers to compliance against national fortification standards. Findings highlight that regulatory agencies and industry disagree on the value that enforcement mechanisms have in ensuring compliance against standards. Perceived political risk of enforcement and poorly resourced inspectorate capacity appear to adversely reinforce each other within an environment of unclear legislation to create a major hurdle for improving overall compliance of fortification programs against national standards. Budget constraints affect the ability of regulatory agencies to create a well-trained inspector cadre and improve the detection and enforcement of non-compliant and underfortified products. Recommendations to improve fortification compliance include improving technical capacity; ensuring sustained leadership, accountability, and funding in both the private and the public sectors; and removing political barriers to ensure consistent detection of

  7. Identifying TF-MiRNA Regulatory Relationships Using Multiple Features.

    Directory of Open Access Journals (Sweden)

    Mingyu Shao

    Full Text Available MicroRNAs are known to play important roles in the transcriptional and post-transcriptional regulation of gene expression. While intensive research has been conducted to identify miRNAs and their target genes in various genomes, there is only limited knowledge about how microRNAs are regulated. In this study, we construct a pipeline that can infer the regulatory relationships between transcription factors and microRNAs from ChIP-Seq data with high confidence. In particular, after identifying candidate peaks from ChIP-Seq data, we formulate the inference as a PU learning (learning from only positive and unlabeled examples problem. Multiple features including the statistical significance of the peaks, the location of the peaks, the transcription factor binding site motifs, and the evolutionary conservation are derived from peaks for training and prediction. To further improve the accuracy of our inference, we also apply a mean reciprocal rank (MRR-based method to the candidate peaks. We apply our pipeline to infer TF-miRNA regulatory relationships in mouse embryonic stem cells. The experimental results show that our approach provides very specific findings of TF-miRNA regulatory relationships.

  8. Association analysis identifies ZNF750 regulatory variants in psoriasis

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    Birnbaum Ramon Y

    2011-12-01

    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  9. POEM: Identifying joint additive effects on regulatory circuits

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    Maya eBotzman

    2016-04-01

    Full Text Available Motivation: Expression Quantitative Trait Locus (eQTL mapping tackles the problem of identifying variation in DNA sequence that have an effect on the transcriptional regulatory network. Major computational efforts are aimed at characterizing the joint effects of several eQTLs acting in concert to govern the expression of the same genes. Yet, progress towards a comprehensive prediction of such joint effects is limited. For example, existing eQTL methods commonly discover interacting loci affecting the expression levels of a module of co-regulated genes. Such ‘modularization’ approaches, however, are focused on epistatic relations and thus have limited utility for the case of additive (non-epistatic effects.Results: Here we present POEM (Pairwise effect On Expression Modules, a methodology for identifying pairwise eQTL effects on gene modules. POEM is specifically designed to achieve high performance in the case of additive joint effects. We applied POEM to transcription profiles measured in bone marrow-derived dendritic cells across a population of genotyped mice. Our study reveals widespread additive, trans-acting pairwise effects on gene modules, characterizes their organizational principles, and highlights high-order interconnections between modules within the immune signaling network. These analyses elucidate the central role of additive pairwise effect in regulatory circuits, and provide computational tools for future investigations into the interplay between eQTLs.Availability: The software described in this article is available at csgi.tau.ac.il/POEM/.

  10. 77 FR 28467 - Identifying and Reducing Regulatory Burdens

    Science.gov (United States)

    2012-05-14

    ... online wherever practicable. Sec. 3. Setting Priorities. In implementing and improving their... regulatory priorities, to promote public participation in retrospective review, to modernize our regulatory..., agencies shall give priority, consistent with law, to those initiatives that will produce significant...

  11. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes.

    Science.gov (United States)

    Parker, Brian J; Moltke, Ida; Roth, Adam; Washietl, Stefan; Wen, Jiayu; Kellis, Manolis; Breaker, Ronald; Pedersen, Jakob Skou

    2011-11-01

    Regulatory RNA structures are often members of families with multiple paralogous instances across the genome. Family members share functional and structural properties, which allow them to be studied as a whole, facilitating both bioinformatic and experimental characterization. We have developed a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein-coding regions comprising 725 individual structures, including 48 families with known structural RNA elements. Known families identified include both noncoding RNAs, e.g., miRNAs and the recently identified MALAT1/MEN β lincRNA family; and cis-regulatory structures, e.g., iron-responsive elements. We also identify tens of new families supported by strong evolutionary evidence and other statistical evidence, such as GO term enrichments. For some of these, detailed analysis has led to the formulation of specific functional hypotheses. Examples include two hypothesized auto-regulatory feedback mechanisms: one involving six long hairpins in the 3'-UTR of MAT2A, a key metabolic gene that produces the primary human methyl donor S-adenosylmethionine; the other involving a tRNA-like structure in the intron of the tRNA maturation gene POP1. We experimentally validate the predicted MAT2A structures. Finally, we identify potential new regulatory networks, including large families of short hairpins enriched in immunity-related genes, e.g., TNF, FOS, and CTLA4, which include known transcript destabilizing elements. Our findings exemplify the diversity of post-transcriptional regulation and provide a resource for further characterization of new regulatory mechanisms and families of noncoding RNAs.

  12. RegRNA: an integrated web server for identifying regulatory RNA motifs and elements

    OpenAIRE

    Huang, Hsi-Yuan; Chien, Chia-Hung; Jen, Kuan-Hua; Huang, Hsien-Da

    2006-01-01

    Numerous regulatory structural motifs have been identified as playing essential roles in transcriptional and post-transcriptional regulation of gene expression. RegRNA is an integrated web server for identifying the homologs of regulatory RNA motifs and elements against an input mRNA sequence. Both sequence homologs and structural homologs of regulatory RNA motifs can be recognized. The regulatory RNA motifs supported in RegRNA are categorized into several classes: (i) motifs in mRNA 5′-untra...

  13. Evidentiary requirements to identify potentially acceptable sites (PAS) in crystalline rock

    International Nuclear Information System (INIS)

    Comella, P.A.; Smith, B.H.

    1985-01-01

    This report contains information on the evidentiary requirements to identify potentially acceptable sites in crystalline rock for waste disposal. Topics addressed include: chronology, key regulatory assumptions, statutory framework for identifying potentially acceptable sites, application of 10 disqualifiers, consideration of favorable and potentially adverse conditions, a composite favorability analysis, and a proposed outline for PAS identification decision document

  14. Enhancing regulatory effectiveness by improving the process for identifying and resolving generic issues

    International Nuclear Information System (INIS)

    Vander Molen, Harold J.

    2001-01-01

    The Generic Issues Program first began formally in response to a Commission directive in October of 1976. In 1983, it became one of the first programs to make successful use of probabilistic risk information to aid in regulatory decision-making. In the 16 years since the program became quantitative, 836 issues have been processed. Of these, 106 reactor safety issues were prioritized as requiring further evaluation to determine the final resolution. Approximately a dozen generic issues remain unresolved. Although there is far less reactor licensing activity than in the 1970s, new issues continue to be identified from research and operational experience. These issues often involve complex and controversial questions of safety and regulation, and an efficient and effective means of addressing these issues is essential for regulatory effectiveness. Issues that involve a significant safety question require swift, effective, enforceable, and cost-effective regulatory actions. Issues that are of little safety significance must be quickly shown to be so and dismissed in an expeditious manner so as to avoid unnecessary expenditure of limited resources and to reduce regulatory uncertainty. Additionally, in the time since the generic issue program began, probabilistic risk assessment techniques have advanced significantly while agency resources have continued to diminish. Accordingly, the paper discusses the steps that have been taken to enhance the effectiveness and efficiency of the generic issue resolution process. Additionally, four resolved issues are discussed, along with key elements of a proposed new procedure for resolving potential generic issues

  15. Regulatory T Cells: Potential Target in Anticancer Immunotherapy

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    Chi-Mou Juang

    2007-09-01

    Full Text Available The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

  16. TransDetect Identifies a New Regulatory Module Controlling Phosphate Accumulation.

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    Pal, Sikander; Kisko, Mushtak; Dubos, Christian; Lacombe, Benoit; Berthomieu, Pierre; Krouk, Gabriel; Rouached, Hatem

    2017-10-01

    Identifying transcription factor (TFs) cooperation controlling target gene expression is still an arduous challenge. The accuracy of current methods at genome scale significantly drops with the increase in number of genes, which limits their applicability to more complex genomes, like animals and plants. Here, we developed an algorithm, TransDetect, able to predict TF combinations controlling the expression level of a given gene. TransDetect was used to identify novel TF modules regulating the expression of Arabidopsis ( Arabidopsis thaliana ) phosphate transporter PHO1;H3 comprising MYB15, MYB84, bHLH35, and ICE1. These TFs were confirmed to interact between themselves and with the PHO1;H3 promoter. Phenotypic and genetic analyses of TF mutants enable the organization of these four TFs and PHO1;H3 in a new gene regulatory network controlling phosphate accumulation in zinc-dependent manner. This demonstrates the potential of TransDetect to extract directionality in nondynamic transcriptomes and to provide a blueprint to identify gene regulatory network involved in a given biological process. © 2017 American Society of Plant Biologists. All Rights Reserved.

  17. Identifying Potential Child Abuse through Oral Examination

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    Jillian N. Printz

    2017-01-01

    Full Text Available Limited reports of oropharyngeal trauma exist in the literature even though this type of injury is extremely common in pediatric populations. There are no widely agreed upon diagnostic and management tools for such injuries in abuse cases, emphasizing the importance of reporting rare cases of orofacial trauma. This case report of a soft palate laceration demonstrates an instance of initially unrecognized potential child abuse. We aim to clarify understanding of such injuries. Furthermore, the report highlights the need for recognition of oral signs of child abuse in order to promote early detection, reporting, and appropriate management.

  18. Genome-wide analysis of regulatory proteases sequences identified through bioinformatics data mining in Taenia solium.

    Science.gov (United States)

    Yan, Hong-Bin; Lou, Zhong-Zi; Li, Li; Brindley, Paul J; Zheng, Yadong; Luo, Xuenong; Hou, Junling; Guo, Aijiang; Jia, Wan-Zhong; Cai, Xuepeng

    2014-06-04

    Cysticercosis remains a major neglected tropical disease of humanity in many regions, especially in sub-Saharan Africa, Central America and elsewhere. Owing to the emerging drug resistance and the inability of current drugs to prevent re-infection, identification of novel vaccines and chemotherapeutic agents against Taenia solium and related helminth pathogens is a public health priority. The T. solium genome and the predicted proteome were reported recently, providing a wealth of information from which new interventional targets might be identified. In order to characterize and classify the entire repertoire of protease-encoding genes of T. solium, which act fundamental biological roles in all life processes, we analyzed the predicted proteins of this cestode through a combination of bioinformatics tools. Functional annotation was performed to yield insights into the signaling processes relevant to the complex developmental cycle of this tapeworm and to highlight a suite of the proteases as potential intervention targets. Within the genome of this helminth parasite, we identified 200 open reading frames encoding proteases from five clans, which correspond to 1.68% of the 11,902 protein-encoding genes predicted to be present in its genome. These proteases include calpains, cytosolic, mitochondrial signal peptidases, ubiquitylation related proteins, and others. Many not only show significant similarity to proteases in the Conserved Domain Database but have conserved active sites and catalytic domains. KEGG Automatic Annotation Server (KAAS) analysis indicated that ~60% of these proteases share strong sequence identities with proteins of the KEGG database, which are involved in human disease, metabolic pathways, genetic information processes, cellular processes, environmental information processes and organismal systems. Also, we identified signal peptides and transmembrane helices through comparative analysis with classes of important regulatory proteases

  19. Regulatory elements of the floral homeotic gene AGAMOUS identified by phylogenetic footprinting and shadowing.

    Energy Technology Data Exchange (ETDEWEB)

    Hong, R. L., Hamaguchi, L., Busch, M. A., and Weigel, D.

    2003-06-01

    OAK-B135 In Arabidopsis thaliana, cis-regulatory sequences of the floral homeotic gene AGAMOUS (AG) are located in the second intron. This 3 kb intron contains binding sites for two direct activators of AG, LEAFY (LFY) and WUSCHEL (WUS), along with other putative regulatory elements. We have used phylogenetic footprinting and the related technique of phylogenetic shadowing to identify putative cis-regulatory elements in this intron. Among 29 Brassicaceae, several other motifs, but not the LFY and WUS binding sites previously identified, are largely invariant. Using reporter gene analyses, we tested six of these motifs and found that they are all functionally important for activity of AG regulatory sequences in A. thaliana. Although there is little obvious sequence similarity outside the Brassicaceae, the intron from cucumber AG has at least partial activity in A. thaliana. Our studies underscore the value of the comparative approach as a tool that complements gene-by-gene promoter dissection, but also highlight that sequence-based studies alone are insufficient for a complete identification of cis-regulatory sites.

  20. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes

    DEFF Research Database (Denmark)

    Parker, Brian John; Moltke, Ida; Roth, Adam

    2011-01-01

    a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein...

  1. Effectively identifying regulatory hotspots while capturing expression heterogeneity in gene expression studies

    Science.gov (United States)

    2014-01-01

    Expression quantitative trait loci (eQTL) mapping is a tool that can systematically identify genetic variation affecting gene expression. eQTL mapping studies have shown that certain genomic locations, referred to as regulatory hotspots, may affect the expression levels of many genes. Recently, studies have shown that various confounding factors may induce spurious regulatory hotspots. Here, we introduce a novel statistical method that effectively eliminates spurious hotspots while retaining genuine hotspots. Applied to simulated and real datasets, we validate that our method achieves greater sensitivity while retaining low false discovery rates compared to previous methods. PMID:24708878

  2. Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data.

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    Taosheng Xu

    Full Text Available Identifying cancer subtypes is an important component of the personalised medicine framework. An increasing number of computational methods have been developed to identify cancer subtypes. However, existing methods rarely use information from gene regulatory networks to facilitate the subtype identification. It is widely accepted that gene regulatory networks play crucial roles in understanding the mechanisms of diseases. Different cancer subtypes are likely caused by different regulatory mechanisms. Therefore, there are great opportunities for developing methods that can utilise network information in identifying cancer subtypes.In this paper, we propose a method, weighted similarity network fusion (WSNF, to utilise the information in the complex miRNA-TF-mRNA regulatory network in identifying cancer subtypes. We firstly build the regulatory network where the nodes represent the features, i.e. the microRNAs (miRNAs, transcription factors (TFs and messenger RNAs (mRNAs and the edges indicate the interactions between the features. The interactions are retrieved from various interatomic databases. We then use the network information and the expression data of the miRNAs, TFs and mRNAs to calculate the weight of the features, representing the level of importance of the features. The feature weight is then integrated into a network fusion approach to cluster the samples (patients and thus to identify cancer subtypes. We applied our method to the TCGA breast invasive carcinoma (BRCA and glioblastoma multiforme (GBM datasets. The experimental results show that WSNF performs better than the other commonly used computational methods, and the information from miRNA-TF-mRNA regulatory network contributes to the performance improvement. The WSNF method successfully identified five breast cancer subtypes and three GBM subtypes which show significantly different survival patterns. We observed that the expression patterns of the features in some mi

  3. Identifying noncoding risk variants using disease-relevant gene regulatory networks.

    Science.gov (United States)

    Gao, Long; Uzun, Yasin; Gao, Peng; He, Bing; Ma, Xiaoke; Wang, Jiahui; Han, Shizhong; Tan, Kai

    2018-02-16

    Identifying noncoding risk variants remains a challenging task. Because noncoding variants exert their effects in the context of a gene regulatory network (GRN), we hypothesize that explicit use of disease-relevant GRNs can significantly improve the inference accuracy of noncoding risk variants. We describe Annotation of Regulatory Variants using Integrated Networks (ARVIN), a general computational framework for predicting causal noncoding variants. It employs a set of novel regulatory network-based features, combined with sequence-based features to infer noncoding risk variants. Using known causal variants in gene promoters and enhancers in a number of diseases, we show ARVIN outperforms state-of-the-art methods that use sequence-based features alone. Additional experimental validation using reporter assay further demonstrates the accuracy of ARVIN. Application of ARVIN to seven autoimmune diseases provides a holistic view of the gene subnetwork perturbed by the combinatorial action of the entire set of risk noncoding mutations.

  4. Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data.

    Science.gov (United States)

    Tsou, Ann-Ping; Sun, Yi-Ming; Liu, Chia-Lin; Huang, Hsien-Da; Horng, Jorng-Tzong; Tsai, Meng-Feng; Liu, Baw-Juine

    2006-07-01

    Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems.

  5. RNA-ID, a Powerful Tool for Identifying and Characterizing Regulatory Sequences.

    Science.gov (United States)

    Brule, C E; Dean, K M; Grayhack, E J

    2016-01-01

    The identification and analysis of sequences that regulate gene expression is critical because regulated gene expression underlies biology. RNA-ID is an efficient and sensitive method to discover and investigate regulatory sequences in the yeast Saccharomyces cerevisiae, using fluorescence-based assays to detect green fluorescent protein (GFP) relative to a red fluorescent protein (RFP) control in individual cells. Putative regulatory sequences can be inserted either in-frame or upstream of a superfolder GFP fusion protein whose expression, like that of RFP, is driven by the bidirectional GAL1,10 promoter. In this chapter, we describe the methodology to identify and study cis-regulatory sequences in the RNA-ID system, explaining features and variations of the RNA-ID reporter, as well as some applications of this system. We describe in detail the methods to analyze a single regulatory sequence, from construction of a single GFP variant to assay of variants by flow cytometry, as well as modifications required to screen libraries of different strains simultaneously. We also describe subsequent analyses of regulatory sequences. © 2016 Elsevier Inc. All rights reserved.

  6. Potential environmental benefits from regulatory consideration of synthetic drilling muds

    International Nuclear Information System (INIS)

    Burke, C.J.; Veil, J.A.

    1995-02-01

    When drilling exploration and production wells for oil and gas, drillers use specialized drilling fluids, referred to as muds, to help maintain well control and to remove drill cuttings from the hole. Historically, either water-based muds (WBMs) or oil-based muds (OBMs) have been used for offshore wells. Recently, in response to US Environmental Protection Agency (EPA) regulations and drilling-waste discharge requirements imposed by North Sea nations, the drilling industry has developed several types of synthetic-based muds (SBMs) that combine the desirable operating qualities of OBMs with the lower toxicity and environmental impact qualities of WBMs. This report describes the operational, environmental, and economic features of all three types of muds and discusses potential EPA regulatory barriers to wider use of SBMs

  7. Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

    Science.gov (United States)

    Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

    2017-04-01

    Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

  8. Close Sequence Comparisons are Sufficient to Identify Humancis-Regulatory Elements

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakar, Shyam; Poulin, Francis; Shoukry, Malak; Afzal, Veena; Rubin, Edward M.; Couronne, Olivier; Pennacchio, Len A.

    2005-12-01

    Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of evolutionarily close and distant sequence comparisons, due to the lack of a universal metric for sequence conservation, and also the paucity of empirically defined benchmark sets of cis-regulatory elements. To address this problem, we developed a general-purpose algorithm (Gumby) that detects slowly-evolving regions in primate, mammalian and more distant comparisons without requiring adjustment of parameters, and ranks conserved elements by P-value using Karlin-Altschul statistics. We benchmarked Gumby predictions against previously identified cis-regulatory elements at diverse genomic loci, and also tested numerous extremely conserved human-rodent sequences for transcriptional enhancer activity using reporter-gene assays in transgenic mice. Human regulatory elements were identified with acceptable sensitivity and specificity by comparison with 1-5 other eutherian mammals or 6 other simian primates. More distant comparisons (marsupial, avian, amphibian and fish) failed to identify many of the empirically defined functional noncoding elements. We derived an intuitive relationship between ancient and recent noncoding sequence conservation from whole genome comparative analysis, which explains some of these findings. Lastly, we determined that, in addition to strength of conservation, genomic location and/or density of surrounding conserved elements must also be considered in selecting candidate enhancers for testing at embryonic time points.

  9. Identifying potential surface water sampling sites for emerging chemical pollutants in Gauteng Province, South Africa

    OpenAIRE

    Petersen, F; Dabrowski, JM; Forbes, PBC

    2017-01-01

    Emerging chemical pollutants (ECPs) are defined as new chemicals which do not have a regulatory status, but which may have an adverse effect on human health and the environment. The occurrence and concentrations of ECPs in South African water bodies are largely unknown, so monitoring is required in order to determine the potential threat that these ECPs may pose. Relevant surface water sampling sites in the Gauteng Province of South Africa were identified utilising a geographic information sy...

  10. Identifying time-delayed gene regulatory networks via an evolvable hierarchical recurrent neural network.

    Science.gov (United States)

    Kordmahalleh, Mina Moradi; Sefidmazgi, Mohammad Gorji; Harrison, Scott H; Homaifar, Abdollah

    2017-01-01

    The modeling of genetic interactions within a cell is crucial for a basic understanding of physiology and for applied areas such as drug design. Interactions in gene regulatory networks (GRNs) include effects of transcription factors, repressors, small metabolites, and microRNA species. In addition, the effects of regulatory interactions are not always simultaneous, but can occur after a finite time delay, or as a combined outcome of simultaneous and time delayed interactions. Powerful biotechnologies have been rapidly and successfully measuring levels of genetic expression to illuminate different states of biological systems. This has led to an ensuing challenge to improve the identification of specific regulatory mechanisms through regulatory network reconstructions. Solutions to this challenge will ultimately help to spur forward efforts based on the usage of regulatory network reconstructions in systems biology applications. We have developed a hierarchical recurrent neural network (HRNN) that identifies time-delayed gene interactions using time-course data. A customized genetic algorithm (GA) was used to optimize hierarchical connectivity of regulatory genes and a target gene. The proposed design provides a non-fully connected network with the flexibility of using recurrent connections inside the network. These features and the non-linearity of the HRNN facilitate the process of identifying temporal patterns of a GRN. Our HRNN method was implemented with the Python language. It was first evaluated on simulated data representing linear and nonlinear time-delayed gene-gene interaction models across a range of network sizes and variances of noise. We then further demonstrated the capability of our method in reconstructing GRNs of the Saccharomyces cerevisiae synthetic network for in vivo benchmarking of reverse-engineering and modeling approaches (IRMA). We compared the performance of our method to TD-ARACNE, HCC-CLINDE, TSNI and ebdbNet across different network

  11. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells.

    Science.gov (United States)

    Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

    2009-08-11

    The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFbeta, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP- cells. Remarkably, CD25+GARP- T cells expanded in culture contained 3-5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25-GARP- cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) -infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation.

  12. Using reporter gene assays to identify cis regulatory differences between humans and chimpanzees.

    Science.gov (United States)

    Chabot, Adrien; Shrit, Ralla A; Blekhman, Ran; Gilad, Yoav

    2007-08-01

    Most phenotypic differences between human and chimpanzee are likely to result from differences in gene regulation, rather than changes to protein-coding regions. To date, however, only a handful of human-chimpanzee nucleotide differences leading to changes in gene regulation have been identified. To hone in on differences in regulatory elements between human and chimpanzee, we focused on 10 genes that were previously found to be differentially expressed between the two species. We then designed reporter gene assays for the putative human and chimpanzee promoters of the 10 genes. Of seven promoters that we found to be active in human liver cell lines, human and chimpanzee promoters had significantly different activity in four cases, three of which recapitulated the gene expression difference seen in the microarray experiment. For these three genes, we were therefore able to demonstrate that a change in cis influences expression differences between humans and chimpanzees. Moreover, using site-directed mutagenesis on one construct, the promoter for the DDA3 gene, we were able to identify three nucleotides that together lead to a cis regulatory difference between the species. High-throughput application of this approach can provide a map of regulatory element differences between humans and our close evolutionary relatives.

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Modelling intelligence-led policing to identify its potential

    NARCIS (Netherlands)

    Hengst-Bruggeling, M. den; Graaf, H.A.L.M. de; Scheepstal, P.G.M. van

    2014-01-01

    lntelligence-led policing is a concept of policing that has been applied throughout the world. Despite some encouraging reports, the effect of intelligence-led policing is largely unknown. This paper presents a method with which it is possible to identify intelligence-led policing's potential to

  16. A GIS methodology to identify potential corn stover collection locations

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Monica A. [Department of Community and Regional Planning, 583 College of Design, Iowa State University, Ames, IA 50011-3095 (United States); Anderson, Paul F. [Department of Landscape Architecture, 481 College of Design, Iowa State University, Ames, IA 50011 (United States); Department of Agronomy, 481 College of Design, Iowa State University, Ames, IA 50011 (United States)

    2008-12-15

    In this study, we use geographic information systems technology to identify potential locations in a Midwestern region for collection and storage of corn stover for use as biomass feedstock. Spatial location models are developed to identify potential collection sites along an existing railroad. Site suitability analysis is developed based on two main models: agronomic productivity potential and environmental costs. The analysis includes the following steps: (1) elaboration of site selection criteria; (2) identification of the study region and service area based on transportation network analysis; (3) reclassification of input spatial layers based on common scales; (4) overlaying the reclassified spatial layers with equal weights to generate the two main models; and (5) overlaying the main models using different weights. A pluralistic approach is adopted, presenting three different scenarios as alternatives for the potential locations. Our results suggest that there is a significant subset of potential sites that meet site selection criteria. Additional studies are needed to evaluate potential sites through field visits, assess economic and social costs, and estimate the proportion of corn producers willing to sell and transport corn stover to collection facilities. (author)

  17. Identifying potential kidney donors using social networking web sites.

    Science.gov (United States)

    Chang, Alexander; Anderson, Emily E; Turner, Hang T; Shoham, David; Hou, Susan H; Grams, Morgan

    2013-01-01

    Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2-69); 88% were US residents. Other posted information included the individual's photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live-donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. © 2013 John Wiley & Sons A/S.

  18. Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis.

    Science.gov (United States)

    Guo, Xing-Ya; He, Chong-Xin; Wang, Yu-Qin; Sun, Chao; Li, Guang-Ming; Su, Qing; Pan, Qin; Fan, Jian-Gao

    2017-01-01

    Circular RNAs (circRNAs) exhibit a wide range of physiological and pathological activities. To uncover their role in hepatic steatosis, we investigated the expression profile of circRNAs in HepG2-based hepatic steatosis induced by high-fat stimulation. Differentially expressed circRNAs were subjected to validation using QPCR and functional analyses using principal component analysis, hierarchical clustering, target prediction, gene ontology (GO), and pathway annotation, respectively. Bioinformatic integration established the circRNA-miRNA-mRNA regulatory network so as to identify the mechanisms underlying circRNAs' metabolic effect. Here we reported that hepatic steatosis was associated with a total of 357 circRNAs. Enrichment of transcription-related GOs, especially GO: 0006355, GO: 004589, GO: 0045944, GO: 0045892, and GO: 0000122, demonstrated their specific actions in transcriptional regulation. Lipin 1 (LPIN1) was recognized to mediate the transcriptional regulatory effect of circRNAs on metabolic pathways. circRNA-miRNA-mRNA network further identified the signaling cascade of circRNA_021412/miR-1972/LPIN1, which was characterized by decreased level of circRNA_021412 and miR-1972-based inhibition of LPIN1. LPIN1-induced downregulation of long chain acyl-CoA synthetases (ACSLs) expression finally resulted in the hepatosteatosis. These findings identify circRNAs to be important regulators of hepatic steatosis. Transcription-dependent modulation of metabolic pathways may underlie their effects, partially by the circRNA_021412/miR-1972/LPIN1 signaling.

  19. Identifying product development crises: The potential of adaptive heuristics

    DEFF Research Database (Denmark)

    Münzberger, C.; Stingl, Verena; Oehmen, Josef

    2017-01-01

    This paper introduces adaptive heuristics as a tool to identify crises in design projects and highlights potential applications of these heuristics as decision support tool for crisis identification. Crises may emerge slowly or suddenly, and often have ambiguous signals. Thus the identification...... for the application of heuristics in design sciences. To achieve this, the paper compares crises to 'business as usual', and presents sixteen indicators for emerging crises. These indicators are potential cues for adaptive heuristics. Specifically three adaptive heuristics, One-single-cue, Fast-and-Frugal-Trees...

  20. Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

    Science.gov (United States)

    Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

    2017-11-17

    Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

  1. Analysis of regulatory structure for a potential fusion reactor industry

    Energy Technology Data Exchange (ETDEWEB)

    1981-03-01

    The report is divided into eight sections. The preface describes the authors of the report, the methodology used in its preparation, and some basic legal terms. The summary describes the principal features of the proposed regulatory system and also includes two flow charts comparing our model with present NRC practices and a summary table briefly outlining the reasoning behind our recommendations. The main body of the report is divided into six sections. This part of the report discusses the existing federal and state programs for regulating electric energy, describes NRC operations and the criticisms of that agency, discusses the features of our proposed regulatory model, recommends certain steps for implementing the proposed model, and states the conclusions of the report.

  2. Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency

    Directory of Open Access Journals (Sweden)

    Yeh Cheng-Yu

    2009-12-01

    Full Text Available Abstract Background Prostate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer. Results To deal with missing values in microarray data, we used a K-nearest-neighbors (KNN algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2 regulated by RUNX1 and STAT3 is correlated to the pathological stage

  3. Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency.

    Science.gov (United States)

    Yeh, Hsiang-Yuan; Cheng, Shih-Wu; Lin, Yu-Chun; Yeh, Cheng-Yu; Lin, Shih-Fang; Soo, Von-Wun

    2009-12-21

    Prostate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer. To deal with missing values in microarray data, we used a K-nearest-neighbors (KNN) algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD) as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2) regulated by RUNX1 and STAT3 is correlated to the pathological stage. We provide a computational framework to reconstruct

  4. kmer-SVM: a web server for identifying predictive regulatory sequence features in genomic data sets

    Science.gov (United States)

    Fletez-Brant, Christopher; Lee, Dongwon; McCallion, Andrew S.; Beer, Michael A.

    2013-01-01

    Massively parallel sequencing technologies have made the generation of genomic data sets a routine component of many biological investigations. For example, Chromatin immunoprecipitation followed by sequence assays detect genomic regions bound (directly or indirectly) by specific factors, and DNase-seq identifies regions of open chromatin. A major bottleneck in the interpretation of these data is the identification of the underlying DNA sequence code that defines, and ultimately facilitates prediction of, these transcription factor (TF) bound or open chromatin regions. We have recently developed a novel computational methodology, which uses a support vector machine (SVM) with kmer sequence features (kmer-SVM) to identify predictive combinations of short transcription factor-binding sites, which determine the tissue specificity of these genomic assays (Lee, Karchin and Beer, Discriminative prediction of mammalian enhancers from DNA sequence. Genome Res. 2011; 21:2167–80). This regulatory information can (i) give confidence in genomic experiments by recovering previously known binding sites, and (ii) reveal novel sequence features for subsequent experimental testing of cooperative mechanisms. Here, we describe the development and implementation of a web server to allow the broader research community to independently apply our kmer-SVM to analyze and interpret their genomic datasets. We analyze five recently published data sets and demonstrate how this tool identifies accessory factors and repressive sequence elements. kmer-SVM is available at http://kmersvm.beerlab.org. PMID:23771147

  5. Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Brian J. Peter

    2008-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP, the currently used HCC marker, misses 30%–50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48 and patients with chronic hepatitis B or C viral infections (n = 19 (both of which are the major risk factors of HCC. We identified 7 proteins that significantly differentiate HCC patients from hepatitis patients (p < 0.05 (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1.Importantly, we also identified 8 proteins that significantly differentiate HCC patients with ‘normal’ levels of AFP (<20 ng/ml from hepatitis patients (p < 0.05 (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL. These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020. In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identified HCC diagnostic markers needs to be systematically evaluated.

  6. An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

    Directory of Open Access Journals (Sweden)

    Daniel Savic

    Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

  7. Newer Approaches to Identify Potential Untoward Effects in Functional Foods.

    Science.gov (United States)

    Marone, Palma Ann; Birkenbach, Victoria L; Hayes, A Wallace

    2016-01-01

    Globalization has greatly accelerated the numbers and variety of food and beverage products available worldwide. The exchange among greater numbers of countries, manufacturers, and products in the United States and worldwide has necessitated enhanced quality measures for nutritional products for larger populations increasingly reliant on functionality. These functional foods, those that provide benefit beyond basic nutrition, are increasingly being used for their potential to alleviate food insufficiency while enhancing quality and longevity of life. In the United States alone, a steady import increase of greater than 15% per year or 24 million shipments, over 70% products of which are food related, is regulated under the Food and Drug Administration (FDA). This unparalleled growth has resulted in the need for faster, cheaper, and better safety and efficacy screening methods in the form of harmonized guidelines and recommendations for product standardization. In an effort to meet this need, the in vitro toxicology testing market has similarly grown with an anticipatory 15% increase between 2010 and 2015 of US$1.3 to US$2.7 billion. Although traditionally occupying a small fraction of the market behind pharmaceuticals and cosmetic/household products, the scope of functional food testing, including additives/supplements, ingredients, residues, contact/processing, and contaminants, is potentially expansive. Similarly, as functional food testing has progressed, so has the need to identify potential adverse factors that threaten the safety and quality of these products. © The Author(s) 2015.

  8. Identifying potential surface water sampling sites for emerging ...

    African Journals Online (AJOL)

    Emerging chemical pollutants (ECPs) are defined as new chemicals which do not have a regulatory status, but which may have an adverse effect on human health and the environment. The occurrence and concentrations of ECPs in South African water bodies are largely unknown, so monitoring is required in order to ...

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Regulatory T Cells As Potential Targets for HIV Cure Research

    Science.gov (United States)

    Kleinman, Adam J.; Sivanandham, Ranjit; Pandrea, Ivona; Chougnet, Claire A.; Apetrei, Cristian

    2018-01-01

    T regulatory cells (Tregs) are a key component of the immune system, which maintain a delicate balance between overactive responses and immunosuppression. As such, Treg deficiencies are linked to autoimmune disorders and alter the immune control of pathogens. In HIV infection, Tregs play major roles, both beneficial and detrimental. They regulate the immune system such that inflammation and spread of virus through activated T cells is suppressed. However, suppression of immune activation also limits viral clearance and promotes reservoir formation. Tregs can be directly targeted by HIV, thereby harboring a fraction of the viral reservoir. The vital role of Tregs in the pathogenesis and control of HIV makes them a subject of interest for manipulation in the search of an HIV cure. Here, we discuss the origin and generation, homeostasis, and functions of Tregs, particularly their roles and effects in HIV infection. We also present various Treg manipulation strategies, including Treg depletion techniques and interventions that alter Treg function, which may be used in different cure strategies, to simultaneously boost HIV-specific immune responses and induce reactivation of the latent virus.

  12. Investigations of potential below regulatory concern (de minimus) wastes

    International Nuclear Information System (INIS)

    Gruhlke, J.M.; Galpin, F.L.

    1983-01-01

    Low-level radioactive waste (LLW) includes a wide variety of waste types. Many organizations are contemplating the merits of declaring certain LLW as de minimus. The concept of de minimus has considerable support, as evidenced by the comments on NRC's rulemaking for 10 CFR Part 61, Licensing Requirements for Land Disposal of Radioactive Waste. Practical and philosophical considerations lend weight to the further investigation of the de minimus concept for LLW. The Environmental Protection Agency (EPA) recognizes the interest and efforts in the concept of de minimus. Because the term de minimus may imply a lack of concern for the risks of disposal, we use the term Below Regulatory Concern (BRC). EPA has developed technical information, cost data, and a methodology for selecting promising candidate waste streams. The NRC's breakdown of LLW, as provided in the supporting documentation for 10 CFR Part 51, serves as a starting point for evaluating individual waste streams. Waste streams may then be ranked on the basis of individual dose, population health impact, and cost/benefit. A set of waste streams consistently ranks near the top in all categories and deserves further analysis. This screening is the initial step in an overall effort to develop a basis for determining the appropriateness and form of generic BRC criteria. 14 references, 8 tables

  13. Identifying cis-regulatory modules by combining comparative and compositional analysis of DNA.

    Science.gov (United States)

    Pierstorff, Nora; Bergman, Casey M; Wiehe, Thomas

    2006-12-01

    Predicting cis-regulatory modules (CRMs) in higher eukaryotes is a challenging computational task. Commonly used methods to predict CRMs based on the signal of transcription factor binding sites (TFBS) are limited by prior information about transcription factor specificity. More general methods that bypass the reliance on TFBS models are needed for comprehensive CRM prediction. We have developed a method to predict CRMs called CisPlusFinder that identifies high density regions of perfect local ungapped sequences (PLUSs) based on multiple species conservation. By assuming that PLUSs contain core TFBS motifs that are locally overrepresented, the method attempts to capture the expected features of CRM structure and evolution. Applied to a benchmark dataset of CRMs involved in early Drosophila development, CisPlusFinder predicts more annotated CRMs than all other methods tested. Using the REDfly database, we find that some 'false positive' predictions in the benchmark dataset correspond to recently annotated CRMs. Our work demonstrates that CRM prediction methods that combine comparative genomic data with statistical properties of DNA may achieve reasonable performance when applied genome-wide in the absence of an a priori set of known TFBS motifs. The program CisPlusFinder can be downloaded at http://jakob.genetik.uni-koeln.de/bioinformatik/people/nora/nora.html. All software is licensed under the Lesser GNU Public License (LGPL).

  14. Distinct forms of the β subunit of GTP-binding regulatory proteins identified by molecular cloning

    International Nuclear Information System (INIS)

    Fong, H.K.W.; Amatruda, T.T. III; Birren, B.W.; Simon, M.I.

    1987-01-01

    Two distinct β subunits of guanine nucleotide-binding regulatory proteins have been identified by cDNA cloning and are referred to as β 1 and β 1 subunits. The bovine transducin β subunit (β 1 ) has been cloned previously. The author now isolated and analyzed cDNA clones that encode the β 2 subunit from bovine adrenal, bovine brain, and a human myeloid leukemia cell line, HL-60. The 340-residue M/sub r/ 37,329 Β 2 protein is 90% identical with β 1 in predicted amino acid sequence, and it is also organized as a series of repetitive homologous segments. The major mRNA that encodes the bovine β 2 subunit is 1.7 kilobases in length. It is expressed at lower levels than β 1 subunit mRNA in all tissues examined. The β 1 and β 2 messages are expressed in cloned human cell lines. Hybridization of cDNA probes to bovine DNA showed that β 1 and β 2 are encoded by separate genes. The amino acid sequences for the bovine and human β 2 subunit are identical, as are the amino acid sequences for the bovine and human β 1 subunit. This evolutionary conservation suggests that the two β subunits have different roles in the signal transduction process

  15. The regulatory framework of special medical group students' physical education: identifying the problem.

    Directory of Open Access Journals (Sweden)

    Mazur Valerij Anatol'evich

    2011-09-01

    Full Text Available The question of regulatory framework for special medical group students' physical education, and their physical condition in particular is elaborated. It is found that in the current program the identified question is missing, although the assessment of individual performance standards for the physical condition of the students was envisaged in the programs of 1977 and 1982. The need for such an assessment is indicated by the large number of Ukrainian and foreign pediatricians and specialists in therapeutic physical culture. At the same time the standards for assessing these indicators are not developed. It complicates the formation of positive motivation of students to regular classes, and does not promote their self-confidence, capabilities and effectiveness of monitoring the effectiveness of exercise in various forms. The findings suggest the need to define the optimal composition of the bulk of tests and functional tests to assess the physical condition of special medical group students with various diseases and to develop appropriate indicators for their evaluation standards.

  16. Potential of DNA sequences to identify zoanthids (Cnidaria: Zoantharia).

    Science.gov (United States)

    Sinniger, Frederic; Reimer, James D; Pawlowski, Jan

    2008-12-01

    The order Zoantharia is known for its chaotic taxonomy and difficult morphological identification. One method that potentially could help for examining such troublesome taxa is DNA barcoding, which identifies species using standard molecular markers. The mitochondrial cytochrome oxidase subunit I (COI) has been utilized to great success in groups such as birds and insects; however, its applicability in many other groups is controversial. Recently, some studies have suggested that barcoding is not applicable to anthozoans. Here, we examine the use of COI and mitochondrial 16S ribosomal DNA for zoanthid identification. Despite the absence of a clear barcoding gap, our results show that for most of 54 zoanthid samples, both markers could separate samples to the species, or species group, level, particularly when easily accessible ecological or distributional data were included. Additionally, we have used the short V5 region of mt 16S rDNA to identify eight old (13 to 50 years old) museum samples. We discuss advantages and disadvantages of COI and mt 16S rDNA as barcodes for Zoantharia, and recommend that either one or both of these markers be considered for zoanthid identification in the future.

  17. Obtaining subjects' consent to publish identifying personal information: current practices and identifying potential issues.

    Science.gov (United States)

    Yoshida, Akiko; Dowa, Yuri; Murakami, Hiromi; Kosugi, Shinji

    2013-11-25

    In studies publishing identifying personal information, obtaining consent is regarded as necessary, as it is impossible to ensure complete anonymity. However, current journal practices around specific points to consider when obtaining consent, the contents of consent forms and how consent forms are managed have not yet been fully examined. This study was conducted to identify potential issues surrounding consent to publish identifying personal information. Content analysis was carried out on instructions for authors and consent forms developed by academic journals in four fields (as classified by Journal Citation Reports): medicine general and internal, genetics and heredity, pediatrics, and psychiatry. An online questionnaire survey of editors working for journals that require the submission of consent forms was also conducted. Instructions for authors were reviewed for 491 academic journals (132 for medicine general and internal, 147 for genetics and heredity, 100 for pediatrics, and 112 for psychiatry). Approximately 40% (203: 74 for medicine general and internal, 31 for genetics and heredity, 58 for pediatrics, and 40 for psychiatry) stated that subject consent was necessary. The submission of consent forms was required by 30% (154) of the journals studied, and 10% (50) provided their own consent forms for authors to use. Two journals mentioned that the possible effects of publication on subjects should be considered. Many journal consent forms mentioned the difficulties in ensuring complete anonymity of subjects, but few addressed the study objective, the subjects' right to refuse consent and the withdrawal of consent. The main reason for requiring the submission of consent forms was to confirm that consent had been obtained. Approximately 40% of journals required subject consent to be obtained. However, differences were observed depending on the fields. Specific considerations were not always documented. There is a need to address issues around the study

  18. Obtaining subjects’ consent to publish identifying personal information: current practices and identifying potential issues

    Science.gov (United States)

    2013-01-01

    Background In studies publishing identifying personal information, obtaining consent is regarded as necessary, as it is impossible to ensure complete anonymity. However, current journal practices around specific points to consider when obtaining consent, the contents of consent forms and how consent forms are managed have not yet been fully examined. This study was conducted to identify potential issues surrounding consent to publish identifying personal information. Methods Content analysis was carried out on instructions for authors and consent forms developed by academic journals in four fields (as classified by Journal Citation Reports): medicine general and internal, genetics and heredity, pediatrics, and psychiatry. An online questionnaire survey of editors working for journals that require the submission of consent forms was also conducted. Results Instructions for authors were reviewed for 491 academic journals (132 for medicine general and internal, 147 for genetics and heredity, 100 for pediatrics, and 112 for psychiatry). Approximately 40% (203: 74 for medicine general and internal, 31 for genetics and heredity, 58 for pediatrics, and 40 for psychiatry) stated that subject consent was necessary. The submission of consent forms was required by 30% (154) of the journals studied, and 10% (50) provided their own consent forms for authors to use. Two journals mentioned that the possible effects of publication on subjects should be considered. Many journal consent forms mentioned the difficulties in ensuring complete anonymity of subjects, but few addressed the study objective, the subjects’ right to refuse consent and the withdrawal of consent. The main reason for requiring the submission of consent forms was to confirm that consent had been obtained. Conclusion Approximately 40% of journals required subject consent to be obtained. However, differences were observed depending on the fields. Specific considerations were not always documented. There is a need

  19. Mutations in the newly identified RAX regulatory sequence are not a frequent cause of micro/anophthalmia.

    Science.gov (United States)

    Chassaing, Nicolas; Vigouroux, Adeline; Calvas, Patrick

    2009-06-01

    Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (SOX2, OTX2, RAX, and CHX10) have been implicated in isolated micro/anophthalmia, but causative mutations of these genes explain less than a quarter of these developmental defects. A specifically conserved SOX2/OTX2-mediated RAX expression regulatory sequence has recently been identified. We postulated that mutations in this sequence could lead to micro/anophthalmia, and thus we performed molecular screening of this regulatory element in patients suffering from micro/anophthalmia. Fifty-one patients suffering from nonsyndromic microphthalmia (n = 40) or anophthalmia (n = 11) were included in this study after negative molecular screening for SOX2, OTX2, RAX, and CHX10 mutations. Mutation screening of the RAX regulatory sequence was performed by direct sequencing for these patients. No mutations were identified in the highly conserved RAX regulatory sequence in any of the 51 patients. Mutations in the newly identified RAX regulatory sequence do not represent a frequent cause of nonsyndromic micro/anophthalmia.

  20. Four essays on offshore wind power potential, development, regulatory framework, and integration

    Science.gov (United States)

    Dhanju, Amardeep

    Offshore wind power is an energy resource whose potential in the US has been recognized only recently. There is now growing interest among the coastal states to harness the resource, particularly in states adjacent to the Mid-Atlantic Bight where the shallow continental shelf allows installation of wind turbines using the existing foundation technology. But the promise of bountiful clean energy from offshore wind could be delayed or forestalled due to policy and regulatory challenges. This dissertation is an effort to identify and address some of the important challenges. Focusing on Delaware as a case study it calculates the extent of the wind resource; considers one means to facilitate resource development---the establishment of statewide and regional public power authorities; analyzes possible regulatory frameworks to manage the resource in state-controlled waters; and assesses the use of distributed storage to manage intermittent output from wind turbines. In order to cover a diversity of topics, this research uses a multi-paper format with four essays forming the body of work. The first essay lays out an accessible methodology to calculate offshore wind resource potential using publicly available data, and uses this methodology to access wind resources off Delaware. The assessment suggests a wind resource approximately four times the average electrical load in Delaware. The second essay examines the potential role of a power authority, a quasi-public institution, in lowering the cost of capital, reducing financial risk of developing and operating a wind farm, and enhancing regional collaboration on resource development and management issues. The analysis suggests that a power authority can lower the cost of offshore wind power by as much as 1/3, thereby preserving the ability to pursue cost-competitive development even if the current federal incentives are removed. The third essay addresses the existing regulatory void in state-controlled waters of Delaware

  1. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

    Directory of Open Access Journals (Sweden)

    Haitao Guo

    2017-01-01

    Full Text Available The discovery of cis-regulatory modules (CRMs is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them.

  2. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

    Science.gov (United States)

    2017-01-01

    The discovery of cis-regulatory modules (CRMs) is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them. PMID:28497059

  3. Identifying Tmem59 related gene regulatory network of mouse neural stem cell from a compendium of expression profiles

    Directory of Open Access Journals (Sweden)

    Guo Xiuyun

    2011-09-01

    Full Text Available Abstract Background Neural stem cells offer potential treatment for neurodegenerative disorders, such like Alzheimer's disease (AD. While much progress has been made in understanding neural stem cell function, a precise description of the molecular mechanisms regulating neural stem cells is not yet established. This lack of knowledge is a major barrier holding back the discovery of therapeutic uses of neural stem cells. In this paper, the regulatory mechanism of mouse neural stem cell (NSC differentiation by tmem59 is explored on the genome-level. Results We identified regulators of tmem59 during the differentiation of mouse NSCs from a compendium of expression profiles. Based on the microarray experiment, we developed the parallelized SWNI algorithm to reconstruct gene regulatory networks of mouse neural stem cells. From the inferred tmem59 related gene network including 36 genes, pou6f1 was identified to regulate tmem59 significantly and might play an important role in the differentiation of NSCs in mouse brain. There are four pathways shown in the gene network, indicating that tmem59 locates in the downstream of the signalling pathway. The real-time RT-PCR results shown that the over-expression of pou6f1 could significantly up-regulate tmem59 expression in C17.2 NSC line. 16 out of 36 predicted genes in our constructed network have been reported to be AD-related, including Ace, aqp1, arrdc3, cd14, cd59a, cds1, cldn1, cox8b, defb11, folr1, gdi2, mmp3, mgp, myrip, Ripk4, rnd3, and sncg. The localization of tmem59 related genes and functional-related gene groups based on the Gene Ontology (GO annotation was also identified. Conclusions Our findings suggest that the expression of tmem59 is an important factor contributing to AD. The parallelized SWNI algorithm increased the efficiency of network reconstruction significantly. This study enables us to highlight novel genes that may be involved in NSC differentiation and provides a shortcut to

  4. Demand response in Germany: Technical potential, benefits and regulatory challenges

    OpenAIRE

    Stede, Jan

    2016-01-01

    An increased flexibility of the electricity demand side through demand response (DR) is an opportunity to support the integration of renewable energies. By optimising the use of the generation, transmission and distribution infrastructure, DR reduces the need for costly investments and contributes to system security. There is a significant technical DR potential for load reduction from industrial production processes in Germany, as well as from cross-cutting technologies in industry and the t...

  5. Future nuclear regulatory challenges

    International Nuclear Information System (INIS)

    Royen, J.

    1998-01-01

    In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

  6. Clinical trial regulation in Argentina: overview and analysis of regulatory framework, use of existing tools, and researchers' perspectives to identify potential barriers Reglamentación de ensayos clínicos en la Argentina: panorama y análisis del marco normativo, uso de los instrumentos existentes y perspectivas de los investigadores para identificar posibles obstáculos

    Directory of Open Access Journals (Sweden)

    Lauren White

    2011-11-01

    Full Text Available OBJECTIVE: To review and analyze the regulatory framework of clinical trial registration, use of existing tools (publicly accessible national/international registration databases, and users' perspectives to identify possible barriers to registration compliance by sponsors and researchers in Argentina. METHODS: Internationally registered trials recruiting patients in Argentina were found through clincialtrials.gov and the International Clinical Trial Registration Platform (ICTRP and compared with publically available clinical trials registered through the National Administration of Drugs, Foods, and Medical Devices (ANMAT. A questionnaire addressing hypothesized attitudinal, knowledge-related, idiomatic, technical, economic, and regulatory barriers that could discourage or impede registration of clinical trials was developed, and semi-structured, in-depth interviews were conducted with a purposively selected sample of researchers (investigators, sponsors, and monitors in Argentina. RESULTS: A response rate of 74.3% (n = 29 was achieved, and 27 interviews were ultimately used for analysis. Results suggested that the high proportion of foreign-sponsored or multinational trials (64.8% of all protocols approved by ANMAT from 1994-2006 may contribute to a communication gap between locally based investigators and foreign-based administrative officials. A lack of knowledge about available international registration tools and limited awareness of the importance of registration were also identified as limiting factors for local investigators and sponsors. CONCLUSIONS: To increase compliance and promote clinical trial registration in Argentina, national health authorities, sponsors, and local investigators could take the following steps: implement a grassroots educational campaign to improve clinical trial regulation, support local investigator-sponsor-initiated clinical trials, and/or encourage local and regional scientific journal compliance with

  7. Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

    Science.gov (United States)

    Ravichandran, Srikanth; Del Sol, Antonio

    2017-02-01

    Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  8. Gene expression profile identifies potential biomarkers for human intervertebral disc degeneration.

    Science.gov (United States)

    Guo, Wei; Zhang, Bin; Li, Yan; Duan, Hui-Quan; Sun, Chao; Xu, Yun-Qiang; Feng, Shi-Qing

    2017-12-01

    The present study aimed to reveal the potential genes associated with the pathogenesis of intervertebral disc degeneration (IDD) by analyzing microarray data using bioinformatics. Gene expression profiles of two regions of the intervertebral disc were compared between patients with IDD and controls. GSE70362 containing two groups of gene expression profiles, 16 nucleus pulposus (NP) samples from patients with IDD and 8 from controls, and 16 annulus fibrosus (AF) samples from patients with IDD and 8 from controls, was downloaded from the Gene Expression Omnibus database. A total of 93 and 114 differentially expressed genes (DEGs) were identified in NP and AF samples, respectively, using a limma software package for the R programming environment. Gene Ontology (GO) function enrichment analysis was performed to identify the associated biological functions of DEGs in IDD, which indicated that the DEGs may be involved in various processes, including cell adhesion, biological adhesion and extracellular matrix organization. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in focal adhesion and the p53 signaling pathway. Further analysis revealed that there were 35 common DEGs observed between the two regions (NP and AF), which may be further regulated by 6 clusters of microRNAs (miRNAs) retrieved with WebGestalt. The genes in the DEG‑miRNA regulatory network were annotated using GO function and KEGG pathway enrichment analysis, among which extracellular matrix organization was the most significant disrupted biological process and focal adhesion was the most significant dysregulated pathway. In addition, the result of protein‑protein interaction network modules demonstrated the involvement of inflammatory cytokine interferon signaling in IDD. These findings may not only advance the understanding of the pathogenesis of IDD, but also identify novel potential

  9. A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity.

    Science.gov (United States)

    Heijink, Anne Margriet; Blomen, Vincent A; Bisteau, Xavier; Degener, Fabian; Matsushita, Felipe Yu; Kaldis, Philipp; Foijer, Floris; van Vugt, Marcel A T M

    2015-12-08

    The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the existence of genetic determinants of Wee1 inhibitor sensitivity other than TP53 status. To optimally facilitate patient selection for Wee1 inhibition and uncover potential resistance mechanisms, identification of these currently unknown genes is necessary. The aim of this study was therefore to identify gene mutations that determine Wee1 inhibitor sensitivity. We performed a genome-wide unbiased functional genetic screen in TP53 mutant near-haploid KBM-7 cells using gene-trap insertional mutagenesis. Insertion site mapping of cells that survived long-term Wee1 inhibition revealed enrichment of G1/S regulatory genes, including SKP2, CUL1, and CDK2. Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the γ-H2AX induction and abrogation of G2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. Remarkably, live cell imaging showed that depletion of SKP2, CUL1, or CDK2 did not rescue the Wee1 inhibition-induced karyokinesis and cytokinesis defects. These data indicate that the activity of the DNA replication machinery, beyond TP53 mutation status, determines Wee1 inhibitor sensitivity, and could serve as a selection criterion for Wee1-inhibitor eligible patients. Conversely, loss of the identified S-phase genes could serve as a mechanism of acquired resistance, which goes along with development of severe genomic instability.

  10. Safeguards decision making in the public and regulatory environment, and the potential role of quantitative approaches

    International Nuclear Information System (INIS)

    Sherr, T.S.

    1981-01-01

    This paper briefly examines the nature of the safeguards program's objectives and constraints, and the inherent limitations on comprehensive quantification. It discusses the nature of the public and regulatory processes employed in safeguards decision making, and examines their implications regarding the potential role of quantitative approaches to safeguards policy and operational decision making

  11. A tool for identifying potential Eucalyptus nitens seed orchard sites ...

    African Journals Online (AJOL)

    Shy seed production in orchards of Eucalyptus nitens is a major barrier to the deployment of genetic gain in South African plantations. A machine learning method was used to identify optimal sites for the establishment of E. nitens seed orchards within the plantation forestry landscape of the summer rainfall region of South ...

  12. Identifying Potential Weapon Systems That Can Be Divested

    Science.gov (United States)

    2016-04-08

    sustainment cost mitigation strategies include reduce supply chain by maximizing multi-role equipment, reduce divestiture obstacles/friction points...question. Extensive search of the internet government websites were used to find government information and open access articles related to the research...they did not use it, and if they use anything thing else to identify these low priority systems. The intent of the survey was not to get into

  13. Identifying improvement potentials in cement production with life cycle assessment.

    Science.gov (United States)

    Boesch, Michael Elias; Hellweg, Stefanie

    2010-12-01

    Cement production is an environmentally relevant process responsible for 5% of total anthropogenic carbon dioxide emissions and 7% of industrial fuel use. In this study, life cycle assessment is used to evaluate improvement potentials in the cement production process in Europe and the USA. With a current fuel substitution rate of 18% in Europe and 11% in the USA, both regions have a substantial potential to reduce greenhouse gas emissions and save virgin resources by further increasing the coprocessing of waste fuels. Upgrading production technology would be particularly effective in the USA where many kiln systems with very low energy efficiency are still in operation. Using best available technology and a thermal substitution rate of 50% for fuels, greenhouse gas emissions could be reduced by 9% for Europe and 18% for the USA per tonne of cement. Since clinker production is the dominant pollution producing step in cement production, the substitution of clinker with mineral components such as ground granulated blast furnace slag or fly ash is an efficient measure to reduce the environmental impact. Blended cements exhibit substantially lower environmental footprints than Portland cement, even if the substitutes feature lower grindability and require additional drying and large transport distances. The highest savings in CO(2) emissions and resource consumption are achieved with a combination of measures in clinker production and cement blending.

  14. Identifying Initial Condition in Degenerate Parabolic Equation with Singular Potential

    Directory of Open Access Journals (Sweden)

    K. Atifi

    2017-01-01

    Full Text Available A hybrid algorithm and regularization method are proposed, for the first time, to solve the one-dimensional degenerate inverse heat conduction problem to estimate the initial temperature distribution from point measurements. The evolution of the heat is given by a degenerate parabolic equation with singular potential. This problem can be formulated in a least-squares framework, an iterative procedure which minimizes the difference between the given measurements and the value at sensor locations of a reconstructed field. The mathematical model leads to a nonconvex minimization problem. To solve it, we prove the existence of at least one solution of problem and we propose two approaches: the first is based on a Tikhonov regularization, while the second approach is based on a hybrid genetic algorithm (married genetic with descent method type gradient. Some numerical experiments are given.

  15. Potential of isotope analysis (C, Cl) to identify dechlorination mechanisms

    Science.gov (United States)

    Cretnik, Stefan; Thoreson, Kristen; Bernstein, Anat; Ebert, Karin; Buchner, Daniel; Laskov, Christine; Haderlein, Stefan; Shouakar-Stash, Orfan; Kliegman, Sarah; McNeill, Kristopher; Elsner, Martin

    2013-04-01

    Chloroethenes are commonly used in industrial applications, and detected as carcinogenic contaminants in the environment. Their dehalogenation is of environmental importance in remediation processes. However, a detailed understanding frequently accounted problem is the accumulation of toxic degradation products such as cis-dichloroethylene (cis-DCE) at contaminated sites. Several studies have addressed the reductive dehalogenation reactions using biotic and abiotic model systems, but a crucial question in this context has remained open: Do environmental transformations occur by the same mechanism as in their corresponding in vitro model systems? The presented study shows the potential to close this research gap using the latest developments in compound specific chlorine isotope analysis, which make it possible to routinely measure chlorine isotope fractionation of chloroethenes in environmental samples and complex reaction mixtures.1,2 In particular, such chlorine isotope analysis enables the measurement of isotope fractionation for two elements (i.e., C and Cl) in chloroethenes. When isotope values of both elements are plotted against each other, different slopes reflect different underlying mechanisms and are remarkably insensitive towards masking. Our results suggest that different microbial strains (G. lovleyi strain SZ, D. hafniense Y51) and the isolated cofactor cobalamin employ similar mechanisms of reductive dechlorination of TCE. In contrast, evidence for a different mechanism was obtained with cobaloxime cautioning its use as a model for biodegradation. The study shows the potential of the dual isotope approach as a tool to directly compare transformation mechanisms of environmental scenarios, biotic transformations, and their putative chemical lab scale systems. Furthermore, it serves as an essential reference when using the dual isotope approach to assess the fate of chlorinated compounds in the environment.

  16. Nanomaterial categorization for assessing risk potential to facilitate regulatory decision-making.

    Science.gov (United States)

    Godwin, Hilary; Nameth, Catherine; Avery, David; Bergeson, Lynn L; Bernard, Daniel; Beryt, Elizabeth; Boyes, William; Brown, Scott; Clippinger, Amy J; Cohen, Yoram; Doa, Maria; Hendren, Christine Ogilvie; Holden, Patricia; Houck, Keith; Kane, Agnes B; Klaessig, Frederick; Kodas, Toivo; Landsiedel, Robert; Lynch, Iseult; Malloy, Timothy; Miller, Mary Beth; Muller, Julie; Oberdorster, Gunter; Petersen, Elijah J; Pleus, Richard C; Sayre, Philip; Stone, Vicki; Sullivan, Kristie M; Tentschert, Jutta; Wallis, Philip; Nel, Andre E

    2015-01-01

    For nanotechnology to meet its potential as a game-changing and sustainable technology, it is important to ensure that the engineered nanomaterials and nanoenabled products that gain entry to the marketplace are safe and effective. Tools and methods are needed for regulatory purposes to allow rapid material categorization according to human health and environmental risk potential, so that materials of high concern can be targeted for additional scrutiny, while material categories that pose the least risk can receive expedited review. Using carbon nanotubes as an example, we discuss how data from alternative testing strategies can be used to facilitate engineered nanomaterial categorization according to risk potential and how such an approach could facilitate regulatory decision-making in the future.

  17. Evaluation of potential regulatory function of breast cancer risk locus at 6q25.1.

    Science.gov (United States)

    Sun, Yaqiong; Ye, Chuanzhong; Guo, Xingyi; Wen, Wanqing; Long, Jirong; Gao, Yu-Tang; Shu, Xiao Ou; Zheng, Wei; Cai, Qiuyin

    2016-02-01

    In a genome-wide association study conducted among Chinese women, we identified the single nucleotide polymorphism (SNP) rs2046210 at 6q25.1 for breast cancer risk. To explore a potential regulatory role for this risk locus, we measured expression levels of nine genes at the locus in breast cancer tissue and adjacent normal tissue samples obtained from 67 patients recruited in the Shanghai Breast Cancer Study. We found that rs2046210 had a statistically significant association with the expression levels of the AKAP12 and ESR1 genes in adjacent normal breast tissues. Women who carry the AA/AG risk genotypes had higher expressions of these two genes compared to those who carry G/G genotypes (P = 0.02 and 0.04 for the AKAP12 and ESR1, respectively). However, no significant differences of SNP rs2046210 with gene expression levels were found in tumor tissues. In The Cancer Genome Atlas samples, the AA/AG risk genotypes of SNP rs2046210 were associated with a significantly higher expression level of the AKAP12 gene and a lower level of the ESR1 gene in tumor tissue. Functional analysis using ENCODE data revealed that SNP rs7763637, which is in strong linkage disequilibrium with SNP rs2046210, is likely a potential functional variant, regulating the AKAP12 gene. Taken together, these results from our study suggest that the association between the 6q25.1 locus and breast cancer risk may be mediated through SNPs that regulate expressions of the AKAP12 gene. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Identifying Cis-Regulatory Changes Involved in the Evolution of Aerobic Fermentation in Yeasts

    Science.gov (United States)

    Lin, Zhenguo; Wang, Tzi-Yuan; Tsai, Bing-Shi; Wu, Fang-Ting; Yu, Fu-Jung; Tseng, Yu-Jung; Sung, Huang-Mo; Li, Wen-Hsiung

    2013-01-01

    Gene regulation change has long been recognized as an important mechanism for phenotypic evolution. We used the evolution of yeast aerobic fermentation as a model to explore how gene regulation has evolved and how this process has contributed to phenotypic evolution and adaptation. Most eukaryotes fully oxidize glucose to CO2 and H2O in mitochondria to maximize energy yield, whereas some yeasts, such as Saccharomyces cerevisiae and its relatives, predominantly ferment glucose into ethanol even in the presence of oxygen, a phenomenon known as aerobic fermentation. We examined the genome-wide gene expression levels among 12 different yeasts and found that a group of genes involved in the mitochondrial respiration process showed the largest reduction in gene expression level during the evolution of aerobic fermentation. Our analysis revealed that the downregulation of these genes was significantly associated with massive loss of binding motifs of Cbf1p in the fermentative yeasts. Our experimental assays confirmed the binding of Cbf1p to the predicted motif and the activator role of Cbf1p. In summary, our study laid a foundation to unravel the long-time mystery about the genetic basis of evolution of aerobic fermentation, providing new insights into understanding the role of cis-regulatory changes in phenotypic evolution. PMID:23650209

  19. Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified

    Energy Technology Data Exchange (ETDEWEB)

    Fardini, Yann [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France); Perez-Cervera, Yobana [Structural and Functional Glycobiology Unit, Lille 1 University, CNRS (UMR 8576), IFR 117, Villeneuve d' Ascq (France); Facultad de Odontología, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca (Mexico); Camoin, Luc [INSERM, U1068, CRCM, Marseille Protéomique IBiSA, Marseille, F-13009 (France); Institut Paoli-Calmettes Team, Cell Polarity, Cell Signaling and Cancer, Marseille, F-13009 (France); Aix-Marseille Université, F-13284, Marseille (France); CNRS, UMR7258, CRCM, Marseille, F-13009 (France); Pagesy, Patrick [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France); Lefebvre, Tony [Structural and Functional Glycobiology Unit, Lille 1 University, CNRS (UMR 8576), IFR 117, Villeneuve d' Ascq (France); Issad, Tarik, E-mail: tarik.issad@inserm.fr [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France)

    2015-06-26

    O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an increase in its transcriptional activity. Four O-GlcNAcylation sites were identified in human FOXO1 but directed mutagenesis of each site individually had modest (T317) or no effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional activity. Moreover, the consequences of mutating all four sites had not been investigated. In the present work, we mutated these sites in the mouse Foxo1 and found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation status and transcriptional activity, and would even tend to increase them. In an attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass spectrometry using High-energy Collisional Dissociation. We identified T646 as a new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this site individually or together with all four previously identified residues did not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results suggest that residues important for the control of Foxo1 activity by O-GlcNAcylation still remain to be identified. - Highlights: • We mutate four previously identified O-GlcNAcylation sites on Foxo1. • Unexpectedly, these mutations do not reduce Foxo1 O-GlcNAcylation. • These mutation do not reduce Foxo1 transcriptional activity. • We identify a new O-GlcNAcylation site on Foxo1 by mass spectrometry. • Mutation of this site increases Foxo1 transcriptional activity.

  20. Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified

    International Nuclear Information System (INIS)

    Fardini, Yann; Perez-Cervera, Yobana; Camoin, Luc; Pagesy, Patrick; Lefebvre, Tony; Issad, Tarik

    2015-01-01

    O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an increase in its transcriptional activity. Four O-GlcNAcylation sites were identified in human FOXO1 but directed mutagenesis of each site individually had modest (T317) or no effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional activity. Moreover, the consequences of mutating all four sites had not been investigated. In the present work, we mutated these sites in the mouse Foxo1 and found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation status and transcriptional activity, and would even tend to increase them. In an attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass spectrometry using High-energy Collisional Dissociation. We identified T646 as a new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this site individually or together with all four previously identified residues did not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results suggest that residues important for the control of Foxo1 activity by O-GlcNAcylation still remain to be identified. - Highlights: • We mutate four previously identified O-GlcNAcylation sites on Foxo1. • Unexpectedly, these mutations do not reduce Foxo1 O-GlcNAcylation. • These mutation do not reduce Foxo1 transcriptional activity. • We identify a new O-GlcNAcylation site on Foxo1 by mass spectrometry. • Mutation of this site increases Foxo1 transcriptional activity

  1. A genomic approach to identify regulatory nodes in the transcriptional network of systemic acquired resistance in plants.

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2006-11-01

    Full Text Available Many biological processes are controlled by intricate networks of transcriptional regulators. With the development of microarray technology, transcriptional changes can be examined at the whole-genome level. However, such analysis often lacks information on the hierarchical relationship between components of a given system. Systemic acquired resistance (SAR is an inducible plant defense response involving a cascade of transcriptional events induced by salicylic acid through the transcription cofactor NPR1. To identify additional regulatory nodes in the SAR network, we performed microarray analysis on Arabidopsis plants expressing the NPR1-GR (glucocorticoid receptor fusion protein. Since nuclear translocation of NPR1-GR requires dexamethasone, we were able to control NPR1-dependent transcription and identify direct transcriptional targets of NPR1. We show that NPR1 directly upregulates the expression of eight WRKY transcription factor genes. This large family of 74 transcription factors has been implicated in various defense responses, but no specific WRKY factor has been placed in the SAR network. Identification of NPR1-regulated WRKY factors allowed us to perform in-depth genetic analysis on a small number of WRKY factors and test well-defined phenotypes of single and double mutants associated with NPR1. Among these WRKY factors we found both positive and negative regulators of SAR. This genomics-directed approach unambiguously positioned five WRKY factors in the complex transcriptional regulatory network of SAR. Our work not only discovered new transcription regulatory components in the signaling network of SAR but also demonstrated that functional studies of large gene families have to take into consideration sequence similarity as well as the expression patterns of the candidates.

  2. Functional analysis of a potential regulatory K+-binding site in the Na+, K+-ATPase

    DEFF Research Database (Denmark)

    Schack, Vivien Rodacker; Vilsen, Bente

    The Na+, K+-ATPase functions by actively transporting 3 Na+ ions out of and 2 K+ ions into the cell, thereby creating ion gradients crucial for many physiological processes. Recently, a combined structural and functional study of the closely related Ca2+-ATPase indicated the presence...... of a regulatory K+-binding site in the P-domain of the enzyme, identifying E732 as being of particular importance (Sorensen, Clausen et al. 2004). In addition, P709 is thought to play a significant role in the structural organization of this site. Both E732 and P709 are highly conserved among P-type ATPases (E732...... is present as either glutamic acid or aspartic acid), which supports their importance and additionally raises the question whether this site may play a general role among P-type ATPases. In Na+, K+-ATPase, K+ functions directly as a substrate for membrane binding sites, however, an additional regulatory...

  3. CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells.

    Science.gov (United States)

    Solstad, Therese; Bains, Simer Jit; Landskron, Johannes; Aandahl, Einar Martin; Thiede, Bernd; Taskén, Kjetil; Torgersen, Knut Martin

    2011-11-10

    Human CD4(+)FoxP3(+) T cells are functionally and phenotypically heterogeneous providing plasticity to immune activation and regulation. To better understand the functional dynamics within this subset, we first used a combined strategy of subcellular fractionation and proteomics to describe differences at the protein level between highly purified human CD4(+)CD25(+) and CD4(+)CD25(-) T-cell populations. This identified a set of membrane proteins highly expressed on the cell surface of human regulatory T cells (Tregs), including CD71, CD95, CD147, and CD148. CD147 (Basigin or Emmprin) divided CD4(+)CD25(+) cells into distinct subsets. Furthermore, CD147, CD25, FoxP3, and in particular CTLA-4 expression correlated. Phenotypical and functional analyses suggested that CD147 marks the switch between resting (CD45RA(+)) and activated (CD45RO(+)) subsets within the FoxP3(+) T-cell population. Sorting of regulatory T cells into CD147(-) and CD147(+) populations demonstrated that CD147 identifies an activated and highly suppressive CD45RO(+) Treg subset. When analyzing CD4(+) T cells for their cytokine producing potential, CD147 levels grouped the FoxP3(+) subset into 3 categories with different ability to produce IL-2, TNF-α, IFN-γ, and IL-17. Together, this suggests that CD147 is a direct marker for activated Tregs within the CD4(+)FoxP3(+) subset and may provide means to manipulate cells important for immune homeostasis.

  4. Least-squares methods for identifying biochemical regulatory networks from noisy measurements

    Directory of Open Access Journals (Sweden)

    Heslop-Harrison Pat

    2007-01-01

    Full Text Available Abstract Background We consider the problem of identifying the dynamic interactions in biochemical networks from noisy experimental data. Typically, approaches for solving this problem make use of an estimation algorithm such as the well-known linear Least-Squares (LS estimation technique. We demonstrate that when time-series measurements are corrupted by white noise and/or drift noise, more accurate and reliable identification of network interactions can be achieved by employing an estimation algorithm known as Constrained Total Least Squares (CTLS. The Total Least Squares (TLS technique is a generalised least squares method to solve an overdetermined set of equations whose coefficients are noisy. The CTLS is a natural extension of TLS to the case where the noise components of the coefficients are correlated, as is usually the case with time-series measurements of concentrations and expression profiles in gene networks. Results The superior performance of the CTLS method in identifying network interactions is demonstrated on three examples: a genetic network containing four genes, a network describing p53 activity and mdm2 messenger RNA interactions, and a recently proposed kinetic model for interleukin (IL-6 and (IL-12b messenger RNA expression as a function of ATF3 and NF-κB promoter binding. For the first example, the CTLS significantly reduces the errors in the estimation of the Jacobian for the gene network. For the second, the CTLS reduces the errors from the measurements that are corrupted by white noise and the effect of neglected kinetics. For the third, it allows the correct identification, from noisy data, of the negative regulation of (IL-6 and (IL-12b by ATF3. Conclusion The significant improvements in performance demonstrated by the CTLS method under the wide range of conditions tested here, including different levels and types of measurement noise and different numbers of data points, suggests that its application will enable

  5. A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency

    Science.gov (United States)

    Artyomov, Maxim; Meissner, Alex; Chakraborty, Arup

    2010-03-01

    Most cells in an organism have the same DNA. Yet, different cell types express different proteins and carry out different functions. This is because of epigenetic differences; i.e., DNA in different cell types is packaged distinctly, making it hard to express certain genes while facilitating the expression of others. During development, upon receipt of appropriate cues, pluripotent embryonic stem cells differentiate into diverse cell types that make up the organism (e.g., a human). There has long been an effort to make this process go backward -- i.e., reprogram a differentiated cell (e.g., a skin cell) to pluripotent status. Recently, this has been achieved by transfecting certain transcription factors into differentiated cells. This method does not use embryonic material and promises the development of patient-specific regenerative medicine, but it is inefficient. The mechanisms that make reprogramming rare, or even possible, are poorly understood. We have developed the first computational model of transcription factor-induced reprogramming. Results obtained from the model are consistent with diverse observations, and identify the rare pathways that allow reprogramming to occur. If validated, our model could be further developed to design optimal strategies for reprogramming and shed light on basic questions in biology.

  6. Clinical potential of regulatory T cell therapy in liver diseases: An overview and current perspectives

    Directory of Open Access Journals (Sweden)

    Hannah Claire Jeffery

    2016-09-01

    Full Text Available The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes, that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg. The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients.Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment and Good Manufacturing Practice (GMP facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases, chronic rejection and post-transplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases (GVHD and solid organ transplantations. There have not been any new therapies for the autoimmune liver diseases for more than three decades; thus the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior and microenvironment of Treg before applying the cells to the patients.

  7. Regulatory potential for increasing small scale grid connected photovoltaic (PV) deployment in Australia

    International Nuclear Information System (INIS)

    Sivaraman, Deepak; Horne, Ralph E.

    2011-01-01

    The last decade has seen significant innovation and change in regulatory incentives to support photovoltaic deployment globally. With high fossil fuel dependency and abundant solar resource availability in Australia, grid connected photovoltaics are a viable low carbon technology option in existing electricity grids. Drawing on international examples, the potential to increase grid PV deployment through government response and regulation is explored. For each renewable energy certificate (REC) earned by small scale photovoltaics until 2012, the market provides four additional certificates under the current banded renewable targets. Our analysis indicates that REC eligibility is not accurately estimated currently, and an energy model is developed to calculate the variance. The energy model estimates as much as 26% additional REC's to be obtained by a 3 kWp PV system, when compared to the currently used regulatory method. Moreover, the provision of REC's increases benefits to PV technologies, in the process distorting CO 2 abatement (0.21 tonne/REC) by 68%, when PV displaces peaking natural gas plants. Consideration of the secondary effects of a banded structure on emissions trading market is important in the context of designing a range of initiatives intended to support a transition to a low carbon electricity sector. - Research Highlights: →Grid connected photovoltaics hedge spikes in peak demand summer electricity prices. →Nationwide feed in tariff and new building regulations needed to increase PV deployment. →Australia has transitioned from a solar rebate to a banded solar credit structure. →The currently used regulatory deeming method underestimates REC eligibility by 27%. →The banded structure can potentially distort CO 2 abatement by as much as 68%.

  8. Localizing potentially active post-transcriptional regulations in the Ewing's sarcoma gene regulatory network

    Directory of Open Access Journals (Sweden)

    Delyon Bernard

    2010-11-01

    Full Text Available Abstract Background A wide range of techniques is now available for analyzing regulatory networks. Nonetheless, most of these techniques fail to interpret large-scale transcriptional data at the post-translational level. Results We address the question of using large-scale transcriptomic observation of a system perturbation to analyze a regulatory network which contained several types of interactions - transcriptional and post-translational. Our method consisted of post-processing the outputs of an open-source tool named BioQuali - an automatic constraint-based analysis mimicking biologist's local reasoning on a large scale. The post-processing relied on differences in the behavior of the transcriptional and post-translational levels in the network. As a case study, we analyzed a network representation of the genes and proteins controlled by an oncogene in the context of Ewing's sarcoma. The analysis allowed us to pinpoint active interactions specific to this cancer. We also identified the parts of the network which were incomplete and should be submitted for further investigation. Conclusions The proposed approach is effective for the qualitative analysis of cancer networks. It allows the integrative use of experimental data of various types in order to identify the specific information that should be considered a priority in the initial - and possibly very large - experimental dataset. Iteratively, new dataset can be introduced into the analysis to improve the network representation and make it more specific.

  9. Therapeutic potential of regulatory macrophages generated from peritoneal dialysate in adriamycin nephropathy.

    Science.gov (United States)

    Cao, Qi; Wang, Yiping; Wang, Changqi; Wang, Xin M; Lee, Vincent W S; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I; Harris, David C H

    2018-04-01

    Cell therapy using macrophages requires large amounts of cells, which are difficult to collect from patients. Patients undergoing peritoneal dialysis (PD) discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages can be modulated to become regulatory macrophages, which have shown great promise as a therapeutic strategy in experimental kidney disease and human kidney transplantation. This study aimed to examine the potential of using peritoneal macrophages (PMs) from peritoneal dialysate to treat kidney disease. Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both patients and mice undergoing PD. PMs from patients and mice undergoing PD were more mature than peripheral monocytes/macrophages, as shown by low expression of C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro culture. PMs from patients and mice undergoing PD displayed normal macrophage function and could be modulated into a regulatory (M2) phenotype. In vivo, adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively protected against kidney injury in mice with adriamycin nephropathy (AN). Importantly, the transfused peritoneal M2 macrophages maintained their M2 phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice undergoing PD exhibited conventional macrophage features. Peritoneal M2 macrophages derived from PD mice are able to reduce kidney injury in AN, suggesting that peritoneal macrophages from patients undergoing PD may have the potential for clinical therapeutic application.

  10. A regulatory perspective on the abuse potential evaluation of novel stimulant drugs in the United States.

    Science.gov (United States)

    Calderon, Silvia N; Klein, Michael

    2014-12-01

    In the United States of America (USA), the abuse potential assessment of a drug is performed as part of the safety evaluation of a drug under development, and to evaluate if the drug needs to be subject to controls that would minimize the abuse of the drug once on the market. The assessment of the abuse potential of new drugs consists of a scientific and medical evaluation of all data related to abuse of the drug. This paper describes the regulatory framework for evaluating the abuse potential of new drugs, in general, including novel stimulants. The role of the United States Food and Drug Administration (FDA) in the evaluation of the abuse potential of drugs, and its role in drug control are also discussed. A definition of abuse potential, an overview of the currently accepted approaches to evaluating the abuse potential of a drug, as well as a description of the criteria that applies when recommending a specific level of control (i.e., a Schedule) for a drug under the Controlled Substances Act (CSA). This article is part of the Special Issue entitled 'CNS Stimulants'. Published by Elsevier Ltd.

  11. Potential environmental and regulatory implications of naturally occurring radioactive materials (NORM)

    International Nuclear Information System (INIS)

    Paschoa, A.S.

    1998-01-01

    The immense volume of naturally occurring radioactive materials (NORM) wastes produced annually by extracting industries throughout the world deserves to come to the attention of international and national environmental protection agencies and regulatory bodies. Although a great deal of work has been done in the fields of radiation protection and remedial actions concerning uranium and other mines, the need to dispose of diffuse NORM wastes will have environmental and regulatory implications that thus far are not fully appreciated. NORM wastes constitute, by and large, unwanted byproducts of industrial activities as diverse as thorium and uranium milling, niobium, tin and gold mining extraction, water treatment, and the production of oil, gas, phosphate fertilizer, coal fire and aluminium. The volumes of NORM wastes produced annually could reach levels so high that the existing low level radioactive waste (LLRW) facilities would be readily occupied by NORM if controlled disposal procedures were not adopted. On the other hand, NORM cannot just be ignored as being below radiological concern (BRC) or lower than exempt concentration levels (ECLs), because sometimes NORM concentrations reach levels as high as 1 x 10 3 kBq/kg for 226 Ra, and not much less for 228 Ra. Unfortunately, thus far, there is not enough information available concerning NORM wastes in key industries, though the international scientific community has been concerned, for a long time now, with technologically enhanced natural radiation exposures (TENRE). This article is written with the intention of examining, to the extent possible, the potential environmental and regulatory implications of NORM wastes being produced in selected industries. (Author)

  12. Transcriptome of Atoh7 retinal progenitor cells identifies new Atoh7-dependent regulatory genes for retinal ganglion cell formation.

    Science.gov (United States)

    Gao, Zhiguang; Mao, Chai-An; Pan, Ping; Mu, Xiuqian; Klein, William H

    2014-11-01

    The bHLH transcription factor ATOH7 (Math5) is essential for establishing retinal ganglion cell (RGC) fate. However, Atoh7-expressing retinal progenitor cells (RPCs) can give rise to all retinal cell types, suggesting that other factors are involved in specifying RGCs. The basis by which a subpopulation of Atoh7-expressing RPCs commits to an RGC fate remains uncertain but is of critical importance to retinal development since RGCs are the earliest cell type to differentiate. To better understand the regulatory mechanisms leading to cell-fate specification, a binary genetic system was generated to specifically label Atoh7-expressing cells with green fluorescent protein (GFP). Fluorescence-activated cell sorting (FACS)-purified GFP(+) and GFP(-) cells were profiled by RNA-seq. Here, we identify 1497 transcripts that were differentially expressed between the two RPC populations. Pathway analysis revealed diminished growth factor signaling in Atoh7-expressing RPCs, indicating that these cells had exited the cell cycle. In contrast, axon guidance signals were enriched, suggesting that axons of Atoh7-expressing RPCs were already making synaptic connections. Notably, many genes enriched in Atoh7-expressing RPCs encoded transcriptional regulators, and several were direct targets of ATOH7, including, and unexpectedly, Ebf3 and Eya2. We present evidence for a Pax6-Atoh7-Eya2 pathway that acts downstream of Atoh7 but upstream of differentiation factor Pou4f2. EYA2 is a protein phosphatase involved in protein-protein interactions and posttranslational regulation. These properties, along with Eya2 as an early target gene of ATOH7, suggest that EYA2 functions in RGC specification. Our results expand current knowledge of the regulatory networks operating in Atoh7-expressing RPCs and offer new directions for exploring the earliest aspects of retinogenesis. © 2014 Wiley Periodicals, Inc.

  13. Different immune regulatory potential of Lactobacillus plantarum and Lactobacillus sakei isolated from Kimchi.

    Science.gov (United States)

    Hong, Yi-Fan; Kim, Hangeun; Kim, Hye Rim; Gim, Min Geun; Chung, Dae Kyun

    2014-12-28

    It is known that lactic acid bacteria (LAB) have many beneficial health effects, including antioxidative activity and immune regulation. In this study, the immune regulatory effects of Lactobacillus sakei and Lactobacillus plantarum, which are found in different types of kimchi, were evaluated. L. sakei and its lipoteichoic acid (LTA) have greater immune stimulating potential in IL-12, IFN-γ, and TNF-α production as compared with L. plantarum in an in vitro condition. On the other hand, L. plantarum is assumed to repress the Th1 immune response in murine experiments. After being injected with LPS, L. plantarum-fed mice maintained a healthier state, and the level of TNF-α in their blood was lower than in other bacterial strainfed mice and in the LPS-only control mice. Additionally, IL-12 production was significantly decreased and the production of IL-4 was greatly increased in the splenocytes from L. plantarum-fed mice. Further experiments revealed that the pre-injection of purified LTA from L. plantarum (pLTA), L. sakei (sLTA), and S. aureus (aLTA) decreased TNF-α and IL-4 production in LPS-injected mice. Mouse IL-12, however, was significantly increased by aLTA pre-injection. In conclusion, the L. sakei and L. plantarum strains have immune regulation effects, but the effects differ in cytokine production and the regulatory effects of the Th1/Th2 immune response.

  14. Electricity distribution as an unsustainable natural monopoly. A potential outcome of New Zealand's regulatory regime

    International Nuclear Information System (INIS)

    Gunn, C.; Sharp, B.

    1999-01-01

    The ongoing reform of New Zealand's electricity supply industry has attempted to separate its potentially competitive elements from those with naturally monopolistic characteristics. Yet, some competition for distribution services is occurring, raising the question as to whether electricity distributors are natural monopolies as is typically assumed. This paper presents a simple model of a representative New Zealand distribution business, and shows that, in a true economic sense, distributors are most probably sustainable natural monopolies as expected. However, the model demonstrates that a mechanism for competition may arise because the financial principles enshrined in the Ministry of Commerce's regulatory regime can produce unsustainable cost structures and unintentionally introduce elements of contestability into the market for distribution services. 15 refs

  15. Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms.

    Science.gov (United States)

    Marei, Hadir; Malliri, Angeliki

    2017-07-03

    Abnormal Rac1 signaling is linked to a number of debilitating human diseases, including cancer, cardiovascular diseases and neurodegenerative disorders. As such, Rac1 represents an attractive therapeutic target, yet the search for effective Rac1 inhibitors is still underway. Given the adverse effects associated with Rac1 signaling perturbation, cells have evolved several mechanisms to ensure the tight regulation of Rac1 signaling. Thus, characterizing these mechanisms can provide invaluable information regarding major cellular events that lead to aberrant Rac1 signaling. Importantly, this information can be utilized to further facilitate the development of effective pharmacological modulators that can restore normal Rac1 signaling. In this review, we focus on the pathological role of Rac1 signaling, highlighting the benefits and potential drawbacks of targeting Rac1 in a clinical setting. Additionally, we provide an overview of available compounds that target key Rac1 regulatory mechanisms and discuss future therapeutic avenues arising from our understanding of these mechanisms.

  16. Regulatory, design and methodological impacts in determining tidal-in-stream power resource potential

    International Nuclear Information System (INIS)

    Atwater, Joel F.; Lawrence, Gregory A.

    2011-01-01

    Tidal-in-Stream energy has been heralded by many as a significant potential source for clean power, a scheme where kinetic energy is extracted from tidal currents. A number of estimates have suggested that tidal power may become a sizeable fraction of overall electricity generation, however these estimates have been largely based on a resource assessment methodology that dramatically oversimplifies the physical phenomenon at play. This paper develops a model that considers the effect of energy extraction on the bulk flow, showing that tidal energy inventories that assess solely kinetic energy flux may represent both an order-of-magnitude overestimation of the resource and a significant oversimplification of regulatory impacts. The interplay between the characteristics of a flow and the regulatory and economic issues will likely limit tidal power generation to levels significantly below the physical maximums. Permitted flow reduction, turbine design and staging of development all have significant and predictable impacts on the extractible resource. Energy planners must therefore understand these relationships in order to appropriately assess the magnitude of generation that can be realistically be produced from tidal energy. - Research highlights: → Inventorying kinetic energy is not appropriate for assessing the tidal energy potential and may overestimate the resource by orders of magnitude. → The physical maximum for tidal power extraction is 38% of the total fluid power of a channel and causes a flow reduction of 42%. → Any amount of tidal power generation will reduce the flow rate in a channel. → Limiting the permitted reduction in flow significantly reduces the available resource. → Turbine efficiency is important as extraneous resistance depletes the resource without providing power generation.

  17. A systems biology approach identified different regulatory networks targeted by KSHV miR-K12-11 in B cells and endothelial cells.

    Science.gov (United States)

    Yang, Yajie; Boss, Isaac W; McIntyre, Lauren M; Renne, Rolf

    2014-08-08

    Kaposi's sarcoma associated herpes virus (KSHV) is associated with tumors of endothelial and lymphoid origin. During latent infection, KSHV expresses miR-K12-11, an ortholog of the human tumor gene hsa-miR-155. Both gene products are microRNAs (miRNAs), which are important post-transcriptional regulators that contribute to tissue specific gene expression. Advances in target identification technologies and molecular interaction databases have allowed a systems biology approach to unravel the gene regulatory networks (GRNs) triggered by miR-K12-11 in endothelial and lymphoid cells. Understanding the tissue specific function of miR-K12-11 will help to elucidate underlying mechanisms of KSHV pathogenesis. Ectopic expression of miR-K12-11 differentially affected gene expression in BJAB cells of lymphoid origin and TIVE cells of endothelial origin. Direct miRNA targeting accounted for a small fraction of the observed transcriptome changes: only 29 genes were identified as putative direct targets of miR-K12-11 in both cell types. However, a number of commonly affected biological pathways, such as carbohydrate metabolism and interferon response related signaling, were revealed by gene ontology analysis. Integration of transcriptome profiling, bioinformatic algorithms, and databases of protein-protein interactome from the ENCODE project identified different nodes of GRNs utilized by miR-K12-11 in a tissue-specific fashion. These effector genes, including cancer associated transcription factors and signaling proteins, amplified the regulatory potential of a single miRNA, from a small set of putative direct targets to a larger set of genes. This is the first comparative analysis of miRNA-K12-11's effects in endothelial and B cells, from tissues infected with KSHV in vivo. MiR-K12-11 was able to broadly modulate gene expression in both cell types. Using a systems biology approach, we inferred that miR-K12-11 establishes its GRN by both repressing master TFs and influencing

  18. Regulatory network analysis of Epstein-Barr virus identifies functional modules and hub genes involved in infectious mononucleosis.

    Science.gov (United States)

    Poorebrahim, Mansour; Salarian, Ali; Najafi, Saeideh; Abazari, Mohammad Foad; Aleagha, Maryam Nouri; Dadras, Mohammad Nasr; Jazayeri, Seyed Mohammad; Ataei, Atousa; Poortahmasebi, Vahdat

    2017-05-01

    Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. The aim of this study was to develop an integrative gene regulatory network (GRN) approach and overlying gene expression data to identify the representative subnetworks for IM and EBV latent infection (LI). After identifying differentially expressed genes (DEGs) in both IM and LI gene expression profiles, functional annotations were applied using gene ontology (GO) and BiNGO tools, and construction of GRNs, topological analysis and identification of modules were carried out using several plugins of Cytoscape. In parallel, a human-EBV GRN was generated using the Hu-Vir database for further analyses. Our analysis revealed that the majority of DEGs in both IM and LI were involved in cell-cycle and DNA repair processes. However, these genes showed a significant negative correlation in the IM and LI states. Furthermore, cyclin-dependent kinase 2 (CDK2) - a hub gene with the highest centrality score - appeared to be the key player in cell cycle regulation in IM disease. The most significant functional modules in the IM and LI states were involved in the regulation of the cell cycle and apoptosis, respectively. Human-EBV network analysis revealed several direct targets of EBV proteins during IM disease. Our study provides an important first report on the response to IM/LI EBV infection in humans. An important aspect of our data was the upregulation of genes associated with cell cycle progression and proliferation.

  19. Potential energy landscape and robustness of a gene regulatory network: toggle switch.

    Directory of Open Access Journals (Sweden)

    Keun-Young Kim

    2007-03-01

    Full Text Available Finding a multidimensional potential landscape is the key for addressing important global issues, such as the robustness of cellular networks. We have uncovered the underlying potential energy landscape of a simple gene regulatory network: a toggle switch. This was realized by explicitly constructing the steady state probability of the gene switch in the protein concentration space in the presence of the intrinsic statistical fluctuations due to the small number of proteins in the cell. We explored the global phase space for the system. We found that the protein synthesis rate and the unbinding rate of proteins to the gene were small relative to the protein degradation rate; the gene switch is monostable with only one stable basin of attraction. When both the protein synthesis rate and the unbinding rate of proteins to the gene are large compared with the protein degradation rate, two global basins of attraction emerge for a toggle switch. These basins correspond to the biologically stable functional states. The potential energy barrier between the two basins determines the time scale of conversion from one to the other. We found as the protein synthesis rate and protein unbinding rate to the gene relative to the protein degradation rate became larger, the potential energy barrier became larger. This also corresponded to systems with less noise or the fluctuations on the protein numbers. It leads to the robustness of the biological basins of the gene switches. The technique used here is general and can be applied to explore the potential energy landscape of the gene networks.

  20. Reactive inspection response of NRC Region III to potential technical deficiencies identified in recent Nuclear Air Cleaning Conference papers

    International Nuclear Information System (INIS)

    Gill, C.F.

    1987-01-01

    In order to effectively meet its responsibility to protect the public health and safety, the Nuclear Regulatory Commission (NRC) nuclear power plant licensing and inspection programs respond to potential technical deficiencies identified by conference and professional society meeting papers when deemed appropriate. The NRC staff's response mechanisms for such technical deficiencies include: generic letters, Bulletins, Information Notices, Standard Review Plan (NUREG-0800) revisions, docketed Final Safety Analysis Report (FSAR) questions, special studies, special (reactive) inspection, and inspection program revisions. This paper describes reactive inspection efforts by Region III in response to potential technical deficiencies identified in recent air cleaning conference papers, including: post-accident effluent sample line deposition losses; failure to implement good engineering practices in the design, construction, and testing of Nuclear Air Treatment Systems (NATS); filter bypass via filter housing drain lines; spinster carbon degradation; use of silicone sealants and other temporary patching material in NATS; filter housing fire protection deluge system problems; lack of charcoal batch traceability; Quality Assurance records problems involving equipment, vendor, filter, and personnel qualifications; inadequate ANSI/ASME N510 acceptance criteria and tests; and failure to adequately demonstrate control room habitability per 10 CFR 50, Appendix A, General Design Criterion-19. Region III inspections indicate that many of these deficiencies appear to be prevalent. Inspection findings and utility responses to the findings are discussed. NRC Region III and Headquarters programmatic reactions to the identified generic problem areas are also discussed

  1. Diagnosis of Lynch Syndrome: Genetic Testing Identifies a Potentially Deadly Hereditary Disease

    Science.gov (United States)

    ... of Lynch Syndrome Follow us A Diagnosis of Lynch Syndrome Genetic testing identifies a potentially deadly hereditary disease ... helped Jack learn what was wrong. Jack had Lynch Syndrome—an inherited disorder. Lynch Syndrome increases the risk ...

  2. IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life.

    Science.gov (United States)

    Hsu, Peter S; Lai, Catherine L; Hu, Mingjing; Santner-Nanan, Brigitte; Dahlstrom, Jane E; Lee, Cheng Hiang; Ajmal, Ayesha; Bullman, Amanda; Arbuckle, Susan; Al Saedi, Ahmed; Gacis, Lou; Nambiar, Reta; Williams, Andrew; Wong, Melanie; Campbell, Dianne E; Nanan, Ralph

    2018-06-15

    Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant β7 integrin + Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA + ) Treg cells later in life. β7 integrin + Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2-induced β7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development. Copyright © 2018 by The American Association of Immunologists, Inc.

  3. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.

    Science.gov (United States)

    Sellers, Edward M

    2018-02-01

    This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.

  4. An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs

    OpenAIRE

    Chang, Tzu-Hao; Huang, Hsi-Yuan; Hsu, Justin Bo-Kai; Weng, Shun-Long; Horng, Jorng-Tzong; Huang, Hsien-Da

    2013-01-01

    Background Functional RNA molecules participate in numerous biological processes, ranging from gene regulation to protein synthesis. Analysis of functional RNA motifs and elements in RNA sequences can obtain useful information for deciphering RNA regulatory mechanisms. Our previous work, RegRNA, is widely used in the identification of regulatory motifs, and this work extends it by incorporating more comprehensive and updated data sources and analytical approaches into a new platform. Methods ...

  5. A high throughput amenable Arabidopsis-P. aeruginosa system reveals a rewired regulatory module and the utility to identify potent anti-infectives.

    Directory of Open Access Journals (Sweden)

    Suresh Gopalan

    2011-01-01

    Full Text Available We previously demonstrated that in a metasystem consisting of Arabidopsis seedlings growing in liquid medium (in 96 well plates even microbes considered to be innocuous such as laboratory strains of E. coli and B. subtilis can cause potent damage to the host. We further posited that such environment-induced adaptations are brought about by 'system status changes' (rewiring of pre-existing cellular signaling networks and components of the host and the microbe, and that prolongation of such a situation could lead to the emergence of pathogenic states in real-life. Here, using this infection model, we show that the master regulator GacA of the human opportunistic pathogen P. aeruginosa (strain PA14 is dispensable for pathogenesis, as evidenced by three independent read-outs. The gene expression profile of the host after infection with wild type PA14 or the gacA mutant are also identical. GacA normally acts upstream of the quorum sensing regulatory circuit (that includes the regulator LasR that controls a subset of virulence factors. Double mutants in gacA and lasR behave similar to the lasR mutant, as seen by abrogation of a characteristic cell type specific host cell damage caused by PA14 or the gacA mutant. This indicates that a previously unrecognized regulatory mechanism is operative under these conditions upstream of LasR. In addition, the detrimental effect of PA14 on Arabidopsis seedlings is resistant to high concentrations of the aminoglycoside antibiotic gentamicin. These data suggest that the Arabidopsis seedling infection system could be used to identify anti-infectives with potentially novel modes of action.

  6. A high throughput amenable Arabidopsis-P. aeruginosa system reveals a rewired regulatory module and the utility to identify potent anti-infectives.

    Science.gov (United States)

    Gopalan, Suresh; Ausubel, Frederick M

    2011-01-21

    We previously demonstrated that in a metasystem consisting of Arabidopsis seedlings growing in liquid medium (in 96 well plates) even microbes considered to be innocuous such as laboratory strains of E. coli and B. subtilis can cause potent damage to the host. We further posited that such environment-induced adaptations are brought about by 'system status changes' (rewiring of pre-existing cellular signaling networks and components) of the host and the microbe, and that prolongation of such a situation could lead to the emergence of pathogenic states in real-life. Here, using this infection model, we show that the master regulator GacA of the human opportunistic pathogen P. aeruginosa (strain PA14) is dispensable for pathogenesis, as evidenced by three independent read-outs. The gene expression profile of the host after infection with wild type PA14 or the gacA mutant are also identical. GacA normally acts upstream of the quorum sensing regulatory circuit (that includes the regulator LasR) that controls a subset of virulence factors. Double mutants in gacA and lasR behave similar to the lasR mutant, as seen by abrogation of a characteristic cell type specific host cell damage caused by PA14 or the gacA mutant. This indicates that a previously unrecognized regulatory mechanism is operative under these conditions upstream of LasR. In addition, the detrimental effect of PA14 on Arabidopsis seedlings is resistant to high concentrations of the aminoglycoside antibiotic gentamicin. These data suggest that the Arabidopsis seedling infection system could be used to identify anti-infectives with potentially novel modes of action.

  7. Spatially conserved regulatory elements identified within human and mouse Cd247 gene using high-throughput sequencing data from the ENCODE project

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Hannibal, Tine Dahlbæk; Bang-Berthelsen, Claus Heiner

    2014-01-01

    . In this study, we have utilized the wealth of high-throughput sequencing data produced during the Encyclopedia of DNA Elements (ENCODE) project to identify spatially conserved regulatory elements within the Cd247 gene from human and mouse. We show the presence of two transcription factor binding sites...

  8. Regulatory RNPs: a novel class of ribonucleoproteins that potentially contribute to ribosome heterogeneity

    Directory of Open Access Journals (Sweden)

    Aaron R. Poole

    2017-09-01

    Full Text Available Many ribonucleoproteins (RNPs, which are comprised of noncoding RNA and associated proteins, are involved in essential cellular processes such as translation and pre-mRNA splicing. One class of RNP is the small Cajal body-specific RNP (scaRNP, which contributes to the biogenesis of small nuclear RNPs (snRNPs that are central components of the spliceosome. Three scaRNAs are internally processed, generating stable nucleolus-enriched RNAs of unknown function. Here, we provide data that show that these RNAs become part of RNPs we term regulatory RNPs (regRNPs. Most modifications within rRNA (predominantly pseudouridylation and ribose 2′-O-methylation are conducted by small nucleolar RNPs (snoRNPs, and we provide evidence that the activity of at least some of these snoRNPs is under the control of regRNPs. Because modifications within rRNA can vary in different physiological or pathological situations, rRNA modifications are thought to be the major source of ribosome heterogeneity. Our identification of regRNPs thus provides a potential mechanism for how ribosome heterogeneity may be accomplished. This work also provides additional functional connections between the Cajal body and the nucleolus.

  9. Cross-cohort analysis identifies a TEAD4 ↔ MYCN positive-feedback loop as the core regulatory element of high-risk neuroblastoma. | Office of Cancer Genomics

    Science.gov (United States)

    High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator (MR) proteins that were conserved across independent cohorts.

  10. Techniques and methodologies to identify potential generated industries of NORM in Angola Republic and evaluate its impacts

    International Nuclear Information System (INIS)

    Diogo, José Manuel Sucumula

    2017-01-01

    Numerous steps have been taken worldwide to identify and quantify the radiological risks associated with the mining of ores containing Naturally Occurrence Radioactive Material (NORM), often resulting in unnecessary exposures to individuals and high environmental damage, with devastating consequences for the health of workers and damage to the economy of many countries due to a lack of regulations or inadequate regulations. For these and other reasons, the objective of this work was to identify industrial potential generating NORM in the Republic of Angola and to estimate its radiological environmental impacts. To achieve this objective, we studied the theoretical aspects, identified the main internationally recognized industrial companies that as generate by NORM. The Brazilian experience in the regulatory aspect was observed in the evaluation criteria to classify industries that generate NORM, the methods of mining and its radiological environmental impacts, as well as the main techniques applied to evaluate the concentrations of radionuclides in a specific environmental matrix and/or a NORM sample. The study approach allowed the elaboration of a NORM map for the main provinces of Angola, establishing the evaluation criteria for implementing the Radiation Protection Plan in the extractive industry, establishing measures to control ionizing radiation in mining, identifying and quantifying radionuclides present in samples of lees oil. However, in order to assess adequately the radiological environmental impact of the NORM industry, it is not enough to identify them, it is important to know the origin, quantify the radioactive material released as liquid and gaseous effluents, identify the main routes of exposure and examine how this material spreads into the environment until it reaches man. (author)

  11. Techno-economic viability assessments of greener propulsion technology under potential environmental regulatory policy scenarios

    International Nuclear Information System (INIS)

    Nalianda, D.K.; Kyprianidis, K.G.; Sethi, V.; Singh, R.

    2015-01-01

    Highlights: • An advanced method is presented for techno-economic assessment under potential environmental regulatory policy scenarios. • The viability of the contra-rotating open rotor concept is investigated under various environmental policies. • CO_2 taxation is needed to drive the aerospace industry towards greener solutions. - Abstract: Sustainability of the aviation industry, as any other industry, depends on the elasticity of demand for the product and profitability through minimising operating costs. Of paramount importance is assessing and understanding the interdependency and effects of environmentally optimised solutions and emission mitigation policies. This paper describes the development and application of assessment methodologies to better understand the effects of environmental taxation/energy policies aimed at environmental pollution reduction and the future potential economic impact they may have on the adaptation of “greener” novel technologies. These studies are undertaken using a Techno-economic Environmental Risk Assessment approach. The methodology demonstrated allows the assessment of the economic viability of new technologies compared to conventional technologies, for various CO_2 emission taxation and fuel price scenarios. It considers relative increases in acquisition price and maintenance costs. A study undertaken as a ‘proof of concept’ compares a Counter Rotating Open Rotor aircraft with a conventional aircraft for short range operations. It indicates that at current fuel price and with no carbon taxation, a highly fuel efficient technology, such as the one considered, could be rendered economically unviable. The work goes on to demonstrate that in comparison to the conventional aircraft, any economic benefits that may be accrued from improvement in fuel consumption through such a technology, may well be negated through increases in acquisition price and maintenance costs. The work further demonstrates that if policy

  12. Scientific Issues Relevant to Setting Regulatory Criteria to Identify Endocrine-Disrupting Substances in the European Union.

    Science.gov (United States)

    Slama, Rémy; Bourguignon, Jean-Pierre; Demeneix, Barbara; Ivell, Richard; Panzica, Giancarlo; Kortenkamp, Andreas; Zoeller, R Thomas

    2016-10-01

    to setting regulatory criteria to identify endocrine disrupting substances in the European Union. Environ Health Perspect 124:1497-1503; http://dx.doi.org/10.1289/EHP217.

  13. Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.

    Science.gov (United States)

    Lange, Karen I; Heinrichs, Jeffrey; Cheung, Karen; Srayko, Martin

    2013-01-15

    Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B', B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.

  14. Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans

    Directory of Open Access Journals (Sweden)

    Karen I. Lange

    2012-11-01

    Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B′, B″ but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts, and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.

  15. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  16. Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder.

    Science.gov (United States)

    Zhang, Tianxiao; Hou, Liping; Chen, David T; McMahon, Francis J; Wang, Jen-Chyong; Rice, John P

    2018-03-01

    Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Robust global identifiability theory using potentials--Application to compartmental models.

    Science.gov (United States)

    Wongvanich, N; Hann, C E; Sirisena, H R

    2015-04-01

    This paper presents a global practical identifiability theory for analyzing and identifying linear and nonlinear compartmental models. The compartmental system is prolonged onto the potential jet space to formulate a set of input-output equations that are integrals in terms of the measured data, which allows for robust identification of parameters without requiring any simulation of the model differential equations. Two classes of linear and non-linear compartmental models are considered. The theory is first applied to analyze the linear nitrous oxide (N2O) uptake model. The fitting accuracy of the identified models from differential jet space and potential jet space identifiability theories is compared with a realistic noise level of 3% which is derived from sensor noise data in the literature. The potential jet space approach gave a match that was well within the coefficient of variation. The differential jet space formulation was unstable and not suitable for parameter identification. The proposed theory is then applied to a nonlinear immunological model for mastitis in cows. In addition, the model formulation is extended to include an iterative method which allows initial conditions to be accurately identified. With up to 10% noise, the potential jet space theory predicts the normalized population concentration infected with pathogens, to within 9% of the true curve. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Regulation and regulatory role of WNT signaling in potentiating FSH action during bovine dominant follicle selection.

    Directory of Open Access Journals (Sweden)

    P S P Gupta

    Full Text Available Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest and F2 (second largest follicles isolated at predeviation (PD and onset of diameter deviation (OD stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM, PD, OD and early dominance (ED stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

  19. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

    Science.gov (United States)

    McKenna, Dennis J

    2004-05-01

    Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

  20. Identifying Regulatory Patterns at the 3'end Regions of Over-expressed and Under-expressed Genes

    KAUST Repository

    Othoum, Ghofran K

    2013-05-01

    Promoters, neighboring regulatory regions and those extending further upstream of the 5’end of genes, are considered one of the main components affecting the expression status of genes in a specific phenotype. More recently research by Chen et al. (2006, 2012) and Mapendano et al. (2010) demonstrated that the 3’end regulatory regions of genes also influence gene expression. However, the association between the regulatory regions surrounding 3’end of genes and their over- or under-expression status in a particular phenotype has not been systematically studied. The aim of this study is to ascertain if regulatory regions surrounding the 3’end of genes contain sufficient regulatory information to correlate genes with their expression status in a particular phenotype. Over- and under-expressed ovarian cancer (OC) genes were used as a model. Exploratory analysis of the 3’end regions were performed by transforming the annotated regions using principal component analysis (PCA), followed by clustering the transformed data thereby achieving a clear separation of genes with different expression status. Additionally, several classification algorithms such as Naïve Bayes, Random Forest and Support Vector Machine (SVM) were tested with different parameter settings to analyze the discriminatory capacity of the 3’end regions of genes related to their gene expression status. The best performance was achieved using the SVM classification model with 10-fold cross-validation that yielded an accuracy of 98.4%, sensitivity of 99.5% and specificity of 92.5%. For gene expression status for newly available instances, based on information derived from the 3’end regions, an SVM predictive model was developed with 10-fold cross-validation that yielded an accuracy of 67.0%, sensitivity of 73.2% and specificity of 61.0%. Moreover, building an SVM with polynomial kernel model to PCA transformed data yielded an accuracy of 83.1%, sensitivity of 92.5% and specificity of 74.8% using

  1. Identifying Regulatory Patterns at the 3'end Regions of Over-expressed and Under-expressed Genes

    KAUST Repository

    Othoum, Ghofran K

    2013-01-01

    Promoters, neighboring regulatory regions and those extending further upstream of the 5’end of genes, are considered one of the main components affecting the expression status of genes in a specific phenotype. More recently research by Chen et al. (2006, 2012) and Mapendano et al. (2010) demonstrated that the 3’end regulatory regions of genes also influence gene expression. However, the association between the regulatory regions surrounding 3’end of genes and their over- or under-expression status in a particular phenotype has not been systematically studied. The aim of this study is to ascertain if regulatory regions surrounding the 3’end of genes contain sufficient regulatory information to correlate genes with their expression status in a particular phenotype. Over- and under-expressed ovarian cancer (OC) genes were used as a model. Exploratory analysis of the 3’end regions were performed by transforming the annotated regions using principal component analysis (PCA), followed by clustering the transformed data thereby achieving a clear separation of genes with different expression status. Additionally, several classification algorithms such as Naïve Bayes, Random Forest and Support Vector Machine (SVM) were tested with different parameter settings to analyze the discriminatory capacity of the 3’end regions of genes related to their gene expression status. The best performance was achieved using the SVM classification model with 10-fold cross-validation that yielded an accuracy of 98.4%, sensitivity of 99.5% and specificity of 92.5%. For gene expression status for newly available instances, based on information derived from the 3’end regions, an SVM predictive model was developed with 10-fold cross-validation that yielded an accuracy of 67.0%, sensitivity of 73.2% and specificity of 61.0%. Moreover, building an SVM with polynomial kernel model to PCA transformed data yielded an accuracy of 83.1%, sensitivity of 92.5% and specificity of 74.8% using

  2. Cross-comparison of the genome sequences from human, chimpanzee, Neanderthal and a Denisovan hominin identifies novel potentially compensated mutations

    Directory of Open Access Journals (Sweden)

    Zhang Guojie

    2011-07-01

    Full Text Available Abstract The recent publication of the draft genome sequences of the Neanderthal and a ~50,000-year-old archaic hominin from Denisova Cave in southern Siberia has ushered in a new age in molecular archaeology. We previously cross-compared the human, chimpanzee and Neanderthal genome sequences with respect to a set of disease-causing/disease-associated missense and regulatory mutations (Human Gene Mutation Database and succeeded in identifying genetic variants which, although apparently pathogenic in humans, may represent a 'compensated' wild-type state in at least one of the other two species. Here, in an attempt to identify further 'potentially compensated mutations' (PCMs of interest, we have compared our dataset of disease-causing/disease-associated mutations with their corresponding nucleotide positions in the Denisovan hominin, Neanderthal and chimpanzee genomes. Of the 15 human putatively disease-causing mutations that were found to be compensated in chimpanzee, Denisovan or Neanderthal, only a solitary F5 variant (Val1736Met was specific to the Denisovan. In humans, this missense mutation is associated with activated protein C resistance and an increased risk of thromboembolism and recurrent miscarriage. It is unclear at this juncture whether this variant was indeed a PCM in the Denisovan or whether it could instead have been associated with disease in this ancient hominin.

  3. Identifying potential risk situations for humans when removing horses from groups

    DEFF Research Database (Denmark)

    Hartmann, Elke; Søndergaard, Eva; Keeling, Linda J.

    2012-01-01

    Removing a horse from its social group may be considered risky, both for the handler and the horse, because other horses can interfere in the catching process. The main aim of this study was to identify where and when these risk situations occur while removing a horse from its group. A potential...

  4. Identifying potentially cost effective chronic care programs for people with COPD

    NARCIS (Netherlands)

    L.M.G. Steuten (Lotte); K.M.M. Lemmens (Karin); A.P. Nieboer (Anna); H.J.M. Vrijhoef (Hubertus)

    2009-01-01

    textabstractObjective: To review published evidence regarding the cost effectiveness of multi-component COPD programs and to illustrate how potentially cost effective programs can be identified. Methods: Systematic search of Medline and Cochrane databases for evaluations of multicomponent disease

  5. Identifying High Academic Potential in Australian Aboriginal Children Using Dynamic Testing

    Science.gov (United States)

    Chaffey, Graham W.; Bailey, Stan B.; Vine, Ken W.

    2015-01-01

    The primary purpose of this study was to determine the effectiveness of dynamic testing as a method for identifying high academic potential in Australian Aboriginal children. The 79 participating Aboriginal children were drawn from Years 3-5 in rural schools in northern New South Wales. The dynamic testing method used in this study involved a…

  6. A universal meteorological method to identify potential risk of wind erosion on heavy-textured soils

    Directory of Open Access Journals (Sweden)

    Středová Hana

    2015-06-01

    Full Text Available The climate of Central Europe, mainly winter seasons with no snow cover at lower altitudes and a spring drought as well, might cause erosion events on heavy-textured soils. The aim of this paper is to define a universal method to identify the potential risk of wind erosion on heavy-textured soils. The categorization of potential wind erosion risk due to meteorological conditions is based on: (i an evaluation of the number of freeze-thaw episodes forming bare soil surfaces during the cold period of year; and (ii, an evaluation of the number of days with wet soil surfaces during the cold period of year. In the period 2001–2012 (from November to March, episodes with temperature changes from positive to negative and vice versa (thaw-freeze and freeze-thaw cycles and the effects of wet soil surfaces in connection with aggregate disintegration, are identified. The data are spatially interpolated by GIS tools for areas in the Czech Republic with heavy-textured soils. Blending critical categories is used to locate potential risks. The level of risk is divided into six classes. Those areas identified as potentially most vulnerable are the same localities where the highest number of erosive episodes on heavy-textured soils was documented.

  7. Mapping industrial networks as an approach to identify inter-organisational collaborative potential in new product development

    DEFF Research Database (Denmark)

    Parraguez, Pedro; Maier, Anja

    2012-01-01

    . Consequently, identifying and selecting potential partners to establish collaboration agreements can be a key activity in the new product development process. This paper explores the implications of mapping industrial networks with the purpose of identifying inter-organisational collaborative potential...

  8. Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

    Science.gov (United States)

    Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

    1995-01-01

    A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

  9. Metabolomic screening using ESI-FT MS identifies potential radiation-responsive molecules in mouse urine

    International Nuclear Information System (INIS)

    Iizuka, Daisuke; Yoshioka, Susumu; Kawai, Hidehiko; Izumi, Shunsuke; Suzuki, Fumio; Kamiya, Kenji

    2017-01-01

    The demand for establishment of high-throughput biodosimetric methods is increasing. Our aim in this study was to identify low-molecular-weight urinary radiation-responsive molecules using electrospray ionization Fourier transform mass spectrometry (ESI-FT MS), and our final goal was to develop a sensitive biodosimetry technique that can be applied in the early triage of a radiation emergency medical system. We identified nine metabolites by statistical comparison of mouse urine before and 8 h after irradiation. Time-course analysis showed that, of these metabolites, thymidine and either thymine or imidazoleacetic acid were significantly increased dose-dependently 8 h after radiation exposure; these molecules have already been reported as potential radiation biomarkers. Phenyl glucuronide was significantly decreased 8 h after radiation exposure, irrespective of the dose. Histamine and 1-methylhistamine were newly identified by MS/MS and showed significant, dose-dependent increases 72 h after irradiation. Quantification of 1-methylhistamine by enzyme-linked immunosorbent assay (ELISA) analysis also showed a significant increase 72 h after 4 Gy irradiation. These results suggest that urinary metabolomics screening using ESI-FT MS can be a powerful tool for identifying promising radiation-responsive molecules, and that urinary 1-methylhistamine is a potential radiation-responsive molecule for acute, high-dose exposure.

  10. Spontaneous swallowing frequency has potential to identify dysphagia in acute stroke.

    Science.gov (United States)

    Crary, Michael A; Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael F

    2013-12-01

    Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. In a cohort of 63 acute stroke cases, swallow frequency rates (swallows per minute [SPM]) were compared with stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with versus without clinically significant dysphagia. Receiver operating characteristic curve analysis was used to identify the optimal threshold in SPM, which was compared with a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was used to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. Receiver operating characteristic curve analysis yielded a threshold of SPM≤0.40 that identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5- to 10-minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel.

  11. Spontaneous Swallowing Frequency [Has Potential to] Identify Dysphagia in Acute Stroke

    Science.gov (United States)

    Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael

    2014-01-01

    Background and Purpose Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. Methods In a cohort of 63 acute stroke cases swallow frequency rates (swallows per minute: SPM) were compared to stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with vs. without clinically significant dysphagia. ROC analysis was used to identify the optimal threshold in SPM which was compared to a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was employed to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. Results SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. ROC analysis yielded a threshold of SPM ≤ 0.40 which identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5 to 10 minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Conclusions Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel. PMID:24149008

  12. Characterization of potential mineralization in Afghanistan: four permissive areas identified using imaging spectroscopy data

    Science.gov (United States)

    King, Trude V.V.; Berger, Byron R.; Johnson, Michaela R.

    2014-01-01

    As part of the U.S. Geological Survey and Department of Defense Task Force for Business and Stability Operations natural resources revitalization activities in Afghanistan, four permissive areas for mineralization, Bamyan 1, Farah 1, Ghazni 1, and Ghazni 2, have been identified using imaging spectroscopy data. To support economic development, the areas of potential mineralization were selected on the occurrence of selected mineral assemblages mapped using the HyMap™ data (kaolinite, jarosite, hydrated silica, chlorite, epidote, iron-bearing carbonate, buddingtonite, dickite, and alunite) that may be indicative of past mineralization processes in areas with limited or no previous mineral resource studies. Approximately 30 sites were initially determined to be candidates for areas of potential mineralization. Additional criteria and material used to refine the selection and prioritization process included existing geologic maps, Landsat Thematic Mapper data, and published literature. The HyMapTM data were interpreted in the context of the regional geologic and tectonic setting and used the presence of alteration mineral assemblages to identify areas with the potential for undiscovered mineral resources. Further field-sampling, mapping, and supporting geochemical analyses are necessary to fully substantiate and verify the specific deposit types in the four areas of potential mineralization.

  13. Identification of Conserved and Potentially Regulatory Small RNAs in Heterocystous Cyanobacteria

    Directory of Open Access Journals (Sweden)

    Manuel eBrenes-Álvarez

    2016-02-01

    Full Text Available Small RNAs (sRNAs are a growing class of non-protein-coding transcripts that participate in the regulation of virtually every aspect of bacterial physiology. Heterocystous cyanobacteria are a group of photosynthetic organisms that exhibit multicellular behaviour and developmental alternatives involving specific transcriptomes exclusive of a given physiological condition or even a cell type. In the context of our ongoing effort to understand developmental decisions in these organisms we have undertaken an approach to the global identification of sRNAs. Using differential RNA-Seq we have previously identified transcriptional start sites for the model heterocystous cyanobacterium Nostoc sp. PCC 7120. Here we combine this dataset with a prediction of Rho-independent transcriptional terminators and an analysis of phylogenetic conservation of potential sRNAs among 89 available cyanobacterial genomes. In contrast to predictive genome-wide approaches, the use of an experimental dataset comprising all active transcriptional start sites (differential RNA-Seq facilitates the identification of bona fide sRNAs. The output of our approach is a dataset of predicted potential sRNAs in Nostoc sp. PCC 7120, with different degrees of phylogenetic conservation across the 89 cyanobacterial genomes analyzed. Previously described sRNAs appear among the predicted sRNAs, demonstrating the performance of the algorithm. In addition, new predicted sRNAs are now identified that can be involved in regulation of different aspects of cyanobacterial physiology, including adaptation to nitrogen stress, the condition that triggers differentiation of heterocysts (specialized nitrogen-fixing cells. Transcription of several predicted sRNAs that appear exclusively in the genomes of heterocystous cyanobacteria is experimentally verified by Northern blot. Cell-specific transcription of one of these sRNAs, NsiR8 (nitrogen stress-induced RNA 8, in developing heterocysts is also

  14. Regulatory roles and therapeutic potential of microRNA in sarcoma.

    Science.gov (United States)

    Lim, Hui Jun; Yang, Jia-Lin

    2016-01-01

    MicroRNAs (miRNAs) are single-stranded noncoding RNAs involved in various biological processes, including cell differentiation and development. They play multiple key roles as tumour suppressors, oncogenes or both in particular cases. This review aims to summarise current findings of the expression of miRNAs and their role in clinical oncology. Current knowledge regarding the involvement of miRNAs in different sarcoma subtypes will be assessed, in conjunction with their potential application as therapeutic targets. Relevant articles in scientific databases were identified using a combination of search terms, including "microRNA," "deregulation," "sarcoma," and "targeted therapy". These databases included Medline, Embase, Cochrane Review, Pubmed and Scopus. Aberrant miRNA expression patterns have been identified in a range of sarcoma subtypes, and differences in miRNA expression profiles between malignant cells and their normal counterparts suggests that miRNAs play key roles in sarcoma development. The identification of unique miRNA patterns in individual tumour types could possibly be used as a diagnostic tool in sarcoma. Moreover, identification of these miRNAs provides novel targets for the development of therapeutic strategies in distinct sarcoma subtypes. miRNAs hold significant potential as diagnostic biomarkers, as well as therapeutic targets in sarcoma. Possible future clinical applications include the use of miRNA pathways as therapeutic targets or miRNA expression profiling as a means of patient selection. The involvement miRNAs will undoubtedly contribute to the advancement of future targeted therapeutic interventions in sarcoma, and further establishment of appropriate delivery systems is vital for their use in clinical settings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Analysis of regulatory structure for a potential fusion-reactor industry

    International Nuclear Information System (INIS)

    1981-03-01

    The report is divided into eight sections. The preface describes the authors of the report, the methodology used in its preparation, and some basic legal terms. The summary describes the principal features of the proposed regulatory system and also includes two flow charts comparing our model with present NRC practices and a summary table briefly outlining the reasoning behind our recommendations. The main body of the report is divided into six sections. This part of the report discusses the existing federal and state programs for regulating electric energy, describes NRC operations and the criticisms of that agency, discusses the features of our proposed regulatory model, recommends certain steps for implementing the proposed model, and states the conclusions of the report

  16. What's the risk? Identifying potential human pathogens within grey-headed flying foxes faeces.

    Directory of Open Access Journals (Sweden)

    Rebekah Henry

    Full Text Available Pteropus poliocephalus (grey-headed flying foxes are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%, Pasteurellaceae (19.9% ± 25.7% and Moraxellaceae (9.4% ± 11.8% dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals.

  17. An automated technique to identify potential inappropriate traditional Chinese medicine (TCM) prescriptions.

    Science.gov (United States)

    Yang, Hsuan-Chia; Iqbal, Usman; Nguyen, Phung Anh; Lin, Shen-Hsien; Huang, Chih-Wei; Jian, Wen-Shan; Li, Yu-Chuan

    2016-04-01

    Medication errors such as potential inappropriate prescriptions would induce serious adverse drug events to patients. Information technology has the ability to prevent medication errors; however, the pharmacology of traditional Chinese medicine (TCM) is not as clear as in western medicine. The aim of this study was to apply the appropriateness of prescription (AOP) model to identify potential inappropriate TCM prescriptions. We used the association rule of mining techniques to analyze 14.5 million prescriptions from the Taiwan National Health Insurance Research Database. The disease and TCM (DTCM) and traditional Chinese medicine-traditional Chinese medicine (TCMM) associations are computed by their co-occurrence, and the associations' strength was measured as Q-values, which often referred to as interestingness or life values. By considering the number of Q-values, the AOP model was applied to identify the inappropriate prescriptions. Afterwards, three traditional Chinese physicians evaluated 1920 prescriptions and validated the detected outcomes from the AOP model. Out of 1920 prescriptions, 97.1% of positive predictive value and 19.5% of negative predictive value were shown by the system as compared with those by experts. The sensitivity analysis indicated that the negative predictive value could improve up to 27.5% when the model's threshold changed to 0.4. We successfully applied the AOP model to automatically identify potential inappropriate TCM prescriptions. This model could be a potential TCM clinical decision support system in order to improve drug safety and quality of care. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Gender Inequality and Reflexive Law: The Potential of different regulatory Mechanisms for making Employment Rights effective

    OpenAIRE

    Deakin, S.; McLaughlin, C.; Chai, D.H.

    2011-01-01

    We review the different regulatory mechanisms which have been used in the UK context to promote gender equality in employment over the past decade, including legal enforcement based on claimant-led litigation, collective bargaining, pay audits, and shareholder pressure. Evidence is drawn from case studies examining the effects of these different mechanisms on organisations in the public and private sectors, and from econometric analysis of the impact of stock market pressures on firms' human ...

  19. Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis.

    Science.gov (United States)

    Zhao, Luyang; Gu, Chenglei; Ye, Mingxia; Zhang, Zhe; Li, Li'an; Fan, Wensheng; Meng, Yuanguang

    2018-01-22

    The etiology and pathophysiology of endometriosis remain unclear. Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis. This study therefore aims to survey the key miRNAs, TFs and genes and further understand the mechanism of endometriosis. Paired expression profiling of miRNA and mRNA in ectopic endometria compared with eutopic endometria were determined by high-throughput sequencing techniques in eight patients with ovarian endometriosis. Binary interactions and circuits among the miRNAs, TFs, and corresponding genes were identified by the Pearson correlation coefficients. miRNA-TF-gene regulatory networks were constructed using bioinformatic methods. Eleven selected miRNAs and TFs were validated by quantitative reverse transcription-polymerase chain reaction in 22 patients. Overall, 107 differentially expressed miRNAs and 6112 differentially expressed mRNAs were identified by comparing the sequencing of the ectopic endometrium group and the eutopic endometrium group. The miRNA-TF-gene regulatory network consists of 22 miRNAs, 12 TFs and 430 corresponding genes. Specifically, some key regulators from the miR-449 and miR-34b/c cluster, miR-200 family, miR-106a-363 cluster, miR-182/183, FOX family, GATA family, and E2F family as well as CEBPA, SOX9 and HNF4A were suggested to play vital regulatory roles in the pathogenesis of endometriosis. Integration analysis of the miRNA and mRNA expression profiles presents a unique insight into the regulatory network of this enigmatic disorder and possibly provides clues regarding replacement therapy for endometriosis.

  20. Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

    Science.gov (United States)

    Dey-Rao, Rama; Sinha, Animesh A

    2017-01-28

    Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address

  1. Identifying Potential Recommendation Domains for Conservation Agriculture in Ethiopia, Kenya, and Malawi

    Science.gov (United States)

    Tesfaye, Kindie; Jaleta, Moti; Jena, Pradyot; Mutenje, Munyaradzi

    2015-02-01

    Conservation agriculture (CA) is being promoted as an option for reducing soil degradation, conserving water, enhancing crop productivity, and maintaining yield stability. However, CA is a knowledge- and technology-intensive practice, and may not be feasible or may not perform better than conventional agriculture under all conditions and farming systems. Using high resolution (≈1 km2) biophysical and socioeconomic geospatial data, this study identified potential recommendation domains (RDs) for CA in Ethiopia, Kenya, and Malawi. The biophysical variables used were soil texture, surface slope, and rainfall while the socioeconomic variables were market access and human and livestock population densities. Based on feasibility and comparative performance of CA over conventional agriculture, the biophysical and socioeconomic factors were first used to classify cultivated areas into three biophysical and three socioeconomic potential domains, respectively. Combinations of biophysical and socioeconomic domains were then used to develop potential RDs for CA based on adoption potential within the cultivated areas. About 39, 12, and 5 % of the cultivated areas showed high biophysical and socioeconomic potential while 50, 39, and 21 % of the cultivated areas showed high biophysical and medium socioeconomic potential for CA in Malawi, Kenya, and Ethiopia, respectively. The results indicate considerable acreages of land with high CA adoption potential in the mixed crop-livestock systems of the studied countries. However, there are large differences among countries depending on biophysical and socio-economic conditions. The information generated in this study could be used for targeting CA and prioritizing CA-related agricultural research and investment priorities in the three countries.

  2. New CSA guideline for the exemption or clearance from regulatory control of materials that contain, or potentially contain, nuclear substances

    International Nuclear Information System (INIS)

    Rhodes, M.; Kwong, A.

    2011-01-01

    The Canadian Standards Association (CSA) guideline N292.5, Guideline for the exemption or clearance from regulatory control of materials that contain, or potentially contain, nuclear substances, was recently developed to address a need for guidance on approaches for clearance of materials from facilities licensed by the Canadian Nuclear Safety Commission (CNSC) consistent with Canadian and international recommendations. This guideline is also applicable to determining if an activity associated with materials that contain nuclear substances is exempt from requiring a CNSC licence. The guideline summarizes the regulatory requirements associated with the exemption and clearance of materials and provides a graded approach to designing a survey based on the risk of residual contamination being present. (author)

  3. Identifying potentially eligible subjects for research: paper-based logs versus the hospital administrative database.

    Science.gov (United States)

    Magee, L A; Massey, K; von Dadelszen, P; Fazio, M; Payne, B; Liston, R

    2011-12-01

    The Canadian Perinatal Network (CPN) is a national database focused on threatened very pre-term birth. Women with one or more conditions most commonly associated with very pre-term birth are included if admitted to a participating tertiary perinatal unit at 22 weeks and 0 days to 28 weeks and 6 days. At BC Women's Hospital and Health Centre, we compared traditional paper-based ward logs and a search of the Canadian Institute for Health Information (CIHI) electronic database of inpatient discharges to identify patients. The study identified 244 women potentially eligible for inclusion in the CPN admitted between April and December 2007. Of the 155 eligible women entered into the CPN database, each method identified a similar number of unique records (142 and 147) not ascertained by the other: 10 (6.4%) by CIHI search and 5 (3.2%) by ward log review. However, CIHI search achieved these results after reviewing fewer records (206 vs. 223) in less time (0.67 vs. 13.6 hours for ward logs). Either method is appropriate for identification of potential research subjects using gestational age criteria. Although electronic methods are less time-consuming, they cannot be performed until after the patient is discharged and records and charts are reviewed. Each method's advantages and disadvantages will dictate use for a specific project.

  4. The potential for research-based information in public health: Identifying unrecognised information needs

    Directory of Open Access Journals (Sweden)

    Forsetlund Louise

    2001-01-01

    Full Text Available Abstract Objective To explore whether there is a potential for greater use of research-based information in public health practice in a local setting. Secondly, if research-based information is relevant, to explore the extent to which this generates questioning behaviour. Design Qualitative study using focus group discussions, observation and interviews. Setting Public health practices in Norway. Participants 52 public health practitioners. Results In general, the public health practitioners had a positive attitude towards research-based information, but believed that they had few cases requiring this type of information. They did say, however, that there might be a potential for greater use. During five focus groups and six observation days we identified 28 questions/cases where it would have been appropriate to seek out research evidence according to our definition. Three of the public health practitioners identified three of these 28 cases as questions for which research-based information could have been relevant. This gap is interpreted as representing unrecognised information needs. Conclusions There is an unrealised potential in public health practice for more frequent and extensive use of research-based information. The practitioners did not appear to reflect on the need for scientific information when faced with new cases and few questions of this type were generated.

  5. Using Helicopter Electromagnetic Surveys to Identify Potential Hazards at Mine Waste Impoundments

    Energy Technology Data Exchange (ETDEWEB)

    Hammack, R.W.

    2008-01-01

    In July 2003, helicopter electromagnetic surveys were conducted at 14 coal waste impoundments in southern West Virginia. The purpose of the surveys was to detect conditions that could lead to impoundment failure either by structural failure of the embankment or by the flooding of adjacent or underlying mine works. Specifically, the surveys attempted to: 1) identify saturated zones within the mine waste, 2) delineate filtrate flow paths through the embankment or into adjacent strata and receiving streams, and 3) identify flooded mine workings underlying or adjacent to the waste impoundment. Data from the helicopter surveys were processed to generate conductivity/depth images. Conductivity/depth images were then spatially linked to georeferenced air photos or topographic maps for interpretation. Conductivity/depth images were found to provide a snapshot of the hydrologic conditions that exist within the impoundment. This information can be used to predict potential areas of failure within the embankment because of its ability to image the phreatic zone. Also, the electromagnetic survey can identify areas of unconsolidated slurry in the decant basin and beneath the embankment. Although shallow, flooded mineworks beneath the impoundment were identified by this survey, it cannot be assumed that electromagnetic surveys can detect all underlying mines. A preliminary evaluation of the data implies that helicopter electromagnetic surveys can provide a better understanding of the phreatic zone than the piezometer arrays that are typically used.

  6. Genome-wide gene expression dataset used to identify potential therapeutic targets in androgenetic alopecia

    Directory of Open Access Journals (Sweden)

    R. Dey-Rao

    2017-08-01

    Full Text Available The microarray dataset attached to this report is related to the research article with the title: “A genomic approach to susceptibility and pathogenesis leads to identifying potential novel therapeutic targets in androgenetic alopecia” (Dey-Rao and Sinha, 2017 [1]. Male-pattern hair loss that is induced by androgens (testosterone in genetically predisposed individuals is known as androgenetic alopecia (AGA. The raw dataset is being made publicly available to enable critical and/or extended analyses. Our related research paper utilizes the attached raw dataset, for genome-wide gene-expression associated investigations. Combined with several in silico bioinformatics-based analyses we were able to delineate five strategic molecular elements as potential novel targets towards future AGA-therapy.

  7. Market potential of nanoremediation in Europe - Market drivers and interventions identified in a deliberative scenario approach.

    Science.gov (United States)

    Bartke, Stephan; Hagemann, Nina; Harries, Nicola; Hauck, Jennifer; Bardos, Paul

    2018-04-01

    A deliberate expert-based scenario approach is applied to better understand the likely determinants of the evolution of the market for nanoparticles use in remediation in Europe until 2025. An initial set of factors had been obtained from a literature review and was complemented by a workshop and key-informant interviews. In further expert engaging formats - focus groups, workshops, conferences, surveys - this initial set of factors was condensed and engaged experts scored the factors regarding their importance for being likely to influence the market development. An interaction matrix was obtained identifying the factors being most active in shaping the market development in Europe by 2025, namely "Science-Policy-Interface" and "Validated information on nanoparticle application potential". Based on these, potential scenarios were determined and development of factors discussed. Conclusions are offered on achievable interventions to enhance nanoremediation deployment. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Identifying Pre-Service Teachers’ Beliefs About Teaching EFL and Their Potential Changes

    Directory of Open Access Journals (Sweden)

    Sergio Andrés Suárez Flórez

    2017-07-01

    Full Text Available This study aims at identifying pre-service teachers’ beliefs about teaching English as a foreign language and tracking their potential changes throughout the teaching practicum. Participants were two pre-service teachers in their fifth year of their Bachelor of Arts in Foreign Languages program in a public university in Colombia. Data were gathered through a modified version of Beliefs about Language Learning Inventory before the practicum, eight weekly journal entries administered during ten weeks, and two semi-structured interviews at the end of the teaching practicum. The findings revealed that most of the pre-service teachers’ beliefs changed once they faced the reality of the classroom.

  9. Geological study for identifying potential aquifer zone in Pakes and Bandung Villages, Konang District, Bangkalan Region

    International Nuclear Information System (INIS)

    I Gde Sukadana

    2010-01-01

    Konang District has a problem on fresh water supply particularly in dry season. Two villages in the district, namely Pakes and Konang, are densely populated areas having agriculture activities, so available of sufficient fresh water is necessary. A fresh water source that can be developed in this area is deep groundwater source from potential aquifers. A geological study has been conducted to identify potential aquifer based on lithological aspect and geological structure. According to the regional stratigraphy. the study area consists of Tawun Formation and Ngrayong Formation. They compose of carbonaceous clay stone (the oldest rock unit), carbonaceous clay stone with sandy limestone intercalations, sandy limestone interbed with carbonaceous clay stone, tuff sandstone with clay stone intercalations, and reef limestone (the youngest) respectively. Strike and dip positions of the rocks layers are N110°E/22° - N150°E/26°, located on the south anticline axis with wavy plan to gentle slope of hilly morphology. Among the rock unit, only sandy limestone has fine sand with sub angular in shape and open pack. Qualitatively. this rock has good porosity and permeability and is enables to save and to flow subsurface water. Thus. the sandy limestone is considered as a potential zone for fresh water resources. Whereas, carbonaceous clay stone with clay grain size has low porosity and permeability, so it is potential as a cap rock. (author)

  10. Medical loss ratio as a potential regulatory tool in the Israeli healthcare system.

    Science.gov (United States)

    Simon-Tuval, Tzahit; Horev, Tuvia; Kaplan, Giora

    2015-01-01

    The growth of the private health insurance sector in Western countries, which is characterized by information deficiencies and limited competition, necessitates the implementation of effective regulatory tools. One measure which is widely used is the medical loss ratio (MLR). Our objective was to analyze how MLR is applied as a regulatory measure in the Israeli voluntary health insurance (VHI) market in order to promote the protection of beneficiaries. The study will examine MLR values and the use of this tool by regulators of VHI in Israel. Descriptive analysis using 2005-2012 data from public reports of the Ministry of Health and the Ministry of Finance on VHI plans in three market segments: nonprofit health plans, group (collective) policies offered by commercial insurance companies and individual policies offered by commercial insurance companies. In 2012, 74% of the Israeli population owned VHI provided by nonprofit health plans and 43% owned VHI offered by for-profit commercial companies. At that time the MLRs of three nonprofit health plans were significantly lower than 80%, mostly in the upper layers of coverage. The MLR in the individual commercial segment was consistently low (38% in 2012). The use of MLR as a regulation tool was, and continues to be, relatively limited in all segments. The VHI in Israel covers several essential services that are not covered by the statutory benefits package as a result of budget constraints. Thus, due to the high penetration rate of VHI in Israel compared to European countries and the lower levels of MLR, in order to assure the protection of beneficiaries it may be warranted to increase the extent of regulation and adjust it to the nature of the services covered. This may include distinguishing between essential and nonessential coverages and implementation of the most suitable regulatory measures (such as an MLR threshold, limitation of services covered and adjusting the actuarial models to the beneficiaries' behavior

  11. PlantPAN: Plant promoter analysis navigator, for identifying combinatorial cis-regulatory elements with distance constraint in plant gene groups

    Directory of Open Access Journals (Sweden)

    Huang Hsien-Da

    2008-11-01

    Full Text Available Abstract Background The elucidation of transcriptional regulation in plant genes is important area of research for plant scientists, following the mapping of various plant genomes, such as A. thaliana, O. sativa and Z. mays. A variety of bioinformatic servers or databases of plant promoters have been established, although most have been focused only on annotating transcription factor binding sites in a single gene and have neglected some important regulatory elements (tandem repeats and CpG/CpNpG islands in promoter regions. Additionally, the combinatorial interaction of transcription factors (TFs is important in regulating the gene group that is associated with the same expression pattern. Therefore, a tool for detecting the co-regulation of transcription factors in a group of gene promoters is required. Results This study develops a database-assisted system, PlantPAN (Plant Promoter Analysis Navigator, for recognizing combinatorial cis-regulatory elements with a distance constraint in sets of plant genes. The system collects the plant transcription factor binding profiles from PLACE, TRANSFAC (public release 7.0, AGRIS, and JASPER databases and allows users to input a group of gene IDs or promoter sequences, enabling the co-occurrence of combinatorial transcription factor binding sites (TFBSs within a defined distance (20 bp to 200 bp to be identified. Furthermore, the new resource enables other regulatory features in a plant promoter, such as CpG/CpNpG islands and tandem repeats, to be displayed. The regulatory elements in the conserved regions of the promoters across homologous genes are detected and presented. Conclusion In addition to providing a user-friendly input/output interface, PlantPAN has numerous advantages in the analysis of a plant promoter. Several case studies have established the effectiveness of PlantPAN. This novel analytical resource is now freely available at http://PlantPAN.mbc.nctu.edu.tw.

  12. Patterns of Seismicity Associated with USGS Identified Areas of Potentially Induced Seismicity.

    Science.gov (United States)

    Barnes, Caitlin; Halihan, Todd

    2018-03-13

    A systematic review across U.S. Geological Survey (USGS) identified potentially induced seismic locations was conducted to discover seismic distance patterns and trends over time away from injection disposal wells. Previous research indicates a 10 km (6 miles) average where the majority of induced seismicity is expected to occur within individual locations, with some areas reporting a larger radius of 35 km (22 miles) to over 70 km (43 miles). This research analyzed earthquake occurrences within nine USGS locations where specified wells were identified as contributors to induced seismicity to determine distance patterns from disposal wells or outward seismic migration over time using established principles of hydrogeology. Results indicate a radius of 31.6 km (20 miles) where 90% of felt earthquakes occur among locations, with the closest proximal felt seismic events, on average, occurring 3 km (1.9 miles) away from injection disposal wells. The results of this research found distance trends across multiple locations of potentially induced seismicity. © 2018, National Ground Water Association.

  13. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2014-05-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  14. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2015-08-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  15. How accurately does the Brief Job Stress Questionnaire identify workers with or without potential psychological distress?

    Science.gov (United States)

    Tsutsumi, Akizumi; Inoue, Akiomi; Eguchi, Hisashi

    2017-07-27

    The manual for the Japanese Stress Check Program recommends use of the Brief Job Stress Questionnaire (BJSQ) from among the program's instruments and proposes criteria for defining "high-stress" workers. This study aimed to examine how accurately the BJSQ identifies workers with or without potential psychological distress. We used an online survey to administer the BJSQ with a psychological distress scale (K6) to randomly selected workers (n=1,650). We conducted receiver operating characteristics curve analyses to estimate the screening performance of the cutoff points that the Stress Check Program manual recommends for the BJSQ. Prevalence of workers with potential psychological distress defined as K6 score ≥13 was 13%. Prevalence of "high-risk" workers defined using criteria recommended by the program manual was 16.7% for the original version of the BJSQ. The estimated values were as follows: sensitivity, 60.5%; specificity, 88.9%; Youden index, 0.504; positive predictive value, 47.3%; negative predictive value, 93.8%; positive likelihood ratio, 6.0; and negative likelihood ratio, 0.4. Analyses based on the simplified BJSQ indicated lower sensitivity compared with the original version, although we expected roughly the same screening performance for the best scenario using the original version. Our analyses in which psychological distress measured by K6 was set as the target condition indicate less than half of the identified "high-stress" workers warrant consideration for secondary screening for psychological distress.

  16. Rapid, computer vision-enabled murine screening system identifies neuropharmacological potential of two new mechanisms

    Directory of Open Access Journals (Sweden)

    Steven L Roberds

    2011-09-01

    Full Text Available The lack of predictive in vitro models for behavioral phenotypes impedes rapid advancement in neuropharmacology and psychopharmacology. In vivo behavioral assays are more predictive of activity in human disorders, but such assays are often highly resource-intensive. Here we describe the successful application of a computer vision-enabled system to identify potential neuropharmacological activity of two new mechanisms. The analytical system was trained using multiple drugs that are used clinically to treat depression, schizophrenia, anxiety, and other psychiatric or behavioral disorders. During blinded testing the PDE10 inhibitor TP-10 produced a signature of activity suggesting potential antipsychotic activity. This finding is consistent with TP-10’s activity in multiple rodent models that is similar to that of clinically used antipsychotic drugs. The CK1ε inhibitor PF-670462 produced a signature consistent with anxiolytic activity and, at the highest dose tested, behavioral effects similar to that of opiate analgesics. Neither TP-10 nor PF-670462 was included in the training set. Thus, computer vision-based behavioral analysis can facilitate drug discovery by identifying neuropharmacological effects of compounds acting through new mechanisms.

  17. Identifying Potential Area and Financial Prospects of Rooftop Solar Photovoltaics (PV

    Directory of Open Access Journals (Sweden)

    Sarawut Ninsawat

    2016-10-01

    Full Text Available In an urban area, the roof is the only available surface that can be utilized for installing solar photovoltaics (PV, and the active surface area depends on the type of roof. Shadows on a solar panel can be caused by nearby tall buildings, construction materials such as water tanks, or the roof configuration itself. The azimuth angle of the sun varies, based on the season and the time of day. Therefore, the simulation of shadow for one or two days or using the rule of thumb may not be sufficient to evaluate shadow effects on solar panels throughout the year. In this paper, a methodology for estimating the solar potential of solar PV on rooftops is presented, which is particularly applicable to urban areas. The objective of this method is to assess how roof type and shadow play a role in potentiality and financial benefit. The method starts with roof type extraction from high-resolution satellite imagery, using Object Base Image Analysis (OBIA, the generation of a 3D structure from height data and roof type, the simulation of shadow throughout the year, and the identification of potential and financial prospects. Based on the results obtained, the system seems to be adequate for calculating the financial benefits of solar PV to a very fine scale. The payback period varied from 7–13 years depending on the roof type, direction, and shadow impact. Based on the potentiality, a homeowner can make a profit of up to 200%. This method could help homeowners to identify potential roof area and economic interest.

  18. Structural and functional analysis of mouse Msx1 gene promoter: sequence conservation with human MSX1 promoter points at potential regulatory elements.

    Science.gov (United States)

    Gonzalez, S M; Ferland, L H; Robert, B; Abdelhay, E

    1998-06-01

    Vertebrate Msx genes are related to one of the most divergent homeobox genes of Drosophila, the muscle segment homeobox (msh) gene, and are expressed in a well-defined pattern at sites of tissue interactions. This pattern of expression is conserved in vertebrates as diverse as quail, zebrafish, and mouse in a range of sites including neural crest, appendages, and craniofacial structures. In the present work, we performed structural and functional analyses in order to identify potential cis-acting elements that may be regulating Msx1 gene expression. To this end, a 4.9-kb segment of the 5'-flanking region was sequenced and analyzed for transcription-factor binding sites. Four regions showing a high concentration of these sites were identified. Transfection assays with fragments of regulatory sequences driving the expression of the bacterial lacZ reporter gene showed that a region of 4 kb upstream of the transcription start site contains positive and negative elements responsible for controlling gene expression. Interestingly, a fragment of 130 bp seems to contain the minimal elements necessary for gene expression, as its removal completely abolishes gene expression in cultured cells. These results are reinforced by comparison of this region with the human Msx1 gene promoter, which shows extensive conservation, including many consensus binding sites, suggesting a regulatory role for them.

  19. Novel modeling of combinatorial miRNA targeting identifies SNP with potential role in bone density.

    Directory of Open Access Journals (Sweden)

    Claudia Coronnello

    Full Text Available MicroRNAs (miRNAs are post-transcriptional regulators that bind to their target mRNAs through base complementarity. Predicting miRNA targets is a challenging task and various studies showed that existing algorithms suffer from high number of false predictions and low to moderate overlap in their predictions. Until recently, very few algorithms considered the dynamic nature of the interactions, including the effect of less specific interactions, the miRNA expression level, and the effect of combinatorial miRNA binding. Addressing these issues can result in a more accurate miRNA:mRNA modeling with many applications, including efficient miRNA-related SNP evaluation. We present a novel thermodynamic model based on the Fermi-Dirac equation that incorporates miRNA expression in the prediction of target occupancy and we show that it improves the performance of two popular single miRNA target finders. Modeling combinatorial miRNA targeting is a natural extension of this model. Two other algorithms show improved prediction efficiency when combinatorial binding models were considered. ComiR (Combinatorial miRNA targeting, a novel algorithm we developed, incorporates the improved predictions of the four target finders into a single probabilistic score using ensemble learning. Combining target scores of multiple miRNAs using ComiR improves predictions over the naïve method for target combination. ComiR scoring scheme can be used for identification of SNPs affecting miRNA binding. As proof of principle, ComiR identified rs17737058 as disruptive to the miR-488-5p:NCOA1 interaction, which we confirmed in vitro. We also found rs17737058 to be significantly associated with decreased bone mineral density (BMD in two independent cohorts indicating that the miR-488-5p/NCOA1 regulatory axis is likely critical in maintaining BMD in women. With increasing availability of comprehensive high-throughput datasets from patients ComiR is expected to become an essential

  20. Use of multi-criteria decision analysis to identify potentially dangerous glacial lakes.

    Science.gov (United States)

    Kougkoulos, Ioannis; Cook, Simon J; Jomelli, Vincent; Clarke, Leon; Symeonakis, Elias; Dortch, Jason M; Edwards, Laura A; Merad, Myriam

    2018-04-15

    Glacial Lake Outburst Floods (GLOFs) represent a significant threat in deglaciating environments, necessitating the development of GLOF hazard and risk assessment procedures. Here, we outline a Multi-Criteria Decision Analysis (MCDA) approach that can be used to rapidly identify potentially dangerous lakes in regions without existing tailored GLOF risk assessments, where a range of glacial lake types exist, and where field data are sparse or non-existent. Our MCDA model (1) is desk-based and uses freely and widely available data inputs and software, and (2) allows the relative risk posed by a range of glacial lake types to be assessed simultaneously within any region. A review of the factors that influence GLOF risk, combined with the strict rules of criteria selection inherent to MCDA, has allowed us to identify 13 exhaustive, non-redundant, and consistent risk criteria. We use our MCDA model to assess the risk of 16 extant glacial lakes and 6 lakes that have already generated GLOFs, and found that our results agree well with previous studies. For the first time in GLOF risk assessment, we employed sensitivity analyses to test the strength of our model results and assumptions, and to identify lakes that are sensitive to the criteria and risk thresholds used. A key benefit of the MCDA method is that sensitivity analyses are readily undertaken. Overall, these sensitivity analyses lend support to our model, although we suggest that further work is required to determine the relative importance of assessment criteria, and the thresholds that determine the level of risk for each criterion. As a case study, the tested method was then applied to 25 potentially dangerous lakes in the Bolivian Andes, where GLOF risk is poorly understood; 3 lakes are found to pose 'medium' or 'high' risk, and require further detailed investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Interprovincial regulatory barriers to procurement in western Canada's oil and gas sector : potential standardization-based solutions : final report

    International Nuclear Information System (INIS)

    Hawkins, R.; Godin, M.; Josty, P.

    2008-01-01

    This study reviewed the regulatory environment related to the oil and gas industry in western Canada in order to identify factors limiting the procurement of goods and services required by the industry. The aim of the study was to identify solutions based on the development of voluntary industry standards. Literature and reports related to interprovincial trade and standards were reviewed. The procurement divisions of oil and gas companies and suppliers to the oil and gas industry were consulted in addition to government official and industry experts. A review of provincial technical regulations was completed. The study identified 3 candidates for specific action within the standards system: (1) modular transport platforms; (2) regulatory conformance procedures; and (3) the mobility of skilled workers. Results of the study indicated that the development of service standards for technical and inspection activities of importance to the petroleum industry will help to facilitate the increased mobility of skilled workers, while initiatives to develop a standard information disclosure and exchange format for all federal, provincial and territorial jurisdictions will address the conflicting regimes to which oil and gas products and services are subjected. 40 refs., 5 tabs.

  2. Proteomic Analysis of Saliva Identifies Potential Biomarkers for Orthodontic Tooth Movement

    Science.gov (United States)

    Ellias, Mohd Faiz; Zainal Ariffin, Shahrul Hisham; Karsani, Saiful Anuar; Abdul Rahman, Mariati; Senafi, Shahidan; Megat Abdul Wahab, Rohaya

    2012-01-01

    Orthodontic treatment has been shown to induce inflammation, followed by bone remodelling in the periodontium. These processes trigger the secretion of various proteins and enzymes into the saliva. This study aims to identify salivary proteins that change in expression during orthodontic tooth movement. These differentially expressed proteins can potentially serve as protein biomarkers for the monitoring of orthodontic treatment and tooth movement. Whole saliva from three healthy female subjects were collected before force application using fixed appliance and at 14 days after 0.014′′ Niti wire was applied. Salivary proteins were resolved using two-dimensional gel electrophoresis (2DE) over a pH range of 3–10, and the resulting proteome profiles were compared. Differentially expressed protein spots were then identified by MALDI-TOF/TOF tandem mass spectrometry. Nine proteins were found to be differentially expressed; however, only eight were identified by MALDI-TOF/TOF. Four of these proteins—Protein S100-A9, immunoglobulin J chain, Ig alpha-1 chain C region, and CRISP-3—have known roles in inflammation and bone resorption. PMID:22919344

  3. Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma.

    Science.gov (United States)

    Wan, Qi; Tang, Jing; Han, Yu; Wang, Dan

    2018-01-01

    Uveal melanoma is an aggressive cancer which has a high percentage recurrence and with a worse prognosis. Identify the potential prognostic markers of uveal melanoma may provide information for early detection of recurrence and treatment. RNA sequence data of uveal melanoma and patient clinic traits were obtained from The Cancer Genome Atlas (TCGA) database. Co-expression modules were built by weighted gene co -expression network analysis (WGCNA) and applied to investigate the relationship underlying modules and clinic traits. Besides, functional enrichment analysis was performed on these co-expression genes from interested modules. First, using WGCNA, identified 21 co-expression modules were constructed by the 10975 genes from the 80 human uveal melanoma samples. The number of genes in these modules ranged from 42 to 5091. Found four co -expression modules significantly correlated with three clinic traits (status, recurrence and recurrence Time). Module red, and purple positively correlated with patient's life status and recurrence Time. Module green positively correlates with recurrence. The result of functional enrichment analysis showed that the module magenta was mainly enriched genetic material assemble processes, the purple module was mainly enriched in tissue homeostasis and melanosome membrane and the module red was mainly enriched metastasis of cell, suggesting its critical role in the recurrence and development of the disease. Additionally, identified the hug gene (top connectivity with other genes) in each module. The hub gene SLC17A7, NTRK2, ABTB1 and ADPRHL1 might play a vital role in recurrence of uveal melanoma. Our findings provided the framework of co-expression gene modules of uveal melanoma and identified some prognostic markers might be detection of recurrence and treatment for uveal melanoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  5. Potentially preventable infant and child deaths identified at autopsy; findings and implications.

    Science.gov (United States)

    Bamber, Andrew R; Mifsud, William; Wolfe, Ingrid; Cass, Hilary; Pryce, Jeremy; Malone, Marian; Sebire, Neil J

    2015-09-01

    The purpose of the study was to determine the proportion of pediatric deaths investigated by HM Coronial autopsy which were potentially preventable deaths due to treatable natural disease, and what implications such findings may have for health policies to reduce their occurrence. A retrospective study of 1779 autopsies of individuals between 7 days and 14 years of age requested by HM Coroner, taking place in one specialist pediatric autopsy center, was undertaken. Cases were included if they involved a definite natural disease process in which appropriate recognition and treatment was likely to have affected their outcome. Strict criteria were used and cases were excluded where the individual had any longstanding condition which might have predisposed them to, or altered the recognition of, acute illness, or its response to therapy. Almost 8% (134/1779) of the study group were potentially preventable deaths as a result of natural disease, the majority occurring in children younger than 2 years of age. Most individuals reported between 1 and 7 days of symptoms before their death, and the majority had sought medical advice during this period, including from general practitioners within working hours, and hospital emergency departments. Of those who had sought medical attention, around one-third had done so more than once (28%, 15/53). Sepsis and pneumonia accounted for the majority of deaths (46 and 34% respectively), with all infections (sepsis, pneumonia and meningitis) accounting for 110/134 (82%). Around 10% of pediatric deaths referred to HM Coroner are potentially preventable, being the result of treatable natural acute illnesses. In many cases medical advice had been sought during the final illness. The results highlight how a review of autopsy data can identify significant findings with the potential to reduce mortality, and the importance of centralized investigation and reporting of pediatric deaths.

  6. Potential Coastal Pumped Hydroelectric Energy Storage Locations Identified using GIS-based Topographic Analysis

    Science.gov (United States)

    Parsons, R.; Barnhart, C. J.; Benson, S. M.

    2013-12-01

    Large-scale electrical energy storage could accommodate variable, weather dependent energy resources such as wind and solar. Pumped hydroelectric energy storage (PHS) and compressed energy storage area (CAES) have life cycle energy and financial costs that are an order of magnitude lower than conventional electrochemical storage technologies. However PHS and CAES storage technologies require specific geologic conditions. Conventional PHS requires an upper and lower reservoir separated by at least 100 m of head, but no more than 10 km in horizontal distance. Conventional PHS also impacts fresh water supplies, riparian ecosystems, and hydrologic environments. A PHS facility that uses the ocean as the lower reservoir benefits from a smaller footprint, minimal freshwater impact, and the potential to be located near off shore wind resources and population centers. Although technologically nascent, today one coastal PHS facility exists. The storage potential for coastal PHS is unknown. Can coastal PHS play a significant role in augmenting future power grids with a high faction of renewable energy supply? In this study we employ GIS-based topographic analysis to quantify the coastal PHS potential of several geographic locations, including California, Chile and Peru. We developed automated techniques that seek local topographic minima in 90 m spatial resolution shuttle radar topography mission (SRTM) digital elevation models (DEM) that satisfy the following criteria conducive to PHS: within 10 km from the sea; minimum elevation 150 m; maximum elevation 1000 m. Preliminary results suggest the global potential for coastal PHS could be very significant. For example, in northern Chile we have identified over 60 locations that satisfy the above criteria. Two of these locations could store over 10 million cubic meters of water or several GWh of energy. We plan to report a global database of candidate coastal PHS locations and to estimate their energy storage capacity.

  7. 5' Region of the human interleukin 4 gene: structure and potential regulatory elements

    Energy Technology Data Exchange (ETDEWEB)

    Eder, A; Krafft-Czepa, H; Krammer, P H

    1988-01-25

    The lymphokine Interleukin 4 (IL-4) is secreted by antigen or mitogen activated T lymphocytes. IL-4 stimulates activation and differentiation of B lymphocytes and growth of T lymphocytes and mast cells. The authors isolated the human IL-4 gene from a lambda EMBL3 genomic library. As a probe they used a synthetic oligonucleotide spanning position 40 to 79 of the published IL-4 cDNA sequence. The 5' promoter region contains several sequence elements which may have a cis-acting regulatory function for IL-4 gene expression. These elements include a TATA-box, three CCAAT-elements (two are on the non-coding strand) and an octamer motif. A comparison of the 5' flanking region of the human murine IL-4 gene (4) shows that the region between position -306 and +44 is highly conserved (83% homology).

  8. pH-Regulatory Proteins as Potential Targets in Breast Cancer

    DEFF Research Database (Denmark)

    Andersen, Anne Poder

    tissues. The focus of the present PhD study is on understanding the mechanisms through which pH-regulatory transporters are regulated by the breast tumor microenvironment, and how these transporters in turn favor cancer progression. In Paper I, we summarized the recent knowledge on the dynamic...... exhibit distinct spatial organization during 3D growth of MCF-7 and MDA-MB-231 breast cancer cells. By pharmacological inhibition and stable shRNA-mediated knockdown, we addressed the specific contributions of the transporters to spheroid growth and show that the specific transporters contribute to breast...... development in the more complex in vivo setting. In Paper III, we found that chemical induction of breast cancer in NBCn1 knockout (KO) mice is delayed and tumor growth rates reduced, compared to those in wildtype (WT) mice, demonstrating a causal link between NBCn1 and breast cancer development. In Paper IV...

  9. USING GIS TO IDENTIFY POTENTIAL AREAS SUSCEPTIBLE TO FLOOD. CASE STUDY: SOLONEŢ RIVER

    Directory of Open Access Journals (Sweden)

    V. TIPLEA

    2011-03-01

    Full Text Available Using GIS to Identify Potential Areas Susceptible to Flood. Case Study: Soloneţ River. In this study, we aim to analyze the impact of different peak flows in territory and also a better understanding of the dynamic of a river flow. The methodology used for flood zone delimitation is based on a quantitative analysis model which requires the use of mathematical, physical and statistical operations in order to emphasize the relations between the different variables that were implied (discharges, grain size, terrain morphology, soil saturation, vegetation etc.. The results cannot be expected to be completely accurate but can provide a good representation of the process. Validation of results will inevitably be difficult and should be measured in the field. The information resulting from this study could be useful for raising awareness about both hazards and possible mitigation measure, a key component of disaster risk reduction planning.

  10. Identifying potential sources of Sudan I contamination in Capsicum fruits over its growth period.

    Science.gov (United States)

    Wu, Naiying; Gao, Wei; Zhou, Li; Lian, Yunhe; Li, Fengfei; Han, Wenjie

    2015-04-15

    Sudan dyes in spices are often assumed to arise from cross-contamination or malicious addition. Here, experiments were carried out to identify the potential source of Sudan I-IV in Capsicum fruits through investigation of their contents in native Capsicum tissues, soils and associated agronomic materials. Sudan II-IV was not detected in any of the tested samples. Sudan I was found in almost all samples except for the mulching film. Sudan I concentrations decreased from stems to leaves and then to fruits or roots. Sudan I levels in soils were significantly elevated by vegetation treatment. These results exclude the possibility of soil as the main source for Sudan I contamination in Capsicum fruits. Further study found out pesticide and fertilizer constitutes the major source of Sudan I contamination. This work represents a preliminary step for a detailed Sudan I assessment to support Capsicum management and protection in the studied region. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A new simplex chemometric approach to identify olive oil blends with potentially high traceability.

    Science.gov (United States)

    Semmar, N; Laroussi-Mezghani, S; Grati-Kamoun, N; Hammami, M; Artaud, J

    2016-10-01

    Olive oil blends (OOBs) are complex matrices combining different cultivars at variable proportions. Although qualitative determinations of OOBs have been subjected to several chemometric works, quantitative evaluations of their contents remain poorly developed because of traceability difficulties concerning co-occurring cultivars. Around this question, we recently published an original simplex approach helping to develop predictive models of the proportions of co-occurring cultivars from chemical profiles of resulting blends (Semmar & Artaud, 2015). Beyond predictive model construction and validation, this paper presents an extension based on prediction errors' analysis to statistically define the blends with the highest predictability among all the possible ones that can be made by mixing cultivars at different proportions. This provides an interesting way to identify a priori labeled commercial products with potentially high traceability taking into account the natural chemical variability of different constitutive cultivars. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Gut Bacteria Missing in Severe Acute Malnutrition, Can We Identify Potential Probiotics by Culturomics?

    Directory of Open Access Journals (Sweden)

    Maryam Tidjani Alou

    2017-05-01

    Full Text Available Severe acute malnutrition is the world-leading cause of children under-five's death. Recent metagenomics studies have established a link between gut microbiota and severe acute malnutrition, describing an immaturity with a striking depletion in oxygen-sensitive prokaryotes. Amoxicillin and therapeutic diet cure most of the children with severe acute malnutrition but an irreversible disruption of the gut microbiota is suspected in the refractory and most severe cases. In these cases, therapeutic diet may be unable to reverse the microbiota alteration leading to persistent impaired development or death. In addition, as enteric sepsis is a major cause of death in this context, identification of missing gut microbes to be tested as probiotics (live bacteria that confer a benefit to the host to restore rapidly the healthy gut microbiota and prevent the gut pathogenic invasion is of foremost importance. In this study, stool samples of malnourished patients with kwashiorkor and healthy children were collected from Niger and Senegal and analyzed by culturomics and metagenomics. We found a globally decreased diversity, a decrease in the hitherto unknown diversity (new species isolation, a depletion in oxygen-sensitive prokaryotes including Methanobrevibacter smithii and an enrichment in potentially pathogenic Proteobacteria, Fusobacteria and Streptococcus gallolyticus. A complex of 12 species identified only in healthy children using culturomics and metagenomics were identified as probiotics candidates, providing a possible, defined, reproducible, safe, and convenient alternative to fecal transplantation to restore a healthy gut microbiota in malnourished children. Microbiotherapy based on selected strains has the potential to improve the current treatment of severe acute malnutrition and prevent relapse and death by reestablishing a healthy gut microbiota.

  13. TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

    Energy Technology Data Exchange (ETDEWEB)

    Das, I. [NYU Langone Medical Center, New York, NY (United States)

    2016-06-15

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.

  14. TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

    International Nuclear Information System (INIS)

    Das, I.

    2016-01-01

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803

  15. Identifying potentially cost effective chronic care programs for people with COPD

    Directory of Open Access Journals (Sweden)

    L M G Steuten

    2008-12-01

    Full Text Available L M G Steuten1, K M M Lemmens2, A P Nieboer2, H JM Vrijhoef31Maastricht University Medical Centre, School for Care and Public Health Research, Department of Health, Organisation, Policy and Economics, Maastricht, The Netherlands; 2Erasmus University Medical Centre, Institute of Health Policy and Management, Rotterdam, The Netherlands; 3Maastricht University Medical Centre, School for Care and Public Health Research, Department of Integrated Care, Maastricht, The NetherlandsObjective: To review published evidence regarding the cost effectiveness of multi-component COPD programs and to illustrate how potentially cost effective programs can be identified.Methods: Systematic search of Medline and Cochrane databases for evaluations of multi-component disease management or chronic care programs for adults with COPD, describing process, intermediate, and end results of care. Data were independently extracted by two reviewers and descriptively summarized.Results: Twenty articles describing 17 unique COPD programs were included. There is little evidence for significant improvements in process and intermediate outcomes, except for increased provision of patient self-management education and improved disease-specific knowledge. Overall, the COPD programs generate end results equivalent to usual care, but programs containing ≥3 components show lower relative risks for hospitalization. There is limited scope for programs to break-even or save money.Conclusion: Identifying cost effective multi-component COPD programs remains a challenge due to scarce methodologically sound studies that demonstrate significant improvements on process, intermediate and end results of care. Estimations of potential cost effectiveness of specific programs illustrated in this paper can, in the absence of ‘perfect data’, support timely decision-making regarding these programs. Nevertheless, well-designed health economic studies are needed to decrease the current decision

  16. Practical In-Depth Analysis of IDS Alerts for Tracing and Identifying Potential Attackers on Darknet

    Directory of Open Access Journals (Sweden)

    Jungsuk Song

    2017-02-01

    Full Text Available The darknet (i.e., a set of unused IP addresses is a very useful solution for observing the global trends of cyber threats and analyzing attack activities on the Internet. Since the darknet is not connected with real systems, in most cases, the incoming packets on the darknet (‘the darknet traffic’ do not contain a payload. This means that we are unable to get real malware from the darknet traffic. This situation makes it difficult for security experts (e.g., academic researchers, engineers, operators, etc. to identify whether the source hosts of the darknet traffic are infected by real malware or not. In this paper, we present the overall procedure of the in-depth analysis between the darknet traffic and IDS alerts using real data collected at the Science and Technology Cyber Security Center (S&T CSC in Korea and provide the detailed in-depth analysis results. The ultimate goal of this paper is to provide practical experience, insight and know-how to security experts so that they are able to identify and trace the root cause of the darknet traffic. The experimental results show that correlation analysis between the darknet traffic and IDS alerts is very useful to discover potential attack hosts, especially internal hosts, and to find out what kinds of malware infected them.

  17. Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

    Science.gov (United States)

    Rodriguez-Flores, Juan L.; Fakhro, Khalid; Hackett, Neil R.; Salit, Jacqueline; Fuller, Jennifer; Agosto-Perez, Francisco; Gharbiah, Maey; Malek, Joel A.; Zirie, Mahmoud; Jayyousi, Amin; Badii, Ramin; Al-Marri, Ajayeb Al-Nabet; Chouchane, Lotfi; Stadler, Dora J.; Hunter-Zinck, Haley; Mezey, Jason G.; Crystal, Ronald G.

    2013-01-01

    Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared to 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Pre-marital genetic screening in Qatar tests for only 4 out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance. PMID:24123366

  18. Identifying potential misfit items in cognitive process of learning engineering mathematics based on Rasch model

    International Nuclear Information System (INIS)

    Ataei, Sh; Mahmud, Z; Khalid, M N

    2014-01-01

    The students learning outcomes clarify what students should know and be able to demonstrate after completing their course. So, one of the issues on the process of teaching and learning is how to assess students' learning. This paper describes an application of the dichotomous Rasch measurement model in measuring the cognitive process of engineering students' learning of mathematics. This study provides insights into the perspective of 54 engineering students' cognitive ability in learning Calculus III based on Bloom's Taxonomy on 31 items. The results denote that some of the examination questions are either too difficult or too easy for the majority of the students. This analysis yields FIT statistics which are able to identify if there is data departure from the Rasch theoretical model. The study has identified some potential misfit items based on the measurement of ZSTD where the removal misfit item was accomplished based on the MNSQ outfit of above 1.3 or less than 0.7 logit. Therefore, it is recommended that these items be reviewed or revised to better match the range of students' ability in the respective course.

  19. Application of positive matrix factorization to identify potential sources of PAHs in soil of Dalian, China

    International Nuclear Information System (INIS)

    Wang Degao; Tian Fulin; Yang Meng; Liu Chenlin; Li Yifan

    2009-01-01

    Soil derived sources of polycyclic aromatic hydrocarbons (PAHs) in the region of Dalian, China were investigated using positive matrix factorization (PMF). Three factors were separated based on PMF for the statistical investigation of the datasets both in summer and winter. These factors were dominated by the pattern of single sources or groups of similar sources, showing seasonal and regional variations. The main sources of PAHs in Dalian soil in summer were the emissions from coal combustion average (46%), diesel engine (30%), and gasoline engine (24%). In winter, the main sources were the emissions from coal-fired boiler (72%), traffic average (20%), and gasoline engine (8%). These factors with strong seasonality indicated that coal combustion in winter and traffic exhaust in summer dominated the sources of PAHs in soil. These results suggested that PMF model was a proper approach to identify the sources of PAHs in soil. - PMF model is a proper approach to identify potential sources of PAHs in soil based on the PAH profiles measured in the field and those published in the literature.

  20. Omen: identifying potential spear-phishing targets before the email is sent.

    Energy Technology Data Exchange (ETDEWEB)

    Wendt, Jeremy Daniel.

    2013-07-01

    We present the results of a two year project focused on a common social engineering attack method called "spear phishing". In a spear phishing attack, the user receives an email with information specifically focused on the user. This email contains either a malware-laced attachment or a link to download the malware that has been disguised as a useful program. Spear phishing attacks have been one of the most effective avenues for attackers to gain initial entry into a target network. This project focused on a proactive approach to spear phishing. To create an effective, user-specific spear phishing email, the attacker must research the intended recipient. We believe that much of the information used by the attacker is provided by the target organization's own external website. Thus when researching potential targets, the attacker leaves signs of his research in the webserver's logs. We created tools and visualizations to improve cybersecurity analysts' abilities to quickly understand a visitor's visit patterns and interests. Given these suspicious visitors and log-parsing tools, analysts can more quickly identify truly suspicious visitors, search for potential spear-phishing targeted users, and improve security around those users before the spear phishing email is sent.

  1. Predicting Fish Growth Potential and Identifying Water Quality Constraints: A Spatially-Explicit Bioenergetics Approach

    Science.gov (United States)

    Budy, Phaedra; Baker, Matthew; Dahle, Samuel K.

    2011-10-01

    Anthropogenic impairment of water bodies represents a global environmental concern, yet few attempts have successfully linked fish performance to thermal habitat suitability and fewer have distinguished co-varying water quality constraints. We interfaced fish bioenergetics, field measurements, and Thermal Remote Imaging to generate a spatially-explicit, high-resolution surface of fish growth potential, and next employed a structured hypothesis to detect relationships among measures of fish performance and co-varying water quality constraints. Our thermal surface of fish performance captured the amount and spatial-temporal arrangement of thermally-suitable habitat for three focal species in an extremely heterogeneous reservoir, but interpretation of this pattern was initially confounded by seasonal covariation of water residence time and water quality. Subsequent path analysis revealed that in terms of seasonal patterns in growth potential, catfish and walleye responded to temperature, positively and negatively, respectively; crappie and walleye responded to eutrophy (negatively). At the high eutrophy levels observed in this system, some desired fishes appear to suffer from excessive cultural eutrophication within the context of elevated temperatures whereas others appear to be largely unaffected or even enhanced. Our overall findings do not lead to the conclusion that this system is degraded by pollution; however, they do highlight the need to use a sensitive focal species in the process of determining allowable nutrient loading and as integrators of habitat suitability across multiple spatial and temporal scales. We provide an integrated approach useful for quantifying fish growth potential and identifying water quality constraints on fish performance at spatial scales appropriate for whole-system management.

  2. Development of a predictive methodology for identifying high radon exhalation potential areas

    International Nuclear Information System (INIS)

    Ielsch, G.

    2001-01-01

    Radon 222 is a radioactive natural gas originating from the decay of radium 226 which itself originates from the decay of uranium 23 8 naturally present in rocks and soil. Inhalation of radon gas and its decay products is a potential health risk for man. Radon can accumulate in confined environments such as buildings, and is responsible for one third of the total radiological exposure of the general public to radiation. The problem of how to manage this risk then arises. The main difficulty encountered is due to the large variability of exposure to radon across the country. A prediction needs to be made of areas with the highest density of buildings with high radon levels. Exposure to radon varies depending on the degree of confinement of the habitat, the lifestyle of the occupants and particularly emission of radon from the surface of the soil on which the building is built. The purpose of this thesis is to elaborate a methodology for determining areas presenting a high potential for radon exhalation at the surface of the soil. The methodology adopted is based on quantification of radon exhalation at the surface, starting from a precise characterization of the main local geological and pedological parameters that control the radon source and its transport to the ground/atmosphere interface. The methodology proposed is innovative in that it combines a cartographic analysis, parameters integrated into a Geographic Information system, and a simplified model for vertical transport of radon by diffusion through pores in the soil. This methodology has been validated on two typical areas, in different geological contexts, and gives forecasts that generally agree with field observations. This makes it possible to identify areas with a high exhalation potential within a range of a few square kilometers. (author)

  3. Exploring the e-cigarette e-commerce marketplace: Identifying Internet e-cigarette marketing characteristics and regulatory gaps.

    Science.gov (United States)

    Mackey, Tim K; Miner, Angela; Cuomo, Raphael E

    2015-11-01

    The electronic cigarette (e-cigarette) market is maturing into a billion-dollar industry. Expansion includes new channels of access not sufficiently assessed, including Internet sales of e-cigarettes. This study identifies unique e-cigarette Internet vendor characteristics, including geographic location, promotional strategies, use of social networking, presence/absence of age verification, and consumer warning representation. We performed structured Internet search engine queries and used inclusion/exclusion criteria to identify e-cigarette vendors. We then conducted content analysis of characteristics of interest. Our examination yielded 57 e-cigarette Internet vendors including 54.4% (n=31) that sold exclusively online. The vast majority of websites (96.5%, n=55) were located in the U.S. Vendors used a variety of sales promotion strategies to market e-cigarettes including 70.2% (n=40) that used more than one social network service (SNS) and 42.1% (n=24) that used more than one promotional sales strategies. Most vendors (68.4%, n=39) displayed one or more health warnings on their website, but often displayed them in smaller font or in their terms and conditions. Additionally, 35.1% (n=20) of vendors did not have any detectable age verification process. E-cigarette Internet vendors are actively engaged in various promotional activities to increase the appeal and presence of their products online. In the absence of FDA regulations specific to the Internet, the e-cigarette e-commerce marketplace is likely to grow. This digital environment poses unique challenges requiring targeted policy-making including robust online age verification, monitoring of SNS marketing, and greater scrutiny of certain forms of marketing promotional practices. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Potential new regulatory options for e-cigarettes in New Zealand.

    Science.gov (United States)

    Wilson, Nick; Edwards, Richard; Hoek, Janet; Thomson, George; Blakely, Tony; van der Deen, Frederieke Sanne; Crane, Julian

    2015-11-20

    While e-cigarette usage has grown rapidly in New Zealand and around the world, the scientific evidence base regarding the net benefits and risks of these types of products at the population level remains uncertain. The health-based policy experience is also minimal. Here, we analyse plausible future regulatory options for e-cigarettes that the New Zealand Government could explore, and that further research could help clarify. These options include: (1) a full free market (an option we doubt is desirable for multiple reasons); (2) controlled increased access through: (a) pharmacy only, (b) pharmacy only plus sales by prescription/ to licensed vapers; (c) additional controls through non-profit supply/distribution (eg, public hospital pharmacies); (3) increased restrictions compared with current (eg, adopting a complete ban on self-imports and use). In addition, we consider mechanisms to improve product quality and safety, and argue that policy makers should take great care when regulating e-cigarettes, given the scientific uncertainty and the role of commercial vested interests.

  5. The potential regulatory roles of NAD(+) and its metabolism in autophagy.

    Science.gov (United States)

    Zhang, Dong-Xia; Zhang, Jia-Ping; Hu, Jiong-Yu; Huang, Yue-Sheng

    2016-04-01

    (Macro)autophagy mediates the bulk degradation of defective organelles, long-lived proteins and protein aggregates in lysosomes and plays a critical role in cellular and tissue homeostasis. Defective autophagy processes have been found to contribute to a variety of metabolic diseases. However, the regulatory mechanisms of autophagy are not fully understood. Increasing data indicate that nicotinamide adenine nucleotide (NAD(+)) homeostasis correlates intimately with autophagy. NAD(+) is a ubiquitous coenzyme that functions primarily as an electron carrier of oxidoreductase in multiple redox reactions. Both NAD(+) homeostasis and its metabolism are thought to play critical roles in regulating autophagy. In this review, we discuss how the regulation of NAD(+) and its metabolism can influence autophagy. We focus on the regulation of NAD(+)/NADH homeostasis and the effects of NAD(+) consumption by poly(ADP-ribose) (PAR) polymerase-1 (PARP-1), NAD(+)-dependent deacetylation by sirtuins and NAD(+) metabolites on autophagy processes and the underlying mechanisms. Future studies should provide more direct evidence for the regulation of autophagy processes by NAD(+). A better understanding of the critical roles of NAD(+) and its metabolites on autophagy will shed light on the complexity of autophagy regulation, which is essential for the discovery of new therapeutic tools for autophagy-related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Developing tools to identify marginal lands and assess their potential for bioenergy production

    Science.gov (United States)

    Galatsidas, Spyridon; Gounaris, Nikolaos; Dimitriadis, Elias; Rettenmaier, Nils; Schmidt, Tobias; Vlachaki, Despoina

    2017-04-01

    The term "marginal land" is currently intertwined in discussions about bioenergy although its definition is neither specific nor firm. The uncertainty arising from marginal land classification and quantification is one of the major constraining factors for its potential use. The clarification of political aims, i.e. "what should be supported?" is also an important constraining factor. Many approaches have been developed to identify marginal lands, based on various definitions according to the management goals. Concerns have been frequently raised regarding the impacts of marginal land use on environment, ecosystem services and sustainability. Current tools of soil quality and land potentials assessment fail to meet the needs of marginal land identification and exploitation for biomass production, due to the lack of comprehensive analysis of interrelated land functions and their quantitative evaluation. Land marginality is determined by dynamic characteristics in many cases and may therefore constitute a transitional state, which requires reassessment in due time. Also, marginal land should not be considered simply a dormant natural resource waiting to be used, since it may already provide multiple benefits and services to society relating to wildlife, biodiversity, carbon sequestration, etc. The consequences of cultivating such lands need to be fully addressed to present a balanced view of their sustainable potential for bioenergy. This framework is the basis for the development of the SEEMLA tools, which aim at supporting the identification, assessment, management of marginal lands in Europe and the decision-making for sustainable biomass production of them using appropriate bioenergy crops. The tools comprise two applications, a web-based one (independent of spatial data) and a GIS-based application (land regionalization on the basis of spatial data), which both incorporate: - Land resource characteristics, restricting the cultivation of agricultural crops but

  7. Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus.

    Directory of Open Access Journals (Sweden)

    Alison P Lee

    Full Text Available The vertebrate Lhx2 is a member of the LIM homeobox family of transcription factors. It is essential for the normal development of the forebrain, eye, olfactory system and liver as well for the differentiation of lymphoid cells. However, despite the highly restricted spatio-temporal expression pattern of Lhx2, nothing is known about its transcriptional regulation. In mammals and chicken, Crb2, Dennd1a and Lhx2 constitute a conserved linkage block, while the intervening Dennd1a is lost in the fugu Lhx2 locus. To identify functional enhancers of Lhx2, we predicted conserved noncoding elements (CNEs in the human, mouse and fugu Crb2-Lhx2 loci and assayed their function in transgenic mouse at E11.5. Four of the eight CNE constructs tested functioned as tissue-specific enhancers in specific regions of the central nervous system and the dorsal root ganglia (DRG, recapitulating partial and overlapping expression patterns of Lhx2 and Crb2 genes. There was considerable overlap in the expression domains of the CNEs, which suggests that the CNEs are either redundant enhancers or regulating different genes in the locus. Using a large set of CNEs (810 CNEs associated with transcription factor-encoding genes that express predominantly in the central nervous system, we predicted four over-represented 8-mer motifs that are likely to be associated with expression in the central nervous system. Mutation of one of them in a CNE that drove reporter expression in the neural tube and DRG abolished expression in both domains indicating that this motif is essential for expression in these domains. The failure of the four functional enhancers to recapitulate the complete expression pattern of Lhx2 at E11.5 indicates that there must be other Lhx2 enhancers that are either located outside the region investigated or divergent in mammals and fishes. Other approaches such as sequence comparison between multiple mammals are required to identify and characterize such enhancers.

  8. Assessing urban potential flooding risk and identifying effective risk-reduction measures.

    Science.gov (United States)

    Cherqui, Frédéric; Belmeziti, Ali; Granger, Damien; Sourdril, Antoine; Le Gauffre, Pascal

    2015-05-01

    Flood protection is one of the traditional functions of any drainage system, and it remains a major issue in many cities because of economic and health impact. Heavy rain flooding has been well studied and existing simulation software can be used to predict and improve level of protection. However, simulating minor flooding remains highly complex, due to the numerous possible causes related to operational deficiencies or negligent behaviour. According to the literature, causes of blockages vary widely from one case to another: it is impossible to provide utility managers with effective recommendations on how to improve the level of protection. It is therefore vital to analyse each context in order to define an appropriate strategy. Here we propose a method to represent and assess the flooding risk, using GIS and data gathered during operation and maintenance. Our method also identifies potential management responses. The approach proposed aims to provide decision makers with clear and comprehensible information. Our method has been successfully applied to the Urban Community of Bordeaux (France) on 4895 interventions related to flooding recorded during the 2009-2011 period. Results have shown the relative importance of different issues, such as human behaviour (grease, etc.) or operational deficiencies (roots, etc.), and lead to identify corrective and proactive. This study also confirms that blockages are not always directly due to the network itself and its deterioration. Many causes depend on environmental and operating conditions on the network and often require collaboration between municipal departments in charge of roads, green spaces, etc. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Visual Indicators on Vaccine Boxes as Early Warning Tools to Identify Potential Freeze Damage.

    Science.gov (United States)

    Angoff, Ronald; Wood, Jillian; Chernock, Maria C; Tipping, Diane

    2015-07-01

    The aim of this study was to determine whether the use of visual freeze indicators on vaccines would assist health care providers in identifying vaccines that may have been exposed to potentially damaging temperatures. Twenty-seven sites in Connecticut involved in the Vaccine for Children Program participated. In addition to standard procedures, visual freeze indicators (FREEZEmarker ® L; Temptime Corporation, Morris Plains, NJ) were affixed to each box of vaccine that required refrigeration but must not be frozen. Temperatures were monitored twice daily. During the 24 weeks, all 27 sites experienced triggered visual freeze indicator events in 40 of the 45 refrigerators. A total of 66 triggered freeze indicator events occurred in all 4 types of refrigerators used. Only 1 of the freeze events was identified by a temperature-monitoring device. Temperatures recorded on vaccine data logs before freeze indicator events were within the 35°F to 46°F (2°C to 8°C) range in all but 1 instance. A total of 46,954 doses of freeze-sensitive vaccine were stored at the time of a visual freeze indicator event. Triggered visual freeze indicators were found on boxes containing 6566 doses (14.0% of total doses). Of all doses stored, 14,323 doses (30.5%) were of highly freeze-sensitive vaccine; 1789 of these doses (12.5%) had triggered indicators on the boxes. Visual freeze indicators are useful in the early identification of freeze events involving vaccines. Consideration should be given to including these devices as a component of the temperature-monitoring system for vaccines.

  10. Prediction of regulatory elements

    DEFF Research Database (Denmark)

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

  11. Chimeric exchange of coronavirus nsp5 proteases (3CLpro) identifies common and divergent regulatory determinants of protease activity.

    Science.gov (United States)

    Stobart, Christopher C; Sexton, Nicole R; Munjal, Havisha; Lu, Xiaotao; Molland, Katrina L; Tomar, Sakshi; Mesecar, Andrew D; Denison, Mark R

    2013-12-01

    Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of severe human respiratory disease. A conserved step of CoV replication is the translation and processing of replicase polyproteins containing 16 nonstructural protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a conserved 3-domain structure and catalytic residues. However, the intra- and intermolecular determinants of nsp5 activity and their conservation across divergent CoVs are unknown, in part due to challenges in cultivating many human and zoonotic CoVs. To test for conservation of nsp5 structure-function determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV) genomes encoding nsp5 proteases of human and bat alphacoronaviruses and betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral recovery with efficient replication albeit with impaired fitness in direct competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear differences in viability and temperature-sensitive phenotypes compared with MHV nsp5. These data indicate tight genetic linkage and coevolution between nsp5 protease and the genomic background and identify differences in intramolecular networks regulating nsp5 function. Our results also provide evidence that chimeric viruses within coronavirus genogroups can be used to test nsp5 determinants of function and inhibition in common isogenic backgrounds and cell types.

  12. 40 CFR Table 5 to Subpart Jj of... - List of VHAP of Potential Concern Identified by Industry

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 10 2010-07-01 2010-07-01 false List of VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION.... 63, Subpt. JJ, Table 5 Table 5 to Subpart JJ of Part 63—List of VHAP of Potential Concern Identified...

  13. Genome-Wide Analysis to Identify HLA Factors Potentially Associated With Severe Dengue

    Directory of Open Access Journals (Sweden)

    Sudheer Gupta

    2018-04-01

    Full Text Available The pathogenesis of dengue hemorrhagic fever (DHF, following dengue virus (DENV infection, is a complex and poorly understood phenomenon. In view of the clinical need of identifying patients with higher likelihood of developing this severe outcome, we undertook a comparative genome-wide association analysis of epitope variants from sequences available in the ViPR database that have been reported to be differentially related to dengue fever and DHF. Having enumerated the incriminated epitope variants, we determined the corresponding HLA alleles in the context of which DENV infection could potentially precipitate DHF. Our analysis considered the development of DHF in three different perspectives: (a as a consequence of primary DENV infection, (b following secondary DENV infection with a heterologous serotype, (c as a result of DENV infection following infection with related flaviviruses like Zika virus, Japanese Encephalitis virus, West Nile virus, etc. Subject to experimental validation, these viral and host markers would be valuable in triaging DENV-infected patients for closer supervision owing to the relatively higher risk of poor prognostic outcome and also for the judicious allocation of scarce institutional resources during large outbreaks.

  14. New approaches for identifying and testing potential new anti-asthma agents.

    Science.gov (United States)

    Licari, Amelia; Castagnoli, Riccardo; Brambilla, Ilaria; Marseglia, Alessia; Tosca, Maria Angela; Marseglia, Gian Luigi; Ciprandi, Giorgio

    2018-01-01

    Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities. Areas covered: The expanding knowledge on the pathogenetic mechanisms of asthma has allowed researchers to investigate a range of new treatment options matched to patient profiles. The aim of this review is to provide a comprehensive and updated overview of the currently available, new and developing approaches for identifying and testing potential treatment options for asthma management. Expert opinion: Future therapeutic strategies for asthma require the identification of reliable biomarkers that can help with diagnosis and endotyping, in order to determine the most effective drug for the right patient phenotype. Furthermore, in addition to the identification of clinical and inflammatory phenotypes, it is expected that a better understanding of the mechanisms of airway remodeling will likely optimize asthma targeted treatment.

  15. Identifying areas under potential risk of illegal construction and demolition waste dumping using GIS tools.

    Science.gov (United States)

    Seror, Nissim; Portnov, Boris A

    2018-05-01

    Construction and demolition (C&D) waste, dumped illegally in ravines and open areas, contaminates soil and can cause underground water pollution and forests fires. Yet, effective monitoring of illegal C&D waste dumping and enforcing legislation against the offenders are often a difficult task due to the large size of geographic areas that need to be monitored, and limited human and financial resources available to environmental law enforcement agencies. In this study, we use Geographic Information System (GIS) tools and geo-statistical modelling to identify the areas under potentially elevated risk of illegal C&D waste dumping in the Haifa district of Israel. As our analysis shows, locational factors, significantly associated with the accumulated amount of waste in the existing illegal C&D waste sites, include: distance to the nearest main road, depth of the ravine present at the site (pwaste dumping for future monitoring. As we suggest, the proposed approach may be useful for environmental law enforcement authorities, by helping them to focus on specific sites for inspection, save resources, and act against the offenders more efficiently. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma.

    Science.gov (United States)

    Arora, Shilpi; Gonzales, Irma M; Hagelstrom, R Tanner; Beaudry, Christian; Choudhary, Ashish; Sima, Chao; Tibes, Raoul; Mousses, Spyro; Azorsa, David O

    2010-08-18

    Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma.

  17. Nanomaterial Categorization for Assessing Risk Potential to Faciliate Regulatory Decision-Making

    Science.gov (United States)

    For nanotechnology to meet its potential as a game-changing and sustainable technology, it is important to ensure that the engineered nanomaterials (ENMs) and nano-enabled products that gain entry to the marketplace are safe and effective. Tools and methods are needed for regul...

  18. A Literature Survey to Identify Potentially Volatile Iodine-Bearing Species Present in Off-Gas Streams

    Energy Technology Data Exchange (ETDEWEB)

    Bruffey, S. H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Spencer, B. B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Strachan, D. M. [Strata-G, Knoxville, TN (United States); Jubin, R. T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Soelberg, N. R. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Riley, B. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-06-30

    Four radionuclides have been identified as being sufficiently volatile in the reprocessing of nuclear fuel that their gaseous release needs to be controlled to meet regulatory requirements (Jubin et al. 2011, 2012). These radionuclides are 3H, 14C, 85Kr, and 129I. Of these, 129I has the longest half-life and potentially high biological impact. Accordingly, control of the release of 129I is most critical with respect to the regulations for the release of radioactive material in stack emissions. It is estimated that current EPA regulations (EPA 2010) would require any reprocessing plant in the United States to limit 129I release to less than 0.05 Ci/MTIHM for a typical fuel burnup of 55 gigawatt days per metric tonne (GWd/t) (Jubin 2011). The study of inorganic iodide in off-gas systems has been almost exclusively limited to I2 and the focus of organic iodide studies has been CH3I. In this document, we provide the results of an examination of publically available literature that is relevant to the presence and sources of both inorganic and organic iodine-bearing species in reprocessing plants. We especially focus on those that have the potential to be poorly sequestered with traditional capture methodologies. Based on the results of the literature survey and some limited thermodynamic modeling, the inorganic iodine species hypoiodous acid (HOI) and iodine monochloride (ICl) were identified as potentially low-sorbing iodine species that could present in off-gas systems. Organic species of interest included both short chain alkyl iodides such as methyl iodide (CH3I) and longer alkyl iodides up to iodododecane (C10H21I). It was found that fuel dissolution may provide conditions conducive to HOI formation and has been shown to result in volatile long-chain alkyl iodides, though these may not volatilize until later in the reprocessing sequence. Solvent extraction processes were found to be significant sources of various organic iodine-bearing species; formation of these

  19. Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.

    Science.gov (United States)

    Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A

    2016-07-27

    Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Enterococcus phages as potential tool for identifying sewage inputs in the Great Lakes region

    Science.gov (United States)

    Vijayavel, K.; Byappanahalli, Muruleedhara N.; Whitman, Richard L.; Ebdon, J.; Taylor, H.; Kashian, D.R.

    2014-01-01

    Bacteriophages are viruses living in bacteria that can be used as a tool to detect fecal contamination in surface waters around the world. However, the lack of a universal host strain makes them unsuitable for tracking fecal sources. We evaluated the suitability of two newly isolated Enterococcus host strains (ENT-49 and ENT-55) capable for identifying sewage contamination in impacted waters by targeting phages specific to these hosts. Both host strains were isolated from wastewater samples and identified as E. faecium by 16S rRNA gene sequencing. Occurrence of Enterococcus phages was evaluated in sewage samples (n = 15) from five wastewater treatment plants and in fecal samples from twenty-two species of wild and domesticated animals (individual samples; n = 22). Levels of Enterococcus phages, F + coliphages, Escherichia coli and enterococci were examined from four rivers, four beaches, and three harbors. Enterococcus phages enumeration was at similar levels (Mean = 6.72 Log PFU/100 mL) to F + coliphages in all wastewater samples, but were absent from all non-human fecal sources tested. The phages infecting Enterococcus spp. and F + coliphages were not detected in the river samples (detection threshold < 10 PFU/100 mL), but were present in the beach and harbor samples (range = 1.83 to 2.86 Log PFU/100 mL). Slightly higher concentrations (range = 3.22 to 3.69 Log MPN/100 mL) of E. coli and enterococci when compared to F + coliphages and Enterococcus phages, were observed in the river, beach and harbor samples. Our findings suggest that the bacteriophages associated with these particular Enterococcus host strains offer potentially sensitive and human-source specific indicators of enteric pathogen risk.

  1. Defense Acquisitions: Antiarmor Munitions Master Plan Does Not Identify Potential Excesses or Support Planned Procurements

    National Research Council Canada - National Science Library

    2000-01-01

    .... According to the report, the plan should identify the projected armored threat and the projected quantity of all antiarmor weapons, whether fielded or in development, with the purpose of identifying...

  2. Multi-temporal terrestrial laser scanning for identifying rockslide modifications: potentialities and problems

    Science.gov (United States)

    Castagnetti, Cristina; Bertacchini, Eleonora; Capra, Alessandro; Rivola, Riccardo

    2013-04-01

    The heart of this research is to provide an efficient methodology for a reliable acquisition and interpretation of Terrestrial Laser Scanner (TLS) data in the application field of landslide monitoring. In particular, rockslides, which are characterized by vertical walls of rock and by a complex morphology, are of great concern in the study. In these cases the airborne laser scanning is not able to provide useful and reliable description and the terrestrial laser scanning might be the only possible choice to obtain a good and reliable description of the geomorphology or to identify the changes occurred over time. The last purpose is still a challenging task when long distances are involved because the accurate and punctual identification of displacements is not possible due to the laser beam divergence. The final purpose of the research is a proposal of a methodology which is based on TLS technology for identifying displacements and extracting geomorphological changes. The approach is clearly based on a multi-temporal analysis which is computed on several repetitions of TLS surveys performed on the area of interest. To achieve best results and optimize the processing strategy, different methods about point clouds alignment have been tested together with algorithms both for filtering and post-processing. The case study is the Collagna Landslide that is located in the North Appennines (Reggio Emilia, Italy) on the right flank of Biola torrent. The large scale composite landslide area is made both by a wide rock slide sector and a more limited earth slide sector that, after high precipitation rates, disrupted the National Road 63 in December 2008. An integrated monitoring system is installed since 2009 and comprises both point-based technologies such as extensometers, total station and global positioning system, and also area-based technologies such as airborne laser scanner, long-range TLS and ground-based radar. This choice allows to couple the advantages of both

  3. A spatial modeling approach to identify potential butternut restoration sites in Mammoth Cave National Park

    Science.gov (United States)

    Thompson, L.M.; Van Manen, F.T.; Schlarbaum, S.E.; DePoy, M.

    2006-01-01

    Incorporation of disease resistance is nearly complete for several important North American hardwood species threatened by exotic fungal diseases. The next important step toward species restoration would be to develop reliable tools to delineate ideal restoration sites on a landscape scale. We integrated spatial modeling and remote sensing techniques to delineate potential restoration sites for Butternut (Juglans cinerea L.) trees, a hardwood species being decimated by an exotic fungus, in Mammoth Cave National Park (MCNP), Kentucky. We first developed a multivariate habitat model to determine optimum Butternut habitats within MCNP. Habitat characteristics of 54 known Butternut locations were used in combination with eight topographic and land use data layers to calculate an index of habitat suitability based on Mahalanobis distance (D2). We used a bootstrapping technique to test the reliability of model predictions. Based on a threshold value for the D2 statistic, 75.9% of the Butternut locations were correctly classified, indicating that the habitat model performed well. Because Butternut seedlings require extensive amounts of sunlight to become established, we used canopy cover data to refine our delineation of favorable areas for Butternut restoration. Areas with the most favorable conditions to establish Butternut seedlings were limited to 291.6 ha. Our study provides a useful reference on the amount and location of favorable Butternut habitat in MCNP and can be used to identify priority areas for future Butternut restoration. Given the availability of relevant habitat layers and accurate location records, our approach can be applied to other tree species and areas. ?? 2006 Society for Ecological Restoration International.

  4. In vitro oxidative stress regulatory potential of Citrullus colocynthis and Tephrosia apollinea

    Directory of Open Access Journals (Sweden)

    Rizvi Tania Shamim

    2018-06-01

    Full Text Available The present study investigates the potential role of medicinal plants Citrullus colocynthis and Tephrosia apollinea in ameliorating the oxidative stress developed during the generation of reactive oxygen species. Organic extracts of different organs (leaf, stem and root of these medicinal plants obtained in n-hexane, chloroform, n-butanol and water were assayed for radical scavenging, total antioxidant capacity, anti-lipid peroxidation and reduced glutathione. The total phenolic content (TPC of both selected medicinal plants was also evaluated. The results indicated that extracts of T. apollinea leaf, stem and root have higher TPC compared to those of C. colocynthis. Similarly, the results of the present study revealed higher bioactivity of C. colocynthis than that of T. apollinea in various antioxidant assays. Various plant parts of each plant were also compared.

  5. Testing the potential of geochemical techniques in identifying hydrological systems within landslides in partly weathered marls

    Science.gov (United States)

    Bogaard, T. A.

    2003-04-01

    This paper’s objectives are twofold: to test the potential of cation exchange capacity (CEC) analysis for refinement of the knowledge of the hydrological system in landslide areas; and to examine two laboratory CEC analysis techniques on their applicability to partly weathered marls. The NH4Ac and NaCl laboratory techniques are tested. The geochemical results are compared with the core descriptions and interpreted with respect to their usefulness. Both analysis techniques give identical results for CEC, and are plausible on the basis of the available clay content information. The determination of the exchangeable cations was more difficult, since part of the marls dissolved. With the ammonium-acetate method more of the marls are dissolved than with the sodium-chloride method. This negatively affects the results of the exchangeable cations. Therefore, the NaCl method is to be preferred for the determination of the cation fractions at the complex, be it that this method has the disadvantage that the sodium fraction cannot be determined. To overcome this problem it is recommended to try and use another salt e.g. SrCl2 as displacement fluid. Both Alvera and Boulc-Mondorès examples show transitions in cation composition with depth. It was shown that the exchangeable cation fractions can be useful in locating boundaries between water types, especially the boundary between the superficial, rain fed hydrological system and the lower, regional ground water system. This information may be important for landslide interventions since the hydrological system and the origin of the water need to be known in detail. It is also plausible that long-term predictions of slope stability may be improved by knowledge of the hydrogeochemical evolution of clayey landslides. In the Boulc-Mondorès example the subsurface information that can be extracted from CEC analyses was presented. In the Boulc-Mondorès cores deviant intervals of CEC could be identified. These are interpreted as

  6. Testing the potential of geochemical techniques for identifying hydrological systems within landslides in partly weathered marls

    Science.gov (United States)

    Bogaard, T. A.; Buma, J. T.; Klawer, C. J. M.

    2004-03-01

    This paper's objective is to determine how useful geochemistry can be in landslide investigations. More specifically, what additional information can be gained by analysing the cation exchange capacity (CEC) and cation composition in respect to the hydrological system of a landslide area in clayey material. Two cores from the Boulc-Mondorès landslide (France) and one core from the Alvera landslide (Italy) were analysed. The NH 4Ac and NaCl laboratory techniques are tested. The geochemical results are compared with the core descriptions and interpreted with respect to their usefulness. Both analysis techniques give identical results for CEC, and are plausible on the basis of the available clay content information. The determination of the exchangeable cations was more difficult, since part of the marls dissolved. With the ammonium-acetate method more of the marls are dissolved than with the sodium-chloride method. The NaCl method is preferred for the determination of the cation fractions at the complex, be it that this method has the disadvantage that the sodium fraction cannot be determined. To overcome this problem, it is recommended to try other displacement fluids. In the Boulc-Mondorès example, the subsurface information that can be extracted from CEC analyses was presented. In the Boulc-Mondorès cores deviant intervals of CEC could be identified. These are interpreted as weathered layers (and preferential flow paths) that may develop or have already developed into slip surfaces. The major problem of the CEC analyses was to explain the origin of the differences found in the core samples. Both Alvera and Boulc-Mondorès examples show transitions in cation composition with depth. It was shown that the exchangeable caution fractions can be useful in locating boundaries between water types, especially the boundary between the superficial, rain-fed hydrological system and the lower, regional groundwater system. This information may be important for landslide

  7. Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

    Directory of Open Access Journals (Sweden)

    Lars Stechemesser

    2017-01-01

    Full Text Available Objective: Elevated serum ferritin has been linked to type 2 diabetes (T2D and adverse health outcomes in subjects with the Metabolic Syndrome (MetS. As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways. Methods: In a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1 lean, healthy controls (n = 53, (2 MetS without hyperferritinemia (n = 54 and (3 MetS with hyperferritinemia (n = 56. An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach. Results: Subjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001, HbA1c (p = 0.035 and 1 h glucose in oral glucose tolerance test (p = 0.002 compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites. Conclusions: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism. Author Video: Author Video Watch what authors say about their articles Keywords: Metabolomics, Hyperferritinemia, Iron overload, Metabolic

  8. Seminar on Biogas in France and in Germany: Regulatory framework, potentials and challenges

    International Nuclear Information System (INIS)

    Abadie, Pierre-Marie; Boettcher, Katharina; Stolpp, Sebastian; Vincent, Eric; Chapron, Thibaut; Schuette, Andreas; Paquin, Laurent; Ingremeau, Claire; Moeller, Kurt; Trommler, Marcus; Denysenko, Velina; Bosso, Valerie

    2014-01-01

    The French-German office for Renewable energies (OFAEnR) organised a Seminar on biogas in France and Germany. In the framework of this French-German exchange of experience, about 120 participants exchanged views on the legal framework, the characteristics of this industry, and the opportunities and technical challenges of biogas use in both countries. Differences and similarities were noticed in both countries, for instance regarding the use of energy cultures and digestates. This document brings together the available presentations (slides) made during this event: 1 - The French biogas in the perspective of 2020 (Pierre-Marie Abadie); 2 - Biogas Opportunities in Germany - Status January 2014 (Katharina Boettcher); 3 - Biogas market in Germany (Sebastian Stolpp); 4 - Biogas in France and Germany, Current status and development outlooks in France (Eric Vincent); 5 - Biogas use in France and Germany - a comparison (Thibaut Chapron); 6 - Alternatives to the use of maize in biogas plants - Current research results from Germany (Andreas Schuette); 7 - Inter-crops in France: analysis of the potentials (Laurent Paquin); 8 - Digestates management in France, legislative and technical advances (Claire Ingremeau); 9 - The management of digestates in Germany: Fertilizer application and status of the art (Kurt Moeller); 10 - Status quo of Biomethane in Germany - Development, Technology and Costs (Marcus Trommler); 11 - GrDF's views and actions on biogas. Biomethane injection in France: state-of-the-art and first status (Valerie Bosso)

  9. Sequence Analysis of Hypothetical Proteins from 26695 to Identify Potential Virulence Factors

    Directory of Open Access Journals (Sweden)

    Ahmad Abu Turab Naqvi

    2016-09-01

    Full Text Available Helicobacter pylori is a Gram-negative bacteria that is responsible for gastritis in human. Its spiral flagellated body helps in locomotion and colonization in the host environment. It is capable of living in the highly acidic environment of the stomach with the help of acid adaptive genes. The genome of H. pylori 26695 strain contains 1,555 coding genes that encode 1,445 proteins. Out of these, 340 proteins are characterized as hypothetical proteins (HP. This study involves extensive analysis of the HPs using an established pipeline which comprises various bioinformatics tools and databases to find out probable functions of the HPs and identification of virulence factors. After extensive analysis of all the 340 HPs, we found that 104 HPs are showing characteristic similarities with the proteins with known functions. Thus, on the basis of such similarities, we assigned probable functions to 104 HPs with high confidence and precision. All the predicted HPs contain representative members of diverse functional classes of proteins such as enzymes, transporters, binding proteins, regulatory proteins, proteins involved in cellular processes and other proteins with miscellaneous functions. Therefore, we classified 104 HPs into aforementioned functional groups. During the virulence factors analysis of the HPs, we found 11 HPs are showing significant virulence. The identification of virulence proteins with the help their predicted functions may pave the way for drug target estimation and development of effective drug to counter the activity of that protein.

  10. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    International Nuclear Information System (INIS)

    Fukunaga, Satoki; Kakehashi, Anna; Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki; Gi, Min; Wanibuchi, Hideki

    2015-01-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis

  11. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2015-08-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.

  12. 7 CFR 170.6 - How are potential market participants identified for the USDA Farmers Market?

    Science.gov (United States)

    2010-01-01

    ... (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA...? Potential market participants are recruited by AMS market management through local farm organizations in the...

  13. Immobilization of defense high-level waste: an assessment of technological strategies and potential regulatory goals. Volume I

    International Nuclear Information System (INIS)

    1979-06-01

    An investigation was made of the high-level radioactive waste immobilization technology programs in the U.S. and Europe, and of the associated regulatory programs and waste management perspectives in the countries studied. Purpose was to assess the ability of those programs to satisfy DOE waste management needs and U.S. regulatory requirements. This volume includes: introduction, immobilization strategies in the context of waste isolation program needs, high-level waste management as an integrated system, regulatory goals, engineered-barrier characteristics, barrier technology, high-level waste disposal programs, analysis of HLW immobilization technology in the context of policy and regulatory requirements, and waste immobilization program option

  14. Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

    OpenAIRE

    Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

    2008-01-01

    The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the...

  15. Data in support of quantitative proteomics to identify potential virulence regulators in Paracoccidioides brasiliensis isolates

    Directory of Open Access Journals (Sweden)

    Alexandre Keiji Tashima

    2015-12-01

    Full Text Available Paracoccidioides genus are the etiologic agents of paracoccidioidomycosis (PCM, a systemic mycosis endemic in Latin America. Few virulence factors have been identified in these fungi. This paper describes support data from the quantitative proteomics of Paracoccidioides brasiliensis attenuated and virulent isolates [1]. The protein compositions of two isolates of the Pb18 strain showing distinct infection profiles were quantitatively assessed by stable isotopic dimethyl labeling and proteomic analysis. The mass spectrometry and the analysis dataset have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with identifier PXD000804.

  16. Identifying the potential of changes to blood sample logistics using simulation

    DEFF Research Database (Denmark)

    Jørgensen, Pelle Morten Thomas; Jacobsen, Peter; Poulsen, Jørgen Hjelm

    2013-01-01

    of the simulation was to evaluate changes made to the transportation of blood samples between wards and the laboratory. The average- (AWT) and maximum waiting time (MWT) from a blood sample was drawn at the ward until it was received at the laboratory, and the distribution of arrivals of blood samples......, each of the scenarios was tested in terms of what amount of resources would give the optimal result. The simulations showed a big improvement potential in implementing a new technology/mean for transporting the blood samples. The pneumatic tube system showed the biggest potential lowering the AWT...

  17. Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms.

    Science.gov (United States)

    Esplin, M Sean; Manuck, Tracy A; Varner, Michael W; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M; Ilekis, John

    2015-09-01

    We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ(2) analysis (PD and DH, P cluster 3 of SPTB. We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Identifying the Potential Organizational Impact of an Educational Peer Review Program

    Science.gov (United States)

    Toth, Kate E.; McKey, Colleen A.

    2010-01-01

    The literature on educational peer review (EPR) has focused on evaluating EPR's impact on faculty and/or student learning outcomes; no literature exists on the potential organizational impact. A qualitative (case study) research design explored perceptions of 17 faculty and 10 administrators within a school of nursing in an Ontario university…

  19. Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis

    Directory of Open Access Journals (Sweden)

    Barker Jeffery L

    2009-08-01

    Full Text Available Abstract Background Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11, E12 and E13 were analyzed. Results Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs. Conclusion These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets.

  20. Identifying electricity-saving potential in rural China: Empirical evidence from a household survey

    International Nuclear Information System (INIS)

    Yu, Yihua; Guo, Jin

    2016-01-01

    In recent years, there has been a fast-growing body of literature examining energy-saving potential in relation to electricity. However, empirical studies focusing on non-Western nations are limited. To fill this gap, this study intends to examine the electricity-saving potential of rural households in China using a unique data set from the China Residential Electricity Consumption Survey (CRECS) in collaboration with the China General Social Survey (CGSS), conducted nationwide at the household level in rural China. We use a stochastic frontier model, which allows us to decompose residential electricity consumption into the minimum necessary amount of consumption based on physical characteristics (e.g. house size, house age, number of televisions or refrigerators) and estimate the consumption slack (i.e. the amount of electricity consumption that could be saved), which depends on various factors. We find that rural households in China are generally efficient in electricity saving and the saving potential is affected by (fast) information feedback and social-demographic characteristics, instead of by the (averaged) electricity price, or energy efficiency labelling signals. In addition, we find no evidence of regional heterogeneity on electricity saving potential for rural households. Policy implications are derived. - Highlights: •Electricity saving potential of rural households in China is examined. •Unique survey data from the CRECS in collaboration with the CGSS are used. •A stochastic frontier model is applied. •Information feedback and social-demographic characteristics matter. •Electricity price or energy efficiency tier rating does not matter.

  1. Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

    Science.gov (United States)

    Hamilton, Natasha A; Tammen, Imke; Raadsma, Herman W

    2013-01-01

    Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

  2. Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

    Directory of Open Access Journals (Sweden)

    Natasha A Hamilton

    Full Text Available Angiotensin converting enzyme (ACE is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

  3. A Novel Gibberellin-Induced Gene from Rice and Its Potential Regulatory Role in Stem Growth1

    Science.gov (United States)

    van der Knaap, Esther; Kim, Jeong Hoe; Kende, Hans

    2000-01-01

    Os-GRF1 (Oryza sativa-GROWTH-REGULATING FACTOR1) was identified in a search for genes that are differentially expressed in the intercalary meristem of deepwater rice (Oryza sativa L.) internodes in response to gibberellin (GA). Os-GRF1 displays general features of transcription factors, contains a functional nuclear localization signal, and has three regions with similarities to sequences in the database. One of these regions is similar to a protein interaction domain of SWI2/SNF2, which is a subunit of a chromatin-remodeling complex in yeast. The two other domains are novel and found only in plant proteins of unknown function. To study its role in plant growth, Os-GRF1 was expressed in Arabidopsis. Stem elongation of transformed plants was severely inhibited, and normal growth could not be recovered by the application of GA. Our results indicate that Os-GRF1 belongs to a novel class of plant proteins and may play a regulatory role in GA-induced stem elongation. PMID:10712532

  4. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  5. Benchmarking to Identify Practice Variation in Test Ordering: A Potential Tool for Utilization Management.

    Science.gov (United States)

    Signorelli, Heather; Straseski, Joely A; Genzen, Jonathan R; Walker, Brandon S; Jackson, Brian R; Schmidt, Robert L

    2015-01-01

    Appropriate test utilization is usually evaluated by adherence to published guidelines. In many cases, medical guidelines are not available. Benchmarking has been proposed as a method to identify practice variations that may represent inappropriate testing. This study investigated the use of benchmarking to identify sites with inappropriate utilization of testing for a particular analyte. We used a Web-based survey to compare 2 measures of vitamin D utilization: overall testing intensity (ratio of total vitamin D orders to blood-count orders) and relative testing intensity (ratio of 1,25(OH)2D to 25(OH)D test orders). A total of 81 facilities contributed data. The average overall testing intensity index was 0.165, or approximately 1 vitamin D test for every 6 blood-count tests. The average relative testing intensity index was 0.055, or one 1,25(OH)2D test for every 18 of the 25(OH)D tests. Both indexes varied considerably. Benchmarking can be used as a screening tool to identify outliers that may be associated with inappropriate test utilization. Copyright© by the American Society for Clinical Pathology (ASCP).

  6. Identifying potential engaging leaders within medical education: The role of positive influence on peers.

    Science.gov (United States)

    Michalec, Barret; Veloski, J Jon; Hojat, Mohammadreza; Tykocinski, Mark L

    2014-08-26

    Abstract Background: Previous research has paid little to no attention towards exploring methods of identifying existing medical student leaders. Aim: Focusing on the role of influence and employing the tenets of the engaging leadership model, this study examines demographic and academic performance-related differences of positive influencers and if students who have been peer-identified as positive influencers also demonstrate high levels of genuine concern for others. Methods: Three separate fourth-year classes were asked to designate classmates that had significant positive influences on their professional and personal development. The top 10% of those students receiving positive influence nominations were compared with the other students on demographics, academic performance, and genuine concern for others. Results: Besides age, no demographic differences were found between positive influencers and other students. High positive influencers were not found to have higher standardized exam scores but did receive significantly higher clinical clerkship ratings. High positive influencers were found to possess a higher degree of genuine concern for others. Conclusion: The findings lend support to (a) utilizing the engaging model to explore leaders and leadership within medical education, (b) this particular method of identifying existing medical student leaders, and (c) return the focus of leadership research to the power of influence.

  7. IDENTIFYING REGIONAL CLUSTER MANAGEMENT POTENTIALS EMPIRICAL RESULTS FROM THREE NORTH RHINEWESTPHALIAN REGIONS

    OpenAIRE

    Rudiger Hamm; Christiane Goebel

    2010-01-01

    The development and support of clusters is an issue that became quite popular by players dealing with regional economic policy. But before a regional development agency can start to implement a cluster-oriented strategy there a two question that have to be answered: 1. What are the regional fields of competence (cluster potentials) that fulfill the requirements for a cluster-oriented regional development policy? 2. If you find such regional fields of competence, are the enterprises willing to...

  8. Report of the US Nuclear Regulatory Commission Piping Review Committee. Volume 3. Evaluation of potential for pipe breaks

    Energy Technology Data Exchange (ETDEWEB)

    1984-11-01

    The Executive Director for Operations (EDO) in establishing the Piping Review Committee concurred in its overall scope that included an evaluation of the potential for pipe breaks. The Pipe Break Task Group has responded to this directive. This report summarizes a review of regulatory documents and contains the Task Group's recommendations for application of the leak-before-break (LBB) approach to the NRC licensing process. The LBB approach means the application of fracture mechanics technology to demonstrate that high energy fluid piping is very unlikely to experience double-ended ruptures or their equivalent as longitudinal or diagonal splits. The Task Group's reommendations and discussion are founded on current and ongoing NRC staff actions as presented in Section 3.0 of this report. Additional more detailed comments and discussion are presented in Section 5.0 and in Appendices A and B. The obvious issues are the reexamination of the large pipe break criteria and the implications of any changes in the criteria as they influence items such as jet loads and pipe whip. The issues have been considered and the Task Group makes the following recommendations.

  9. Report of the US Nuclear Regulatory Commission Piping Review Committee. Volume 3. Evaluation of potential for pipe breaks

    International Nuclear Information System (INIS)

    1984-11-01

    The Executive Director for Operations (EDO) in establishing the Piping Review Committee concurred in its overall scope that included an evaluation of the potential for pipe breaks. The Pipe Break Task Group has responded to this directive. This report summarizes a review of regulatory documents and contains the Task Group's recommendations for application of the leak-before-break (LBB) approach to the NRC licensing process. The LBB approach means the application of fracture mechanics technology to demonstrate that high energy fluid piping is very unlikely to experience double-ended ruptures or their equivalent as longitudinal or diagonal splits. The Task Group's reommendations and discussion are founded on current and ongoing NRC staff actions as presented in Section 3.0 of this report. Additional more detailed comments and discussion are presented in Section 5.0 and in Appendices A and B. The obvious issues are the reexamination of the large pipe break criteria and the implications of any changes in the criteria as they influence items such as jet loads and pipe whip. The issues have been considered and the Task Group makes the following recommendations

  10. Identifying the potential of changes to blood sample logistics using simulation.

    Science.gov (United States)

    Jørgensen, Pelle; Jacobsen, Peter; Poulsen, Jørgen Hjelm

    2013-01-01

    Using simulation as an approach to display and improve internal logistics at hospitals has great potential. This study shows how a simulation model displaying the morning blood-taking round at a Danish public hospital can be developed and utilized with the aim of improving the logistics. The focus of the simulation was to evaluate changes made to the transportation of blood samples between wards and the laboratory. The average- (AWT) and maximum waiting time (MWT) from a blood sample was drawn at the ward until it was received at the laboratory, and the distribution of arrivals of blood samples in the laboratory were used as the evaluation criteria. Four different scenarios were tested and compared with the current approach: (1) Using AGVs (mobile robots), (2) using a pneumatic tube system, (3) using porters that are called upon, or (4) using porters that come to the wards every 45 minutes. Furthermore, each of the scenarios was tested in terms of what amount of resources would give the optimal result. The simulations showed a big improvement potential in implementing a new technology/mean for transporting the blood samples. The pneumatic tube system showed the biggest potential lowering the AWT and MWT with approx. 36% and 18%, respectively. Additionally, all of the scenarios had a more even distribution of arrivals except for porters coming to the wards every 45 min. As a consequence of the results obtained in the study, the hospital decided to implement a pneumatic tube system.

  11. Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

    Directory of Open Access Journals (Sweden)

    Karacali Bilge

    2007-10-01

    Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

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

    Science.gov (United States)

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

    2015-01-01

    NASA's Aeronautics Research Mission Directorate (ARMD) collaborates with the FAA and industry to provide concepts and technologies that enhance the transition to the next-generation air-traffic management system (NextGen). To facilitate this collaboration, ARMD has a series of Airspace Technology Demonstration (ATD) sub-projects that develop, demonstrate, and transitions NASA technologies and concepts for implementation in the National Airspace System (NAS). The second of these sub-projects, ATD-2, is focused on the potential benefits to NAS stakeholders of integrated arrival, departure, surface (IADS) operations. To determine the project objectives and assess the benefits of a potential solution, NASA surveyed NAS stakeholders to understand the existing issues in arrival, departure, and surface operations, and the perceived benefits of better integrating these operations. NASA surveyed a broad cross-section of stakeholders representing the airlines, airports, air-navigation service providers, and industry providers of NAS tools. The survey indicated that improving the predictability of flight times (schedules) could improve efficiency in arrival, departure, and surface operations. Stakeholders also mentioned the need for better strategic and tactical information on traffic constraints as well as better information sharing and a coupled collaborative planning process that allows stakeholders to coordinate IADS operations. To assess the impact of a potential solution, NASA sketched an initial departure scheduling concept and assessed its viability by surveying a select group of stakeholders for a second time. The objective of the departure scheduler was to enable flights to move continuously from gate to cruise with minimal interruption in a busy metroplex airspace environment using strategic and tactical scheduling enhanced by collaborative planning between airlines and service providers. The stakeholders agreed that this departure concept could improve schedule

  13. Web-based Tool Identifies and Quantifies Potential Cost Savings Measures at the Hanford Site

    International Nuclear Information System (INIS)

    Renevitz, Marisa J.; Peschong, Jon C.; Charboneau, Briant L.; Simpson, Brett C.

    2014-01-01

    The Technical Improvement system is an approachable web-based tool that is available to Hanford DOE staff, site contractors, and general support service contractors as part of the baseline optimization effort underway at the Hanford Site. Finding and implementing technical improvements are a large part of DOE's cost savings efforts. The Technical Improvement dashboard is a key tool for brainstorming and monitoring the progress of submitted baseline optimization and potential cost/schedule efficiencies. The dashboard is accessible to users over the Hanford Local Area Network (HLAN) and provides a highly visual and straightforward status to management on the ideas provided, alleviating the need for resource intensive weekly and monthly reviews

  14. Potential use of ionic species for identifying source land-uses of stormwater runoff.

    Science.gov (United States)

    Lee, Dong Hoon; Kim, Jin Hwi; Mendoza, Joseph A; Lee, Chang-Hee; Kang, Joo-Hyon

    2017-02-01

    Identifying critical land-uses or source areas is important to prioritize resources for cost-effective stormwater management. This study investigated the use of information on ionic composition as a fingerprint to identify the source land-use of stormwater runoff. We used 12 ionic species in stormwater runoff monitored for a total of 20 storm events at five sites with different land-use compositions during the 2012-2014 wet seasons. A stepwise forward discriminant function analysis (DFA) with the jack-knifed cross validation approach was used to select ionic species that better discriminate the land-use of its source. Of the 12 ionic species, 9 species (K + , Mg 2+ , Na + , NH 4 + , Br - , Cl - , F - , NO 2 - , and SO 4 2- ) were selected for better performance of the DFA. The DFA successfully differentiated stormwater samples from urban, rural, and construction sites using concentrations of the ionic species (70%, 95%, and 91% of correct classification, respectively). Over 80% of the new data cases were correctly classified by the trained DFA model. When applied to data cases from a mixed land-use catchment and downstream, the DFA model showed the greater impact of urban areas and rural areas respectively in the earlier and later parts of a storm event.

  15. Using Market Research to Characterize College Students and Identify Potential Targets for Influencing Health Behaviors

    Science.gov (United States)

    Berg, Carla J.; Ling, Pamela M.; Guo, Hongfei; Windle, Michael; Thomas, Janet L.; Ahluwalia, Jasjit S.; An, Lawrence C.

    2013-01-01

    Marketing campaigns, such as those developed by the tobacco industry, are based on market research, which defines segments of a population by assessing psychographic characteristics (i.e., attitudes, interests). This study uses a similar approach to define market segments of college smokers, to examine differences in their health behaviors (smoking, drinking, binge drinking, exercise, diet), and to determine the validity of these segments. A total of 2,265 undergraduate students aged 18–25 years completed a 108-item online survey in fall 2008 assessing demographic, psychographic (i.e., attitudes, interests), and health-related variables. Among the 753 students reporting past 30-day smoking, cluster analysis was conducted using 21 psychographic questions and identified three market segments – Stoic Individualists, Responsible Traditionalists, and Thrill-Seeking Socializers. We found that segment membership was related to frequency of alcohol use, binge drinking, and limiting dietary fat. We then developed three messages targeting each segment and conducted message testing to validate the segments on a subset of 73 smokers representing each segment in spring 2009. As hypothesized, each segment indicated greater relevance and salience for their respective message. These findings indicate that identifying qualitatively different subgroups of young adults through market research may inform the development of engaging interventions and health campaigns targeting college students. PMID:25264429

  16. Identifying and sequencing a Mycobacterium sp. strain F4 as a potential bioremediation agent for quinclorac.

    Science.gov (United States)

    Li, Yingying; Chen, Wu; Wang, Yunsheng; Luo, Kun; Li, Yue; Bai, Lianyang; Luo, Feng

    2017-01-01

    Quinclorac is a widely used herbicide in rice filed. Unfortunately, quinclorac residues are phytotoxic to many crops/vegetables. The degradation of quinclorac in nature is very slow. On the other hand, degradation of quinclorac using bacteria can be an effective and efficient method to reduce its contamination. In this study, we isolated a quinclorac bioremediation bacterium strain F4 from quinclorac contaminated soils. Based on morphological characteristics and 16S rRNA gene sequence analysis, we identified strain F4 as Mycobacterium sp. We investigated the effects of temperature, pH, inoculation size and initial quinclorac concentration on growth and degrading efficiency of F4 and determined the optimal quinclorac degrading condition of F4. Under optimal degrading conditions, F4 degraded 97.38% of quinclorac from an initial concentration of 50 mg/L in seven days. Our indoor pot experiment demonstrated that the degradation products were non-phytotoxic to tobacco. After analyzing the quinclorac degradation products of F4, we proposed that F4 could employ two pathways to degrade quinclorac: one is through methylation, the other is through dechlorination. Furthermore, we reconstructed the whole genome of F4 through single molecular sequencing and de novo assembly. We identified 77 methyltransferases and eight dehalogenases in the F4 genome to support our hypothesized degradation path.

  17. Identifying potential maternal genes of Bombyx mori using digital gene expression profiling

    Science.gov (United States)

    Xu, Pingzhen

    2018-01-01

    Maternal genes present in mature oocytes play a crucial role in the early development of silkworm. Although maternal genes have been widely studied in many other species, there has been limited research in Bombyx mori. High-throughput next generation sequencing provides a practical method for gene discovery on a genome-wide level. Herein, a transcriptome study was used to identify maternal-related genes from silkworm eggs. Unfertilized eggs from five different stages of early development were used to detect the changing situation of gene expression. The expressed genes showed different patterns over time. Seventy-six maternal genes were annotated according to homology analysis with Drosophila melanogaster. More than half of the differentially expressed maternal genes fell into four expression patterns, while the expression patterns showed a downward trend over time. The functional annotation of these material genes was mainly related to transcription factor activity, growth factor activity, nucleic acid binding, RNA binding, ATP binding, and ion binding. Additionally, twenty-two gene clusters including maternal genes were identified from 18 scaffolds. Altogether, we plotted a profile for the maternal genes of Bombyx mori using a digital gene expression profiling method. This will provide the basis for maternal-specific signature research and improve the understanding of the early development of silkworm. PMID:29462160

  18. Identifying and sequencing a Mycobacterium sp. strain F4 as a potential bioremediation agent for quinclorac.

    Directory of Open Access Journals (Sweden)

    Yingying Li

    Full Text Available Quinclorac is a widely used herbicide in rice filed. Unfortunately, quinclorac residues are phytotoxic to many crops/vegetables. The degradation of quinclorac in nature is very slow. On the other hand, degradation of quinclorac using bacteria can be an effective and efficient method to reduce its contamination. In this study, we isolated a quinclorac bioremediation bacterium strain F4 from quinclorac contaminated soils. Based on morphological characteristics and 16S rRNA gene sequence analysis, we identified strain F4 as Mycobacterium sp. We investigated the effects of temperature, pH, inoculation size and initial quinclorac concentration on growth and degrading efficiency of F4 and determined the optimal quinclorac degrading condition of F4. Under optimal degrading conditions, F4 degraded 97.38% of quinclorac from an initial concentration of 50 mg/L in seven days. Our indoor pot experiment demonstrated that the degradation products were non-phytotoxic to tobacco. After analyzing the quinclorac degradation products of F4, we proposed that F4 could employ two pathways to degrade quinclorac: one is through methylation, the other is through dechlorination. Furthermore, we reconstructed the whole genome of F4 through single molecular sequencing and de novo assembly. We identified 77 methyltransferases and eight dehalogenases in the F4 genome to support our hypothesized degradation path.

  19. New potential markers of in vitro tomato morphogenesis identified by mRNA differential display.

    Science.gov (United States)

    Torelli, A; Soragni, E; Bolchi, A; Petrucco, S; Ottonello, S; Branca, C

    1996-12-01

    The identification of plant genes involved in early phases of in vitro morphogenesis can not only contribute to our understanding of the processes underlying growth regulator-controlled determination, but also provide novel markers for evaluating the outcome of in vitro regeneration experiments. To search for such genes and to monitor changes in gene expression accompanying in vitro regeneration, we have adapted the mRNA differential display technique to the comparative analysis of a model system of tomato cotyledons that can be driven selectively toward either shoot or callus formation by means of previously determined growth regulator supplementations. Hormone-independent transcriptional modulation (mainly down-regulation) has been found to be the most common event, indicating that a non-specific reprogramming of gene expression quantitatively predominates during the early phases of in vitro culture. However, cDNA fragments representative of genes that are either down-regulated or induced in a programme-specific manner could also be identified, and two of them (G35, G36) were further characterized. One of these cDNA fragments, G35, corresponds to an mRNA that is down-regulated much earlier in callus- (day 2) than in shoot-determined explants (day 6). The other, G36, identifies an mRNA that is transiently expressed in shoot-determined explants only, well before any macroscopic signs of differentiation become apparent, and thus exhibits typical features of a morphogenetic marker.

  20. First update to the US Nuclear Regulatory Commission's regulatory strategy for the high-level waste repository program

    International Nuclear Information System (INIS)

    Johnson, R.L.; Linehan, J.J.

    1991-01-01

    The US Nuclear Regulatory Commission (NRC) staff has updated its initial regulatory strategy for the High-Level Waste Repository Licensing Program. The update describes changes to the initial strategy and summarizes progress and future activities. This paper summarizes the first update of the regulatory strategy. In general the overall strategy of identifying and reducing uncertainties is unchanged. Identifying regulatory and institutional uncertainties is essentially complete, and therefore, the current and future emphasis is on reducing those regulatory and institutional uncertainties identified to date. The NRC staff has improved the methods of reducing regulatory uncertainties by (1) enhancing the technical basis preparation process for potential rulemakings and guidance and (2) designing a new guidance document, called a staff position, for clarifying regulatory uncertainties. For guiding the US DOE's reduction of technical uncertainties, the NRC staff will give more emphasis to prelicense application reviews and less emphasis on preparing staff technical positions

  1. Melatonin identified in meats and other food stuffs: potentially nutritional impact.

    Science.gov (United States)

    Tan, Dun-Xian; Zanghi, Brian M; Manchester, Lucien C; Reiter, Russel J

    2014-09-01

    Melatonin has been identified in primitive photosynthetic bacteria, fungi, plants, and animals including humans. Vegetables, fruits, cereals, wine, and beers all contain melatonin. However, the melatonin content in meats has not been reported previously. Here, for the first time, we report melatonin in meats, eggs, colostrum, and in other edible food products. The levels of melatonin measured by HPLC, in lamb, beef, pork, chicken, and fish, are comparable to other food stuffs (in the range of ng/g). These levels are significantly higher than melatonin concentrations in the blood of vertebrates. As melatonin is a potent antioxidant, its presence in the meat could contribute to shelf life duration as well as preserve their quality and taste. In addition, the consumption of these foods by humans or animals could have health benefits considering the important functions of melatonin as a potent free radical scavenger and antioxidant. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. A Complementary Bioinformatics Approach to Identify Potential Plant Cell Wall Glycosyltransferase-Encoding Genes

    DEFF Research Database (Denmark)

    Egelund, Jack; Skjøt, Michael; Geshi, Naomi

    2004-01-01

    Plant cell wall (CW) synthesizing enzymes can be divided into the glycan (i.e. cellulose and callose) synthases, which are multimembrane spanning proteins located at the plasma membrane, and the glycosyltransferases (GTs), which are Golgi localized single membrane spanning proteins, believed....... Although much is known with regard to composition and fine structures of the plant CW, only a handful of CW biosynthetic GT genes-all classified in the CAZy system-have been characterized. In an effort to identify CW GTs that have not yet been classified in the CAZy database, a simple bioinformatics...... approach was adopted. First, the entire Arabidopsis proteome was run through the Transmembrane Hidden Markov Model 2.0 server and proteins containing one or, more rarely, two transmembrane domains within the N-terminal 150 amino acids were collected. Second, these sequences were submitted...

  3. Cheap and Nasty? The Potential Perils of Using Management Costs to Identify Global Conservation Priorities

    Science.gov (United States)

    McCreless, Erin; Visconti, Piero; Carwardine, Josie; Wilcox, Chris; Smith, Robert J.

    2013-01-01

    The financial cost of biodiversity conservation varies widely around the world and such costs should be considered when identifying countries to best focus conservation investments. Previous global prioritizations have been based on global models for protected area management costs, but this metric may be related to other factors that negatively influence the effectiveness and social impacts of conservation. Here we investigate such relationships and first show that countries with low predicted costs are less politically stable. Local support and capacity can mitigate the impacts of such instability, but we also found that these countries have less civil society involvement in conservation. Therefore, externally funded projects in these countries must rely on government agencies for implementation. This can be problematic, as our analyses show that governments in countries with low predicted costs score poorly on indices of corruption, bureaucratic quality and human rights. Taken together, our results demonstrate that using national-level estimates for protected area management costs to set global conservation priorities is simplistic, as projects in apparently low-cost countries are less likely to succeed and more likely to have negative impacts on people. We identify the need for an improved approach to develop global conservation cost metrics that better capture the true costs of avoiding or overcoming such problems. Critically, conservation scientists must engage with practitioners to better understand and implement context-specific solutions. This approach assumes that measures of conservation costs, like measures of conservation value, are organization specific, and would bring a much-needed focus on reducing the negative impacts of conservation to develop projects that benefit people and biodiversity. PMID:24260502

  4. Cheap and nasty? The potential perils of using management costs to identify global conservation priorities.

    Directory of Open Access Journals (Sweden)

    Erin McCreless

    Full Text Available The financial cost of biodiversity conservation varies widely around the world and such costs should be considered when identifying countries to best focus conservation investments. Previous global prioritizations have been based on global models for protected area management costs, but this metric may be related to other factors that negatively influence the effectiveness and social impacts of conservation. Here we investigate such relationships and first show that countries with low predicted costs are less politically stable. Local support and capacity can mitigate the impacts of such instability, but we also found that these countries have less civil society involvement in conservation. Therefore, externally funded projects in these countries must rely on government agencies for implementation. This can be problematic, as our analyses show that governments in countries with low predicted costs score poorly on indices of corruption, bureaucratic quality and human rights. Taken together, our results demonstrate that using national-level estimates for protected area management costs to set global conservation priorities is simplistic, as projects in apparently low-cost countries are less likely to succeed and more likely to have negative impacts on people. We identify the need for an improved approach to develop global conservation cost metrics that better capture the true costs of avoiding or overcoming such problems. Critically, conservation scientists must engage with practitioners to better understand and implement context-specific solutions. This approach assumes that measures of conservation costs, like measures of conservation value, are organization specific, and would bring a much-needed focus on reducing the negative impacts of conservation to develop projects that benefit people and biodiversity.

  5. Identifying and acting on potentially inappropriate care? Inadequacy of current hospital coding for this task.

    Science.gov (United States)

    Cooper, P David; Smart, David R

    2017-06-01

    Recent Australian attempts to facilitate disinvestment in healthcare, by identifying instances of 'inappropriate' care from large Government datasets, are subject to significant methodological flaws. Amongst other criticisms has been the fact that the Government datasets utilized for this purpose correlate poorly with datasets collected by relevant professional bodies. Government data derive from official hospital coding, collected retrospectively by clerical personnel, whilst professional body data derive from unit-specific databases, collected contemporaneously with care by clinical personnel. Assessment of accuracy of official hospital coding data for hyperbaric services in a tertiary referral hospital. All official hyperbaric-relevant coding data submitted to the relevant Australian Government agencies by the Royal Hobart Hospital, Tasmania, Australia for financial year 2010-2011 were reviewed and compared against actual hyperbaric unit activity as determined by reference to original source documents. Hospital coding data contained one or more errors in diagnoses and/or procedures in 70% of patients treated with hyperbaric oxygen that year. Multiple discrete error types were identified, including (but not limited to): missing patients; missing treatments; 'additional' treatments; 'additional' patients; incorrect procedure codes and incorrect diagnostic codes. Incidental observations of errors in surgical, anaesthetic and intensive care coding within this cohort suggest that the problems are not restricted to the specialty of hyperbaric medicine alone. Publications from other centres indicate that these problems are not unique to this institution or State. Current Government datasets are irretrievably compromised and not fit for purpose. Attempting to inform the healthcare policy debate by reference to these datasets is inappropriate. Urgent clinical engagement with hospital coding departments is warranted.

  6. Cheap and nasty? The potential perils of using management costs to identify global conservation priorities.

    Science.gov (United States)

    McCreless, Erin; Visconti, Piero; Carwardine, Josie; Wilcox, Chris; Smith, Robert J

    2013-01-01

    The financial cost of biodiversity conservation varies widely around the world and such costs should be considered when identifying countries to best focus conservation investments. Previous global prioritizations have been based on global models for protected area management costs, but this metric may be related to other factors that negatively influence the effectiveness and social impacts of conservation. Here we investigate such relationships and first show that countries with low predicted costs are less politically stable. Local support and capacity can mitigate the impacts of such instability, but we also found that these countries have less civil society involvement in conservation. Therefore, externally funded projects in these countries must rely on government agencies for implementation. This can be problematic, as our analyses show that governments in countries with low predicted costs score poorly on indices of corruption, bureaucratic quality and human rights. Taken together, our results demonstrate that using national-level estimates for protected area management costs to set global conservation priorities is simplistic, as projects in apparently low-cost countries are less likely to succeed and more likely to have negative impacts on people. We identify the need for an improved approach to develop global conservation cost metrics that better capture the true costs of avoiding or overcoming such problems. Critically, conservation scientists must engage with practitioners to better understand and implement context-specific solutions. This approach assumes that measures of conservation costs, like measures of conservation value, are organization specific, and would bring a much-needed focus on reducing the negative impacts of conservation to develop projects that benefit people and biodiversity.

  7. The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells

    Directory of Open Access Journals (Sweden)

    Robert Drynda

    2018-02-01

    Full Text Available Background/Aims: Insulin-secreting islet β-cells adapt to the insulin resistance associated with pregnancy by increasing functional β-cell mass, but the placental signals involved in this process are not well defined. In the current study, we analysed expression of G-protein coupled receptor (GPCR mRNAs in mouse islets and islet GPCR ligand mRNAs in placenta during pregnancy to generate an atlas of potential interactions between the placenta and β-cells to inform future functional studies of islet adaptive responses to pregnancy. Methods: Quantative RT-PCR arrays were used to measure mRNA expression levels of: (i 342 GPCRs in islets from non-pregnant mice, and in islets isolated from mice on gestational days 12 and 18; (ii 126 islet GPCR ligands in mouse placenta at gestational days 12 and 18. Results: At gestational day 12, a time of rapid expansion of the β-cell mass, 189 islet GPCR mRNAs were quantifiable, while 79 of the 126 known islet GPCR ligand mRNAs were detectable in placental extracts. Approximately half of the quantifiable placental GPCR ligand genes were of unknown function in β-cells. The expression of some islet GPCR and placental ligand mRNAs varied during pregnancy, with altered expression of both GPCR and ligand mRNAs by gestational day 18. Conclusion: The current study has revealed numerous potential routes for interaction between the placenta and islets, and offers an atlas to inform further functional studies of their roles in adaptive responses to pregnancy, and in the regulation of the β-cell mass.

  8. Identifying potential environmental impacts of waste handling strategies in textile industry.

    Science.gov (United States)

    Yacout, Dalia M M; Hassouna, M S

    2016-08-01

    Waste management is a successful instrument to minimize generated waste and improve environmental conditions. In spite of the large share of developing countries in the textile industry, limited information is available concerning the waste management strategies implemented for textiles on those countries and their environmental impacts. In the current study, two waste management approaches for hazardous solid waste treatment of acrylic fibers (landfill and incineration) were investigated. The main research questions were: What are the different impacts of each waste management strategy? Which waste management strategy is more ecofriendly? Life cycle assessment was employed in order to model the environmental impacts of each waste streaming approach separately then compare them together. Results revealed that incineration was the more ecofriendly approach. Highest impacts of both approaches were on ecotoxicity and carcinogenic potentials due to release of metals from pigment wastes. Landfill had an impact of 46.8 % on human health as compared to 28 % by incineration. Incineration impact on ecosystem quality was higher than landfill impact (68.4 and 51.3 %, respectively). As for resources category, incineration had a higher impact than landfill (3.5 and 2.0 %, respectively). Those impacts could be mitigated if state-of-the-art landfill or incinerator were used and could be reduced by applying waste to energy approaches for both management systems In conclusion, shifting waste treatment from landfill to incineration would decrease the overall environmental impacts and allow energy recovery. The potential of waste to energy approach by incineration with heat recovery could be considered in further studies. Future research is needed in order to assess the implementation of waste management systems and the preferable waste management strategies in the textile industry on developing countries.

  9. Using event related potentials to identify a user's behavioural intention aroused by product form design.

    Science.gov (United States)

    Ding, Yi; Guo, Fu; Zhang, Xuefeng; Qu, Qingxing; Liu, Weilin

    2016-07-01

    The capacity of product form to arouse user's behavioural intention plays a decisive role in further user experience, even in purchase decision, while traditional methods rarely give a fully understanding of user experience evoked by product form, especially the feeling of anticipated use of product. Behavioural intention aroused by product form designs has not yet been investigated electrophysiologically. Hence event related potentials (ERPs) were applied to explore the process of behavioural intention when users browsed different smart phone form designs with brand and price not taken into account for mainly studying the brain activity evoked by variety of product forms. Smart phone pictures with different anticipated user experience were displayed with equiprobability randomly. Participants were asked to click the left mouse button when certain picture gave them a feeling of behavioural intention to interact with. The brain signal of each participant was recorded by Curry 7.0. The results show that pictures with an ability to arouse participants' behavioural intention for further experience can evoke enhanced N300 and LPPs (late positive potentials) in central-parietal, parietal and occipital regions. The scalp topography shows that central-parietal, parietal and occipital regions are more activated. The results indicate that the discrepancy of ERPs can reflect the neural activities of behavioural intention formed or not. Moreover, amplitude of ERPs occurred in corresponding brain areas can be used to measure user experience. The exploring of neural correlated with behavioural intention provide an accurate measurement method of user's perception and help marketers to know which product can arouse users' behavioural intention, maybe taken as an evaluating indicator of product design. Copyright © 2016 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  10. Effective Drug Delivery in Diffuse Intrinsic Pontine Glioma: A Theoretical Model to Identify Potential Candidates

    Directory of Open Access Journals (Sweden)

    Fatma E. El-Khouly

    2017-10-01

    Full Text Available Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG, patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB. We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED may increase their therapeutic potential. Physicochemical properties (lipophilicity, molecular weight, and charge in physiological environment of anticancer drugs historically and currently administered to DIPG patients, that affect passive diffusion over the BBB, were included in the model. Subsequently, the likelihood of BBB passage of these drugs was ascertained, as well as their potential for intratumoral administration via CED. As only non-molecularly charged, lipophilic, and relatively small sized drugs are likely to passively diffuse through the BBB, out of 51 drugs modeled, only 8 (15%—carmustine, lomustine, erlotinib, vismodegib, lenalomide, thalidomide, vorinostat, and mebendazole—are theoretically qualified for systemic administration in DIPG. Local administration via CED might create more therapeutic options, excluding only positively charged drugs and drugs that are either prodrugs and/or only available as oral formulation. A wide variety of drugs have been administered systemically to DIPG patients. Our model shows that only few are likely to penetrate the BBB via passive diffusion, which may partly explain the lack of efficacy. Drug distribution via CED is less dependent on physicochemical properties and may increase the therapeutic options for DIPG.

  11. 3D geostatistical modelling for identifying sinkhole disaster potential zones around the Verkhnekamskoye potash deposit (Russia)

    Science.gov (United States)

    Royer, J. J.; Litaudon, J.; Filippov, L. O.; Lyubimova, T.; Maximovich, N.

    2017-07-01

    This work results from a cooperative scientific program between the Perm State University (Russia) and the University of Lorraine (France). Its objectives are to integrate modern 3D geomodeling in order to improve sustainable mining extraction, especially for predicting and avoiding the formation of sinkholes disaster potential zones. Systematic exploration drill holes performed in the Verkhnekamskoye potash deposit (Perm region, Russia) have been used to build a comprehensive 3D model for better understanding the spatial repartition of the ore quality (geometallurgy). A precise modelling of the mineralized layers allows an estimation of the in-situ ore reserves after interpolating by kriging the potassium (K) and magnesium (Mg) contents at the node of a regular centred grid (over a million cells). Total resources in potassium vary according to the cut-off between 4.7Gt @ 16.1 % K2O; 0.32 % MgCl2 for a cut-off grade at 13.1% K2O and 2.06 Gt @ 18.2 % K2O; 0.32 % MgCl2 at a cut-off of 16.5% K2O. Most of reserves are located in the KPI, KPII and KPIII layers, the KPI being the richest, and KPIII the largest in terms of tonnage. A systematic study of the curvature calculated along the roof of the mineralized layers points out the location of potential main faults which play a major role in the formation of sinkhole during exploitation. A risk map is then derived from this attribute.

  12. A method to identify important dynamical states in Boolean models of regulatory networks: application to regulation of stomata closure by ABA in A. thaliana.

    Science.gov (United States)

    Bugs, Cristhian A; Librelotto, Giovani R; Mombach, José C M

    2011-12-22

    We introduce a method to analyze the states of regulatory Boolean models that identifies important network states and their biological influence on the global network dynamics. It consists in (1) finding the states of the network that are most frequently visited and (2) the identification of variable and frozen nodes of the network. The method, along with a simulation that includes random features, is applied to the study of stomata closure by abscisic acid (ABA) in A. thaliana proposed by Albert and coworkers. We find that for the case of study, that the dynamics of wild and mutant networks have just two states that are highly visited in their space of states and about a third of all nodes of the wild network are variable while the rest remain frozen in True or False states. This high number of frozen elements explains the low cardinality of the space of states of the wild network. Similar results are observed in the mutant networks. The application of the method allowed us to explain how wild and mutants behave dynamically in the SS and determined an essential feature of the activation of the closure node (representing stomata closure), i.e. its synchronization with the AnionEm node (representing anion efflux at the plasma membrane). The dynamics of this synchronization explains the efficiency reached by the wild and each of the mutant networks. For the biological problem analyzed, our method allows determining how wild and mutant networks differ 'phenotypically'. It shows that the different efficiencies of stomata closure reached among the simulated wild and mutant networks follow from a dynamical behavior of two nodes that are always synchronized. Additionally, we predict that the involvement of the anion efflux at the plasma membrane is crucial for the plant response to ABA. The algorithm used in the simulations is available upon request.

  13. Proteomic analysis of polyribosomes identifies splicing factors as potential regulators of translation during mitosis.

    Science.gov (United States)

    Aviner, Ranen; Hofmann, Sarah; Elman, Tamar; Shenoy, Anjana; Geiger, Tamar; Elkon, Ran; Ehrlich, Marcelo; Elroy-Stein, Orna

    2017-06-02

    Precise regulation of mRNA translation is critical for proper cell division, but little is known about the factors that mediate it. To identify mRNA-binding proteins that regulate translation during mitosis, we analyzed the composition of polysomes from interphase and mitotic cells using unbiased quantitative mass-spectrometry (LC-MS/MS). We found that mitotic polysomes are enriched with a subset of proteins involved in RNA processing, including alternative splicing and RNA export. To demonstrate that these may indeed be regulators of translation, we focused on heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a test case and confirmed that it is recruited to elongating ribosomes during mitosis. Then, using a combination of pulsed SILAC, metabolic labeling and ribosome profiling, we showed that knockdown of hnRNP C affects both global and transcript-specific translation rates and found that hnRNP C is specifically important for translation of mRNAs that encode ribosomal proteins and translation factors. Taken together, our results demonstrate how proteomic analysis of polysomes can provide insight into translation regulation under various cellular conditions of interest and suggest that hnRNP C facilitates production of translation machinery components during mitosis to provide daughter cells with the ability to efficiently synthesize proteins as they enter G1 phase. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Feasibility Study to Identify Potential Reductions in Energy Use in Tribal Buildings

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, Willie [Confederated Salish and Kootenai Tribes, Pablo, MT (United States)

    2017-03-30

    Under this project, the Confederated Salish and Kootenai Tribes (CSKT) assessed the technical and economic feasibility of energy efficiency improvements to existing Tribally-owned buildings. The feasibility study followed a systematic approach in identifying, selecting, and ranking recommended measures, recognizing that the appropriateness of a measure would depend not only on technical issues but also on institutional and organizational issues, such as financing options and occupant requirements. The completed study provided the Tribes with the information needed to commit necessary resources to reduce the energy use and cost in approximately 40 Tribal buildings, including the changes that may be needed in each facility’s operation and maintenance and personnel requirements. It also presented an economic analysis of energy-efficiency capital improvements and an annotated list of financing options and possible funding sources for implementation and an overall strategy for implementation. This project was located in various Tribal communities located throughout the Flathead Indian Reservation in Western Montana. Notice: The following is a compilation of Annual Program Review Presentations, Award Modifications, and Quarterly Progress Reports submitted to the Department of Energy’s (DOE) Office of Indian Energy Policy and Programs by the Confederated Salish and Kootenai Tribes under agreement DE-EE0005171. This report covers project activities from September 30, 2011 through December 31, 2014 and has been uploaded to OSTI by DOE as a substitute for the required Final Technical Report which was not received by DOE from the project recipient.

  15. Historical uses of saffron: Identifying potential new avenues for modern research

    Directory of Open Access Journals (Sweden)

    Seyedeh Zeinab Mousavi

    2011-09-01

    Full Text Available Objective: During the ancient times, saffron (Crocus sativus L. had many uses around the world; however, some of these uses were forgotten throughout the history. But a newly formed interest in natural active compounds brought back the attention toward historical uses of saffron. Understanding different uses of saffron in the past can help us finding the best uses at present. In this study, we reviewed different uses of saffron throughout the history among different nations.Methods: ISI web of Science and Medline, along with references of traditional Iranian medicine were searched for historical uses of saffron.Results: Saffron has been known since more than 3000 years ago by many nations. It was valued not only as a culinary condiment, but also as a dye, perfume and as a medicinal herb. Its medicinal uses ranged from treating eye problems to genitourinary and many other diseases in various cultures. It was also used as a tonic agent and antidepressant drug among many nations. Conclusion(s: Saffron has had many different uses such as a food additive and a palliative agent for many human diseases. Thus, as an important medicinal herb, it is a good candidate with many promising potentials to be considered for new drug design.

  16. Spatial Interaction Modeling to Identify Potentially Exposed Populations during RDD or IND Terrorism Incidents

    International Nuclear Information System (INIS)

    Regens, J.L.; Gunter, J.T.; Gupta, S.

    2009-01-01

    Homeland Security Presidential Directive no.5 (HSPD-5) Management of Domestic Incidents and Department of Homeland Security (DHS) Planning Guidance for Protection and Recovery Following Radiological Dispersal Device (RDD) and Improvised Nuclear Device (IND) Incidents underscore the need to delineate radiological emergency guidance applicable to remedial action and recovery following an RDD or IND incident. Rapid delineation of the population potentially exposed to ionizing radiation from fallout during terrorist incidents involving RDDs or low-yield nuclear devices (≤ 20 KT) is necessary for effective medical response and incident management as part of the recovery process. This paper illustrates the application of spatial interaction models to allocate population data for a representative U.S. urban area (≅1.3M people; 1,612.27 km 2 area) at a geographical scale relevant for accurately estimating risk given dose concentrations. Estimated total dose equivalents (TEDE) are calculated for isopleths moving away from the detonation point for typical release scenarios. Population is estimated within the TEDE zones using Euclidean distances between zip code polygon centroids generated in ArcGIS version 9.1 with distance decay determined by regression analysis to apportion origin-destination pairs to a population count and density matrix on a spatial basis for daytime and night-time release scenarios. (authors)

  17. Identifying the Potential for Robotics to Assist Older Adults in Different Living Environments

    Science.gov (United States)

    Mitzner, Tracy L.; Chen, Tiffany L.; Kemp, Charles C.; Rogers, Wendy A.

    2014-01-01

    As the older adult population grows and becomes more diverse, so will their needs and preferences for living environments. Many adults over 65 years of age require some assistance [1, 2]; yet it is important for their feelings of well-being that the assistance not restrict their autonomy [3]. Not only is autonomy correlated with quality of life [4], autonomy enhancement may improve functionality [2, 5]. The goal of this paper is to provide guidance for the development of technology to enhance autonomy and quality of life for older adults. We explore the potential for robotics to meet these needs. We evaluated older adults' diverse living situations and the predictors of residential moves to higher levels of care in the United States. We also examined older adults' needs for assistance with activities of daily living (ADLs), instrumental activities of daily living (IADLs), and medical conditions when living independently or in a long-term care residence. By providing support for older adults, mobile manipulator robots may reduce need-driven, undesired moves from residences with lower levels of care (i.e., private homes, assisted living) to those with higher levels of care (i.e., skilled nursing). PMID:24729800

  18. Historical uses of saffron: Identifying potential new avenues for modern research

    Directory of Open Access Journals (Sweden)

    Seyedeh Zeinab Mousavi

    2011-09-01

    Full Text Available Objective: During the ancient times, saffron (Crocus sativus L. had many uses around the world; however, some of these uses were forgotten throughout the history. But a newly formed interest in natural active compounds brought back the attention toward historical uses of saffron. Understanding different uses of saffron in the past can help us finding the best uses at present.In this study, wereviewed different uses of saffron throughout the history among different nations. Methods: ISI web of Science and Medline, along with references of traditional Iranian medicine were searched for historical uses of saffron. Results: Saffron has been known since more than 3000 years ago by many nations. It was valued not only as a culinary condiment, but also as a dye, perfume and as a medicinal herb. Its medicinal uses ranged from treating eye problems to genitourinary and many other diseases in various cultures. It was also used as a tonic agent and antidepressant drug among many nations. Conclusion(s: Saffron has had many different uses such as a food additive and a palliative agent for many human diseases. Thus, as an important medicinal herb, it is a good candidate with many promising potentials to be considered for new drug design.

  19. 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.

  20. Using Smoke Injection in Drains to Identify Potential Preferential Pathways in a Drained Arable Field

    Science.gov (United States)

    Nielsen, M. H.; Petersen, C. T.; Hansen, S.

    2014-12-01

    Macropores forming a continuous pathway between the soil surface and subsurface drains favour the transport of many contaminants from agricultural fields to surface waters. The smoke injection method presented by Shipitalo and Gibbs (2000) used for demonstrating and quantifying such pathways has been further developed and used on a drained Danish sandy loam. In order to identify the preferential pathways to drains, smoke was injected in three 1.15 m deep tile drains (total drain length 93 m), and smoke emitting macropores (SEMP) at the soil surface were counted and characterized as producing either strong or weak plumes compared to reference plumes from 3 and 6 mm wide tubes. In the two situations investigated in the present study - an early spring and an autumn situation, smoke only penetrated the soil surface layer via earthworm burrows located in a 1.0 m wide belt directly above the drain lines. However, it is known from previous studies that desiccation fractures in a dry summer situation also can contribute to the smoke pattern. The distance between SEMP measured along the drain lines was on average 0.46 m whereas the average spacing between SEMP with strong plumes was 2.3 m. Ponded water was applied in 6 cm wide rings placed above 52 burrows including 17 reference burrows which did not emit smoke. Thirteen pathways in the soil were examined using dye tracer and profile excavation. SEMP with strong plumes marked the entrance of highly efficient transport pathways conducting surface applied water and dye tracer into the drain. However, no single burrow was traced all the way from the surface into the drain, the dye patterns branched off in a network of other macropores. Water infiltration rates were significantly higher (P drains and surface waters, pathways being associated primarily with unevenly distributed SEMP producing strong smoke plumes.

  1. IDENTIFYING POTENTIAL MARKERS OF THE SUN'S GIANT CONVECTIVE SCALE

    Energy Technology Data Exchange (ETDEWEB)

    McIntosh, Scott W.; Wang, Xin [High Altitude Observatory, National Center for Atmospheric Research, P.O. Box 3000, Boulder, CO 80307 (United States); Leamon, Robert J. [Department of Physics, Montana State University, Bozeman, MT 59717 (United States); Scherrer, Philip H. [W. W. Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305 (United States)

    2014-04-01

    Line-of-sight magnetograms from the Helioseismic and Magnetic Imager (HMI) of the Solar Dynamics Observatory (SDO) are analyzed using a diagnostic known as the magnetic range of influence (MRoI). The MRoI is a measure of the length over which a photospheric magnetogram is balanced and so its application gives the user a sense of the connective length scales in the outer solar atmosphere. The MRoI maps and histograms inferred from the SDO/HMI magnetograms primarily exhibit four scales: a scale of a few megameters that can be associated with granulation, a scale of a few tens of megameters that can be associated with super-granulation, a scale of many hundreds to thousands of megameters that can be associated with coronal holes and active regions, and a hitherto unnoticed scale that ranges from 100 to 250 Mm. We infer that this final scale is an imprint of the (rotationally driven) giant convective scale on photospheric magnetism. This scale appears in MRoI maps as well-defined, spatially distributed concentrations that we have dubbed ''g-nodes''. Furthermore, using coronal observations from the Atmospheric Imaging Assembly on SDO, we see that the vicinity of these g-nodes appears to be a preferred location for the formation of extreme-ultraviolet (and likely X-Ray) brightpoints. These observations and straightforward diagnostics offer the potential of a near real-time mapping of the Sun's largest convective scale, a scale that possibly reaches to the very bottom of the convective zone.

  2. Declines in Crime and Teen Childbearing: Identifying Potential Explanations for Contemporaneous Trends

    Science.gov (United States)

    Colen, Cynthia G.; Ramey, David M.; Browning, Christopher R.

    2016-01-01

    Objectives The previous 25 years have witnessed remarkable upheavals in the social landscape of the United States. Two of the most notable trends have been dramatic declines in levels of crime as well as teen childbearing. Much remains unknown about the underlying conditions that might be driving these changes. More importantly, we do not know if the same distal factors that are responsible for the drop in the crime rate are similarly implicated in falling rates of teen births. We examine four overarching potential explanations: fluctuations in economic opportunity, shifting population demographics, differences in state-level policies, and changes in expectations regarding health and mortality. Methods We combine state-specific data from existing secondary sources and model trajectories of violent crime, homicides, robberies, and teen fertility over a 20-year period from 1990 to 2010 using simultaneous fixed-effects regression models. Results We find that 4 of the 21 predictors examined - growth in the service sector of the labor market, increasing racial diversity especially among Hispanics, escalating levels of migration, and the expansion of family planning services to low-income women – offer the most convincing explanations for why rates of violent crime and teen births have been steadily decreasing over time. Moreover, we are able to account for almost a quarter of the joint declines in violent crime and teen births. Conclusions Our conclusions underscore the far reaching effects that aggregate level demographic conditions and policies are likely to have on important social trends that might, at first glance, seem unrelated. Furthermore, the effects of policy efforts designed to target outcomes in one area are likely to spill over into other domains. PMID:27695160

  3. Distribution and incidence of atoxigenic Aspergillus flavus VCG in tree crop orchards in California: a strategy for identifying potential antagonists

    Science.gov (United States)

    To identify predominant isolates for potential use as biocontrol agents, Aspergillus flavus isolates collected soils of almond, pistachio and fig orchard in the Central Valley of California were tested for their membership to 16 atoxigenic vegetative compatibility groups(VCGs), including YV36, the V...

  4. Next-Generation Sequencing of Genomic DNA Fragments Bound to a Transcription Factor in Vitro Reveals Its Regulatory Potential

    Directory of Open Access Journals (Sweden)

    Yukio Kurihara

    2014-12-01

    Full Text Available Several transcription factors (TFs coordinate to regulate expression of specific genes at the transcriptional level. In Arabidopsis thaliana it is estimated that approximately 10% of all genes encode TFs or TF-like proteins. It is important to identify target genes that are directly regulated by TFs in order to understand the complete picture of a plant’s transcriptome profile. Here, we investigate the role of the LONG HYPOCOTYL5 (HY5 transcription factor that acts as a regulator of photomorphogenesis. We used an in vitro genomic DNA binding assay coupled with immunoprecipitation and next-generation sequencing (gDB-seq instead of the in vivo chromatin immunoprecipitation (ChIP-based methods. The results demonstrate that the HY5-binding motif predicted here was similar to the motif reported previously and that in vitro HY5-binding loci largely overlapped with the HY5-targeted candidate genes identified in previous ChIP-chip analysis. By combining these results with microarray analysis, we identified hundreds of HY5-binding genes that were differentially expressed in hy5. We also observed delayed induction of some transcripts of HY5-binding genes in hy5 mutants in response to blue-light exposure after dark treatment. Thus, an in vitro gDNA-binding assay coupled with sequencing is a convenient and powerful method to bridge the gap between identifying TF binding potential and establishing function.

  5. Isolation of a solventogenic Clostridium sp. strain: fermentation of glycerol to n-butanol, analysis of the bcs operon region and its potential regulatory elements.

    Science.gov (United States)

    Panitz, J C; Zverlov, V V; Pham, V T T; Stürzl, S; Schieder, D; Schwarz, W H

    2014-02-01

    A new solventogenic bacterium, strain GT6, was isolated from standing water sediment. 16S-rRNA gene analysis revealed that GT6 belongs to the heterogeneous Clostridium tetanomorphum group of bacteria exhibiting 99% sequence identity with C. tetanomorphum 4474(T). GT6 can utilize a wide range of carbohydrate substrates including glucose, fructose, maltose, xylose and glycerol to produce mainly n-butanol without any acetone. Additional products of GT6 metabolism were ethanol, butyric acid, acetic acid, and trace amounts of 1,3-propanediol. Medium and substrate composition, and culture conditions such as pH and temperature influenced product formation. The major fermentation product from glycerol was n-butanol with a final concentration of up to 11.5 g/L. 3% (v/v) glycerol lead to a total solvent concentration of 14 g/L within 72 h. Growth was not inhibited by glycerol concentrations as high as 15% (v/v). The solventogenesis genes crt, bcd, etfA/B and hbd composing the bcs (butyryl-CoA synthesis) operon of C. tetanomorphum GT6 were sequenced. They occur in a genomic arrangement identical to those in other solventogenic clostridia. Furthermore, the sequence of a potential regulator gene highly similar to that of the NADH-sensing Rex family of regulatory genes was found upstream of the bcs operon. Potential binding sites for Rex have been identified in the promoter region of the bcs operon of solvent producing clostridia as well as upstream of other genes involved in NADH oxidation. This indicates a fundamental role of Rex in the regulation of fermentation products in anaerobic, and especially in solventogenic bacteria. Copyright © 2013 Elsevier GmbH. All rights reserved.

  6. Decreased Numbers of CD57+CD3- Cells Identify Potential Innate Immune Differences in Patients with Autism Spectrum Disorder.

    Science.gov (United States)

    Siniscalco, Dario; Mijatovic, Tatjana; Bosmans, Eugene; Cirillo, Alessandra; Kruzliak, Peter; Lombardi, Vincent C; De Meirleir, Kenny; Antonucci, Nicola

    2016-01-01

    Autism spectrum disorders (ASD) are complex, and severe heterogeneous neurodevelopmental pathologies with accepted but complex immune system abnormalities. Additional knowledge regarding potential immune dysfunctions may provide a greater understanding of this malady. The aim of this study was to evaluate the CD57(+)CD3(-) mature lymphocyte subpopulation of natural killer cells as a marker of immune dysfunction in ASD. Three-color flow cytometry-based analysis of fresh peripheral blood samples from children with autism was utilized to measure CD57(+)CD3(-) lymphocytes. A reduction of CD57(+)CD3(-) lymphocyte count was recorded in a significant number of patients with autism. We demonstrated that the number of peripheral CD57(+)CD3(-) cells in children with autism often falls below the clinically accepted normal range. This implies that a defect in the counter-regulatory functions necessary for balancing pro-inflammatory cytokines exists, thus opening the way to chronic inflammatory conditions associated with ASD. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. The importance of Foxp3 antibody and fixation/permeabilization buffer combinations in identifying CD4+CD25+Foxp3+ regulatory T cells.

    Science.gov (United States)

    Law, Jacqueline P; Hirschkorn, Dale F; Owen, Rachel E; Biswas, Hope H; Norris, Philip J; Lanteri, Marion C

    2009-12-01

    Foxp3 is a key marker for CD4(+) regulatory T cells (T(regs)) and was used in developing a multiparameter flow cytometric panel to identify T(regs). Achieving reproducible staining and analysis first required optimization of Foxp3 staining. We present a comparative study of PCH101, 236A/E7, 3G3, 206D, 150D, and 259D/C7 clones of anti-human-Foxp3 antibodies used in combination with five different fixation/permeabilization buffers. Staining for CD25, CD152, and CD127 was also compared between fixation/permeabilization treatments. Promising antibody/buffer combinations were tested in a panel of peripheral blood mononuclear cells from 10 individuals, and then on fresh versus frozen cells from four individuals. Finally, different fluorochromes coupled to two representative antibodies were compared to optimize separation of Foxp3(+) from Foxp3(-) events. Foxp3 gates were set using two gating strategies based on CD127(+)CD25(-) "non-T(regs)" or based on isotype controls. For Foxp3 staining, the best conditions for fixation/permeabilization were obtained using the eBioscience Foxp3, Imgenex, BioLegend, and BD Foxp3 buffers. Comparing results from 10 subjects, 259D/C7, PCH101, 236A/E7, and 206D antibodies yielded statistically higher levels of Foxp3 cells than those by 150D and 3G3 antibodies (mean = 6.9, 5.1, 4.7, and 3.7% compared with 1.7, and 0.3% of CD25(+)Foxp3(+) events within CD4(+) cells, respectively). Importantly, the "nonspecificity" of some antibodies observed with a Foxp3 gate based on isotype controls could be eliminated by setting the Foxp3 gate on "non-T(regs)". Better separation of Foxp3(+) and Foxp3(-) populations was observed using the PCH101 clone coupled to Alexa647 compared with FITC or the 259D/C7 clone coupled to PE compared with Alexa488 fluorochrome. Foxp3 staining can be highly variable and depends on the choice of antibody/buffer pair and the fluorochrome used. Selecting the correct population for setting the Foxp3 gate is critical to avoid

  8. Use of a scenario-development procedure to identify potentially disruptive scenarios, Greater Confinement Disposal facility, Area 5, Nevada Test Site

    International Nuclear Information System (INIS)

    Guzowski, R.V.; Sandia National Labs., Albuquerque, NM

    1994-01-01

    The Greater Confinement Disposal (GCD) facility includes four boreholes that contain transuranic (TRLT) waste. Presence of the TRU waste means that this facility must comply with the US Environmental Protection Agency's Environmental Radiation Protection Standards for Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Waste-Final Rule 40 CFR Part 191. To comply with the Containment Requirements of this rule, all potentially disruptive events and processes, and by implication all potentially disruptive combinations of events and processes (scenarios), must be identified for possible inclusion in performance assessments. Screening of the FEPs identified four events for scenario development: exploratory drilling for natural resources, drilling withdrawal wells, irrigation, and subsidence. Recent environmental-isotope analyses of the vadose zone suggest that radionuclide transport from the boreholes to the water table by infiltration is not a feasible transport mechanism within the time frame of regulatory concern. For this reason, the event of drilling withdrawal wells was merged with exploratory drilling for resources. The descriptions of the remaining three events were modified slightly to aid in estimation of event probabilities and consequence analyses. The three events are: exploratory drilling for resources penetrates a TRU borehole, irrigation occurs at the Radioactive Waste Management Site (RWMS), and subsidence occurs at the RWMS. Use of a logic diagram with these three events resulted in the construction of eight scenarios, including base-case (undisturbed) conditions. Screening these scenarios at this stage of scenario development was beyond the scope of this task. Based on the implementation assumptions, this scenario-development procedure produced a comprehensive set of mutually exclusive scenarios that are reproducible and auditable for use in GCD performance assessments

  9. Application of biclustering of gene expression data and gene set enrichment analysis methods to identify potentially disease causing nanomaterials

    Directory of Open Access Journals (Sweden)

    Andrew Williams

    2015-12-01

    Full Text Available Background: The presence of diverse types of nanomaterials (NMs in commerce is growing at an exponential pace. As a result, human exposure to these materials in the environment is inevitable, necessitating the need for rapid and reliable toxicity testing methods to accurately assess the potential hazards associated with NMs. In this study, we applied biclustering and gene set enrichment analysis methods to derive essential features of altered lung transcriptome following exposure to NMs that are associated with lung-specific diseases. Several datasets from public microarray repositories describing pulmonary diseases in mouse models following exposure to a variety of substances were examined and functionally related biclusters of genes showing similar expression profiles were identified. The identified biclusters were then used to conduct a gene set enrichment analysis on pulmonary gene expression profiles derived from mice exposed to nano-titanium dioxide (nano-TiO2, carbon black (CB or carbon nanotubes (CNTs to determine the disease significance of these data-driven gene sets.Results: Biclusters representing inflammation (chemokine activity, DNA binding, cell cycle, apoptosis, reactive oxygen species (ROS and fibrosis processes were identified. All of the NM studies were significant with respect to the bicluster related to chemokine activity (DAVID; FDR p-value = 0.032. The bicluster related to pulmonary fibrosis was enriched in studies where toxicity induced by CNT and CB studies was investigated, suggesting the potential for these materials to induce lung fibrosis. The pro-fibrogenic potential of CNTs is well established. Although CB has not been shown to induce fibrosis, it induces stronger inflammatory, oxidative stress and DNA damage responses than nano-TiO2 particles.Conclusion: The results of the analysis correctly identified all NMs to be inflammogenic and only CB and CNTs as potentially fibrogenic. In addition to identifying several

  10. Molecular analysis of faecal samples from birds to identify potential crop pests and useful biocontrol agents in natural areas.

    Science.gov (United States)

    King, R A; Symondson, W O C; Thomas, R J

    2015-06-01

    Wild habitats adjoining farmland are potentially valuable sources of natural enemies, but also of pests. Here we tested the utility of birds as 'sampling devices', to identify the diversity of prey available to predators and particularly to screen for pests and natural enemies using natural ecosystems as refugia. Here we used PCR to amplify prey DNA from three sympatric songbirds foraging on small invertebrates in Phragmites reedbed ecosystems, namely the Reed Warbler (Acrocephalus scirpaceus), Sedge Warbler (Acrocephalus schoenobaenus) and Cetti's Warbler (Cettia cetti). A recently described general invertebrate primer pair was used for the first time to analyse diets. Amplicons were cloned and sequenced, then identified by reference to the Barcoding of Life Database and to our own sequences obtained from fresh invertebrates. Forty-five distinct prey DNA sequences were obtained from 11 faecal samples, of which 39 could be identified to species or genus. Targeting three warbler species ensured that species-specific differences in prey choice broadened the range of prey taken. Amongst the prey found in reedbeds were major pests (including the tomato moth Lacanobia oleracea) as well as many potentially valuable natural enemies including aphidophagous hoverflies and braconid wasps. Given the mobility of birds, this approach provides a practical way of sampling a whole habitat at once, providing growers with information on possible invasion by locally resident pests and the colonization potential of natural enemies from local natural habitats.

  11. Milestone Report - M3FT-15OR03120213 - A Literature Survey to Identify Potentially Problematic Volatile Iodine-Bearing Species Present in Off-Gas Streams

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Brian [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Soelberg, Nick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Jubin, Robert Thomas [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bruffey, Stephanie H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Strachan, Denis M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-06-30

    Four radionuclides have been identified as being sufficiently volatile in the reprocessing of nuclear fuel that their gaseous release needs to be controlled to meet U.S. regulatory requirements (Jubin et al. 2011, 2012). These radionuclides are 3H, 14C, 85Kr, and 129I. Of these, 129I has the longest half-life and potentially highest biological impact. Accordingly, control of the release of 129I is most critical with respect to U.S. regulations for the release of radioactive material in stack emissions. Current U.S. Environmental Protection Agency regulation governing nuclear facilities (40 CFR 190) states that the total quantity of radioactive materials entering the general environment from the entire uranium fuel cycle, per gigawatt-year of electrical energy produced by the fuel cycle, must contain less than 5 mCi of 129I. The study of inorganic iodide in off-gas systems has been almost exclusively limited to I2, and the focus of organic iodide studies has been CH3I.

  12. Can inbound and domestic medical tourism improve your bottom line? Identifying the potential of a U.S. tourism market.

    Science.gov (United States)

    Fottler, Myron D; Malvey, Donna; Asi, Yara; Kirchner, Sarah; Warren, Natalia A

    2014-01-01

    In large part due to current economic conditions and the political uncertainties of healthcare reform legislation, hospitals need to identify new sources of revenue. Two potentially untapped sources are inbound (international) and domestic (within the United States) medical tourists. This case study uses data from a large, urban healthcare system in the southeastern United States to quantify its potential market opportunities for medical tourism. The data were mined from electronic health records, and descriptive frequency analysis was used to provide a preliminary market assessment. This approach permits healthcare systems to move beyond anecdotal information and assess the relative market potential of their particular geographic area and the diagnostic services they offer for attracting inbound and domestic medical tourists. Implications for healthcare executives and guidance on how they can focus marketing efforts are discussed.

  13. Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles.

    Directory of Open Access Journals (Sweden)

    Ella R Thompson

    2012-09-01

    Full Text Available Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multi-generational breast cancer predisposition is unknown. In this study, we used whole-exome sequencing of thirty-three individuals from 15 breast cancer families to identify potential predisposing genes. Our analysis identified families with heterozygous, deleterious mutations in the DNA repair genes FANCC and BLM, which are responsible for the autosomal recessive disorders Fanconi Anemia and Bloom syndrome. In total, screening of all exons in these genes in 438 breast cancer families identified three with truncating mutations in FANCC and two with truncating mutations in BLM. Additional screening of FANCC mutation hotspot exons identified one pathogenic mutation among an additional 957 breast cancer families. Importantly, none of the deleterious mutations were identified among 464 healthy controls and are not reported in the 1,000 Genomes data. Given the rarity of Fanconi Anemia and Bloom syndrome disorders among Caucasian populations, the finding of multiple deleterious mutations in these critical DNA repair genes among high-risk breast cancer families is intriguing and suggestive of a predisposing role. Our data demonstrate the utility of intra-family exome-sequencing approaches to uncover cancer predisposition genes, but highlight the major challenge of definitively validating candidates where the incidence of sporadic disease is high, germline mutations are not fully penetrant, and individual predisposition genes may only account for a tiny proportion of breast cancer families.

  14. Where we stand, where we are moving: Surveying computational techniques for identifying miRNA genes and uncovering their regulatory role

    KAUST Repository

    Kleftogiannis, Dimitrios A.; Korfiati, Aigli; Theofilatos, Konstantinos A.; Likothanassis, Spiridon D.; Tsakalidis, Athanasios K.; Mavroudi, Seferina P.

    2013-01-01

    Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step. © 2013 Elsevier Inc.

  15. Where we stand, where we are moving: Surveying computational techniques for identifying miRNA genes and uncovering their regulatory role

    KAUST Repository

    Kleftogiannis, Dimitrios A.

    2013-06-01

    Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3\\'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step. © 2013 Elsevier Inc.

  16. RNA-ID, a highly sensitive and robust method to identify cis-regulatory sequences using superfolder GFP and a fluorescence-based assay.

    Science.gov (United States)

    Dean, Kimberly M; Grayhack, Elizabeth J

    2012-12-01

    We have developed a robust and sensitive method, called RNA-ID, to screen for cis-regulatory sequences in RNA using fluorescence-activated cell sorting (FACS) of yeast cells bearing a reporter in which expression of both superfolder green fluorescent protein (GFP) and yeast codon-optimized mCherry red fluorescent protein (RFP) is driven by the bidirectional GAL1,10 promoter. This method recapitulates previously reported progressive inhibition of translation mediated by increasing numbers of CGA codon pairs, and restoration of expression by introduction of a tRNA with an anticodon that base pairs exactly with the CGA codon. This method also reproduces effects of paromomycin and context on stop codon read-through. Five key features of this method contribute to its effectiveness as a selection for regulatory sequences: The system exhibits greater than a 250-fold dynamic range, a quantitative and dose-dependent response to known inhibitory sequences, exquisite resolution that allows nearly complete physical separation of distinct populations, and a reproducible signal between different cells transformed with the identical reporter, all of which are coupled with simple methods involving ligation-independent cloning, to create large libraries. Moreover, we provide evidence that there are sequences within a 9-nt library that cause reduced GFP fluorescence, suggesting that there are novel cis-regulatory sequences to be found even in this short sequence space. This method is widely applicable to the study of both RNA-mediated and codon-mediated effects on expression.

  17. B7-H4-Ig treatment of normal mice changes lymphocyte homeostasis and increases the potential of regulatory T cells

    DEFF Research Database (Denmark)

    Kristensen, Nanna N; Schmidt, Esben G W; Rasmussen, Susanne

    2013-01-01

    Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed by professio......Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed...... of severe combined immune-deficient (SCID) mice undergoing T cell transfer colitis did not influence the course of disease probably reflecting the lack of Tregs in this model of chronic colitis. In conclusion, we show that treatment with B7-H4-Ig in vivo changes lymphocyte homeostasis and increases...

  18. Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

    Science.gov (United States)

    Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

    2014-01-01

    Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:49–56; http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

  19. Identifying Potential Conservation Corridors Along the Mongolia-Russia Border Using Resource Selection Functions: A Case Study on Argali Sheep

    Directory of Open Access Journals (Sweden)

    Buyanaa Chimeddorj

    2013-12-01

    Full Text Available The disruption of animal movements is known to affect wildlife populations, particularly large bodied, free-ranging mammals that require large geographic ranges to survive. Corridors commonly connect fragmented wildlife populations and their habitats, yet identifying corridors rarely uses data on habitat selection and movements of target species. New technologies and analytical tools make it possible to better integrate landscape patterns with spatial behavioral data. We show how resource selection functions can describe habitat suitability using continuous and multivariate metrics to determine potential wildlife movement corridors. During 2005–2010, we studied movements of argali sheep ( Ovis ammon near the Mongolia-Russia border using radio-telemetry and modeled their spatial distribution in relation to landscape features to create a spatially explicit habitat suitability surface to identify potential transboundary conservation corridors. Argali sheep habitat selection in western Mongolia positively correlated with elevation, ruggedness index, and distance to border. In other words, argali were tended use areas with higher elevation, rugged topography, and distances farther from the international border. We suggest that these spatial modeling approaches offer ways to design and identify wildlife corridors more objectively and holistically, and can be applied to many other target species.

  20. Environmental isotope and geophysical techniques to identify groundwater potential zones in drought prone areas of Amravati District, Maharashtra, India

    International Nuclear Information System (INIS)

    Jacob, Noble

    2017-01-01

    The groundwater potential of Anjangaon village in Amaravati district of Maharashtra is generally poor and the water quality is saline in most of the places. Farmers dig open wells (up to 30 m depth) and drill bore wells (100-150 m depth) for domestic and irrigation purposes. Most of the wells failed and farmers are struggling for fresh water in this region. To evaluate the groundwater recharge and to identify the groundwater potential zones an environmental isotope and geophysical study was carried out. Water samples were collected from rain, springs, open wells, bore wells and detention tanks and measured for environmental isotopes such as "1"8O, "2H and "3H. Isotope results indicate that the groundwater is getting modern component of recharge from the rain as well as from the detention tanks. The percentage contributions from the detention tanks were estimated to be about 40 to 90 %. In the southern part of the Anjagaon village, an electrical resistivity survey of the geological formation was carried out and a groundwater potential zone was delineated at 45m depth. The farmers were asked to drill bore wells at the identified depth. The drilled five bore wells yielded perennial source of good quality water

  1. Identifying factors for optimal development of health-related websites: a delphi study among experts and potential future users.

    Science.gov (United States)

    Schneider, Francine; van Osch, Liesbeth; de Vries, Hein

    2012-02-14

    The Internet has become a popular medium for offering tailored and targeted health promotion programs to the general public. However, suboptimal levels of program use in the target population limit the public health impact of these programs. Optimizing program development is considered as one of the main processes to increase usage rates. To distinguish factors potentially related to optimal development of health-related websites by involving both experts and potential users. By considering and incorporating the opinions of experts and potential users in the development process, involvement in the program is expected to increase, consequently resulting in increased appreciation, lower levels of attrition, and higher levels of sustained use. We conducted a systematic three-round Delphi study through the Internet. Both national and international experts (from the fields of health promotion, health psychology, e-communication, and technical Web design) and potential users were invited via email to participate. During this study an extensive list of factors potentially related to optimal development of health-related websites was identified, by focusing on factors related to layout, general and risk information provision, questionnaire use, additional services, and ease of use. Furthermore, we assessed the extent to which experts and potential users agreed on the importance of these factors. Differences as well as similarities among experts and potentials users were deduced. In total, 20 of 62 contacted experts participated in the first round (32% response rate); 60 of 200 contacted experts (30% response rate) and 210 potential users (95% response rate) completed the second-round questionnaire, and 32 of 60 contacted experts completed the third round (53% response rate). Results revealed important factors consented upon by experts and potential users (eg, ease of use, clear structure, and detailed health information provision), as well as differences regarding

  2. Target based screening of small molecule library identifies pregnelonene, a Nrf2 agonist, as a potential radioprotector in zebrafish

    International Nuclear Information System (INIS)

    Joshi, Jayadev; Ghosh, Subhajit; Dimri, Manali; Shrivastava, Nitisha; Indracanti, Prem Kumar; Ray, Jharna

    2014-01-01

    Reactive oxygen species, cellular oxidative stress, tissue inflammation and cell death are the downstream consequences of radiation exposures which ultimately could lead to organism death. Present study aims at identifying potential targets and screening of small molecule compound library for identifying novel and effective radioprotectors. In-silco analysis of known radioprotectors revealed three main function, antioxidant, anti-inflammation and antiapoptosis. In this study, a collection of small molecules (John Hopkins Clinical Compound Library, JHCCL) were screened for these different functions using the biological activity database of NCBI with the help of in-house developed python script. Further, filtering of the JHCCL was done by searching for molecules which are known to be active against target of radiobiological significance, Nrf-2. Close observation of potential hits identified, pregnenolone, as an Nrf-2 agonist which was further evaluated for radioprotection in zebrafish model. Pregnenolone rendered significant protection (at 40 μM; added 1 hour prior to 20 Gy gamma radiation) in terms of damage manifestations (pericardial edema, microcephaly, micropthalmia, yolk sac resorption, curvature of spine, blood flow, body length, heart-beat, blood clot, roughness of skin) and survival advantage (60%) when compared to irradiated control. Further, the ability of pregnenolone to act as a neuroprotectant was also carried out using in-house developed software for assessing neuromotor functions. In comparison to radiation alone group, pregnenolone was found to possess significant neuroactive functions and diminished radiation induced neuronal impairment. Over all these results suggests that pregnenolone is an effective radioprotector which warrants further investigation for validation of its radioprotective action in higher vertebrates. Apart from that the utility of approach to screen out bioactivity data base of various chemical compound libraries for possible

  3. Decision tool for clients with medical issues: a framework for identifying driving risk and potential to return to driving.

    Science.gov (United States)

    Dickerson, Anne E; Bédard, Michel

    2014-04-01

    This paper offers occupational therapy generalists and specialists a new framework by which to consider clinical evaluation data and an older adult's driving risk and potential to resume this previously learned skill. Based on Michon's model describing the hierarchy of driving levels, clinical questions identify the factors that may affect a client's fitness to drive. The first part is intended to support clinical judgment of whether a client needs a driving evaluation by a driver rehabilitation specialist. The second part offers a framework to organize clinical data that are already known and determine what other evaluation information is justified and necessary to make a driving recommendation. Methods and rational for use are discussed.

  4. Differentially expressed plasma microRNAs and the potential regulatory function of Let-7b in chronic thromboembolic pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Lijuan Guo

    Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1 thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2 Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3 ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs. These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of

  5. Differentially Expressed Plasma MicroRNAs and the Potential Regulatory Function of Let-7b in Chronic Thromboembolic Pulmonary Hypertension

    Science.gov (United States)

    Guo, Lijuan; Yang, Yuanhua; Liu, Jie; Wang, Lei; Li, Jifeng; Wang, Ying; Liu, Yan; Gu, Song; Gan, Huili; Cai, Jun; Yuan, Jason X.-J.; Wang, Jun; Wang, Chen

    2014-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1) thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2) Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3) ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by

  6. Eco-Efficient Process Improvement at the Early Development Stage: Identifying Environmental and Economic Process Hotspots for Synergetic Improvement Potential.

    Science.gov (United States)

    Piccinno, Fabiano; Hischier, Roland; Seeger, Stefan; Som, Claudia

    2018-05-15

    We present here a new eco-efficiency process-improvement method to highlight combined environmental and costs hotspots of the production process of new material at a very early development stage. Production-specific and scaled-up results for life cycle assessment (LCA) and production costs are combined in a new analysis to identify synergetic improvement potentials and trade-offs, setting goals for the eco-design of new processes. The identified hotspots and bottlenecks will help users to focus on the relevant steps for improvements from an eco-efficiency perspective and potentially reduce their associated environmental impacts and production costs. Our method is illustrated with a case study of nanocellulose. The results indicate that the production route should start with carrot pomace, use heat and solvent recovery, and deactivate the enzymes with bleach instead of heat. To further improve the process, the results show that focus should be laid on the carrier polymer, sodium alginate, and the production of the GripX coating. Overall, the method shows that the underlying LCA scale-up framework is valuable for purposes beyond conventional LCA studies and is applicable at a very early stage to provide researchers with a better understanding of their production process.

  7. The National Radiation Protection Authority and its regulatory programme. Potential benefits of the CTBT and thoughts on cooperation

    International Nuclear Information System (INIS)

    Gebeyehu, G.

    1999-01-01

    In the past years Ethiopia became an active participant in the scientific and political development as well as supporter of the CTBT. This paper describes the designated institution for the CTBT implementation in the area of Radionuclides in Ethiopia and its scientific and regulatory program as well as main activities concerning application techniques. The second part of the paper accounts for the links between the objectives of the national institute with the CTBT. It draws substantive details about benefits that could arise from participating in CTBT implementation and summarizes the discussion by suggesting modalities for building partnership and cooperation

  8. A Point Source of a Different Color: Identifying a Gap in United States Regulatory Policy for “Green” CSO Treatment Using Constructed Wetlands

    Directory of Open Access Journals (Sweden)

    Zeno F. Levy

    2014-04-01

    Full Text Available Up to 850 billion gallons of untreated combined sewer overflow (CSO is discharged into waters of the United States each year. Recent changes in CSO management policy support green infrastructure (GI technologies as “front of the pipe” approaches to discharge mitigation by detention/reduction of urban stormwater runoff. Constructed wetlands for CSO treatment have been considered among suites of GI solutions. However, these wetlands differ fundamentally from other GI technologies in that they are “end of the pipe” treatment systems that discharge from a point source, and are therefore regulated in the U.S. under the National Pollution Discharge Elimination System (NPDES. We use a comparative regulatory analysis to examine the U.S. policy framework for CSO treatment wetlands. We find in all cases that permitting authorities have used best professional judgment to determine effluent limits and compliance monitoring requirements, referencing technology and water quality-based standards originally developed for traditional “grey” treatment systems. A qualitative comparison with Europe shows less stringent regulatory requirements, perhaps due to institutionalized design parameters. We recommend that permitting authorities develop technical guidance documents for evaluation of “green” CSO treatment systems that account for their unique operational concerns and benefits with respect to sustainable development.

  9. A big data pipeline: Identifying dynamic gene regulatory networks from time-course Gene Expression Omnibus data with applications to influenza infection.

    Science.gov (United States)

    Carey, Michelle; Ramírez, Juan Camilo; Wu, Shuang; Wu, Hulin

    2018-07-01

    A biological host response to an external stimulus or intervention such as a disease or infection is a dynamic process, which is regulated by an intricate network of many genes and their products. Understanding the dynamics of this gene regulatory network allows us to infer the mechanisms involved in a host response to an external stimulus, and hence aids the discovery of biomarkers of phenotype and biological function. In this article, we propose a modeling/analysis pipeline for dynamic gene expression data, called Pipeline4DGEData, which consists of a series of statistical modeling techniques to construct dynamic gene regulatory networks from the large volumes of high-dimensional time-course gene expression data that are freely available in the Gene Expression Omnibus repository. This pipeline has a consistent and scalable structure that allows it to simultaneously analyze a large number of time-course gene expression data sets, and then integrate the results across different studies. We apply the proposed pipeline to influenza infection data from nine studies and demonstrate that interesting biological findings can be discovered with its implementation.

  10. Transcriptome analysis of the Cryptocaryon irritans tomont stage identifies potential genes for the detection and control of cryptocaryonosis

    Directory of Open Access Journals (Sweden)

    Wan Kiew-Lian

    2010-01-01

    Full Text Available Abstract Background Cryptocaryon irritans is a parasitic ciliate that causes cryptocaryonosis (white spot disease in marine fish. Diagnosis of cryptocaryonosis often depends on the appearance of white spots on the surface of the fish, which are usually visible only during later stages of the disease. Identifying suitable biomarkers of this parasite would aid the development of diagnostic tools and control strategies for C. irritans. The C. irritans genome is virtually unexplored; therefore, we generated and analyzed expressed sequence tags (ESTs of the parasite to identify genes that encode for surface proteins, excretory/secretory proteins and repeat-containing proteins. Results ESTs were generated from a cDNA library of C. irritans tomonts isolated from infected Asian sea bass, Lates calcarifer. Clustering of the 5356 ESTs produced 2659 unique transcripts (UTs containing 1989 singletons and 670 consensi. BLAST analysis showed that 74% of the UTs had significant similarity (E-value -5 to sequences that are currently available in the GenBank database, with more than 15% of the significant hits showing unknown function. Forty percent of the UTs had significant similarity to ciliates from the genera Tetrahymena and Paramecium. Comparative gene family analysis with related taxa showed that many protein families are conserved among the protozoans. Based on gene ontology annotation, functional groups were successfully assigned to 790 UTs. Genes encoding excretory/secretory proteins and membrane and membrane-associated proteins were identified because these proteins often function as antigens and are good antibody targets. A total of 481 UTs were classified as encoding membrane proteins, 54 were classified as encoding for membrane-bound proteins, and 155 were found to contain excretory/secretory protein-coding sequences. Amino acid repeat-containing proteins and GPI-anchored proteins were also identified as potential candidates for the development of

  11. Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers.

    Science.gov (United States)

    Laíns, Inês; Kelly, Rachel S; Miller, John B; Silva, Rufino; Vavvas, Demetrios G; Kim, Ivana K; Murta, Joaquim N; Lasky-Su, Jessica; Miller, Joan W; Husain, Deeba

    2018-02-01

    To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS). Cross-sectional observational study. We prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease. All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages. We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10 -9 ) among these metabolites. Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest

  12. Identifying Potential Areas of Human Zika Infection in the City of Los Angeles, California by Use of Remote Sensing Imagery

    Science.gov (United States)

    Lee, J.

    2017-12-01

    As of April 2017, California is the third most prevalent state on the United States for Zika Infection and Southern California has an ever growing population of Aedes mosquitos. Zika is a disease which poses a significant risk to humans and other mammals due to its effects on pregnancy. This emerging disease is highly contagious due to its spread of infection primarily by Aedes aegypti mosquitos. Aedes mosquitos are able to breed in small rain collecting containers which allow the species to persevere in urban and semi urban environments. We hope to identify potential areas with risk of human infection within Los Angeles and its surrounding areas. This study integrates remote sensing, GIS, statistical, and environmental techniques to study favorable habitats for this particular species of mosquitos and their larvae. The study of the geographic and landscape factors which promote the larvae development allow for the disease spread to be analyzed and modeled. There are several goals in the development of this study. These include the coordination of statistical data with local epidemiology departments, identify workflows to improve efficiency, create models which can be utilized for disease prevention, and identify geographic risk factors for the spread of Zika.

  13. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  14. Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Min-Yi Lee

    Full Text Available Inflammation plays a key role in coronary artery disease (CAD and other manifestations of atherosclerosis. Recently, urinary proteins were found to be useful markers for reflecting inflammation status of different organs. To identify potential biomarker for diagnosis of CAD, we performed one-dimensional SDS-gel electrophoresis followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS. Among the proteins differentially expressed in urine samples, monocyte antigen CD14 was found to be consistently expressed in higher amounts in the CAD patients as compared to normal controls. Using enzyme-linked immunosorbent assays to analyze the concentrations of CD14 in urine and serum, we confirmed that urinary CD14 levels were significantly higher in patients (n = 73 with multi-vessel and single vessel CAD than in normal control (n = 35 (P < 0.001. Logistic regression analysis further showed that urinary CD14 concentration level is associated with severity or number of diseased vessels and SYNTAX score after adjustment for potential confounders. Concomitantly, the proportion of CD14+ monocytes was significantly increased in CAD patients (59.7 ± 3.6% as compared with healthy controls (14.9 ± 2.1% (P < 0.001, implicating that a high level of urinary CD14 may be potentially involved in mechanism(s leading to CAD pathogenesis. By performing shotgun proteomics, we further revealed that CD14-associated inflammatory response networks may play an essential role in CAD. In conclusion, the current study has demonstrated that release of CD14 in urine coupled with more CD14+ monocytes in CAD patients is significantly correlated with severity of CAD, pointing to the potential application of urinary CD14 as a novel noninvasive biomarker for large-scale diagnostic screening of susceptible CAD patients.

  15. A GIS-based approach for identifying potential runoff harvesting sites in the Thukela River basin, South Africa

    Science.gov (United States)

    de Winnaar, G.; Jewitt, G. P. W.; Horan, M.

    Water scarce countries such as South Africa are subject to various hydrological constraints which can often be attributed to poor rainfall partitioning, particularly within resource poor farming communities that are reliant on rainfed agriculture. Recent initiatives to address this have shifted focus to explore more efficient alternatives to water supply and the recognition of numerous opportunities to implement runoff harvesting as a means to supplement water availability. However, increasing the implementation of runoff harvesting, without encountering unintended impacts on downstream hydrological and ecological systems, requires better understanding of the hydrologic and environmental impacts at catchment scale. In this paper the representation of spatial variations in landscape characteristics such as soil, land use, rainfall and slope information is shown to be an important step in identifying potential runoff harvesting sites, after which modelling the hydrological response in catchments where extensive runoff harvesting is being considered can be performed and likely impacts assessed. Geographic information systems (GIS) was utilised as an integrating tool to store, analyse and manage spatial information and when linked to hydrological response models, provided a rational means to facilitate decision making by providing catchment level identification, planning and assessment of runoff harvesting sites as illustrated by a case study at the Potshini catchment, a small sub-catchment in the Thukela River basin, South Africa. Through the linked GIS, potential runoff harvesting sites are identified relative to areas that concentrate runoff and where the stored water will be appropriately distributed. Based on GIS analysis it was found that 17% percent of the Potshini catchment area has a high potential for generating surface runoff, whereas an analysis of all factors which influence the location of such systems, shows that 18% is highly suitable for runoff

  16. Energy Efficiency of Technological Equipment at the Economic Agent by Identifying the Points with Recoverable Heat Potential

    Directory of Open Access Journals (Sweden)

    Arina Negoiţescu

    2017-11-01

    Full Text Available For an energy-efficient future, the EU needs to step up its efforts to maximize energy savings. In this context, the paper addresses the steps needed to establish energy efficiency measures and proposes effective measures to reduce consumption by recovering large amounts of energy lost to industrial consumers. The points with the highest recoverable energy potential have been identified and it is proposed to install the heat recovery systems on the flue gas exhaust circuits and polluted air from Industrial Technological Equipment (ITE such as dyeing/drying cabins (DDC. Therefore, whenever possible and as small as energy saving, energy recovery solutions at any level, but especially at local level, need to be applied. In conclusion, by concentrating all the energy-saving efforts that are still being wasted, Europe can contribute, by saving energy, to ensuring a sustainable energy future

  17. TH-B-BRC-00: How to Identify and Resolve Potential Clinical Errors Before They Impact Patients Treatment: Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.

  18. TH-B-BRC-00: How to Identify and Resolve Potential Clinical Errors Before They Impact Patients Treatment: Lessons Learned

    International Nuclear Information System (INIS)

    2016-01-01

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803

  19. General Approach to Identifying Potential Targets for Cancer Imaging by Integrated Bioinformatics Analysis of Publicly Available Genomic Profiles

    Directory of Open Access Journals (Sweden)

    Yongliang Yang

    2011-03-01

    Full Text Available Molecular imaging has moved to the forefront of drug development and biomedical research. The identification of appropriate imaging targets has become the touchstone for the accurate diagnosis and prognosis of human cancer. Particularly, cell surface- or membrane-bound proteins are attractive imaging targets for their aberrant expression, easily accessible location, and unique biochemical functions in tumor cells. Previously, we published a literature mining of potential targets for our in-house enzyme-mediated cancer imaging and therapy technology. Here we present a simple and integrated bioinformatics analysis approach that assembles a public cancer microarray database with a pathway knowledge base for ascertaining and prioritizing upregulated genes encoding cell surface- or membrane-bound proteins, which could serve imaging targets. As examples, we obtained lists of potential hits for six common and lethal human tumors in the prostate, breast, lung, colon, ovary, and pancreas. As control tests, a number of well-known cancer imaging targets were detected and confirmed by our study. Further, by consulting gene-disease and protein-disease databases, we suggest a number of significantly upregulated genes as promising imaging targets, including cell surface-associated mucin-1, prostate-specific membrane antigen, hepsin, urokinase plasminogen activator receptor, and folate receptors. By integrating pathway analysis, we are able to organize and map “focused” interaction networks derived from significantly dysregulated entity pairs to reflect important cellular functions in disease processes. We provide herein an example of identifying a tumor cell growth and proliferation subnetwork for prostate cancer. This systematic mining approach can be broadly applied to identify imaging or therapeutic targets for other human diseases.

  20. Planting sentinel European trees in eastern Asia as a novel method to identify potential insect pest invaders.

    Science.gov (United States)

    Roques, Alain; Fan, Jian-Ting; Courtial, Béatrice; Zhang, Yan-Zhuo; Yart, Annie; Auger-Rozenberg, Marie-Anne; Denux, Olivier; Kenis, Marc; Baker, Richard; Sun, Jiang-Hua

    2015-01-01

    Quarantine measures to prevent insect invasions tend to focus on well-known pests but a large proportion of the recent invaders were not known to cause significant damage in their native range, or were not even known to science before their introduction. A novel method is proposed to detect new potential pests of woody plants in their region of origin before they are introduced to a new continent. Since Asia is currently considered to be the main supplier of insect invaders to Europe, sentinel trees were planted in China during 2007-2011 as an early warning tool to identify the potential for additional Asian insect species to colonize European trees. Seedlings (1-1.5 m tall) of five broadleaved (Quercus petraea, Q. suber, Q. ilex, Fagus sylvatica, and Carpinus betulus) and two conifer species (Abies alba and Cupressus sempervirens) were planted in blocks of 100 seedlings at two widely separated sites (one in a nursery near Beijing and the other in a forest environment near Fuyang in eastern China), and then regularly surveyed for colonization by insects. A total of 104 insect species, mostly defoliators, were observed on these new hosts, and at least six species were capable of larval development. Although a number of the insects observed were probably incidental feeders, 38 species had more than five colonization events, mostly infesting Q. petraea, and could be considered as being capable of switching to European trees if introduced to Europe. Three years was shown to be an appropriate duration for the experiment, since the rate of colonization then tended to plateau. A majority of the identified species appeared to have switched from agricultural crops and fruit trees rather than from forest trees. Although these results are promising, the method is not appropriate for xylophagous pests and other groups developing on larger trees. Apart from the logistical problems, the identification to species level of the specimens collected was a major difficulty. This

  1. Quantitative structure-activity relationships for predicting potential ecological hazard of organic chemicals for use in regulatory risk assessments.

    Science.gov (United States)

    Comber, Mike H I; Walker, John D; Watts, Chris; Hermens, Joop

    2003-08-01

    The use of quantitative structure-activity relationships (QSARs) for deriving the predicted no-effect concentration of discrete organic chemicals for the purposes of conducting a regulatory risk assessment in Europe and the United States is described. In the United States, under the Toxic Substances Control Act (TSCA), the TSCA Interagency Testing Committee and the U.S. Environmental Protection Agency (U.S. EPA) use SARs to estimate the hazards of existing and new chemicals. Within the Existing Substances Regulation in Europe, QSARs may be used for data evaluation, test strategy indications, and the identification and filling of data gaps. To illustrate where and when QSARs may be useful and when their use is more problematic, an example, methyl tertiary-butyl ether (MTBE), is given and the predicted and experimental data are compared. Improvements needed for new QSARs and tools for developing and using QSARs are discussed.

  2. Environmental concerns and regulatory initiatives related to hydraulic fracturing in shale gas formations: potential implications for North American gas supply

    Energy Technology Data Exchange (ETDEWEB)

    Sumi, Lisa [Earthworks (Canada)

    2010-09-15

    Shale gas resources have been referred to as a game changer for North America and it is expected that shale gas will account for over 30% of the natural gas production in North America by 2020. However, the development of this resource has raised several concerns, notably in terms of water use and contamination; more stringent regulations could be implemented in the coming years. The aim of this paper is to present the effect that more stringent regulations would have on gas development in the Marcellus shale, which accounts for 20% of North American shale gas production. Information on hydraulic fracturing and its environmental impacts is provided herein, along with information on the regulatory initiatives underway in the Marcellus shale region. This paper pointed out that novel regulations relating to shale gas development could significantly reduce the growth in shale gas production.

  3. 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.

  4. In silico repositioning-chemogenomics strategy identifies new drugs with potential activity against multiple life stages of Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Bruno J Neves

    2015-01-01

    Full Text Available Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD, DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes.

  5. Can empathy, other personality attributes, and level of positive social influence in medical school identify potential leaders in medicine?

    Science.gov (United States)

    Hojat, Mohammadreza; Michalec, Barret; Veloski, J Jon; Tykocinski, Mark L

    2015-04-01

    To test the hypotheses that medical students recognized by peers as the most positive social influencers would score (1) high on measures of engaging personality attributes that are conducive to relationship building (empathy, sociability, activity, self-esteem), and (2) low on disengaging personality attributes that are detrimental to interpersonal relationships (loneliness, neuroticism, aggression-hostility, impulsive sensation seeking). The study included 666 Jefferson Medical College students who graduated in 2011-2013. Students used a peer nomination instrument to identify classmates who had a positive influence on their professional and personal development. At matriculation, these students had completed a survey that included the Jefferson Scale of Empathy and Zuckerman-Kuhlman Personality Questionnaire short form and abridged versions of the Rosenberg Self-Esteem Scale and UCLA Loneliness Scale. In multivariate analyses of variance, the method of contrasted groups was used to compare the personality attributes of students nominated most frequently by their peers as positive influencers (top influencers [top 25% in their class distribution], n = 176) with those of students nominated least frequently (bottom influencers [bottom 25%], n = 171). The top influencers scored significantly higher on empathy, sociability, and activity and significantly lower on loneliness compared with the bottom influencers. However, the effect size estimates of the differences were moderate at best. The research hypotheses were partially confirmed. Positive social influencers appear to possess personality attributes conducive to relationship building, which is an important feature of effective leadership. The findings have implications for identifying and training potential leaders in medicine.

  6. Identifying potential effects of climate change on the development of water resources in Pinios River Basin, Central Greece

    Science.gov (United States)

    Arampatzis, G.; Panagopoulos, A.; Pisinaras, V.; Tziritis, E.; Wendland, F.

    2018-05-01

    The aim of the present study is to assess the future spatial and temporal distribution of precipitation and temperature, and relate the corresponding change to water resources' quantitative status in Pinios River Basin (PRB), Thessaly, Greece. For this purpose, data from four Regional Climate Models (RCMs) for the periods 2021-2100 driven by several General Circulation Models (GCMs) were collected and bias-correction was performed based on linear scaling method. The bias-correction was made based on monthly precipitation and temperature data collected for the period 1981-2000 from 57 meteorological stations in total. The results indicate a general trend according to which precipitation is decreasing whilst temperature is increasing to an extent that varies depending on each particular RCM-GCM output. On the average, annual precipitation change for the period 2021-2100 was about - 80 mm, ranging between - 149 and + 35 mm, while the corresponding change for temperature was 2.81 °C, ranging between 1.48 and 3.72 °C. The investigation of potential impacts to the water resources demonstrates that water availability is expected to be significantly decreased in the already water-stressed PRB. The water stresses identified are related to the potential decreasing trend in groundwater recharge and the increasing trend in irrigation demand, which constitutes the major water consumer in PRB.

  7. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

    Science.gov (United States)

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

    2017-11-01

    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. Experimental antibiotic treatment identifies potential pathogens of white band disease in the endangered Caribbean coral Acropora cervicornis.

    Science.gov (United States)

    Sweet, M J; Croquer, A; Bythell, J C

    2014-08-07

    of the other potential pathogens identified in this study.

  9. Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma.

    Directory of Open Access Journals (Sweden)

    Rebecca King

    2018-01-01

    Full Text Available Central corneal thickness (CCT is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG. The present study uses the BXD Recombinant Inbred (RI strains to identify novel quantitative trait loci (QTLs modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60-100 days of age. The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org. The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2 contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2, with the highest significance level of p = 10-6 for

  10. Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

    Science.gov (United States)

    Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

    2015-12-01

    Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

  11. What's down below? Current and potential future applications of geophysical techniques to identify subsurface permafrost conditions (Invited)

    Science.gov (United States)

    Douglas, T. A.; Bjella, K.; Campbell, S. W.

    2013-12-01

    For infrastructure design, operations, and maintenance requirements in the North the ability to accurately and efficiently detect the presence (or absence) of ground ice in permafrost terrains is a serious challenge. Ground ice features including ice wedges, thermokarst cave-ice, and segregation ice are present in a variety of spatial scales and patterns. Currently, most engineering applications use borehole logging and sampling to extrapolate conditions at the point scale. However, there is high risk of over or under estimating the presence of frozen or unfrozen features when relying on borehole information alone. In addition, boreholes are costly, especially for planning linear structures like roads or runways. Predicted climate warming will provide further challenges for infrastructure development and transportation operations where permafrost degradation occurs. Accurately identifying the subsurface character in permafrost terrains will allow engineers and planners to cost effectively create novel infrastructure designs to withstand the changing environment. There is thus a great need for a low cost rapidly deployable, spatially extensive means of 'measuring' subsurface conditions. Geophysical measurements, both terrestrial and airborne, have strong potential to revolutionize our way of mapping subsurface conditions. Many studies in continuous and discontinuous permafrost have used geophysical measurements to identify discrete features and repeatable patterns in the subsurface. The most common measurements include galvanic and capacitive coupled resistivity, ground penetrating radar, and multi frequency electromagnetic induction techniques. Each of these measurements has strengths, weaknesses, and limitations. By combining horizontal geophysical measurements, downhole geophysics, multispectral remote sensing images, LiDAR measurements, and soil and vegetation mapping we can start to assemble a holistic view of how surface conditions and standoff measurements

  12. Enzymatic study on AtCCD4 and AtCCD7 and their potential to form acyclic regulatory metabolites

    KAUST Repository

    Bruno, Mark

    2016-09-29

    The Arabidopsis carotenoid cleavage dioxygenase 4 (AtCCD4) is a negative regulator of the carotenoid content of seeds and has recently been suggested as a candidate for the generation of retrograde signals that are thought to derive from the cleavage of poly-cis-configured carotene desaturation intermediates. In this work, we investigated the activity of AtCCD4 in vitro and used dynamic modeling to determine its substrate preference. Our results document strict regional specificity for cleavage at the C9–C10 double bond in carotenoids and apocarotenoids, with preference for carotenoid substrates and an obstructing effect on hydroxyl functions, and demonstrate the specificity for all-trans-configured carotenes and xanthophylls. AtCCD4 cleaved substrates with at least one ionone ring and did not convert acyclic carotene desaturation intermediates, independent of their isomeric states. These results do not support a direct involvement of AtCCD4 in generating the supposed regulatory metabolites. In contrast, the strigolactone biosynthetic enzyme AtCCD7 converted 9-cis-configured acyclic carotenes, such as 9-cis-ζ-carotene, 9\\'-cis-neurosporene, and 9-cis-lycopene, yielding 9-cis-configured products and indicating that AtCCD7, rather than AtCCD4, is the candidate for forming acyclic retrograde signals.

  13. Enzymatic study on AtCCD4 and AtCCD7 and their potential to form acyclic regulatory metabolites

    KAUST Repository

    Bruno, Mark; Koschmieder, Julian; Wuest, Florian; Schaub, Patrick; Fehling-Kaschek, Mirjam; Timmer, Jens; Beyer, Peter; Al-Babili, Salim

    2016-01-01

    The Arabidopsis carotenoid cleavage dioxygenase 4 (AtCCD4) is a negative regulator of the carotenoid content of seeds and has recently been suggested as a candidate for the generation of retrograde signals that are thought to derive from the cleavage of poly-cis-configured carotene desaturation intermediates. In this work, we investigated the activity of AtCCD4 in vitro and used dynamic modeling to determine its substrate preference. Our results document strict regional specificity for cleavage at the C9–C10 double bond in carotenoids and apocarotenoids, with preference for carotenoid substrates and an obstructing effect on hydroxyl functions, and demonstrate the specificity for all-trans-configured carotenes and xanthophylls. AtCCD4 cleaved substrates with at least one ionone ring and did not convert acyclic carotene desaturation intermediates, independent of their isomeric states. These results do not support a direct involvement of AtCCD4 in generating the supposed regulatory metabolites. In contrast, the strigolactone biosynthetic enzyme AtCCD7 converted 9-cis-configured acyclic carotenes, such as 9-cis-ζ-carotene, 9'-cis-neurosporene, and 9-cis-lycopene, yielding 9-cis-configured products and indicating that AtCCD7, rather than AtCCD4, is the candidate for forming acyclic retrograde signals.

  14. Enzymatic study on AtCCD4 and AtCCD7 and their potential to form acyclic regulatory metabolites

    Science.gov (United States)

    Bruno, Mark; Koschmieder, Julian; Wuest, Florian; Schaub, Patrick; Fehling-Kaschek, Mirjam; Timmer, Jens; Beyer, Peter; Al-Babili, Salim

    2016-01-01

    The Arabidopsis carotenoid cleavage dioxygenase 4 (AtCCD4) is a negative regulator of the carotenoid content of seeds and has recently been suggested as a candidate for the generation of retrograde signals that are thought to derive from the cleavage of poly-cis-configured carotene desaturation intermediates. In this work, we investigated the activity of AtCCD4 in vitro and used dynamic modeling to determine its substrate preference. Our results document strict regional specificity for cleavage at the C9–C10 double bond in carotenoids and apocarotenoids, with preference for carotenoid substrates and an obstructing effect on hydroxyl functions, and demonstrate the specificity for all-trans-configured carotenes and xanthophylls. AtCCD4 cleaved substrates with at least one ionone ring and did not convert acyclic carotene desaturation intermediates, independent of their isomeric states. These results do not support a direct involvement of AtCCD4 in generating the supposed regulatory metabolites. In contrast, the strigolactone biosynthetic enzyme AtCCD7 converted 9-cis-configured acyclic carotenes, such as 9-cis-ζ-carotene, 9'-cis-neurosporene, and 9-cis-lycopene, yielding 9-cis-configured products and indicating that AtCCD7, rather than AtCCD4, is the candidate for forming acyclic retrograde signals. PMID:27811075

  15. Planting sentinel European trees in eastern Asia as a novel method to identify potential insect pest invaders.

    Directory of Open Access Journals (Sweden)

    Alain Roques

    Full Text Available Quarantine measures to prevent insect invasions tend to focus on well-known pests but a large proportion of the recent invaders were not known to cause significant damage in their native range, or were not even known to science before their introduction. A novel method is proposed to detect new potential pests of woody plants in their region of origin before they are introduced to a new continent. Since Asia is currently considered to be the main supplier of insect invaders to Europe, sentinel trees were planted in China during 2007-2011 as an early warning tool to identify the potential for additional Asian insect species to colonize European trees. Seedlings (1-1.5 m tall of five broadleaved (Quercus petraea, Q. suber, Q. ilex, Fagus sylvatica, and Carpinus betulus and two conifer species (Abies alba and Cupressus sempervirens were planted in blocks of 100 seedlings at two widely separated sites (one in a nursery near Beijing and the other in a forest environment near Fuyang in eastern China, and then regularly surveyed for colonization by insects. A total of 104 insect species, mostly defoliators, were observed on these new hosts, and at least six species were capable of larval development. Although a number of the insects observed were probably incidental feeders, 38 species had more than five colonization events, mostly infesting Q. petraea, and could be considered as being capable of switching to European trees if introduced to Europe. Three years was shown to be an appropriate duration for the experiment, since the rate of colonization then tended to plateau. A majority of the identified species appeared to have switched from agricultural crops and fruit trees rather than from forest trees. Although these results are promising, the method is not appropriate for xylophagous pests and other groups developing on larger trees. Apart from the logistical problems, the identification to species level of the specimens collected was a major

  16. Using Satellite Data to Identify the Causes of and Potential Solutions for Yield Gaps in India's Wheat Belt

    Science.gov (United States)

    Jain, M.; Singh, B.; Srivastava, A.; Malik, R. K.; McDonald, A.; Lobell, D. B.

    2017-12-01

    Food security will be increasingly challenged by climate change, natural resource degradation, and population growth. Wheat yields, in particular, have already stagnated in many regions and will be further affected by warming temperatures. Despite these challenges, wheat yields can be increased by improving management practices in regions with existing yield gaps. We present two studies that are using satellite data to better understand the factors contributing to yield gaps and potential interventions to close yield gaps in India's main wheat belt, the Indo-Gangetic Plains (IGP). To identify the magnitude and causes of current yield gaps, we produced 30 meter resolution yield maps from 2001 to 2015 using Landsat sallite data and a new method that translates satellite vegetation indices to yield estimates using crop model simulations, bypassing the need for ground calibration data. This is one of the first attempts to apply this method to a smallholder agriculture system, where ground calibration data are rarely available. We find that yields can be increased by 11% on average and up to 32% in the eastern IGP by improving management to current best practices within a given district. Additionally, if current best practices from the highest-yielding state of Punjab are implemented in the eastern IGP, yields could increase by almost 110%. Considering the factors that most influence yields, later sow dates and warmer temperatures are most associated with low yields across the IGP. This suggests that strategies to reduce the negative effects of heat stress, like earlier sowing and planting heat-tolerant wheat varieties, are critical to increasing wheat yields in this globally-important agricultural region. We also apply this method to high-resolution micro-satellite data (impacts of a new fertilizer spreader technology and identify whether satellite data can be used to appropriately target this intervention.

  17. Kinase Gene Expression Profiling of Metastatic Clear Cell Renal Cell Carcinoma Tissue Identifies Potential New Therapeutic Targets.

    Directory of Open Access Journals (Sweden)

    Pooja Ghatalia

    Full Text Available Kinases are therapeutically actionable targets. Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR and mammalian target of rapamycin (mTOR improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC, but are not curative. Metastatic tumor tissue has not been comprehensively studied for kinase gene expression. Paired intra-patient kinase gene expression analysis in primary tumor (T, matched normal kidney (N and metastatic tumor tissue (M may assist in identifying drivers of metastasis and prioritizing therapeutic targets. We compared the expression of 519 kinase genes using NanoString in T, N and M in 35 patients to discover genes over-expressed in M compared to T and N tissue. RNA-seq data derived from ccRCC tumors in The Cancer Genome Atlas (TCGA were used to demonstrate differential expression of genes in primary tumor tissue from patients that had metastasis at baseline (n = 79 compared to those that did not develop metastasis for at least 2 years (n = 187. Functional analysis was conducted to identify key signaling pathways by using Ingenuity Pathway Analysis. Of 10 kinase genes overexpressed in metastases compared to primary tumor in the discovery cohort, 9 genes were also differentially expressed in TCGA primary tumors with metastasis at baseline compared to primary tumors without metastasis for at least 2 years: EPHB2, AURKA, GSG2, IKBKE, MELK, CSK, CHEK2, CDC7 and MAP3K8; p<0.001. The top pathways overexpressed in M tissue were pyridoxal 5'-phosphate salvage, salvage pathways of pyrimidine ribonucleotides, NF-kB signaling, NGF signaling and cell cycle control of chromosomal replication. The 9 kinase genes validated to be over-expressed in metastatic ccRCC may represent currently unrecognized but potentially actionable therapeutic targets that warrant functional validation.

  18. Identifying Faults Associated with the 2001 Avoca Induced(?) Seismicity Sequence of Western New York State Using Potential Field Wavelets.

    Science.gov (United States)

    Horowitz, F. G.; Ebinger, C.; Jordan, T. E.

    2017-12-01

    Results from recent DOE and USGS sponsored projects in the (intraplate) northeastern portions of the US and southeastern portions of Canada have identified locations of steeply dipping structures - many previously unknown - from a Poisson wavelet multiscale edge ('worm') analysis of gravity and magnetic fields. The Avoca sequence of induced(?) seismicity in western New York state occurred during January and February of 2001. The Avoca earthquake sequence is associated with industrial hydraulic fracturing activity "related to a proposed natural gas storage facility near Avoca to be constructed by solution mining" (Kim, 2001). The main Avoca event was a felt Mb = 3.2 earthquake on Feb. 3, 2001 recorded by the Lamont Cooperative Seismic Network. Earlier, smaller events were located by the Canadian Geological Survey's seismic network north of the Canadian border - implying that the event locations might be biased because they occurred off the southern edge of the array. Some of these events were also felt locally, according to local newspaper reports. By plotting the location of the seismic events and that of the injection well - reported via it's API number - we find a strong correlation with structures detected via our potential field worms. The injection occurred near a NE-SW striking structure that was not activated. All but one of the earthquakes occurred about 5 km north of the injection well on or nearby to an E-W striking structure that appears to intersect the NE-SW structure. The final, small (MN=2.2) earthquake was located on a different complex structure about 10 km north of the other events. We suggest that potential field methods such as ours might be appropriate to locating structures of concern for induced seismic activity in association with industrial activity. Reference: Kim, W.-Y. (2001). The Lamont cooperative seismic network and the national seismic system: Earthquake hazard studies in the northeastern United States. Tech. Rep. 98-01, Lamont

  19. Identifying and Mitigating Potential Nutrient and Sediment Hot Spots under a Future Scenario in the Missouri River Basin

    Energy Technology Data Exchange (ETDEWEB)

    Wu, May [Argonne National Lab. (ANL), Argonne, IL (United States); Zhang, Zhonglong [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-09-01

    Using the Soil and Water Assessment Tool (SWAT) for large-scale watershed modeling could be useful for evaluating the quality of the water in regions that are dominated by nonpoint sources in order to identify potential “hot spots” for which mitigating strategies could be further developed. An analysis of water quality under future scenarios in which changes in land use would be made to accommodate increased biofuel production was developed for the Missouri River Basin (MoRB) based on a SWAT model application. The analysis covered major agricultural crops and biofuel feedstock in the MoRB, including pasture land, hay, corn, soybeans, wheat, and switchgrass. The analysis examined, at multiple temporal and spatial scales, how nitrate, organic nitrogen, and total nitrogen; phosphorus, organic phosphorus, inorganic phosphorus, and total phosphorus; suspended sediments; and water flow (water yield) would respond to the shifts in land use that would occur under proposed future scenarios. The analysis was conducted at three geospatial scales: (1) large tributary basin scale (two: Upper MoRB and Lower MoRB); (2) regional watershed scale (seven: Upper Missouri River, Middle Missouri River, Middle Lower Missouri River, Lower Missouri River, Yellowstone River, Platte River, and Kansas River); and (3) eight-digit hydrologic unit (HUC-8) subbasin scale (307 subbasins). Results showed that subbasin-level variations were substantial. Nitrogen loadings decreased across the entire Upper MoRB, and they increased in several subbasins in the Lower MoRB. Most nitrate reductions occurred in lateral flow. Also at the subbasin level, phosphorus in organic, sediment, and soluble forms was reduced by 35%, 45%, and 65%, respectively. Suspended sediments increased in 68% of the subbasins. The water yield decreased in 62% of the subbasins. In the Kansas River watershed, the water quality improved significantly with regard to every nitrogen and phosphorus compound. The improvement was

  20. Three newly identified galectin homologues from triangle sail mussel (Hyriopsis cumingii) function as potential pattern-recognition receptors.

    Science.gov (United States)

    Zhao, Ling-Ling; Hui, Kaimin; Wang, Yu-Qing; Wang, Yue; Ren, Qian; Li, Xin-Cang

    2018-05-01

    Galactoside-binding lectins, also known as galectins, play crucial roles in innate immune response in invertebrates. In this study, three cDNA sequences from Hyriopsis cumingii were identified and collectively called HcGalec genes. Each of the three deduced HcGalec proteins contained a galactose-binding lectin domain or a GLECT domain. All the three HcGalec genes are mainly present in the hepatopancreas and gills, and their expression is induced at 24 h after bacterial challenge. Three recombinant HcGalec proteins can bind and agglutinate (Ca 2+ -dependent) various microorganisms, including Gram-positive and Gram-negative bacteria. These proteins can attach to mannan and peptidoglycan. Meanwhile, the expression of the three HcGalec genes in the gills were significantly down-regulated after dsRNA interference (HcGalec1-RNAi, HcGalec2-RNAi, and HcGalec3-RNAi) and Vibrio parahaemolyticus injection. The expression levels of some antimicrobial peptides, including lysozyme 1 and lysozyme 2, were also markedly decreased after dsRNA interference. Overall, these results suggested that these three HcGalec proteins may function as potential receptors participating in the innate immune responses of H. cumingii against bacterial infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Next Generation Sequencing Identifies Five Major Classes of Potentially Therapeutic Enzymes Secreted by Lucilia sericata Medical Maggots.

    Science.gov (United States)

    Franta, Zdeněk; Vogel, Heiko; Lehmann, Rüdiger; Rupp, Oliver; Goesmann, Alexander; Vilcinskas, Andreas

    2016-01-01

    Lucilia sericata larvae are used as an alternative treatment for recalcitrant and chronic wounds. Their excretions/secretions contain molecules that facilitate tissue debridement, disinfect, or accelerate wound healing and have therefore been recognized as a potential source of novel therapeutic compounds. Among the substances present in excretions/secretions various peptidase activities promoting the wound healing processes have been detected but the peptidases responsible for these activities remain mostly unidentified. To explore these enzymes we applied next generation sequencing to analyze the transcriptomes of different maggot tissues (salivary glands, gut, and crop) associated with the production of excretions/secretions and/or with digestion as well as the rest of the larval body. As a result we obtained more than 123.8 million paired-end reads, which were assembled de novo using Trinity and Oases assemblers, yielding 41,421 contigs with an N50 contig length of 2.22 kb and a total length of 67.79 Mb. BLASTp analysis against the MEROPS database identified 1729 contigs in 577 clusters encoding five peptidase classes (serine, cysteine, aspartic, threonine, and metallopeptidases), which were assigned to 26 clans, 48 families, and 185 peptidase species. The individual enzymes were differentially expressed among maggot tissues and included peptidase activities related to the therapeutic effects of maggot excretions/secretions.

  2. 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.

  3. A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa.

    Science.gov (United States)

    Geldenhuys, Marike; Mortlock, Marinda; Weyer, Jacqueline; Bezuidt, Oliver; Seamark, Ernest C J; Kearney, Teresa; Gleasner, Cheryl; Erkkila, Tracy H; Cui, Helen; Markotter, Wanda

    2018-01-01

    Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and

  4. Identifying areas of high economic-potential copper mineralization using ASTER data in the Urumieh-Dokhtar Volcanic Belt, Iran

    Science.gov (United States)

    Pour, Amin Beiranvand; Hashim, Mazlan

    2012-02-01

    This study investigates the application of spectral image processing methods to ASTER data for mapping hydrothermal alteration zones associated with porphyry copper mineralization and related host rock. The study area is located in the southeastern segment of the Urumieh-Dokhtar Volcanic Belt of Iran. This area has been selected because it is a potential zone for exploration of new porphyry copper deposits. Spectral transform approaches, namely principal component analysis, band ratio and minimum noise fraction were used for mapping hydrothermally altered rocks and lithological units at regional scale. Spectral mapping methods, including spectral angle mapper, linear spectral unmixing, matched filtering and mixture tuned matched filtering were applied to differentiate hydrothermal alteration zones associated with porphyry copper mineralization such as phyllic, argillic and propylitic mineral assemblages.Spectral transform methods enhanced hydrothermally altered rocks associated with the known porphyry copper deposits and new identified prospects using shortwave infrared (SWIR) bands of ASTER. These methods showed the discrimination of quartz rich igneous rocks from the magmatic background and the boundary between igneous and sedimentary rocks using the thermal infrared (TIR) bands of ASTER at regional scale. Spectral mapping methods distinguished the sericitically- and argillically-altered rocks (the phyllic and argillic alteration zones) that surrounded by discontinuous to extensive zones of propylitized rocks (the propylitic alteration zone) using SWIR bands of ASTER at both regional and district scales. Linear spectral unmixing method can be best suited for distinguishing specific high economic-potential hydrothermal alteration zone (the phyllic zone) and mineral assemblages using SWIR bands of ASTER. Results have proven to be effective, and in accordance with the results of field surveying, spectral reflectance measurements and X-ray diffraction (XRD) analysis

  5. Putative 3-nitrotyrosine detoxifying genes identified in the yeast Debaryomyces hansenii: In silico search of regulatory sequences responsive to salt and nitrogen stress

    Directory of Open Access Journals (Sweden)

    Daniela E. Castro

    2017-09-01

    Conclusions: D. hansenii can grow in the presence of 3-nitrotyrosine as the only nitrogen source and has a high specific denitrase activity to degrade 3-nitrotyrosine in 1 and 2 M NaCl stress conditions. The results suggest that given the lack of information on transcriptional factors in D. hansenii, the genes identified in our in silico analysis may help explain 3-nitrotyrosine assimilation mechanisms.

  6. Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination.

    Directory of Open Access Journals (Sweden)

    Jill M Brooks

    2016-04-01

    Full Text Available Epstein-Barr virus, a B-lymphotropic herpesvirus, is the cause of infectious mononucleosis, has strong aetiologic links with several malignancies and has been implicated in certain autoimmune diseases. Efforts to develop a prophylactic vaccine to prevent or reduce EBV-associated disease have, to date, focused on the induction of neutralising antibody responses. However, such vaccines might be further improved by inducing T cell responses capable of recognising and killing recently-infected B cells. In that context, EBNA2, EBNA-LP and BHRF1 are the first viral antigens expressed during the initial stage of B cell growth transformation, yet have been poorly characterised as CD8+ T cell targets. Here we describe CD8+ T cell responses against each of these three "first wave" proteins, identifying target epitopes and HLA restricting alleles. While EBNA-LP and BHRF1 each contained one strong CD8 epitope, epitopes within EBNA2 induced immunodominant responses through several less common HLA class I alleles (e.g. B*3801 and B*5501, as well as subdominant responses through common class I alleles (e.g. B7 and C*0304. Importantly, such EBNA2-specific CD8+ T cells recognised B cells within the first day post-infection, prior to CD8+ T cells against well-characterised latent target antigens such as EBNA3B or LMP2, and effectively inhibited outgrowth of EBV-transformed B cell lines. We infer that "first wave" antigens of the growth-transforming infection, especially EBNA2, constitute potential CD8+ T cell immunogens for inclusion in prophylactic EBV vaccine design.

  7. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signalling

    Directory of Open Access Journals (Sweden)

    Mehanathan eMuthamilarasan

    2015-10-01

    Full Text Available Transcription factors (TFs are major players in stress signalling and constitute an integral part of signalling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4 model plants, Setaria italica (SiWRKY and S. viridis (SvWRKY, respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins that were computationally analysed for their physicochemical properties. Sequence alignment and phylogenetic analysis classified these proteins into three major groups, namely I, II and III with majority of WRKY proteins belonging to group II (53 SiWRKY and 23 SvWRKY, followed by group III (39 SiWRKY and 11 SvWRKY and group I (10 SiWRKY and 6 SvWRKY. Group II proteins were further classified into 5 subgroups (IIa to IIe based on their phylogeny. Domain analysis showed the presence of WRKY motif and zinc finger-like structures in these proteins along with additional domains in a few proteins. All SiWRKY genes were physically mapped on the S. italica genome and their duplication analysis revealed that 10 and 8 gene pairs underwent tandem and segmental duplications, respectively. Comparative mapping of SiWRKY and SvWRKY genes in related C4 panicoid genomes demonstrated the orthologous relationships between these genomes. In silico expression analysis of SiWRKY and SvWRKY genes showed their differential expression patterns in different tissues and stress conditions. Expression profiling of candidate SiWRKY genes in response to stress (dehydration and salinity and hormone treatments (abscisic acid, salicylic acid and methyl jasmonate suggested the putative involvement of SiWRKY066 and SiWRKY082 in stress and hormone signalling. These genes could be potential candidates for further characterization to delineate their functional roles in abiotic stress signalling.

  8. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signaling.

    Science.gov (United States)

    Muthamilarasan, Mehanathan; Bonthala, Venkata S; Khandelwal, Rohit; Jaishankar, Jananee; Shweta, Shweta; Nawaz, Kashif; Prasad, Manoj

    2015-01-01

    Transcription factors (TFs) are major players in stress signaling and constitute an integral part of signaling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4model plants, Setaria italica (SiWRKY) and S. viridis (SvWRKY), respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins that were computationally analyzed for their physicochemical properties. Sequence alignment and phylogenetic analysis classified these proteins into three major groups, namely I, II, and III with majority of WRKY proteins belonging to group II (53 SiWRKY and 23 SvWRKY), followed by group III (39 SiWRKY and 11 SvWRKY) and group I (10 SiWRKY and 6 SvWRKY). Group II proteins were further classified into 5 subgroups (IIa to IIe) based on their phylogeny. Domain analysis showed the presence of WRKY motif and zinc finger-like structures in these proteins along with additional domains in a few proteins. All SiWRKY genes were physically mapped on the S. italica genome and their duplication analysis revealed that 10 and 8 gene pairs underwent tandem and segmental duplications, respectively. Comparative mapping of SiWRKY and SvWRKY genes in related C4 panicoid genomes demonstrated the orthologous relationships between these genomes. In silico expression analysis of SiWRKY and SvWRKY genes showed their differential expression patterns in different tissues and stress conditions. Expression profiling of candidate SiWRKY genes in response to stress (dehydration and salinity) and hormone treatments (abscisic acid, salicylic acid, and methyl jasmonate) suggested the putative involvement of SiWRKY066 and SiWRKY082 in stress and hormone signaling. These genes could be potential candidates for further characterization to delineate their functional roles in abiotic stress signaling.

  9. Post Mortem Validation of MRI-Identified Veins on the Surface of the Cerebral Cortex as Potential Landmarks for Neurosurgery

    Directory of Open Access Journals (Sweden)

    Günther Grabner

    2017-06-01

    Full Text Available Background and Objective: Image-guided neurosurgery uses information from a wide spectrum of methods to inform the neurosurgeon's judgement about which tissue to resect and which to spare. Imaging data are registered to the patient's skull so that they correspond to the intraoperative macro- and microscopic view. The correspondence between imaging and optical systems breaks down during surgery, however, as a result of cerebro-spinal fluid drain age, tissue resection, and gravity-based brain shift. In this work we investigate whether a map of surface veins, automatically segmented from MRI, could serve as additional reference system.Methods: Gradient-echo based T2*-weighted imaging was performed on two human cadavers heads using a 7 Tesla MRI scanner. Automatic vessel segmentation was performed using the Frangi vesselness filter, and surface renderings of vessels compared with photographs of the surface of the brain following craniotomy.Results: A high level of correspondence was established between vessel maps and the post autopsy photographs. Corresponding veins, including the prominent superior anastomotic veins, could be identified in all brain lobes.Conclusion: Automatic surface vessel segmentation is feasible and the high correspondence to post autopsy photographs indicates that they could be used as an additional reference system for image-guided neurosurgery in order to maintain the correspondence between imaging and optical systems.This has the advantage over a skull-based reference system that veins are clearly visible to the surgeon and move and deform with the underlying tissue, potentially making this surface net of landmarks robust to brain shift.

  10. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signaling

    Science.gov (United States)

    Muthamilarasan, Mehanathan; Bonthala, Venkata S.; Khandelwal, Rohit; Jaishankar, Jananee; Shweta, Shweta; Nawaz, Kashif; Prasad, Manoj

    2015-01-01

    Transcription factors (TFs) are major players in stress signaling and constitute an integral part of signaling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4model plants, Setaria italica (SiWRKY) and S. viridis (SvWRKY), respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins that were computationally analyzed for their physicochemical properties. Sequence alignment and phylogenetic analysis classified these proteins into three major groups, namely I, II, and III with majority of WRKY proteins belonging to group II (53 SiWRKY and 23 SvWRKY), followed by group III (39 SiWRKY and 11 SvWRKY) and group I (10 SiWRKY and 6 SvWRKY). Group II proteins were further classified into 5 subgroups (IIa to IIe) based on their phylogeny. Domain analysis showed the presence of WRKY motif and zinc finger-like structures in these proteins along with additional domains in a few proteins. All SiWRKY genes were physically mapped on the S. italica genome and their duplication analysis revealed that 10 and 8 gene pairs underwent tandem and segmental duplications, respectively. Comparative mapping of SiWRKY and SvWRKY genes in related C4 panicoid genomes demonstrated the orthologous relationships between these genomes. In silico expression analysis of SiWRKY and SvWRKY genes showed their differential expression patterns in different tissues and stress conditions. Expression profiling of candidate SiWRKY genes in response to stress (dehydration and salinity) and hormone treatments (abscisic acid, salicylic acid, and methyl jasmonate) suggested the putative involvement of SiWRKY066 and SiWRKY082 in stress and hormone signaling. These genes could be potential candidates for further characterization to delineate their functional roles in abiotic stress signaling. PMID:26635818

  11. MALDI-TOF and SELDI-TOF analysis: “tandem” techniques to identify potential biomarker in fibromyalgia

    Directory of Open Access Journals (Sweden)

    A. Lucacchini

    2011-11-01

    Full Text Available Fibromyalgia (FM is characterized by the presence of chronic widespread pain throughout the musculoskeletal system and diffuse tenderness. Unfortunately, no laboratory tests have been appropriately validated for FM and correlated with the subsets and activity. The aim of this study was to apply a proteomic technique in saliva of FM patients: the Surface Enhance Laser Desorption/Ionization Time-of-Flight (SELDI-TOF. For this study, 57 FM patients and 35 HC patients were enrolled. The proteomic analysis of saliva was carried out using SELDI-TOF. The analysis was performed using different chip arrays with different characteristics of binding. The statistical analysis was performed using cluster analysis and the difference between two groups was underlined using Student’s t-test. Spectra analysis highlighted the presence of several peaks differently expressed in FM patients compared with controls. The preliminary results obtained by SELDI-TOF analysis were compared with those obtained in our previous study performed on whole saliva of FM patients by using electrophoresis. The m/z of two peaks, increased in FM patients, seem to overlap well with the molecular weight of calgranulin A and C and Rho GDP-dissociation inhibitor 2, which we had found up-regulated in our previous study. These preliminary results showed the possibility of identifying potential salivary biomarker through salivary proteomic analysis with MALDI-TOF and SELDI-TOF in FM patients. The peaks observed allow us to focus on some of the particular pathogenic aspects of FM, the oxidative stress which contradistinguishes this condition, the involvement of proteins related to the cytoskeletal arrangements, and central sensibilization.

  12. THP-1 monocytes but not macrophages as a potential alternative for CD34+ dendritic cells to identify chemical skin sensitizers

    International Nuclear Information System (INIS)

    Lambrechts, Nathalie; Verstraelen, Sandra; Lodewyckx, Hanne; Felicio, Ana; Hooyberghs, Jef; Witters, Hilda; Tendeloo, Viggo van; Cauwenberge, Paul van; Nelissen, Inge; Heuvel, Rosette van den; Schoeters, Greet

    2009-01-01

    Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34 + progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (L-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.

  13. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  14. Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle

    Directory of Open Access Journals (Sweden)

    A. Manimaran

    2016-01-01

    Full Text Available Among the various systemic reactions against infection or injury, the acute phase response is the cascade of reaction and mostly coordinated by cytokines-mediated acute phase proteins (APPs production. Since APPs are sensitive innate immune molecules, they are useful for early detection of inflammation in bovines and believed to be better discriminators than routine hematological parameters. Therefore, the possibility of using APPs as a diagnostic and prognostic marker of inflammation in major bovine health disorders including postpartum uterine infection has been explored by many workers. In this review, we discussed specifically importance of postpartum uterine infection, the role of energy balance in uterine infections and potential of APPs as a predictor of postpartum uterine infections during the transition period and its regulatory mechanism in dairy cattle.

  15. Contrasting exome constancy and regulatory region variation in the gene encoding CYP3A4: an examination of the extent and potential implications.

    Science.gov (United States)

    Creemer, Olivia J; Ansari-Pour, Naser; Ekong, Rosemary; Tarekegn, Ayele; Plaster, Christopher; Bains, Ripudaman K; Itan, Yuval; Bekele, Endashaw; Bradman, Neil

    2016-06-01

    CYP3A4 expression varies up to 100-fold among individuals, and, to date, genetic causes remain elusive. As a major drug-metabolizing enzyme, elucidation of such genetic causes would increase the potential for introducing personalized dose adjustment of therapies involving CYP3A4 drug substrates. The foetal CYP3A isoform, CYP3A7, is reported to be expressed in ∼10% of European adults and may thus contribute towards the metabolism of endogenous substances and CYP3A drug substrates. However, little is known about the distribution of the variant expressed in the adult. We resequenced the exons, flanking introns, regulatory elements and 3'UTR of CYP3A4 in five Ethiopian populations and incorporated data from the 1000 Genomes Project. Using bioinformatic analysis, we assessed likely consequences of observed CYP3A4 genomic variation. We also conducted the first extensive geographic survey of alleles associated with adult expression of CYP3A7 - that is, CYP3A7*1B and CYP3A7*1C. Ethiopia contained 60 CYP3A4 variants (26 novel) and more variants (>1%) than all non-African populations combined. No nonsynonymous mutation was found in the homozygous form or at more than 2.8% in any population. Seventy-nine per cent of haplotypes contained 3'UTR and/or regulatory region variation with striking pairwise population differentiation, highlighting the potential for interethnic variation in CYP3A4 expression. Conversely, coding region variation showed that significant interethnic variation is unlikely at the protein level. CYP3A7*1C was found at up to 17.5% in North African populations and in significant linkage disequilibrium with CYP3A5*3, indicating that adult expression of the foetal isoform is likely to be accompanied by reduced or null expression of CYP3A5.

  16. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

  17. Novel peptide marker corresponding to salivary protein gSG6 potentially identifies exposure to Anopheles bites.

    Directory of Open Access Journals (Sweden)

    Anne Poinsignon

    2008-06-01

    Full Text Available In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites.Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i their potential antigenic properties and ii the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1.This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could

  18. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    International Nuclear Information System (INIS)

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-01-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  19. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  20. Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor.

    Science.gov (United States)

    Litchfield, Kevin; Levy, Max; Orlando, Giulia; Loveday, Chey; Law, Philip J; Migliorini, Gabriele; Holroyd, Amy; Broderick, Peter; Karlsson, Robert; Haugen, Trine B; Kristiansen, Wenche; Nsengimana, Jérémie; Fenwick, Kerry; Assiotis, Ioannis; Kote-Jarai, ZSofia; Dunning, Alison M; Muir, Kenneth; Peto, Julian; Eeles, Rosalind; Easton, Douglas F; Dudakia, Darshna; Orr, Nick; Pashayan, Nora; Bishop, D Timothy; Reid, Alison; Huddart, Robert A; Shipley, Janet; Grotmol, Tom; Wiklund, Fredrik; Houlston, Richard S; Turnbull, Clare

    2017-07-01

    Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes. Our findings implicate widespread disruption of developmental transcriptional regulators as a basis of TGCT susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in oncogenesis. Defective microtubule assembly and dysregulation of KIT-MAPK signaling also feature as recurrently disrupted pathways. Our findings support a polygenic model of risk and provide insight into the biological basis of TGCT.

  1. Identifying Potential Mediators and Moderators of the Association between Child Maltreatment and Bullying Perpetration and Victimization in School

    Science.gov (United States)

    Hong, Jun Sung; Espelage, Dorothy L.; Grogan-Kaylor, Andrew; Allen-Meares, Paula

    2012-01-01

    A growing body of literature is demonstrating associations between childhood maltreatment and bullying involvement at school. In this literature review, four potential mediators (explanatory) and three potential moderators (mitigates or exacerbates) of the association between childhood maltreatment and school bullying are proposed. Mediators…

  2. Clearing the corpses: regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain

    Directory of Open Access Journals (Sweden)

    Irune Diaz-Aparicio

    2016-01-01

    Full Text Available Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro. Nevertheless, these indirect methods present several limitations and, thus, direct observation and quantification of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. These parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inflammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to find and engulf apoptotic cells, resulting in accumulation of debris and inflammation. Herein, we advocate that the efficiency of microglial phagocytosis should be routinely tested in neurodegenerative and neurological disorders, in order to determine the extent to which it contributes to apoptosis and inflammation found in these conditions. Finally, our findings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inflammation, and accelerate recovery in brain diseases.

  3. Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a newly identified cause of congenital ear malformation

    Directory of Open Access Journals (Sweden)

    Lely A. Quina

    2012-11-01

    Hmx1 is a homeodomain transcription factor expressed in the developing eye, peripheral ganglia, and branchial arches of avian and mammalian embryos. Recent studies have identified a loss-of-function allele at the HMX1 locus as the causative mutation in the oculo-auricular syndrome (OAS in humans, characterized by ear and eye malformations. The mouse dumbo (dmbo mutation, with similar effects on ear and eye development, also results from a loss-of-function mutation in the Hmx1 gene. A recessive dmbo mutation causing ear malformation in rats has been mapped to the chromosomal region containing the Hmx1 gene, but the nature of the causative allele is unknown. Here we show that dumbo rats and mice exhibit similar neonatal ear and eye phenotypes. In midgestation embryos, dumbo rats show a specific loss of Hmx1 expression in neural-crest-derived craniofacial mesenchyme (CM, whereas Hmx1 is expressed normally in retinal progenitors, sensory ganglia and in CM, which is derived from mesoderm. High-throughput resequencing of 1 Mb of rat chromosome 14 from dmbo/dmbo rats, encompassing the Hmx1 locus, reveals numerous divergences from the rat genomic reference sequence, but no coding changes in Hmx1. Fine genetic mapping narrows the dmbo critical region to an interval of ∼410 kb immediately downstream of the Hmx1 transcription unit. Further sequence analysis of this region reveals a 5777-bp deletion located ∼80 kb downstream in dmbo/dmbo rats that is not apparent in 137 other rat strains. The dmbo deletion region contains a highly conserved domain of ∼500 bp, which is a candidate distal enhancer and which exhibits a similar relationship to Hmx genes in all vertebrate species for which data are available. We conclude that the rat dumbo phenotype is likely to result from loss of function of an ultraconserved enhancer specifically regulating Hmx1 expression in neural-crest-derived CM. Dysregulation of Hmx1 expression is thus a candidate mechanism for congenital ear

  4. RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

    DEFF Research Database (Denmark)

    Salleh, M. S.; Mazzoni, G.; Höglund, J. K.

    2017-01-01

    -throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate...... genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency....... On average, 57 million reads (short reads or short mRNA sequences ...

  5. MicroRNAs regulate T-cell production of interleukin-9 and identify hypoxia-inducible factor-2α as an important regulator of T helper 9 and regulatory T-cell differentiation.

    Science.gov (United States)

    Singh, Yogesh; Garden, Oliver A; Lang, Florian; Cobb, Bradley S

    2016-09-01

    MicroRNAs (miRNAs) regulate many aspects of helper T cell (Th) development and function. Here we found that they are required for the suppression of interleukin-9 (IL-9) expression in Th9 cells and other Th subsets. Two highly related miRNAs (miR-15b and miR-16) that we previously found to play an important role in regulatory T (Treg) cell differentiation were capable of suppressing IL-9 expression when they were over-expressed in Th9 cells. We used these miRNAs as tools to identify novel regulators of IL-9 expression and found that they could regulate the expression of Epas1, which encodes hypoxia-inducible factor (HIF)-2α. HIF proteins regulate metabolic pathway usage that is important in determining appropriate Th differentiation. The related protein, HIF-1α enhances Th17 differentiation and inhibits Treg cell differentiation. Here we found that HIF-2α was required for IL-9 expression in Th9 cells, but its expression was not sufficient in other Th subsets. Furthermore, HIF-2α suppressed Treg cell differentiation like HIF-1α, demonstrating both similar and distinct roles of the HIF proteins in Th differentiation and adding a further dimension to their function. Ironically, even though miR-15b and miR-16 suppressed HIF-2α expression in Treg cells, inhibiting their function in Treg cells did not lead to an increase in IL-9 expression. Therefore, the physiologically relevant miRNAs that regulate IL-9 expression in Treg cells and other subsets remain unknown. Nevertheless, the analysis of miR-15b and miR-16 function led to the discovery of the importance of HIF-2α so this work demonstrated the utility of studying miRNA function to identify novel regulatory pathways in helper T-cell development. © 2016 John Wiley & Sons Ltd.

  6. Identifying potential heirs properties in the Southeastern United States: a new GIS methodology utilizing mass appraisal data

    Science.gov (United States)

    Scott Pippin; Shana Jones; Cassandra. Johnson Gaither

    2017-01-01

    This report presents a methodology for identifying land parcels that have an increased probability of being heirs property. Heirs property is inherited land passed to successive generations intestate, without clear title, typically to family members. This land ownership type is widespread among rural, African-American populations and is also thought to be pervasive in...

  7. Point to a Referent, and Say, "What Is This?" Gesture as a Potential Cue to Identify Referents in a Discourse

    Science.gov (United States)

    So, Wing Chee; Lim, Jia Yi

    2012-01-01

    This study explored whether caregivers' gestures followed the discourse-pragmatic principle of information status of referents (given vs. new) and how their children responded to those gestures when identifying referents. Ten Chinese-speaking and eight English-speaking caregivers were videotaped while interacting spontaneously with their children.…

  8. Virtual Reality and Its Potential Use in Special Education. Identifying Emerging Issues and Trends in Technology for Special Education.

    Science.gov (United States)

    Woodward, John

    As part of a 3-year study to identify emerging issues and trends in technology for special education, this paper addresses the possible contributions of virtual reality technology to educational services for students with disabilities. An example of the use of virtual reality in medical imaging introduces the paper and leads to a brief review of…

  9. Identifying potential types of guidance for supporting student inquiry when using virtual and remote labs in science: a literature review

    NARCIS (Netherlands)

    Zacharia, Zacharias C.; Manoli, Constantinos; Xenofontos, Nikoletta; de Jong, Anthonius J.M.; Pedaste, Margus; van Riesen, Siswa; Kamp, E.T.; Kamp, Ellen T.; Mäeots, Mario; Siiman, Leo; Tsourlidaki, Eleftheria

    2015-01-01

    The aim of this review is to identify specific types of guidance for supporting student use of online labs, that is, virtual and remote labs, in an inquiry context. To do so, we reviewed the literature on providing guidance within computer supported inquiry learning (CoSIL) environments in science

  10. Identifying deliberate attempts to fake memory impairment through the combined use of reaction time and event-related potential measures

    NARCIS (Netherlands)

    van Hooff, Johanna C.; Sargeant, Elizabeth; Foster, Jonathan K.; Schmand, Ben A.

    2009-01-01

    The central aim of this study was to evaluate the value of reaction time (RT) measures and event-related potentials (ERPs) for the assessment of simulated memory impairment. In two identical experiments (N = 24), healthy volunteers carried out an adapted version of the Amsterdam Short-Term Memory

  11. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signaling

    OpenAIRE

    Muthamilarasan, Mehanathan; Bonthala, Venkata S.; Khandelwal, Rohit; Jaishankar, Jananee; Shweta, Shweta; Nawaz, Kashif; Prasad, Manoj

    2015-01-01

    Transcription factors (TFs) are major players in stress signalling and constitute an integral part of signalling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4 model plants, Setaria italica (SiWRKY) and S. viridis (SvWRKY), respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins t...

  12. Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Brinkmeyer-Langford, Candice; Balog-Alvarez, Cynthia; Cai, James J; Davis, Brian W; Kornegay, Joe N

    2016-08-22

    Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes. We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers. The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes.

  13. Crowd-sourced Ontology for Photoleukocoria: Identifying Common Internet Search Terms for a Potentially Important Pediatric Ophthalmic Sign.

    Science.gov (United States)

    Staffieri, Sandra E; Kearns, Lisa S; Sanfilippo, Paul G; Craig, Jamie E; Mackey, David A; Hewitt, Alex W

    2018-02-01

    Leukocoria is the most common presenting sign for pediatric eye disease including retinoblastoma and cataract, with worse outcomes if diagnosis is delayed. We investigated whether individuals could identify leukocoria in photographs (photoleukocoria) and examined their subsequent Internet search behavior. Using a web-based questionnaire, in this cross-sectional study we invited adults aged over 18 years to view two photographs of a child with photoleukocoria, and then search the Internet to determine a possible diagnosis and action plan. The most commonly used search terms and websites accessed were recorded. The questionnaire was completed by 1639 individuals. Facebook advertisement was the most effective recruitment strategy. The mean age of all respondents was 38.95 ± 14.59 years (range, 18-83), 94% were female, and 59.3% had children. An abnormality in the images presented was identified by 1613 (98.4%) participants. The most commonly used search terms were: "white," "pupil," "photo," and "eye" reaching a variety of appropriate websites or links to print or social media articles. Different words or phrases were used to describe the same observation of photoleukocoria leading to a range of websites. Variations in the description of observed signs and search words influenced the sites reached, information obtained, and subsequent help-seeking intentions. Identifying the most commonly used search terms for photoleukocoria is an important step for search engine optimization. Being directed to the most appropriate websites informing of the significance of photoleukocoria and the appropriate actions to take could improve delays in diagnosis of important pediatric eye disease such as retinoblastoma or cataract.

  14. Kennecott Utah Copper Corporation: Facility Utilizes Energy Assessments to Identify $930,000 in Potential Annual Savings

    Energy Technology Data Exchange (ETDEWEB)

    2004-07-01

    Kennecott Utah Copper Corporation (KUCC) used targeted energy assessments in the smelter and refinery at its Bingham Canyon Mine, near Salt Lake City, Utah. The assessment focused mainly on the energy-intensive processes of copper smelting and refining. By implementing the projects identified, KUCC could realize annual cost savings of $930,000 and annual energy savings of 452,000 MMBtu. The projects would also reduce maintenance, repair costs, waste, and environmental emissions. One project would use methane gas from an adjacent municipal dump to replace natural gas currently used to heat the refinery electrolyte.

  15. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Friis, Esbern

    2010-01-01

    Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection......, and a novel protein, C7orf24, was identified as being upregulated in cancer cells. Protein expression levels of C7orf24 were evaluated by immunohistochemical assays to qualify deregulation of this protein. Analysis of C7orf24 expression showed up-regulation in 36.4 and 23.4% of cases present in the discovery...

  16. An in silico high-throughput screen identifies potential selective inhibitors for the non-receptor tyrosine kinase Pyk2

    Directory of Open Access Journals (Sweden)

    Meirson T

    2017-05-01

    Full Text Available Tomer Meirson, Abraham O Samson, Hava Gil-Henn Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel Abstract: The non-receptor tyrosine kinase proline-rich tyrosine kinase 2 (Pyk2 is a critical mediator of signaling from cell surface growth factor and adhesion receptors to cell migration, proliferation, and survival. Emerging evidence indicates that signaling by Pyk2 regulates hematopoietic cell response, bone density, neuronal degeneration, angiogenesis, and cancer. These physiological and pathological roles of Pyk2 warrant it as a valuable therapeutic target for invasive cancers, osteoporosis, Alzheimer’s disease, and inflammatory cellular response. Despite its potential as a therapeutic target, no potent and selective inhibitor of Pyk2 is available at present. As a first step toward discovering specific potential inhibitors of Pyk2, we used an in silico high-throughput screening approach. A virtual library of six million lead-like compounds was docked against four different high-resolution Pyk2 kinase domain crystal structures and further selected for predicted potency and ligand efficiency. Ligand selectivity for Pyk2 over focal adhesion kinase (FAK was evaluated by comparative docking of ligands and measurement of binding free energy so as to obtain 40 potential candidates. Finally, the structural flexibility of a subset of the docking complexes was evaluated by molecular dynamics simulation, followed by intermolecular interaction analysis. These compounds may be considered as promising leads for further development of highly selective Pyk2 inhibitors. Keywords: virtual screen, efficiency metrics, MM-GBSA, molecular dynamics

  17. Proteomic profiling of mammary carcinomas identifies C7orf24, a gamma-glutamyl cyclotransferase, as a potential cancer biomarker

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Friis, Esbern

    2010-01-01

    Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection...... in different types of cancer suggests deregulation of C7orf24 to be a general event in epithelial carcinogenesis, indicating that this protein may play an important role in cancer cell biology and thus constitute a novel therapeutic target. Furthermore, as C7orf24 is externalized to the tissue extracellular...... fluid and can be detected in serum, this protein also represents a potential serological marker....

  18. Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients.

    Science.gov (United States)

    Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario

    2017-10-01

    Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. cDNA Library Screening Identifies Protein Interactors Potentially Involved in Non-telomeric Roles of Arabidopsis Telomerase

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    Ladislav eDokládal

    2015-11-01

    Full Text Available Telomerase-reverse transcriptase (TERT plays an essential catalytic role in maintaining telomeres. However, in animal systems telomerase plays additional non-telomeric functional roles. We previously screened an Arabidopsis cDNA library for proteins that interact with the C-terminal extension (CTE TERT domain and identified a nuclear-localized protein that contains a RNA recognition motif (RRM. This RRM-protein forms homodimers in both plants and yeast. Mutation of the gene encoding the RRM-protein had no detectable effect on plant growth and development, nor did it affect telomerase activity or telomere length in vivo, suggesting a non-telomeric role for TERT/RRM-protein complexes. The gene encoding the RRM-protein is highly expressed in leaf and reproductive tissues. We further screened an Arabidopsis cDNA library for proteins that interact with the RRM-protein and identified five interactors. These proteins are involved in numerous non-telomere-associated cellular activities. In plants, the RRM-protein, both alone and in a complex with its interactors, localizes to nuclear speckles. Transcriptional analyses in wild-type and rrm mutant plants, as well as transcriptional co-analyses, suggest that TERT, the RRM-protein, and the RRM-protein interactors may play important roles in non-telomeric cellular functions.

  20. Potential use of multispectral imaging technology to identify moisture content and water-holding capacity in cooked pork sausages.

    Science.gov (United States)

    Ma, Fei; Zhang, Bin; Wang, Wu; Li, Peijun; Niu, Xiangli; Chen, Conggui; Zheng, Lei

    2018-03-01

    The traditional detection methods for moisture content (MC) and water-holding capacity (WHC) in cooked pork sausages (CPS) are destructive, time consuming, require skilled personnel and are not suitable for online industry applications. The goal of this work was to explore the potential of multispectral imaging (MSI) in combination with multivariate analysis for the identification of MC and WHC in CPS. Spectra and textures of 156 CPS treated by six salt concentrations (0-2.5%) were analyzed using different calibration models to find the most optimal results of predicting MC and WHC in CPS. By using the fused data of spectra and textures, partial least squares regression models performed well for determining the MC and WHC, with a correlation coefficient (r) of 0.949 and 0.832, respectively. Additionally, their spatial distribution in CPS could be visualized via applying prediction equations to transfer each pixel in the image. Results of satisfactory detection and visualization of the MC and WHC showed that MSI has the potential to serve as a rapid and non-destructive method for use in sausage industry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  1. Towards Quantitative Optical Cross Sections in Entomological Laser Radar - Potential of Temporal and Spherical Parameterizations for Identifying Atmospheric Fauna.

    Directory of Open Access Journals (Sweden)

    Mikkel Brydegaard

    Full Text Available In recent years, the field of remote sensing of birds and insects in the atmosphere (the aerial fauna has advanced considerably, and modern electro-optic methods now allow the assessment of the abundance and fluxes of pests and beneficials on a landscape scale. These techniques have the potential to significantly increase our understanding of, and ability to quantify and manage, the ecological environment. This paper presents a concept whereby laser radar observations of atmospheric fauna can be parameterized and table values for absolute cross sections can be catalogued to allow for the study of focal species such as disease vectors and pests. Wing-beat oscillations are parameterized with a discrete set of harmonics and the spherical scatter function is parameterized by a reduced set of symmetrical spherical harmonics. A first order spherical model for insect scatter is presented and supported experimentally, showing angular dependence of wing beat harmonic content. The presented method promises to give insights into the flight heading directions of species in the atmosphere and has the potential to shed light onto the km-range spread of pests and disease vectors.

  2. High-protein goat's milk diet identified through newborn screening: clinical warning of a potentially dangerous dietetic practice.

    Science.gov (United States)

    Maines, Evelina; Gugelmo, Giorgia; Tadiotto, Elisa; Pietrobelli, Angelo; Campostrini, Natascia; Pasini, Andrea; Ion-Popa, Florina; Vincenzi, Monica; Teofoli, Francesca; Camilot, Marta; Bordugo, Andrea

    2017-10-01

    Breast-feeding is an unequalled way of providing optimal food for infants' healthy growth and development and the WHO recommends that infants should be exclusively breast-fed for the first 6 months of life. For mothers who are unable to breast-feed or who decide not to, infant formulas are the safest alternative. Despite recommendations, it is possible that parents make potentially harmful nutritional choices for their children because of cultural beliefs or misinformation on infant nutrition. We describe a possible health risk of not breast-feeding, highlighting a potentially dangerous dietetic practice. Design/Setting/Subjects We report the case of a newborn who was fed with undiluted goat's milk because her mother could not breast-feed and was not aware of infant formulas. The dietary mistake was detected because of a positive expanded newborn screening result, characterized by severe hypertyrosinaemia with high methionine and phenylalanine levels, a pattern suggestive of severe liver impairment. The pattern of plasma amino acids was related to a goat's milk diet, because of its very different composition compared with human milk and infant formula. Our experience demonstrates that, when breast-feeding is not possible or is not exclusive, infants may be at risk of dangerous nutritional practices, including diets with very high protein content, such as a goat's milk diet. Families of not breast-fed infants may need appropriate advice on safe alternatives for infant nutrition to avoid the risks of inappropriate diets.

  3. Genome-wide analysis of gene expression and protein secretion of Babesia canis during virulent infection identifies potential pathogenicity factors.

    Science.gov (United States)

    Eichenberger, Ramon M; Ramakrishnan, Chandra; Russo, Giancarlo; Deplazes, Peter; Hehl, Adrian B

    2017-06-13

    Infections of dogs with virulent strains of Babesia canis are characterized by rapid onset and high mortality, comparable to complicated human malaria. As in other apicomplexan parasites, most Babesia virulence factors responsible for survival and pathogenicity are secreted to the host cell surface and beyond where they remodel and biochemically modify the infected cell interacting with host proteins in a very specific manner. Here, we investigated factors secreted by B. canis during acute infections in dogs and report on in silico predictions and experimental analysis of the parasite's exportome. As a backdrop, we generated a fully annotated B. canis genome sequence of a virulent Hungarian field isolate (strain BcH-CHIPZ) underpinned by extensive genome-wide RNA-seq analysis. We find evidence for conserved factors in apicomplexan hemoparasites involved in immune-evasion (e.g. VESA-protein family), proteins secreted across the iRBC membrane into the host bloodstream (e.g. SA- and Bc28 protein families), potential moonlighting proteins (e.g. profilin and histones), and uncharacterized antigens present during acute crisis in dogs. The combined data provides a first predicted and partially validated set of potential virulence factors exported during fatal infections, which can be exploited for urgently needed innovative intervention strategies aimed at facilitating diagnosis and management of canine babesiosis.

  4. The Health Informatics Trial Enhancement Project (HITE: Using routinely collected primary care data to identify potential participants for a depression trial

    Directory of Open Access Journals (Sweden)

    Lyons Ronan A

    2010-04-01

    Full Text Available Abstract Background Recruitment to clinical trials can be challenging. We identified anonymous potential participants to an existing pragmatic randomised controlled depression trial to assess the feasibility of using routinely collected data to identify potential trial participants. We discuss the strengths and limitations of this approach, assess its potential value, report challenges and ethical issues encountered. Methods Swansea University's Health Information Research Unit's Secure Anonymised Information Linkage (SAIL database of routinely collected health records was interrogated, using Structured Query Language (SQL. Read codes were used to create an algorithm of inclusion/exclusion criteria with which to identify suitable anonymous participants. Two independent clinicians rated the eligibility of the potential participants' identified. Inter-rater reliability was assessed using the kappa statistic and inter-class correlation. Results The study population (N = 37263 comprised all adults registered at five general practices in Swansea UK. Using the algorithm 867 anonymous potential participants were identified. The sensitivity and specificity results > 0.9 suggested a high degree of accuracy from the algorithm. The inter-rater reliability results indicated strong agreement between the confirming raters. The Intra Class Correlation Coefficient (Cronbach's Alpha > 0.9, suggested excellent agreement and Kappa coefficient > 0.8; almost perfect agreement. Conclusions This proof of concept study showed that routinely collected primary care data can be used to identify potential participants for a pragmatic randomised controlled trial of folate augmentation of antidepressant therapy for the treatment of depression. Further work will be needed to assess generalisability to other conditions and settings and the inclusion of this approach to support Electronic Enhanced Recruitment (EER.

  5. Identifying potential differences in ontogentic ages between modern and archaeological Nacella deaurata shells, Tierra del Fuego, Argentina

    Science.gov (United States)

    Surge, D. M.; Godino, I. B. I.; Álvarez, M.; López, M. B. I.

    2017-12-01

    Patelloid limpet shells are common constituents of rocky shore habitats along the eastern Atlantic basin and are often found in archaeological shell middens. Nacella deaurata is an intertidal species found in the Magellanic Province along the southern tip of South America. Recent discoveries of archaeological shell middens in Tierra del Fuego, Argentina, identify N. deaurata as one of the abundant shells in these deposits. Preliminary observations reveal that modern N. deaurata shells achieve larger sizes compared to those found in the archaeological middens. Here, we provide preliminary data to test the hypothesis that the larger, modern specimens grow to older ontogenetic ages than the smaller archaeological specimens. Our results may provide insights into harvesting pressures on this species during the time when the archaeological sites were inhabited. Understanding their annual growth patterns also has important implications for generating oxygen isotope proxy data to reconstruct seasonal variation in sea surface temperature.

  6. Analysis of copy number variations in Holstein cows identify potential mechanisms contributing to differences in residual feed intake.

    Science.gov (United States)

    Hou, Yali; Bickhart, Derek M; Chung, Hoyoung; Hutchison, Jana L; Norman, H Duane; Connor, Erin E; Liu, George E

    2012-11-01

    Genomic structural variation is an important and abundant source of genetic and phenotypic variation. In this study, we performed an initial analysis of copy number variations (CNVs) using BovineHD SNP genotyping data from 147 Holstein cows identified as having high or low feed efficiency as estimated by residual feed intake (RFI). We detected 443 candidate CNV regions (CNVRs) that represent 18.4 Mb (0.6 %) of the genome. To investigate the functional impacts of CNVs, we created two groups of 30 individual animals with extremely low or high estimated breeding values (EBVs) for RFI, and referred to these groups as low intake (LI; more efficient) or high intake (HI; less efficient), respectively. We identified 240 (~9.0 Mb) and 274 (~10.2 Mb) CNVRs from LI and HI groups, respectively. Approximately 30-40 % of the CNVRs were specific to the LI group or HI group of animals. The 240 LI CNVRs overlapped with 137 Ensembl genes. Network analyses indicated that the LI-specific genes were predominantly enriched for those functioning in the inflammatory response and immunity. By contrast, the 274 HI CNVRs contained 177 Ensembl genes. Network analyses indicated that the HI-specific genes were particularly involved in the cell cycle, and organ and bone development. These results relate CNVs to two key variables, namely immune response and organ and bone development. The data indicate that greater feed efficiency relates more closely to immune response, whereas cattle with reduced feed efficiency may have a greater capacity for organ and bone development.

  7. Measurement of compartment elasticity using pressure related ultrasound: a method to identify patients with potential compartment syndrome.

    Science.gov (United States)

    Sellei, R M; Hingmann, S J; Kobbe, P; Weber, C; Grice, J E; Zimmerman, F; Jeromin, S; Gansslen, A; Hildebrand, F; Pape, H C

    2015-01-01

    PURPOSE OF THE STUDY Decision-making in treatment of an acute compartment syndrome is based on clinical assessment, supported by invasive monitoring. Thus, evolving compartment syndrome may require repeated pressure measurements. In suspected cases of potential compartment syndromes clinical assessment alone seems to be unreliable. The objective of this study was to investigate the feasibility of a non-invasive application estimating whole compartmental elasticity by ultrasound, which may improve accuracy of diagnostics. MATERIAL AND METHODS In an in-vitro model, using an artificial container simulating dimensions of the human anterior tibial compartment, intracompartmental pressures (p) were raised subsequently up to 80 mm Hg by infusion of saline solution. The compartmental depth (mm) in the cross-section view was measured before and after manual probe compression (100 mm Hg) upon the surface resulting in a linear compartmental displacement (Δd). This was repeated at rising compartmental pressures. The resulting displacements were related to the corresponding intra-compartmental pressures simulated in our model. A hypothesized relationship between pressures related compartmental displacement and the elasticity at elevated compartment pressures was investigated. RESULTS With rising compartmental pressures, a non-linear, reciprocal proportional relation between the displacement (mm) and the intra-compartmental pressure (mm Hg) occurred. The Pearson's coefficient showed a high correlation (r2 = -0.960). The intraobserver reliability value kappa resulted in a statistically high reliability (κ = 0.840). The inter-observer value indicated a fair reliability (κ = 0.640). CONCLUSIONS Our model reveals that a strong correlation between compartmental strain displacements assessed by ultrasound and the intra-compartmental pressure changes occurs. Further studies are required to prove whether this assessment is transferable to human muscle tissue. Determining the complete

  8. Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure.

    Science.gov (United States)

    Bourdon, Julie A; Williams, Andrew; Kuo, Byron; Moffat, Ivy; White, Paul A; Halappanavar, Sabina; Vogel, Ulla; Wallin, Håkan; Yauk, Carole L

    2013-01-07

    New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose-response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  9. A Regulatory Network Analysis of Orphan Genes in Arabidopsis Thaliana

    Science.gov (United States)

    Singh, Pramesh; Chen, Tianlong; Arendsee, Zebulun; Wurtele, Eve S.; Bassler, Kevin E.

    Orphan genes, which are genes unique to each particular species, have recently drawn significant attention for their potential usefulness for organismal robustness. Their origin and regulatory interaction patterns remain largely undiscovered. Recently, methods that use the context likelihood of relatedness to infer a network followed by modularity maximizing community detection algorithms on the inferred network to find the functional structure of regulatory networks were shown to be effective. We apply improved versions of these methods to gene expression data from Arabidopsis thaliana, identify groups (clusters) of interacting genes with related patterns of expression and analyze the structure within those groups. Focusing on clusters that contain orphan genes, we compare the identified clusters to gene ontology (GO) terms, regulons, and pathway designations and analyze their hierarchical structure. We predict new regulatory interactions and unravel the structure of the regulatory interaction patterns of orphan genes. Work supported by the NSF through Grants DMR-1507371 and IOS-1546858.

  10. Potential sources of Triatoma infestans reinfesting peridomiciles identified by morphological characterization in Los Llanos, La Rioja, Argentina

    Directory of Open Access Journals (Sweden)

    María Laura Hernández

    2013-02-01

    Full Text Available The presence of Triatoma infestans in habitats treated with insecticides constitutes a frequent problem in endemic areas. Basing our study on the hypothesis that descendants of a residual population should be more similar to the pre-treatment population than to any other, we compared the indications of two quantitative morphological approaches. This study seeks to find the origin of 247 T. infestans from three populations found in two chicken coops and a goat corral after treatment with insecticides. The results obtained by quantitative morphology suggest that the T. infestans found between three-34 months after the application of insecticides formed mixed populations with insects derived from residual foci and neighbouring habitats. Our analyses also showed the presence of a phenotype which does not resemble neither the pre-treatment phenotype nor the one from neighbouring populations, suggesting the presence of a particular post-treatment phenotype. The heads size showed some variations in males from different populations and remained unchanged in females, which reinforces the hypothesis of an intraspecific competition for food with priority for females. This article presents, for the first time, the combined analysis of geometric morphometry of heads and antennal phenotypes to identify the composition of reinfesting populations.

  11. 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)].

  12. Comprehensive Analysis of the COBRA-Like (COBL) Gene Family in Gossypium Identifies Two COBLs Potentially Associated with Fiber Quality

    Science.gov (United States)

    Niu, Erli; Shang, Xiaoguang; Cheng, Chaoze; Bao, Jianghao; Zeng, Yanda; Cai, Caiping; Du, Xiongming; Guo, Wangzhen

    2015-01-01

    COBRA-Like (COBL) genes, which encode a plant-specific glycosylphosphatidylinositol (GPI) anchored protein, have been proven to be key regulators in the orientation of cell expansion and cellulose crystallinity status. Genome-wide analysis has been performed in A. thaliana, O. sativa, Z. mays and S. lycopersicum, but little in Gossypium. Here we identified 19, 18 and 33 candidate COBL genes from three sequenced cotton species, diploid cotton G. raimondii, G. arboreum and tetraploid cotton G. hirsutum acc. TM-1, respectively. These COBL members were anchored onto 10 chromosomes in G. raimondii and could be divided into two subgroups. Expression patterns of COBL genes showed highly developmental and spatial regulation in G. hirsutum acc. TM-1. Of them, GhCOBL9 and GhCOBL13 were preferentially expressed at the secondary cell wall stage of fiber development and had significantly co-upregulated expression with cellulose synthase genes GhCESA4, GhCESA7 and GhCESA8. Besides, GhCOBL9 Dt and GhCOBL13 Dt were co-localized with previously reported cotton fiber quality quantitative trait loci (QTLs) and the favorable allele types of GhCOBL9 Dt had significantly positive correlations with fiber quality traits, indicating that these two genes might play an important role in fiber development. PMID:26710066

  13. Gonad Transcriptome Analysis of the Pacific Oyster Crassostrea gigas Identifies Potential Genes Regulating the Sex Determination and Differentiation Process.

    Science.gov (United States)

    Yue, Chenyang; Li, Qi; Yu, Hong

    2018-04-01

    The Pacific oyster Crassostrea gigas is a commercially important bivalve in aquaculture worldwide. C. gigas has a fascinating sexual reproduction system consisting of dioecism, sex change, and occasional hermaphroditism, while knowledge of the molecular mechanisms of sex determination and differentiation is still limited. In this study, the transcriptomes of male and female gonads at different gametogenesis stages were characterized by RNA-seq. Hierarchical clustering based on genes differentially expressed revealed that 1269 genes were expressed specifically in female gonads and 817 genes were expressed increasingly over the course of spermatogenesis. Besides, we identified two and one gene modules related to female and male gonad development, respectively, using weighted gene correlation network analysis (WGCNA). Interestingly, GO and KEGG enrichment analysis showed that neurotransmitter-related terms were significantly enriched in genes related to ovary development, suggesting that the neurotransmitters were likely to regulate female sex differentiation. In addition, two hub genes related to testis development, lncRNA LOC105321313 and Cg-Sh3kbp1, and one hub gene related to ovary development, Cg-Malrd1-like, were firstly investigated. This study points out the role of neurotransmitter and non-coding RNA regulation during gonad development and produces lists of novel relevant candidate genes for further studies. All of these provided valuable information to understand the molecular mechanisms of C. gigas sex determination and differentiation.

  14. A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes

    Directory of Open Access Journals (Sweden)

    Slifer Susan

    2011-07-01

    Full Text Available Abstract Background Left ventricular mass (LVM is an important risk factor for cardiovascular disease. Previously we found evidence for linkage to chromosome 12p11 in Dominican families, with a significant increase in a subset of families with high average waist circumference (WC. In the present study, we use association analysis to further study the genetic effect on LVM. Methods Association analysis with LVM was done in the one LOD critical region of the linkage peak in an independent sample of 897 Caribbean Hispanics. Genotype data were available on 7085 SNPs from 23 to 53 MB on chromosome 12p11. Adjustment was made for vascular risk factors and population substructure using an additive genetic model. Subset analysis by WC was performed to test for a difference in genetic effects between the high and low WC subsets. Results In the overall analysis, the most significant association was found to rs10743465, downstream of the SOX5 gene (p = 1.27E-05. Also, 19 additional SNPs had nominal p TMTC1. Twelve additional SNPs in or near 6 genes had p Conclusions The current study supports previously identified evidence by linkage for a genetic effect on LVM on chromosome 12p11 using association analysis in population-based Caribbean Hispanic cohort. SOX5 may play an important role in the regulation of LVM. An interaction of TMTC1 with abdominal obesity may contribute to phenotypic variation of LVM.

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

    Science.gov (United States)

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

    2010-01-01

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

  16. Spatially extended versus frontal cerebral near-infrared spectroscopy during cardiac surgery: a case series identifying potential advantages

    Science.gov (United States)

    Rummel, Christian; Basciani, Reto; Nirkko, Arto; Schroth, Gerhard; Stucki, Monika; Reineke, David; Eberle, Balthasar; Kaiser, Heiko A.

    2018-01-01

    Stroke due to hypoperfusion or emboli is a devastating adverse event of cardiac surgery, but early detection and treatment could protect patients from an unfavorable postoperative course. Hypoperfusion and emboli can be detected with transcranial Doppler of the middle cerebral artery (MCA). The measured blood flow velocity correlates with cerebral oxygenation determined clinically by near-infrared spectroscopy (NIRS) of the frontal cortex. We tested the potential advantage of a spatially extended NIRS in detecting critical events in three cardiac surgery patients with a whole-head fiber holder of the FOIRE-3000 continuous-wave NIRS system. Principle components analysis was performed to differentiate between global and localized hypoperfusion or ischemic territories of the middle and anterior cerebral arteries. In one patient, we detected a critical hypoperfusion of the right MCA, which was not apparent in the frontal channels but was accompanied by intra- and postoperative neurological correlates of ischemia. We conclude that spatially extended NIRS of temporal and parietal vascular territories could improve the detection of critically low cerebral perfusion. Even in severe hemispheric stroke, NIRS of the frontal lobe may remain normal because the anterior cerebral artery can be supplied by the contralateral side directly or via the anterior communicating artery.

  17. A Human Error Analysis Procedure for Identifying Potential Error Modes and Influencing Factors for Test and Maintenance Activities

    International Nuclear Information System (INIS)

    Kim, Jae Whan; Park, Jin Kyun

    2010-01-01

    Periodic or non-periodic test and maintenance (T and M) activities in large, complex systems such as nuclear power plants (NPPs) are essential for sustaining stable and safe operation of the systems. On the other hand, it also has been raised that human erroneous actions that might occur during T and M activities has the possibility of incurring unplanned reactor trips (RTs) or power derate, making safety-related systems unavailable, or making the reliability of components degraded. Contribution of human errors during normal and abnormal activities of NPPs to the unplanned RTs is known to be about 20% of the total events. This paper introduces a procedure for predictively analyzing human error potentials when maintenance personnel perform T and M tasks based on a work procedure or their work plan. This procedure helps plant maintenance team prepare for plausible human errors. The procedure to be introduced is focusing on the recurrent error forms (or modes) in execution-based errors such as wrong object, omission, too little, and wrong action

  18. Global Health Education: a cross-sectional study among German medical students to identify needs, deficits and potential benefits (Part 2 of 2: Knowledge gaps and potential benefits).

    Science.gov (United States)

    Bozorgmehr, Kayvan; Menzel-Severing, Johannes; Schubert, Kirsten; Tinnemann, Peter

    2010-10-08

    In Germany, educational deficits or potential benefits involved in global health education have not been analysed till now. We assess the importance medical students place on learning about social determinants of health (SDH) and assess their knowledge of global health topics in relation to (i) mobility patterns, their education in (ii) tropical medicine or (iii) global health. Cross-sectional study among medical students from all 36 medical schools in Germany using a web-based, semi-structured questionnaire. Participants were recruited via mailing-lists of students' unions, all medical students registered in 2007 were eligible to participate in the study. We captured international mobility patterns, exposure to global health learning opportunities and attitudes to learning about SDH. Both an objective and subjective knowledge assessment were performed. 1126 online-replies were received and analysed. International health electives in developing countries correlated significantly with a higher importance placed on all provided SDH (p ≤ 0.006). Participation in tropical medicine (p educational system' (p = 0.007) and the 'health system structure' (p = 0.007), while the item 'politics' was marginally significant (p = 0.053).In the knowledge assessment students achieved an average score of 3.6 (SD 1.5; Mdn 4.0), 75% achieved a score of 4.0 or less (Q25 = 3.0; Q75 = 4.0) from a maximum achievable score of 8.0. A better performance was associated with international health electives (p = 0.032), participation in tropical medicine (p = 0.038) and global health (p = 0.258) courses. The importance medical students in our sample placed on learning about SDH strongly interacts with students' mobility, and participation in tropical medicine and global health courses. The knowledge assessment revealed deficits and outlined needs to further analyse education gaps in global health. Developing concerted educational interventions aimed at fostering students' engagement with SDH

  19. Using satellite data to identify the causes of and potential solutions for yield gaps in India’s Wheat Belt

    Science.gov (United States)

    Jain, M.; Singh, Balwinder; Srivastava, A. A. K.; Malik, R. K.; McDonald, A. J.; Lobell, D. B.

    2017-09-01

    Food security will be increasingly challenged by climate change, natural resource degradation, and population growth. Wheat yields, in particular, have already stagnated in many regions and will be further affected by warming temperatures. Despite these challenges, wheat yields can be increased by improving management practices in regions with existing yield gaps. To identify the magnitude and causes of current yield gaps in India, one of the largest wheat producers globally, we produced 30 meter resolution yield maps from 2001 to 2015 across the Indo-Gangetic Plains (IGP), the nation’s main wheat belt. Yield maps were derived using a new method that translates satellite vegetation indices to yield estimates using crop model simulations, bypassing the need for ground calibration data. This is one of the first attempts to apply this method to a smallholder agriculture system, where ground calibration data are rarely available. We find that yields can be increased by 11% on average and up to 32% in the eastern IGP by improving management to current best practices within a given district. Additionally, if current best practices from the highest-yielding state of Punjab are implemented in the eastern IGP, yields could increase by almost 110%. Considering the factors that most influence yields, later sow dates and warmer temperatures are most associated with low yields across the IGP. This suggests that strategies to reduce the negative effects of heat stress, like earlier sowing and planting heat-tolerant wheat varieties, are critical to increasing wheat yields in this globally-important agricultural region.

  20. Plasma membrane proteomics of human breast cancer cell lines identifies potential targets for breast cancer diagnosis and treatment.

    Directory of Open Access Journals (Sweden)

    Yvonne S Ziegler

    Full Text Available The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

  1. Gamma-Irradiated Mannheimia (Pasteurella) Haemolytica Identified by rRNA Gene Sequencing as a Potential Vaccine in Mice

    International Nuclear Information System (INIS)

    Araby, E.

    2014-01-01

    Pneumonic pasteurellosis is a significant disease in beef production medicine. The most information suggests that this disease is a $700 million dollar per year economic burden in bovine food animal production. The current study was designed to assess the immune efficacy of whole cell killed of M. haemolytica strain from satisfactory cases (infected lung from sheep). The efficacy of gamma- irradiated M. haemolytica vaccine (GIV) was evaluated in mice in comparison to the classical aqueous formalized (AFV) one. The bacteria under study were cultivation on blood agar, purification and genetically identified. Then the bacterial cells were exposed to different doses of gamma radiation (2- 20 kGy) with 2 kGy intervals and the dose response curve of the survivors was plotted and 20 kGy was selected as the dose for the preparation of the vaccine. A total of 30 male mice (two weeks – old) were used for the further experimental investigations. Animals were divided into three equal groups each of 10 animals. The first group (group A) was given GIV . The second group (group B) received AFV. The third group (group C) was injected with sterile saline solution and represents the control. Animals were vaccinated via intraperitoneal (i.p) injection with 1x10 8 CFU per treated mouse. After vaccination, the immuno response was determined by cellular surface antigens-reactive antibodies using a modified protein- electrophoresis procedure. Antibody-antigen hybrids was visualized at molecular weight more than 225 KDa in samples represented M. haemolytica antibodies group (A, B) against both bacterial samples (M. haemolytica and Pasteurella multocida ) , while non-treated bacterial cells in which cells incubated with serum of mice group (C) revealed no hybridization reaction, this results verify that, there is shared cellular surface antigens among the two Pasteurella species. Also, the bacterial distribution with (LD 50 ) 2x10 7 CFU of a live M. heamolytica into vaccinated and non

  2. Identifying conditions for elimination and epidemic potential of methicillin-resistant Staphylococcus aureus in nursing homes

    Directory of Open Access Journals (Sweden)

    Nataliya G. Batina

    2016-09-01

    Full Text Available Abstract Background Residents of nursing homes are commonly colonized with methicillin-resistant Staphylococcus aureus (MRSA but there is a limited understanding of the dynamics and determinants of spread in this setting. To address this gap, we sought to use mathematical modeling to assess the epidemic potential of MRSA in nursing homes and to determine conditions under which non-USA300 and USA300 MRSA could be eliminated or reduced in the facilities. Methods Model parameters were estimated from data generated during a longitudinal study of MRSA in 6 Wisconsin nursing homes. The data included subject colonization status with strain-specific MRSA collected every 3 months for up to 1 year. Deterministic and stochastic co-colonization and single-strain models were developed to describe strain-specific dynamics of MRSA in these facilities. Basic reproduction numbers of strain-independent MRSA, non-USA300 and USA300 MRSA were estimated numerically. The impact of antibiotic use in the past 3 months on the prevalence of strain-specific MRSA and associated basic reproduction numbers were evaluated. Results Our models predicted that MRSA would persist in Wisconsin nursing homes, and non-USA300 would remain the dominant circulating strain. MRSA eradication was theoretically achievable by elimination of MRSA-positive admissions over the course of years. Substantial reductions in MRSA prevalence could be attained through marked increase in clearance rates or reduction in MRSA-positive admissions sustained over years. The basic reproduction number of strain-independent MRSA was 0.18 (95 % CI = 0.13–0.23. Recent antibiotic use increased the prevalence of strain-specific MRSA and associated basic reproduction numbers, but was unlikely to lead to an outbreak. Conclusions Based on our model, MRSA elimination from nursing homes, while theoretically possible, was unlikely to be achieved in practice. Decolonization therapy that can sustain higher

  3. ISD97, a computer program to analyze data from a series of in situ measurements on a grid and identify potential localized areas of elevated activity

    International Nuclear Information System (INIS)

    Reginatto, M.; Shebell, P.; Miller, K.M.

    1997-10-01

    A computer program, ISD97, was developed to analyze data from a series of in situ measurements on a grid and identify potential localized areas of elevated activity. The ISD97 code operates using a two-step process. A deconvolution of the data is carried out using the maximum entropy method, and a map of activity on the ground that fits the data within experimental error is generated. This maximum entropy map is then analyzed to determine the locations and magnitudes of potential areas of elevated activity that are consistent with the data. New deconvolutions are then carried out for each potential area of elevated activity identified by the code. Properties of the algorithm are demonstrated using data from actual field measurements

  4. Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy.

    Science.gov (United States)

    Maddur, Mohan S; Stephen-Victor, Emmanuel; Das, Mrinmoy; Prakhar, Praveen; Sharma, Varun K; Singh, Vikas; Rabin, Magalie; Trinath, Jamma; Balaji, Kithiganahalli N; Bolgert, Francis; Vallat, Jean-Michel; Magy, Laurent; Kaveri, Srini V; Bayry, Jagadeesh

    2017-03-20

    Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (T reg ) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4-5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA. The fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with T reg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and T reg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. T reg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α. T reg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. T reg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.

  5. Default values for assessment of potential dermal exposure of the hands to industrial chemicals in the scope of regulatory risk assessments.

    Science.gov (United States)

    Marquart, Hans; Warren, Nicholas D; Laitinen, Juha; van Hemmen, Joop J

    2006-07-01

    Dermal exposure needs to be addressed in regulatory risk assessment of chemicals. The models used so far are based on very limited data. The EU project RISKOFDERM has gathered a large number of new measurements on dermal exposure to industrial chemicals in various work situations, together with information on possible determinants of exposure. These data and information, together with some non-RISKOFDERM data were used to derive default values for potential dermal exposure of the hands for so-called 'TGD exposure scenarios'. TGD exposure scenarios have similar values for some very important determinant(s) of dermal exposure, such as amount of substance used. They form narrower bands within the so-called 'RISKOFDERM scenarios', which cluster exposure situations according to the same purpose of use of the products. The RISKOFDERM scenarios in turn are narrower bands within the so-called Dermal Exposure Operation units (DEO units) that were defined in the RISKOFDERM project to cluster situations with similar exposure processes and exposure routes. Default values for both reasonable worst case situations and typical situations were derived, both for single datasets and, where possible, for combined datasets that fit the same TGD exposure scenario. The following reasonable worst case potential hand exposures were derived from combined datasets: (i) loading and filling of large containers (or mixers) with large amounts (many litres) of liquids: 11,500 mg per scenario (14 mg cm(-2) per scenario with surface of the hands assumed to be 820 cm(2)); (ii) careful mixing of small quantities (tens of grams in default values are considered useful for estimating exposure for similar substances in similar situations with low uncertainty. Several other default values based on single datasets can also be used, but lead to estimates with a higher uncertainty, due to their more limited basis. Sufficient analogy in all described parameters of the scenario, including duration, is needed

  6. Development of computational fluid dynamics--habitat suitability (CFD-HSI) models to identify potential passage--Challenge zones for migratory fishes in the Penobscot River

    Science.gov (United States)

    Haro, Alexander J.; Dudley, Robert W.; Chelminski, Michael

    2012-01-01

    A two-dimensional computational fluid dynamics-habitat suitability (CFD–HSI) model was developed to identify potential zones of shallow depth and high water velocity that may present passage challenges for five anadromous fish species in the Penobscot River, Maine, upstream from two existing dams and as a result of the proposed future removal of the dams. Potential depth-challenge zones were predicted for larger species at the lowest flow modeled in the dam-removal scenario. Increasing flows under both scenarios increased the number and size of potential velocity-challenge zones, especially for smaller species. This application of the two-dimensional CFD–HSI model demonstrated its capabilities to estimate the potential effects of flow and hydraulic alteration on the passage of migratory fish.

  7. Assessment of regulatory effectiveness. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    1999-09-01

    This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

  8. Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

    Science.gov (United States)

    Gazestani, Vahid H; Salavati, Reza

    2015-01-01

    Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

  9. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  10. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

    Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...... by the International Transitional Administrations (ITAs) in Kosovo and Iraq as well as global supply chains and their impact on the garment industry in Bangladesh....

  11. Default values for assessment of potential dermal exposure of the hands to industrial chemicals in the scope of regulatory risk assessments

    NARCIS (Netherlands)

    Marquart, H.; Warren, N.D.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    Dermal exposure needs to be addressed in regulatory risk assessment of chemicals. The models used so far are based on very limited data. The EU project RISKOFDERM has gathered a large number of new measurements on dermal exposure to industrial chemicals in various work situations, together with

  12. Integration analysis of quantitative proteomics and transcriptomics data identifies potential targets of frizzled-8 protein-related antiproliferative factor in vivo.

    Science.gov (United States)

    Yang, Wei; Kim, Yongsoo; Kim, Taek-Kyun; Keay, Susan K; Kim, Kwang Pyo; Steen, Hanno; Freeman, Michael R; Hwang, Daehee; Kim, Jayoung

    2012-12-01

    What's known on the subject? and What does the study add? Interstitial cystitis (IC) is a prevalent and debilitating pelvic disorder generally accompanied by chronic pain combined with chronic urinating problems. Over one million Americans are affected, especially middle-aged women. However, its aetiology or mechanism remains unclear. No efficient drug has been provided to patients. Several urinary biomarker candidates have been identified for IC; among the most promising is antiproliferative factor (APF), whose biological activity is detectable in urine specimens from >94% of patients with both ulcerative and non-ulcerative IC. The present study identified several important mediators of the effect of APF on bladder cell physiology, suggesting several candidate drug targets against IC. In an attempt to identify potential proteins and genes regulated by APF in vivo, and to possibly expand the APF-regulated network identified by stable isotope labelling by amino acids in cell culture (SILAC), we performed an integration analysis of our own SILAC data and the microarray data of Gamper et al. (2009) BMC Genomics 10: 199. Notably, two of the proteins (i.e. MAPKSP1 and GSPT1) that are down-regulated by APF are involved in the activation of mTORC1, suggesting that the mammalian target of rapamycin (mTOR) pathway is potentially a critical pathway regulated by APF in vivo. Several components of the mTOR pathway are currently being studied as potential therapeutic targets in other diseases. Our analysis suggests that this pathway might also be relevant in the design of diagnostic tools and medications targeting IC. • To enhance our understanding of the interstitial cystitis urine biomarker antiproliferative factor (APF), as well as interstitial cystitis biology more generally at the systems level, we reanalyzed recently published large-scale quantitative proteomics and in vivo transcriptomics data sets using an integration analysis tool that we have developed. • To

  13. Criteria to identify and define territories with productive development potential to establish Special Economic Zones of Development (SEZD in Costa Rica

    Directory of Open Access Journals (Sweden)

    Rafael Arias Ramírez

    2015-07-01

    Full Text Available This study is aimed to identify, based on a series of variables and indicators, territories that have characteristics to propitiate an endogenous development, from the basis of the resource endowment they have, along with a productive policy, at the national and local level to promote it. A county´s index of productive potential is built around three components (productive, infrastructure and institutions; then a cluster analysis is applied. The outcomes of the study are not only new for the country, also they make a contribution with the elaboration of a matrix of variables and indicators, which provide criteria, empirically validated, to identify and define Special Economic Zones of Development (SEZD for Costa Rica.

  14. Pan-Genome Analysis of Human Gastric Pathogen H. pylori: Comparative Genomics and Pathogenomics Approaches to Identify Regions Associated with Pathogenicity and Prediction of Potential Core Therapeutic Targets

    DEFF Research Database (Denmark)

    Ali, Amjad; Naz, Anam; Soares, Siomar C.

    2015-01-01

    -genome approach; the predicted conserved gene families (1,193) constitute similar to 77% of the average H. pylori genome and 45% of the global gene repertoire of the species. Reverse vaccinology strategies have been adopted to identify and narrow down the potential core-immunogenic candidates. Total of 28 nonhost....... Pan-genome analyses of the global representative H. pylori isolates consisting of 39 complete genomes are presented in this paper. Phylogenetic analyses have revealed close relationships among geographically diverse strains of H. pylori. The conservation among these genomes was further analyzed by pan...

  15. SCS-CN and GIS-based approach for identifying potential water harvesting sites in the Kali Watershed, Mahi River Basin, India

    Science.gov (United States)

    Ramakrishnan, D.; Bandyopadhyay, A.; Kusuma, K. N.

    2009-08-01

    The Kali sub-watershed is situated in the semi-arid region of Gujarat, India and forms a part of the Mahi River Watershed. This watershed receives an average annual rainfall of 900mm mainly between July and September. Due to high runoff potential, evapo-transpiration and poor infiltration, drought like situation prevails in this area from December to June almost every year. In this paper, augmentation of water resource is proposed by construction of runoff harvesting structures like check dam, percolation pond, farm pond, well and subsurface dyke. The site suitability for different water harvesting structures is determined by considering spatially varying parameters like runoff potential, slope, fracture pattern and micro-watershed area. GIS is utilised as a tool to store, analyse and integrate spatial and attribute information pertaining to runoff, slope, drainage and fracture. The runoff derived by SCS-CN method is a function of runoff potential which can be expressed in terms of runoff coefficient (ratio between the runoff and rainfall) which can be classified into three classes, viz., high (>40%), moderate (20-40%) and low (<20%). In addition to IMSD, FAO specifications for water harvesting/recharging structures, parameters such as effective storage, rock mass permeability are herein considered to augment effective storage. Using the overlay and decision tree concepts in GIS, potential water harvesting sites are identified. The derived sites are field investigated for suitability and implementation. In all, the accuracy of the site selection at implementation level varies from 80-100%.

  16. Regulatory and licensee surveys

    International Nuclear Information System (INIS)

    2009-01-01

    Prior to the workshop two CSNI/WGHOF surveys were distributed. One survey was directed at regulatory bodies and the other was directed at plant licensees. The surveys were: 1 - Regulatory Expectations of Licensees' Arrangements to Ensure Suitable Organisational Structure, Resources and Competencies to Manage Safety (sent to WGHOF regulatory members). The survey requested that the respondents provide a brief overview of the situation related to plant organisations in their country, their regulatory expectations and their formal requirements. The survey addressed three subjects: the demonstration and documentation of organisational structures, resources and competencies, organisational changes, issues for improvement (for both current and new plants). Responses were received from eleven regulatory bodies. 2 - Approaches to Justify Organisational Suitability (sent to selected licensees). The purpose of the survey to was to gain an understanding of how licensees ensure organisational suitability, resources and competencies. This information was used to assist in the development of the issues and subjects that were addressed at the group discussion sessions. Responses were received from over fifteen licensees from nine countries. The survey requested that the licensees provide information on how they ensure effective organisational structures at their plants. The survey grouped the questions into the following four categories: organisational safety functions, resource and competence, decision-making and communication, good examples and improvement needs. The findings from these surveys were used in conjunction with other factors to identify the key issues for the workshop discussion sessions. The responses from these two surveys are discussed briefly in Sections 4 and 5 of this report. More extensive reviews of the regulatory and licensee responses are provided in Appendix 1

  17. Regulatory Promotion of Emergent CCS Technology

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Lincoln; Uchitel, Kirsten; Johnson, David

    2014-01-01

    Despite the growing inevitability of climate change and the attendant need for mitigation strategies, carbon capture and sequestration (CCS) has yet to gain much traction in the United States. Recent regulatory proposals by the U.S. Environmental Protection Agency (EPA), limited in scope to new-build power plants, represent the only significant policy initiative intended to mandate diffusion of CCS technology. Phase I of this Project assessed barriers to CCS deployment as prioritized by the CCS community. That research concluded that there were four primary barriers: (1) cost, (2) lack of a carbon price, (3) liability, and (4) lack of a comprehensive regulatory regime. Phase II of this Project, as presented in this Report, assesses potential regulatory models for CCS and examines where those models address the hurdles to diffusing CCS technology identified in Phase I. It concludes (1) that a CCS-specific but flexible standard, such as a technology performance standard or a very particular type of market-based regulation, likely will promote CCS diffusion, and (2) that these policies cannot work alone, but rather, should be combined with other measures, such as liability limits and a comprehensive CCS regulatory regime.

  18. The use of lead isotope analysis to identify potential sources of lead toxicosis in a juvenile bald eagle (Haliaeetus leucocephalus) with ventricular foreign bodies

    Science.gov (United States)

    Franzen-Klein, Dana; McRuer, David; Slabe, Vincent; Katzner, Todd

    2018-01-01

    A male juvenile bald eagle (Haliaeetus leucocephalus) was admitted to the Wildlife Center of Virginia with a left humeral fracture a large quantity of anthropogenic debris in the ventriculus, a blood lead level of 0.616 ppm, and clinical signs consistent with chronic lead toxicosis. Because of the poor prognosis for recovery and release, the eagle was euthanatized. Lead isotope analysis was performed to identify potential anthropogenic sources of lead in this bird. The lead isotope ratios in the eagle's femur (0.8773), liver (0.8761), and kidneys (0.8686) were most closely related to lead paint (0.8925), leaded gasoline (0.8450), and zinc smelting (0.8240). The lead isotope ratios were dissimilar to lead ammunition (0.8179) and the anthropogenic debris in the ventriculus. This case report documents foreign body ingestion in a free-ranging bald eagle and demonstrates the clinical utility of lead isotope analysis to potentially identify or exclude anthropogenic sources of lead poisoning in wildlife patients.

  19. Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis.

    Science.gov (United States)

    Song, Zhenhua; Zhang, Chi; He, Lingxiao; Sui, Yanfang; Lin, Xiafei; Pan, Jingjing

    2018-05-01

    Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Regulatory Control of Radiation Sources. Safety Guide

    International Nuclear Information System (INIS)

    2009-01-01

    This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

  1. The availability of hydrogeologic data associated with areas identified by the US Geological Survey as experiencing potentially induced seismicity resulting from subsurface injection

    Science.gov (United States)

    Barnes, Caitlin; Halihan, Todd

    2018-05-01

    A critical need exists for site-specific hydrogeologic data in order to determine potential hazards of induced seismicity and to manage risk. By 2015, the United States Geological Survey (USGS) had identified 17 locations in the USA that are experiencing an increase in seismicity, which may be potentially induced through industrial subsurface injection. These locations span across seven states, which vary in geological setting, industrial exposure and seismic history. Comparing the research across the 17 locations revealed patterns for addressing induced seismicity concerns, despite the differences between geographical locations. Most induced seismicity studies evaluate geologic structure and seismic data from areas experiencing changes in seismic activity levels, but the inherent triggering mechanism is the transmission of hydraulic pressure pulses. This research conducted a systematic review of whether data are available in these locations to generate accurate hydrogeologic predictions, which could aid in managing seismicity. After analyzing peer-reviewed research within the 17 locations, this research confirms a lack of site-specific hydrogeologic data availability for at-risk areas. Commonly, formation geology data are available for these sites, but hydraulic parameters for the seismically active injection and basement zones are not available to researchers conducting peer-reviewed research. Obtaining hydrogeologic data would lead to better risk management for injection areas and provide additional scientific evidential support for determining a potentially induced seismic area.

  2. Multiplex polymerase chain reaction to identify and determine the toxigenicity of Corynebacterium spp with zoonotic potential and an overview of human and animal infections

    Directory of Open Access Journals (Sweden)

    Luciene de Fátima Costa Torres

    2013-05-01

    Full Text Available Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis constitute a group of potentially toxigenic microorganisms that are related to different infectious processes in animal and human hosts. Currently, there is a lack of information on the prevalence of disease caused by these pathogens, which is partially due to a reduction in the frequency of routine laboratory testing. In this study, a multiplex polymerase chain reaction (mPCR assay that can simultaneously identify and determine the toxigenicity of these corynebacterial species with zoonotic potential was developed. This assay uses five primer pairs targeting the following genes: rpoB (Corynebacterium spp, 16S rRNA (C. ulcerans and C. pseudotuberculosis, pld (C. pseudotuberculosis, dtxR (C. diphtheriae and tox [diphtheria toxin (DT ]. In addition to describing this assay, we review the literature regarding the diseases caused by these pathogens. Of the 213 coryneform strains tested, the mPCR results for all toxigenic and non-toxigenic strains of C . diphtheriae, C. ulcerans and C. pseudotuberculosis were in 100% agreement with the results of standard biochemical tests and PCR-DT. As an alternative to conventional methods, due to its advantages of specificity and speed, the mPCR assay used in this study may successfully be applied for the diagnosis of human and/or animal diseases caused by potentially toxigenic corynebacterial species.

  3. Flash visual evoked potentials are not specific enough to identify parieto-occipital lobe involvement in term neonates after significant hypoglycaemia.

    Science.gov (United States)

    Hu, Liyuan; Gu, Qiufang; Zhu, Zhen; Yang, Chenhao; Chen, Chao; Cao, Yun; Zhou, Wenhao

    2014-08-01

    Hypoglycaemia is a significant problem in high-risk neonates and predominant parieto-occipital lobe involvement has been observed after severe hypoglycaemic insult. We explored the use of flash visual evoked potentials (FVEP) in detecting parieto-occipital lobe involvement after significant hypoglycaemia. Full-term neonates (n = 15) who underwent FVEP from January 2008 to May 2013 were compared with infants (n = 11) without hypoglycaemia or parietal-occipital lobe injury. Significant hypoglycaemia was defined as being symptomatic or needing steroids, glucagon or a glucose infusion rate of ≥12 mg/kg/min. The hypoglycaemia group exhibited delayed latency of the first positive waveform on FVEP. The initial detected time for hypoglycaemia was later in the eight subjects with seizures (median 51-h-old) than those without (median 22-h-old) (P = 0.003). Magnetic resonance imaging showed that 80% of the hypoglycaemia group exhibited occipital-lobe injuries, and they were more likely to exhibit abnormal FVEP morphology (P = 0.007) than the controls. FVEP exhibited 100% sensitivity, but only 25% specificity, for detecting injuries to the parieto-occipital lobes. Flash visual evoked potential (FVEP) was sensitive, but not sufficiently specific, in identifying parieto-occipital lobe injuries among term neonates exposed to significant hypoglycaemia. Larger studies exploring the potential role of FVEP in neonatal hypoglycaemia are required. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  4. Metrics for Identifying Food Security Status and the Population with Potential to Benefit from Nutrition Interventions in the Lives Saved Tool (LiST).

    Science.gov (United States)

    Jackson, Bianca D; Walker, Neff; Heidkamp, Rebecca

    2017-11-01

    Background: The Lives Saved Tool (LiST) uses the poverty head-count ratio at $1.90/d as a proxy for food security to identify the percentage of the population with the potential to benefit from balanced energy supplementation and complementary feeding (CF) interventions, following the approach used for the Lancet 's 2008 series on Maternal and Child Undernutrition. Because much work has been done in the development of food security indicators, a re-evaluation of the use of this indicator was warranted. Objective: The aim was to re-evaluate the use of the poverty head-count ratio at $1.90/d as the food security proxy indicator in LiST. Methods: We carried out a desk review to identify available indicators of food security. We identified 3 indicators and compared them by using scatterplots, Spearman's correlations, and Bland-Altman plot analysis. We generated LiST projections to compare the modeled impact results with the use of the different indicators. Results: There are many food security indicators available, but only 3 additional indicators were identified with the data availability requirements to be used as the food security indicator in LiST. As expected, analyzed food security indicators were significantly positively correlated ( P security indicators that were used in the meta-analyses that produced the effect estimates. These are the poverty head-count ratio at $1.90/d for CF interventions and the prevalence of a low body mass index in women of reproductive age for balanced energy supplementation interventions. © 2017 American Society for Nutrition.

  5. Developing regulatory approaches

    International Nuclear Information System (INIS)

    Axelsson, Lars

    2012-01-01

    Lars Axelsson presented SSM progress on oversight of LMfS/SC since the Chester 1 Workshop in 2007. Current SSM approaches for safety culture oversight include targeted safety management and safety culture inspections, compliance inspections which cover aspects of safety management/safety culture and multi-disciplinary team inspections. Examples of themes for targeted inspections include management of ambiguous operational situations or other weak signals, understanding of and attitudes to Human Performance tools, the Safety Department's role and authority and Leadership for safety. All regulatory activities provide inputs for the SSM yearly safety evaluation of each licensee. A form has been developed to capture safety culture observations from inspections and other interactions with licensees. Analysis will be performed to identify patterns and provide information to support planning of specific Safety Culture activities. Training has been developed for regulatory staff to enhance the quality of regulatory interventions on safety culture. This includes a half-day seminar to provide an overview of safety culture, and a workshop which provides more in-depth discussion on cultural issues and how to capture those during regulatory activities. Future plans include guidance for inspectors, and informal seminars on safety culture with licensees

  6. Screening-level exposure-based prioritization to identify potential POPs, vPvBs and planetary boundary threats among Arctic contaminants

    Directory of Open Access Journals (Sweden)

    Efstathios Reppas-Chrysovitsinos

    2017-06-01

    Full Text Available A report that reviews Arctic contaminants that are not currently regulated as persistent organic pollutants (POPs under international treaties was recently published by the Arctic Monitoring and Assessment Programme (AMAP. We evaluated 464 individual chemicals mentioned in the AMAP report according to hazard profiles for POPs, very persistent and very bioaccumulative (vPvB chemicals, and two novel and distinct hazard profiles we derived from the planetary boundary threat framework. The two planetary boundary threat profiles assign high priority to chemicals that will be mobile and poorly reversible environmental contaminants. Utilizing persistence as a proxy for poor reversibility, we defined two exposure-based hazard profiles; airborne persistent contaminants (APCs and waterborne persistent contaminants (WPCs that are potential planetary boundary threats. We used in silico estimates of physicochemical properties and multimedia models to calculate hazard metrics for persistence, bioaccumulation and long-range transport potential, then we synthesized this information into four exposure-based hazard scores of the potential of each AMAP chemical to fit each of the POP, vPvB, APC and WPC exposure-based hazard profiles. As an alternative to adopting a “bright line” score that represented cause for concern, we scored the AMAP chemicals by benchmarking against a reference set of 148 known and relatively well-studied contaminants and expressed their exposure-based hazard scores as percentile ranks against the scores of the reference set chemicals. Our results show that scores in the four exposure-based hazard profiles provide complementary information about the potential environmental exposure-based hazards of the AMAP chemicals. Our POP, vPvB, APC and WPC exposure-based hazard scores identify high priority chemicals for further study from among the AMAP contaminants.

  7. miR Profiling Identifies Cyclin-Dependent Kinase 6 Downregulation as a Potential Mechanism of Acquired Cisplatin Resistance in Non-Small-Cell Lung Carcinoma.

    Science.gov (United States)

    Bar, Jair; Gorn-Hondermann, Ivan; Moretto, Patricia; Perkins, Theodore J; Niknejad, Nima; Stewart, David J; Goss, Glenwood D; Dimitroulakos, Jim

    2015-11-01

    To identify the mechanisms of cisplatin resistance, global microRNA (miR) expression was tested. The expression of miR-145 was consistently higher in resistant cells. The expression of cyclin-dependent kinase 6 (CDK6), a potential target of miR-145, was lower in resistant cells, and inhibition of CDK4/6 protected cells from cisplatin. Cell cycle inhibition, currently being tested in clinical trials, might be antagonistic to cisplatin and other cytotoxic drugs. Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death. Platinum-based chemotherapeutic drugs are the most active agents in treating advanced disease. Resistance to these drugs is common and multifactorial; insight into the molecular mechanisms involved will likely enhance efficacy. A set of NSCLC platinum-resistant sublines was created from the Calu6 cell line. Cell viability was quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Differentially expressed microRNAs (miRs) in these lines were identified using Affymetrix miR arrays. The potential genes targeted by these miRs were searched using the TargetScan algorithm. The expression levels of miRs and mRNA were tested using real-time polymerase chain reaction. miR-145 was reproducibly elevated in all the resistant sublines tested; however, modulation of miR-145 levels alone in these cells did not affect their response to cisplatin. A potential target of miR-145 is cyclin-dependent kinase 6 (CDK6), an important regulator of cell proliferation. The mRNA and protein levels of CDK6 were both downregulated in the resistant sublines. An inhibitor of CDK4/6 (PD0332991) protected parental NSCLC cells from cisplatin cytotoxicity. In the present study, we identified miRs differentially expressed in cisplatin-resistant cell lines, including miR-145. A predicted target of miR-145 is CDK6, and its expression was found to be downregulated in the resistant sublines, although not directly by miR-145. Inhibition

  8. Reconstruction of the gene regulatory network involved in the sonic hedgehog pathway with a potential role in early development of the mouse brain.

    Directory of Open Access Journals (Sweden)

    Jinhua Liu

    2014-10-01

    Full Text Available The Sonic hedgehog (Shh signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1- and Shh-Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh-Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1- domain and down-regulates the genes characteristic of the Shh-Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.

  9. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Monika Tschochner

    Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

  10. Summary of cost projection for regulatory uncertainties in the back end of the fuel cycle

    International Nuclear Information System (INIS)

    Raudenbush, M.H.; Geller, L.

    1977-01-01

    Fuel recycle cost deviations resulting from regulatory changes in the back end of the fuel cycle are examined from a number of different data sources, and three potentially large cost uncertainties are identified; HLW disposal, alpha-waste criteria, and in-plant material control/accountability for safeguards. Present and past methods of regulatory cost effectiveness determinations are critiqued and in some cases found wanting

  11. Expression and Regulatory Network Analysis of miR-140-3p, a New Potential Serum Biomarker for Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Matilde Cirnigliaro

    2017-08-01

    Full Text Available Given its prevalence and social impact, Autism Spectrum Disorder (ASD is drawing much interest. Molecular basis of ASD is heterogeneous and only partially known. Many factors, including disorders comorbid with ASD, like TS (Tourette Syndrome, complicate ASD behavior-based diagnosis and make it vulnerable to bias. To further investigate ASD etiology and to identify potential biomarkers to support its precise diagnosis, we used TaqMan Low Density Array technology to profile serum miRNAs from ASD, TS, and TS+ASD patients, and unaffected controls (NCs. Through validation assays in 30 ASD, 24 TS, and 25 TS+ASD patients and 25 NCs, we demonstrated that miR-140-3p is upregulated in ASD vs.: NC, TS, and TS+ASD (Tukey's test, p-values = 0.03, = 0.01, < 0.0001, respectively. ΔCt values for miR-140-3p and YGTSS (Yale Global Tic Severity Scale scores are positively correlated (Spearman r = 0.33; Benjamini-Hochberg p = 0.008 and show a linear relationship (p = 0.002. Network functional analysis showed that nodes controlled by miR-140-3p, especially CD38 and NRIP1 which are its validated targets, are involved in processes convergingly dysregulated in ASD, such as synaptic plasticity, immune response, and chromatin binding. Biomarker analysis proved that serum miR-140-3p can discriminate among: (1 ASD and NC (Area under the ROC curve, AUC: 0.70; sensitivity: 63.33%; specificity: 68%; (2 ASD and TS (AUC: 0.72; sensitivity: 66.66%; specificity: 70.83%; (3 ASD and TS+ASD (AUC: 0.78; sensitivity: 73.33%; specificity: 76%. Characterization of miR-140-3p network would contribute to further clarify ASD etiology. Serum miR-140-3p could represent a potential non-invasive biomarker for ASD, easy to test through liquid biopsy.

  12. Energy transport corridors: the potential role of Federal lands in states identified by the Energy Policy Act of 2005, section 368(b).

    Energy Technology Data Exchange (ETDEWEB)

    Krummel, J.; Hlohowskyj, I.; Kuiper, J.; Kolpa, R.; Moore, R.; May, J.; VanKuiken, J.C.; Kavicky, J.A.; McLamore, M.R.; Shamsuddin, S. (Decision and Information Sciences); ( EVS)

    2011-09-01

    106 of the National Historic Preservation Act (NHPA). Under Section 368, Congress divided the United States into two groups of states: the 11 contiguous western states and the remaining states. Direction for energy transportation corridor analysis and selection in the 11 western states was addressed in Section 368(a) of EPAct, while direction for energy transportation corridor analysis and selection in all other states was addressed under Section 368(b) of EPAct. It was clearly the priority of Congress to conduct corridor location studies and designation first on federal lands in the western states. Under Section 368(a), the Agencies produced a programmatic environmental impact statement (EIS), Designation of Energy Corridors on Federal Land in the 11 Western States (DOE and DOI 2008), that was used in part as the basis for designating more than 6,000 mi (9,656 km) of energy transportation corridors on federal land in 11 western states. Under Section 368(a) of EPAct, Congress clearly stated the Agencies needed to (1) designate energy transportation corridors on federal land, (2) conduct the necessary environmental review of the designated corridors, and (3) incorporate the designated corridors into the appropriate land use plans. Congressional direction under Section 368(b) of EPAct differs from that provided under Section 368(a). Specifically, Section 368(b) requires the secretaries of the Agencies, in consultation with the Federal Energy Regulatory Commission (FERC), affected utility industries, and other interested persons, to jointly: (1) Identify corridors for oil, gas, and hydrogen pipelines and electricity transmission and distribution facilities on federal land in states other than the 11 western states identified under Section 368(a) of EPAct, and (2) Schedule prompt action to identify, designate, and incorporate the corridors into the applicable land use plans. While Section 368(a) clearly directs designation as a necessary first step for energy

  13. Potential diagnostic value of regional myocardial adrenergic imaging using {sup 123}I-MIBG SPECT to identify patients with Lewy body diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lebasnier, Adrien; Peyronnet, Damien; Bouvard, Gerard [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Lamotte, Guillaume; Defer, Gilles [University Hospital Center of Caen, Department of Neurology, Caen (France); Manrique, Alain [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Cyceron PET Centre, Caen (France); Normandie Universite, Caen (France); Agostini, Denis [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Normandie Universite, Caen (France)

    2015-01-28

    The aim of this study was to determine the potential diagnostic value of regional myocardial adrenergic {sup 123}I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) imaging to identify patients with Lewy body diseases (LBD+). Sixty-four consecutive patients who underwent cardiac {sup 123}I-MIBG SPECT to differentiate LBD+, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), from patients without LBD (LBD-) were retrospectively reviewed. A neurologist expert in memory disorders determined the final clinical diagnosis by using international clinical diagnostic criteria. Planar [heart to mediastinum ratio (HMR)] and {sup 123}I-MIBG SPECT[innervation defect score (IDS)] using the 17-segment left ventricular model (five-point scale) were obtained 4 h after the injection of {sup 123}I-MIBG on a low-energy high-resolution (LEHR) collimator. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal HMR and IDS cut-off values to discriminate LBD+ from LBD-. Of the 64 patients, 45 (70 %) were diagnosed LBD+ (DLB, n = 27; PD, n = 18) and 19 were diagnosed LBD- (5 other dementias, 14 other parkinsonisms). The HMR and IDS of LBD+ were significantly different from those of LBD- (1.30 ± 0.21 vs 1.65 ± 0.26, p < 0.001; 39 ± 28 vs 8 ± 16, p = 0.001). The optimal HMR and IDS cut-off values to discriminate LBD+ (n = 45) from LBD- (n = 19) were 1.47 and 6/68, providing a sensitivity and specificity of 82.2 and 84.2 % and 86.7 and 73.7 %, respectively. Regional myocardial adrenergic {sup 123}I-MIBG imaging SPECT has a potential diagnostic value to identify LBD+. (orig.)

  14. Object-Based Classification as an Alternative Approach to the Traditional Pixel-Based Classification to Identify Potential Habitat of the Grasshopper Sparrow

    Science.gov (United States)

    Jobin, Benoît; Labrecque, Sandra; Grenier, Marcelle; Falardeau, Gilles

    2008-01-01

    The traditional method of identifying wildlife habitat distribution over large regions consists of pixel-based classification of satellite images into a suite of habitat classes used to select suitable habitat patches. Object-based classification is a new method that can achieve the same objective based on the segmentation of spectral bands of the image creating homogeneous polygons with regard to spatial or spectral characteristics. The segmentation algorithm does not solely rely on the single pixel value, but also on shape, texture, and pixel spatial continuity. The object-based classification is a knowledge base process where an interpretation key is developed using ground control points and objects are assigned to specific classes according to threshold values of determined spectral and/or spatial attributes. We developed a model using the eCognition software to identify suitable habitats for the Grasshopper Sparrow, a rare and declining species found in southwestern Québec. The model was developed in a region with known breeding sites and applied on other images covering adjacent regions where potential breeding habitats may be present. We were successful in locating potential habitats in areas where dairy farming prevailed but failed in an adjacent region covered by a distinct Landsat scene and dominated by annual crops. We discuss the added value of this method, such as the possibility to use the contextual information associated to objects and the ability to eliminate unsuitable areas in the segmentation and land cover classification processes, as well as technical and logistical constraints. A series of recommendations on the use of this method and on conservation issues of Grasshopper Sparrow habitat is also provided.

  15. Technical support for the Ohio Clean Coal Technology Program. Volume 2, Baseline of knowledge concerning process modification opportunities, research needs, by-product market potential, and regulatory requirements: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Olfenbuttel, R.; Clark, S.; Helper, E.; Hinchee, R.; Kuntz, C.; Means, J.; Oxley, J.; Paisley, M.; Rogers, C.; Sheppard, W.; Smolak, L. [Battelle, Columbus, OH (United States)

    1989-08-28

    This report was prepared for the Ohio Coal Development Office (OCDO) under Grant Agreement No. CDO/R-88-LR1 and comprises two volumes. Volume 1 presents data on the chemical, physical, and leaching characteristics of by-products from a wide variety of clean coal combustion processes. Volume 2 consists of a discussion of (a) process modification waste minimization opportunities and stabilization considerations; (b) research and development needs and issues relating to clean coal combustion technologies and by-products; (c) the market potential for reusing or recycling by-product materials; and (d) regulatory considerations relating to by-product disposal or reuse.

  16. Scoping review to identify potential non-antimicrobial interventions to mitigate antimicrobial resistance in commensal enteric bacteria in North American cattle production systems.

    Science.gov (United States)

    Murphy, C P; Fajt, V R; Scott, H M; Foster, M J; Wickwire, P; McEwen, S A

    2016-01-01

    A scoping review was conducted to identify modifiable non-antimicrobial factors to reduce the occurrence of antimicrobial resistance in cattle populations. Searches were developed to retrieve peer-reviewed published studies in animal, human and in vitro microbial populations. Citations were retained when modifiable non-antimicrobial factors or interventions potentially associated with antimicrobial resistance were described. Studies described resistance in five bacterial genera, species or types, and 40 antimicrobials. Modifiable non-antimicrobial factors or interventions ranged widely in type, and the depth of evidence in animal populations was shallow. Specific associations between a factor or intervention with antimicrobial resistance in a population (e.g. associations between organic systems and tetracycline susceptibility in E. coli from cattle) were reported in a maximum of three studies. The identified non-antimicrobial factors or interventions were classified into 16 themes. Most reported associations between the non-antimicrobial modifiable factors or interventions and antimicrobial resistance were not statistically significant (P > 0·05 and a confidence interval including 1), but when significant, the results were not consistent in direction (increase or decrease in antimicrobial resistance) or magnitude. Research is needed to better understand the impacts of promising modifiable factors or interventions on the occurrence of antimicrobial resistance before any recommendations can be offered or adopted.

  17. Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet’s Disease by Gas Chromatography/Time-of-Flight−Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Joong Kyong Ahn

    2017-11-01

    Full Text Available Diagnosing Behcet’s disease (BD is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight–mass spectrometry (GC/TOF−MS. Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC were assessed using GC/TOF−MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF−MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA model were R2X of 0.231, R2Y of 0.804, and Q2 of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974. OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%. We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF−MS.

  18. Indices of heart rate variability as potential early markers of metabolic stress and compromised regulatory capacity in dried-off high-yielding dairy cows.

    Science.gov (United States)

    Erdmann, S; Mohr, E; Derno, M; Tuchscherer, A; Schäff, C; Börner, S; Kautzsch, U; Kuhla, B; Hammon, H M; Röntgen, M

    2017-10-25

    High performing dairy cows experience distinct metabolic stress during periods of negative energy balance. Subclinical disorders of the cow's energy metabolism facilitate failure of adaptational responses resulting in health problems and reduced performance. The autonomic nervous system (ANS) with its sympathetic and parasympathetic branches plays a predominant role in adaption to inadequate energy and/or fuel availability and mediation of the stress response. Therefore, we hypothesize that indices of heart rate variability (HRV) that reflect ANS activity and sympatho-vagal balance could be early markers of metabolic stress, and possibly useful to predict cows with compromised regulatory capacity. In this study we analysed the autonomic regulation and stress level of 10 pregnant dried-off German Holstein cows before, during and after a 10-h fasting period by using a wide range of HRV parameters. In addition heat production (HP), energy balance, feed intake, rumen fermentative activity, physical activity, non-esterified fatty acids, β-hydroxybutyric acid, cortisol and total ghrelin plasma concentrations, and body temperature (BT) were measured. In all cows fasting induced immediate regulatory adjustments including increased lipolysis (84%) and total ghrelin levels (179%), reduction of HP (-16%), standing time (-38%) and heart rate (-15%). However, by analysing frequency domain parameters of HRV (high-frequency (HF) and low-frequency (LF) components, ratio LF/HF) cows could be retrospectively assigned to groups reacting to food removal with increased or decreased activity of the parasympathetic branch of the ANS. Regression analysis reveals that under control conditions (feeding ad libitum) group differences were best predicted by the nonlinear domain HRV component Maxline (L MAX, R 2=0.76, threshold; TS=258). Compared with cows having L MAX values above TS (>L MAX: 348±17), those with L MAX values below TS (fasting with a shift of their sympatho-vagal balance

  19. The potential of circulating extracellular small RNAs (smexRNA) in veterinary diagnostics-Identifying biomarker signatures by multivariate data analysis.

    Science.gov (United States)

    Melanie, Spornraft; Benedikt, Kirchner; Pfaffl, Michael W; Irmgard, Riedmaier

    2015-09-01

    Worldwide growth and performance-enhancing substances are used in cattle husbandry to increase productivity. In certain countries however e.g., in the EU, these practices are forbidden to prevent the consumers from potential health risks of substance residues in food. To maximize economic profit, 'black sheep' among farmers might circumvent the detection methods used in routine controls, which highlights the need for an innovative and reliable detection method. Transcriptomics is a promising new approach in the discovery of veterinary medicine biomarkers and also a missing puzzle piece, as up to date, metabolomics and proteomics are paramount. Due to increased stability and easy sampling, circulating extracellular small RNAs (smexRNAs) in bovine plasma were small RNA-sequenced and their potential to serve as biomarker candidates was evaluated using multivariate data analysis tools. After running the data evaluation pipeline, the proportion of miRNAs (microRNAs) and piRNAs (PIWI-interacting small non-coding RNAs) on the total sequenced reads was calculated. Additionally, top 10 signatures were compared which revealed that the readcount data sets were highly affected by the most abundant miRNA and piRNA profiles. To evaluate the discriminative power of multivariate data analyses to identify animals after veterinary drug application on the basis of smexRNAs, OPLS-DA was performed. In summary, the quality of miRNA models using all mapped reads for both treatment groups (animals treated with steroid hormones or the β-agonist clenbuterol) is predominant to those generated with combined data sets or piRNAs alone. Using multivariate projection methodologies like OPLS-DA have proven the best potential to generate discriminative miRNA models, supported by small RNA-Seq data. Based on the presented comparative OPLS-DA, miRNAs are the favorable smexRNA biomarker candidates in the research field of veterinary drug abuse.

  20. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  1. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  2. Inappropriate pharmacological treatment in older adults affected by cardiovascular disease and other chronic comorbidities: a systematic literature review to identify potentially inappropriate prescription indicators

    Directory of Open Access Journals (Sweden)

    Lucenteforte E

    2017-10-01

    Full Text Available Ersilia Lucenteforte,1 Niccolò Lombardi,1,* Davide Liborio Vetrano,2,* Domenico La Carpia,2,* Zuzana Mitrova,3 Ursula Kirchmayer,3 Giovanni Corrao,4 Francesco Lapi,5 Alessandro Mugelli,1 Alfredo Vannacci1 On behalf of the Italian Group for Appropriate Drug prescription in the Elderly (I-GrADE 1Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA, University of Florence, Florence, Italy; 2Department of Geriatrics Catholic University, Rome, Italy; 3Department of Epidemiology, ASL 1 Rome, Italy; 4Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy; 5Epidemiology Unit, ARS Toscana, Florence, Italy *These authors contributed equally to this work Abstract: Avoiding medications in which the risks outweigh the benefits in the elderly patient is a challenge for physicians, and different criteria to identify inappropriate prescription (IP exist to aid prescribers. Definition of IP indicators in the Italian geriatric population affected by cardiovascular disease and chronic comorbidities could be extremely useful for prescribers and could offer advantages from a public health perspective. The purpose of the present study was to identify IP indicators by means of a systematic literature review coupled with consensus criteria. A systematic search of PubMed, EMBASE, and CENTRAL databases was conducted, with the search structured around four themes and combining each with the Boolean operator “and”. The first regarded “prescriptions”, the second “adverse events”, the third “cardiovascular conditions”, and the last was planned to identify studies on “older people”. Two investigators independently reviewed titles, abstracts, full texts, and selected articles addressing IP in the elderly affected by cardiovascular condition using the following inclusion criteria: studies on people aged ≥65 years; studies on patients with no restriction on age but with data on subjects

  3. Regulatory-associated protein of TOR (RAPTOR) alters the hormonal and metabolic composition of Arabidopsis seeds, controlling seed morphology, viability and germination potential.

    Science.gov (United States)

    Salem, Mohamed A; Li, Yan; Wiszniewski, Andrew; Giavalisco, Patrick

    2017-11-01

    Target of Rapamycin (TOR) is a positive regulator of growth and development in all eukaryotes, which positively regulates anabolic processes like protein synthesis, while repressing catabolic processes, including autophagy. To better understand TOR function we decided to analyze its role in seed development and germination. We therefore performed a detailed phenotypic analysis using mutants of the REGULATORY-ASSOCIATED PROTEIN OF TOR 1B (RAPTOR1B), a conserved TOR interactor, acting as a scaffold protein, which recruits substrates for the TOR kinase. Our results show that raptor1b plants produced seeds that were delayed in germination and less resistant to stresses, leading to decreased viability. These physiological phenotypes were accompanied by morphological changes including decreased seed-coat pigmentation and reduced production of seed-coat mucilage. A detailed molecular analysis revealed that many of these morphological changes were associated with significant changes of the metabolic content of raptor1b seeds, including elevated levels of free amino acids, as well as reduced levels of protective secondary metabolites and storage proteins. Most of these observed changes were accompanied by significantly altered phytohormone levels in the raptor1b seeds, with increases in abscisic acid, auxin and jasmonic acid, which are known to inhibit germination. Delayed germination and seedling growth, observed in the raptor1b seeds, could be partially restored by the exogenous supply of gibberellic acid, indicating that TOR is at the center of a regulatory hub controlling seed metabolism, maturation and germination. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  4. RNA regulatory elements and polyadenylation in plants

    Directory of Open Access Journals (Sweden)

    Arthur G. Hunt

    2012-01-01

    Full Text Available Alternative poly(A site choice (also known as alternative polyadenylation, or APA has the potential to affect gene expression in qualitative and quantitative ways. Alternative polyadenylation may affect as many as 82% of all expressed genes in a plant. The consequences of APA include the generation of transcripts with differing 3’-UTRs (and thus differing potential regulatory potential and of transcripts with differing protein-coding potential. Genome-wide studies of possible APA suggest a linkage with pre-mRNA splicing, and indicate a coincidence of and perhaps cooperation between RNA regulatory elements that affect splicing efficiency and the recognition of novel intronic poly(A sites. These studies also raise the possibility of the existence of a novel class of polyadenylation-related cis elements that are distinct from the well-characterized plant polyadenylation signal. Many potential APA events, however, have not been associated with identifiable cis elements. The present state of the field reveals a broad scope of APA, and also numerous opportunities for research into mechanisms that govern both choice and regulation of poly(A sites in plants.

  5. Distribution and incidence of atoxigenic Aspergillus flavus VCG in tree crop orchards in California: A strategy for identifying potential antagonists, the example of almonds.

    Science.gov (United States)

    Picot, Adeline; Doster, Mark; Islam, Md-Sajedul; Callicott, Kenneth; Ortega-Beltran, Alejandro; Cotty, Peter; Michailides, Themis

    2018-01-16

    To identify predominant isolates for potential use as biocontrol agents, Aspergillus flavus isolates collected from soils of almond, pistachio and fig orchard in the Central Valley of California were tested for their membership to 16 atoxigenic vegetative compatibility groups (VCGs), including YV36, the VCG to which AF36, an atoxigenic isolate commercialized in the United States as biopesticide, belongs. A surprisingly large proportion of isolates belonged to YV36 (13.3%, 7.2% and 6.6% of the total almond, pistachio and fig populations, respectively), while the percentage of isolates belonging to the other 15 VCGs ranged from 0% to 2.3%. In order to gain a better insight into the structure and diversity of atoxigenic A. flavus populations and to further identify predominant isolates, seventeen SSR markers were then used to genetically characterize AF36, the 15 type-isolates of the VCGs and 342 atoxigenic isolates of the almond population. There was considerable genetic diversity among isolates with a lack of differentiation among micro-geographical regions or years. Since isolates sharing identical SSR profiles from distinct orchards were rare, we separated them into groups of at least 3 closely-related isolates from distinct orchards that shared identical alleles for at least 15 out of the 17 loci. This led to the identification of 15 groups comprising up to 24 closely-related isolates. The group which contained the largest number of isolates were members of YV36 while five groups were also found to be members of our studied atoxigenic VCGs. These results suggest that these 15 groups, and AF36 in particular, are well adapted to various environmental conditions in California and to tree crops and, as such, are good candidates for use as biocontrol agents. Published by Elsevier B.V.

  6. On a European collaboration to identify organizational models, potential shortcomings and improvement options in out-of-hours primary health care.

    Science.gov (United States)

    Leutgeb, Ruediger; Walker, Nicola; Remmen, Roy; Klemenc-Ketis, Zalika; Szecsenyi, Joachim; Laux, Gunter

    2014-09-01

    Abstract Background: Out-of-hours care (OOHC) provision is an increasingly challenging aspect in the delivery of primary health care services. Although many European countries have implemented organizational models for out-of-hours primary care, which has been traditionally delivered by general practitioners, health care providers throughout Europe are still looking to resolve current challenges in OOHC. It is within this context that the European Research Network for Out-of-Hours Primary Health Care (EurOOHnet) was established in 2010 to investigate the provision of out-of-hours care across European countries, which have diverse political and health care systems. In this paper, we report on the EurOOHnet work related to OOHC organizational models, potential shortcomings and improvement options in out-of-hours primary health care. Needs assessment: The EurOOHnet expert working party proposed that models for OOHC should be reviewed to evaluate the availability and accessibility of OOHC for patients while also seeking ways to make the delivery of care more satisfying for service providers. To move towards resolution of OOHC challenges in primary care, as the first stage, the EurOOHnet expert working party identified the following key needs: clear and uniform definitions of the different OOHC models between different countries; adequate-ideally transnational-definitions of urgency levels and corresponding data; and educational programmes for nurses and doctors (e.g. in the use of a standardized triage system for OOHC). Finally, the need for a modern system of data transfer between different health care providers in regular care and providers in OOHC to prevent information loss was identified.

  7. Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

    Science.gov (United States)

    Bogenpohl, James W; Mignogna, Kristin M; Smith, Maren L; Miles, Michael F

    2017-01-01

    Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce nonbiased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA, and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x

  8. The yeast three-hybrid system as an experimental platform to identify proteins interacting with small signaling molecules in plant cells: Potential and limitations

    Directory of Open Access Journals (Sweden)

    Stéphanie eCottier

    2011-12-01

    Full Text Available Chemical genetics is a powerful scientific strategy that utilizes small bioactive molecules as experimental tools to unravel biological processes. Bioactive compounds occurring in nature represent an enormous diversity of structures that can be used to dissect functions of biological systems. Once the bioactivity of a natural or synthetic compound has been critically evaluated the challenge remains to identify its molecular target and mode of action, which usually is a time consuming and labor-intensive process. To facilitate this task, we decided to implement the yeast three-hybrid (Y3H technology as a general experimental platform to scan the whole Arabidopsis proteome for targets of small signaling molecules. The Y3H technology is based on the yeast two-hybrid system and allows direct cloning of proteins that interact in vivo with a synthetic hybrid ligand, which comprises the biologically active molecule of interest covalently linked to methotrexate (Mtx. In yeast nucleus the hybrid ligand connects two fusion proteins: the Mtx part binding to dihydrofolate reductase fused to a DNA binding domain (encoded in the yeast strain, and the bioactive molecule part binding to its potential protein target fused to a DNA activating domain (encoded on a cDNA expression vector. During cDNA library screening, the formation of this ternary, transcriptional activator complex leads to reporter gene activation in yeast cells, and thereby allows selection of the putative targets of small bioactive molecules of interest. Here we present the strategy and experimental details for construction and application of a Y3H platform, including chemical synthesis of different hybrid ligands, construction of suitable cDNA libraries, the choice of yeast strains, and appropriate screening conditions. Based on the results obtained and the current literature we discussed the perspectives and limitations of the Y3H approach for identifying targets of small bioactive molecules.

  9. Identifying potential areas for biofuel production and evaluating the environmental effects: a case study of the James River Basin in the Midwestern United States

    Science.gov (United States)

    Wu, Yiping; Liu, Shu-Guang; Li, Zhengpeng

    2012-01-01

    Biofuels are now an important resource in the United States because of the Energy Independence and Security Act of 2007. Both increased corn growth for ethanol production and perennial dedicated energy crop growth for cellulosic feedstocks are potential sources to meet the rising demand for biofuels. However, these measures may cause adverse environmental consequences that are not yet fully understood. This study 1) evaluates the long-term impacts of increased frequency of corn in the crop rotation system on water quantity and quality as well as soil fertility in the James River Basin and 2) identifies potential grasslands for cultivating bioenergy crops (e.g. switchgrass), estimating the water quality impacts. We selected the soil and water assessment tool, a physically based multidisciplinary model, as the modeling approach to simulate a series of biofuel production scenarios involving crop rotation and land cover changes. The model simulations with different crop rotation scenarios indicate that decreases in water yield and soil nitrate nitrogen (NO3-N) concentration along with an increase in NO3-N load to stream water could justify serious concerns regarding increased corn rotations in this basin. Simulations with land cover change scenarios helped us spatially classify the grasslands in terms of biomass productivity and nitrogen loads, and we further derived the relationship of biomass production targets and the resulting nitrogen loads against switchgrass planting acreages. The suggested economically efficient (planting acreage) and environmentally friendly (water quality) planting locations and acreages can be a valuable guide for cultivating switchgrass in this basin. This information, along with the projected environmental costs (i.e. reduced water yield and increased nitrogen load), can contribute to decision support tools for land managers to seek the sustainability of biofuel development in this region.

  10. The identification of transcription factors expressed in the notochord of Ciona intestinalis adds new potential players to the brachyury gene regulatory network.

    Science.gov (United States)

    José-Edwards, Diana S; Kerner, Pierre; Kugler, Jamie E; Deng, Wei; Jiang, Di; Di Gregorio, Anna

    2011-07-01

    The notochord is the distinctive characteristic of chordates; however, the knowledge of the complement of transcription factors governing the development of this structure is still incomplete. Here we present the expression patterns of seven transcription factor genes detected in the notochord of the ascidian Ciona intestinalis at various stages of embryonic development. Four of these transcription factors, Fos-a, NFAT5, AFF and Klf15, have not been directly associated with the notochord in previous studies, while the others, including Spalt-like-a, Lmx-like, and STAT5/6-b, display evolutionarily conserved expression in this structure as well as in other domains. We examined the hierarchical relationships between these genes and the transcription factor Brachyury, which is necessary for notochord development in all chordates. We found that Ciona Brachyury regulates the expression of most, although not all, of these genes. These results shed light on the genetic regulatory program underlying notochord formation in Ciona and possibly other chordates. Copyright © 2011 Wiley-Liss, Inc.

  11. Bifidobacterium infantis Potentially Alleviates Shrimp Tropomyosin-Induced Allergy by Tolerogenic Dendritic Cell-Dependent Induction of Regulatory T Cells and Alterations in Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Linglin Fu

    2017-11-01

    Full Text Available Shellfish is one of the major allergen sources worldwide, and tropomyosin (Tm is the predominant allergic protein in shellfish. Probiotics has been appreciated for its beneficial effects on the host, including anti-allergic and anti-inflammatory effects, although the underlying mechanisms were not fully understood. In this study, oral administration of probiotic strain Bifidobacterium infantis 14.518 (Binf effectively suppressed Tm-induced allergic response in a mouse model by both preventive and therapeutic strategies. Further results showed that Binf stimulated dendritic cells (DCs maturation and CD103+ tolerogenic DCs accumulation in gut-associated lymphoid tissue, which subsequently induced regulatory T cells differentiation for suppressing Th2-biased response. We also found that Binf regulates the alterations of gut microbiota composition. Specifically, the increase of Dorea and decrease of Ralstonia is highly correlated with Th2/Treg ratio and may contribute to alleviating Tm-induced allergic responses. Our findings provide molecular insight into the application of Binf in alleviating food allergy and even gut immune homeostasis.

  12. Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Aman C. Kaushik

    2018-02-01

    Full Text Available GPR142 (G protein receptor 142 is a novel orphan GPCR (G protein coupled receptor belonging to “Class A” of GPCR family and expressed in β cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling, and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

  13. Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

    Science.gov (United States)

    Kaushik, Aman C.; Kumar, Sanjay; Wei, Dong Q.; Sahi, Shakti

    2018-02-01

    GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to ‘Class A’ of GPCR family and expressed in beta cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

  14. Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease

    Directory of Open Access Journals (Sweden)

    Francesco Gentile

    2018-04-01

    Full Text Available The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF is a heterodimeric endonuclease essential for the nucleotide excision repair (NER DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells. Currently, there are no structures available for the catalytic site of the human ERCC1-XPF, which performs the metal-mediated cleavage of a DNA damaged strand at 5′. We adopted a homology modeling strategy to build a structural model of the human XPF nuclease domain which contained the active site and to extract dominant conformations of the domain using molecular dynamics simulations followed by clustering of the trajectory. We investigated the binding modes of known small molecule inhibitors targeting the active site to build a pharmacophore model. We then performed a virtual screening of the ZINC Is Not Commercial 15 (ZINC15 database to identify new ERCC1-XPF endonuclease inhibitors. Our work provides structural insights regarding the binding mode of small molecules targeting the ERCC1-XPF active site that can be used to rationally optimize such compounds. We also propose a set of new potential DNA repair inhibitors to be considered for combination cancer therapy strategies.

  15. A genome-wide RNAi screen identifies novel targets of neratinib resistance leading to identification of potential drug resistant genetic markers.

    Science.gov (United States)

    Seyhan, Attila A; Varadarajan, Usha; Choe, Sung; Liu, Wei; Ryan, Terence E

    2012-04-01

    Neratinib (HKI-272) is a small molecule tyrosine kinase inhibitor of the ErbB receptor family currently in Phase III clinical trials. Despite its efficacy, the mechanism of potential cellular resistance to neratinib and genes involved with it remains unknown. We have used a pool-based lentiviral genome-wide functional RNAi screen combined with a lethal dose of neratinib to discover chemoresistant interactions with neratinib. Our screen has identified a collection of genes whose inhibition by RNAi led to neratinib resistance including genes involved in oncogenesis (e.g. RAB33A, RAB6A and BCL2L14), transcription factors (e.g. FOXP4, TFEC, ZNF), cellular ion transport (e.g. CLIC3, TRAPPC2P1, P2RX2), protein ubiquitination (e.g. UBL5), cell cycle (e.g. CCNF), and genes known to interact with breast cancer-associated genes (e.g. CCNF, FOXP4, TFEC, several ZNF factors, GNA13, IGFBP1, PMEPA1, SOX5, RAB33A, RAB6A, FXR1, DDO, TFEC, OLFM2). The identification of novel mediators of cellular resistance to neratinib could lead to the identification of new or neoadjuvant drug targets. Their use as patient or treatment selection biomarkers could make the application of anti-ErbB therapeutics more clinically effective.

  16. BIOSENSORS FOR ENVIRONMENTAL MONITORING: A REGULATORY PERSPECTIVE

    Science.gov (United States)

    Biosensors show the potential to complement laboratory-based analytical methods for environmental applications. Although biosensors for potential environmental-monitoring applications have been reported for a wide range of environmental pollutants, from a regulatory perspective, ...

  17. Strengthening Regulatory Competence in Pakistan

    International Nuclear Information System (INIS)

    Sadiq, M.

    2016-01-01

    Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

  18. Identification and Functional Analysis of Gene Regulatory Sequences Interacting with Colorectal Tumor Suppressors

    DEFF Research Database (Denmark)

    Dahlgaard, Katja; Troelsen, Jesper

    2018-01-01

    Several tumor suppressors possess gene regulatory activity. Here, we describe how promoter and promoter/enhancer reporter assays can be used to characterize a colorectal tumor suppressor proteins’ gene regulatory activity of possible target genes. In the first part, a bioinformatic approach...... of the quick and efficient In-Fusion cloning method, and how to carry out transient transfections of Caco-2 colon cancer cells with the produced luciferase reporter plasmids using polyethyleneimine (PEI). A plan describing how to set up and carry out the luciferase expression assay is presented. The luciferase...... to identify relevant gene regulatory regions of potential target genes is presented. In the second part, it is demonstrated how to prepare and carry out the functional assay. We explain how to clone the bioinformatically identified gene regulatory regions into luciferase reporter plasmids by the use...

  19. TGF-β1 exerts opposing effects on grass carp leukocytes: implication in teleost immunity, receptor signaling and potential self-regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Mu Yang

    Full Text Available In fish immunity, the regulatory role of transforming growth factor-β1 (TGF-β1 has not been fully characterized. Here we examined the immunoregulatory effects of TGF-β1 in grass carp peripheral blood leukocytes (PBL and head kidney leukocytes (HKL. It is interesting that TGF-β1 consistently stimulated the cell viability and the mRNA levels of pro-inflammatory cytokines (Tnfα and Ifnγ and T/B cell markers [Cd4-like (Cd4l, Cd8α, Cd8β and Igμ] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-β1 type I receptor, activin receptor-like kinase 5 (ALK5, was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5(+ leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes.

  20. Regulatory alerts for dietary supplements in Canada and the United States, 2005-13.

    Science.gov (United States)

    Abe, Andrew M; Hein, Darren J; Gregory, Philip J

    2015-06-01

    Dietary supplement regulatory alerts published by the Food and Drug Administration (FDA) and Health Canada were evaluated and characterized. FDA MedWatch and Health Canada websites were reviewed to identify regulatory alerts regarding dietary supplements from January 1, 2005, through December 31, 2013. Alerts were analyzed to identify product characteristics that may be predictive of product quality issues and potential patient harm. A total of 1560 dietary supplement-related regulatory alerts were identified. Of those, 1287 (83%) were identified through Health Canada, and 273 (18%) were identified through FDA MedWatch. The country of origin of dietary supplements associated with regulatory alerts was not provided in most regulatory alerts; however, when their origin was provided, the United States was the most common. Dietary supplements intended for sexual enhancement were the subject of 33% of all regulatory alerts identified. Products purchased online were the most likely to be associated with a regulatory alert. Dietary supplements intended for sexual enhancement, weight loss, and bodybuilding or athletic performance appeared to pose the greatest risk for patient harm due to product contamination with a pharmaceutical such as a phosphodiesterase-5 inhibitor or sibutramine. Analysis of Canadian and U.S. regulatory alerts concerning dietary supplements revealed that more than 80% of the composite alerts were issued by Health Canada. The most common intended uses of supplements for which alerts were issued were sexual enhancement, weight loss, and bodybuilding or athletic performance. The most common reason for alerts was the presence of a pharmaceutical contaminant. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  1. A global regulatory science agenda for vaccines.

    Science.gov (United States)

    Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

    2013-04-18

    The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

  2. Bipolar disorder: The importance of clinical assessment in identifying prognostic factors - An Audit. Part 1: An analysis of potential prognostic factors.

    Science.gov (United States)

    Verdolini, Norma; Dean, Jonathon; Elisei, Sandro; Quartesan, Roberto; Zaman, Rashid; Agius, Mark

    2014-11-01

    these two groups of patients. We have identified several trends in our patients with bipolar disorder that agree with previous research. Our sample suggested that the assignation of a care coordinator is not done on a clinical basis. In our sample, some patients were found not to have information available so we suggest that a questionnaire to remind clinicians of potentially useful information would be helpful to aid in prognostication. In particular, specific features of the disease, like family history, age at onset, and features of depressive episodes may be highlighted as our sample suggests that these are often unrecorded when not known or negative.

  3. Advanced Reactor Technology -- Regulatory Technology Development Plan (RTDP)

    Energy Technology Data Exchange (ETDEWEB)

    Moe, Wayne Leland [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-05-01

    This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However, it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory

  4. Advanced Reactor Technology -- Regulatory Technology Development Plan (RTDP)

    International Nuclear Information System (INIS)

    Moe, Wayne Leland

    2015-01-01

    This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a ''critical path'' for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However, it is also important to remember that certain ''minimum'' levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial ''first step'' in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by

  5. Advanced Reactor Technologies - Regulatory Technology Development Plan (RTDP)

    Energy Technology Data Exchange (ETDEWEB)

    Moe, Wayne L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-08-23

    This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However, it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory

  6. Review of Federal Motor Vehicle Safety Standards (FMVSS) for Automated Vehicles : Identifying Potential Barriers and Challenges for the Certification of Automated Vehicles Using Existing FMVSS

    Science.gov (United States)

    2016-03-11

    The purpose of this work is to identify instances where the existing Federal Motor Vehicle Safety Standards may pose challenges to the introduction of automated vehicles. It identifies standards requiring further review - both to ensure that existing...

  7. A flexible regulatory framework

    International Nuclear Information System (INIS)

    Silvennoinen, T.

    2000-01-01

    Regulatory reform of the Finnish electricity market meant opening up potentially competitive parts of the electricity sector to competition and eliminating all unnecessary forms of regulation covering generation, wholesale supply, retail supply, and foreign trade in electricity. New types of control and regulatory mechanisms and institutions were set up for those parts of the electricity industry that were excluded from competition, such as network operations. Network activities now have to be licensed, whereas no licence is needed for generation or supply. A new sector-specific regulatory authority was established in 1995 to coincide with the implementation of the Electricity Market Act, known as the Electricity Market Authority. This is responsible for regulating network activities and retail supply to captive customers. The core function of the authority, which employs some 14 people, is to promote the smooth operation of the Finnish electricity market and to oversee the implementation of the Electricity Market Act and its provisions. Its most important duties are linked to overseeing the process by which network companies price their electricity. As price regulation no longer exists, all the companies in the electricity sector set their tariffs independently, even network companies. The job of controlling the pricing of network services is handed by the Electricity Market Authority, following the principles of competition control. Pricing control takes place ex post - after a pricing system has been adopted by a company and concentrates on individual cases and companies. There is no ex ante system of setting or approving prices and tariffs by the regulator. The tariffs and pricing of network services can be evaluated, however, by both the Electricity Market Authority and the Finnish Competition Authority, which have overlapping powers as regards the pricing of network activities. The Finnish regulatory framework can be described as a system of light

  8. Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

    International Nuclear Information System (INIS)

    Illizastigui, P.F.

    2016-01-01

    The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

  9. Modeling Dynamic Regulatory Processes in Stroke

    Science.gov (United States)

    McDermott, Jason E.; Jarman, Kenneth; Taylor, Ronald; Lancaster, Mary; Shankaran, Harish; Vartanian, Keri B.; Stevens, Susan L.; Stenzel-Poore, Mary P.; Sanfilippo, Antonio

    2012-01-01

    The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implica