Using the Developmental Gene Bicoid to Identify Species of Forensically Important Blowflies (Diptera: Calliphoridae)

PubMed Central

Park, Seong Hwan; Park, Chung Hyun; Zhang, Yong; Piao, Huguo; Chung, Ukhee; Kim, Seong Yoon; Ko, Kwang Soo; Yi, Cheong-Ho; Jo, Tae-Ho; Hwang, Juck-Joon

2013-01-01

Identifying species of insects used to estimate postmortem interval (PMI) is a major subject in forensic entomology. Because forensic insect specimens are morphologically uniform and are obtained at various developmental stages, DNA markers are greatly needed. To develop new autosomal DNA markers to identify species, partial genomic sequences of the bicoid (bcd) genes, containing the homeobox and its flanking sequences, from 12 blowfly species (Aldrichina grahami, Calliphora vicina, Calliphora lata, Triceratopyga calliphoroides, Chrysomya megacephala, Chrysomya pinguis, Phormia regina, Lucilia ampullacea, Lucilia caesar, Lucilia illustris, Hemipyrellia ligurriens and Lucilia sericata; Calliphoridae: Diptera) were determined and analyzed. This study first sequenced the ten blowfly species other than C. vicina and L. sericata. Based on the bcd sequences of these 12 blowfly species, a phylogenetic tree was constructed that discriminates the subfamilies of Calliphoridae (Luciliinae, Chrysomyinae, and Calliphorinae) and most blowfly species. Even partial genomic sequences of about 500 bp can distinguish most blowfly species. The short intron 2 and coding sequences downstream of the bcd homeobox in exon 3 could be utilized to develop DNA markers for forensic applications. These gene sequences are important in the evolution of insect developmental biology and are potentially useful for identifying insect species in forensic science. PMID:23586044

Genes Important for Schizosaccharomyces pombe Meiosis Identified Through a Functional Genomics Screen

PubMed Central

Blyth, Julie; Makrantoni, Vasso; Barton, Rachael E.; Spanos, Christos; Rappsilber, Juri; Marston, Adele L.

2018-01-01

Meiosis is a specialized cell division that generates gametes, such as eggs and sperm. Errors in meiosis result in miscarriages and are the leading cause of birth defects; however, the molecular origins of these defects remain unknown. Studies in model organisms are beginning to identify the genes and pathways important for meiosis, but the parts list is still poorly defined. Here we present a comprehensive catalog of genes important for meiosis in the fission yeast, Schizosaccharomyces pombe. Our genome-wide functional screen surveyed all nonessential genes for roles in chromosome segregation and spore formation. Novel genes important at distinct stages of the meiotic chromosome segregation and differentiation program were identified. Preliminary characterization implicated three of these genes in centrosome/spindle pole body, centromere, and cohesion function. Our findings represent a near-complete parts list of genes important for meiosis in fission yeast, providing a valuable resource to advance our molecular understanding of meiosis. PMID:29259000

Newer Approaches to Identify Potential Untoward Effects in Functional Foods.

PubMed

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.

STUDY TO IDENTIFY IMPORTANT PARAMETERS FOR CHARACTERIZING PESTICIDE RESIDUE TRANSFER EFFICIENCIES

EPA Science Inventory

To reduce the uncertainty associated with current estimates of children's exposure to pesticides by dermal contact and non-dietary ingestion, residue transfer data are required. Prior to conducting exhaustive studies, a screening study to identify the important parameters for...

Molecular Modeling of Environmentally Important Processes: Reduction Potentials

ERIC Educational Resources Information Center

Lewis, Anne; Bumpus, John A.; Truhlar, Donald G.; Cramer, Christopher J.

2004-01-01

The increasing use of computational quantum chemistry in the modeling of environmentally important processes is described. The employment of computational quantum mechanics for the prediction of oxidation-reduction potential for solutes in an aqueous medium is discussed.

Use of Event-Related Potentials to Identify Language and Reading Skills

ERIC Educational Resources Information Center

Molfese, Victoria J.; Molfese, Dennis L.; Beswick, Jennifer L.; Jacobi-Vessels, Jill; Molfese, Peter J.; Molnar, Andrew E.; Wagner, Mary C.; Haines, Brittany L.

2008-01-01

The extent to which oral language and emergent literacy skills are influenced by event-related potential measures of phonological processing was examined. Results revealed that event-related potential responses identify differences in letter naming but not receptive language skills.

Identifying potential kidney donors using social networking web sites.

PubMed

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.

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

PubMed

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.

Positive selection moments identify potential functional residues in human olfactory receptors

NASA Technical Reports Server (NTRS)

Singer, M. S.; Weisinger-Lewin, Y.; Lancet, D.; Shepherd, G. M.

1996-01-01

Correlated mutation analysis and molecular models of olfactory receptors have provided evidence that residues in the transmembrane domains form a binding pocket for odor ligands. As an independent test of these results, we have calculated positive selection moments for the alpha-helical sixth transmembrane domain (TM6) of human olfactory receptors. The moments can be used to identify residues that have been preferentially affected by positive selection and are thus likely to interact with odor ligands. The results suggest that residue 622, which is commonly a serine or threonine, could form critical H-bonds. In some receptors a dual-serine subsite, formed by residues 622 and 625, could bind hydroxyl determinants on odor ligands. The potential importance of these residues is further supported by site-directed mutagenesis in the beta-adrenergic receptor. The findings should be of practical value for future physiological studies, binding assays, and site-directed mutagenesis.

Identifying Outcomes that Are Important to Living Kidney Donors: A Nominal Group Technique Study.

PubMed

Hanson, Camilla S; Chapman, Jeremy R; Gill, John S; Kanellis, John; Wong, Germaine; Craig, Jonathan C; Teixeira-Pinto, Armando; Chadban, Steve J; Garg, Amit X; Ralph, Angelique F; Pinter, Jule; Lewis, Joshua R; Tong, Allison

2018-06-07

Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices. Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically. Across 14 groups, 123 donors aged 27-78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0-1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility. Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings. Copyright © 2018 by the American Society of Nephrology.

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma.

PubMed

Chow, Yock Ping; Tan, Lu Ping; Chai, San Jiun; Abdul Aziz, Norazlin; Choo, Siew Woh; Lim, Paul Vey Hong; Pathmanathan, Rajadurai; Mohd Kornain, Noor Kaslina; Lum, Chee Lun; Pua, Kin Choo; Yap, Yoke Yeow; Tan, Tee Yong; Teo, Soo Hwang; Khoo, Alan Soo-Beng; Patel, Vyomesh

2017-03-03

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

PubMed Central

Chow, Yock Ping; Tan, Lu Ping; Chai, San Jiun; Abdul Aziz, Norazlin; Choo, Siew Woh; Lim, Paul Vey Hong; Pathmanathan, Rajadurai; Mohd Kornain, Noor Kaslina; Lum, Chee Lun; Pua, Kin Choo; Yap, Yoke Yeow; Tan, Tee Yong; Teo, Soo Hwang; Khoo, Alan Soo-Beng; Patel, Vyomesh

2017-01-01

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies. PMID:28256603

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

PubMed

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

Mixed Potentials: Experimental Illustrations of an Important Concept in Practical Electrochemistry.

ERIC Educational Resources Information Center

Power, G. P.; Ritchie, I. M.

1983-01-01

Presents a largely experimental approach to the concept of mixed potentials, pointing out the close parallel that exists between equilibrium potentials. Describes several important examples of mixed potentials, providing current-voltage and polarization curves and half reactions as examples. Includes a discussion of corrosion reactions and…

Using a watershed-centric approach to identify potentially impacted beaches

EPA Science Inventory

Beaches can be affected by a variety of contaminants. Of particular concern are beaches impacted by human fecal contamination and urban runoff. This poster demonstrates a methodology to identify potentially impacted beaches using Geographic Information Systems (GIS). Since h...

Resampling procedures to identify important SNPs using a consensus approach.

PubMed

Pardy, Christopher; Motyer, Allan; Wilson, Susan

2011-11-29

Our goal is to identify common single-nucleotide polymorphisms (SNPs) (minor allele frequency > 1%) that add predictive accuracy above that gained by knowledge of easily measured clinical variables. We take an algorithmic approach to predict each phenotypic variable using a combination of phenotypic and genotypic predictors. We perform our procedure on the first simulated replicate and then validate against the others. Our procedure performs well when predicting Q1 but is less successful for the other outcomes. We use resampling procedures where possible to guard against false positives and to improve generalizability. The approach is based on finding a consensus regarding important SNPs by applying random forests and the least absolute shrinkage and selection operator (LASSO) on multiple subsamples. Random forests are used first to discard unimportant predictors, narrowing our focus to roughly 100 important SNPs. A cross-validation LASSO is then used to further select variables. We combine these procedures to guarantee that cross-validation can be used to choose a shrinkage parameter for the LASSO. If the clinical variables were unavailable, this prefiltering step would be essential. We perform the SNP-based analyses simultaneously rather than one at a time to estimate SNP effects in the presence of other causal variants. We analyzed the first simulated replicate of Genetic Analysis Workshop 17 without knowledge of the true model. Post-conference knowledge of the simulation parameters allowed us to investigate the limitations of our approach. We found that many of the false positives we identified were substantially correlated with genuine causal SNPs.

27 CFR 478.92 - How must licensed manufacturers and licensed importers identify firearms, armor piercing...

Code of Federal Regulations, 2010 CFR

2010-04-01

... Conduct of Business § 478.92 How must licensed manufacturers and licensed importers identify firearms... business; and (E) In the case of an imported firearm, the name of the country in which it was manufactured... place of business. For additional requirements relating to imported firearms, see Customs regulations at...

Identifying hub stations and important lines of bus networks: A case study in Xiamen, China

NASA Astrophysics Data System (ADS)

Zhang, Hui; Zhuge, Chengxiang; Yu, Xiaohua

2018-07-01

Hub stations and important lines play key roles in transfers between stations. In this paper, a node failure model is proposed to identify hub stations. In the model, we introduce two new indicators called neighborhood degree ratio and transfer index to evaluate the importance of stations, which consider neighborhood stations' degree of station and the initial transfer times between stations. Moreover, line accessibility is developed to measure the importance of lines in the bus network. Xiamen bus network in 2016 is utilized to test the model. The results show that the two introduced indicators are more effective to identify hub stations compared with traditional complex network indicators such as degree, clustering coefficient and betweenness.

Important caves to be identified

NASA Astrophysics Data System (ADS)

Criteria to identify significant caves on federal land are being developed by the Interior Department's Bureau of Land Management and the Agriculture Department's Forest Service under requirements of the Federal Cave Resources Protection Act of 1988. The departments gave advance notice of proposed rulemaking March 3 and invited suggestions and comments from the public for 30 days.The law requires protection, to the extent practical, of significant caves on lands administered by the Secretaries of Agriculture and Interior and includes authority to issue and revoke permits for collection and removal of cave resources and special provisions for regulation of cave resources on Indian lands. Final regulations must be published by August 18, 1989.

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

PubMed

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

Discovering Potential Pathogens among Fungi Identified as Nonsporulating Molds▿

PubMed Central

Pounder, June I.; Simmon, Keith E.; Barton, Claudia A.; Hohmann, Sheri L.; Brandt, Mary E.; Petti, Cathy A.

2007-01-01

Fungal infections are increasing, particularly among immunocompromised hosts, and a rapid diagnosis is essential to initiate antifungal therapy. Often fungi cannot be identified by conventional methods and are classified as nonsporulating molds (NSM).We sequenced internal transcribed spacer regions from 50 cultures of NSM and found 16 potential pathogens that can be associated with clinical disease. In selected clinical settings, identification of NSM could prove valuable and have an immediate impact on patient management. PMID:17135442

Proteomics-based approach identified differentially expressed proteins with potential roles in endometrial carcinoma.

PubMed

Li, Zhengyu; Min, Wenjiao; Huang, Canhua; Bai, Shujun; Tang, Minghai; Zhao, Xia

2010-01-01

We used proteomic approaches to identify altered expressed proteins in endometrial carcinoma, with the aim of discovering potential biomarkers or therapeutic targets for endometrial carcinoma. The global proteins extracted from endometrial carcinoma and normal endometrial tissues were separated by 2-dimensional electrophoresis and analyzed with PDQuest (Bio-Rad, Hercules, Calif) software. The differentially expressed spots were identified by mass spectrometry and searched against NCBInr protein database. Those proteins with potential roles were confirmed by Western blotting and immunohistochemical assays. Ninety-nine proteins were identified by mass spectrometry, and a cluster diagram analysis indicated that these proteins were involved in metabolism, cell transformation, protein folding, translation and modification, proliferation and apoptosis, signal transduction, cytoskeleton, and so on. In confirmatory immunoblotting and immunohistochemical analyses, overexpressions of epidermal fatty acid-binding protein, calcyphosine, and cyclophilin A were also observed in endometrial carcinoma tissues, which were consistent with the proteomic results. Our results suggested that these identified proteins, including epidermal fatty acid-binding protein, calcyphosine, and cyclophilin A, might be of potential values in the studies of endometrial carcinogenesis or investigations of diagnostic biomarkers or treatment targets for endometrial carcinoma.

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

PubMed

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.

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

PubMed

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.

Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleijnen, J.P.C.; Helton, J.C.

1999-04-01

The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (1) linear relationships with correlation coefficients, (2) monotonic relationships with rank correlation coefficients, (3) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (4) trends in variability as defined by variances and interquartile ranges, and (5) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are consideredmore » for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (1) Type I errors are unavoidable, (2) Type II errors can occur when inappropriate analysis procedures are used, (3) physical explanations should always be sought for why statistical procedures identify variables as being important, and (4) the identification of important variables tends to be stable for independent Latin hypercube samples.« less

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

PubMed

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.

Recognition of an important water quality issue at zoos: prevalence and potential threat of toxic cyanobacteria.

PubMed

Doster, Enrique; Chislock, Michael F; Roberts, John F; Kottwitz, Jack J; Wilson, Alan E

2014-03-01

Zoo animals may be particularly vulnerable to water sources contaminated with cyanobacterial toxins given their nonvoluntary close association with this resource. However, the prevalence and potential threat of toxic cyanobacteria in this setting are unknown. Several otherwise unexplained yellow-bellied slider (Trachemys scripta scripta) deaths were documented in a zoo moat with recurring blooms of toxic Microcystis aeruginosa. Furthermore, an extremely high and potentially lethal concentration of the hepatotoxin microcystin (166 ng/g) was found in the liver of a necropsied turtle that died in this moat. A subsequent monthly survey of water quality revealed detectable concentrations of microcystin in all moats (0.0001 to 7.5 microg/L), with moats higher than 1 microg/L being significantly higher than the threshold for safe drinking water recommended by the World Health Organization. These results demonstrate that cyanobacterial blooms are an important water quality issue in zoos, and future research is necessary to identify potential associations among water quality, zoo animal health, and moat management strategies.

OXIDATION-REDUCTION POTENTIAL MEASUREMENTS OF IMPORTANT OXIDANTS IN DRINKING WATER

EPA Science Inventory

Oxidation-reduction (redox) reactions are important in drinking water treatment and distribution. Oxidation-reduction potential (ORP) measurements of water reflect the tendency of major constituents in the water to accept or lose electrons. Although ORP measurements are valuable...

Different approaches for identifying important concepts in probabilistic biomedical text summarization.

PubMed

Moradi, Milad; Ghadiri, Nasser

2018-01-01

Automatic text summarization tools help users in the biomedical domain to acquire their intended information from various textual resources more efficiently. Some of biomedical text summarization systems put the basis of their sentence selection approach on the frequency of concepts extracted from the input text. However, it seems that exploring other measures rather than the raw frequency for identifying valuable contents within an input document, or considering correlations existing between concepts, may be more useful for this type of summarization. In this paper, we describe a Bayesian summarization method for biomedical text documents. The Bayesian summarizer initially maps the input text to the Unified Medical Language System (UMLS) concepts; then it selects the important ones to be used as classification features. We introduce six different feature selection approaches to identify the most important concepts of the text and select the most informative contents according to the distribution of these concepts. We show that with the use of an appropriate feature selection approach, the Bayesian summarizer can improve the performance of biomedical summarization. Using the Recall-Oriented Understudy for Gisting Evaluation (ROUGE) toolkit, we perform extensive evaluations on a corpus of scientific papers in the biomedical domain. The results show that when the Bayesian summarizer utilizes the feature selection methods that do not use the raw frequency, it can outperform the biomedical summarizers that rely on the frequency of concepts, domain-independent and baseline methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Identifying important motivational factors for professionals in Greek hospitals

PubMed Central

Kontodimopoulos, Nick; Paleologou, Victoria; Niakas, Dimitris

2009-01-01

Background The purpose of this study was to identify important motivational factors according to the views of health-care professionals in Greek hospitals and particularly to determine if these might differ in the public and private sectors. Methods A previously developed -and validated- instrument addressing four work-related motivators (job attributes, remuneration, co-workers and achievements) was used. Three categories of health care professionals, doctors (N = 354), nurses (N = 581) and office workers (N = 418), working in public and private hospitals, participated and motivation was compared across socio-demographic and occupational variables. Results The range of reported motivational factors was mixed and Maslow's conclusions that lower level motivational factors must be met before ascending to the next level were not confirmed. The highest ranked motivator for the entire sample, and by professional subgroup, was achievements (P < 0.001). Within subgroups, motivators were similar, and only one significant difference was observed, namely between doctors and nurses in respect to co-workers (P < 0.05). Remuneration (and salary in particular) was reported as a significant incentive only for professionals in managerial positions. Health professionals in private hospitals were motivated by all factors significantly more than their public-hospital counterparts. Conclusion The results are in agreement with the literature which focuses attention to management approaches employing both monetary and non-monetary incentives to motivate health care workers. This study showed that intrinsic factors are particularly important and should become a target for effective employee motivation. PMID:19754968

Identifying potential impact of lead contamination using a geographic information system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bocco, G.; Sanchez, R.

1997-01-01

The main objective of this research was to identify the potential hazards associated with lead contamination from fixed sources in the city of Tijuana. An exploratory model is presented that describes the potential polluting sources as well as the exposed universe. The results of the analysis provide a clear picture of the geographic distribution of hazards areas for potential lead pollution in Tijuana. The findings are indicative of the dramatic consequences of rapid industrialization and urbanization in a city where there have not been significant planning efforts to mitigate the negative effects of this growth. The approach followed helps tomore » narrow the universe of potential pollution sources, which can help to direct attention, research priorities, and resources to the most critical areas. 16 refs.« less

Targeting imported malaria through social networks: a potential strategy for malaria elimination in Swaziland.

PubMed

Koita, Kadiatou; Novotny, Joseph; Kunene, Simon; Zulu, Zulizile; Ntshalintshali, Nyasatu; Gandhi, Monica; Gosling, Roland

2013-06-27

Swaziland has made great progress towards its goal of malaria elimination by 2015. However, malaria importation from neighbouring high-endemic Mozambique through Swaziland's eastern border remains a major factor that could prevent elimination from being achieved. In order to reach elimination, Swaziland must rapidly identify and treat imported malaria cases before onward transmission occurs. A nationwide formative assessment was conducted over eight weeks to determine if the imported cases of malaria identified by the Swaziland National Malaria Control Programme could be linked to broader social networks and to explore methods to access these networks. Using a structured format, interviews were carried out with malaria surveillance agents (6), health providers (10), previously identified imported malaria cases (19) and people belonging to the networks identified through these interviews (25). Most imported malaria cases were Mozambicans (63%, 12/19) making a living in Swaziland and sustaining their families in Mozambique. The majority of imported cases (73%, 14/19) were labourers and self-employed contractors who travelled frequently to Mozambique to visit their families and conduct business. Social networks of imported cases with similar travel patterns were identified through these interviews. Nearly all imported cases (89%, 17/19) were willing to share contact information to enable network members to be interviewed. Interviews of network members and key informants revealed common congregation points, such as the urban market places in Manzini and Malkerns, as well as certain bus stations, where people with similar travel patterns and malaria risk behaviours could be located and tested for malaria. This study demonstrated that imported cases of malaria belonged to networks of people with similar travel patterns. This study may provide novel methods for screening high-risk groups of travellers using both snowball sampling and time-location sampling of networks to

The perceived importance and the presence of creative potential in the health professional's work environment.

PubMed

Lukersmith, Sue; Burgess-Limerick, Robin

2013-01-01

The value of creative employees to an organisation's growth and innovative development, productivity, quality and sustainability is well established. This study examined the perceived relationship between creativity and work environment factors of 361 practicing health professionals, and whether these factors were present (realised) in their work environment. Job design (challenges, team work, task rotation, autonomy) and leadership (coaching supervisor, time for thinking, creative goals, recognition and incentives for creative ideas and results) were perceived as the most important factors for stimulating creativity. There was room for improvement of these in the work environment. Many aspects of the physical work environment were less important. Public health sector employers and organisations should adopt sustainable strategies which target the important work environment factors to support employee creativity and so enhance service quality, productivity, performance and growth. Implications of the results for ergonomists and workplace managers are discussed with a participatory ergonomics approach recommended. Creative employees are important to an organisation's innovation, productivity and sustainability. The survey identified health professionals perceive a need to improve job design and leadership factors at work to enhance and support employee creativity. There are implications for organisations and ergonomists to investigate the creative potential of work environments.

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

PubMed

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.

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

PubMed

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.

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

PubMed Central

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

Identifying Potential Norovirus Epidemics in China via Internet Surveillance

PubMed Central

Chen, Bin; Jiang, Tao; Cai, Gaofeng; Jiang, Zhenggang; Chen, Yongdi; Wang, Zhengting; Gu, Hua; Chai, Chengliang

2017-01-01

Background Norovirus is a common virus that causes acute gastroenteritis worldwide, but a monitoring system for norovirus is unavailable in China. Objective We aimed to identify norovirus epidemics through Internet surveillance and construct an appropriate model to predict potential norovirus infections. Methods The norovirus-related data of a selected outbreak in Jiaxing Municipality, Zhejiang Province of China, in 2014 were collected from immediate epidemiological investigation, and the Internet search volume, as indicated by the Baidu Index, was acquired from the Baidu search engine. All correlated search keywords in relation to norovirus were captured, screened, and composited to establish the composite Baidu Index at different time lags by Spearman rank correlation. The optimal model was chosen and possibly predicted maps in Zhejiang Province were presented by ArcGIS software. Results The combination of two vital keywords at a time lag of 1 day was ultimately identified as optimal (ρ=.924, P<.001). The exponential curve model was constructed to fit the trend of this epidemic, suggesting that a one-unit increase in the mean composite Baidu Index contributed to an increase of norovirus infections by 2.15 times during the outbreak. In addition to Jiaxing Municipality, Hangzhou Municipality might have had some potential epidemics in the study time from the predicted model. Conclusions Although there are limitations with early warning and unavoidable biases, Internet surveillance may be still useful for the monitoring of norovirus epidemics when a monitoring system is unavailable. PMID:28790023

Identifying key areas of ecosystem services potential to improve ecological management in Chongqing City, southwest China.

PubMed

Xiao, Yang; Xiao, Qiang

2018-03-29

Because natural ecosystems and ecosystem services (ES) are both critical to the well-being of humankind, it is important to understand their relationships and congruence for conservation planning. Spatial conservation planning is required to set focused preservation priorities and to assess future ecological implications. This study uses the combined measures of ES models and ES potential to estimate and analyze all four groups of ecosystem services to generate opportunities to maximize ecosystem services. Subsequently, we identify the key areas of conservation priorities as future forestation and conservation hotspot zones to improve the ecological management in Chongqing City, located in the upper reaches of the Three Gorges Reservoir Area, China. Results show that ecosystem services potential is extremely obvious. Compared to ecosystem services from 2000, we determined that soil conservation could be increased by 59.11%, carbon sequestration by 129.51%, water flow regulation by 83.42%, and water purification by 84.42%. According to our prioritization results, approximately 48% of area converted to forests exhibited high improvements in all ecosystem services (categorized as hotspot-1, hotspot-2, and hotspot-3). The hotspots identified in this study can be used as an excellent surrogate for evaluation ecological engineering benefits and can be effectively applied in improving ecological management planning.

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

PubMed

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.

Using Social Media Data to Identify Potential Candidates for Drug Repurposing: A Feasibility Study.

PubMed

Rastegar-Mojarad, Majid; Liu, Hongfang; Nambisan, Priya

2016-06-16

Drug repurposing (defined as discovering new indications for existing drugs) could play a significant role in drug development, especially considering the declining success rates of developing novel drugs. Typically, new indications for existing medications are identified by accident. However, new technologies and a large number of available resources enable the development of systematic approaches to identify and validate drug-repurposing candidates. Patients today report their experiences with medications on social media and reveal side effects as well as beneficial effects of those medications. Our aim was to assess the feasibility of using patient reviews from social media to identify potential candidates for drug repurposing. We retrieved patient reviews of 180 medications from an online forum, WebMD. Using dictionary-based and machine learning approaches, we identified disease names in the reviews. Several publicly available resources were used to exclude comments containing known indications and adverse drug effects. After manually reviewing some of the remaining comments, we implemented a rule-based system to identify beneficial effects. The dictionary-based system and machine learning system identified 2178 and 6171 disease names respectively in 64,616 patient comments. We provided a list of 10 common patterns that patients used to report any beneficial effects or uses of medication. After manually reviewing the comments tagged by our rule-based system, we identified five potential drug repurposing candidates. To our knowledge, this is the first study to consider using social media data to identify drug-repurposing candidates. We found that even a rule-based system, with a limited number of rules, could identify beneficial effect mentions in patient comments. Our preliminary study shows that social media has the potential to be used in drug repurposing.

Three challenges described for identifying participants with missing data in trials reports, and potential solutions suggested to systematic reviewers.

PubMed

Akl, Elie A; Kahale, Lara A; Ebrahim, Shanil; Alonso-Coello, Pablo; Schünemann, Holger J; Guyatt, Gordon H

2016-08-01

To categorize the challenges in determining the extent of missing participant data in randomized trials and suggest potential solutions for systematic review authors. During the process of updating a series of Cochrane systematic reviews on the topic of anticoagulation in patients with cancer, we identified challenges and used an iterative approach to improve, and a consensus process to agree on the challenges identified, and to suggest potential ways of dealing with them. The five systematic reviews included 58 trials and 75 meta-analyses for patient-important dichotomous outcomes with 27,037 randomized participants. We identified three categories of challenges: (1) Although systematic reviewers require information about missing data to be reported by outcome, trialists typically report the information by participant; (2) It is not always clear whether the trialists followed up participants in certain categories (e.g., noncompliers), that is, whether some categories of participants did or did not have missing data; (3) It is not always clear how the trialists dealt with missing data in their analysis (e.g., exclusion from the denominator vs. assumptions made for the numerator). We discuss potential solutions for each one of these challenges and suggest further research work. Current reporting of missing data is often not explicit and transparent, and although our potential solutions to problems of suboptimal reporting may be helpful, reliable and valid characterization of the extent and nature of missing data remains elusive. Reporting of missing data in trials needs further improvement. Copyright © 2016 Elsevier Inc. All rights reserved.

Desulfovibrio species are potentially important in regressive autism.

PubMed

Finegold, Sydney M

2011-08-01

Autism is a complex disorder with no specific diagnostic test so the disease is defined by its characteristics including cognitive defects, social, communication and behavioral problems, repetitive behaviors, unusual sensitivity to stimuli such as noise, restricted interests, and self stimulation. The incidence of this disease has increased remarkably in recent years and was 110/10,000 children (∼1%) in multiple areas of the US in 2007. The financial burden on families and communities is enormous. In terms of predisposing factors, heredity plays a role in some subjects, but it is clear that environmental factors are also important. Environmental toxins can affect the immune system adversely. Intestinal bacteria are recognized by a few investigators as potentially important and we have proposed that certain antimicrobial drugs may be a key factor in modifying the intestinal bacterial flora adversely, selecting out potentially harmful bacteria that are normally suppressed by an intact normal intestinal flora. We had felt that clostridia in the gut might be involved in autism because they are virulent organisms and spore-formers; spores would resist antibacterial agents so that when antibiotics were discontinued the spores would germinate and by toxin production or another mechanism lead to autism. However, a recent study of ours employing the powerful pyrosequencing technique on stools of subjects with regressive autism showed that Desulfovibrio was more common in autistic subjects than in controls. We subsequently confirmed this with pilot cultural and real-time PCR studies and found siblings of autistic children had counts of Desulfovibrio that were intermediate, suggesting possible spread of the organism in the family environment. Desulfovibrio is an anaerobic bacillus that does not produce spores but is nevertheless resistant to aerobic and other adverse conditions by other mechanisms and is commonly resistant to certain antimicrobial agents (such as

Identifying High Academic Potential in Australian Aboriginal Children Using Dynamic Testing

ERIC Educational Resources Information Center

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…

The importance of the external potential on group electronegativity.

PubMed

Leyssens, Tom; Geerlings, Paul; Peeters, Daniel

2005-11-03

The electronegativity of groups placed in a molecular environment is obtained using CCSD calculations of the electron affinity and ionization energy. A point charge model is used as an approximation of the molecular environment. The electronegativity values obtained in the presence of a point charge model are compared to the isolated group property to estimate the importance of the external potential on the group's electronegativity. The validity of the "group in molecule" electronegativities is verified by comparing EEM (electronegativity equalization method) charge transfer values to the explicitly calculated natural population analysis (NPA) ones, as well as by comparing the variation in electronegativity between the isolated functional group and the functional group in the presence of a modeled environment with the variation based on a perturbation expansion of the chemical potential.

Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

DTIC Science & Technology

2015-04-01

step of the Plasmodium mammalian cycle . Inhibiting this step can block malaria at an early step. However, few anti-malarials target liver infection...points in the life cycle of malaria parasites. PLoS Biol 12: e1001806. 2. Falae A, Combe A, Amaladoss A, Carvalho T, Menard R, et al. (2010) Role of...AWARD NUMBER: W81XWH-13-1-0429 TITLE: Using "Click Chemistry" to Identify Potential Drug Targets in Plasmodium PRINCIPAL INVESTIGATOR: Dr. Purnima

Phosphorus Import Dependency and Recycling Potential in the Global Phosphorus Mosaic

NASA Astrophysics Data System (ADS)

Powers, S. M.

2017-12-01

Nations differ widely in terms of recent P consumption trends and fertilizer trade dependencies, reflecting dynamic and globally uneven P fertilizer production, consumption, export, and import. Recovered P from urban and agricultural wastes can provide renewable sources that supplant the need to import P fertilizer, but to date, research on P recycling potential has been highly spatially segregated. Understanding of the global distribution of P recycling potential and options, and how these intersect with P import dependencies, could be used to guide long-term, spatially-prioritized planning for P, food, and water security. We integrated recent data on national P fertilizer flows, subnational P use, and landscape features within a global grid to understand how these constraints on future options for P use are distributed worldwide. This analysis illustrates several regions where combinations of high population density, cropland extent, and manure P production provide islands of opportunity for P recycling in mixed crop-livestock and populous agricultural areas. At the same time, nations with lower import ratios (net P import:consumption) contained a disproportionately large share of manure-rich croplands and populous croplands. As a further demonstration of the kinds of integrated comparisons that are possible using global land use data sets in combination with P, worldwide similarities and distinctions for P emerged from a cluster analysis. These kinds of socioeconomic-geographic patterns may foretell distinct P futures as societies address spatially uneven options for P, food, and water security.

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

PubMed Central

Tidjani Alou, Maryam; Million, Matthieu; Traore, Sory I.; Mouelhi, Donia; Khelaifia, Saber; Bachar, Dipankar; Caputo, Aurelia; Delerce, Jeremy; Brah, Souleymane; Alhousseini, Daouda; Sokhna, Cheikh; Robert, Catherine; Diallo, Bouli A.; Diallo, Aldiouma; Parola, Philippe; Golden, Michael; Lagier, Jean-Christophe

2017-01-01

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. PMID:28588566

Estimate variable importance for recurrent event outcomes with an application to identify hypoglycemia risk factors.

PubMed

Duan, Ran; Fu, Haoda

2015-08-30

Recurrent event data are an important data type for medical research. In particular, many safety endpoints are recurrent outcomes, such as hypoglycemic events. For such a situation, it is important to identify the factors causing these events and rank these factors by their importance. Traditional model selection methods are not able to provide variable importance in this context. Methods that are able to evaluate the variable importance, such as gradient boosting and random forest algorithms, cannot directly be applied to recurrent events data. In this paper, we propose a two-step method that enables us to evaluate the variable importance for recurrent events data. We evaluated the performance of our proposed method by simulations and applied it to a data set from a diabetes study. Copyright © 2015 John Wiley & Sons, Ltd.

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

NASA Astrophysics Data System (ADS)

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

Identifying potential markers in Breast Cancer subtypes using plasma label-free proteomics.

PubMed

Corrêa, Stephany; Panis, Carolina; Binato, Renata; Herrera, Ana Cristina; Pizzatti, Luciana; Abdelhay, Eliana

2017-01-16

Breast Cancer (BC) is the most common neoplasia among women and has a high mortality rate worldwide. Over the past several decades, increasing molecular knowledge of BC has resulted in its stratification into 4 major molecular subtypes according to hormonal receptor expression. Unfortunately, although the data accumulated thus far has improved BC prognosis and treatment, there have been few achievements in its diagnosis. In this study, we applied a Label-free Nano-LC/MSMS approach to reveal systemic molecular features and possible plasma markers for BC patients. Compared to healthy control plasma donors, we identified 191, 166, 182, and 186 differentially expressed proteins in the Luminal, Lumina-HER2, HER2, and TN subtypes. In silico analysis demonstrated an overall downregulation of cellular basal machinery and, more importantly, brought new focus to the known pathways and signaling molecules in BC that are related to immune system alterations. Moreover, using western blot analysis, we verified high levels of BCAS3, IRX1, IRX4 and IRX5 in BC plasma samples, thus highlighting the potential use of plasma proteomics in investigations into cancer biomarkers. The results of this study provide new insight into Breast Cancer (BC). We determined the plasma proteomic profile of BC subtypes. Furthermore, we report that the signaling pathways correlating with late processes in BC already exhibit plasma alterations in less aggressive subtypes. Additionally, we validated the high levels of particular proteins in patient samples, which suggests the use of these proteins as potential disease markers.

Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi

PubMed Central

Agaba, Morris; Cavener, Douglas R.

2017-01-01

Background The capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe’s visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with many of them. The extent to which the giraffe’s unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. Methods The recent availability of giraffe and okapi genomes provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site tests of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and orthologous sequences from other mammals. Results Signatures of selection were identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW. Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. Discussion By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with

Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi.

PubMed

Ishengoma, Edson; Agaba, Morris; Cavener, Douglas R

2017-01-01

The capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe's visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with many of them. The extent to which the giraffe's unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. The recent availability of giraffe and okapi genomes provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site tests of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and orthologous sequences from other mammals. Signatures of selection were identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW . Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptations. At

Identifying Hydrologic Flowpaths on Arctic Hillslopes Using Electrical Resistivity and Self Potential

NASA Astrophysics Data System (ADS)

Voytek, E.; Rushlow, C. R.; Godsey, S.; Singha, K.

2015-12-01

Shallow subsurface flow is a dominant process controlling hillslope runoff generation, soil development, and solute reaction and transport. Despite their importance, the location and geometry of flowpaths are difficult to determine. In arctic environments, shallow subsurface flowpaths are limited to a thin zone of seasonal thaw above continuous permafrost, which is traditionally assumed to mimic to surface topography. Here we use a combined approach of electrical resistivity imaging (ERI) and self-potential measurements (SP) to map shallow subsurface flowpaths in and around water tracks, drainage features common to arctic hillslopes. ERI measurements delineate thawed zones in the subsurface that control flowpaths, while SP is sensitive to groundwater flow. We find that areas of low electrical resistivity in the water tracks are deeper than manual thaw depth estimates and variations from surface topography. This finding suggests that traditional techniques significantly underestimate active layer thaw and the extent of the flowpath network on arctic hillslopes. SP measurements identify complex 3-D flowpaths in the thawed zone. Our results lay the groundwork for investigations into the seasonal dynamics, hydrologic connectivity, and climate sensitivity of spatially distributed flowpath networks on arctic hillslopes.

Structured methods for identifying and correcting potential human errors in aviation operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, W.R.

1997-10-01

Human errors have been identified as the source of approximately 60% of the incidents and accidents that occur in commercial aviation. It can be assumed that a very large number of human errors occur in aviation operations, even though in most cases the redundancies and diversities built into the design of aircraft systems prevent the errors from leading to serious consequences. In addition, when it is acknowledged that many system failures have their roots in human errors that occur in the design phase, it becomes apparent that the identification and elimination of potential human errors could significantly decrease the risksmore » of aviation operations. This will become even more critical during the design of advanced automation-based aircraft systems as well as next-generation systems for air traffic management. Structured methods to identify and correct potential human errors in aviation operations have been developed and are currently undergoing testing at the Idaho National Engineering and Environmental Laboratory (INEEL).« less

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

PubMed

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.

Spider Transcriptomes Identify Ancient Large-Scale Gene Duplication Event Potentially Important in Silk Gland Evolution

PubMed Central

Clarke, Thomas H.; Garb, Jessica E.; Hayashi, Cheryl Y.; Arensburger, Peter; Ayoub, Nadia A.

2015-01-01

The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (order Scorpionida) and spiders (order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk glands. Transcripts that are expressed exclusively or primarily within black widow silk glands are more likely to have a paralog descended from the ancient duplication event and have elevated amino acid replacement rates compared with other transcripts. Thus, an ancient large-scale gene duplication event within the spider lineage was likely an important source of molecular novelty during the evolution of silk gland-specific expression. This duplication event may have provided genetic material for subsequent silk gland diversification in the true spiders (Araneomorphae). PMID:26058392

Computational identification of post-translational modification-based nuclear import regulations by characterizing nuclear localization signal-import receptor interaction.

PubMed

Lin, Jhih-Rong; Liu, Zhonghao; Hu, Jianjun

2014-10-01

The binding affinity between a nuclear localization signal (NLS) and its import receptor is closely related to corresponding nuclear import activity. PTM-based modulation of the NLS binding affinity to the import receptor is one of the most understood mechanisms to regulate nuclear import of proteins. However, identification of such regulation mechanisms is challenging due to the difficulty of assessing the impact of PTM on corresponding nuclear import activities. In this study we proposed NIpredict, an effective algorithm to predict nuclear import activity given its NLS, in which molecular interaction energy components (MIECs) were used to characterize the NLS-import receptor interaction, and the support vector regression machine (SVR) was used to learn the relationship between the characterized NLS-import receptor interaction and the corresponding nuclear import activity. Our experiments showed that nuclear import activity change due to NLS change could be accurately predicted by the NIpredict algorithm. Based on NIpredict, we developed a systematic framework to identify potential PTM-based nuclear import regulations for human and yeast nuclear proteins. Application of this approach has identified the potential nuclear import regulation mechanisms by phosphorylation of two nuclear proteins including SF1 and ORC6. © 2014 Wiley Periodicals, Inc.

Identifying Pre-Service Teachers' Beliefs about Teaching EFL and Their Potential Changes

ERIC Educational Resources Information Center

Suárez Flórez, Sergio Andrés; Basto Basto, Edwin Arley

2017-01-01

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…

Spider Transcriptomes Identify Ancient Large-Scale Gene Duplication Event Potentially Important in Silk Gland Evolution.

PubMed

Clarke, Thomas H; Garb, Jessica E; Hayashi, Cheryl Y; Arensburger, Peter; Ayoub, Nadia A

2015-06-08

The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (order Scorpionida) and spiders (order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk glands. Transcripts that are expressed exclusively or primarily within black widow silk glands are more likely to have a paralog descended from the ancient duplication event and have elevated amino acid replacement rates compared with other transcripts. Thus, an ancient large-scale gene duplication event within the spider lineage was likely an important source of molecular novelty during the evolution of silk gland-specific expression. This duplication event may have provided genetic material for subsequent silk gland diversification in the true spiders (Araneomorphae). © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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

PubMed

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

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

PubMed Central

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

Proteomic Analysis of Saliva Identifies Potential Biomarkers for Orthodontic Tooth Movement

PubMed Central

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

Pharmacophore modeling and virtual screening to identify potential RET kinase inhibitors.

PubMed

Shih, Kuei-Chung; Shiau, Chung-Wai; Chen, Ting-Shou; Ko, Ching-Huai; Lin, Chih-Lung; Lin, Chun-Yuan; Hwang, Chrong-Shiong; Tang, Chuan-Yi; Chen, Wan-Ru; Huang, Jui-Wen

2011-08-01

Chemical features based 3D pharmacophore model for REarranged during Transfection (RET) tyrosine kinase were developed by using a training set of 26 structurally diverse known RET inhibitors. The best pharmacophore hypothesis, which identified inhibitors with an associated correlation coefficient of 0.90 between their experimental and estimated anti-RET values, contained one hydrogen-bond acceptor, one hydrogen-bond donor, one hydrophobic, and one ring aromatic features. The model was further validated by a testing set, Fischer's randomization test, and goodness of hit (GH) test. We applied this pharmacophore model to screen NCI database for potential RET inhibitors. The hits were docked to RET with GOLD and CDOCKER after filtering by Lipinski's rules. Ultimately, 24 molecules were selected as potential RET inhibitors for further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Time-saving impact of an algorithm to identify potential surgical site infections.

PubMed

Knepper, B C; Young, H; Jenkins, T C; Price, C S

2013-10-01

To develop and validate a partially automated algorithm to identify surgical site infections (SSIs) using commonly available electronic data to reduce manual chart review. Retrospective cohort study of patients undergoing specific surgical procedures over a 4-year period from 2007 through 2010 (algorithm development cohort) or over a 3-month period from January 2011 through March 2011 (algorithm validation cohort). A single academic safety-net hospital in a major metropolitan area. Patients undergoing at least 1 included surgical procedure during the study period. Procedures were identified in the National Healthcare Safety Network; SSIs were identified by manual chart review. Commonly available electronic data, including microbiologic, laboratory, and administrative data, were identified via a clinical data warehouse. Algorithms using combinations of these electronic variables were constructed and assessed for their ability to identify SSIs and reduce chart review. The most efficient algorithm identified in the development cohort combined microbiologic data with postoperative procedure and diagnosis codes. This algorithm resulted in 100% sensitivity and 85% specificity. Time savings from the algorithm was almost 600 person-hours of chart review. The algorithm demonstrated similar sensitivity on application to the validation cohort. A partially automated algorithm to identify potential SSIs was highly sensitive and dramatically reduced the amount of manual chart review required of infection control personnel during SSI surveillance.

Ranking Coal Ash Materials for Their Potential to Leach Arsenic and Selenium: Relative Importance of Ash Chemistry and Site Biogeochemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, Grace E.; Hower, James C.; Phillips, Allison L.

The chemical composition of coal ash is highly heterogeneous and dependent on the origin of the source coal, combustion parameters, and type and configuration of air pollution control devices. This heterogeneity results in uncertainty in the evaluation of leaching potential of contaminants from coal ash. The goal of this work was to identify whether a single leaching protocol could roughly group high-leaching potential coal ash from low-leaching potential coal ash, with respect to arsenic (As) and selenium (Se). We used four different leaching tests, including the Toxicity Characteristic Leaching Protocol (TCLP), natural pH, aerobic sediment microcosms, and anaerobic sediment microcosmsmore » on 10 different coal ash materials, including fly ash, lime-treated ash, and flue gas desulfurization materials. Leaching tests showed promise in categorizing high and low-leaching potential ash materials, indicating that a single point test could act as a first screening measure to identify high-risk ash materials. However, the amount of contaminant leached varied widely across tests, reflecting the importance of ambient conditions (pH, redox state) on leaching. These results demonstrate that on-site geochemical conditions play a critical role in As and Se mobilization from coal ash, underscoring the need to develop a situation-based risk assessment framework for contamination by coal ash pollutants.« less

Ranking Coal Ash Materials for Their Potential to Leach Arsenic and Selenium: Relative Importance of Ash Chemistry and Site Biogeochemistry

DOE PAGES

Schwartz, Grace E.; Hower, James C.; Phillips, Allison L.; ...

2018-01-23

The chemical composition of coal ash is highly heterogeneous and dependent on the origin of the source coal, combustion parameters, and type and configuration of air pollution control devices. This heterogeneity results in uncertainty in the evaluation of leaching potential of contaminants from coal ash. The goal of this work was to identify whether a single leaching protocol could roughly group high-leaching potential coal ash from low-leaching potential coal ash, with respect to arsenic (As) and selenium (Se). We used four different leaching tests, including the Toxicity Characteristic Leaching Protocol (TCLP), natural pH, aerobic sediment microcosms, and anaerobic sediment microcosmsmore » on 10 different coal ash materials, including fly ash, lime-treated ash, and flue gas desulfurization materials. Leaching tests showed promise in categorizing high and low-leaching potential ash materials, indicating that a single point test could act as a first screening measure to identify high-risk ash materials. However, the amount of contaminant leached varied widely across tests, reflecting the importance of ambient conditions (pH, redox state) on leaching. These results demonstrate that on-site geochemical conditions play a critical role in As and Se mobilization from coal ash, underscoring the need to develop a situation-based risk assessment framework for contamination by coal ash pollutants.« less

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

Code of Federal Regulations, 2010 CFR

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...

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

USGS Publications Warehouse

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.

Identifying external nutrient reduction requirements and potential in the hypereutrophic Lake Taihu Basin, China.

PubMed

Peng, Jiao-Ting; Zhu, Xiao-Dong; Sun, Xiang; Song, Xiao-Wei

2018-04-01

Reducing external nutrient loads is the first step for controlling eutrophication. Here, we identified external nutrient reduction requirements and potential of strategies for achieving reductions to remediate a eutrophic water body, Lake Taihu, China. A mass balance approach based on the entire lake was used to identify nutrient reduction requirements; an empirical export coefficient approach was introduced to estimate the nutrient reduction potential of the overall program on integrated regulation of Taihu Lake Basin (hereafter referred to as the "Guideline"). Reduction requirements included external total nitrogen (TN) and total phosphorus (TP) loads, which should be reduced by 41-55 and 25-50%, respectively, to prevent nutrient accumulation in Lake Taihu and to meet the planned water quality targets. In 2010, which is the most seriously polluted calendar year during the 2008-2014 period, the nutrient reduction requirements were estimated to be 36,819 tons of N and 2442 tons of P, and the potential nutrient reduction strategies would reduce approximately 25,821 tons of N and 3024 tons of P. Since there is a net N remaining in the reduction requirements, it should be the focus and deserves more attention in identifying external nutrient reduction strategies. Moreover, abatement measures outlined in the Guideline with high P reduction potential required large monetary investments. Achieving TP reduction requirement using the cost-effective strategy costs about 80.24 million USD. The design of nutrient reduction strategies should be enacted according to regional and sectoral differences and the cost-effectiveness of abatement measures.

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

PubMed Central

Galbraith, Penelope; Coutts, Scott; Prosser, Toby; Boyce, John; McCarthy, David T.

2018-01-01

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. PMID:29360880

Researchers identify potential therapeutic targets for a rare childhood cancer | Center for Cancer Research

Cancer.gov

CCR researchers have identified the mechanism behind a rare but extremely aggressive childhood cancer called alveolar rhabdomyosarcoma (ARMS) and have pinpointed a potential drug target for its treatment. Learn more...

Surveillance methods for identifying, characterizing, and monitoring tobacco products: potential reduced exposure products as an example

PubMed Central

O’Connor, Richard J.; Cummings, K. Michael; Rees, Vaughan W.; Connolly, Gregory N.; Norton, Kaila J.; Sweanor, David; Parascandola, Mark; Hatsukami, Dorothy K.; Shields, Peter G.

2015-01-01

Tobacco products are widely sold and marketed, yet integrated data systems for identifying, tracking, and characterizing products are lacking. Tobacco manufacturers recently have developed potential reduction exposure products (PREPs) with implied or explicit health claims. Currently, a systematic approach for identifying, defining, and evaluating PREPs sold at the local, state or national levels in the US has not been developed. Identifying, characterizing, and monitoring new tobacco products could be greatly enhanced with a responsive surveillance system. This paper critically reviews available surveillance data sources for identifying and tracking tobacco products, including PREPs, evaluating strengths and weaknesses of potential data sources in light of their reliability and validity. Absent regulations mandating disclosure of product-specific information, it is likely that public health officials will need to rely on a variety of imperfect data sources to help identify, characterize, and monitor tobacco products, including PREPs. PMID:19959680

Drought Tolerance during Reproductive Development is Important for Increasing wheat yield Potential under Climate change in Europe.

PubMed

Senapati, Nimai; Stratonovitch, Pierre; Paul, Matthew J; Semenov, Mikhail A

2018-06-12

Drought stress during reproductive development could drastically reduce grain number and wheat yield, but quantitative evaluation of such effect is unknown under climate change. The objectives of this study were to a) evaluate potential yield benefits of drought tolerance during reproductive development for wheat ideotypes under climate change in Europe, and b) identify potential cultivar parameters for improvement. We used the Sirius wheat model to optimise drought tolerant (DT) and drought sensitive (DS) wheat ideotypes under future 2050 climate scenario at 13 contrasting sites, representing major wheat growing regions in Europe. Averaged over the sites, DT ideotypes achieved 13.4% greater yield compared to DS, with the double yield stability for DT. However, the performances of the ideotypes were site dependent. Mean yield of DT was 28-37% greater compared to DS in southern Europe. In contrast, no yield difference (≤ 1%) between ideotypes was found in north-western Europe. An intermediate yield benefit of 10-23% was found due to drought tolerance in central and eastern Europe. We conclude that tolerance to drought stress during reproductive development is important for high yield potentials and greater yield stability of wheat under climate change in Europe.

A landscape ecology approach identifies important drivers of urban biodiversity.

PubMed

Turrini, Tabea; Knop, Eva

2015-04-01

Cities are growing rapidly worldwide, yet a mechanistic understanding of the impact of urbanization on biodiversity is lacking. We assessed the impact of urbanization on arthropod diversity (species richness and evenness) and abundance in a study of six cities and nearby intensively managed agricultural areas. Within the urban ecosystem, we disentangled the relative importance of two key landscape factors affecting biodiversity, namely the amount of vegetated area and patch isolation. To do so, we a priori selected sites that independently varied in the amount of vegetated area in the surrounding landscape at the 500-m scale and patch isolation at the 100-m scale, and we hold local patch characteristics constant. As indicator groups, we used bugs, beetles, leafhoppers, and spiders. Compared to intensively managed agricultural ecosystems, urban ecosystems supported a higher abundance of most indicator groups, a higher number of bug species, and a lower evenness of bug and beetle species. Within cities, a high amount of vegetated area increased species richness and abundance of most arthropod groups, whereas evenness showed no clear pattern. Patch isolation played only a limited role in urban ecosystems, which contrasts findings from agro-ecological studies. Our results show that urban areas can harbor a similar arthropod diversity and abundance compared to intensively managed agricultural ecosystems. Further, negative consequences of urbanization on arthropod diversity can be mitigated by providing sufficient vegetated space in the urban area, while patch connectivity is less important in an urban context. This highlights the need for applying a landscape ecological approach to understand the mechanisms shaping urban biodiversity and underlines the potential of appropriate urban planning for mitigating biodiversity loss. © 2015 John Wiley & Sons Ltd.

Identifying Elements of ICU Care That Families Report as Important But Unsatisfactory

PubMed Central

Osborn, Tristan R.; Curtis, J. Randall; Nielsen, Elizabeth L.; Back, Anthony L.; Shannon, Sarah E.

2012-01-01

Background: One in five deaths in the United States occurs in the ICU, and many of these deaths are experienced as less than optimal by families of dying people. The current study investigated the relationship between family satisfaction with ICU care and overall ratings of the quality of dying as a means of identifying targets for improving end-of-life experiences for patients and families. Methods: This multisite cross-sectional study surveyed families of patients who died in the ICU in one of 15 hospitals in western Washington State. Measures included the Family Satisfaction in the ICU (FS-ICU) and the Single-Item Quality of Dying (QOD-1) questionnaires. Associations between FS-ICU items and the QOD-1 were examined using multivariate linear regression controlling for patient and family demographics and hospital site. Results: Questionnaires were returned for 1,290 of 2,850 decedents (45%). Higher QOD-1 scores were significantly associated (all P < .05) with (1) perceived nursing skill and competence (β = 0.15), (2) support for family as decision-makers (β = 0.10), (3) family control over the patient’s care (β = 0.18), and (4) ICU atmosphere (β = 0.12). FS-ICU items that received low ratings and correlated with higher QOD-1 scores (ie, important items with room for improvement) were (1) support of family as decision-maker, (2) family control over patient’s care, and (3) ICU atmosphere. Conclusions: Increased support for families as decision-makers and for their desired level of control over patient care along with improvements in the ICU atmosphere were identified as aspects of the ICU experience that may be important targets for quality improvement. Trial registry: ClinicalTrials.gov; No.: NCT00685893; URL: www.clinicaltrials.gov. PMID:22661455

A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients

PubMed Central

Pamungkas, Aryo D.; Medriano, Carl A.; Sim, Eunjung; Lee, Sungyong; Park, Youngja H.

2017-01-01

The most common type of lung cancer is non-small cell lung cancer (NSCLC), which is frequently characterized by a mutation in the epidermal growth factor receptor (EGFR). Determining the presence of an EGFR mutation in lung cancer is important, as it determines the type of treatment that a patients will receive. Therefore, the aim of the present study was to apply high-resolution metabolomics (HRM) using liquid chromatography-mass spectrometry to identify significant compounds in human plasma samples obtained from South Korean NSCLC patients, as potential biomarkers for providing early detection and diagnosis of minimally-invasive NSCLC. The metabolic differences between lung cancer patients without EGFR mutations were compared with patients harboring EGFR mutations. Univariate analysis was performed, with a false discovery rate of q=0.05, in order to identify significant metabolites between the two groups. In addition, hierarchical clustering analysis was performed to discriminate between the metabolic profiles of the two groups. Furthermore, the significant metabolites were identified and mapped using Mummichog software, in order to generate a potential metabolic network model. Using metabolome-wide association studies, metabolic alterations were identified. Linoleic acid [303.23 m/z, (M+Na)+], 5-methyl tetrahydrofolate [231.10 m/z, (M+2H)+] and N-succinyl-L-glutamate-5 semialdehyde [254.06 m/z, (M+Na)+], were observed to be elevated in patients harboring EGFR mutations, whereas tetradecanoyl carnitine [394.29 m/z, (M+Na)+] was observed to be reduced. This suggests that these compounds may be affected by the EGFR mutation. In conclusion, the present study identified four potential biomarkers in patients with EGFR mutations, using HRM combined with pathway analysis. These results may facilitate the development of novel diagnostic tools for EGFR mutation detection in patients with lung cancer. PMID:28487968

Phylogenomic detection and functional prediction of genes potentially important for plant meiosis.

PubMed

Zhang, Luoyan; Kong, Hongzhi; Ma, Hong; Yang, Ji

2018-02-15

Meiosis is a specialized type of cell division necessary for sexual reproduction in eukaryotes. A better understanding of the cytological procedures of meiosis has been achieved by comprehensive cytogenetic studies in plants, while the genetic mechanisms regulating meiotic progression remain incompletely understood. The increasing accumulation of complete genome sequences and large-scale gene expression datasets has provided a powerful resource for phylogenomic inference and unsupervised identification of genes involved in plant meiosis. By integrating sequence homology and expression data, 164, 131, 124 and 162 genes potentially important for meiosis were identified in the genomes of Arabidopsis thaliana, Oryza sativa, Selaginella moellendorffii and Pogonatum aloides, respectively. The predicted genes were assigned to 45 meiotic GO terms, and their functions were related to different processes occurring during meiosis in various organisms. Most of the predicted meiotic genes underwent lineage-specific duplication events during plant evolution, with about 30% of the predicted genes retaining only a single copy in higher plant genomes. The results of this study provided clues to design experiments for better functional characterization of meiotic genes in plants, promoting the phylogenomic approach to the evolutionary dynamics of the plant meiotic machineries. Copyright © 2017 Elsevier B.V. All rights reserved.

Identifying Leadership Potential: The Process of Principals within a Charter School Network

ERIC Educational Resources Information Center

Waidelich, Lynn A.

2012-01-01

The importance of strong educational leadership for American K-12 schools cannot be overstated. As such, school districts need to actively recruit and develop leaders. One way to do so is for school officials to become more strategic in leadership identification and development. If contemporary leaders are strategic about whom they identify and…

Nationwide outbreak of Salmonella Montevideo infections associated with contaminated imported black and red pepper: warehouse membership cards provide critical clues to identify the source.

PubMed

Gieraltowski, L; Julian, E; Pringle, J; Macdonald, K; Quilliam, D; Marsden-Haug, N; Saathoff-Huber, L; Von Stein, D; Kissler, B; Parish, M; Elder, D; Howard-King, V; Besser, J; Sodha, S; Loharikar, A; Dalton, S; Williams, I; Barton Behravesh, C

2013-06-01

In November 2009, we initiated a multistate investigation of Salmonella Montevideo infections with pulsed-field gel electrophoresis pattern JIXX01.0011. We identified 272 cases in 44 states with illness onset dates ranging from 1 July 2009 to 14 April 2010. To help generate hypotheses, warehouse store membership card information was collected to identify products consumed by cases. These records identified 19 ill persons who purchased company A salami products before onset of illness. A case-control study was conducted. Ready-to-eat salami consumption was significantly associated with illness (matched odds ratio 8·5, 95% confidence interval 2·1-75·9). The outbreak strain was isolated from company A salami products from an environmental sample from one manufacturing plant, and sealed containers of black and red pepper at the facility. This outbreak illustrates the importance of using membership card information to assist in identifying suspect vehicles, the potential for spices to contaminate ready-to-eat products, and preventing raw ingredient contamination of these products.

Identifying pneumonia outbreaks of public health importance: can emergency department data assist in earlier identification?

PubMed

Hope, Kirsty; Durrheim, David N; Muscatello, David; Merritt, Tony; Zheng, Wei; Massey, Peter; Cashman, Patrick; Eastwood, Keith

2008-08-01

To retrospectively review the performance of a near real-time Emergency Department (ED) Syndromic Surveillance System operating in New South Wales for identifying pneumonia outbreaks of public health importance. Retrospective data was obtained from the NSW Emergency Department data collection for a rural hospital that has experienced a cluster of pneumonia diagnoses among teenage males in August 2006. ED standard reports were examined for signals in the overall count for each respiratory syndrome, and for elevated counts in individual subgroups including; age, sex and admission to hospital status. Using the current thresholds, the ED syndromic surveillance system would have trigged a signal for pneumonia syndrome in children aged 5-16 years four days earlier than the notification by a paediatrician and this signal was maintained for 14 days. If the ED syndromic surveillance system had been operating it could have identified the outbreak earlier than the paediatrician's notification. This may have permitted an earlier public health response. By understanding the behaviour of syndromes during outbreaks of public health importance, response protocols could be developed to facilitate earlier implementation of control measures.

On the importance of identifying, characterizing, and predicting fundamental phenomena towards microbial electrochemistry applications.

PubMed

Torres, César Iván

2014-06-01

The development of microbial electrochemistry research toward technological applications has increased significantly in the past years, leading to many process configurations. This short review focuses on the need to identify and characterize the fundamental phenomena that control the performance of microbial electrochemical cells (MXCs). Specifically, it discusses the importance of recent efforts to discover and characterize novel microorganisms for MXC applications, as well as recent developments to understand transport limitations in MXCs. As we increase our understanding of how MXCs operate, it is imperative to continue modeling efforts in order to effectively predict their performance, design efficient MXC technologies, and implement them commercially. Thus, the success of MXC technologies largely depends on the path of identifying, understanding, and predicting fundamental phenomena that determine MXC performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identifying Potential Ventilator Auto-Triggering Among Organ Procurement Organization Referrals.

PubMed

Henry, Nicholas R; Russian, Christopher J; Nespral, Joseph

2016-06-01

Ventilator auto-trigger is the delivery of an assisted mechanical ventilated breath over the set ventilator frequency in the absence of a spontaneous inspiratory effort and can be caused by inappropriate ventilator trigger sensitivity. Ventilator auto-trigger can be misinterpreted as a spontaneous breath and has the potential to delay or prevent brain death testing and confuse health-care professionals and/or patient families. To determine the frequency of organ donor referrals from 1 Organ Procurement Organization (OPO) that could benefit from an algorithm designed to assist organ recovery coordinators to identify and correct ventilator auto-triggering. This retrospective analysis evaluated documentation of organ donor referrals from 1 OPO in central Texas during the 2013 calendar year that resulted in the withdrawal of care by the patient's family and the recovery of organs. The frequency of referrals that presented with absent brain stem reflexes except for additional respirations over the set ventilator rate was determined to assess for the need of the proposed algorithm. Documentation of 672 organ procurement organization referrals was evaluated. Documentation from 42 referrals that resulted in the withdrawal of care and 21 referrals that resulted in the recovery of organs were identified with absent brain stem reflexes except for spontaneous respirations on the mechanical ventilator. As a result, an algorithm designed to identify and correct ventilator auto-trigger could have been used 63 times during the 2013 calendar year. © 2016, NATCO.

Identification of important and potentially avoidable risk factors in a prospective audit study of neonatal deaths in a paediatric hospital in Vietnam.

PubMed

Kruse, Alexandra Y; Phuong, Cam N; Ho, Binh T T; Stensballe, Lone G; Pedersen, Freddy K; Greisen, Gorm

2014-02-01

Neonatal deaths (≤28 days) account for more than half of child mortality in Vietnam. Presumably most die in hospital, but data are scarce. This study aimed to identify risk factors of death among hospitalised neonates. We prospectively studied all neonatal deaths and expected deaths (discharged alive after withdrawal of life-sustaining treatment) in a Vietnamese tertiary paediatric hospital during a 12-month period in 2009-2010. The medical files were audited classifying admission prognosis, discharge outcome, cause of death/expected death according to two classifications, and important and potentially avoidable risk factors during the hospital stay. Among 5763 neonates admitted, 235 deaths and 67 expected deaths were included. According to both classifications, major causes were congenital malformations, prematurity and severe infections. Six risk factors were identified in 85% (60/71) of the neonates with a relatively good prognosis: recognition or response to danger signs, internal transfers, nosocomial infections, sepsis management, access to usual equipment/staff, and family perception. Among 302 neonatal deaths/expected deaths, the major causes were congenital malformations, prematurity and severe infections. Six important and potentially avoidable risk factors could be addressed in the subgroup with relatively good admission prognosis, without implementing new technology or major organisational changes. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

77 FR 41406 - Evaluation of In Vitro Tests for Identifying Eye Injury Hazard Potential of Chemicals and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Evaluation of In Vitro Tests for Identifying Eye Injury...-animal testing strategies proposed for identifying eye injury hazard potential of chemicals and products... Panel and submission of data from substances tested in in vitro tests for identifying eye injury hazard...

Identifying potential recommendation domains for conservation agriculture in Ethiopia, Kenya, and Malawi.

PubMed

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 km(2)) 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.

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

NASA Astrophysics Data System (ADS)

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.

Systems to identify potentially inappropriate prescribing in people with advanced dementia: a systematic review.

PubMed

Disalvo, Domenica; Luckett, Tim; Agar, Meera; Bennett, Alexandra; Davidson, Patricia Mary

2016-05-31

Systems for identifying potentially inappropriate medications in older adults are not immediately transferrable to advanced dementia, where the management goal is palliation. The aim of the systematic review was to identify and synthesise published systems and make recommendations for identifying potentially inappropriate prescribing in advanced dementia. Studies were included if published in a peer-reviewed English language journal and concerned with identifying the appropriateness or otherwise of medications in advanced dementia or dementia and palliative care. The quality of each study was rated using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. Synthesis was narrative due to heterogeneity among designs and measures. Medline (OVID), CINAHL, the Cochrane Database of Systematic Reviews (2005 - August 2014) and AMED were searched in October 2014. Reference lists of relevant reviews and included articles were searched manually. Eight studies were included, all of which were scored a high quality using the STROBE checklist. Five studies used the same system developed by the Palliative Excellence in Alzheimer Care Efforts (PEACE) Program. One study used number of medications as an index, and two studies surveyed health professionals' opinions on appropriateness of specific medications in different clinical scenarios. Future research is needed to develop and validate systems with clinical utility for improving safety and quality of prescribing in advanced dementia. Systems should account for individual clinical context and distinguish between deprescribing and initiation of medications.

Global Sensitivity Analysis for Identifying Important Parameters of Nitrogen Nitrification and Denitrification under Model and Scenario Uncertainties

NASA Astrophysics Data System (ADS)

Ye, M.; Chen, Z.; Shi, L.; Zhu, Y.; Yang, J.

2017-12-01

Nitrogen reactive transport modeling is subject to uncertainty in model parameters, structures, and scenarios. While global sensitivity analysis is a vital tool for identifying the parameters important to nitrogen reactive transport, conventional global sensitivity analysis only considers parametric uncertainty. This may result in inaccurate selection of important parameters, because parameter importance may vary under different models and modeling scenarios. By using a recently developed variance-based global sensitivity analysis method, this paper identifies important parameters with simultaneous consideration of parametric uncertainty, model uncertainty, and scenario uncertainty. In a numerical example of nitrogen reactive transport modeling, a combination of three scenarios of soil temperature and two scenarios of soil moisture leads to a total of six scenarios. Four alternative models are used to evaluate reduction functions used for calculating actual rates of nitrification and denitrification. The model uncertainty is tangled with scenario uncertainty, as the reduction functions depend on soil temperature and moisture content. The results of sensitivity analysis show that parameter importance varies substantially between different models and modeling scenarios, which may lead to inaccurate selection of important parameters if model and scenario uncertainties are not considered. This problem is avoided by using the new method of sensitivity analysis in the context of model averaging and scenario averaging. The new method of sensitivity analysis can be applied to other problems of contaminant transport modeling when model uncertainty and/or scenario uncertainty are present.

Comparative genomics of biotechnologically important yeasts

USDA-ARS?s Scientific Manuscript database

Ascomycete yeasts are metabolically diverse, with great potential for biotechnology. Here, we report the comparative genome analysis of 29 taxonomically and biotechnologically important yeasts, including 16 newly sequenced. We identify a genetic code change, CUG-Ala, in Pachysolen tannophilus in the...

Identifying Potentially Preventable Emergency Department Visits by Nursing Home Residents in the United States.

PubMed

Burke, Robert E; Rooks, Sean P; Levy, Cari; Schwartz, Robert; Ginde, Adit A

2015-05-01

To identify and describe potentially preventable emergency department (ED) visits by nursing home (NH) residents in the United States. These visits are important because they are common, frequently lead to hospitalization, and can be associated with significant cost to the patient and the health care system. Retrospective analysis of the 2005-2010 National Hospital Ambulatory Care Survey (NHAMCS), comparing ED visits by nursing home residents that did not lead to hospital admission (potentially preventable) with those that led to admission (less likely preventable). Nationally representative sample of US EDs; federal hospitals and hospitals with fewer than 6 beds were excluded. Older (age ≥65 years) NH residents with an ED visit during this time period. Patient demographics, ED visit information including testing performed, interventions (both procedures and medications) provided, and diagnoses treated. Older NH residents accounted for 3857 of 208,956 ED visits during the time period of interest (1.8%). When weighted to be nationally representative, these represent 13.97 million ED visits, equivalent to 1.8 ED visits annually per NH resident in the United States. More than half of visits (53.5%) did not lead to hospital admission; of those discharged from the ED, 62.8% had normal vital signs on presentation and 18.9% did not have any diagnostic testing before ED discharge. Injuries were 1.78 times more likely to be discharged than admitted (44.8% versus 25.3%, respectively, P < .001), whereas infections were 2.06 times as likely to be admitted as discharged (22.9% versus 11.1%, respectively). Computed tomography (CT) scans were performed in 25.4% and 30.1% of older NH residents who were discharged from the ED and admitted to the hospital, respectively, and more than 70% of these were CTs of the head. NH residents received centrally acting, sedating medications before ED discharge in 9.4% of visits. This nationally representative sample of older NH residents

Identifying 1st instar larvae for three forensically important blowfly species using "fingerprint" cuticular hydrocarbon analysis.

PubMed

Moore, Hannah E; Adam, Craig D; Drijfhout, Falko P

2014-07-01

Calliphoridae are known to be the most forensically important insects when it comes to establishing the minimum post mortem interval (PMImin) in criminal investigations. The first step in calculating the PMImin is to identify the larvae present to species level. Accurate identification which is conventionally carried out by morphological analysis is crucial because different insects have different life stage timings. Rapid identification in the immature larvae stages would drastically cut time in criminal investigations as it would eliminate the need to rear larvae to adult flies to determine the species. Cuticular hydrocarbon analysis on 1st instar larvae has been applied to three forensically important blowflies; Lucilia sericata, Calliphora vicina and Calliphora vomitoria, using gas chromatography-mass spectrometry (GC-MS) and principal component analysis (PCA). The results show that each species holds a distinct "fingerprint" hydrocarbon profile, allowing for accurate identification to be established in 1-day old larvae, when it can be challenging to apply morphological criteria. Consequently, this GC-MS based technique could accelerate and strengthen the identification process, not only for forensically important species, but also for other entomological samples which are hard to identify using morphological features. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE PAGES

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric; ...

2015-03-30

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

Report: EPA Can Better Reduce Risks From Illegal Pesticides by Effectively Identifying Imports for Inspection and Sampling

EPA Pesticide Factsheets

Report #17-P-0412, September 28, 2017. Low rates of inspections and sampling can create a risk that the EPA may not be identifying and deterring the import of pesticides harmful to people or the environment.

Authentic early experience in Medical Education: a socio-cultural analysis identifying important variables in learning interactions within workplaces.

PubMed

Yardley, Sarah; Brosnan, Caragh; Richardson, Jane; Hays, Richard

2013-12-01

This paper addresses the question 'what are the variables influencing social interactions and learning during Authentic Early Experience (AEE)?' AEE is a complex educational intervention for new medical students. Following critique of the existing literature, multiple qualitative methods were used to create a study framework conceptually orientated to a socio-cultural perspective. Study participants were recruited from three groups at one UK medical school: students, workplace supervisors, and medical school faculty. A series of intersecting spectra identified in the data describe dyadic variables that make explicit the parameters within which social interactions are conducted in this setting. Four of the spectra describe social processes related to being in workplaces and developing the ability to manage interactions during authentic early experiences. These are: (1) legitimacy expressed through invited participation or exclusion; (2) finding a role-a spectrum from student identity to doctor mindset; (3) personal perspectives and discomfort in transition from lay to medical; and, (4) taking responsibility for 'risk'-moving from aversion to management through graded progression of responsibility. Four further spectra describe educational consequences of social interactions. These spectra identify how the reality of learning is shaped through social interactions and are (1) generic-specific objectives, (2) parallel-integrated-learning, (3) context specific-transferable learning and (4) performing or simulating-reality. Attention to these variables is important if educators are to maximise constructive learning from AEE. Application of each of the spectra could assist workplace supervisors to maximise the positive learning potential of specific workplaces.

Nightmares in the general population: identifying potential causal factors.

PubMed

Rek, Stephanie; Sheaves, Bryony; Freeman, Daniel

2017-09-01

Nightmares are inherently distressing, prevent restorative sleep, and are associated with a number of psychiatric problems, but have rarely been the subject of empirical study. Negative affect, linked to stressful events, is generally considered the key trigger of nightmares; hence nightmares have most often been considered in the context of post-traumatic stress disorder (PTSD). However, many individuals with heightened negative affect do not have nightmares. The objective of this study was to identify mechanistically plausible factors, beyond negative affect, that may explain why individuals experience nightmares. 846 participants from the UK general population completed an online survey about nightmare occurrence and severity (pre-occupation, distress, and impairment), negative affect, worry, depersonalisation, hallucinatory experiences, paranoia, alcohol use, sleep duration, physical activity levels, PTSD symptoms, and stressful life events. Associations of nightmares with the putative predictive factors were tested controlling for levels of negative affect. Analyses were also repeated controlling for levels of PTSD and the recent occurrence of stressful life events. Nightmare occurrence, adjusting for negative affect, was associated with higher levels of worry, depersonalisation, hallucinatory experiences, paranoia, and sleep duration (odds ratios 1.25-1.45). Nightmare severity, controlling for negative affect, was associated with higher levels of worry, depersonalisation, hallucinatory experiences, and paranoia (R 2 s: 0.33-0.39). Alcohol use and physical activity levels were not associated with nightmares. The study identifies a number of potential predictors of the occurrence and severity of nightmares. Causal roles require testing in future longitudinal, experimental, and treatment studies.

Integration analysis of quantitative proteomics and transcriptomics data identifies potential targets of frizzled-8 protein-related antiproliferative factor in vivo.

PubMed

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

Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia.

PubMed

Fingerlin, Tasha E; Zhang, Weiming; Yang, Ivana V; Ainsworth, Hannah C; Russell, Pamela H; Blumhagen, Rachel Z; Schwarz, Marvin I; Brown, Kevin K; Steele, Mark P; Loyd, James E; Cosgrove, Gregory P; Lynch, David A; Groshong, Steve; Collard, Harold R; Wolters, Paul J; Bradford, Williamson Z; Kossen, Karl; Seiwert, Scott D; du Bois, Roland M; Garcia, Christine Kim; Devine, Megan S; Gudmundsson, Gunnar; Isaksson, Helgi J; Kaminski, Naftali; Zhang, Yingze; Gibson, Kevin F; Lancaster, Lisa H; Maher, Toby M; Molyneaux, Philip L; Wells, Athol U; Moffatt, Miriam F; Selman, Moises; Pardo, Annie; Kim, Dong Soon; Crapo, James D; Make, Barry J; Regan, Elizabeth A; Walek, Dinesha S; Daniel, Jerry J; Kamatani, Yoichiro; Zelenika, Diana; Murphy, Elissa; Smith, Keith; McKean, David; Pedersen, Brent S; Talbert, Janet; Powers, Julia; Markin, Cheryl R; Beckman, Kenneth B; Lathrop, Mark; Freed, Brian; Langefeld, Carl D; Schwartz, David A

2016-06-07

Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci. We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta  = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 × 10(-7) and DQB1*06:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16)). We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential

Identifying Potential Collapse Features Under Highways

DOT National Transportation Integrated Search

2003-01-01

In 1994, subsidence features were identified on Interstate 70 in eastern Ohio. These : features were caused by collapse of old mine workings beneath the highway. An attempt : was made to delineate these features using geophysical methods with no avai...

Identifying potential collapse features under highways.

DOT National Transportation Integrated Search

2003-03-01

In 1994, subsidence features were identified on Interstate 70 in eastern Ohio. These features were caused by collapse of old mine workings beneath the highway. An attempt was made to delineate these features using geophysical methods with no avail. T...

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

NASA Astrophysics Data System (ADS)

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

Using high frequency consumption data to identify demand response potential for solar energy integration

NASA Astrophysics Data System (ADS)

Jin, L.; Borgeson, S.; Fredman, D.; Hans, L.; Spurlock, A.; Todd, A.

2015-12-01

California's renewable portfolio standard (2012) requires the state to get 33% of its electricity from renewable sources by 2020. Increased share of variable renewable sources such as solar and wind in the California electricity system may require more grid flexibility to insure reliable power services. Such grid flexibility can be potentially provided by changes in end use electricity consumptions in response to grid conditions (demand-response). In the solar case, residential consumption in the late afternoon can be used as reserve capacity to balance the drop in solar generation. This study presents our initial attempt to identify, from a behavior perspective, residential demand response potentials in relation to solar ramp events using a data-driven approach. Based on hourly residential energy consumption data, we derive representative daily load shapes focusing on discretionary consumption with an innovative clustering analysis technique. We aggregate the representative load shapes into behavior groups in terms of the timing and rhythm of energy use in the context of solar ramp events. Households of different behavior groups that are active during hours with high solar ramp rates are identified for capturing demand response potential. Insights into the nature and predictability of response to demand-response programs are provided.

American Bird conservancy's approach to the U.S. Important Bird Area Program - identifying the top 500 global sites

Treesearch

Robert M. Chipley

2005-01-01

The idea for the Important Bird Area Program originated in a series of studies in the early 1980s conducted by BirdLife International. Recognizing that these studies could become a powerful tool for conservation, BirdLife International began an effort to identify and gather data regarding the most important areas for birds in Europe and to make this information...

Identifying important and feasible policies and actions for health at community sports clubs: a consensus-generating approach.

PubMed

Kelly, Bridget; King, Lesley; Bauman, Adrian E; Baur, Louise A; Macniven, Rona; Chapman, Kathy; Smith, Ben J

2014-01-01

Children's high participation in organised sport in Australia makes sport an ideal setting for health promotion. This study aimed to generate consensus on priority health promotion objectives for community sports clubs, based on informed expert judgements. Delphi survey using three structured questionnaires. Forty-six health promotion, nutrition, physical activity and sport management/delivery professionals were approached to participate in the survey. Questionnaires used an iterative process to determine aspects of sports clubs deemed necessary for developing healthy sporting environments for children. Initially, participants were provided with a list of potential standards for a range of health promotion areas and asked to rate standards based on their importance and feasibility, and any barriers to implementation. Subsequently, participants were provided with information that summarised ratings for each standard to indicate convergence of the group, and asked to review and potentially revise their responses where they diverged. In a third round, participants ranked confirmed standards by priority. 26 professionals completed round 1, 21 completed round 2, and 18 completed round 3. The highest ranked standards related to responsible alcohol practices, availability of healthy food and drinks at sports canteens, smoke-free club facilities, restricting the sale and consumption of alcohol during junior sporting activities, and restricting unhealthy food and beverage company sponsorship. Identifying and prioritising health promotion areas that are relevant to children's sports clubs assists in focusing public health efforts and may guide future engagement of sports clubs. Approaches for providing informational and financial support to clubs to operationalise these standards are proposed. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Onset dynamics of action potentials in rat neocortical neurons and identified snail neurons: quantification of the difference.

PubMed

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

2008-04-09

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 difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics.

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

PubMed Central

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 difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics. PMID:18398478

Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

PubMed Central

Chen, Yi-Hsuan; Lu, Ru-Band; Hung, Hung; Kuo, Po-Hsiu

2014-01-01

Bipolar disorder is a complex psychiatric disorder with high heritability, but its genetic determinants are still largely unknown. Copy number variation (CNV) is one of the sources to explain part of the heritability. However, it is a challenge to estimate discrete values of the copy numbers using continuous signals calling from a set of markers, and to simultaneously perform association testing between CNVs and phenotypic outcomes. The goal of the present study is to perform a series of data filtering and analysis procedures using a DNA pooling strategy to identify potential CNV regions that are related to bipolar disorder. A total of 200 normal controls and 200 clinically diagnosed bipolar patients were recruited in this study, and were randomly divided into eight control and eight case pools. Genome-wide genotyping was employed using Illumina Human Omni1-Quad array with approximately one million markers for CNV calling. We aimed at setting a series of criteria to filter out the signal noise of marker data and to reduce the chance of false-positive findings for CNV regions. We first defined CNV regions for each pool. Potential CNV regions were reported based on the different patterns of CNV status between cases and controls. Genes that were mapped into the potential CNV regions were examined with association testing, Gene Ontology enrichment analysis, and checked with existing literature for their associations with bipolar disorder. We reported several CNV regions that are related to bipolar disorder. Two CNV regions on chromosome 11 and 22 showed significant signal differences between cases and controls (p < 0.05). Another five CNV regions on chromosome 6, 9, and 19 were overlapped with results in previous CNV studies. Experimental validation of two CNV regions lent some support to our reported findings. Further experimental and replication studies could be designed for these selected regions. PMID:27605030

Functional Roles of microRNAs in Agronomically Important Plants—Potential as Targets for Crop Improvement and Protection

PubMed Central

Djami-Tchatchou, Arnaud T.; Sanan-Mishra, Neeti; Ntushelo, Khayalethu; Dubery, Ian A.

2017-01-01

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have recently emerged as important regulators of gene expression, mainly through cleavage and/or translation inhibition of the target mRNAs during or after transcription. miRNAs play important roles by regulating a multitude of biological processes in plants which include maintenance of genome integrity, development, metabolism, and adaptive responses toward environmental stresses. The increasing population of the world and their food demands requires focused efforts for the improvement of crop plants to ensure sustainable food production. Manipulation of mRNA transcript abundance via miRNA control provides a unique strategy for modulating differential plant gene expression and miRNAs are thus emerging as the next generation targets for genetic engineering for improvement of the agronomic properties of crops. However, a deeper understanding of its potential and the mechanisms involved will facilitate the design of suitable strategies to obtain the desirable traits with minimum trade-offs in the modified crops. In this regard, this review highlights the diverse roles of conserved and newly identified miRNAs in various food and industrial crops and recent advances made in the uses of miRNAs to improve plants of agronomically importance so as to significantly enhance crop yields and increase tolerance to various environmental stress agents of biotic—or abiotic origin. PMID:28382044

Identifying Conservation Successes, Failures and Future Opportunities; Assessing Recovery Potential of Wild Ungulates and Tigers in Eastern Cambodia

PubMed Central

O'Kelly, Hannah J.; Evans, Tom D.; Stokes, Emma J.; Clements, Tom J.; Dara, An; Gately, Mark; Menghor, Nut; Pollard, Edward H. B.; Soriyun, Men; Walston, Joe

2012-01-01

Conservation investment, particularly for charismatic and wide-ranging large mammal species, needs to be evidence-based. Despite the prevalence of this theme within the literature, examples of robust data being generated to guide conservation policy and funding decisions are rare. We present the first published case-study of tiger conservation in Indochina, from a site where an evidence-based approach has been implemented for this iconic predator and its prey. Despite the persistence of extensive areas of habitat, Indochina's tiger and ungulate prey populations are widely supposed to have precipitously declined in recent decades. The Seima Protection Forest (SPF), and broader Eastern Plains Landscape, was identified in 2000 as representing Cambodia's best hope for tiger recovery; reflected in its designation as a Global Priority Tiger Conservation Landscape. Since 2005 distance sampling, camera-trapping and detection-dog surveys have been employed to assess the recovery potential of ungulate and tiger populations in SPF. Our results show that while conservation efforts have ensured that small but regionally significant populations of larger ungulates persist, and density trends in smaller ungulates are stable, overall ungulate populations remain well below theoretical carrying capacity. Extensive field surveys failed to yield any evidence of tiger, and we contend that there is no longer a resident population within the SPF. This local extirpation is believed to be primarily attributable to two decades of intensive hunting; but importantly, prey densities are also currently below the level necessary to support a viable tiger population. Based on these results and similar findings from neighbouring sites, Eastern Cambodia does not currently constitute a Tiger Source Site nor meet the criteria of a Global Priority Tiger Landscape. However, SPF retains global importance for many other elements of biodiversity. It retains high regional importance for ungulate

Identifying conservation successes, failures and future opportunities; assessing recovery potential of wild ungulates and tigers in Eastern Cambodia.

PubMed

O'Kelly, Hannah J; Evans, Tom D; Stokes, Emma J; Clements, Tom J; Dara, An; Gately, Mark; Menghor, Nut; Pollard, Edward H B; Soriyun, Men; Walston, Joe

2012-01-01

Conservation investment, particularly for charismatic and wide-ranging large mammal species, needs to be evidence-based. Despite the prevalence of this theme within the literature, examples of robust data being generated to guide conservation policy and funding decisions are rare. We present the first published case-study of tiger conservation in Indochina, from a site where an evidence-based approach has been implemented for this iconic predator and its prey. Despite the persistence of extensive areas of habitat, Indochina's tiger and ungulate prey populations are widely supposed to have precipitously declined in recent decades. The Seima Protection Forest (SPF), and broader Eastern Plains Landscape, was identified in 2000 as representing Cambodia's best hope for tiger recovery; reflected in its designation as a Global Priority Tiger Conservation Landscape. Since 2005 distance sampling, camera-trapping and detection-dog surveys have been employed to assess the recovery potential of ungulate and tiger populations in SPF. Our results show that while conservation efforts have ensured that small but regionally significant populations of larger ungulates persist, and density trends in smaller ungulates are stable, overall ungulate populations remain well below theoretical carrying capacity. Extensive field surveys failed to yield any evidence of tiger, and we contend that there is no longer a resident population within the SPF. This local extirpation is believed to be primarily attributable to two decades of intensive hunting; but importantly, prey densities are also currently below the level necessary to support a viable tiger population. Based on these results and similar findings from neighbouring sites, Eastern Cambodia does not currently constitute a Tiger Source Site nor meet the criteria of a Global Priority Tiger Landscape. However, SPF retains global importance for many other elements of biodiversity. It retains high regional importance for ungulate

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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/depthmore » 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.« less

Predicting essential genes for identifying potential drug targets in Aspergillus fumigatus.

PubMed

Lu, Yao; Deng, Jingyuan; Rhodes, Judith C; Lu, Hui; Lu, Long Jason

2014-06-01

Aspergillus fumigatus (Af) is a ubiquitous and opportunistic pathogen capable of causing acute, invasive pulmonary disease in susceptible hosts. Despite current therapeutic options, mortality associated with invasive Af infections remains unacceptably high, increasing 357% since 1980. Therefore, there is an urgent need for the development of novel therapeutic strategies, including more efficacious drugs acting on new targets. Thus, as noted in a recent review, "the identification of essential genes in fungi represents a crucial step in the development of new antifungal drugs". Expanding the target space by rapidly identifying new essential genes has thus been described as "the most important task of genomics-based target validation". In previous research, we were the first to show that essential gene annotation can be reliably transferred between distantly related four Prokaryotic species. In this study, we extend our machine learning approach to the much more complex Eukaryotic fungal species. A compendium of essential genes is predicted in Af by transferring known essential gene annotations from another filamentous fungus Neurospora crassa. This approach predicts essential genes by integrating diverse types of intrinsic and context-dependent genomic features encoded in microbial genomes. The predicted essential datasets contained 1674 genes. We validated our results by comparing our predictions with known essential genes in Af, comparing our predictions with those predicted by homology mapping, and conducting conditional expressed alleles. We applied several layers of filters and selected a set of potential drug targets from the predicted essential genes. Finally, we have conducted wet lab knockout experiments to verify our predictions, which further validates the accuracy and wide applicability of the machine learning approach. The approach presented here significantly extended our ability to predict essential genes beyond orthologs and made it possible to

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... the USDA Farmers Market? 170.6 Section 170.6 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market participants identified for the USDA Farmers Market...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... the USDA Farmers Market? 170.6 Section 170.6 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market participants identified for the USDA Farmers Market...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... the USDA Farmers Market? 170.6 Section 170.6 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market participants identified for the USDA Farmers Market...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... the USDA Farmers Market? 170.6 Section 170.6 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market participants identified for the USDA Farmers Market...

Using SCOPE to identify potential regulatory motifs in coregulated genes.

PubMed

Martyanov, Viktor; Gross, Robert H

2011-05-31

SCOPE is an ensemble motif finder that uses three component algorithms in parallel to identify potential regulatory motifs by over-representation and motif position preference. Each component algorithm is optimized to find a different kind of motif. By taking the best of these three approaches, SCOPE performs better than any single algorithm, even in the presence of noisy data. In this article, we utilize a web version of SCOPE to examine genes that are involved in telomere maintenance. SCOPE has been incorporated into at least two other motif finding programs and has been used in other studies. The three algorithms that comprise SCOPE are BEAM, which finds non-degenerate motifs (ACCGGT), PRISM, which finds degenerate motifs (ASCGWT), and SPACER, which finds longer bipartite motifs (ACCnnnnnnnnGGT). These three algorithms have been optimized to find their corresponding type of motif. Together, they allow SCOPE to perform extremely well. Once a gene set has been analyzed and candidate motifs identified, SCOPE can look for other genes that contain the motif which, when added to the original set, will improve the motif score. This can occur through over-representation or motif position preference. Working with partial gene sets that have biologically verified transcription factor binding sites, SCOPE was able to identify most of the rest of the genes also regulated by the given transcription factor. Output from SCOPE shows candidate motifs, their significance, and other information both as a table and as a graphical motif map. FAQs and video tutorials are available at the SCOPE web site which also includes a "Sample Search" button that allows the user to perform a trial run. Scope has a very friendly user interface that enables novice users to access the algorithm's full power without having to become an expert in the bioinformatics of motif finding. As input, SCOPE can take a list of genes, or FASTA sequences. These can be entered in browser text fields, or read from

Scanning genomic areas under selection sweep and association mapping as tools to identify horticultural important genes in watermelon

USDA-ARS?s Scientific Manuscript database

Watermelon (Citrullus lanatus var. lanatus) contains 88% water, sugars, and several important health-related compounds, including lycopene, citrulline, arginine, and glutathione. The current genetic diversity study uses microsatellites with known map positions to identify genomic regions that under...

Kidney disease models: tools to identify mechanisms and potential therapeutic targets

PubMed Central

Bao, Yin-Wu; Yuan, Yuan; Chen, Jiang-Hua; Lin, Wei-Qiang

2018-01-01

Acute kidney injury (AKI) and chronic kidney disease (CKD) are worldwide public health problems affecting millions of people and have rapidly increased in prevalence in recent years. Due to the multiple causes of renal failure, many animal models have been developed to advance our understanding of human nephropathy. Among these experimental models, rodents have been extensively used to enable mechanistic understanding of kidney disease induction and progression, as well as to identify potential targets for therapy. In this review, we discuss AKI models induced by surgical operation and drugs or toxins, as well as a variety of CKD models (mainly genetically modified mouse models). Results from recent and ongoing clinical trials and conceptual advances derived from animal models are also explored. PMID:29515089

Identifying the domains of context important to implementation science: a study protocol.

PubMed

Squires, Janet E; Graham, Ian D; Hutchinson, Alison M; Michie, Susan; Francis, Jill J; Sales, Anne; Brehaut, Jamie; Curran, Janet; Ivers, Noah; Lavis, John; Linklater, Stefanie; Fenton, Shannon; Noseworthy, Thomas; Vine, Jocelyn; Grimshaw, Jeremy M

2015-09-28

There is growing recognition that "context" can and does modify the effects of implementation interventions aimed at increasing healthcare professionals' use of research evidence in clinical practice. However, conceptual clarity about what exactly comprises "context" is lacking. The purpose of this research program is to develop, refine, and validate a framework that identifies the key domains of context (and their features) that can facilitate or hinder (1) healthcare professionals' use of evidence in clinical practice and (2) the effectiveness of implementation interventions. A multi-phased investigation of context using mixed methods will be conducted. The first phase is a concept analysis of context using the Walker and Avant method to distinguish between the defining and irrelevant attributes of context. This phase will result in a preliminary framework for context that identifies its important domains and their features according to the published literature. The second phase is a secondary analysis of qualitative data from 13 studies of interviews with 312 healthcare professionals on the perceived barriers and enablers to their application of research evidence in clinical practice. These data will be analyzed inductively using constant comparative analysis. For the third phase, we will conduct semi-structured interviews with key health system stakeholders and change agents to elicit their knowledge and beliefs about the contextual features that influence the effectiveness of implementation interventions and healthcare professionals' use of evidence in clinical practice. Results from all three phases will be synthesized using a triangulation protocol to refine the context framework drawn from the concept analysis. The framework will then be assessed for content validity using an iterative Delphi approach with international experts (researchers and health system stakeholders/change agents). This research program will result in a framework that identifies the

The Health Informatics Trial Enhancement Project (HITE): Using routinely collected primary care data to identify potential participants for a depression trial

PubMed Central

2010-01-01

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). PMID:20398303

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

USGS Publications Warehouse

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.

National variety trials identify clones with high potential

USDA-ARS?s Scientific Manuscript database

Quality potato varieties are the backbone of a strong potato industry. Variety trials have been used to identify promising new varieties for well over a century. Trials are repeated and information collected over many years in order to confidently identify lines that may be well suited for productio...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 attackermore » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, I.

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 ofmore » 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.« less

Altered Protein S-Glutathionylation Identifies a Potential Mechanism of Resistance to Acetaminophen-Induced Hepatotoxicity

PubMed Central

McGarry, David J.; Chakravarty, Probir; Wolf, C. Roland

2015-01-01

Acetaminophen (APAP) is the most commonly used over-the-counter analgesic. However, hepatotoxicity induced by APAP is a major clinical issue, and the factors that define sensitivity to APAP remain unclear. We have previously demonstrated that mice nulled for glutathione S-transferase Pi (GSTP) are resistant to APAP-induced hepatotoxicity. This study aims to exploit this difference to delineate pathways of importance in APAP toxicity. We used mice nulled for GSTP and heme oxygenase-1 oxidative stress reporter mice, together with a novel nanoflow liquid chromatography–tandem mass spectrometry methodology to investigate the role of oxidative stress, cell signaling, and protein S-glutathionylation in APAP hepatotoxicity. We provide evidence that the sensitivity difference between wild-type and Gstp1/2−/− mice is unrelated to the ability of APAP to induce oxidative stress, despite observing significant increases in c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation in wild-type mice. The major difference in response to APAP was in the levels of protein S-glutathionylation: Gstp1/2−/− mice exhibited a significant increase in the number of S-glutathionylated proteins compared with wild-type animals. Remarkably, these S-glutathionylated proteins are involved in oxidative phosphorylation, respiratory complexes, drug metabolism, and mitochondrial apoptosis. Furthermore, we found that S-glutathionylation of the rate-limiting glutathione-synthesizing enzyme, glutamate cysteine ligase, was markedly increased in Gstp1/2−/− mice in response to APAP. The data demonstrate that S-glutathionylation provides an adaptive response to APAP and, as a consequence, suggest that this is an important determinant in APAP hepatotoxicity. This work identifies potential novel avenues associated with cell survival for the treatment of chemical-induced hepatotoxicity. PMID:26311813

Application of near infrared reflectance (NIR) spectroscopy to identify potential PSE meat.

PubMed

Li, Xiao; Feng, Fang; Gao, Runze; Wang, Lu; Qian, Ye; Li, Chunbao; Zhou, Guanghong

2016-07-01

Pale, soft and exudative (PSE) meat is a quality problem that causes a large economic loss to the pork industry. In the present work, near infrared (NIR) quantification and identification methods were used to investigate the feasibility of differentiating potential PSE meat from normal meat. NIR quantification models were developed to estimate meat pH and colour attributes (L*, a*, b*). Promising results were reported for prediction of muscle pH (R(2) CV  = 70.10%, RPDCV = 1.83) and L* (R(2) CV  = 77.18%, RPDCV = 1.91), but it is still hard to promote to practical application at this level. The Factorisation Method applied to NIR spectra could differentiate potential PSE meat from normal meat at 3 h post-mortem. Correlation analysis showed significant relationship between NIR data and LF-NMR T2 components that were indicative of water distribution and mobility in muscle. PSE meat had unconventionally faster energy metabolism than normal meat, which caused greater water mobility. NIR spectra coupled with the Factorisation Method could be a promising technology to identify potential PSE meat. The difference in the intensity of H2 O absorbance peaks between PSE and normal meat might be the basis of this identification method. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

An Australasian model license reassessment procedure for identifying potentially unsafe drivers.

PubMed

Fildes, Brian N; Charlton, Judith; Pronk, Nicola; Langford, Jim; Oxley, Jennie; Koppel, Sjaanie

2008-08-01

Most licensing jurisdictions in Australia currently employ age-based assessment programs as a means to manage older driver safety, yet available evidence suggests that these programs have no safety benefits. This paper describes a community referral-based model license re assessment procedure for identifying and assessing potentially unsafe drivers. While the model was primarily developed for assessing older driver fitness to drive, it could be applicable to other forms of driver impairment associated with increased crash risk. It includes a three-tier process of assessment, involving the use of validated and relevant assessment instruments. A case is argued that this process is a more systematic, transparent and effective process for managing older driver safety and thus more likely to be widely acceptable to the target community and licensing authorities than age-based practices.

Rapid, Potentially Automatable, Method Extract Biomarkers for HPLC/ESI/MS/MS to Detect and Identify BW Agents

DTIC Science & Technology

1997-11-01

status can sometimes be reflected in the infectious potential or drug resistance of those pathogens. For example, in Mycobacterium tuberculosis ... Mycobacterium tuberculosis , its antibiotic resistance and prediction of pathogenicity amongst Mycobacterium spp. based on signature lipid biomarkers ...TITLE AND SUBTITLE Rapid, Potentially Automatable, Method Extract Biomarkers for HPLC/ESI/MS/MS to Detect and Identify BW Agents 5a. CONTRACT NUMBER 5b

Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.

PubMed

Kurashige, Junji; Hasegawa, Takanori; Niida, Atsushi; Sugimachi, Keishi; Deng, Niantao; Mima, Kosuke; Uchi, Ryutaro; Sawada, Genta; Takahashi, Yusuke; Eguchi, Hidetoshi; Inomata, Masashi; Kitano, Seigo; Fukagawa, Takeo; Sasako, Mitsuru; Sasaki, Hiroki; Sasaki, Shin; Mori, Masaki; Yanagihara, Kazuyoshi; Baba, Hideo; Miyano, Satoru; Tan, Patrick; Mimori, Koshi

2016-03-03

Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.

Triangulating Principal Effectiveness: How Perspectives of Parents, Teachers, and Assistant Principals Identify the Central Importance of Managerial Skills

ERIC Educational Resources Information Center

Grissom, Jason A.; Loeb, Susanna

2011-01-01

While the importance of effective principals is undisputed, few studies have identified specific skills that principals need to promote school success. This study draws on unique data combining survey responses from principals, assistant principals, teachers, and parents with rich administrative data to determine which principal skills correlate…

Identifying the "Truly Disadvantaged": A Comprehensive Biosocial Approach

ERIC Educational Resources Information Center

Barnes, J. C.; Beaver, Kevin M.; Connolly, Eric J.; Schwartz, Joseph A.

2016-01-01

There has been significant interest in examining the developmental factors that predispose individuals to chronic criminal offending. This body of research has identified some social-environmental risk factors as potentially important. At the same time, the research producing these results has generally failed to employ genetically sensitive…

Identifying geoscience knowledge likely to affect foreign policy

NASA Astrophysics Data System (ADS)

Kelmelis, J. A.

2006-12-01

The earth sciences play an important role in foreign policy and have done so throughout history. Whether it is access to resources, knowledge of weather or other earth system conditions, planning for or responding to disasters, protecting the environment, facilitating transportation and communication, or any of a number of other important topics, the geosciences continue to inform our decision making. The importance of science, technology, and health (STH) is being increasingly recognized in the foreign policy community. The National Research Council (NRC) recommended that the Department of State (State) expand its scientific base to address the importance of STH issues. In part, this consists of increasing the number of scientists within State. Another important aspect is not only identifying the STH issues that are of current concern, but also the issues that will be of importance in the future. A number of studies funded by the U.S. Government have identified some important STH areas of concern at a high level. These provide a basis for more in-depth investigations. However, there are additional phenomena, beyond those identified in the studies, which have foreign policy implications. The scientific findings may be well known to scientists but their foreign policy importance is not always obvious. The scientific and foreign policy communities could improve their dialog to better develop strategies for foreign policy and future scientific research. One way to help facilitate that is to ease identification of scientific issues with potential significance to foreign policy and to clarify uncertainties around those issues. A qualitative method relating the likelihood that the scientific finding has foreign policy importance to the potential level of foreign policy importance has been used to clarify the significance of a variety of scientific findings including Arctic warming, methane hydrates, atmospheric dust, disease, and natural hazards. From a foreign policy

Imported Asian swamp eels (Synbranchidae: Monopterus) in North American live food markets: Potential vectors of non-native parasites

USGS Publications Warehouse

Nico, Leo G.; Sharp, Paul; Collins, Timothy M.

2011-01-01

Since the 1990s, possibly earlier, large numbers of Asian swamp eels (Synbranchidae: Monopterus spp.), some wild-caught, have been imported live from various countries in Asia and sold in ethnic food markets in cities throughout the USA and parts of Canada. Such markets are the likely introduction pathway of some, perhaps most, of the five known wild populations of Asian swamp eels present in the continental United States. This paper presents results of a pilot study intended to gather baseline data on the occurrence and abundance of internal macroparasites infecting swamp eels imported from Asia to North American retail food markets. These data are important in assessing the potential role that imported swamp eels may play as possible vectors of non-native parasites. Examination of the gastrointestinal tracts and associated tissues of 19 adult-sized swamp eels—identified as M. albus "Clade C"—imported from Vietnam and present in a U.S. retail food market revealed that 18 (95%) contained macroparasites. The 394 individual parasites recovered included a mix of nematodes, acanthocephalans, cestodes, digeneans, and pentastomes. The findings raise concern because of the likelihood that some parasites infecting market swamp eels imported from Asia are themselves Asian taxa, some possibly new to North America. The ecological risk is exacerbated because swamp eels sold in food markets are occasionally retained live by customers and a few reportedly released into the wild. For comparative purposes, M. albus "Clade C" swamp eels from a non-native population in Florida (USA) were also examined and most (84%) were found to be infected with internal macroparasites. The current level of analysis does not allow us to confirm whether these are non-native parasites.

Dent and Flint maize diversity panels reveal important genetic potential for increasing biomass production.

PubMed

Rincent, R; Nicolas, S; Bouchet, S; Altmann, T; Brunel, D; Revilla, P; Malvar, R A; Moreno-Gonzalez, J; Campo, L; Melchinger, A E; Schipprack, W; Bauer, E; Schoen, C-C; Meyer, N; Ouzunova, M; Dubreuil, P; Giauffret, C; Madur, D; Combes, V; Dumas, F; Bauland, C; Jamin, P; Laborde, J; Flament, P; Moreau, L; Charcosset, A

2014-11-01

Genetic and phenotypic analysis of two complementary maize panels revealed an important variation for biomass yield. Flowering and biomass QTL were discovered by association mapping in both panels. The high whole plant biomass productivity of maize makes it a potential source of energy in animal feeding and biofuel production. The variability and the genetic determinism of traits related to biomass are poorly known. We analyzed two highly diverse panels of Dent and Flint lines representing complementary heterotic groups for Northern Europe. They were genotyped with the 50 k SNP-array and phenotyped as hybrids (crossed to a tester of the complementary pool) in a western European field trial network for traits related to flowering time, plant height, and biomass. The molecular information revealed to be a powerful tool for discovering different levels of structure and relatedness in both panels. This study revealed important variation and potential genetic progress for biomass production, even at constant precocity. Association mapping was run by combining genotypes and phenotypes in a mixed model with a random polygenic effect. This permitted the detection of significant associations, confirming height and flowering time quantitative trait loci (QTL) found in literature. Biomass yield QTL were detected in both panels but were unstable across the environments. Alternative kinship estimator only based on markers unlinked to the tested SNP increased the number of significant associations by around 40% with a satisfying control of the false positive rate. This study gave insights into the variability and the genetic architectures of biomass-related traits in Flint and Dent lines and suggests important potential of these two pools for breeding high biomass yielding hybrid varieties.

A Riemannian geometric mapping technique for identifying incompressible equivalents to subsonic potential flows

NASA Astrophysics Data System (ADS)

German, Brian Joseph

much the same way that general relativity ascribes gravitational forces to the curvature of space-time. Although the analogy with general relativity is fruitful, it is important not to overstate the similarities between compressibility and the physics of gravity, as the interest for this thesis is primarily in the mathematical framework and not physical phenomenology or epistemology. The thesis presents the philosophy and theory for the transformation method followed by a numerical method for practical solutions of equivalent incompressible flows over arbitrary closed profiles. The numerical method employs an iterative approach involving the solution of the equivalent incompressible flow with a panel method, the calculation of the metric tensor for the gauge transformation, and the solution of the curvilinear coordinate mapping to the canonical flow with a finite difference approach for the elliptic boundary value problem. This method is demonstrated for non-circulatory flow over a circular cylinder and both symmetric and lifting flows over a NACA 0012 profile. Results are validated with accepted subcritical full potential test cases available in the literature. For chord-preserving mapping boundary conditions, the results indicate that the equivalent incompressible profiles thicken with Mach number and develop a leading edge droop with increased angle of attack. Two promising areas of potential applicability of the method have been identified. The first is in airfoil inverse design methods leveraging incompressible flow knowledge including heuristics and empirical data for the potential field effects on viscous phenomena such as boundary layer transition and separation. The second is in aerodynamic testing using distorted similarity-scaled models.

Preceptor Perceptions of the Importance of Experiential Guidelines

PubMed Central

Godwin, Donald; Thompson, Megan E.; Wittstrom, Kristina

2013-01-01

Objectives. To assess preceptors’ perceptions of the importance of experiential guidelines and identify and compare differences in perceptions. Methods. Active advanced and introductory pharmacy practice experience preceptors for the University of New Mexico were invited to participate in an anonymous electronic survey regarding the importance of specific tasks and abilities expected in new pharmacist practitioners as outlined in Appendix C of the Accreditation Council for Pharmacy Education (ACPE) Standards and Guidelines. Results. While the majority of preceptors rated most tasks (eg, communication, patient counseling) as very important or important, emerging tasks (eg, health literacy, public health, physical assessment) were not rated as highly by a majority of preceptors. Conclusion. The deficiencies identified in the study suggest potential reductions in the transfer of learning from preceptors to experiential students. Preceptor training programs should be structured to raise the perceived level of importance of these tasks. PMID:24052647

Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits

PubMed Central

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Del-Aguila, Jorge L.; Fernandez, Maria Victoria; Carrell, David; Black, Kathleen; Budde, John; Ma, ShengMei; Saef, Benjamin; Howells, Bill; Bertelsen, Sarah; Bailey, Matthew; Ridge, Perry G.; Hefti, Franz; Fillit, Howard; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Carrillo, Maria; Fleisher, Adam; Reeder, Stephanie; Trncic, Nadira; Burke, Anna; Tariot, Pierre; Reiman, Eric M.; Chen, Kewei; Sabbagh, Marwan N.; Beiden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Green, Robert C.; Marshall, Gad; Johnson, Keith A.; Sperling, Reisa A.; Snyder, Peter; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Bernick, Charles; Munic, Donna; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Relkin, Norman; Chaing, Gloria; Ravdin, Lisa; Paul, Steven; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Friedl, Karl; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Borges-Neto, Salvador; James, Olga; Wong, Terence; Coleman, Edward; Schwartz, Adam; Cellar, Janet S.; Levey, Allan L.; Lah, James J.; Behan, Kelly; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Farlow, Martin R.; Saykin, Andrew J.; Foroud, Tatiana M.; Shen, Li; Faber, Kelly; Kim, Sungeun; Nho, Kwangsik; Marie Hake, Ann; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Albert, Marilyn; Onyike, Chiadi; D’Agostino, Daniel; Kielb, Stephanie; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Petersen, Ronald; Jack, Clifford R.; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Chertkow, Howard; Hosein, Chris; Mintzer, Jacob; Spicer, Kenneth; Bachman, David; Grossman, Hillel; Mitsis, Effie; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Potter, William; Buckholtz, Neil; Hsiao, John; Kittur, Smita; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Johnson, Nancy; Chuang-Kuo; Kerwin, Diana; Bonakdarpour, Borna; Weintraub, Sandra; Grafman, Jordan; Lipowski, Kristine; Mesulam, Marek-Marsel; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Borrie, Michael; Lee, T-Y; Bartha, Rob; Martinez, Walter; Villena, Teresa; Sadowsky, Carl; Khachaturian, Zaven; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Frank, Richard; Fleischman, Debra; Arfanakis, Konstantinos; Shah, Raj C.; deToledo-Morrell, Leyla; Sorensen, Greg; Finger, Elizabeth; Pasternack, Stephen; Rachinsky, Irina; Drost, Dick; Rogers, John; Kertesz, Andrew; Furst, Ansgar J.; Chad, Stevan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Mudge, Benita; Assaly, Michele; Fox, Nick; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Ekstam Smith, Karen; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Natelson Love, Marissa; DeCarli, Charles; Carmichael, Owen; Olichney, John; Maillard, Pauline; Fletcher, Evan; Nguyen, Dana; Preda, Andrian; Potkin, Steven; Mulnard, Ruth A.; Thai, Gaby; McAdams-Ortiz, Catherine; Landau, Susan; Jagust, William; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Thompson, Paul; Donohue, Michael; Thomas, Ronald G.; Walter, Sarah; Gessert, Devon; Brewer, James; Vanderswag, Helen; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Aisen, Paul; Davis, Melissa; Morrison, Rosemary; Harvey, Danielle; Thal, Lean; Beckett, Laurel; Neylan, Thomas; Finley, Shannon; Weiner, Michael W.; Hayes, Jacqueline; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Massoglia, Dino; Brawman-Mentzer, Olga; Schuff, Norbert; Smith, Charles D.; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Koeppe, Robert A.; Lord, Joanne L.; Heidebrink, Judith L.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Trojanowki, John Q.; Shaw, Leslie M.; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Foster, Norm; Montine, Tom; Fruehling, J. Jay; Harding, Sandra; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Petrie, Eric C.; Peskind, Elaine; Li, Gail; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Kuller, Lew; Mathis, Chet; Ann Oakley, Mary; Lopez, Oscar L.; Simpson, Donna M.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Cairns, Nigel J.; Raichle, Marc; Morris, John C.; Householder, Erin; Taylor-Reinwald, Lisa; Holtzman, David; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Varma, Pradeep; MacAvoy, Martha G.; Carson, Richard E.; van Dyck, Christopher H.; Davies, Peter; Holtzman, David; Morris, John C.; Bales, Kelly; Pickering, Eve H.; Lee, Jin-Moo; Heitsch, Laura; Kauwe, John; Goate, Alison; Piccio, Laura; Cruchaga, Carlos

2016-01-01

Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes, and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels, and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r, and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects, and complex disease associations in the same locus.

Importance of geologic characterization of potential low-level radioactive waste disposal sites

USGS Publications Warehouse

Weibel, C.P.; Berg, R.C.

1991-01-01

Using the example of the Geff Alternative Site in Wayne County, Illinois, for the disposal of low-level radioactive waste, this paper demonstrates, from a policy and public opinion perspective, the importance of accurately determining site stratigraphy. Complete and accurate characterization of geologic materials and determination of site stratigraphy at potential low-level waste disposal sites provides the frame-work for subsequent hydrologic and geochemical investigations. Proper geologic characterization is critical to determine the long-term site stability and the extent of interactions of groundwater between the site and its surroundings. Failure to adequately characterize site stratigraphy can lead to the incorrect evaluation of the geology of a site, which in turn may result in a lack of public confidence. A potential problem of lack of public confidence was alleviated as a result of the resolution and proper definition of the Geff Alternative Site stratigraphy. The integrity of the investigation was not questioned and public perception was not compromised. ?? 1991 Springer-Verlag New York Inc.

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

NASA Astrophysics Data System (ADS)

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

2013-04-01

approaches. The research focuses on TLS surveys for trying to detect displacements which might be responsible for instability. Four point clouds acquired in the last two years allow to monitor the spatial displacements of the whole slope, especially focusing on the rockslide sector. It is worth to underline an important aspect which contributes to highlight the significance of the work: the mean scanning distance is about 1.3 km. Few examples exist in literature about the use of very long-range TLS for displacements investigation. By sequentially analyzing TLS surfaces, displacement maps have been obtained for the rockslide area. Confirmation have been achieved by comparing results with movements of reflectors sited on the entire slope and continuously measured by total station. Such validation strengthens the idea that TLS has serious potentialities to be successfully used for analyzing instability. Comparing surfaces is not easy at all, thus a discussion about the encountered problems will be taken into account: any significant detail about potentialities and difficulties of the alignment strategy and the processing procedure will be given together with details about the specific algorithm implemented for filtering displacements by taking into account actual geomorphological conditions.

A high-throughput phenotypic screen identifies clofazimine as a potential treatment for cryptosporidiosis

PubMed Central

Jumani, Rajiv S.; Wright, Timothy M.; Chatterjee, Arnab K.; Huston, Christopher D.; Schultz, Peter G.; McNamara, Case W.

2017-01-01

Cryptosporidiosis has emerged as a leading cause of non-viral diarrhea in children under five years of age in the developing world, yet the current standard of care to treat Cryptosporidium infections, nitazoxanide, demonstrates limited and immune-dependent efficacy. Given the lack of treatments with universal efficacy, drug discovery efforts against cryptosporidiosis are necessary to find therapeutics more efficacious than the standard of care. To date, cryptosporidiosis drug discovery efforts have been limited to a few targeted mechanisms in the parasite and whole cell phenotypic screens against small, focused collections of compounds. Using a previous screen as a basis, we initiated the largest known drug discovery effort to identify novel anticryptosporidial agents. A high-content imaging assay for inhibitors of Cryptosporidium parvum proliferation within a human intestinal epithelial cell line was miniaturized and automated to enable high-throughput phenotypic screening against a large, diverse library of small molecules. A screen of 78,942 compounds identified 12 anticryptosporidial hits with sub-micromolar activity, including clofazimine, an FDA-approved drug for the treatment of leprosy, which demonstrated potent and selective in vitro activity (EC50 = 15 nM) against C. parvum. Clofazimine also displayed activity against C. hominis–the other most clinically-relevant species of Cryptosporidium. Importantly, clofazimine is known to accumulate within epithelial cells of the small intestine, the primary site of Cryptosporidium infection. In a mouse model of acute cryptosporidiosis, a once daily dosage regimen for three consecutive days or a single high dose resulted in reduction of oocyst shedding below the limit detectable by flow cytometry. Recently, a target product profile (TPP) for an anticryptosporidial compound was proposed by Huston et al. and highlights the need for a short dosing regimen (< 7 days) and formulations for children < 2 years

Imported chicken meat as a potential source of quinolone-resistant Escherichia coli producing extended-spectrum beta-lactamases in the UK.

PubMed

Warren, R E; Ensor, V M; O'Neill, P; Butler, V; Taylor, J; Nye, K; Harvey, M; Livermore, D M; Woodford, N; Hawkey, P M

2008-03-01

Escherichia coli producing CTX-M-15 enzyme began to rapidly spread in the UK from around 2003 but other types also occur, notably CTX-M-14. We examined breasts from UK-reared (n = 62) and imported (n = 27) chickens as potential sources of quinolone-resistant E. coli with bla(CTX-M) genes. A further 40 samples for which the country of rearing could not be identified were examined. During 2006, 129 fresh and frozen chicken breast fillets were purchased from retail outlets in the West Midlands. These were cultured for E. coli on CLED agar containing 8 mg/L ciprofloxacin and carrying a 10 microg cefpodoxime disc. Resistant isolates were identified and typed by RAPD fingerprinting; bla(CTX-M) was identified by PCR and genotyped by reverse-line hybridization. The country of rearing was identified from the packaging for 89 of 129 purchased samples. Only one of the 62 UK-reared chicken samples carried E. coli producing a CTX-M-1 enzyme, whereas 10 of 27 samples reared overseas had E. coli with CTX-M enzymes. Specifically, 4/10 Brazilian, 3/4 Brazilian/Polish/French, and 2/2 Dutch samples had E. coli with CTX-M-2 enzymes. Six of 40 samples for which the country of rearing was not known had producers of CTX-M enzymes, 5 of them with CTX-M-14. Quinolone-resistant E. coli with various CTX-M beta-lactamase genes that are common in human infections worldwide were found in imported chicken breasts, indicating a possible source for gut colonization. Samples from Brazil were commonly positive for E. coli with CTX-M-2, the dominant bla(CTX-M) genotype from human infections in South America, which is currently rare in clinical infections in the UK. CTX-M-15, the dominant CTX-M type in human infections in the UK, was not found in chicken isolates, suggesting that the UK-reared chickens are not a reservoir of CTX-M-15.

Linking the salt transcriptome with physiological responses of a salt-resistant Populus species as a strategy to identify genes important for stress acclimation.

PubMed

Brinker, Monika; Brosché, Mikael; Vinocur, Basia; Abo-Ogiala, Atef; Fayyaz, Payam; Janz, Dennis; Ottow, Eric A; Cullmann, Andreas D; Saborowski, Joachim; Kangasjärvi, Jaakko; Altman, Arie; Polle, Andrea

2010-12-01

To investigate early salt acclimation mechanisms in a salt-tolerant poplar species (Populus euphratica), the kinetics of molecular, metabolic, and physiological changes during a 24-h salt exposure were measured. Three distinct phases of salt stress were identified by analyses of the osmotic pressure and the shoot water potential: dehydration, salt accumulation, and osmotic restoration associated with ionic stress. The duration and intensity of these phases differed between leaves and roots. Transcriptome analysis using P. euphratica-specific microarrays revealed clusters of coexpressed genes in these phases, with only 3% overlapping salt-responsive genes in leaves and roots. Acclimation of cellular metabolism to high salt concentrations involved remodeling of amino acid and protein biosynthesis and increased expression of molecular chaperones (dehydrins, osmotin). Leaves suffered initially from dehydration, which resulted in changes in transcript levels of mitochondrial and photosynthetic genes, indicating adjustment of energy metabolism. Initially, decreases in stress-related genes were found, whereas increases occurred only when leaves had restored the osmotic balance by salt accumulation. Comparative in silico analysis of the poplar stress regulon with Arabidopsis (Arabidopsis thaliana) orthologs was used as a strategy to reduce the number of candidate genes for functional analysis. Analysis of Arabidopsis knockout lines identified a lipocalin-like gene (AtTIL) and a gene encoding a protein with previously unknown functions (AtSIS) to play roles in salt tolerance. In conclusion, by dissecting the stress transcriptome of tolerant species, novel genes important for salt endurance can be identified.

Metabolomic profiling to identify potential serum biomarkers for schizophrenia and risperidone action.

PubMed

Xuan, Jiekun; Pan, Guihua; Qiu, Yunping; Yang, Lun; Su, Mingming; Liu, Yumin; Chen, Jian; Feng, Guoyin; Fang, Yiru; Jia, Wei; Xing, Qinghe; He, Lin

2011-12-02

Despite recent advances in understanding the pathophysiology of schizophrenia and the mechanisms of antipsychotic drug action, the development of biomarkers for diagnosis and therapeutic monitoring in schizophrenia remains challenging. Metabolomics provides a powerful approach to discover diagnostic and therapeutic biomarkers by analyzing global changes in an individual's metabolic profile in response to pathophysiological stimuli or drug intervention. In this study, we performed gas chromatography-mass spectrometry based metabolomic profiling in serum of unmedicated schizophrenic patients before and after an 8-week risperidone monotherapy, to detect potential biomarkers associated with schizophrenia and risperidone treatment. Twenty-two marker metabolites contributing to the complete separation of schizophrenic patients from matched healthy controls were identified, with citrate, palmitic acid, myo-inositol, and allantoin exhibiting the best combined classification performance. Twenty marker metabolites contributing to the complete separation between posttreatment and pretreatment patients were identified, with myo-inositol, uric acid, and tryptophan showing the maximum combined classification performance. Metabolic pathways including energy metabolism, antioxidant defense systems, neurotransmitter metabolism, fatty acid biosynthesis, and phospholipid metabolism were found to be disturbed in schizophrenic patients and partially normalized following risperidone therapy. Further study of these metabolites may facilitate the development of noninvasive biomarkers and more efficient therapeutic strategies for schizophrenia.

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

NASA Astrophysics Data System (ADS)

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.

Causal network analysis of head and neck keloid tissue identifies potential master regulators.

PubMed

Garcia-Rodriguez, Laura; Jones, Lamont; Chen, Kang Mei; Datta, Indrani; Divine, George; Worsham, Maria J

2016-10-01

To generate novel insights and hypotheses in keloid development from potential master regulators. Prospective cohort. Six fresh keloid and six normal skin samples from 12 anonymous donors were used in a prospective cohort study. Genome-wide profiling was done previously on the cohort using the Infinium HumanMethylation450 BeadChip (Illumina, San Diego, CA). The 190 statistically significant CpG islands between keloid and normal tissue mapped to 152 genes (P < .05). The top 10 statistically significant genes (VAMP5, ACTR3C, GALNT3, KCNAB2, LRRC61, SCML4, SYNGR1, TNS1, PLEKHG5, PPP1R13-α, false discovery rate <.015) were uploaded into the Ingenuity Pathway Analysis software's Causal Network Analysis (QIAGEN, Redwood City, CA). To reflect expected gene expression direction in the context of methylation changes, the inverse of the methylation ratio from keloid versus normal tissue was used for the analysis. Causal Network Analysis identified disease-specific master regulator molecules based on downstream differentially expressed keloid-specific genes and expected directionality of expression (hypermethylated vs. hypomethylated). Causal Network Analysis software identified four hierarchical networks that included four master regulators (pyroxamide, tributyrin, PRKG2, and PENK) and 19 intermediate regulators. Causal Network Analysis of differentiated methylated gene data of keloid versus normal skin demonstrated four causal networks with four master regulators. These hierarchical networks suggest potential driver roles for their downstream keloid gene targets in the pathogenesis of the keloid phenotype, likely triggered due to perturbation/injury to normal tissue. NA Laryngoscope, 126:E319-E324, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Integrating virtual screening and biochemical experimental approach to identify potential anti-cancer agents from drug databank.

PubMed

Deka, Suman Jyoti; Roy, Ashalata; Manna, Debasis; Trivedi, Vishal

2018-06-01

Chemical libraries constitute a reservoir of pharmacophoric molecules to identify potent anti-cancer agents. Virtual screening of heterocyclic compound library in conjugation with the agonist-competition assay, toxicity-carcinogenicity analysis, and string-based structural searches enabled us to identify several drugs as potential anti-cancer agents targeting protein kinase C (PKC) as a target. Molecular modeling study indicates that Cinnarizine fits well within the PKC C2 domain and exhibits extensive interaction with the protein residues. Molecular dynamics simulation of PKC-Cinnarizine complex at different temperatures (300, 325, 350, 375, and 400[Formula: see text]K) confirms that Cinnarizine fits nicely into the C2 domain and forms a stable complex. The drug Cinnarizine was found to bind PKC with a dissociation constant Kd of [Formula: see text]M. The breast cancer cells stimulated with Cinnarizine causes translocation of PKC-[Formula: see text] to the plasma membrane as revealed by immunoblotting and immunofluorescence studies. Cinnarizine also dose dependently reduced the viability of MDAMB-231 and MCF-7 breast cancer cells with an IC[Formula: see text] of [Formula: see text] and [Formula: see text]g/mL, respectively. It is due to the disturbance of cell cycle of breast cancer cells with reduction of S-phase and accumulation of cells in G1-phase. It disturbs mitochondrial membrane potentials to release cytochrome C into the cytosol and activates caspase-3 to induce apoptosis in cancer cells. The cell death was due to induction of apoptosis involving mitochondrial pathway. Hence, the current study has assigned an additional role to Cinnarizine as an activator of PKC and potentials of the approach to identify new molecules for anti-cancer therapy. Thus, in silico screening along with biochemical experimentation is a robust approach to assign additional roles to the drugs present in the databank for anti-cancer therapy.

Genome-Wide Association Mapping Combined with Reverse Genetics Identifies New Effectors of Low Water Potential-Induced Proline Accumulation in Arabidopsis1[W][OPEN

PubMed Central

Verslues, Paul E.; Lasky, Jesse R.; Juenger, Thomas E.; Liu, Tzu-Wen; Kumar, M. Nagaraj

2014-01-01

Arabidopsis (Arabidopsis thaliana) exhibits natural genetic variation in drought response, including varying levels of proline (Pro) accumulation under low water potential. As Pro accumulation is potentially important for stress tolerance and cellular redox control, we conducted a genome-wide association (GWAS) study of low water potential-induced Pro accumulation using a panel of natural accessions and publicly available single-nucleotide polymorphism (SNP) data sets. Candidate genomic regions were prioritized for subsequent study using metrics considering both the strength and spatial clustering of the association signal. These analyses found many candidate regions likely containing gene(s) influencing Pro accumulation. Reverse genetic analysis of several candidates identified new Pro effector genes, including thioredoxins and several genes encoding Universal Stress Protein A domain proteins. These new Pro effector genes further link Pro accumulation to cellular redox and energy status. Additional new Pro effector genes found include the mitochondrial protease LON1, ribosomal protein RPL24A, protein phosphatase 2A subunit A3, a MADS box protein, and a nucleoside triphosphate hydrolase. Several of these new Pro effector genes were from regions with multiple SNPs, each having moderate association with Pro accumulation. This pattern supports the use of summary approaches that incorporate clusters of SNP associations in addition to consideration of individual SNP probability values. Further GWAS-guided reverse genetics promises to find additional effectors of Pro accumulation. The combination of GWAS and reverse genetics to efficiently identify new effector genes may be especially applicable for traits difficult to analyze by other genetic screening methods. PMID:24218491

Identifying the needs of elderly, hearing-impaired persons: the importance and utility of hearing aid attributes.

PubMed

Meister, Hartmut; Lausberg, Isabel; Kiessling, Juergen; von Wedel, Hasso; Walger, Martin

2002-11-01

Older patients represent the majority of hearing-aid users. The needs of elderly, hearing-impaired subjects are not entirely identified. The present study aims to determine the importance of fundamental hearing-aid attributes and to elicit the utility of associated hypothetical hearing aids for older patients. This was achieved using a questionnaire-based conjoint analysis--a decompositional approach to preference measurement offering a realistic study design. A random sample of 200 experienced hearing-aid users participated in the study. Though three out of the six examined attributes revealed age-related dependencies, the only significant effect was found for the attribute "handling", which was considerably more important for older than younger hearing-aid users. A trend of decreasing importance of speech intelligibility in noise and increasing significance of speech in quiet was observed for subjects older than 70 years. In general, the utility of various hypothetical hearing aids was similar for older and younger subjects. Apart from the attribute "handling", older and younger subjects have comparable needs regarding hearing-aid features. On the basis of the examined attributes, there is no requirement for hearing aids designed specifically for elderly hearing-aid users, provided that ergonomic features are considered and the benefits of modern technology are made fully available for older patients.

USE OF qRTPCR TO IDENTIFY POTENTIAL BIOMARKERS OF BROMATE EXPOSURE IN F344 MALE RAT KIDNEYS

EPA Science Inventory

Potassium bromate (KBrO3) is a drinking water disinfection by-product that is nephrotoxic and carcinogenic. To identify potential biomarkers of carcinogenicity, male F344 rats were chronically exposed to a carcinogenic dose (400mg/l) of KBrO3 in their drinking water. Kidneys were...

Systematic reviews identify important methodological flaws in stroke rehabilitation therapy primary studies: review of reviews.

PubMed

Santaguida, Pasqualina; Oremus, Mark; Walker, Kathryn; Wishart, Laurie R; Siegel, Karen Lohmann; Raina, Parminder

2012-04-01

A "review of reviews" was undertaken to assess methodological issues in studies evaluating nondrug rehabilitation interventions in stroke patients. MEDLINE, CINAHL, PsycINFO, and the Cochrane Database of Systematic Reviews were searched from January 2000 to January 2008 within the stroke rehabilitation setting. Electronic searches were supplemented by reviews of reference lists and citations identified by experts. Eligible studies were systematic reviews; excluded citations were narrative reviews or reviews of reviews. Review characteristics and criteria for assessing methodological quality of primary studies within them were extracted. The search yielded 949 English-language citations. We included a final set of 38 systematic reviews. Cochrane reviews, which have a standardized methodology, were generally of higher methodological quality than non-Cochrane reviews. Most systematic reviews used standardized quality assessment criteria for primary studies, but not all were comprehensive. Reviews showed that primary studies had problems with randomization, allocation concealment, and blinding. Baseline comparability, adverse events, and co-intervention or contamination were not consistently assessed. Blinding of patients and providers was often not feasible and was not evaluated as a source of bias. The eligible systematic reviews identified important methodological flaws in the evaluated primary studies, suggesting the need for improvement of research methods and reporting. Copyright © 2012 Elsevier Inc. All rights reserved.

An event-related potential paradigm for identifying (rare negative) attitude stimuli that people intentionally misreport.

PubMed

Crites, Stephen L; Mojica, Andrew J; Corral, Guadalupe; Taylor, Jennifer H

2010-09-01

This experiment explored whether a late positive potential (LPP) of the event-related brain potential is useful for examining attitudes that people attempt to conceal. Participants identified a set of liked, neutral, and disliked people and viewed sequences consisting of either names or pictures of these people. Disliked people appeared rarely among liked people, and participants either: (1) always accurately reported their negative attitudes toward the people; (2) misreported negative attitudes as positive when they saw a picture of a disliked person; or (3) misreported negative attitudes as positive when they saw a name of a disliked person. Rare negative stimuli evoked a larger-amplitude LPP than frequent positive stimuli. Misreporting attitudes significantly reduced the amplitude difference between rare negative and frequent positive stimuli, though it remained significant.

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

Identifying important comorbidity among cancer populations using administrative data: Prevalence and impact on survival.

PubMed

Sarfati, Diana; Gurney, Jason; Lim, Bee Teng; Bagheri, Nasser; Simpson, Andrew; Koea, Jonathan; Dennett, Elizabeth

2016-03-01

Our study sought to optimize the identification and investigate the impact of comorbidity in cancer patients using routinely collected hospitalization data. We undertook an iterative process of classification of important clinical conditions involving evaluation of relevant literature and consultation with clinicians. Patients diagnosed with colon, rectal, breast, ovarian, uterine, stomach, liver, renal or bladder cancers (n = 14,096) between 2006 and 2008 were identified from the New Zealand Cancer Registry. Conditions were identified using data on diagnoses from hospital admissions for 5 years prior to cancer diagnosis. Patients were followed up until end of 2009 using routine mortality data. Prevalence estimates for each condition by site were calculated. All-cause mortality impact of common conditions was investigated using Cox regression models adjusted for age and stage at diagnosis. Patients with liver and stomach cancers tended to have higher comorbidity and those with breast cancer, lower comorbidity than other cancer patients. Of the 50 conditions, the most common were hypertension (prevalence 8.0-20.9%), cardiac conditions (2.1-13.5%) and diabetes with (2.3-13.3%) and without (2.9-12.9%) complications. Comorbidity was associated with higher all-cause mortality but the impact varied by condition and across cancer site, with impact less for cancers with poor prognoses. Conditions most consistently associated with adverse outcomes across all cancer sites were renal disease, coagulopathies and congestive heart failure. Comorbidity is highly prevalent in cancer populations, but prevalence and impact of conditions differ markedly by cancer type. © 2013 Wiley Publishing Asia Pty Ltd.

A side-effect free method for identifying cancer drug targets.

PubMed

Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

2018-04-27

Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

A new process sensitivity index to identify important system processes under process model and parametric uncertainty

DOE PAGES

Dai, Heng; Ye, Ming; Walker, Anthony P.; ...

2017-03-28

A hydrological model consists of multiple process level submodels, and each submodel represents a process key to the operation of the simulated system. Global sensitivity analysis methods have been widely used to identify important processes for system model development and improvement. The existing methods of global sensitivity analysis only consider parametric uncertainty, and are not capable of handling model uncertainty caused by multiple process models that arise from competing hypotheses about one or more processes. To address this problem, this study develops a new method to probe model output sensitivity to competing process models by integrating model averaging methods withmore » variance-based global sensitivity analysis. A process sensitivity index is derived as a single summary measure of relative process importance, and the index includes variance in model outputs caused by uncertainty in both process models and their parameters. Here, for demonstration, the new index is used to assign importance to the processes of recharge and geology in a synthetic study of groundwater reactive transport modeling. The recharge process is simulated by two models that convert precipitation to recharge, and the geology process is simulated by two models of hydraulic conductivity. Each process model has its own random parameters. Finally, the new process sensitivity index is mathematically general, and can be applied to a wide range of problems in hydrology and beyond.« less

A new process sensitivity index to identify important system processes under process model and parametric uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Heng; Ye, Ming; Walker, Anthony P.

A hydrological model consists of multiple process level submodels, and each submodel represents a process key to the operation of the simulated system. Global sensitivity analysis methods have been widely used to identify important processes for system model development and improvement. The existing methods of global sensitivity analysis only consider parametric uncertainty, and are not capable of handling model uncertainty caused by multiple process models that arise from competing hypotheses about one or more processes. To address this problem, this study develops a new method to probe model output sensitivity to competing process models by integrating model averaging methods withmore » variance-based global sensitivity analysis. A process sensitivity index is derived as a single summary measure of relative process importance, and the index includes variance in model outputs caused by uncertainty in both process models and their parameters. Here, for demonstration, the new index is used to assign importance to the processes of recharge and geology in a synthetic study of groundwater reactive transport modeling. The recharge process is simulated by two models that convert precipitation to recharge, and the geology process is simulated by two models of hydraulic conductivity. Each process model has its own random parameters. Finally, the new process sensitivity index is mathematically general, and can be applied to a wide range of problems in hydrology and beyond.« less

Identification and toxigenic potential of the industrially important fungi, Aspergillus oryzae and Aspergillus sojae.

PubMed

Jørgensen, Thomas R

2007-12-01

Mold strains belonging to the species Aspergillus oryzae and Aspergillus sojae are highly valued as koji molds in the traditional preparation of fermented foods, such as miso, sake, and shoyu, and as protein production hosts in modern industrial processes. A. oryzae and A. sojae are relatives of the wild molds Aspergillus flavus and Aspergillus parasiticus. All four species are classified to the A. flavus group. Strains of the A. flavus group are characterized by a high degree of morphological similarity. Koji mold species are generally perceived of as being nontoxigenic, whereas wild molds are associated with the carcinogenic aflatoxins. Thus, reliable identification of individual strains is very important for application purposes. This review considers the pheno- and genotypic markers used in the classification of A. flavus group strains and specifically in the identification of A. oryzae and A. sojae strains. Separation of A. oryzae and A. sojae from A. flavus and A. parasiticus, respectively, is inconsistent, and both morphologic and molecular evidence support conspecificity. The high degree of identity is reflected by the divergent identification of reference cultures maintained in culture collections. As close relatives of aflatoxin-producing wild molds, koji molds possess an aflatoxin gene homolog cluster. Some strains identified as A. oryzae and A. sojae have been implicated in aflatoxin production. Identification of a strain as A. oryzae or A. sojae is no guarantee of its inability to produce aflatoxins or other toxic metabolites. Toxigenic potential must be determined specifically for individual strains. The species taxa, A. oryzae and A. sojae, are currently conserved by societal issues.

Global sensitivity analysis for identifying important parameters of nitrogen nitrification and denitrification under model uncertainty and scenario uncertainty

NASA Astrophysics Data System (ADS)

Chen, Zhuowei; Shi, Liangsheng; Ye, Ming; Zhu, Yan; Yang, Jinzhong

2018-06-01

Nitrogen reactive transport modeling is subject to uncertainty in model parameters, structures, and scenarios. By using a new variance-based global sensitivity analysis method, this paper identifies important parameters for nitrogen reactive transport with simultaneous consideration of these three uncertainties. A combination of three scenarios of soil temperature and two scenarios of soil moisture creates a total of six scenarios. Four alternative models describing the effect of soil temperature and moisture content are used to evaluate the reduction functions used for calculating actual reaction rates. The results show that for nitrogen reactive transport problem, parameter importance varies substantially among different models and scenarios. Denitrification and nitrification process is sensitive to soil moisture content status rather than to the moisture function parameter. Nitrification process becomes more important at low moisture content and low temperature. However, the changing importance of nitrification activity with respect to temperature change highly relies on the selected model. Model-averaging is suggested to assess the nitrification (or denitrification) contribution by reducing the possible model error. Despite the introduction of biochemical heterogeneity or not, fairly consistent parameter importance rank is obtained in this study: optimal denitrification rate (Kden) is the most important parameter; reference temperature (Tr) is more important than temperature coefficient (Q10); empirical constant in moisture response function (m) is the least important one. Vertical distribution of soil moisture but not temperature plays predominant role controlling nitrogen reaction. This study provides insight into the nitrogen reactive transport modeling and demonstrates an effective strategy of selecting the important parameters when future temperature and soil moisture carry uncertainties or when modelers face with multiple ways of establishing nitrogen

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 11 2014-07-01 2014-07-01 false List of VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 11 2012-07-01 2012-07-01 false List of VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 11 2013-07-01 2013-07-01 false List of VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 10 2011-07-01 2011-07-01 false List of VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National...

Identifying Potential Collapse Features Under Highways : Executive Summary

DOT National Transportation Integrated Search

2003-03-01

In 1994, subsidence features were identified on Interstate 70 in eastern Ohio. These : features were caused by collapse of old mine workings beneath the highway. An attempt : was made to delineate these features using geophysical methods with no avai...

Identifying potential conflict associated with oil and gas exploration in Texas state coastal waters: A multicriteria spatial analysis.

PubMed

Brody, Samuel D; Grover, Himanshu; Bernhardt, Sarah; Tang, Zhenghong; Whitaker, Bianca; Spence, Colin

2006-10-01

Recent interest in expanding offshore oil production within waters of the United States has been met with opposition by groups concerned with recreational, environmental, and aesthetic values associated with the coastal zone. Although the proposition of new oil platforms off the coast has generated conflict over how coastal resources should be utilized, little research has been conducted on where these user conflicts might be most intense and which sites might be most suitable for locating oil production facilities in light of the multiple, and often times, competing interests. In this article, we develop a multiple-criteria spatial decision support tool that identifies the potential degree of conflict associated with oil and gas production activities for existing lease tracts in the coastal margin of Texas. We use geographic information systems to measure and map a range of potentially competing representative values impacted by establishing energy extraction infrastructure and then spatially identify which leased tracts are the least contentious sites for oil and gas production in Texas state waters. Visual and statistical results indicate that oil and gas lease blocks within the study area vary in their potential to generate conflict among multiple stakeholders.

A bootstrap based Neyman-Pearson test for identifying variable importance.

PubMed

Ditzler, Gregory; Polikar, Robi; Rosen, Gail

2015-04-01

Selection of most informative features that leads to a small loss on future data are arguably one of the most important steps in classification, data analysis and model selection. Several feature selection (FS) algorithms are available; however, due to noise present in any data set, FS algorithms are typically accompanied by an appropriate cross-validation scheme. In this brief, we propose a statistical hypothesis test derived from the Neyman-Pearson lemma for determining if a feature is statistically relevant. The proposed approach can be applied as a wrapper to any FS algorithm, regardless of the FS criteria used by that algorithm, to determine whether a feature belongs in the relevant set. Perhaps more importantly, this procedure efficiently determines the number of relevant features given an initial starting point. We provide freely available software implementations of the proposed methodology.

Immunoblotting Quantification Approach for Identifying Potential Hypoallergenic Citrus Cultivars.

PubMed

Wu, Jinlong; Deng, Wenjun; Lin, Dingbo; Deng, Xiuxin; Ma, Zhaocheng

2018-02-28

The inherent allergens of citrus fruits, such as Cit s 1, Cit s 2, Cit s 3 can cause allergic reactions. A better understanding of the genetic factors (cultivar to cultivar) affecting the allergenic potential of citrus fruits would be beneficial for further identification of hypoallergenic genotypes. In the present study, an immunoblotting quantification approach was adopted to assess the potential allergenicity of 21 citrus cultivars, including nine subgroups (tangerine, satsuma, orange, pummelo, grapefruit, lemon, kumquat, tangor, and tangelo). To prepare highly sensitive and specific rabbit polyclonal antibodies, antigenicity of purified rCit s 1.01, rCit s 2.01, and rCit s 3.01 peptides were enhanced with high epitope density in a single protein molecule. The data integration of three citrus allergen quantifications demonstrated that the four pummelo cultivars (Kao Phuang Pummelo, Wanbai Pummelo, Shatian Pummelo, and Guanxi Pummelo) were potential hypoallergenic, compared with other 8 subgroups. Moreover, the immunological analyses with sera of allergic subjects revealed that Shatian Pummelo and Guanxi Pummelo showed the lowest immunoreactivity in 8 representative citrus cultivars. These potential hypoallergenic genotypes are of great significance to not only allergic consumers but also citrus breeders in the genetic improvement of hypoallergenic citrus as breeding resources.

Identifying specific beliefs to target to improve restaurant employees' intentions for performing three important food safety behaviors.

PubMed

Pilling, Valerie K; Brannon, Laura A; Shanklin, Carol W; Howells, Amber D; Roberts, Kevin R

2008-06-01

Current national food safety training programs appear ineffective at improving food safety practices in foodservice operations, given the substantial number of Americans affected by foodborne illnesses after eating in restaurants each year. The Theory of Planned Behavior (TpB) was used to identify important beliefs that may be targeted to improve foodservice employees' intentions for three food safety behaviors that have the most substantial affect on public health: hand washing, using thermometers, and proper handling of food contact surfaces. In a cross-sectional design, foodservice employees (n=190) across three midwestern states completed a survey assessing TpB components and knowledge for the three food safety behaviors. Multiple regression analyses were performed on the TpB components for each behavior. Independent-samples t tests identified TpB beliefs that discriminated between participants who absolutely intend to perform the behaviors and those with lower intention. Employees' attitudes were the one consistent predictor of intentions for performing all three behaviors. However, a unique combination of important predictors existed for each separate behavior. Interventions for improving employees' behavioral intentions for food safety should focus on TpB components that predict intentions for each behavior and should bring all employees' beliefs in line with those of the employees who already intend to perform the food safety behaviors. Registered dietitians; dietetic technicians, registered; and foodservice managers can use these results to enhance training sessions and motivational programs to improve employees' food safety behaviors. Results also assist these professionals in recognizing their responsibility for enforcing and providing adequate resources for proper food safety behaviors.

Imported Wines: Identifying and Removing Wines Contaminated with Diethylene Glycol.

DTIC Science & Technology

1986-03-01

at controlling health risks, BATF has used its labeling authority to prohibit the marketing of alcoholic beverages that are mislabeled by virtue of...or beverages contaminated with harmful substances into the U.S. market . DEG, a toxic substance, would be such a contaminant. The BATF’S authority in...representing a significant risk to health are identified and removed from k the market . BATF did not conduct a risk assessment or seek an assess- ment from

Identifying potential academic leaders: Predictors of willingness to undertake leadership roles in an academic department of family medicine.

PubMed

White, David; Krueger, Paul; Meaney, Christopher; Antao, Viola; Kim, Florence; Kwong, Jeffrey C

2016-02-01

To identify variables associated with willingness to undertake leadership roles among academic family medicine faculty. Web-based survey. Bivariate and multivariable analyses (logistic regression) were used to identify variables associated with willingness to undertake leadership roles. Department of Family and Community Medicine at the University of Toronto in Ontario. A total of 687 faculty members. Variables related to respondents' willingness to take on various academic leadership roles. Of all 1029 faculty members invited to participate in the survey, 687 (66.8%) members responded. Of the respondents, 596 (86.8%) indicated their level of willingness to take on various academic leadership roles. Multivariable analysis revealed that the predictors associated with willingness to take on leadership roles were as follows: pursuit of professional development opportunities (odds ratio [OR] 3.79, 95% CI 2.29 to 6.27); currently holding at least 1 leadership role (OR 5.37, 95% CI 3.38 to 8.53); a history of leadership training (OR 1.86, 95% CI 1.25 to 2.78); the perception that mentorship is important for one's current role (OR 2.25, 95% CI 1.40 to 3.60); and younger age (OR 0.97, 95% CI 0.95 to 0.99). Willingness to undertake new or additional leadership roles was associated with 2 variables related to leadership experiences, 2 variables related to perceptions of mentorship and professional development, and 1 demographic variable (younger age). Interventions that support opportunities in these areas might expand the pool and strengthen the academic leadership potential of faculty members.

Volcanic Centers in the East Africa Rift: Volcanic Processes with Seismic Stresses to Identify Potential Hydrothermal Vents

NASA Astrophysics Data System (ADS)

Patlan, E.; Wamalwa, A. M.; Kaip, G.; Velasco, A. A.

2015-12-01

The Geothermal Development Company (GDC) in Kenya actively seeks to produce geothermal energy, which lies within the East African Rift System (EARS). The EARS, an active continental rift zone, appears to be a developing tectonic plate boundary and thus, has a number of active as well as dormant volcanoes throughout its extent. These volcanic centers can be used as potential sources for geothermal energy. The University of Texas at El Paso (UTEP) and the GDC deployed seismic sensors to monitor several volcanic centers: Menengai, Silali, and Paka, and Korosi. We identify microseismic, local events, and tilt like events using automatic detection algorithms and manual review to identify potential local earthquakes within our seismic network. We then perform the double-difference location method of local magnitude less than two to image the boundary of the magma chamber and the conduit feeding the volcanoes. In the process of locating local seismicity, we also identify long-period, explosion, and tremor signals that we interpret as magma passing through conduits of the magma chamber and/or fluid being transported as a function of magma movement or hydrothermal activity. We used waveform inversion and S-wave shear wave splitting to approximate the orientation of the local stresses from the vent or fissure-like conduit of the volcano. The microseismic events and long period events will help us interpret the activity of the volcanoes. Our goal is to investigate basement structures beneath the volcanoes and identify the extent of magmatic modifications of the crust. Overall, these seismic techniques will help us understand magma movement and volcanic processes in the region.

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

PubMed

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.

Proteomic profiling identifies the inorganic pyrophosphatase (PPA1) protein as a potential biomarker of metastasis in laryngeal squamous cell carcinoma.

PubMed

Bodnar, Magdalena; Luczak, Magdalena; Bednarek, Kinga; Szylberg, Lukasz; Marszalek, Andrzej; Grenman, Reidar; Szyfter, Krzysztof; Jarmuz-Szymczak, Malgorzata; Giefing, Maciej

2016-06-01

Relapse and metastasis are the main causes of unfavorable outcome in head and neck cancers. Whereas, understanding of the molecular background of these processes is far from being complete. Therefore, in this study we aimed to identify potential biomarker candidates of relapse and metastasis in laryngeal squamous cell carcinoma (LSCC) by combining the 2D electrophoresis based protein screen and immunohistochemical analysis of candidate proteins. We screened three groups of LSCC cell lines derived from primary tumors, recurrent tumors and metastases and identified seven proteins that differed significantly in relative abundance between the analyzed groups. Among the identified proteins were the heat shock proteins HSP60 and HSP70 that were significantly downregulated both in recurrences- and metastases-derived cell lines but not in primary tumor-derived cell lines. Moreover, we identified significant upregulation of the annexin V, calreticulin and the inorganic pyrophosphatase (PPA1) exclusively in the metastases-derived cell lines. As these upregulated proteins could potentially become novel biomarkers of metastasis, we have compared their abundance in primary tumor LSCC N(0) cases, primary tumor LSCC N(+) cases as well as in LSCC metastases N(+). Our results show an intense increase of cytoplasmic PPA1 abundance in the N(+) (p = 0.000042) compared to the N(0) group. In summary, we show a group of proteins deregulated in recurrences and metastases of LSCC. Moreover, we suggest the PPA1 protein as a potential new biomarker for metastasis in this cancer.

A NEW HIGH RESOLUTION MASS SPECTROMETRY TECHNIQUE FOR IDENTIFYING PHARMACEUTICALS AND POTENTIAL ENDOCRINE DISRUPTORS IN DRINKING WATER SOURCES

EPA Science Inventory

A New High Resolution Mass Spectrometry Technique for Identifying Pharmaceuticals and Potential Endocrine Disruptors in Drinking Water Sources

Andrew H. Grange and G. Wayne Sovocool U.S.EPA, ORD, NERL, ESD, ECB, P.O. Box 93478, Las Vegas, NV 891933478

Mass spectra...

In Silico Screening-Level Prioritization of 8468 Chemicals Produced in OECD Countries to Identify Potential Planetary Boundary Threats.

PubMed

Reppas-Chrysovitsinos, Efstathios; Sobek, Anna; MacLeod, Matthew

2018-01-01

Legislation such as the Stockholm Convention and REACH aim to identify and regulate the production and use of chemicals that qualify as persistent organic pollutants (POPs) and very persistent and very bioaccumulative (vPvB) chemicals, respectively. Recently, a series of studies on planetary boundary threats proposed seven chemical hazard profiles that are distinct from the POP and vPvB profiles. We previously defined two exposure-based hazard profiles; airborne persistent contaminants (APCs) and waterborne persistent contaminants (WPCs) that correspond to two profiles of chemicals that are planetary boundary threats. Here, we extend our method to screen a database of chemicals consisting of 8648 substances produced within the OECD countries. We propose a new scoring scheme to disentangle the POP, vPvB, APC and WPC profiles by focusing on the spatial range of exposure potential, discuss the relationship between high exposure hazard and elemental composition of chemicals, and identify chemicals with high exposure hazard potential.

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

PubMed

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.

A new multimedia contaminant fate model for China: how important are environmental parameters in influencing chemical persistence and long-range transport potential?

PubMed

Zhu, Ying; Price, Oliver R; Tao, Shu; Jones, Kevin C; Sweetman, Andy J

2014-08-01

We present a new multimedia chemical fate model (SESAMe) which was developed to assess chemical fate and behaviour across China. We apply the model to quantify the influence of environmental parameters on chemical overall persistence (POV) and long-range transport potential (LRTP) in China, which has extreme diversity in environmental conditions. Sobol sensitivity analysis was used to identify the relative importance of input parameters. Physicochemical properties were identified as more influential than environmental parameters on model output. Interactive effects of environmental parameters on POV and LRTP occur mainly in combination with chemical properties. Hypothetical chemicals and emission data were used to model POV and LRTP for neutral and acidic chemicals with different KOW/DOW, vapour pressure and pKa under different precipitation, wind speed, temperature and soil organic carbon contents (fOC). Generally for POV, precipitation was more influential than the other environmental parameters, whilst temperature and wind speed did not contribute significantly to POV variation; for LRTP, wind speed was more influential than the other environmental parameters, whilst the effects of other environmental parameters relied on specific chemical properties. fOC had a slight effect on POV and LRTP, and higher fOC always increased POV and decreased LRTP. Example case studies were performed on real test chemicals using SESAMe to explore the spatial variability of model output and how environmental properties affect POV and LRTP. Dibenzofuran released to multiple media had higher POV in northwest of Xinjiang, part of Gansu, northeast of Inner Mongolia, Heilongjiang and Jilin. Benzo[a]pyrene released to the air had higher LRTP in south Xinjiang and west Inner Mongolia, whilst acenaphthene had higher LRTP in Tibet and west Inner Mongolia. TCS released into water had higher LRTP in Yellow River and Yangtze River catchments. The initial case studies demonstrated that SESAMe

An Algorithm to Identify Compounded Non-Sterile Products that Can Be Formulated on a Commercial Scale or Imported to Promote Safer Medication Use in Children

PubMed Central

Bhatt-Mehta, Varsha; MacArthur, Robert B.; Löbenberg, Raimar; Cies, Jeffrey J.; Cernak, Ibolja; Parrish, Richard H.

2015-01-01

The lack of commercially-available pediatric drug products and dosage forms is well-known. A group of clinicians and scientists with a common interest in pediatric drug development and medicines-use systems developed a practical framework for identifying a list of active pharmaceutical ingredients (APIs) with the greatest market potential for development to use in pediatric patients. Reliable and reproducible evidence-based drug formulations designed for use in pediatric patients are needed vitally, otherwise safe and consistent clinical practices and outcomes assessments will continue to be difficult to ascertain. Identification of a prioritized list of candidate APIs for oral formulation using the described algorithm provides a broader integrated clinical, scientific, regulatory, and market basis to allow for more reliable dosage forms and safer, effective medicines use in children of all ages. Group members derived a list of candidate API molecules by factoring in a number of pharmacotherapeutic, scientific, manufacturing, and regulatory variables into the selection algorithm that were absent in other rubrics. These additions will assist in identifying and categorizing prime API candidates suitable for oral formulation development. Moreover, the developed algorithm aids in prioritizing useful APIs with finished oral liquid dosage forms available from other countries with direct importation opportunities to North America and beyond. PMID:28975916

Genomic Analyses Yield Markers for Identifying Agronomically Important Genes in Potato

USDA-ARS?s Scientific Manuscript database

This study explores the genetic architecture underling the potato evolution through a comprehensive assessment of wild and cultivated potato species based on the re-sequencing of 201 accessions of Solanum section Petota with >12 × genome coverage. We identified 450 domesticated genes, which showed e...

Constructing an atomic-resolution model of human P2X7 receptor followed by pharmacophore modeling to identify potential inhibitors.

PubMed

Ahmadi, Mehdi; Nowroozi, Amin; Shahlaei, Mohsen

2015-09-01

The P2X purinoceptor 7 (P2X7R) is a trimeric ATP-activated ion channel gated by extracellular ATP. P2X7R has important role in numerous diseases including pain, neurodegeneration, and inflammatory diseases such as rheumatoid arthritis and osteoarthritis. In this prospective, the discovery of small-molecule inhibitors for P2X7R as a novel therapeutic target has received considerable attention in recent years. At first, 3D structure of P2X7R was built by using homology modeling (HM) and a 50ns molecular dynamics simulation (MDS). Ligand-based quantitative pharmacophore modeling methodology of P2X7R antagonists were developed based on training set of 49 compounds. The best four-feature pharmacophore model, includes two hydrophobic aromatic, one hydrophobic and one aromatic ring features, has the highest correlation coefficient (0.874), cost difference (368.677), low RMSD (2.876), as well as it shows a high goodness of fit and enrichment factor. Consequently, some hit compounds were introduced as final candidates by employing virtual screening and molecular docking procedure simultaneously. Among these compounds, six potential molecule were identified as potential virtual leads which, as such or upon further optimization, can be used to design novel P2X7R inhibitors. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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.

Engaging police to identify challenging school crossings and potential improvements.

PubMed

Bull, Catherine B; Von Hagen, Leigh Ann; Lubin, Andrea; Shivaraman, Gayathri; Chibbaro, Daniel

2018-04-26

This paper discusses the value of police officers as vital sources of information regarding pedestrian safety in their communities by presenting results from a survey of traffic safety police officers. The survey requested information on school crossings that the officers considered most challenging for pedestrians. Officers specified the intersections or mid-block locations with school crossings, and answered questions about elements of the locations, such as what makes the locations challenging, and what might be done to improve conditions at these locations. A key finding from the survey is the police officers' identification of challenging intersections or other crossing locations by criteria other than the occurrence of crashes, including reported pedestrian-vehicle near-miss incidents. A broad literature review of pedestrian safety studies provides context for the use of near-miss data in discussions of improvements to pedestrian crossings. Although not typically considered a primary resource for pedestrian safety information, police officers are most often very familiar with their communities, work in locations where pedestrian and motor vehicle traffic can be experienced and observed, and receive information from their staff and members of the public who use pedestrian crossings. The survey findings demonstrate that police officer insights and near-miss data may serve as important supplementary sources of information in the effort to identify locations in need of interventions before crash occurrence. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Importance of Reading Naturally: Evidence from Combined Recordings of Eye Movements and Electric Brain Potentials

ERIC Educational Resources Information Center

Metzner, Paul; von der Malsburg, Titus; Vasishth, Shravan; Rösler, Frank

2017-01-01

How important is the ability to freely control eye movements for reading comprehension? And how does the parser make use of this freedom? We investigated these questions using coregistration of eye movements and event-related brain potentials (ERPs) while participants read either freely or in a computer-controlled word-by-word format (also known…

The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks

PubMed Central

Nakahata, Yasukazu; Akashi, Makoto; Trcka, Daniel; Yasuda, Akio; Takumi, Toru

2006-01-01

Background Circadian rhythms are endogenous, self-sustained oscillations with approximately 24-hr rhythmicity that are manifested in various physiological and metabolic processes. The circadian organization of these processes in mammals is governed by the master oscillator within the suprachiasmatic nuclei (SCN) of the hypothalamus. Recent findings revealed that circadian oscillators exist in most organs, tissues, and even in immortalized cells, and that the oscillators in peripheral tissues are likely to be coordinated by SCN, the master oscillator. Some candidates for endogenous entrainment factors have sporadically been reported, however, their details remain mainly obscure. Results We developed the in vitro real-time oscillation monitoring system (IV-ROMS) by measuring the activity of luciferase coupled to the oscillatory gene promoter using photomultiplier tubes and applied this system to screen and identify factors able to influence circadian rhythmicity. Using this IV-ROMS as the primary screening of entrainment factors for circadian clocks, we identified 12 candidates as the potential entrainment factor in a total of 299 peptides and bioactive lipids. Among them, four candidates (endothelin-1, all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid) have already been reported as the entrainment factors in vivo and in vitro. We demonstrated that one of the novel candidates, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-γ (PPAR-γ), triggers the rhythmic expression of endogenous clock genes in NIH3T3 cells. Furthermore, we showed that 15d-PGJ2 transiently induces Cry1, Cry2, and Rorα mRNA expressions and that 15d-PGJ2-induced entrainment signaling pathway is PPAR-γ – and MAPKs (ERK, JNK, p38MAPK)-independent. Conclusion Here, we identified 15d-PGJ2 as an entrainment factor in vitro. Using our developed IV-ROMS to screen 299 compounds, we found eight novel and four known

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

PubMed

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.

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

PubMed Central

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

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

PubMed

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.

Identifying selectively important amino acid positions associated with alternative habitat environments in fish mitochondrial genomes.

PubMed

Xia, Jun Hong; Li, Hong Lian; Zhang, Yong; Meng, Zi Ning; Lin, Hao Ran

2018-05-01

Fish species inhabitating seawater (SW) or freshwater (FW) habitats have to develop genetic adaptations to alternative environment factors, especially salinity. Functional consequences of the protein variations associated with habitat environments in fish mitochondrial genomes have not yet received much attention. We analyzed 829 complete fish mitochondrial genomes and compared the amino acid differences of 13 mitochondrial protein families between FW and SW fish groups. We identified 47 specificity determining sites (SDS) that associated with FW or SW environments from 12 mitochondrial protein families. Thirty-two (68%) of the SDS sites are hydrophobic, 13 (28%) are neutral, and the remaining sites are acidic or basic. Seven of those SDS from ND1, ND2 and ND5 were scored as probably damaging to the protein structures. Furthermore, phylogenetic tree based Bayes Empirical Bayes analysis also detected 63 positive sites associated with alternative habitat environments across ten mtDNA proteins. These signatures could be important for studying mitochondrial genetic variation relevant to fish physiology and ecology.

Identifying geographic hot spots of reassortment in a multipartite plant virus

PubMed Central

Savory, Fiona R; Varma, Varun; Ramakrishnan, Uma

2014-01-01

Reassortment between different species or strains plays a key role in the evolution of multipartite plant viruses and can have important epidemiological implications. Identifying geographic locations where reassortant lineages are most likely to emerge could be a valuable strategy for informing disease management and surveillance efforts. We developed a predictive framework to identify potential geographic hot spots of reassortment based upon spatially explicit analyses of genome constellation diversity. To demonstrate the utility of this approach, we examined spatial variation in the potential for reassortment among Cardamom bushy dwarf virus (CBDV; Nanoviridae, Babuvirus) isolates in Northeast India. Using sequence data corresponding to six discrete genome components for 163 CBDV isolates, a quantitative measure of genome constellation diversity was obtained for locations across the sampling region. Two key areas were identified where viruses with highly distinct genome constellations cocirculate, and these locations were designated as possible geographic hot spots of reassortment, where novel reassortant lineages could emerge. Our study demonstrates that the potential for reassortment can be spatially dependent in multipartite plant viruses and highlights the use of evolutionary analyses to identify locations which could be actively managed to facilitate the prevention of outbreaks involving novel reassortant strains. PMID:24944570

Potential importance of B cells in aging and aging-associated neurodegenerative diseases.

PubMed

Biragyn, Arya; Aliseychik, Maria; Rogaev, Evgeny

2017-04-01

Our understanding of B cells as merely antibody producers is slowly changing. Alone or in concert with antibody, they control outcomes of seemingly different diseases such as cancer, rheumatoid arthritis, diabetes, and multiple sclerosis. While their role in activation of effector immune cells is beneficial in cancer but bad in autoimmune diseases, their immunosuppressive and regulatory subsets (Bregs) inhibit autoimmune and anticancer responses. These pathogenic and suppressive functions are not static and appear to be regulated by the nature and strength of inflammation. Although aging increases inflammation and changes the composition and function of B cells, surprisingly, little is known whether the change affects aging-associated neurodegenerative disease, such as Alzheimer's disease (AD). Here, by analyzing B cells in cancer and autoimmune and neuroinflammatory diseases, we elucidate their potential importance in AD and other aging-associated neuroinflammatory diseases.

Triangulating Principal Effectiveness: How Perspectives of Parents, Teachers, and Assistant Principals Identify the Central Importance of Managerial Skills. Working Paper 35

ERIC Educational Resources Information Center

Grissom, Jason A.; Loeb, Susanna

2009-01-01

While the importance of effective principals is undisputed, few studies have addressed what specific skills principals need to promote school success. This study draws on unique data combining survey responses from principals, assistant principals, teachers and parents with rich administrative data to identify which principal skills matter most…

miR Profiling Identifies Cyclin-Dependent Kinase 6 Downregulation as a Potential Mechanism of Acquired Cisplatin Resistance in Non-Small-Cell Lung Carcinoma.

PubMed

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

Systemic analysis of different colorectal cancer cell lines and TCGA datasets identified IGF-1R/EGFR-PPAR-CASPASE axis as important indicator for radiotherapy sensitivity.

PubMed

Chen, Lin; Zhu, Zhe; Gao, Wei; Jiang, Qixin; Yu, Jiangming; Fu, Chuangang

2017-09-05

Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO). The irradiation induced apoptosis rates of wild type and EGFR agonist (EGF) or IGF-1R inhibitor (NVP-ADW742) treated HT29 and SW480 cells were quantified by flow cytometry. As a result, the apoptosis rate of EGF and NVP-ADW742 treated HT29 cells was significantly higher than that of those wild type ones, which indicated that high EGFR and low IGF-1R expression level in CRC was associated with the high sensitivity to radiotherapy. We next conducted systemic bioinformatics analysis of genome-wide expression profiles of CRC samples from the Cancer Genome Atlas (TCGA). Differential expression analysis between IGF-1R and EGFR abnormal CRC samples, i.e. CRC samples with higher IGF-1R and lower EGFR expression levels based on their median expression values, and the rest of CRC samples identified potential genes contribute to radiotherapy sensitivity. Functional enrichment of analysis of those differential expression genes (DEGs) in the Database for Annotation, Visualization and Integrated Discovery (DAVID) indicated PPAR signaling pathway as an important pathway for the radio-resistance of CRC. Our study identified the potential biomarkers for the rational selection of radiotherapy for CRC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes.

PubMed

Xue, Ruidan; Lynes, Matthew D; Dreyfuss, Jonathan M; Shamsi, Farnaz; Schulz, Tim J; Zhang, Hongbin; Huang, Tian Lian; Townsend, Kristy L; Li, Yiming; Takahashi, Hirokazu; Weiner, Lauren S; White, Andrew P; Lynes, Maureen S; Rubin, Lee L; Goodyear, Laurie J; Cypess, Aaron M; Tseng, Yu-Hua

2015-07-01

Targeting brown adipose tissue (BAT) content or activity has therapeutic potential for treating obesity and the metabolic syndrome by increasing energy expenditure. However, both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here we generated clones of brown and white preadipocytes from human neck fat and characterized their adipogenic and thermogenic differentiation. We combined an uncoupling protein 1 (UCP1) reporter system and expression profiling to define novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of the cells once they were maturated. Knocking out the positive UCP1 regulators, PREX1 and EDNRB, in brown preadipocytes using CRISPR-Cas9 markedly abolished the high level of UCP1 in brown adipocytes differentiated from the preadipocytes. Finally, we were able to prospectively isolate adipose progenitors with great thermogenic potential using the cell surface marker CD29. These data provide new insights into the cellular heterogeneity in human fat and offer potential biomarkers for identifying thermogenically competent preadipocytes.

Linking the Salt Transcriptome with Physiological Responses of a Salt-Resistant Populus Species as a Strategy to Identify Genes Important for Stress Acclimation1[W][OA

PubMed Central

Brinker, Monika; Brosché, Mikael; Vinocur, Basia; Abo-Ogiala, Atef; Fayyaz, Payam; Janz, Dennis; Ottow, Eric A.; Cullmann, Andreas D.; Saborowski, Joachim; Kangasjärvi, Jaakko; Altman, Arie; Polle, Andrea

2010-01-01

To investigate early salt acclimation mechanisms in a salt-tolerant poplar species (Populus euphratica), the kinetics of molecular, metabolic, and physiological changes during a 24-h salt exposure were measured. Three distinct phases of salt stress were identified by analyses of the osmotic pressure and the shoot water potential: dehydration, salt accumulation, and osmotic restoration associated with ionic stress. The duration and intensity of these phases differed between leaves and roots. Transcriptome analysis using P. euphratica-specific microarrays revealed clusters of coexpressed genes in these phases, with only 3% overlapping salt-responsive genes in leaves and roots. Acclimation of cellular metabolism to high salt concentrations involved remodeling of amino acid and protein biosynthesis and increased expression of molecular chaperones (dehydrins, osmotin). Leaves suffered initially from dehydration, which resulted in changes in transcript levels of mitochondrial and photosynthetic genes, indicating adjustment of energy metabolism. Initially, decreases in stress-related genes were found, whereas increases occurred only when leaves had restored the osmotic balance by salt accumulation. Comparative in silico analysis of the poplar stress regulon with Arabidopsis (Arabidopsis thaliana) orthologs was used as a strategy to reduce the number of candidate genes for functional analysis. Analysis of Arabidopsis knockout lines identified a lipocalin-like gene (AtTIL) and a gene encoding a protein with previously unknown functions (AtSIS) to play roles in salt tolerance. In conclusion, by dissecting the stress transcriptome of tolerant species, novel genes important for salt endurance can be identified. PMID:20959419

Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus.

PubMed

Josset, Laurence; Menachery, Vineet D; Gralinski, Lisa E; Agnihothram, Sudhakar; Sova, Pavel; Carter, Victoria S; Yount, Boyd L; Graham, Rachel L; Baric, Ralph S; Katze, Michael G

2013-04-30

A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus. Identification of a novel coronavirus causing fatal respiratory infection in humans raises concerns about a possible widespread outbreak of severe respiratory infection similar to the one caused by SARS-CoV. Using a human lung epithelial cell line and global transcriptomic profiling, we identified differences in the host response between HCoV-EMC and SARS-CoV. This enables rapid assessment of viral properties and the

Ligand- and structure-based in silico studies to identify kinesin spindle protein (KSP) inhibitors as potential anticancer agents.

PubMed

Balakumar, Chandrasekaran; Ramesh, Muthusamy; Tham, Chuin Lean; Khathi, Samukelisiwe Pretty; Kozielski, Frank; Srinivasulu, Cherukupalli; Hampannavar, Girish A; Sayyad, Nisar; Soliman, Mahmoud E; Karpoormath, Rajshekhar

2017-11-29

Kinesin spindle protein (KSP) belongs to the kinesin superfamily of microtubule-based motor proteins. KSP is responsible for the establishment of the bipolar mitotic spindle which mediates cell division. Inhibition of KSP expedites the blockade of the normal cell cycle during mitosis through the generation of monoastral MT arrays that finally cause apoptotic cell death. As KSP is highly expressed in proliferating/cancer cells, it has gained considerable attention as a potential drug target for cancer chemotherapy. Therefore, this study envisaged to design novel KSP inhibitors by employing computational techniques/tools such as pharmacophore modelling, virtual database screening, molecular docking and molecular dynamics. Initially, the pharmacophore models were generated from the data-set of highly potent KSP inhibitors and the pharmacophore models were validated against in house test set ligands. The validated pharmacophore model was then taken for database screening (Maybridge and ChemBridge) to yield hits, which were further filtered for their drug-likeliness. The potential hits retrieved from virtual database screening were docked using CDOCKER to identify the ligand binding landscape. The top-ranked hits obtained from molecular docking were progressed to molecular dynamics (AMBER) simulations to deduce the ligand binding affinity. This study identified MB-41570 and CB-10358 as potential hits and evaluated these experimentally using in vitro KSP ATPase inhibition assays.

Geospatial analysis identifies critical mineral-resource potential in Alaska

USGS Publications Warehouse

Karl, Susan M.; Labay, Keith A.; Jacques, Katherine; Landowski, Claire

2017-03-03

Alaska consists of more than 663,000 square miles (1,717,000 square kilometers) of land—more than a sixth of the total area of the United States—and large tracts of it have not been systematically studied or sampled for mineral-resource potential. Many regions of the State are known to have significant mineral-resource potential, and there are currently six operating mines in the State along with numerous active mineral exploration projects. The U.S. Geological Survey and the Alaska Division of Geological & Geophysical Surveys have developed a new geospatial tool that integrates and analyzes publicly available databases of geologic information and estimates the mineral-resource potential for critical minerals, which was recently used to evaluate Alaska. The results of the analyses highlight areas that have known mineral deposits and also reveal areas that were not previously considered to be prospective for these deposit types. These results will inform land management decisions by Federal, State, and private landholders, and will also help guide future exploration activities and scientific investigations in Alaska.

The Force Exerted by the Membrane Potential During Protein Import into the Mitochondrial Matrix

NASA Technical Reports Server (NTRS)

Shariff, Karim; Ghosal, Sandip; Matouschek, Andreas

2002-01-01

The electrostatic force exerted on a targeting sequence by the electrical potential across the inner mitochondrial membrane is calculated and found to vary from 1.4 pN to 2.2 pN (per unit elementary charge) as the radius of the inner membrane pore (assumed aqueous) is varied from 12 to 6.5 Angstroms, its measured range. Since the pore is not very much wider than the distance between water molecules, the full shielding effect of water may not be present; the extreme case of a nonaqueous pore gives a force of 3.1 pN per unit charge, which represents an upper limit. When applied to mitochondrial import experiments on the protein harness, these results imply that a force of 11 plus or minus 4 pN is sufficient to catalyze the unfolding of harness during import. Comparison of these results with unfolding forces measured using atomic force microscopy suggests that the two are not inconsistent.

The importance of environmental quality and catch potential to fishing site selection by freshwater anglers in Mississippi

USGS Publications Warehouse

Schramm, H.L.; Gerard, P.D.; Gill, D.A.

2003-01-01

We measured the importance of 24 fishing site attributes to Mississippi freshwater anglers. Factor analysis identified four multiattribute factors as important in the selection of fishing location: CLEAN ENVIRONMENT CATCH, COST AND HARVEST and AMENITIES AND SAFETY. In general, the importance of site selection factors differed little among anglers grouped by preferred type of fish, preferred fishing location (lakes and reservoirs, rivers and streams, ponds, or reservoir tailwaters), usual manner of fishing (engine-powered boat, nonpowered boat, or shore), or change in fishing frequency. COST AND HARVEST was more important to anglers with high harvest orientations. We found low correlations between site selection factor importance scores and angler age, fishing frequency, fishing expenditures, or fishing motivation factors. We suggest that the general lack of differences in site selection factors among angler groups indicates that management strategies to improve fishing site attributes should benefit all angler groups. Clean fishing environments and awareness of the availability of desired sport fishes were "very" or "extremely" important to fishing site selection by more than 70% of Mississippi freshwater anglers and should be priority management objectives.

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

NASA Astrophysics Data System (ADS)

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.

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

NASA Astrophysics Data System (ADS)

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

2014-04-01

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.

De Novo Sequencing of Hypericum perforatum Transcriptome to Identify Potential Genes Involved in the Biosynthesis of Active Metabolites

PubMed Central

He, Miao; Wang, Ying; Hua, Wenping; Zhang, Yuan; Wang, Zhezhi

2012-01-01

Background Hypericum perforatum L. (St. John’s wort) is a medicinal plant with pharmacological properties that are antidepressant, anti-inflammatory, antiviral, anti-cancer, and antibacterial. Its major active metabolites are hypericins, hyperforins, and melatonin. However, little genetic information is available for this species, especially that concerning the biosynthetic pathways for active ingredients. Methodology/Principal Findings Using de novo transcriptome analysis, we obtained 59,184 unigenes covering the entire life cycle of these plants. In all, 40,813 unigenes (68.86%) were annotated and 2,359 were assigned to secondary metabolic pathways. Among them, 260 unigenes are involved in the production of hypericin, hyperforin, and melatonin. Another 2,291 unigenes are classified as potential Type III polyketide synthase. Our BlastX search against the AGRIS database reveals 1,772 unigenes that are homologous to 47 known Arabidopsis transcription factor families. Further analysis shows that 10.61% (6,277) of these unigenes contain 7,643 SSRs. Conclusion We have identified a set of putative genes involved in several secondary metabolism pathways, especially those related to the synthesis of its active ingredients. Our results will serve as an important platform for public information about gene expression, genomics, and functional genomics in H. perforatum. PMID:22860059

Epitope presentation is an important determinant of the utility of antigens identified from protein arrays in the development of autoantibody diagnostic assays.

PubMed

Murphy, Mairead A; O'Connell, David J; O'Kane, Sara L; O'Brien, John K; O'Toole, Sharon; Martin, Cara; Sheils, Orla; O'Leary, John J; Cahill, Dolores J

2012-08-03

Autoantibodies represent an attractive biomarker for diagnostic assays principally due to the stability of immunoglobulin in patient serum facilitating measurement with conventional assays. Immune responses to tumorigenesis may facilitate detection of ovarian cancer in the early stages of the disease with identification of a panel of tumour specific autoantibodies. Despite the reporting of many tumour associated autoantibodies using arrays of tumour antigens, this has not led to the advance in diagnostic capability as rapidly as was initially expected. Here we examine the potential diagnostic utility of candidate autoantibody biomarkers identified via screening of serum samples on a high content human protein array from a unique cohort of early stage and late stage ovarian cancer patients. We analyse the performance of autoantibodies to the tumour suppressor protein p53 and the novel autoantigens alpha adducin and endosulfine alpha identified in our array screen. Each antigen has different performance characteristics using conventional ELISA format and Western blot immunoassay. The high attrition rate of promising autoantigens identified by array screening can in part be explained by the presentation of the epitope of the antigen in the subsequent method of validation and this study provides directions on maximising the potential of candidate biomarkers. This article is part of a Special Issue entitled: Translational Proteomics. Copyright © 2012 Elsevier B.V. All rights reserved.

Identifying unintended consequences of quality indicators: a qualitative study.

PubMed

Lester, Helen E; Hannon, Kerin L; Campbell, Stephen M

2011-12-01

For the first 5 years of the UK primary care pay for performance scheme, the Quality and Outcomes Framework (QOF), quality indicators were introduced without piloting. However, in 2009, potential new indicators were piloted in a nationally representative sample of practices. This paper describes an in-depth exploration of family physician, nurse and other primary-care practice staff views of the value of piloting with a particular focus on unintended consequences of 13 potential new QOF indicators. Fifty-seven family-practice professionals were interviewed in 24 representative practices across England. Almost all interviewees emphasised the value of piloting in terms of an opportunity to identify unintended consequences of potential QOF indicators in 'real world' settings with staff who deliver day-to-day care to patients. Four particular types of unintended consequences were identified: measure fixation, tunnel vision, misinterpretation and potential gaming. 'Measure fixation,' an inappropriate attention on isolated aspects of care, appeared to be the key unintended consequence. In particular, if the palliative care indicator had been introduced without piloting, this might have incentivised poorer care in a minority of practices with potential harm to vulnerable patients. It is important to identify concerns and experiences about unintended consequences of indicators at an early stage when there is time to remove or adapt problem indicators. Since the UK government currently spends over £1 billion each year on QOF, the £150,000 spent on each piloting cohort (0.0005% of the total QOF budget) appears to be good value for money.

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

PubMed

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.

Descriptive study of important energy-conservation content for industrial arts in North Carolina and potential constraints to implementation of the content

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, C.D.

The purpose of this study was to determine the important energy-conservation content for industrial arts in North Carolina. The continuing purpose was to identify constraints to implementation of the identified important content. Fifty-three energy-conservation-content items were identified from the literature. This content was rated on importance by seven industrial arts/energy-conservation specialists in North Carolina. An analysis of the specialists scores resulted in the identification of the 20 most important energy-conservation-content items for industrial arts in North Carolina. Identification of possible constraints to the implementation of the important content was accomplished by surveying the certified industrial arts teachers in North Carolina.more » On the survey, teachers rated each content item in relation to their instructional practices, knowledge level, and perception of content appropriateness. Almost 67% of the industrial arts teachers in North Carolina responded to the survey. The study revealed that overall, industrial arts teachers believed energy conservation was moderately to highly appropriate for industrial arts. Knowledge of energy conservation was at a comparatively lower level, and was considered a possible constraint to content implementation. Although energy-conservation instructional practices were at a low level, 88% of the teachers in the survey sample included at least one of the energy-conservation-content items in their curriculum.« less

Identifying criteria for the assessment of pharmacy students' communication skills with patients.

PubMed

Mackellar, Adele; Ashcroft, Darren M; Bell, Dawn; James, Delyth Higman; Marriott, John

2007-06-15

To identify criteria by which patients can assess the communication skills of pharmacy students. Potential assessment criteria were generated from 2 main sources: a literature review and a focus group discussion. A modified two-round Delphi survey was subsequently conducted with 35 professionals who were actively involved in teaching and assessing communication skills of pharmacy students to determine the importance and reliability of each criterion. Consensus ratings identified 7 criteria that were important measures of pharmacy students' communication skills and could be reliably assessed by patients. A modified two-round Delphi consultation survey successfully identified criteria that can be used by patients to assess the communication skills of pharmacy undergraduates. Future work will examine the feasibility of using patients as assessors of communication skills of pharmacy students, preregistration pharmacists, and qualified pharmacists.

Quantitative DNA Methylation Analysis Identifies a Single CpG Dinucleotide Important for ZAP-70 Expression and Predictive of Prognosis in Chronic Lymphocytic Leukemia

PubMed Central

Claus, Rainer; Lucas, David M.; Stilgenbauer, Stephan; Ruppert, Amy S.; Yu, Lianbo; Zucknick, Manuela; Mertens, Daniel; Bühler, Andreas; Oakes, Christopher C.; Larson, Richard A.; Kay, Neil E.; Jelinek, Diane F.; Kipps, Thomas J.; Rassenti, Laura Z.; Gribben, John G.; Döhner, Hartmut; Heerema, Nyla A.; Marcucci, Guido; Plass, Christoph; Byrd, John C.

2012-01-01

Purpose Increased ZAP-70 expression predicts poor prognosis in chronic lymphocytic leukemia (CLL). Current methods for accurately measuring ZAP-70 expression are problematic, preventing widespread application of these tests in clinical decision making. We therefore used comprehensive DNA methylation profiling of the ZAP-70 regulatory region to identify sites important for transcriptional control. Patients and Methods High-resolution quantitative DNA methylation analysis of the entire ZAP-70 gene regulatory regions was conducted on 247 samples from patients with CLL from four independent clinical studies. Results Through this comprehensive analysis, we identified a small area in the 5′ regulatory region of ZAP-70 that showed large variability in methylation in CLL samples but was universally methylated in normal B cells. High correlation with mRNA and protein expression, as well as activity in promoter reporter assays, revealed that within this differentially methylated region, a single CpG dinucleotide and neighboring nucleotides are particularly important in ZAP-70 transcriptional regulation. Furthermore, by using clustering approaches, we identified a prognostic role for this site in four independent data sets of patients with CLL using time to treatment, progression-free survival, and overall survival as clinical end points. Conclusion Comprehensive quantitative DNA methylation analysis of the ZAP-70 gene in CLL identified important regions responsible for transcriptional regulation. In addition, loss of methylation at a specific single CpG dinucleotide in the ZAP-70 5′ regulatory sequence is a highly predictive and reproducible biomarker of poor prognosis in this disease. This work demonstrates the feasibility of using quantitative specific ZAP-70 methylation analysis as a relevant clinically applicable prognostic test in CLL. PMID:22564988

Analytical approaches to identify potential migrants in polyester-polyurethane can coatings.

PubMed

Louise Bradley, Emma; Driffield, Malcolm; Guthrie, James; Harmer, Nick; Thomas Oldring, Peter Kenneth; Castle, Laurence

2009-12-01

The safety of a polyester-polyurethane can coating has been assessed using a suite of complementary analytical methods to identify and estimate the concentrations of potential chemical migrants. The polyester was based on phthalic acids and aliphatic diols. The polyisocyanate cross-linking agent was 1-isocyanato-3-isocyanatomethyl-3,5,5-trimethyl cyclohexane homopolymer (IPDI) blocked with methylethylketone oxime (MEKO) to make a one-part formulation. The overall migrate, obtained using solvent extraction of cured films, comprised almost completely of 12 cyclic and one linear polyester oligomer up to molecular weight 800 and containing up to six monomer units. These 13 oligomers covered a total of 28 isomeric forms. Other minor components detected were plasticisers and surfactants as well as impurities present in the starting materials. There was no detectable residue of either the blocked isocyanate (<0.01 microg/dm(2)) used as the starting substance or the unblocked isocyanate (<0.02 microg/dm(2)). The level of extractable IPDI was used as an indicator of the completeness of cure in experimental coatings. These studies revealed that there was an influence of time, temperature and catalyst content. Polymerisation was also influenced by the additives used and by the ageing of the wet coating formulation over several months. These studies allow parameters to be specified to ensure that commercial production coatings receive a full cure giving low migration characteristics.

A new process sensitivity index to identify important system processes under process model and parametric uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai, Heng; Ye, Ming; Walker, Anthony P.

Hydrological models are always composed of multiple components that represent processes key to intended model applications. When a process can be simulated by multiple conceptual-mathematical models (process models), model uncertainty in representing the process arises. While global sensitivity analysis methods have been widely used for identifying important processes in hydrologic modeling, the existing methods consider only parametric uncertainty but ignore the model uncertainty for process representation. To address this problem, this study develops a new method to probe multimodel process sensitivity by integrating the model averaging methods into the framework of variance-based global sensitivity analysis, given that the model averagingmore » methods quantify both parametric and model uncertainty. A new process sensitivity index is derived as a metric of relative process importance, and the index includes variance in model outputs caused by uncertainty in both process models and model parameters. For demonstration, the new index is used to evaluate the processes of recharge and geology in a synthetic study of groundwater reactive transport modeling. The recharge process is simulated by two models that converting precipitation to recharge, and the geology process is also simulated by two models of different parameterizations of hydraulic conductivity; each process model has its own random parameters. The new process sensitivity index is mathematically general, and can be applied to a wide range of problems in hydrology and beyond.« less

Identifying suitable sites for Florida panther reintroduction

USGS Publications Warehouse

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

2006-01-01

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

Identifying the Most Important 21st Century Workforce Competencies: An Analysis of the Occupational Information Network (O*NET). Research Report. ETS RR-13-21

ERIC Educational Resources Information Center

Burrus, Jeremy; Jackson, Teresa; Xi, Nuo; Steinberg, Jonathan

2013-01-01

To identify the most important competencies for college graduates to succeed in the 21st century workforce, we conducted an analysis of the Occupational Information Network (O*NET) database. O*NET is a large job analysis operated and maintained by the U.S. Department of Labor. We specifically analyzed ratings of the importance of abilities (52…

Analysis of copy number variations in Holstein cows identify potential mechanisms contributing to differences in residual feed intake

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. In this study, we performed an initial analysis of CNVs using BovineHD SNP genotyping data from 147 Holstein cows identified as having high or low feed efficiency as estimated by residual feed intak...

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

PubMed

Lee, E S; Jung, S Y; Kim, J Y; Kim, J J; Yoo, T K; Kim, Y G; Lee, K S; Lee, E S; Kim, E K; Min, J W; Han, W; Noh, D Y; Moon, H G

2016-05-01

We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All

Importance and use of correlational research.

PubMed

Curtis, Elizabeth A; Comiskey, Catherine; Dempsey, Orla

2016-07-01

The importance of correlational research has been reported in the literature yet few research texts discuss design in any detail. To discuss important issues and considerations in correlational research, and suggest ways to avert potential problems during the preparation and application of the design. This article targets the gap identified in the literature regarding correlational research design. Specifically, it discusses the importance and purpose of correlational research, its application, analysis and interpretation with contextualisations to nursing and health research. Findings from correlational research can be used to determine prevalence and relationships among variables, and to forecast events from current data and knowledge. In spite of its many uses, prudence is required when using the methodology and analysing data. To assist researchers in reducing mistakes, important issues are singled out for discussion and several options put forward for analysing data. Correlational research is widely used and this paper should be particularly useful for novice nurse researchers. Furthermore, findings generated from correlational research can be used, for example, to inform decision-making, and to improve or initiate health-related activities or change.

Phosphoproteomic Analysis Identifies Focal Adhesion Kinase 2 (FAK2) as a Potential Therapeutic Target for Tamoxifen Resistance in Breast Cancer*

PubMed Central

Wu, Xinyan; Zahari, Muhammad Saddiq; Renuse, Santosh; Nirujogi, Raja Sekhar; Kim, Min-Sik; Manda, Srikanth S.; Stearns, Vered; Gabrielson, Edward; Sukumar, Saraswati; Pandey, Akhilesh

2015-01-01

Tamoxifen, an estrogen receptor-α (ER) antagonist, is an important agent for the treatment of breast cancer. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying this resistance, we treated the MCF7 breast cancer cell line with tamoxifen for over six months and showed that this cell line acquired resistance to tamoxifen in vitro and in vivo. We performed SILAC-based quantitative phosphoproteomic profiling on the tamoxifen resistant and vehicle-treated sensitive cell lines to quantify the phosphorylation alterations associated with tamoxifen resistance. From >5600 unique phosphopeptides identified, 1529 peptides exhibited hyperphosphorylation and 409 peptides showed hypophosphorylation in the tamoxifen resistant cells. Gene set enrichment analysis revealed that focal adhesion pathway was one of the most enriched signaling pathways activated in tamoxifen resistant cells. Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally up-regulated in tamoxifen resistant cells. FAK2 suppression by specific siRNA knockdown or a small molecule inhibitor repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 is significantly associated with shorter metastasis-free survival in estrogen receptor-positive breast cancer patients treated with tamoxifen. Our studies suggest that FAK2 is a potential therapeutic target for the management of hormone-refractory breast cancers. PMID:26330541

The Potential Importance of Conservation, Restoration and Altered Management Practices for Water Quality in the Wabash River Watershed

EPA Science Inventory

The Potential Importance of Conservation, Restoration and Altered Management Practices for Water Quality in the Wabash River Watershed Guoxiang Yang1, Elly P.H. Best2, Staci Goodwin3 1 ORISE Postdoc Research Associate at U.S. Environmental Protection Agency, National Risk...

Isolated severe tricuspid regurgitation: the importance of identifying underlying mechanism.

PubMed

Poh, Kian Keong; Solis, Jorge; Hung, Judy

2008-07-21

An 88-year-old woman presented with right heart failure, history of diarrhoea, abdominal pain, weight lost, dyspnoea over several weeks and a new pan-systolic murmur. Echocardiography showed retracted tricuspid leaflets with incomplete coaptation resulting in severe regurgitation. Subcostal view showed an adjacent hepatic cyst leading to biopsy, which revealed neoplastic neuroendocrine cells. Her 24-hour urinary 5-hydroxyindoleacetic acid level was elevated. The unifying diagnosis was carcinoid syndrome for which she was treated. Echocardiography is an important tool for diagnosis, management and prognosis of carcinoid heart disease.

Perceived cultural importance and actual self-importance of values in cultural identification.

PubMed

Wan, Ching; Chiu, Chi-yue; Tam, Kim-pong; Lee, Sau-lai; Lau, Ivy Yee-man; Peng, Siqing

2007-02-01

Cross-cultural psychologists assume that core cultural values define to a large extent what a culture is. Typically, core values are identified through an actual self-importance approach, in which core values are those that members of the culture as a group strongly endorse. In this article, the authors propose a perceived cultural importance approach to identifying core values, in which core values are values that members of the culture as a group generally believe to be important in the culture. In 5 studies, the authors examine the utility of the perceived cultural importance approach. Results consistently showed that, compared with values of high actual self-importance, values of high perceived cultural importance play a more important role in cultural identification. These findings have important implications for conceptualizing and measuring cultures. ((c) 2007 APA, all rights reserved).

RNA-seq analysis identifies potential modulators of gravity response in spores of Ceratopteris (Parkeriaceae): evidence for modulation by calcium pumps and apyrase activity.

PubMed

Bushart, Thomas J; Cannon, Ashley E; Ul Haque, Aeraj; San Miguel, Phillip; Mostajeran, Kathy; Clark, Gregory B; Porterfield, D Marshall; Roux, Stanley J

2013-01-01

Gravity regulates the magnitude and direction of a trans-cell calcium current in germinating spores of Ceratopteris richardii. Blocking this current with nifedipine blocks the spore's downward polarity alignment, a polarization that is fixed by gravity ∼10 h after light induces the spores to germinate. RNA-seq analysis at 10 h was used to identify genes potentially important for the gravity response. The data set will be valuable for other developmental and phylogenetic studies. De novo Newbler assembly of 958 527 reads from Roche 454 sequencing was executed. The sequences were identified and analyzed using in silico methods. The roles of endomembrane Ca(2+)-ATPase pumps and apyrases in the gravity response were further tested using pharmacological agents. Transcripts related to calcium signaling and ethylene biosynthesis were identified as notable constituents of the transcriptome. Inhibiting the activity of endomembrane Ca(2+)-ATPase pumps with 2,5-di-(t-butyl)-1,4-hydroquinone diminished the trans-cell current, but increased the orientation of the polar axis to gravity. The effects of applied nucleotides and purinoceptor antagonists gave novel evidence implicating extracellular nucleotides as regulators of the gravity response in these fern spores. In addition to revealing general features of the transcriptome of germinating spores, the results highlight a number of calcium-responsive and light-receptive transcripts. Pharmacologic assays indicate endomembrane Ca(2+)-ATPases and extracellular nucleotides may play regulatory roles in the gravity response of Ceratopteris spores.

TCGA Bladder Cancer Study Reveals Potential Drug Targets - TCGA

Cancer.gov

Investigators with the TCGA Research Network have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease.

Characterisation of surface antigens of Strongylus vulgaris of potential immunodiagnostic importance.

PubMed

Nichol, C; Masterson, W J

1987-08-01

When antigens prepared by detergent washes of Strongylus vulgaris and Parascaris equorum were probed in an enzyme-linked immunosorbent assay test with horse sera from single species infections of S. vulgaris and P. equorum, a high degree of cross-reaction between the species was demonstrated. Western blot analysis of four common horse nematode species showed a large number of common antigens when probed with horse infection sera. Antisera raised in rabbits against the four species, including S. vulgaris, were also found to cross-react considerably. Rabbit anti-S. vulgaris sera were affinity adsorbed over a series of affinity chromatography columns, bound with cross-reactive surface antigens, to obtain S. vulgaris-specific antisera and thereby identify S. vulgaris-specific antigens by Western blotting. These studies revealed potentially specific antigens of apparent molecular weights of 100,000, 52,000, and 36,000. Of these bands, only the 52 kDa and 36 kDa appeared to be found on the surface as judged by 125I-labelling of intact worms by the Iodogen method, although neither protein was immunoprecipitated by horse infection sera. Finally, immunoprecipitation of in vitro translated proteins derived from larval S. vulgaris RNA suggests that two proteins may be parasite-derived. These findings are discussed both with respect to the surface of S. vulgaris and to the use of these species-specific antigens in immunodiagnosis.

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

PubMed

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.

IDENTIFYING POTENTIAL SOURCES OF BACKGROUND CONTAMINATION IN RT-PCR

EPA Science Inventory

Extraction of nucleic acids from low biomass samples, such as drinking water, is particularly sensitive to potential background contamination because the contaminating material is minimally diluted by the sample. The presence of bacterial DNA in Taq DNA polymerase is wel...

Identifying and tracing potential energy surfaces of electronic excitations with specific character via their transition origins: application to oxirane.

PubMed

Li, Jian-Hao; Zuehlsdorff, T J; Payne, M C; Hine, N D M

2015-05-14

We show that the transition origins of electronic excitations identified by quantified natural transition orbital (QNTO) analysis can be employed to connect potential energy surfaces (PESs) according to their character across a wide range of molecular geometries. This is achieved by locating the switching of transition origins of adiabatic potential surfaces as the geometry changes. The transition vectors for analysing transition origins are provided by linear response time-dependent density functional theory (TDDFT) calculations under the Tamm-Dancoff approximation. We study the photochemical CO ring opening of oxirane as an example and show that the results corroborate the traditional Gomer-Noyes mechanism derived experimentally. The knowledge of specific states for the reaction also agrees well with that given by previous theoretical work using TDDFT surface-hopping dynamics that was validated by high-quality quantum Monte Carlo calculations. We also show that QNTO can be useful for considerably larger and more complex systems: by projecting the excitations to those of a reference oxirane molecule, the approach is able to identify and analyse specific excitations of a trans-2,3-diphenyloxirane molecule.

Short communication: Development of a direct in vivo screening model to identify potential probiotic bacteria using Caenorhabditis elegans.

PubMed

Park, M R; Yun, H S; Son, S J; Oh, S; Kim, Y

2014-11-01

Caenorhabditis elegans is an accepted model host to study host-bacteria interactions in the gut, in addition to being a simple model with which to study conserved aspects of biological signaling pathways in intestinal environments, because these nematode worms have similar intestinal cells to those of humans. Here, we used C. elegans to develop a new in vivo screening system for potential probiotic lactic acid bacteria (LAB). Initially, critical colonization ability of LAB strains isolated from Korean infant feces was screened in the worm intestinal tract over a period of 5 d. Furthermore, we investigated host health-promoting activities, including longevity-extending effects and immune-enhancing activities against foodborne pathogen infection. We identified 4 LAB strains that were highly persistent in the nematode gut and that significantly prolonged the longevity of C. elegans and improved the survival of C. elegans in response to infection by Staphylococcus aureus. The 4 LAB strains we identified showed resistance to acid and bile conditions, assimilated cholesterol, and were able to attach to a mucus layer. The 4 LAB isolates were identified as Lactobacillus plantarum using 16S rRNA sequencing analysis. Taken together, we developed a direct in vivo screening system using C. elegans to study host health-promoting LAB. Our system is simple, rapid, cost-effective, and reliable, and we anticipate that this system will result in the discovery of many more potential probiotic bacteria for dairy foods. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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...

Identifying Important Career Indicators of Undergraduate Geoscience Students Upon Completion of Their Degree

NASA Astrophysics Data System (ADS)

Wilson, C. E.; Keane, C. M.; Houlton, H. R.

2012-12-01

The American Geosciences Institute (AGI) decided to create the National Geoscience Student Exit Survey in order to identify the initial pathways into the workforce for these graduating students, as well as assess their preparedness for entering the workforce upon graduation. The creation of this survey stemmed from a combination of experiences with the AGI/AGU Survey of Doctorates and discussions at the following Science Education Research Center (SERC) workshops: "Developing Pathways to Strong Programs for the Future", "Strengthening Your Geoscience Program", and "Assessing Geoscience Programs". These events identified distinct gaps in understanding the experiences and perspectives of geoscience students during one of their most profound professional transitions. Therefore, the idea for the survey arose as a way to evaluate how the discipline is preparing and educating students, as well as identifying the students' desired career paths. The discussions at the workshops solidified the need for this survey and created the initial framework for the first pilot of the survey. The purpose of this assessment tool is to evaluate student preparedness for entering the geosciences workforce; identify student decision points for entering geosciences fields and remaining in the geosciences workforce; identify geosciences fields that students pursue in undergraduate and graduate school; collect information on students' expected career trajectories and geosciences professions; identify geosciences career sectors that are hiring new graduates; collect information about salary projections; overall effectiveness of geosciences departments regionally and nationally; demonstrate the value of geosciences degrees to future students, the institutions, and employers; and establish a benchmark to perform longitudinal studies of geosciences graduates to understand their career pathways and impacts of their educational experiences on these decisions. AGI's Student Exit Survey went through

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

PubMed Central

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

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

PubMed Central

Gala, Manish; Abecasis, Goncalo; Bezieau, Stephane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Conti, David V.; Curtis, Keith R.; Duggan, David; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Leal, Suzanne M.; Newcomb, Polly A.; Nickerson, Deborah A.; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Hsu, Li; Chan, Andrew T.; White, Emily; Berndt, Sonja I.; Peters, Ulrike

2016-01-01

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). PMID:27379672

Experimental assessment of the importance of amino acid positions identified by an entropy-based correlation analysis of multiple-sequence alignments.

PubMed

Dietrich, Susanne; Borst, Nadine; Schlee, Sandra; Schneider, Daniel; Janda, Jan-Oliver; Sterner, Reinhard; Merkl, Rainer

2012-07-17

The analysis of a multiple-sequence alignment (MSA) with correlation methods identifies pairs of residue positions whose occupation with amino acids changes in a concerted manner. It is plausible to assume that positions that are part of many such correlation pairs are important for protein function or stability. We have used the algorithm H2r to identify positions k in the MSAs of the enzymes anthranilate phosphoribosyl transferase (AnPRT) and indole-3-glycerol phosphate synthase (IGPS) that show a high conn(k) value, i.e., a large number of significant correlations in which k is involved. The importance of the identified residues was experimentally validated by performing mutagenesis studies with sAnPRT and sIGPS from the archaeon Sulfolobus solfataricus. For sAnPRT, five H2r mutant proteins were generated by replacing nonconserved residues with alanine or the prevalent residue of the MSA. As a control, five residues with conn(k) values of zero were chosen randomly and replaced with alanine. The catalytic activities and conformational stabilities of the H2r and control mutant proteins were analyzed by steady-state enzyme kinetics and thermal unfolding studies. Compared to wild-type sAnPRT, the catalytic efficiencies (k(cat)/K(M)) were largely unaltered. In contrast, the apparent thermal unfolding temperature (T(M)(app)) was lowered in most proteins. Remarkably, the strongest observed destabilization (ΔT(M)(app) = 14 °C) was caused by the V284A exchange, which pertains to the position with the highest correlation signal [conn(k) = 11]. For sIGPS, six H2r mutant and four control proteins with alanine exchanges were generated and characterized. The k(cat)/K(M) values of four H2r mutant proteins were reduced between 13- and 120-fold, and their T(M)(app) values were decreased by up to 5 °C. For the sIGPS control proteins, the observed activity and stability decreases were much less severe. Our findings demonstrate that positions with high conn(k) values have an

A Targeted Metabolomics MRM-MS Study on Identifying Potential Hypertension Biomarkers in Human Plasma and Evaluating Acupuncture Effects.

PubMed

Yang, Mingxiao; Yu, Zheng; Deng, Shufang; Chen, Xiaomin; Chen, Liang; Guo, Zhenyu; Zheng, Hui; Chen, Lin; Cai, Dingjun; Wen, Bo; Wu, Qiaofeng; Liang, Fanrong

2016-05-16

The critical role of metabolic abnormality in hypertension is increasingly recognized, but its biomarkers are not clearly identified. In this study, 47 chemical compounds recorded by literature were employed as target metabolites of essential hypertension (EH). We detected their content in the plasma of EH patients and healthy subjects by using the Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS). After screening the most altered compounds, acupuncture was used to treat patients for 3 months and these plasma metabolites were tested again. The results showed that oleic acid (OA) and myoinositol (MI) were the most important differential metabolites between the hypertensive plasma and the healthy plasma. They were also closely correlated with 24-hour blood pressure and nocturnal dipping. Moreover, plasma OA and MI could be restored to normal levels by acupuncture, accompanying with reduction of 24-hour systolic and diastolic blood pressure [from 145.10 ± 9.28 mm Hg to 140.70 ± 9.59 mm Hg (P < 0.0001), and 88.35 ± 7.92 mm Hg to 85.86 ± 7.95 mm Hg (P = 0.0024), respectively] and improvement of circadian blood pressure rhythm. This study demonstrated that plasma OA and MI were potential hypertension biomarkers and they could be used to preliminarily assess the treating effects such as acupuncture.

CPTAC Investigators Identify Rogue Breast Tumor Proteins That Point To Potential Drug Therapies | Office of Cancer Clinical Proteomics Research

Cancer.gov

For patients with difficult-to-treat cancers, doctors increasingly rely on genomic testing of tumors to identify errors in the DNA that indicate a tumor can be targeted by existing therapies. But this approach overlooks another potential marker — rogue proteins — that may be driving cancer cells and also could be targeted with existing treatments.

Component analysis of somatosensory evoked potentials for identifying spinal cord injury location.

PubMed

Wang, Yazhou; Li, Guangsheng; Luk, Keith D K; Hu, Yong

2017-05-24

This study aims to determine whether the time-frequency components (TFCs) of somatosensory evoked potentials (SEPs) can be used to identify the specific location of a compressive spinal cord injury using a classification technique. Waveforms of SEPs after compressive injuries at various locations (C4, C5 and C6) in rat spinal cords were decomposed into a series of TFCs using a high-resolution time-frequency analysis method. A classification method based on support vector machine (SVM) was applied to the distributions of these TFCs among different pathological locations. The difference among injury locations manifests itself in different categories of SEP TFCs. High-energy TFCs of normal-state SEPs have significantly higher power and frequency than those of injury-state SEPs. The location of C5 is characterized by a unique distribution pattern of middle-energy TFCs. The difference between C4 and C6 is evidenced by the distribution pattern of low-energy TFCs. The proposed classification method based on SEP TFCs offers a discrimination accuracy of 80.2%. In this study, meaningful information contained in various SEP components was investigated and used to propose a new application of SEPs for identification of the location of pathological changes in the cervical spinal cord.

TCGA bladder cancer study reveals potential drug targets

Cancer.gov

Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

Endothelial cell palmitoylproteomics identifies novel lipid modified targets and potential substrates for protein acyl transferases

PubMed Central

Marin, Ethan P.; Derakhshan, Behrad; Lam, TuKiet T.; Davalos, Alberto; Sessa, William C.

2012-01-01

Rationale Protein S-palmitoylation is the post-translational attachment of a saturated 16-carbon palmitic acid to a cysteine side chain via a thioester bond. Palmitoylation can affect protein localization, trafficking, stability, and function. The extent and roles of palmitoylation in endothelial cell (EC) biology is not well understood, in part due to technological limits on palmitoylprotein detection. Objective To develop a method using acyl-biotinyl exchange (ABE) technology coupled with mass spectrometry to globally isolate and identify palmitoylproteins in EC. Methods and Results More than 150 putative palmitoyl proteins were identified in EC using ABE and mass spectrometry. Among the novel palmitoylproteins identified is superoxide dismutase 1 (SOD1), an intensively studied enzyme that protects all cells from oxidative damage. Mutation of cysteine 6 prevents palmitoylation, leads to reduction in SOD1 activity in vivo and in vitro, and inhibits nuclear localization, thereby supporting a functional role for SOD1 palmitoylation. Moreover, we used ABE to search for substrates of particular protein acyl transferases in EC. We found that palmitoylation of the cell adhesion protein PECAM1 is dependent on the protein acyl transferase ZDHHC21. We show that knockdown of ZDHHC21 leads to reduced levels of PECAM1 at the cell surface. Conclusions Our data demonstrate the utility of EC palmitoylproteomics to reveal new insights into the role of this important post-translational lipid modification in EC biology. PMID:22496122

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

PubMed

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.

Forge into the Future: Identifying Core Competencies and Important Skills, Knowledge, and Abilities (SKAs) for Junior Navy Medical Service Corps Officers

DTIC Science & Technology

2008-10-20

operations and business practices, drug therapy management, and leadership, where as senior pharmacists placed a greater emphasis on the importance of SKAs...Commanders reviewed , sorted, and identified competencies from Wave I into 11 domains. From the expert analysis, the researcher developed a ...Y, a force of as many as 70 million are now beginning to embark on their career including the military health system. This generation as suggested

Identifying High Potential Well Targets with 3D Seismic and Mineralogy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mellors, R. J.

2015-10-30

Seismic reflection the primary tool used in petroleum exploration and production, but use in geothermal exploration is less standard, in part due to cost but also due to the challenges in identifying the highly-permeable zones essential for economic hydrothermal systems [e.g. Louie et al., 2011; Majer, 2003]. Newer technology, such as wireless sensors and low-cost high performance computing, has helped reduce the cost and effort needed to conduct 3D surveys. The second difficulty, identifying permeable zones, has been less tractable so far. Here we report on the use of seismic attributes from a 3D seismic survey to identify and mapmore » permeable zones in a hydrothermal area.« less

Identifying 2 prenylflavanones as potential hepatotoxic compounds in the ethanol extract of Sophora flavescens.

PubMed

Yu, Qianqian; Cheng, Nengneng; Ni, Xiaojun

2013-11-01

Zhixue capsule is a prescription for hemorrhoid commonly used in traditional Chinese medicine. This drug was recalled by the State Food and Drug Administration in 2008 because of severe adverse hepatic reactions. Zhixue capsule is composed of ethanol extracts of Cortex Dictamni (ECD) and Sophora flavescens (ESF). In our preliminary study, we observed the hepatotoxic effects of ESF on rat primary hepatocytes. However, ECD did not exhibit hepatotoxicity at the same concentration range. In this study, ESF was evaluated for its potential hepatotoxic effects on rats. Bioassay-guided isolation was used to identify the material basis for hepatotoxicity. Treatment with 1.25 g/kg and 2.5 g/kg ESF significantly elevated the alanine aminotransferase and aspartate aminotransferase levels in the serum. The changes in the levels of transaminases were supported by the remarkable fatty degeneration of liver histopathology. Further investigations using bioassay-guided isolation and analysis indicated that prenylated flavanones accounted for the positive hepatotoxic results. Two isolated compounds were identified, kurarinone and sophoraflavanone G, using nuclear magnetic resonance and mass spectrometry techniques. These compounds have potent toxic effects on primary rat hepatocytes (with IC50 values of 29.9 μM and 16.5 μM) and human HL-7702 liver cells (with IC50 values of 48.2 μM and 40.3 μM), respectively. Consequently, the hepatotoxic constituents of S. flavescens were determined to be prenylated flavanones, kurarinone, and sophoraflavanone G. © 2013 Institute of Food Technologists®

SOCIODEMOGRAPHIC DATA USED FOR IDENTIFYING ...

EPA Pesticide Factsheets

Due to unique social and demographic characteristics, various segments of the population may experience exposures different from those of the general population, which, in many cases, may be greater. When risk assessments do not characterize subsets of the general population, the populations that may experience the greatest risk remain unidentified. When such populations are not identified, the social and demographic data relevant to these populations is not considered when preparing exposure estimates, which can underestimate exposure and risk estimates for at-risk populations. Thus, it is necessary for risk or exposure assessors characterizing a diverse population, to first identify and then enumerate certain groups within the general population who are at risk for greater contaminant exposures. The document entitled Sociodemographic Data Used for Identifying Potentially Highly Exposed Populations (also referred to as the Highly Exposed Populations document), assists assessors in identifying and enumerating potentially highly exposed populations. This document presents data relating to factors which potentially impact an individual or group's exposure to environmental contaminants based on activity patterns (how time is spent), microenvironments (locations where time is spent), and other socio-demographic data such as age, gender, race and economic status. Populations potentially more exposed to various chemicals of concern, relative to the general population

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

PubMed Central

Luo, Yanzhang; Mok, Tin Seak; Lin, Xiuxian; Zhang, Wanling; Cui, Yizhi; Guo, Jiahui; Chen, Xing; Zhang, Tao; Wang, Tong

2017-01-01

Nasopharyngeal carcinoma (NPC) is a serious threat to public health, and the biomarker discovery is of urgent needs. The data-independent mode (DIA) based sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry (MS) has been proved to be precise in protein quantitation and efficient for cancer biomarker researches. In this study, we performed the first SWATH-MS analysis comparing the NPC and normal tissues. Spike-in stable isotope labeling by amino acids in cell culture (super-SILAC) MS was used as a shotgun reference. We identified and quantified 1414 proteins across all SWATH-MS analyses. We found that SWATH-MS had a unique feature to preferentially detect proteins with smaller molecular weights than either super-SILAC MS or human proteome background. With SWATH-MS, 29 significant differentially express proteins (DEPs) were identified. Among them, carbonic anhydrase 2 (CA2) was selected for further validation per novelty, MS quality and other supporting rationale. With the tissue microarray analysis, we found that CA2 had an AUC of 0.94 in differentiating NPC from normal tissue samples. In conclusion, SWATH-MS has unique features in proteome analysis, and it leads to the identification of CA2 as a potentially new diagnostic biomarker for NPC. PMID:28117408

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

PubMed

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.

How important is importance for prospective memory? A review

PubMed Central

Walter, Stefan; Meier, Beat

2014-01-01

Forgetting to carry out an intention as planned can have serious consequences in everyday life. People sometimes even forget intentions that they consider as very important. Here, we review the literature on the impact of importance on prospective memory performance. We highlight different methods used to manipulate the importance of a prospective memory task such as providing rewards, importance relative to other ongoing activities, absolute importance, and providing social motives. Moreover, we address the relationship between importance and other factors known to affect prospective memory and ongoing task performance such as type of prospective memory task (time-, event-, or activity-based), cognitive loads, and processing overlaps. Finally, we provide a connection to motivation, we summarize the effects of task importance and we identify important venues for future research. PMID:25018743

Results of an Assessment to Identify Potential Barriers to Sustainable Agriculture on American Indian Reservations in the Western United States

ERIC Educational Resources Information Center

Singletary, Loretta; Emm, Staci; Brummer, Fara Ann; Hill, George C.; Lewis, Steve; Hebb, Vicki

2016-01-01

Purpose: This paper reports the results of survey research conducted with tribal producers between 2011 and 2012 on 19 of the largest American Indian reservations in Idaho, Nevada, North Dakota, Oregon, South Dakota, and Washington. The purpose of the research was to identify potential barriers to sustainable agriculture on reservation lands. This…

An integrative strategy to identify the entire protein coding potential of prokaryotic genomes by proteogenomics.

PubMed

Omasits, Ulrich; Varadarajan, Adithi R; Schmid, Michael; Goetze, Sandra; Melidis, Damianos; Bourqui, Marc; Nikolayeva, Olga; Québatte, Maxime; Patrignani, Andrea; Dehio, Christoph; Frey, Juerg E; Robinson, Mark D; Wollscheid, Bernd; Ahrens, Christian H

2017-12-01

Accurate annotation of all protein-coding sequences (CDSs) is an essential prerequisite to fully exploit the rapidly growing repertoire of completely sequenced prokaryotic genomes. However, large discrepancies among the number of CDSs annotated by different resources, missed functional short open reading frames (sORFs), and overprediction of spurious ORFs represent serious limitations. Our strategy toward accurate and complete genome annotation consolidates CDSs from multiple reference annotation resources, ab initio gene prediction algorithms and in silico ORFs (a modified six-frame translation considering alternative start codons) in an integrated proteogenomics database (iPtgxDB) that covers the entire protein-coding potential of a prokaryotic genome. By extending the PeptideClassifier concept of unambiguous peptides for prokaryotes, close to 95% of the identifiable peptides imply one distinct protein, largely simplifying downstream analysis. Searching a comprehensive Bartonella henselae proteomics data set against such an iPtgxDB allowed us to unambiguously identify novel ORFs uniquely predicted by each resource, including lipoproteins, differentially expressed and membrane-localized proteins, novel start sites and wrongly annotated pseudogenes. Most novelties were confirmed by targeted, parallel reaction monitoring mass spectrometry, including unique ORFs and single amino acid variations (SAAVs) identified in a re-sequenced laboratory strain that are not present in its reference genome. We demonstrate the general applicability of our strategy for genomes with varying GC content and distinct taxonomic origin. We release iPtgxDBs for B. henselae , Bradyrhizobium diazoefficiens and Escherichia coli and the software to generate both proteogenomics search databases and integrated annotation files that can be viewed in a genome browser for any prokaryote. © 2017 Omasits et al.; Published by Cold Spring Harbor Laboratory Press.

Importance of multi-modal approaches to effectively identify cataract cases from electronic health records.

PubMed

Peissig, Peggy L; Rasmussen, Luke V; Berg, Richard L; Linneman, James G; McCarty, Catherine A; Waudby, Carol; Chen, Lin; Denny, Joshua C; Wilke, Russell A; Pathak, Jyotishman; Carrell, David; Kho, Abel N; Starren, Justin B

2012-01-01

There is increasing interest in using electronic health records (EHRs) to identify subjects for genomic association studies, due in part to the availability of large amounts of clinical data and the expected cost efficiencies of subject identification. We describe the construction and validation of an EHR-based algorithm to identify subjects with age-related cataracts. We used a multi-modal strategy consisting of structured database querying, natural language processing on free-text documents, and optical character recognition on scanned clinical images to identify cataract subjects and related cataract attributes. Extensive validation on 3657 subjects compared the multi-modal results to manual chart review. The algorithm was also implemented at participating electronic MEdical Records and GEnomics (eMERGE) institutions. An EHR-based cataract phenotyping algorithm was successfully developed and validated, resulting in positive predictive values (PPVs) >95%. The multi-modal approach increased the identification of cataract subject attributes by a factor of three compared to single-mode approaches while maintaining high PPV. Components of the cataract algorithm were successfully deployed at three other institutions with similar accuracy. A multi-modal strategy incorporating optical character recognition and natural language processing may increase the number of cases identified while maintaining similar PPVs. Such algorithms, however, require that the needed information be embedded within clinical documents. We have demonstrated that algorithms to identify and characterize cataracts can be developed utilizing data collected via the EHR. These algorithms provide a high level of accuracy even when implemented across multiple EHRs and institutional boundaries.

Importance of multi-modal approaches to effectively identify cataract cases from electronic health records

PubMed Central

Rasmussen, Luke V; Berg, Richard L; Linneman, James G; McCarty, Catherine A; Waudby, Carol; Chen, Lin; Denny, Joshua C; Wilke, Russell A; Pathak, Jyotishman; Carrell, David; Kho, Abel N; Starren, Justin B

2012-01-01

Objective There is increasing interest in using electronic health records (EHRs) to identify subjects for genomic association studies, due in part to the availability of large amounts of clinical data and the expected cost efficiencies of subject identification. We describe the construction and validation of an EHR-based algorithm to identify subjects with age-related cataracts. Materials and methods We used a multi-modal strategy consisting of structured database querying, natural language processing on free-text documents, and optical character recognition on scanned clinical images to identify cataract subjects and related cataract attributes. Extensive validation on 3657 subjects compared the multi-modal results to manual chart review. The algorithm was also implemented at participating electronic MEdical Records and GEnomics (eMERGE) institutions. Results An EHR-based cataract phenotyping algorithm was successfully developed and validated, resulting in positive predictive values (PPVs) >95%. The multi-modal approach increased the identification of cataract subject attributes by a factor of three compared to single-mode approaches while maintaining high PPV. Components of the cataract algorithm were successfully deployed at three other institutions with similar accuracy. Discussion A multi-modal strategy incorporating optical character recognition and natural language processing may increase the number of cases identified while maintaining similar PPVs. Such algorithms, however, require that the needed information be embedded within clinical documents. Conclusion We have demonstrated that algorithms to identify and characterize cataracts can be developed utilizing data collected via the EHR. These algorithms provide a high level of accuracy even when implemented across multiple EHRs and institutional boundaries. PMID:22319176

The Near-Earth Object Human Space Flight Accessible Targets Study (NHATS) List of Near-Earth Asteroids: Identifying Potential Targets for Future Exploration

NASA Technical Reports Server (NTRS)

Abell, Paul A.; Barbee, B. W.; Mink, R. G.; Alberding, C. M.; Adamo, D. R.; Mazanek, D. D.; Johnson, L. N.; Yeomans, D. K.; Chodas, P. W.; Chamberlin, A. B.;

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

PubMed

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.

Use of a latency-based demand assessment to identify potential demands for functional analyses.

PubMed

Call, Nathan A; Miller, Sarah J; Mintz, Joslyn Cynkus; Mevers, Joanna Lomas; Scheithauer, Mindy C; Eshelman, Julie E; Beavers, Gracie A

2016-12-01

Unlike potential tangible positive reinforcers, which are typically identified for inclusion in functional analyses empirically using preference assessments, demands are most often selected arbitrarily or based on caregiver report. The present study evaluated the use of a demand assessment with 12 participants who exhibited escape-maintained problem behavior. Participants were exposed to 10 demands, with aversiveness measured by average latency to the first instance of problem behavior. In subsequent functional analyses, results of a demand condition that included the demand with the shortest latency to problem behavior resulted in identification of an escape function for 11 of the participants. In contrast, a demand condition that included the demand with the longest latency resulted in identification of an escape function for only 5 participants. The implication of these findings is that for the remaining 7 participants, selection of the demand for the functional analysis without using the results of the demand assessment could have produced a false-negative finding. © 2016 Society for the Experimental Analysis of Behavior.

Identifying Potential Mechanisms Enabling Acidophily in the Ammonia-Oxidizing Archaeon "Candidatus Nitrosotalea devanaterra".

PubMed

Lehtovirta-Morley, Laura E; Sayavedra-Soto, Luis A; Gallois, Nicolas; Schouten, Stefan; Stein, Lisa Y; Prosser, James I; Nicol, Graeme W

2016-05-01

Ammonia oxidation is the first and rate-limiting step in nitrification and is dominated by two distinct groups of microorganisms in soil: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). AOA are often more abundant than AOB and dominate activity in acid soils. The mechanism of ammonia oxidation under acidic conditions has been a long-standing paradox. While high rates of ammonia oxidation are frequently measured in acid soils, cultivated ammonia oxidizers grew only at near-neutral pH when grown in standard laboratory culture. Although a number of mechanisms have been demonstrated to enable neutrophilic AOB growth at low pH in the laboratory, these have not been demonstrated in soil, and the recent cultivation of the obligately acidophilic ammonia oxidizer "Candidatus Nitrosotalea devanaterra" provides a more parsimonious explanation for the observed high rates of activity. Analysis of the sequenced genome, transcriptional activity, and lipid content of "Ca Nitrosotalea devanaterra" reveals that previously proposed mechanisms used by AOB for growth at low pH are not essential for archaeal ammonia oxidation in acidic environments. Instead, the genome indicates that "Ca Nitrosotalea devanaterra" contains genes encoding both a predicted high-affinity substrate acquisition system and potential pH homeostasis mechanisms absent in neutrophilic AOA. Analysis of mRNA revealed that candidate genes encoding the proposed homeostasis mechanisms were all expressed during acidophilic growth, and lipid profiling by high-performance liquid chromatography-mass spectrometry (HPLC-MS) demonstrated that the membrane lipids of "Ca Nitrosotalea devanaterra" were not dominated by crenarchaeol, as found in neutrophilic AOA. This study for the first time describes a genome of an obligately acidophilic ammonia oxidizer and identifies potential mechanisms enabling this unique phenotype for future biochemical characterization. Copyright © 2016 Lehtovirta-Morley et al.

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

NASA Astrophysics Data System (ADS)

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 (< 5 m) to map field and sub-field level yields across villages in Bihar in the eastern IGP. Using these data, we assess the impacts of a new fertilizer spreader technology and identify whether

Identifying Potentially Hazardous Co-orbiting Material of Known NEOs Using Magnetic Signatures Produced in Destructive Collisions

NASA Astrophysics Data System (ADS)

Lai, Hairong; Russell, Christopher; Jia, Yingdong; Wei, Hanying; Connors, Martin

2015-04-01

It is estimated that over 99% of near-Earth objects (NEOs) with diameters of about tens of meters are undiscovered. However, simulations show that they result in the most damage per year. Many of these bodies, produced in non-destructive collisions with larger well-characterized NEOs, are co-orbiting with their parent objects. Thereafter, scattering will occur due to gravitational perturbations when the co-orbiters have close encounters to any planets. Such gravitational scattering may not affect the orbits of the parent body. Therefore "safe" NEOs which have negligible impact probability with the Earth may be accompanied by potentially hazardous co-orbiting material. Those co-orbitals do reveal their existence in collisions with meteoroids, which are numerous and can be as small as tens of centimeters in diameter. Clouds of fine dust/gas particles released in such collisions become charged after generation and interact coherently with the solar wind electromagnetically. The interplanetary magnetic field is then perturbed. The resultant structures have been called interplanetary field enhancements (IFEs). They are readily identified when they pass spacecraft equipped with magnetometers. Although the co-orbitals responsible for the IFEs were disrupted in collisions, they are valid samples of the remaining co-orbiting material. Therefore, we can use IFEs to identify the spatial and mass distribution of such co-orbitals. With statistical studies of IFE occurrence, we identified asteroid 2201 Oljato and asteroid 138175 to have such co-orbiting material. The mass of the co-orbitals can be inferred by combining the results from observations and MHD simulations. Multi-spacecraft simultaneous observations measure the dimensions of the magnetic perturbations and the forces lifting them away from the Sun, while multi-fluid simulations give the accelerations of the perturbations. In summary, our technique not only helps us to identify which NEOs are accompanied by hazardous

Comparative transcriptome analysis of shoot and root tissue of Bacopa monnieri identifies potential genes related to triterpenoid saponin biosynthesis.

PubMed

Jeena, Gajendra Singh; Fatima, Shahnoor; Tripathi, Pragya; Upadhyay, Swati; Shukla, Rakesh Kumar

2017-06-28

Bacopa monnieri commonly known as Brahmi is utilized in Ayurveda to improve memory and many other human health benefits. Bacosides enriched standardized extract of Bacopa monnieri is being marketed as a memory enhancing agent. In spite of its well known pharmacological properties it is not much studied in terms of transcripts involved in biosynthetic pathway and its regulation that controls the secondary metabolic pathway in this plant. The aim of this study was to identify the potential transcripts and provide a framework of identified transcripts involved in bacosides production through transcriptome assembly. We performed comparative transcriptome analysis of shoot and root tissue of Bacopa monnieri in two independent biological replicate and obtained 22.48 million and 22.0 million high quality processed reads in shoot and root respectively. After de novo assembly and quantitative assessment total 26,412 genes got annotated in root and 18,500 genes annotated in shoot sample. Quality of raw reads was determined by using SeqQC-V2.2. Assembled sequences were annotated using BLASTX against public database such as NR or UniProt. Searching against the KEGG pathway database indicated that 37,918 unigenes from root and 35,130 unigenes from shoot were mapped to 133 KEGG pathways. Based on the DGE data we found that most of the transcript related to CYP450s and UDP-glucosyltransferases were specifically upregulated in shoot tissue as compared to root tissue. Finally, we have selected 43 transcripts related to secondary metabolism including transcription factor families which are differentially expressed in shoot and root tissues were validated by qRT-PCR and their expression level were monitored after MeJA treatment and wounding for 1, 3 and 5 h. This study not only represents the first de novo transcriptome analysis of Bacopa monnieri but also provides information about the identification, expression and differential tissues specific distribution of transcripts related

Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coteron, Jose M.; Marco, Maria; Esquivias, Jorge

2012-02-27

Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model,more » can be synthesized by a simple route, and rodent pharmacokinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.« less

Potential High-Temperature Shape-Memory Alloys Identified in the Ti(Ni,Pt) System

NASA Technical Reports Server (NTRS)

Noebe, Ronald D.; Biles, Tiffany A.; Garg, Anita; Nathal, Michael V.

2004-01-01

"Shape memory" is a unique property of certain alloys that, when deformed (within certain strain limits) at low temperatures, will remember and recover to their original predeformed shape upon heating. It occurs when an alloy is deformed in the low-temperature martensitic phase and is then heated above its transformation temperature back to an austenitic state. As the material passes through this solid-state phase transformation on heating, it also recovers its original shape. This behavior is widely exploited, near room temperature, in commercially available NiTi alloys for connectors, couplings, valves, actuators, stents, and other medical and dental devices. In addition, there are limitless applications in the aerospace, automotive, chemical processing, and many other industries for materials that exhibit this type of shape-memory behavior at higher temperatures. But for high temperatures, there are currently no commercial shape-memory alloys. Although there are significant challenges to the development of high-temperature shape-memory alloys, at the NASA Glenn Research Center we have identified a series of alloy compositions in the Ti-Ni-Pt system that show great promise as potential high-temperature shape-memory materials.

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

PubMed

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.

Identifying Important Atlantic Areas for the conservation of Balearic shearwaters: Spatial overlap with conservation areas

NASA Astrophysics Data System (ADS)

Pérez-Roda, Amparo; Delord, Karine; Boué, Amélie; Arcos, José Manuel; García, David; Micol, Thierry; Weimerskirch, Henri; Pinaud, David; Louzao, Maite

2017-07-01

Marine protected areas (MPAs) are considered one of the main tools in both fisheries and conservation management to protect threatened species and their habitats around the globe. However, MPAs are underrepresented in marine environments compared to terrestrial environments. Within this context, we studied the Atlantic non-breeding distribution of the southern population of Balearic shearwaters (Puffinus mauretanicus) breeding in Eivissa during the 2011-2012 period based on global location sensing (GLS) devices. Our objectives were (1) to identify overall Important Atlantic Areas (IAAs) from a southern population, (2) to describe spatio-temporal patterns of oceanographic habitat use, and (3) to assess whether existing conservation areas (Natura 2000 sites and marine Important Bird Areas (IBAs)) cover the main IAAs of Balearic shearwaters. Our results highlighted that the Atlantic staging (from June to October in 2011) dynamic of the southern population was driven by individual segregation at both spatial and temporal scales. Individuals ranged in the North-East Atlantic over four main IAAs (Bay of Biscay: BoB, Western Iberian shelf: WIS, Gulf of Cadiz: GoC, West of Morocco: WoM). While most individuals spent more time on the WIS or in the GoC, a small number of birds visited IAAs at the extremes of their Atlantic distribution range (i.e., BoB and WoM). The chronology of the arrivals to the IAAs showed a latitudinal gradient with northern areas reached earlier during the Atlantic staging. The IAAs coincided with the most productive areas (higher chlorophyll a values) in the NE Atlantic between July and October. The spatial overlap between IAAs and conservation areas was higher for Natura 2000 sites than marine IBAs (areas with and without legal protection, respectively). Concerning the use of these areas, a slightly higher proportion of estimated positions fell within marine IBAs compared to designated Natura 2000 sites, with Spanish and Portuguese conservation

New species, hyper-diversity and potential importance of Calonectria spp. from Eucalyptus in South China

PubMed Central

Lombard, L.; Chen, S.F.; Mou, X.; Zhou, X.D.; Crous, P.W.; Wingfield, M.J.

2015-01-01

Plantation forestry is expanding rapidly in China to meet an increasing demand for wood and pulp products globally. Fungal pathogens including species of Calonectria represent a serious threat to the growth and sustainability of this industry. Surveys were conducted in the Guangdong, Guangxi and Hainan Provinces of South China, where Eucalyptus trees in plantations or cuttings in nurseries displayed symptoms of leaf blight. Isolations from symptomatic leaves and soils collected close to infected trees resulted in a large collection of Calonectria isolates. These isolates were identified using the Consolidated Species Concept, employing morphological characters and DNA sequence comparisons for the β-tubulin, calmodulin, histone H3 and translation elongation factor 1-alpha gene regions. Twenty-one Calonectria species were identified of which 18 represented novel taxa. Of these, 12 novel taxa belonged to Sphaero-Naviculate Group and the remaining six to the Prolate Group. Southeast Asia appears to represent a centre of biodiversity for the Sphaero-Naviculate Group and this fact could be one of the important constraints to Eucalyptus forestry in China. The remarkable diversity of Calonectria species in a relatively small area of China and associated with a single tree species is surprising. PMID:26955194

Identifying high risk medications causing potential drug-drug interactions in outpatients: A prescription database study based on an online surveillance system.

PubMed

Toivo, T M; Mikkola, J A V; Laine, K; Airaksinen, M

2016-01-01

Drug-drug interactions (DDIs) are a significant cause for adverse drug events (ADEs). DDIs are often predictable and preventable, but their prevention and management require systematic service development. Most DDI studies focus on interaction rates in hospitalized patients. Less is known of DDIs in outpatients, particularly how community pharmacists could contribute to DDI management by applying their surveillance systems for identifying high-risk medications. The study was related to the implementation of the first online DDI surveillance system in Finnish community pharmacies. The goal was to demonstrate how community pharmacies can utilize their prospective surveillance system 1) for identifying high risk medications causing potential DDIs in outpatients, 2) for collaborative service development with local physicians, and 3) for academic risk management research purposes. All DDI alerts given by the online surveillance system were collected during a one-month period in 16 out of 17 University Pharmacy outlets in Finland, covering approximately 10% of the national outpatient prescription volume. The surveillance system was based on the FASS database, which categorizes DDIs into four classes (A-D) according to their clinical significance. Potential drug-drug DDIs were analyzed for 276,891 dispensed community pharmacy prescriptions. Potential DDIs were associated with 10.8%, or 31,110 of these prescriptions. Clinically significant interaction alerts categorized as FASS classes D (most severe, should be avoided) and C (clinically significant but controllable) were associated with 0.5% and 7.0% of the prescriptions, respectively. Methotrexate and warfarin had the highest risk of causing potentially serious (class D) interactions. These interaction alerts were most frequently between methotrexate and NSAIDs and warfarin and NSAIDs. In general, NSAIDs were the most commonly interacting drugs in this study. This study demonstrates that community pharmacies can actively

Identifying airborne fungi in Seoul, Korea using metagenomics.

PubMed

Oh, Seung-Yoon; Fong, Jonathan J; Park, Myung Soo; Chang, Limseok; Lim, Young Woon

2014-06-01

Fungal spores are widespread and common in the atmosphere. In this study, we use a metagenomic approach to study the fungal diversity in six total air samples collected from April to May 2012 in Seoul, Korea. This springtime period is important in Korea because of the peak in fungal spore concentration and Asian dust storms, although the year of this study (2012) was unique in that were no major Asian dust events. Clustering sequences for operational taxonomic unit (OTU) identification recovered 1,266 unique OTUs in the combined dataset, with between 223᾿96 OTUs present in individual samples. OTUs from three fungal phyla were identified. For Ascomycota, Davidiella (anamorph: Cladosporium) was the most common genus in all samples, often accounting for more than 50% of all sequences in a sample. Other common Ascomycota genera identified were Alternaria, Didymella, Khuskia, Geosmitha, Penicillium, and Aspergillus. While several Basidiomycota genera were observed, Chytridiomycota OTUs were only present in one sample. Consistency was observed within sampling days, but there was a large shift in species composition from Ascomycota dominant to Basidiomycota dominant in the middle of the sampling period. This marked change may have been caused by meteorological events. A potential set of 40 allergy-inducing genera were identified, accounting for a large proportion of the diversity present (22.5᾿7.2%). Our study identifies high fungal diversity and potentially high levels of fungal allergens in springtime air of Korea, and provides a good baseline for future comparisons with Asian dust storms.

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

PubMed Central

Kuusanmäki, Heikki; Dufva, Olli; Parri, Elina; van Adrichem, Arjan J.; Rajala, Hanna; Majumder, Muntasir M.; Yadav, Bhagwan; Parsons, Alun; Chan, Wing C.; Wennerberg, Krister; Mustjoki, Satu; Heckman, Caroline A.

2017-01-01

Constitutive JAK/STAT3 signaling contributes to disease progression in many lymphoproliferative disorders. Recent genetic analyses have revealed gain-of-function STAT3 mutations in lymphoid cancers leading to hyperactivation of STAT3, which may represent a potential therapeutic target. Using a functional reporter assay, we screened 306 compounds with selective activity against various target molecules to identify drugs capable of inhibiting the cellular activity of STAT3. Top hits were further validated with additional models including STAT3-mutated natural killer (NK)-cell leukemia/lymphoma cell lines and primary large granular lymphocytic (LGL) leukemia cells to assess their ability to inhibit STAT3 phosphorylation and STAT3 dependent cell viability. We identified JAK, mTOR, Hsp90 and CDK inhibitors as potent inhibitors of both WT and mutant STAT3 activity. The Hsp90 inhibitor luminespib was highly effective at reducing the viability of mutant STAT3 NK cell lines and LGL leukemia patient samples. Luminespib decreased the phosphorylation of mutant STAT3 at Y705, whereas JAK1/JAK2 inhibitor ruxolitinib had reduced efficacy on mutant STAT3 phosphorylation. Additionally, combinations involving Hsp90, JAK and mTOR inhibitors were more effective at reducing cell viability than single agents. Our findings show alternative approaches to inhibit STAT3 activity and suggest Hsp90 as a therapeutic target in lymphoproliferative disorders with constitutively active STAT3. PMID:29228628

Genome-wide screen identifies a novel prognostic signature for breast cancer survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Xuan Y.; Lee, Matthew J.; Zhu, Jeffrey

Large genomic datasets in combination with clinical data can be used as an unbiased tool to identify genes important in patient survival and discover potential therapeutic targets. We used a genome-wide screen to identify 587 genes significantly and robustly deregulated across four independent breast cancer (BC) datasets compared to normal breast tissue. Gene expression of 381 genes was significantly associated with relapse-free survival (RFS) in BC patients. We used a gene co-expression network approach to visualize the genetic architecture in normal breast and BCs. In normal breast tissue, co-expression cliques were identified enriched for cell cycle, gene transcription, cell adhesion,more » cytoskeletal organization and metabolism. In contrast, in BC, only two major co-expression cliques were identified enriched for cell cycle-related processes or blood vessel development, cell adhesion and mammary gland development processes. Interestingly, gene expression levels of 7 genes were found to be negatively correlated with many cell cycle related genes, highlighting these genes as potential tumor suppressors and novel therapeutic targets. A forward-conditional Cox regression analysis was used to identify a 12-gene signature associated with RFS. A prognostic scoring system was created based on the 12-gene signature. This scoring system robustly predicted BC patient RFS in 60 sampling test sets and was further validated in TCGA and METABRIC BC data. Our integrated study identified a 12-gene prognostic signature that could guide adjuvant therapy for BC patients and includes novel potential molecular targets for therapy.« less

Genome-wide screen identifies a novel prognostic signature for breast cancer survival

DOE PAGES

Mao, Xuan Y.; Lee, Matthew J.; Zhu, Jeffrey; ...

2017-01-21

Large genomic datasets in combination with clinical data can be used as an unbiased tool to identify genes important in patient survival and discover potential therapeutic targets. We used a genome-wide screen to identify 587 genes significantly and robustly deregulated across four independent breast cancer (BC) datasets compared to normal breast tissue. Gene expression of 381 genes was significantly associated with relapse-free survival (RFS) in BC patients. We used a gene co-expression network approach to visualize the genetic architecture in normal breast and BCs. In normal breast tissue, co-expression cliques were identified enriched for cell cycle, gene transcription, cell adhesion,more » cytoskeletal organization and metabolism. In contrast, in BC, only two major co-expression cliques were identified enriched for cell cycle-related processes or blood vessel development, cell adhesion and mammary gland development processes. Interestingly, gene expression levels of 7 genes were found to be negatively correlated with many cell cycle related genes, highlighting these genes as potential tumor suppressors and novel therapeutic targets. A forward-conditional Cox regression analysis was used to identify a 12-gene signature associated with RFS. A prognostic scoring system was created based on the 12-gene signature. This scoring system robustly predicted BC patient RFS in 60 sampling test sets and was further validated in TCGA and METABRIC BC data. Our integrated study identified a 12-gene prognostic signature that could guide adjuvant therapy for BC patients and includes novel potential molecular targets for therapy.« less

Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth.

PubMed

D'Silva, Arlene M; Hyett, Jon A; Coorssen, Jens R

2018-04-30

Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current diagnostics and interventions have not reduced the rate of this serious healthcare burden. This study characterizes differential protein profiles and post-translational modifications (PTMs) in first trimester maternal serum using a refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to directly compare subsequent term and preterm labour events and identify marked protein differences. 30 proteoforms were found to be significantly increased or decreased in the sPTB group including 9 phosphoproteins and 11 glycoproteins. Changes occurred in proteins associated with immune and defence responses. We identified protein species that are associated with several clinically relevant biological processes, including interrelated biological networks linked to regulation of the complement cascade and coagulation pathways, immune modulation, metabolic processes and cell signalling. The finding of altered proteoforms in maternal serum from pregnancies that delivered preterm suggests these as potential early biomarkers of sPTB and also possible mediators of the disorder. Identifying changes in protein profiles is critical in the study of cell biology, and disease treatment and prevention. Identifying consistent changes in the maternal serum proteome during early pregnancy, including specific protein PTMs (e.g. phosphorylation, glycosylation), is likely to provide better opportunities for prediction, intervention and prevention of preterm birth. This is the first study to examine first trimester maternal serum using a highly refined top-down proteomic analytical approach based on high resolution 2DE coupled with mass spectrometry to directly compare preterm (<37 weeks) and preterm (≥37 weeks) events and identify select protein differences between these conditions. As such, the data present a promising avenue for translation of biomarker discovery to a

Field potential soil variability index to identify precision agriculture opportunity

USDA-ARS?s Scientific Manuscript database

Precision agriculture (PA) technologies used for identifying and managing within-field variability are not widely used despite decades of advancement. Technological innovations in agronomic tools, such as canopy reflectance or electrical conductivity sensors, have created opportunities to achieve a ...

Bacterial biofilms of importance to medicine and bioterrorism: proteomic techniques to identify novel vaccine components and drug targets.

PubMed

Hassett, Daniel J; Limbach, Patrick A; Hennigan, Robert F; Klose, Karl E; Hancock, Robert E W; Platt, Mark D; Hunt, Donald F

2003-12-01

Biofilms are highly ordered microbial communities enmeshed in a carefully sculpted matrix designed for survival of organisms either in multi- or mono-genus/species in a specific microniche. In human disease, biofilm infections are some of the most recalcitrant to treat. Even with rigorous antibiotic regimens, some biofilms, such as those within the thick airway mucus of cystic fibrosis (CF) patients, persist throughout the course of the disease process. In this editorial, discussion will cover the utility of using advanced proteomic techniques to help identify potential weaknesses in the already impressive defensive armamentarium of biofilm bacteria. Two biofilm systems will be discussed herein, one of which is that of Pseudomonas aeruginosa biofilms within CF airway biofilms. The other is referred to as persistent 'bioterrorist agent biofilms' in which Francisella tularensis can grow on surfaces where environmental amoeba can phagocytose them, allowing for growth of F. tularensis within the amoebae.

The Effect of a Human Potential Lab Experience on Perceived Importance of Goals and Awareness of Strengths in Non-Traditional Aged Undergraduates

ERIC Educational Resources Information Center

Pickens, Bryon C.

2013-01-01

The purpose of this study was to examine the effect of a positively oriented group experience (human potential lab) on the awareness of personal strengths and perceived importance of goal setting in non-traditional aged undergraduates. The research questions that were posed were: 1) Does participation in the human potential lab experience increase…

Critical research needs for identifying future changes in Gulf coral reef ecosystems.

PubMed

Feary, David A; Burt, John A; Bauman, Andrew G; Al Hazeem, Shaker; Abdel-Moati, Mohamed A; Al-Khalifa, Khalifa A; Anderson, Donald M; Amos, Carl; Baker, Andrew; Bartholomew, Aaron; Bento, Rita; Cavalcante, Geórgenes H; Chen, Chaolun Allen; Coles, Steve L; Dab, Koosha; Fowler, Ashley M; George, David; Grandcourt, Edwin; Hill, Ross; John, David M; Jones, David A; Keshavmurthy, Shashank; Mahmoud, Huda; Moradi Och Tapeh, Mahdi; Mostafavi, Pargol Ghavam; Naser, Humood; Pichon, Michel; Purkis, Sam; Riegl, Bernhard; Samimi-Namin, Kaveh; Sheppard, Charles; Vajed Samiei, Jahangir; Voolstra, Christian R; Wiedenmann, Joerg

2013-07-30

Expert opinion was assessed to identify current knowledge gaps in determining future changes in Arabian/Persian Gulf (thereafter 'Gulf') coral reefs. Thirty-one participants submitted 71 research questions that were peer-assessed in terms of scientific importance (i.e., filled a knowledge gap and was a research priority) and efficiency in resource use (i.e., was highly feasible and ecologically broad). Ten research questions, in six major research areas, were highly important for both understanding Gulf coral reef ecosystems and also an efficient use of limited research resources. These questions mirrored global evaluations of the importance of understanding and evaluating biodiversity, determining the potential impacts of climate change, the role of anthropogenic impacts in structuring coral reef communities, and economically evaluating coral reef communities. These questions provide guidance for future research on coral reef ecosystems within the Gulf, and enhance the potential for assessment and management of future changes in this globally significant region. Copyright © 2013 Elsevier Ltd. All rights reserved.

Critical research needs for identifying future changes in Gulf coral reef ecosystems

PubMed Central

Feary, David A.; Burt, John A.; Bauman, Andrew G.; Al Hazeem, Shaker; Abdel-Moati, Mohamed A.; Al-Khalifa, Khalifa A.; Anderson, Donald M.; Amos, Carl; Baker, Andrew; Bartholomew, Aaron; Bento, Rita; Cavalcante, Geórgenes H.; Chen, Chaolun Allen; Coles, Steve L.; Dab, Koosha; Fowler, Ashley M.; George, David; Grandcourt, Edwin; Hill, Ross; John, David M.; Jones, David A.; Keshavmurthy, Shashank; Mahmoud, Huda; Moradi Och Tapeh, Mahdi; Mostafavi, Pargol Ghavam; Naser, Humood; Pichon, Michel; Purkis, Sam; Riegl, Bernhard; Samimi-Namin, Kaveh; Sheppard, Charles; Vajed Samiei, Jahangir; Voolstra, Christian R.; Wiedenmann, Joerg

2014-01-01

Expert opinion was assessed to identify current knowledge gaps in determining future changes in Arabian/ Persian Gulf (thereafter ‘Gulf’) coral reefs. Thirty-one participants submitted 71 research questions that were peer-assessed in terms of scientific importance (i.e., filled a knowledge gap and was a research priority) and efficiency in resource use (i.e., was highly feasible and ecologically broad). Ten research questions, in six major research areas, were highly important for both understanding Gulf coral reef ecosystems and also an efficient use of limited research resources. These questions mirrored global evaluations of the importance of understanding and evaluating biodiversity, determining the potential impacts of climate change, the role of anthropogenic impacts in structuring coral reef communities, and economically evaluating coral reef communities. These questions provide guidance for future research on coral reef ecosystems within the Gulf, and enhance the potential for assessment and management of future changes in this globally significant region. PMID:23643407

Identifying Potential Markets for Behind-the-Meter Battery Energy Storage:

Science.gov Websites

interval (usually 15 minutes) during a billing period. In many cases, these demand charges can account for therefore potential business cases for energy storage-were found in states not typically known for having

Somatic mutations in histiocytic sarcoma identified by next generation sequencing.

PubMed

Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Hornick, Jason L; Woda, Bruce; Yu, Hongbo

2016-08-01

Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.

The importance of accurate interaction potentials in the melting of argon nanoclusters

NASA Astrophysics Data System (ADS)

Pahl, E.; Calvo, F.; Schwerdtfeger, P.

The melting temperatures of argon clusters ArN (N = 13, 55, 147, 309, 561, and 923) and of bulk argon have been obtained from exchange Monte Carlo simulations and are compared using different two-body interaction potentials, namely the standard Lennard-Jones (LJ), Aziz and extended Lennard-Jones (ELJ) potentials. The latter potential has many advantages: while maintaining the computational efficiency of the commonly used LJ potential, it is as accurate as the Aziz potential but the computer time scales more favorably with increasing cluster size. By applying the ELJ form and extrapolating the cluster data to the infinite system, we are able to extract the melting point of argon already in good agreement with experimental measurements. By considering the additional Axilrod-Teller three-body contribution as well, we calculate a melting temperature of T meltELJ = 84.7 K compared to the experimental value of T meltexp = 83.85 K, whereas the LJ potential underestimates the melting point by more than 7 K. Thus melting temperatures within 1 K accuracy are now feasible.

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

PubMed Central

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 < 0.05]. More than 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP. Conclusions: Our multiplexed qHTS approach allowed us to generate a robust and reliable data set to evaluate the ability of thousands of drugs and environmental compounds to decrease MMP. The use of structure-based clustering analysis allowed us to identify molecular features that are likely responsible for the observed activity. Citation: Attene-Ramos MS, Huang R, Michael S, Witt KL, Richard A, Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox

Identifying Indices of Happiness and Unhappiness Among Adults With Autism: Potential Targets for Behavioral Assessment and Intervention

PubMed Central

Parsons, Marsha B; Bentley, Erik; Inman, Amy; Lattimore, L. Perry

2012-01-01

Research is increasingly demonstrating the importance of monitoring indices of happiness as part of behavioral programs for individuals who have severe intellectual disabilities. We evaluated a practitioner-oriented process for identifying and validating individualized indices of this private event among three adults with autism who were nonvocal or minimally vocal. Caregiver surveys were administered to obtain agreement regarding behavior displayed when the individuals were happy and unhappy, as well as situations in which they were likely to experience happiness and unhappiness. Observations corroborated caregiver opinion in that participants displayed more happiness indices in situations reported to be accompanied by happiness, and for the most part, more unhappiness indices in reported unhappiness situations. Subsequent choices by each participant supported the validity of the individualized indices. Results are discussed regarding how identifying happiness indices can be a useful component of behavioral applications, as well as guidelines and cautions regarding use of the indices in routine practice. PMID:23326627

Distributed design approach in persistent identifiers systems

NASA Astrophysics Data System (ADS)

Golodoniuc, Pavel; Car, Nicholas; Klump, Jens

2017-04-01

The need to identify both digital and physical objects is ubiquitous in our society. Past and present persistent identifier (PID) systems, of which there is a great variety in terms of technical and social implementations, have evolved with the advent of the Internet, which has allowed for globally unique and globally resolvable identifiers. PID systems have catered for identifier uniqueness, integrity, persistence, and trustworthiness, regardless of the identifier's application domain, the scope of which has expanded significantly in the past two decades. Since many PID systems have been largely conceived and developed by small communities, or even a single organisation, they have faced challenges in gaining widespread adoption and, most importantly, the ability to survive change of technology. This has left a legacy of identifiers that still exist and are being used but which have lost their resolution service. We believe that one of the causes of once successful PID systems fading is their reliance on a centralised technical infrastructure or a governing authority. Golodoniuc et al. (2016) proposed an approach to the development of PID systems that combines the use of (a) the Handle system, as a distributed system for the registration and first-degree resolution of persistent identifiers, and (b) the PID Service (Golodoniuc et al., 2015), to enable fine-grained resolution to different information object representations. The proposed approach solved the problem of guaranteed first-degree resolution of identifiers, but left fine-grained resolution and information delivery under the control of a single authoritative source, posing risk to the long-term availability of information resources. Herein, we develop these approaches further and explore the potential of large-scale decentralisation at all levels: (i) persistent identifiers and information resources registration; (ii) identifier resolution; and (iii) data delivery. To achieve large-scale decentralisation

Novel Approach to Identify Potential Bioactive Plant Metabolites: Pharmacological and Metabolomics Analyses of Ethanol and Hot Water Extracts of Several Canadian Medicinal Plants of the Cree of Eeyou Istchee.

PubMed

Shang, Nan; Saleem, Ammar; Musallam, Lina; Walshe-Roussel, Brendan; Badawi, Alaa; Cuerrier, Alain; Arnason, John T; Haddad, Pierre S

2015-01-01

We evaluated and compared the antidiabetic potential and molecular mechanisms of 17 Cree plants' ethanol extracts (EE) and hot water extracts (HWE) on glucose homeostasis in vitro and used metabolomics to seek links with the content of specific phytochemicals. Several EE of medical plants stimulated muscle glucose uptake and inhibited hepatic G6Pase activity. Some HWE partially or completely lost these antidiabetic activities in comparison to EE. Only R. groenlandicum retained similar potential between EE and HWE in both assays. In C2C12 muscle cells, EE of R. groenlandicum, A. incana and S. purpurea stimulated glucose uptake by activating AMP-activated protein kinase (AMPK) pathway and increasing glucose transporter type 4 (GLUT4) expression. In comparison to EE, HWE of R. groenlandicum exhibited similar activities; HWE of A. incana completely lost its effect on all parameters; interestingly, HWE of S. purpurea activated insulin pathway instead of AMPK pathway to increase glucose uptake. In the liver, for a subset of 5 plants, HWE and EE activated AMPK pathway whereas the EE and HWE of S. purpurea and K. angustifolia also activated insulin pathways. Quercetin-3-O-galactoside and quercetin 3-O-α-L-arabinopyranoside, were successfully identified by discriminant analysis as biomarkers of HWE plant extracts that stimulate glucose uptake in vitro. More importantly, the latter compound was not identified by previous bioassay-guided fractionation.

A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

PubMed

Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

2015-11-24

Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

Interspecific variation in potential importance of planktivorous damselfishes as predators of Acanthaster sp. eggs

NASA Astrophysics Data System (ADS)

Cowan, Zara-Louise; Ling, Scott D.; Dworjanyn, Symon A.; Caballes, Ciemon F.; Pratchett, Morgan S.

2017-06-01

Coral-eating crown-of-thorns starfish ( Acanthaster sp.) often exhibit dramatic population outbreaks, suggesting that their local abundance may be relatively unchecked by predators. This may be due to high concentrations of anti-predator chemicals (saponins and plancitoxins), but the effectiveness of chemical deterrents in protecting Acanthaster sp., especially spawned eggs, from predation remains controversial. We show that planktivorous damselfishes will readily consume food pellets with low proportions (≤80%) of eggs of crown-of-thorns starfish. However, all fishes exhibited increasing rejection of food pellets with higher proportions of starfish eggs, suggesting that chemicals in eggs of crown-of-thorns starfish do deter potential predators. Interestingly, palatability thresholds varied greatly among the nine species of planktivorous fish tested. Most notably, Amblyglyphidodon curacao consumed food pellets comprising 100% starfish eggs 1.5 times more than any other fish species, and appeared largely insensitive to increases in the concentration of starfish eggs. After standardising for size, smaller fish species consumed a disproportionate amount of pellets comprising high proportions of starfish eggs, indicating that abundant small-bodied fishes could be particularly important in regulating larval abundance and settlement success of crown-of-thorns starfish. Collectively, this study shows that reef fishes vary in their tolerance to anti-predator chemicals in crown-of-thorns starfish and may represent important predators on early life-history stages.

Using individualized predictive disease modeling to identify patients with the potential to benefit from a disease management program for diabetes mellitus.

PubMed

Weber, Christian; Neeser, Kurt

2006-08-01

Diabetes is an increasing health problem, but efforts to handle this pandemic by disease management programs (DMP) have shown conflicting results. Our hypothesis is that, in addition to a program's content and setting, the choice of the right patients is crucial to a program's efficacy and effectiveness. We used individualized predictive disease modeling (IPDM) on a cohort of 918 patients with type 2 diabetes to identify those patients with the greatest potential to benefit from inclusion in a DMP. A portion of the patients (4.7%) did not have even a theoretical potential for an increase in life expectancy and would therefore be unlikely to benefit from a DMP. Approximately 16.1% had an increase in life expectancy of less than half a year. Stratification of the entire cohort by surrogate parameters like preventable 10-year costs or gain in life expectancy was much more effective than stratification by classical clinical parameters such as high HbA1c level. Preventable costs increased up to 50.6% (or 1,010 per patient (1 = US dollars 1.28), p < 0.01) and life expectancy increased up to 54.8% (or 2.3 years, p < 0.01). IPDM is a valuable strategy to identify those patients with the greatest potential to avoid diabetes-related complications and thus can improve the overall effectiveness and efficacy of DMPs for diabetes mellitus.

Peptide microarray profiling identifies phospholipase C gamma 1 (PLC-γ1) as a potential target for t(8;21) AML

PubMed Central

Mahmud, Hasan; Scherpen, Frank J.G.; de Boer, Tiny Meeuwsen; Lourens, Harm-Jan; Schoenherr, Caroline; Eder, Matthias; Scherr, Michaela; Guryev, Victor; De Bont, Eveline S.

2017-01-01

The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) which has a need for improved therapeutic strategies. We found PLC-γ1 as one of the highest phosphorylated peptides in t(8;21) AML samples compared to NBM or CN-AML in our previous peptide microarray. PLC-γ1 is known to play a role in cancer progression, however, the impact of PLC-γ1 in AML is currently unknown. Therefore, we aimed to study the functional role of PLC-γ1 by investigating the cellular growth, survival and its underlying mechanism in t(8;21) AML. In this study, PLC-γ1 expression was significantly higher in t(8;21) AML compared to other karyotypes. The PLC-γ1 protein expression was suppressed in AML1-ETO knock down cells indicating that it might induce kasumi-1 cell death. ShRNA-mediated PLC-γ1 knockdown in kasumi-1 cells significantly blocked cell growth, induced apoptosis and cell cycle arrest which was explained by the increased activation of apoptotic related and cell cycle regulatory protein expressions. Gene expression array analysis showed the up-regulation of apoptotic and DNA damage response genes together with the downregulation of cell growth, proliferation and differentiation genes in the PLC-γ1 suppressed kasumi-1 cells, consistent with the observed phenotypic effects. Importantly, PLC-γ1 suppressed kasumi-1 cells showed higher chemosensitivity to the chemotherapeutic drug treatments and lower cell proliferation upon hypoxic stress. Taken together, these in vitro finding strongly support an important role for PLC-γ1 in the survival of t(8;21) AML mimicking kasumi-1 cells and identify PLC-γ1 as a potential therapeutic target for t(8;21) AML treatment. PMID:28978037

Gene expression profiling to identify the toxicities and potentially relevant human disease outcomes associated with environmental heavy metal exposure.

PubMed

Korashy, Hesham M; Attafi, Ibraheem M; Famulski, Konrad S; Bakheet, Saleh A; Hafez, Mohammed M; Alsaad, Abdulaziz M S; Al-Ghadeer, Abdul Rahman M

2017-02-01

Heavy metals are the most commonly encountered toxic substances that increase susceptibility to various diseases after prolonged exposure. We have previously shown that healthy volunteers living near a mining area had significant contamination with heavy metals associated with significant changes in the expression of some detoxifying genes, xenobiotic metabolizing enzymes, and DNA repair genes. However, alterations of most of the molecular target genes associated with diseases are still unknown. Thus, the aims of this study were to (a) evaluate the gene expression profile and (b) identify the toxicities and potentially relevant human disease outcomes associated with long-term human exposure to environmental heavy metals in mining area using microarray analysis. For this purpose, 40 healthy male volunteers who were residents of a heavy metal-polluted area (Mahd Al-Dhahab city, Saudi Arabia) and 20 healthy male volunteers who were residents of a non-heavy metal-polluted area were included in the study. Total RNA was isolated from whole blood using PAXgene Blood RNA tubes and then reversed transcribed and hybridized to the gene array using the Affymetrix U219 GeneChip. Microarray analysis showed about 2129 genes were identified and differentially altered, among which a shared set of 425 genes was differentially expressed in the heavy metal-exposed groups. Ingenuity pathway analysis revealed that the most altered gene-regulated diseases in heavy metal-exposed groups included hematological and developmental disorders and mostly renal and urological diseases. Quantitative real-time polymerase chain reaction closely matched the microarray data for some genes tested. Importantly, changes in gene-related diseases were attributed to alterations in the genes encoded for protein synthesis. Renal and urological diseases were the diseases that were most frequently associated with the heavy metal-exposed group. Therefore, there is a need for further studies to validate these

Integrative biology approach identifies cytokine targeting strategies for psoriasis.

PubMed

Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

2014-02-12

Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

Identifying and Solving Lead Issues from Water Systems with Materials/Device Replacement in Schools and other Buildings

EPA Science Inventory

Identifying and assessing lead contamination and exposure potential in single-family residences is difficult enough, but doing the same kind of assessment and remediation in buildings, schools, and day care centers is even more challenging. It is of particular importance because ...

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

PubMed Central

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

Emory University: MEDICI (Mining Essentiality Data to Identify Critical Interactions) for Cancer Drug Target Discovery and Development | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at Emory University has developed a computational methodology to combine high-throughput knockdown data with known protein network topologies to infer the importance of protein-protein interactions (PPIs) for the survival of cancer cells.  Applying these data to the Achilles shRNA results, the CCLE cell line characterizations, and known and newly identified PPIs provides novel insights for potential new drug targets for cancer therapies and identifies important PPI hubs.

Combining Methods to Describe Important Marine Habitats for Top Predators: Application to Identify Biological Hotspots in Tropical Waters.

PubMed

Thiers, Laurie; Louzao, Maite; Ridoux, Vincent; Le Corre, Matthieu; Jaquemet, Sébastien; Weimerskirch, Henri

2014-01-01

In tropical waters resources are usually scarce and patchy, and predatory species generally show specific adaptations for foraging. Tropical seabirds often forage in association with sub-surface predators that create feeding opportunities by bringing prey close to the surface, and the birds often aggregate in large multispecific flocks. Here we hypothesize that frigatebirds, a tropical seabird adapted to foraging with low energetic costs, could be a good predictor of the distribution of their associated predatory species, including other seabirds (e.g. boobies, terns) and subsurface predators (e.g., dolphins, tunas). To test this hypothesis, we compared distribution patterns of marine predators in the Mozambique Channel based on a long-term dataset of both vessel- and aerial surveys, as well as tracking data of frigatebirds. By developing species distribution models (SDMs), we identified key marine areas for tropical predators in relation to contemporaneous oceanographic features to investigate multi-species spatial overlap areas and identify predator hotspots in the Mozambique Channel. SDMs reasonably matched observed patterns and both static (e.g. bathymetry) and dynamic (e.g. Chlorophyll a concentration and sea surface temperature) factors were important explaining predator distribution patterns. We found that the distribution of frigatebirds included the distributions of the associated species. The central part of the channel appeared to be the best habitat for the four groups of species considered in this study (frigatebirds, brown terns, boobies and sub-surface predators).

To identify or not to identify parathyroid glands during total thyroidectomy.

PubMed

Chang, Yuk Kwan; Lang, Brian H H

2017-12-01

Hypoparathyroidism is one of the most common complications after total thyroidectomy and may impose a significant burden to both the patient and clinician. The extent of thyroid resection, surgical techniques, concomitant central neck dissection, parathyroid gland (PG) autotransplantation and inadvertent parathyroidectomy have long been some of the risk factors for postoperative hypoparathyroidism. Although routine identification of PGs has traditionally been advocated by surgeons, recent evidence has suggested that perhaps identifying fewer number of in situ PGs during surgery (i.e., selective identification) may further lower the risk of hypoparathyroidism. One explanation is that visual identification may often lead to subtle damages to the nearby blood supply of the in situ PGs and that may increase the risk of hypoparathyroidism. However, it is worth highlighting the current literature supporting either approach (i.e., routine vs. selective) remains scarce and because of the significant differences in study design, inclusions, definitions and management protocol between studies, a pooled analysis on this important but controversial topic remains an impossible task. Furthermore, it is worth nothing that identification of PGs does not equal safe preservation, as some studies demonstrated that it is not the number of PGs identified, but the number of PG preserved in situ that matters. Therefore a non-invasive, objective and reliable way to localize PGs and assess their viability intra-operatively is warranted. In this aspect, modern technology such as the indocyanine green (ICG) as near-infrared fluorescent dye for real-time in situ PG perfusion monitoring may have a potential role in the future.

Using Nurse Ratings of Physician Communication in the ICU To Identify Potential Targets for Interventions To Improve End-of-Life Care.

PubMed

Ramos, Kathleen J; Downey, Lois; Nielsen, Elizabeth L; Treece, Patsy D; Shannon, Sarah E; Curtis, J Randall; Engelberg, Ruth A

2016-03-01

Communication among doctors, nurses, and families contributes to high-quality end-of-life care, but is difficult to improve. Our objective was to identify aspects of communication appropriate for interventions to improve quality of dying in the intensive care unit (ICU). This observational study used data from a cluster-randomized trial of an interdisciplinary intervention to improve end-of-life care at 15 Seattle/Tacoma area hospitals (2003-2008). Nurses completed surveys for patients dying in the ICU. We examined associations between nurse-assessed predictors (physician-nurse communication, physician-family communication) and nurse ratings of patients' quality of dying (nurse-QODD-1). Based on 1173 nurse surveys, four of six physician-nurse communication topics were positively associated with nurse-QODD-1: family questions, family dynamics, spiritual/religious issues, and cultural issues. Discussions between nurses and physicians about nurses' concerns for patients or families were negatively associated. All physician-family communication ratings, as assessed by nurses, were positively associated with nurse-QODD-1: answering family's questions, listening to family, asking about treatments patient would want, helping family decide patient's treatment wishes, and overall communication. Path analysis suggested overall physician-family communication and helping family incorporate patient's wishes were directly associated with nurse-QODD-1. Several topics of physician-nurse communication, as rated by nurses, were associated with higher nurse-rated quality of dying, whereas one topic, nurses' concerns for patient or family, was associated with poorer ratings. Higher nurse ratings of physician-family communication were uniformly associated with higher quality of dying, highlighting the importance of this communication. Physician support of family decision making was particularly important, suggesting a potential target for interventions to improve end-of-life care.

Identifying Corridors among Large Protected Areas in the United States.

PubMed

Belote, R Travis; Dietz, Matthew S; McRae, Brad H; Theobald, David M; McClure, Meredith L; Irwin, G Hugh; McKinley, Peter S; Gage, Josh A; Aplet, Gregory H

2016-01-01

Conservation scientists emphasize the importance of maintaining a connected network of protected areas to prevent ecosystems and populations from becoming isolated, reduce the risk of extinction, and ultimately sustain biodiversity. Keeping protected areas connected in a network is increasingly recognized as a conservation priority in the current era of rapid climate change. Models that identify suitable linkages between core areas have been used to prioritize potentially important corridors for maintaining functional connectivity. Here, we identify the most "natural" (i.e., least human-modified) corridors between large protected areas in the contiguous Unites States. We aggregated results from multiple connectivity models to develop a composite map of corridors reflecting agreement of models run under different assumptions about how human modification of land may influence connectivity. To identify which land units are most important for sustaining structural connectivity, we used the composite map of corridors to evaluate connectivity priorities in two ways: (1) among land units outside of our pool of large core protected areas and (2) among units administratively protected as Inventoried Roadless (IRAs) or Wilderness Study Areas (WSAs). Corridor values varied substantially among classes of "unprotected" non-core land units, and land units of high connectivity value and priority represent diverse ownerships and existing levels of protections. We provide a ranking of IRAs and WSAs that should be prioritized for additional protection to maintain minimal human modification. Our results provide a coarse-scale assessment of connectivity priorities for maintaining a connected network of protected areas.

Development of computational fluid dynamics--habitat suitability (CFD-HSI) models to identify potential passage--Challenge zones for migratory fishes in the Penobscot River

USGS Publications Warehouse

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.

The importance of scattering, surface potential, and vanguard counter-potential in terahertz emission from gallium arsenide

NASA Astrophysics Data System (ADS)

Cortie, D. L.; Lewis, R. A.

2012-06-01

It is well established that under excitation by short (<1 ps), above-band-gap optical pulses, semiconductor surfaces may emit terahertz-frequency electromagnetic radiation via photocarrier diffusion (the dominant mechanism in InAs) or photocarrier drift (dominant in GaAs). Our three-dimensional ensemble Monte Carlo simulations allow multiple physical parameters to vary over wide ranges and provide unique direct insight into the factors controlling terahertz emission. We find for GaAs (in contrast to InAs), scattering and the surface potential are key factors. We further delineate in GaAs (as in InAs) the role of a vanguard counter-potential. The effects of varying dielectric constant, band-gap, and effective mass are similar in both emitter types.

Identifying Potential Mechanisms Enabling Acidophily in the Ammonia-Oxidizing Archaeon “Candidatus Nitrosotalea devanaterra”

PubMed Central

Sayavedra-Soto, Luis A.; Gallois, Nicolas; Schouten, Stefan; Stein, Lisa Y.; Prosser, James I.; Nicol, Graeme W.

2016-01-01

Ammonia oxidation is the first and rate-limiting step in nitrification and is dominated by two distinct groups of microorganisms in soil: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). AOA are often more abundant than AOB and dominate activity in acid soils. The mechanism of ammonia oxidation under acidic conditions has been a long-standing paradox. While high rates of ammonia oxidation are frequently measured in acid soils, cultivated ammonia oxidizers grew only at near-neutral pH when grown in standard laboratory culture. Although a number of mechanisms have been demonstrated to enable neutrophilic AOB growth at low pH in the laboratory, these have not been demonstrated in soil, and the recent cultivation of the obligately acidophilic ammonia oxidizer “Candidatus Nitrosotalea devanaterra” provides a more parsimonious explanation for the observed high rates of activity. Analysis of the sequenced genome, transcriptional activity, and lipid content of “Ca. Nitrosotalea devanaterra” reveals that previously proposed mechanisms used by AOB for growth at low pH are not essential for archaeal ammonia oxidation in acidic environments. Instead, the genome indicates that “Ca. Nitrosotalea devanaterra” contains genes encoding both a predicted high-affinity substrate acquisition system and potential pH homeostasis mechanisms absent in neutrophilic AOA. Analysis of mRNA revealed that candidate genes encoding the proposed homeostasis mechanisms were all expressed during acidophilic growth, and lipid profiling by high-performance liquid chromatography–mass spectrometry (HPLC-MS) demonstrated that the membrane lipids of “Ca. Nitrosotalea devanaterra” were not dominated by crenarchaeol, as found in neutrophilic AOA. This study for the first time describes a genome of an obligately acidophilic ammonia oxidizer and identifies potential mechanisms enabling this unique phenotype for future biochemical characterization. PMID:26896134

Distribution of potential eye and tissue donors within an Australian teaching hospital.

PubMed

Dutch, Martin J; Denahy, Anthony F

2017-12-11

Eye and Tissue donation has the capacity to transform lives, yet the vast majority of potential in-hospital donors are not recognised. Studies which describe the relative importance of specific units or wards in determining the size of the donor pool are limited. The aim of this study was to map the distribution of potential Eye and Tissue donors within the study hospital. A 12-month retrospective analysis of all patient deaths at the study hospital was undertaken. The ability to donate corneal, heart valve, bone and skin tissue was investigated. Patients were classified as potential donors if they met specific age criteria and had an absence of contraindications based on electronic database search. There were 985 deaths during the study period. Deaths occurred under the care of 26 separate clinical units, and within 28 unique wards and treatment spaces. Four hundred and forty nine (45.6%) patients were identified as potential eye or tissue donors. The majority of potential donors occurred in ICU, Emergency and palliative care units. Of the subset of 328 deaths ≤ 70 years, the frequency of potential tissue donors was 55% (n = 181). ED and ICU had significantly higher frequencies of potential donor than other wards (86 and 77%, p < 0.01). The current study has identified the ED, ICU and PCUs are being important sites for potential Eye and Tissue Donors within our hospital. These will provide an important focus for future interventions to improve the rate of eye and tissue donation.

Potential economic impact of introduction and spread of the red imported fire ant, Solenopsis invicta, in Hawaii

USGS Publications Warehouse

Gutrich, J.J.; VanGelder, E.; Loope, L.

2007-01-01

Globally, many invasive alien species have caused extensive ecological and economic damage from either accidental or intentional introduction. The red imported fire ant, Solenopsis invicta, has created billions of dollars in costs annually, spreading as an invasive species across the southern United States. In 1998, the red imported fire ant spread into California creating a highly probable future introduction via shipped products to Hawaii. This paper presents the estimation of potential economic impacts of the red imported fire ant (RIFA) to the state of Hawaii. Evaluation of impacts focuses on the economic sectors of (1) households, (2) agriculture (cattle and crop production), (3) infrastructure (cemeteries, churches, cities, electrical, telephone, and cable services, highways, hospitals and schools), (4) recreation, tourism and business (hotels/resort areas, golf courses, commercial businesses and tourists), and (5) government expenditures (with minimal intervention). The full annual economic costs of the red imported fire ant to Hawaii are estimated (in US$ 2006) to be $211 million/year, comprised of $77 million in damages and expenditures and $134 million in foregone outdoor opportunities to households and tourists. The present value of the projected costs of RIFA over a 20-year period after introduction total $2.5 billion. RIFA invasions across the globe indicate that economic cost-effective action in Hawaii entails implementation of prevention, early detection and rapid response treatment programs for RIFA. ?? 2007 Elsevier Ltd. All rights reserved.

Identifying Chemical Groups for Biomonitoring

PubMed Central

Krowech, Gail; Hoover, Sara; Plummer, Laurel; Sandy, Martha; Zeise, Lauren; Solomon, Gina

2016-01-01

Summary: Regulatory agencies face daunting challenges identifying emerging chemical hazards because of the large number of chemicals in commerce and limited data on exposure and toxicology. Evaluating one chemical at a time is inefficient and can lead to replacement with uncharacterized chemicals or chemicals with structural features already linked to toxicity. The Office of Environmental Health Hazard Assessment (OEHHA) has developed a process for constructing and assessing chemical groups for potential biomonitoring in California. We screen for chemicals with significant exposure potential and propose possible chemical groups, based on structure and function. To support formal consideration of these groups by Biomonitoring California’s Scientific Guidance Panel, we conduct a detailed review of exposure and toxicity data and examine the likelihood of detection in biological samples. To date, 12 chemical groups have been constructed and added to the pool of chemicals that can be selected for Biomonitoring California studies, including p,p´-bisphenols, brominated and chlorinated organic compounds used as flame retardants, non-halogenated aromatic phosphates, and synthetic polycyclic musks. Evaluating chemical groups, rather than individual chemicals, is an efficient way to respond to shifts in chemical use and the emergence of new chemicals. This strategy can enable earlier identification of important chemicals for monitoring and intervention. PMID:27905275

The Near-Earth Object Human Space Flight Accessible Targets Study (NHATS) List of Near-Earth Asteroids: Identifying Potential Targets for Future Exploration

NASA Astrophysics Data System (ADS)

Abell, Paul; Barbee, B. W.; Mink, R. G.; Adamo, D. R.; Alberding, C. M.; Mazanek, D. D.; Johnson, L. N.; Yeomans, D. K.; Chodas, P. W.; Chamberlin, A. B.; Benner, L. A. M.; Drake, B. G.; Friedensen, V. P.

2012-10-01

Introduction: Much attention has recently been focused on human exploration of near-Earth asteroids (NEAs). Detailed planning for deep space exploration and identification of potential NEA targets for human space flight requires selecting objects from the growing list of known NEAs. NASA therefore initiated the Near-Earth Object Human Space Flight Accessible Target Study (NHATS), which uses dynamical trajectory performance constraints to identify potentially accessible NEAs. Accessibility Criteria: Future NASA human space flight capability is being defined while the Orion Multi-Purpose Crew Vehicle and Space Launch System are under development. Velocity change and mission duration are two of the most critical factors in any human spaceflight endeavor, so the most accessible NEAs tend to be those with orbits similar to Earth’s. To be classified as NHATS-compliant, a NEA must offer at least one round-trip trajectory solution satisfying purposely inclusive constraints, including total mission change in velocity ≤ 12 km/s, mission duration ≤ 450 days (with at least 8 days at the NEA), Earth departure between Jan 1, 2015 and Dec 31, 2040, Earth departure C3 ≤ 60 km2/s2, and Earth return atmospheric entry speed ≤ 12 km/s. Monitoring and Updates: The NHATS list of potentially accessible targets is continuously updated as NEAs are discovered and orbit solutions for known NEAs are improved. The current list of accessible NEAs identified as potentially viable for future human exploration under the NHATS criteria is available to the international community via a website maintained by NASA’s NEO Program Office (http://neo.jpl.nasa.gov/nhats/). This website also lists predicted optical and radar observing opportunities for each NHATS-compliant NEA to facilitate acquisition of follow-up observations. Conclusions: This list of NEAs will be useful for analyzing robotic mission opportunities, identifying optimal round trip human space flight trajectories, and

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

PubMed

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.

The Body of Knowledge & Content Framework. Identifying the Important Knowledge Required for Productive Performance of a Plastics Machine Operator. Blow Molding, Extrusion, Injection Molding, Thermoforming.

ERIC Educational Resources Information Center

Society of the Plastics Industry, Inc., Washington, DC.

Designed to guide training and curriculum development to prepare machine operators for the national certification exam, this publication identifies the important knowledge required for productive performance by a plastics machine operator. Introductory material discusses the rationale for a national standard, uses of the Body of Knowledge,…

Why is gas phase 2-nitrophenol photolysis a potentially important source of OH radicals in the polluted atmosphere?

NASA Astrophysics Data System (ADS)

Zhu, L.

2017-12-01

2-Nitrophenol is an important component of "brown carbon" in the atmosphere. The concentration of 2-nitrophenol is higher in polluted urban areas where there are increased emissions of aromatic hydrocarbons. To assess the air quality impacts of pollutant emissions, it is important to understand the oxidant formation potential of the emitted species. Photolysis is the dominant atmospheric removal process for 2-nitrophenol. Although photodissociation dynamics studies of 2-nitrophenol have reported OH formation at photolysis wavelengths of 266 nm, 355 nm, and over the 361-390 nm range, and HONO has been observed as a product from 2-nitrophenol photolysis in an environmental chamber, the lack of quantitative absorption cross section and product quantum yield information has prevented quantitative assessment of the extent of oxidant formation from the photolysis of 2-nitrophenol in the atmosphere. My group determined the gas phase absorption cross sections of 2-nitrophenol in the 295-400 nm region by using cavity ring-down spectroscopy. The OH, HONO, and NO2 formation channels following the gas phase photolysis of 2-nitrophenol at 308 and 351 nm were investigated. Direct NO2 formation was not observed. OH and HONO were direct products from the 2-nitrophenol photolysis, and their quantum yields were obtained. The sum of the OH and the HONO quantum yields was about unity at both photolysis wavelengths. The estimated photolysis rate constant of 2-nitrophenol was about twice that of NO2. I will discuss the importance of 2-nitrophenol gas phase photolysis as a potential source of OH and HONO in regions of high anthropogenic emissions.

Health Systems Science Curricula in Undergraduate Medical Education: Identifying and Defining a Potential Curricular Framework.

PubMed

Gonzalo, Jed D; Dekhtyar, Michael; Starr, Stephanie R; Borkan, Jeffrey; Brunett, Patrick; Fancher, Tonya; Green, Jennifer; Grethlein, Sara Jo; Lai, Cindy; Lawson, Luan; Monrad, Seetha; O'Sullivan, Patricia; Schwartz, Mark D; Skochelak, Susan

2017-01-01

The authors performed a review of 30 Accelerating Change in Medical Education full grant submissions and an analysis of the health systems science (HSS)-related curricula at the 11 grant recipient schools to develop a potential comprehensive HSS curricular framework with domains and subcategories. In phase 1, to identify domains, grant submissions were analyzed and coded using constant comparative analysis. In phase 2, a detailed review of all existing and planned syllabi and curriculum documents at the grantee schools was performed, and content in the core curricular domains was coded into subcategories. The lead investigators reviewed and discussed drafts of the categorization scheme, collapsed and combined domains and subcategories, and resolved disagreements via group discussion. Analysis yielded three types of domains: core, cross-cutting, and linking. Core domains included health care structures and processes; health care policy, economics, and management; clinical informatics and health information technology; population and public health; value-based care; and health system improvement. Cross-cutting domains included leadership and change agency; teamwork and interprofessional education; evidence-based medicine and practice; professionalism and ethics; and scholarship. One linking domain was identified: systems thinking. This broad framework aims to build on the traditional definition of systems-based practice and highlight the need for medical and other health professions schools to better align education programs with the anticipated needs of the systems in which students will practice. HSS will require a critical investigation into existing curricula to determine the most efficient methods for integration with the basic and clinical sciences.

Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

PubMed

Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

2012-01-01

Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site

A Target-Based Whole Cell Screen Approach To Identify Potential Inhibitors of Mycobacterium tuberculosis Signal Peptidase

PubMed Central

2016-01-01

The general secretion (Sec) pathway is a conserved essential pathway in bacteria and is the primary route of protein export across the cytoplasmic membrane. During protein export, the signal peptidase LepB catalyzes the cleavage of the signal peptide and subsequent release of mature proteins into the extracellular space. We developed a target-based whole cell assay to screen for potential inhibitors of LepB, the sole signal peptidase in Mycobacterium tuberculosis, using a strain engineered to underexpress LepB (LepB-UE). We screened 72,000 compounds against both the Lep-UE and wild-type (wt) strains. We identified the phenylhydrazone (PHY) series as having higher activity against the LepB-UE strain. We conducted a limited structure–activity relationship determination around a representative PHY compound with differential activity (MICs of 3.0 μM against the LepB-UE strain and 18 μM against the wt); several analogues were less potent against the LepB overexpressing strain. A number of chemical modifications around the hydrazone moiety resulted in improved potency. Inhibition of LepB activity was observed for a number of compounds in a biochemical assay using cell membrane fraction derived from M. tuberculosis. Compounds did not increase cell permeability, dissipate membrane potential, or inhibit an unrelated mycobacterial enzyme, suggesting a specific mode of action related to the LepB secretory mechanism. PMID:27642770

Identifying Potential Implications of Technologies on Military and Security Options

DTIC Science & Technology

2006-06-01

Technology Readiness Level (TRL) ratings. THE DISCUSSION Technology surprise occurs through the use of rapidly-emerging and disruptive technologies by...NATO RTB Systems Analysis and Studies Panel, Exploratory Team on the Impact of Disruptive Technologies The objectives of this task group (TG...Workshop on Emerging Disruptive Technologies and the Implications for Defence advanced the view that TTCP should examine the potential of emerging

Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination

PubMed Central

Brooks, Jill M.; Long, Heather M.; Tierney, Rose J.; Shannon-Lowe, Claire; Leese, Alison M.; Fitzpatrick, Martin; Taylor, Graham S.; Rickinson, Alan B.

2016-01-01

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. PMID:27096949

Using terrestrial ecosystem survey data to identify potential habitat for the Mexican spotted owl on National Forest System lands: a pilot study

Treesearch

Joseph L. Ganey; Mary Ann Benoit

2002-01-01

We assessed the usefulness of Terrestrial Ecosystem Survey (TES) data as a means of identifying habitat for the Mexican spotted owl (Strix occidentalis lucida) in three National Forests in Arizona. This spatial data set incorporates information on soils, vegetation, and climatic conditions in defining a set of ecological "map units" showing potential...

Feeling too hot or cold after breast cancer: Is it just a nuisance or a potentially important prognostic factor?

PubMed Central

KOKOLUS, KATHLEEN M.; HONG, CHI-CHEN; REPASKY, ELIZABETH A.

2010-01-01

There is widespread recognition among both patients and caregivers that breast cancer patients often experience debilitating deficiencies in their ability to achieve thermal comfort, feeling excessively hot or cold under circumstances when others are comfortable. However, this symptom receives little clinical or scientific attention beyond identification and testing of drugs that minimise menopausal-like symptoms. Could some of these symptoms represent an important prognostic signal? Could thermal discomfort be among other cytokine-driven sickness behaviour symptoms seen in many breast cancer patients? While the literature reveals a strong link between treatment for breast cancer and some menopausal vasomotor symptoms (e.g. hot flashes also known as “hot flushes”), there is little data on quantitative assessment of severity of different types of symptoms and their possible prognostic potential. However, recent, intriguing studies indicating a correlation between the presence of hot flashes and reduced development of breast cancer recurrence strongly suggests that more study on this topic is needed. In comparison to reports on the phenomenon of breast cancer-associated hot flashes, there is essentially no scientific study on the large number of women who report feeling excessively cold after breast cancer treatment. Since similar acquired thermal discomfort symptoms can occur in patients with cancers other than breast cancer, there may be as yet unidentified cancer – or treatment-driven factor related to temperature dysregulation. In general, there is surprisingly little information on the physiological relationship between body temperature regulation, vasomotor symptoms, and cancer growth and progression. The goal of this article is twofold: (1) to review the scientific literature egarding acquired deficits inthermoregulation among breast cancer survivors and (2) to propose some speculative ideas regarding the possible basis for thermal discomfort among some

Identifying obstacles and ranking common biological control research priorities for Europe to manage most economically important pests in arable, vegetable and perennial crops.

PubMed

Lamichhane, Jay Ram; Bischoff-Schaefer, Monika; Bluemel, Sylvia; Dachbrodt-Saaydeh, Silke; Dreux, Laure; Jansen, Jean-Pierre; Kiss, Jozsef; Köhl, Jürgen; Kudsk, Per; Malausa, Thibaut; Messéan, Antoine; Nicot, Philippe C; Ricci, Pierre; Thibierge, Jérôme; Villeneuve, François

2017-01-01

EU agriculture is currently in transition from conventional crop protection to integrated pest management (IPM). Because biocontrol is a key component of IPM, many European countries recently have intensified their national efforts on biocontrol research and innovation (R&I), although such initiatives are often fragmented. The operational outputs of national efforts would benefit from closer collaboration among stakeholders via transnationally coordinated approaches, as most economically important pests are similar across Europe. This paper proposes a common European framework on biocontrol R&I. It identifies generic R&I bottlenecks and needs as well as priorities for three crop types (arable, vegetable and perennial crops). The existing gap between the market offers of biocontrol solutions and the demand of growers, the lengthy and expensive registration process for biocontrol solutions and their varying effectiveness due to variable climatic conditions and site-specific factors across Europe are key obstacles hindering the development and adoption of biocontrol solutions in Europe. Considering arable, vegetable and perennial crops, a dozen common target pests are identified for each type of crop and ranked by order of importance at European level. Such a ranked list indicates numerous topics on which future joint transnational efforts would be justified. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Identifying and Solving Lead Issues from Water Systems with Materials/Device Replacement in Schools and other Buildings - slides

EPA Science Inventory

Identifying and assessing lead contamination and exposure potential in single-family residences is difficult enough, but doing the same kind of assessment and remediation in buildings, schools, and day care centers is even more challenging. It is of particular importance because ...

Canonical transient receptor potential channel 2 (TRPC2): old name-new games. Importance in regulating of rat thyroid cell physiology.

PubMed

Törnquist, Kid; Sukumaran, Pramod; Kemppainen, Kati; Löf, Christoffer; Viitanen, Tero

2014-11-01

In addition to the TSH-cyclic AMP signalling pathway, calcium signalling is of crucial importance in thyroid cells. Although the importance of calcium signalling has been thoroughly investigated for several decades, the nature of the calcium channels involved in signalling is unknown. In a recent series of investigations using the well-studied rat thyroid FRTL-5 cell line, we showed that these cells exclusively express the transient receptor potential canonical 2 (TRPC2) channel. Our results suggested that the TRPC2 channel is of significant importance in regulating thyroid cell function. These investigations were the first to show that thyroid cells express a member of the TRPC family of ion channels. In this review, we will describe the importance of the TRPC2 channel in regulating TSH receptor expression, thyroglobulin maturation, intracellular calcium and iodide homeostasis and that the channel also regulates thyroid cell proliferation.

Identifying research priorities for public health research to address health inequalities: use of Delphi-like survey methods.

PubMed

Turner, S; Ollerhead, E; Cook, A

2017-10-09

In the funding of health research and public health research it is vital that research questions posed are important and that funded research meets a research need or a gap in evidence. Many methods are used in the identification of research priorities, however, these can be resource intensive, costly and logistically challenging. Identifying such research priorities can be particularly challenging for complex public health problems as there is a need to consult a number of experts across disciplines and with a range of expertise. This study investigated the use of Delphi-like survey methods in identifying important research priorities relating to health inequalities and framing tractable research questions for topic areas identified. The study was conducted in two phases, both using Delphi-like survey methods. Firstly, public health professionals with an interest in health inequalities were asked to identify research priorities. Secondly academic researchers were asked to frame tractable research questions relating to the priorities identified. These research priorities identified using Delphi-like survey methods were subsequently compared to those identified using different methods. A total of 52 public health professionals and 21 academics across the United Kingdom agreed to take part. The response rates were high, from public health professionals across three survey rounds (69%, 50% and 40%) and from academics across one round (52%), indicating that participants were receptive to the method and motivated to respond. The themes identified as encompassing the most important research priorities were mental health, healthy environment and health behaviours. Within these themes, the topic areas that emerged most strongly included community interventions for prevention of mental health problems and the food and alcohol environment. Some responses received from academic researchers were (as requested) in the form of tractable research questions, whereas others

Challenges in Identifying Patients with Type 2 Diabetes for Quality-Improvement Interventions in Primary Care Settings and the Importance of Valid Disease Registries.

PubMed

Wozniak, Lisa; Soprovich, Allison; Rees, Sandra; Johnson, Steven T; Majumdar, Sumit R; Johnson, Jeffrey A

2015-10-01

Patient registries are considered an important foundation of chronic disease management, and diabetes patient registries are associated with better processes and outcomes of care. The purpose of this article is to describe the development and use of registries in the Alberta's Caring for Diabetes (ABCD) project to identify and reach target populations for quality-improvement interventions in the primary care setting. We applied the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework and expanded the definition of reach beyond the individual (i.e. patient) level to include the ability to identify target populations at an organizational level. To characterize reach and the implementation of registries, semistructured interviews were conducted with key informants, and a usual-care checklist was compiled for each participating Primary Care Network (PCN). Content analysis was used to analyze qualitative data. Using registries to identify and recruit participants for the ABCD interventions proved challenging. The quality of the registries depended on whether physicians granted PCN access to patient lists, the strategies used in development, the reliability of diagnostic information and the data elements collected. In addition, once a diabetes registry was developed, there was limited ability to update it. Proactive management of chronic diseases like diabetes requires the ability to reach targeted patients at the population level. We observed several challenges to the development and application of patient registries. Given the importance of valid registries, strong collaborations and novel strategies that involve policy-makers, PCNs and providers are needed to help find solutions to improve registry quality and resolve maintenance issues. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

A Text Searching Tool to Identify Patients with Idiosyncratic Drug-Induced Liver Injury.

PubMed

Heidemann, Lauren; Law, James; Fontana, Robert J

2017-03-01

Idiosyncratic drug-induced liver injury (DILI) is an uncommon but important cause of liver disease that is challenging to diagnose and identify in the electronic medical record (EMR). To develop an accurate, reliable, and efficient method of identifying patients with bonafide DILI in an EMR system. In total, 527,000 outpatient and ER encounters in an EPIC-based EMR were searched for potential DILI cases attributed to eight drugs. A searching algorithm that extracted 200 characters of text around 14 liver injury terms in the EMR were extracted and collated. Physician investigators reviewed the data outputs and used standardized causality assessment methods to adjudicate the potential DILI cases. A total of 101 DILI cases were identified from the 2564 potential DILI cases that included 62 probable DILI cases, 25 possible DILI cases, nine historical DILI cases, and five allergy-only cases. Elimination of the term "liver disease" from the search strategy improved the search recall from 4 to 19 %, while inclusion of the four highest yield liver injury terms further improved the positive predictive value to 64 % but reduced the overall case detection rate by 47 %. RUCAM scores of the 57 probable DILI cases were generally high and concordant with expert opinion causality assessment scores. A novel text searching tool was developed that identified a large number of DILI cases from a widely used EMR system. A computerized extraction of dictated text followed by the manual review of text snippets can rapidly identify bona fide cases of idiosyncratic DILI.

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

PubMed

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a

Serum Immunoproteomics Combined With Pathological Reassessment of Surgical Specimens Identifies TCP-1ζ Autoantibody as a Potential Biomarker in Thyroid Neoplasia.

PubMed

Belousov, Pavel V; Bogolyubova, Apollinariya V; Kim, Yan S; Abrosimov, Alexander Y; Kopylov, Arthur T; Tvardovskiy, Andrey A; Lanshchakov, Kirill V; Sazykin, Alexei Y; Dvinskikh, Nina Y; Bobrovskaya, Yana I; Selivanova, Lilia S; Shilov, Evgeniy S; Schwartz, Anton M; Shebzukhov, Yuriy V; Severskaia, Natalya V; Vanushko, Vladimir E; Moshkovskii, Sergei A; Nedospasov, Sergei A; Kuprash, Dmitry V

2015-09-01

Current methods of preoperative diagnostics frequently fail to discriminate between benign and malignant thyroid neoplasms. In encapsulated follicular-patterned tumors (EnFPT), this discrimination is challenging even using histopathological analysis. Autoantibody response against tumor-associated antigens is a well-documented phenomenon with prominent diagnostic potential; however, autoantigenicity of thyroid tumors remains poorly explored. Objectives were exploration of tumor-associated antigen repertoire of thyroid tumors and identification of candidate autoantibody biomarkers capable of discrimination between benign and malignant thyroid neoplasms. Proteins isolated from FTC-133 cells were subjected to two-dimensional Western blotting using pooled serum samples of patients originally diagnosed with either papillary thyroid carcinoma (PTC) or EnFPT represented by apparently benign follicular thyroid adenomas, as well as healthy individuals. Immunoreactive proteins were identified using liquid chromatography-tandem mass-spectrometry. Pathological reassessment of EnFPT was performed applying nonconservative criteria for capsular invasion and significance of focal PTC nuclear changes (PTC-NCs). Recombinant T-complex protein 1 subunitζ (TCP-1ζ) was used to examine an expanded serum sample set of patients with various thyroid neoplasms (n = 89) for TCP-1ζ autoantibodies. All patients were included in tertiary referral centers. A protein demonstrating a distinct pattern of EnFPT-specific seroreactivity was identified as TCP-1ζ protein. A subsequent search for clinicopathological correlates of TCP-1ζ seroreactivity revealed nonclassical capsular invasion or focal PTC-NC in all TCP-1ζ antibody-positive cases. Further studies in an expanded sample set confirmed the specificity of TCP-1ζ autoantibodies to malignant EnFPT. We identified TCP-1ζ autoantibodies as a potential biomarker for presurgical discrimination between benign and malignant encapsulated follicular

Classification accuracy of claims-based methods for identifying providers failing to meet performance targets.

PubMed

Hubbard, Rebecca A; Benjamin-Johnson, Rhondee; Onega, Tracy; Smith-Bindman, Rebecca; Zhu, Weiwei; Fenton, Joshua J

2015-01-15

Quality assessment is critical for healthcare reform, but data sources are lacking for measurement of many important healthcare outcomes. With over 49 million people covered by Medicare as of 2010, Medicare claims data offer a potentially valuable source that could be used in targeted health care quality improvement efforts. However, little is known about the operating characteristics of provider profiling methods using claims-based outcome measures that may estimate provider performance with error. Motivated by the example of screening mammography performance, we compared approaches to identifying providers failing to meet guideline targets using Medicare claims data. We used data from the Breast Cancer Surveillance Consortium and linked Medicare claims to compare claims-based and clinical estimates of cancer detection rate. We then demonstrated the performance of claim-based estimates across a broad range of operating characteristics using simulation studies. We found that identification of poor performing providers was extremely sensitive to algorithm specificity, with no approach identifying more than 65% of poor performing providers when claims-based measures had specificity of 0.995 or less. We conclude that claims have the potential to contribute important information on healthcare outcomes to quality improvement efforts. However, to achieve this potential, development of highly accurate claims-based outcome measures should remain a priority. Copyright © 2014 John Wiley & Sons, Ltd.

Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies

PubMed Central

2014-01-01

Background Mutations in the gene encoding thymidine kinase 2 (TK2) result in the myopathic form of mitochondrial DNA depletion syndrome which is a mitochondrial encephalomyopathy presenting in children. In order to unveil some of the mechanisms involved in this pathology and to identify potential biomarkers and therapeutic targets we have investigated the gene expression profile of human skeletal muscle deficient for TK2 using cDNA microarrays. Results We have analysed the whole transcriptome of skeletal muscle from patients with TK2 mutations and compared it to normal muscle and to muscle from patients with other mitochondrial myopathies. We have identified a set of over 700 genes which are differentially expressed in TK2 deficient muscle. Bioinformatics analysis reveals important changes in muscle metabolism, in particular, in glucose and glycogen utilisation, and activation of the starvation response which affects aminoacid and lipid metabolism. We have identified those transcriptional regulators which are likely to be responsible for the observed changes in gene expression. Conclusion Our data point towards the tumor suppressor p53 as the regulator at the centre of a network of genes which are responsible for a coordinated response to TK2 mutations which involves inflammation, activation of muscle cell death by apoptosis and induction of growth and differentiation factor 15 (GDF-15) in muscle and serum. We propose that GDF-15 may represent a potential novel biomarker for mitochondrial dysfunction although further studies are required. PMID:24484525

Potential environmental contaminant risks to avian species at important bird areas in the northeastern United States

USGS Publications Warehouse

Rattner, B.A.; Ackerson, B.K.

2007-01-01

Environmental contaminants, acting at molecular through population levels of biological organization, can have profound effects upon birds. A screening level risk assessment was conducted that examined potential contaminant threats at 52 Important Bird Areas (IBAs) in the northeastern Atlantic coast drainage. Using geographic information system methodology, data layers describing or integrating pollutant hazards (impaired waters, fish or wildlife consumption advisories, toxic release inventory data, estimated pesticide use and hazard) were overlaid on buffered IBA boundaries, and the relative contaminant threat for each site was ranked. The 10 sites identified as having the greatest contaminant threats included Jefferson National Forest, Stewart B. McKinney National Wildlife Refuge, Great Dismal Swamp National Wildlife Refuge, Blue Ridge Parkway, Shenandoah National Park, Adirondack Park, Edwin B. Forsythe National Wildlife Refuge, George Washington National Forest, Green Mountain National Forest, and Long Island Piping Plover Beaches. These sites accounted for over 50% of the entire study area, and in general had moderate to high percentages of impaired waters, fish consumption advisories related to mercury and PCBs, and were located in counties with substantial application rates of pesticides known to be toxic to birds. Avian species at these IBAs include Federally endangered Roseate terns (Sterna dougallii), threatened piping plovers (Charadrius melodus), neotropical migrants, Bicknell?s thrush (Catharus bicknelli), Swainson?s warbler (Limnothlypis swainsonii) and wintering brant geese (Branta bernicla). Extant data for free-ranging birds from the Contaminant Exposure and Effects--Terrestrial Vertebrates database were examined within the buffered boundaries of each IBA, and for a moderate number of sites there was qualitative concordance between the perceived risk and actual contaminant exposure data. However, several of the IBAs with substantial contaminant

Using Nurse Ratings of Physician Communication in the ICU To Identify Potential Targets for Interventions To Improve End-of-Life Care

PubMed Central

Downey, Lois; Nielsen, Elizabeth L.; Treece, Patsy D.; Shannon, Sarah E.; Curtis, J. Randall; Engelberg, Ruth A.

2016-01-01

Abstract Background: Communication among doctors, nurses, and families contributes to high-quality end-of-life care, but is difficult to improve. Objective: Our objective was to identify aspects of communication appropriate for interventions to improve quality of dying in the intensive care unit (ICU). Methods: This observational study used data from a cluster-randomized trial of an interdisciplinary intervention to improve end-of-life care at 15 Seattle/Tacoma area hospitals (2003–2008). Nurses completed surveys for patients dying in the ICU. We examined associations between nurse-assessed predictors (physician-nurse communication, physician-family communication) and nurse ratings of patients' quality of dying (nurse-QODD-1). Results: Based on 1173 nurse surveys, four of six physician-nurse communication topics were positively associated with nurse-QODD-1: family questions, family dynamics, spiritual/religious issues, and cultural issues. Discussions between nurses and physicians about nurses' concerns for patients or families were negatively associated. All physician-family communication ratings, as assessed by nurses, were positively associated with nurse-QODD-1: answering family's questions, listening to family, asking about treatments patient would want, helping family decide patient's treatment wishes, and overall communication. Path analysis suggested overall physician-family communication and helping family incorporate patient's wishes were directly associated with nurse-QODD-1. Conclusions: Several topics of physician-nurse communication, as rated by nurses, were associated with higher nurse-rated quality of dying, whereas one topic, nurses' concerns for patient or family, was associated with poorer ratings. Higher nurse ratings of physician-family communication were uniformly associated with higher quality of dying, highlighting the importance of this communication. Physician support of family decision making was particularly important, suggesting a

Identifying Corridors among Large Protected Areas in the United States

PubMed Central

Belote, R. Travis; Dietz, Matthew S.; McRae, Brad H.; Theobald, David M.; McClure, Meredith L.; Irwin, G. Hugh; McKinley, Peter S.; Gage, Josh A.; Aplet, Gregory H.

2016-01-01

Conservation scientists emphasize the importance of maintaining a connected network of protected areas to prevent ecosystems and populations from becoming isolated, reduce the risk of extinction, and ultimately sustain biodiversity. Keeping protected areas connected in a network is increasingly recognized as a conservation priority in the current era of rapid climate change. Models that identify suitable linkages between core areas have been used to prioritize potentially important corridors for maintaining functional connectivity. Here, we identify the most “natural” (i.e., least human-modified) corridors between large protected areas in the contiguous Unites States. We aggregated results from multiple connectivity models to develop a composite map of corridors reflecting agreement of models run under different assumptions about how human modification of land may influence connectivity. To identify which land units are most important for sustaining structural connectivity, we used the composite map of corridors to evaluate connectivity priorities in two ways: (1) among land units outside of our pool of large core protected areas and (2) among units administratively protected as Inventoried Roadless (IRAs) or Wilderness Study Areas (WSAs). Corridor values varied substantially among classes of “unprotected” non-core land units, and land units of high connectivity value and priority represent diverse ownerships and existing levels of protections. We provide a ranking of IRAs and WSAs that should be prioritized for additional protection to maintain minimal human modification. Our results provide a coarse-scale assessment of connectivity priorities for maintaining a connected network of protected areas. PMID:27104683

The medically important aerobic actinomycetes: epidemiology and microbiology.

PubMed Central

McNeil, M M; Brown, J M

1994-01-01

The aerobic actinomycetes are soil-inhabiting microorganisms that occur worldwide. In 1888, Nocard first recognized the pathogenic potential of this group of microorganisms. Since then, several aerobic actinomycetes have been a major source of interest for the commercial drug industry and have proved to be extremely useful microorganisms for producing novel antimicrobial agents. They have also been well known as potential veterinary pathogens affecting many different animal species. The medically important aerobic actinomycetes may cause significant morbidity and mortality, in particular in highly susceptible severely immunocompromised patients, including transplant recipients and patients infected with human immunodeficiency virus. However, the diagnosis of these infections may be difficult, and effective antimicrobial therapy may be complicated by antimicrobial resistance. The taxonomy of these microorganisms has been problematic. In recent revisions of their classification, new pathogenic species have been recognized. The development of additional and more reliable diagnostic tests and of a standardized method for antimicrobial susceptibility testing and the application of molecular techniques for the diagnosis and subtyping of these microorganisms are needed to better diagnose and treat infected patients and to identify effective control measures for these unusual pathogens. We review the epidemiology and microbiology of the major medically important aerobic actinomycetes. Images PMID:7923055

Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.

PubMed

Saunus, Jodi M; Quinn, Michael C J; Patch, Ann-Marie; Pearson, John V; Bailey, Peter J; Nones, Katia; McCart Reed, Amy E; Miller, David; Wilson, Peter J; Al-Ejeh, Fares; Mariasegaram, Mythily; Lau, Queenie; Withers, Teresa; Jeffree, Rosalind L; Reid, Lynne E; Da Silva, Leonard; Matsika, Admire; Niland, Colleen M; Cummings, Margaret C; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Kassahn, Karin S; Narayanan, Vairavan; Taib, Nur Aishah; Teo, Soo-Hwang; Chow, Yock Ping; kConFab; Jat, Parmjit S; Brandner, Sebastian; Flanagan, Adrienne M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Grimmond, Sean M; Simpson, Peter T; Waddell, Nicola; Lakhani, Sunil R

2015-11-01

Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting

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

NASA Astrophysics Data System (ADS)

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

Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas.

PubMed

Gorkhali, Neena Amatya; Dong, Kunzhe; Yang, Min; Song, Shen; Kader, Adiljian; Shrestha, Bhola Shankar; He, Xiaohong; Zhao, Qianjun; Pu, Yabin; Li, Xiangchen; Kijas, James; Guan, Weijun; Han, Jianlin; Jiang, Lin; Ma, Yuehui

2016-07-22

Sheep has successfully adapted to the extreme high-altitude Himalayan region. To identify genes underlying such adaptation, we genotyped genome-wide single nucleotide polymorphisms (SNPs) of four major sheep breeds living at different altitudes in Nepal and downloaded SNP array data from additional Asian and Middle East breeds. Using a di value-based genomic comparison between four high-altitude and eight lowland Asian breeds, we discovered the most differentiated variants at the locus of FGF-7 (Keratinocyte growth factor-7), which was previously reported as a good protective candidate for pulmonary injuries. We further found a SNP upstream of FGF-7 that appears to contribute to the divergence signature. First, the SNP occurred at an extremely conserved site. Second, the SNP showed an increasing allele frequency with the elevated altitude in Nepalese sheep. Third, the electrophoretic mobility shift assays (EMSA) analysis using human lung cancer cells revealed the allele-specific DNA-protein interactions. We thus hypothesized that FGF-7 gene potentially enhances lung function by regulating its expression level in high-altitude sheep through altering its binding of specific transcription factors. Especially, FGF-7 gene was not implicated in previous studies of other high-altitude species, suggesting a potential novel adaptive mechanism to high altitude in sheep at the Himalayas.

Cell-Based Small-Molecule Compound Screen Identifies Fenretinide as Potential Therapeutic for Translocation-Positive Rhabdomyosarcoma

PubMed Central

Herrero Martín, David; Boro, Aleksandar; Schäfer, Beat W.

2013-01-01

A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ß. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma. PMID:23372815

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

USGS Publications Warehouse

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.

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

PubMed

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

Planting Sentinel European Trees in Eastern Asia as a Novel Method to Identify Potential Insect Pest Invaders

PubMed Central

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

Airborne Quercus pollen in SW Spain: Identifying favourable conditions for atmospheric transport and potential source areas.

PubMed

Maya-Manzano, José María; Fernández-Rodríguez, Santiago; Smith, Matt; Tormo-Molina, Rafael; Reynolds, Andrew M; Silva-Palacios, Inmaculada; Gonzalo-Garijo, Ángela; Sadyś, Magdalena

2016-11-15

The pollen grains of Quercus spp. (oak trees) are allergenic. This study investigates airborne Quercus pollen in SW Spain with the aim identifying favourable conditions for atmospheric transport and potential sources areas. Two types of Quercus distribution maps were produced. Airborne Quercus pollen concentrations were measured at three sites located in the Extremadura region (SW Spain) for 3 consecutive years. The seasonal occurrence of Quercus pollen in the air was investigated, as well as days with pollen concentrations ≥80Pm(-3). The distance that Quercus pollen can be transported in appreciable numbers was calculated using clusters of back trajectories representing the air mass movement above the source areas (oak woodlands), and by using a state-of-the-art dispersion model. The two main potential sources of Quercus airborne pollen captured in SW Spain are Q. ilex subsp. ballota and Q. suber. The minimum distances between aerobiological stations and Quercus woodlands have been estimated as: 40km (Plasencia), 66km (Don Benito), 62km (Zafra) from the context of this study. Daily mean Quercus pollen concentration can exceed 1,700Pm(-3), levels reached not less than 24 days in a single year. High Quercus pollen concentration were mostly associated with moderate wind speed events (6-10ms(-1)), whereas that a high wind speed (16-20ms(-1)) seems to be associated with low concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Alu expression in human cell lines and their retrotranspositional potential.

PubMed

Oler, Andrew J; Traina-Dorge, Stephen; Derbes, Rebecca S; Canella, Donatella; Cairns, Brad R; Roy-Engel, Astrid M

2012-06-20

The vast majority of the 1.1 million Alu elements are retrotranspositionally inactive, where only a few loci referred to as 'source elements' can generate new Alu insertions. The first step in identifying the active Alu sources is to determine the loci transcribed by RNA polymerase III (pol III). Previous genome-wide analyses from normal and transformed cell lines identified multiple Alu loci occupied by pol III factors, making them candidate source elements. Analysis of the data from these genome-wide studies determined that the majority of pol III-bound Alus belonged to the older subfamilies Alu S and Alu J, which varied between cell lines from 62.5% to 98.7% of the identified loci. The pol III-bound Alus were further scored for estimated retrotransposition potential (ERP) based on the absence or presence of selected sequence features associated with Alu retrotransposition capability. Our analyses indicate that most of the pol III-bound Alu loci candidates identified lack the sequence characteristics important for retrotransposition. These data suggest that Alu expression likely varies by cell type, growth conditions and transformation state. This variation could extend to where the same cell lines in different laboratories present different Alu expression patterns. The vast majority of Alu loci potentially transcribed by RNA pol III lack important sequence features for retrotransposition and the majority of potentially active Alu loci in the genome (scored high ERP) belong to young Alu subfamilies. Our observations suggest that in an in vivo scenario, the contribution of Alu activity on somatic genetic damage may significantly vary between individuals and tissues.

Assessing potential impacts of the EVFTA on Vietnam's pharmaceutical imports from the EU: an application of SMART analysis.

PubMed

Vu, Huong Thanh

2016-01-01

This paper by adopting the Software on Market Analysis and Restrictions on Trade assessed the ex-ante impact of tariff elimination under the European-Vietnam free trade agreement (EVFTA) on Vietnam's pharmaceutical imports from the EU based on two scenarios. The results showed that although Vietnam's tariff removal for the EU's medicines would not result in a significant increase in Vietnam's imports from the EU, Vietnam's deeper integration with ASEAN + 3 and TPP (the Trans-Pacific Partnership) nations would affect quite slightly on its imports from the EU. Therefore, the EU would be still the most important and biggest source of pharmaceuticals for Vietnam in the near future. In addition, there might be an uneven distribution in Vietnam's import increases by the EU nation, pharmaceutical group and product. The simulation results also pointed out that the EVFTA's trade creation effect would be higher than trade diversion effect and therefore the agreement would improve welfare of Vietnam. When Vietnam extends its coverage of tariff elimination to also TPP and ASEAN + 3, Vietnam's welfare would potentially increase more but Vietnam would face with the relatively high increases of pharmaceutical imports from not only the EU but also the US, Australia, South Korea, Thailand and China. Bases on these results, the paper argued that both the Vietnamese government and pharmaceutical enterprises should not neglect the EVFTA and its impacts on the pharmaceutical sector, and perceive clearly the uneven distribution of Vietnam's import changes from the EU by nation and by product to design appropriate business and investment strategy. In addition, Vietnam should take measures to diversify its European import markets to be less dependent on the traditional ones in the current context of the EU. Finally, Vietnam should promote the integration in the pharmaceutical sector with all three groups of nations, especially ASEAN and ASEAN's key partners, to reduce trade diversion

Potential Susceptibility Loci Identified for Renal Cell Carcinoma by Targeting Obesity-Related Genes.

PubMed

Shu, Xiang; Purdue, Mark P; Ye, Yuanqing; Tu, Huakang; Wood, Christopher G; Tannir, Nizar M; Wang, Zhaoming; Albanes, Demetrius; Gapstur, Susan M; Stevens, Victoria L; Rothman, Nathaniel; Chanock, Stephen J; Wu, Xifeng

2017-09-01

Background: Obesity is an established risk factor for renal cell carcinoma (RCC). Although genome-wide association studies (GWAS) of RCC have identified several susceptibility loci, additional variants might be missed due to the highly conservative selection. Methods: We conducted a multiphase study utilizing three independent genome-wide scans at MD Anderson Cancer Center (MDA RCC GWAS and MDA RCC OncoArray) and National Cancer Institute (NCI RCC GWAS), which consisted of a total of 3,530 cases and 5,714 controls, to investigate genetic variations in obesity-related genes and RCC risk. Results: In the discovery phase, 32,946 SNPs located at ±10 kb of 2,001 obesity-related genes were extracted from MDA RCC GWAS and analyzed using multivariable logistic regression. Proxies ( R 2 > 0.8) were searched or imputation was performed if SNPs were not directly genotyped in the validation sets. Twenty-one SNPs with P < 0.05 in both MDA RCC GWAS and NCI RCC GWAS were subsequently evaluated in MDA RCC OncoArray. In the overall meta-analysis, significant ( P < 0.05) associations with RCC risk were observed for SNP mapping to IL1RAPL2 [rs10521506-G: OR meta = 0.87 (0.81-0.93), P meta = 2.33 × 10 -5 ], PLIN2 [rs2229536-A: OR meta = 0.87 (0.81-0.93), P meta = 2.33 × 10 -5 ], SMAD3 [rs4601989-A: OR meta = 0.86 (0.80-0.93), P meta = 2.71 × 10 -4 ], MED13L [rs10850596-A: OR meta = 1.14 (1.07-1.23), P meta = 1.50 × 10 -4 ], and TSC1 [rs3761840-G: OR meta = 0.90 (0.85-0.97), P meta = 2.47 × 10 -3 ]. We did not observe any significant cis-expression quantitative trait loci effect for these SNPs in the TCGA KIRC data. Conclusions: Taken together, we found that genetic variation of obesity-related genes could influence RCC susceptibility. Impact: The five identified loci may provide new insights into disease etiology that reveal importance of obesity-related genes in RCC development. Cancer Epidemiol Biomarkers Prev; 26(9); 1436-42. ©2017 AACR . ©2017 American Association for

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

PubMed

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.

Molecular characterization of NRXN1 deletions from 19,263 clinical microarray cases identifies exons important for neurodevelopmental disease expression

PubMed Central

Lowther, Chelsea; Speevak, Marsha; Armour, Christine M.; Goh, Elaine S.; Graham, Gail E.; Li, Chumei; Zeesman, Susan; Nowaczyk, Malgorzata J.M.; Schultz, Lee-Anne; Morra, Antonella; Nicolson, Rob; Bikangaga, Peter; Samdup, Dawa; Zaazou, Mostafa; Boyd, Kerry; Jung, Jack H.; Siu, Victoria; Rajguru, Manjulata; Goobie, Sharan; Tarnopolsky, Mark A.; Prasad, Chitra; Dick, Paul T.; Hussain, Asmaa S.; Walinga, Margreet; Reijenga, Renske G.; Gazzellone, Matthew; Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.; Stavropoulos, Dimitri J.; McCready, Elizabeth; Bassett, Anne S.

2016-01-01

Purpose The purpose of the current study was to assess the penetrance of NRXN1 deletions. Methods We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant CNVs was used as a proxy to estimate the relative penetrance of NRXN1 deletions. Results We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability, significantly greater than in controls [OR=8.14 (95% CI 2.91–22.72), p< 0.0001)]. Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3′ end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5′ NRXN1 deletion [OR=7.47 (95% CI 2.36–23.61), p=0.0006]. The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (p=0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV, a two-fold greater prevalence than for exonic NRXN1 deletion cases (p=0.0035). Conclusions The results support the importance of exons near the 5′ end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes. PMID:27195815

Molecular characterization of NRXN1 deletions from 19,263 clinical microarray cases identifies exons important for neurodevelopmental disease expression.

PubMed

Lowther, Chelsea; Speevak, Marsha; Armour, Christine M; Goh, Elaine S; Graham, Gail E; Li, Chumei; Zeesman, Susan; Nowaczyk, Malgorzata J M; Schultz, Lee-Anne; Morra, Antonella; Nicolson, Rob; Bikangaga, Peter; Samdup, Dawa; Zaazou, Mostafa; Boyd, Kerry; Jung, Jack H; Siu, Victoria; Rajguru, Manjulata; Goobie, Sharan; Tarnopolsky, Mark A; Prasad, Chitra; Dick, Paul T; Hussain, Asmaa S; Walinga, Margreet; Reijenga, Renske G; Gazzellone, Matthew; Lionel, Anath C; Marshall, Christian R; Scherer, Stephen W; Stavropoulos, Dimitri J; McCready, Elizabeth; Bassett, Anne S

2017-01-01

The purpose of the current study was to assess the penetrance of NRXN1 deletions. We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P < 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3' end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5' NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). The results support the importance of exons near the 5' end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61.

Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus

PubMed Central

Josset, Laurence; Menachery, Vineet D.; Gralinski, Lisa E.; Agnihothram, Sudhakar; Sova, Pavel; Carter, Victoria S.; Yount, Boyd L.; Graham, Rachel L.; Baric, Ralph S.; Katze, Michael G.

2013-01-01

ABSTRACT A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus. PMID:23631916

Identifying improvement potentials in cement production with life cycle assessment.

PubMed

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.

Promoting wellbeing in young unemployed adults: the importance of identifying meaningful patterns of time use.

PubMed

Scanlan, Justin Newton; Bundy, Anita C; Matthews, Lynda R

2011-04-01

This study set out to explore the differences in time use between 'unemployed', 'unemployed but in education' and part-time and full-time employed 18- to 25-year-old Australians. Unemployed individuals generally experience poor health and this may be related to the way they use their time. Activity-based interventions may be one health-promoting strategy. This knowledge is important for all occupational therapists, as many service users are likely to be unemployed. Time use of unemployed 18- to 25-year-olds (measured using the Modified Occupational Questionnaire) was compared with the time use of part- and full-time employed 18- to 25-year-olds (from the 2006 Australian Time Use Survey). Individuals in the 'unemployed' groups spent significantly less time engaged in work-related activities than their employed peers. This time was reallocated mainly to recreation and leisure and household work (for both men and women) and child care and sleeping (women only). Recreation and leisure activities were generally passive, home-based activities such as watching television or 'doing nothing'. Individuals in the 'unemployed but in education' groups also spent less time in employment-related activities, but the majority of this time was reallocated to education activities. Individuals in the 'unemployed' groups spent large amounts of time engaged in potentially non-directed use of time (e.g. watching television or 'doing nothing'). Such patterns of time use have previously been associated with poor health. To support the health of unemployed individuals more effectively, occupational therapy interventions must focus on enhancing the quality of time use for this population. © 2010 The Authors. Australian Occupational Therapy Journal © 2010 Australian Association of Occupational Therapists.

Utilization of solar energy in developing countries: Identifying some potential markets

NASA Technical Reports Server (NTRS)

Hein, G. F.; Siddiqi, T. A.

1978-01-01

The potential use of solar electricity generated from photovoltaic cells is examined for nineteen developing nations. Energy and economic profiles are summarized for each country. A comparison is made between the use of autogeneration and photovoltaics in a rural area of Haiti.

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

NASA Astrophysics Data System (ADS)

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.

Loneliness: Clinical Import and Interventions

PubMed Central

Cacioppo, Stephanie; Grippo, Angela J.; London, Sarah; Goossens, Luc; Cacioppo, John T.

2014-01-01

In 1978, when the Task Panel report to the US President’s Commission on Mental Health emphasized the importance of improving health care and easing the pain of those suffering from emotional distress syndromes including loneliness, few anticipated that this issue would still need to be addressed 40 years later. A meta-analysis (Masi et al., 2011) on the efficacy of treatments to reduce loneliness identified a need for well-controlled randomized clinical trials focusing on the rehabilitation of maladaptive social cognition. We review assessments of loneliness and build on this meta-analysis to discuss the efficacy of various treatments for loneliness. With the advances made over the past 5 years in the identification of the psychobiological and pharmaceutical mechanisms associated with loneliness and maladaptive social cognition, there is increasing evidence for the potential efficacy of integrated interventions that combine (social) cognitive behavioral therapy with short-term adjunctive pharmacological treatments. PMID:25866548

A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera.

PubMed

Lappan, Rachael; Imbrogno, Kara; Sikazwe, Chisha; Anderson, Denise; Mok, Danny; Coates, Harvey; Vijayasekaran, Shyan; Bumbak, Paul; Blyth, Christopher C; Jamieson, Sarra E; Peacock, Christopher S

2018-02-20

Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies. Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear. Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM.

Identification of Potential Hazard using Hazard Identification and Risk Assessment

NASA Astrophysics Data System (ADS)

Sari, R. M.; Syahputri, K.; Rizkya, I.; Siregar, I.

2017-03-01

This research was conducted in the paper production’s company. These Paper products will be used as a cigarette paper. Along in the production’s process, Company provides the machines and equipment that operated by workers. During the operations, all workers may potentially injured. It known as a potential hazard. Hazard identification and risk assessment is one part of a safety and health program in the stage of risk management. This is very important as part of efforts to prevent occupational injuries and diseases resulting from work. This research is experiencing a problem that is not the identification of potential hazards and risks that would be faced by workers during the running production process. The purpose of this study was to identify the potential hazards by using hazard identification and risk assessment methods. Risk assessment is done using severity criteria and the probability of an accident. According to the research there are 23 potential hazard that occurs with varying severity and probability. Then made the determination Risk Assessment Code (RAC) for each potential hazard, and gained 3 extreme risks, 10 high risks, 6 medium risks and 3 low risks. We have successfully identified potential hazard using RAC.

Development of fine-leaved Festuca grass populations identified genetic resources having potential for improved forage production and wildfire control in the western United States

USDA-ARS?s Scientific Manuscript database

Drought and heat tolerant fine-leaved fescue (Festuca ssp.) grasses have potential as components in rangeland greenstrips for wildfire control in semi-arid climates. However, such fine-leaved grasses have been difficult to identify because of specific adaptations, lack of late maturity, and often p...

An Inside Look at the Potential for Violence and Suicide.

ERIC Educational Resources Information Center

Reilly, Thomas

1999-01-01

The parent of a murdered daughter (who is also an educator) examines student potential for violence and suicide and stresses the importance of early intervention for violence prevention. Teachers are urged to establish meaningful connections with students to identify students who fit the profile of alienation that typifies those who actually…

Physician Rating Websites: What Aspects Are Important to Identify a Good Doctor, and Are Patients Capable of Assessing Them? A Mixed-Methods Approach Including Physicians’ and Health Care Consumers’ Perspectives

PubMed Central

Schulz, Peter J

2017-01-01

Background Physician rating websites (PRWs) offer health care consumers the opportunity to evaluate their doctor anonymously. However, physicians’ professional training and experience create a vast knowledge gap in medical matters between physicians and patients. This raises ethical concerns about the relevance and significance of health care consumers’ evaluation of physicians’ performance. Objective To identify the aspects physician rating websites should offer for evaluation, this study investigated the aspects of physicians and their practice relevant for identifying a good doctor, and whether health care consumers are capable of evaluating these aspects. Methods In a first step, a Delphi study with physicians from 4 specializations was conducted, testing various indicators to identify a good physician. These indicators were theoretically derived from Donabedian, who classifies quality in health care into pillars of structure, process, and outcome. In a second step, a cross-sectional survey with health care consumers in Switzerland (N=211) was launched based on the indicators developed in the Delphi study. Participants were asked to rate the importance of these indicators to identify a good physician and whether they would feel capable to evaluate those aspects after the first visit to a physician. All indicators were ordered into a 4×4 grid based on evaluation and importance, as judged by the physicians and health care consumers. Agreement between the physicians and health care consumers was calculated applying Holsti’s method. Results In the majority of aspects, physicians and health care consumers agreed on what facets of care were important and not important to identify a good physician and whether patients were able to evaluate them, yielding a level of agreement of 74.3%. The two parties agreed that the infrastructure, staff, organization, and interpersonal skills are both important for a good physician and can be evaluated by health care

Microbiological profile and potential hazards associated with imported and local brands of tomato paste in Nigeria.

PubMed

Efiuvwevwere, B J; Atirike, O I

1998-03-01

Cans of three tomato paste brands (two of which are imported and one produced locally) showing defective or normal appearance were purchased from various retail outlets and analysed for microbial composition and pH values. Substantially higher total viable counts were observed in samples from defective cans but the lowest population was found in the local brand. Ratio of mesophilic to thermophilic micro-organisms increased in samples obtained from cans showing visible defects. Anaerobic spore counts were higher than the aerobic population in both normal and defective cans, but the counts varied with the brands. Four dominant bacterial genera (Bacillus, Clostridium, Lactobacillus and Leuconostoc) were isolated from the samples with the greater proportion being spore-formers. Percentage occurrence of Clostridium thermosaccharolyticum was appreciably higher in samples from defective cans while a preponderance of Lactobacillus occurred in samples from normal cans. Of the moulds isolated, Absidia and Aspergillus fumigatus showed a higher percentage in defective cans. pH values higher than the critical safe level of 4.6 were found in cans with visible defects and greater microbial diversity with higher microbial load was more often associated with these samples. Imported brands showed more undesirable microbial quality and pH values, making them potentially hazardous.

Immunoproteomically identified GBAA_0345, alkyl hydroperoxide reductase subunit C is a potential target for multivalent anthrax vaccine.

PubMed

Kim, Yeon Hee; Kim, Kyung Ae; Kim, Yu-Ri; Choi, Min Kyung; Kim, Hye Kyeong; Choi, Ki Ju; Chun, Jeong-Hoon; Cha, Kiweon; Hong, Kee-Jong; Lee, Na Gyong; Yoo, Cheon-Kwon; Oh, Hee-Bok; Kim, Tae Sung; Rhie, Gi-eun

2014-01-01

Anthrax is caused by the spore-forming bacterium Bacillus anthracis, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (malonyl CoA-acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent-spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Importation of dengue by soldiers returning from East Timor to north Queensland, Australia.

PubMed

Kitchener, Scott; Leggat, Peter A; Brennan, Leonard; McCall, Bradley

2002-01-01

Soldiers based in Townsville, Australia, returned from East Timor following peacekeeping operations during the wet season of 1999 to 2000. This represented the potential to import dengue virus into north Queensland, a dengue receptive area of Australia. This article seeks to outline the measures taken by the Australian Defence Force (ADF) to prevent local transmission and to present the outcomes. Soldiers returning to north Queensland were provided with education on dengue fever and in the fortnight before return, their living areas were subjected to intensive vector control measures, in order to reduce the risk of acquisition of dengue. They were further encouraged to present early with any febrile illness following their return to Townsville. Provisionally diagnosed dengue cases were notified to the state public health authorities immediately and cases were isolated until suitable vector control programs were implemented or the potentially viremic period exceeded. Serologic and virologic investigations were undertaken to identify the passage and probable serotype or confirm the presence and serotype of dengue virus. Nine serologically confirmed cases of dengue were identified as viremic in north Queensland. Six cases were identified as arising from dengue serotype 2, two were from serotype 3, and one case was ill defined. No dengue cases have been reported in the local population 4 months following these ADF cases. Local outbreaks of dengue fever have occurred in north Queensland following the importation of dengue virus in returned travelers. The successful prevention of local transmission in these circumstances was contributed to by early notification of cases and prevention of transmission through isolation of cases and collaboration between ADF and state and local public health authorities in vector control. The management of potentially viremic returning service personnel represents a future challenge for the ADF.

An integrated molecular analysis of lung adenocarcinomas identifies potential therapeutic targets among TTF1-negative tumors including DNA repair proteins and Nrf2

PubMed Central

Cardnell, Robert J.G.; Behrens, Carmen; Diao, Lixia; Fan, YouHong; Tang, Ximing; Tong, Pan; John D., Minna; Mills, Gordon B.; Heymach, John V.; Wistuba, Ignacio I.; Wang, Jing; Byers., Lauren A.

2015-01-01

Purpose Thyroid transcription factor-1 (TTF1) immunohistochemistry (IHC) is used clinically to differentiate primary lung adenocarcinomas (LUAD) from squamous lung cancers and metastatic adenocarcinomas from other primary sites. However, a subset of LUAD (15-20%) does not express TTF1 and TTF1-negative patients have worse clinical outcomes. As there are no established targeted agents with activity in TTF1-negative LUAD, we performed an integrated molecular analysis to identify potential therapeutic targets. Experimental Design Using two clinical LUAD cohorts (274 tumors), one from our institution (PROSPECT) and the TCGA, we interrogated proteomic profiles (by reverse-phase protein array (RPPA)), gene expression, and mutational data. Drug response data from 74 cell lines were used to validate potential therapeutic agents. Results Strong correlations were observed between TTF1 IHC and TTF1 measurements by RPPA (Rho=0.57, p<0.001) and gene expression (NKX2-1, Rho=0.61, p<0.001). Established driver mutations (e.g. BRAF and EGFR) were associated with high TTF1 expression. In contrast, TTF1-negative LUAD had a higher frequency of inactivating KEAP1 mutations (p=0.001). Proteomic profiling identified increased expression of DNA repair proteins (e.g., Chk1 and the DNA repair score) and suppressed PI3K/MAPK signaling among TTF1-negative tumors, with differences in total proteins confirmed at the mRNA level. Cell line analysis showed drugs targeting DNA repair to be more active in TTF1-low cell lines. Conclusions Combined genomic and proteomic analyses demonstrated infrequent alteration of validated lung cancer targets (including the absence of BRAF mutations in TTF1-negative LUAD), but identified novel potential targets for TTF1-negative LUAD includingKEAP1/Nrf2 and DNA repair pathways. PMID:25878335

Dental students' beliefs about culture in patient care: self-reported knowledge and importance.

PubMed

Wagner, Julie A; Redford-Badwal, Deborah

2008-05-01

In order to decrease the well-documented disparities in oral health and oral health care, the next generation of dentists must be prepared to serve a diverse patient population. This article describes dental students' self-reported knowledge of culture and importance of using culturally sensitive dental practices. Three consecutive graduating classes (n=111) were surveyed anonymously in their sophomore years. Students indicated their self-rated knowledge of oral health and oral health care for their own culture and the cultures of patients they are likely to see in dental practice. Students also rated their perceived importance of culturally sensitive dental practice. Overall, students reported low knowledge of the cultures of the patients they will see in practice. Few students could identify any cultural group that they knew well. However, students as a group indicated that using culturally sensitive practices in dentistry is important. Students who could identify at least one cultural group they knew well perceived cultural sensitivity in dental practice as more important than students who could not. These results suggest that students need cross-cultural training and believe that such training is important. The results also suggest that a specific curriculum that increases knowledge of other cultures may have the potential to ultimately increase the use of culturally sensitive practices.

Beta-Lactamase Producing Escherichia coli Isolates in Imported and Locally Produced Chicken Meat from Ghana

PubMed Central

Rasmussen, Mette Marie; Opintan, Japheth A.; Frimodt-Møller, Niels; Styrishave, Bjarne

2015-01-01

The use of antibiotics in food animals is of public health concern, because resistant zoonotic pathogens can be transmitted to humans. Furthermore, global trade with food may rapidly spread multi-resistant pathogens between countries and even continents. The purpose of the study was to investigate whether imported chicken meat and meat from locally reared chicken are potential sources for human exposure to multi resistant Escherichia coli isolates. 188 samples from imported and locally produced chicken meat were sampled and analyzed. 153 bacteria isolates were successfully cultured and identified as E. coli using MALDI-ToF. Of these 109 isolates were from meat whereas the remaining 44 were isolated from the cloaca of locally reared live chickens. Antimicrobial susceptibility test was done on the identified E. coli isolates. Additionally, beta-lactamases production (ESBL and/or AmpC) were phenotypically confirmed on all isolates showing resistance to cefpodoxime. Beta-lactamase producing (BLP) E. coli meat isolates were further genotyped. Antimicrobial resistance to four antibiotic markers with highest resistance was detected more frequently in isolates from local chickens compared to imported chickens (tetracycline 88.9% vs. 57.5%, sulphonamide 75.0% vs. 46.6%, ampicillin 69.4% vs. 61.6% and trimethoprim 66.7% vs. 38.4%). Beta-lactamase production was found in 29 E. coli meat isolates, with 56.9% of them being multiple drug resistant (≥ 3). The predominant phylogroup identified was B1 followed by A and D, with similar distribution among the isolates from meat of locally reared chickens and imported chickens. Beta-lactamase producing genotype bla CTX-M-15 (50%; 10/20) was the most frequently drug resistant gene detected. More BLP E. coli isolates were found in imported chicken meat compared to locally reared chickens, demonstrating that these isolates may be spreading through food trade. In conclusion, both imported and locally produced chicken meats are potential

Beta-Lactamase Producing Escherichia coli Isolates in Imported and Locally Produced Chicken Meat from Ghana.

PubMed

Rasmussen, Mette Marie; Opintan, Japheth A; Frimodt-Møller, Niels; Styrishave, Bjarne

2015-01-01

The use of antibiotics in food animals is of public health concern, because resistant zoonotic pathogens can be transmitted to humans. Furthermore, global trade with food may rapidly spread multi-resistant pathogens between countries and even continents. The purpose of the study was to investigate whether imported chicken meat and meat from locally reared chicken are potential sources for human exposure to multi resistant Escherichia coli isolates. 188 samples from imported and locally produced chicken meat were sampled and analyzed. 153 bacteria isolates were successfully cultured and identified as E. coli using MALDI-ToF. Of these 109 isolates were from meat whereas the remaining 44 were isolated from the cloaca of locally reared live chickens. Antimicrobial susceptibility test was done on the identified E. coli isolates. Additionally, beta-lactamases production (ESBL and/or AmpC) were phenotypically confirmed on all isolates showing resistance to cefpodoxime. Beta-lactamase producing (BLP) E. coli meat isolates were further genotyped. Antimicrobial resistance to four antibiotic markers with highest resistance was detected more frequently in isolates from local chickens compared to imported chickens (tetracycline 88.9% vs. 57.5%, sulphonamide 75.0% vs. 46.6%, ampicillin 69.4% vs. 61.6% and trimethoprim 66.7% vs. 38.4%). Beta-lactamase production was found in 29 E. coli meat isolates, with 56.9% of them being multiple drug resistant (≥ 3). The predominant phylogroup identified was B1 followed by A and D, with similar distribution among the isolates from meat of locally reared chickens and imported chickens. Beta-lactamase producing genotype blaCTX-M-15 (50%; 10/20) was the most frequently drug resistant gene detected. More BLP E. coli isolates were found in imported chicken meat compared to locally reared chickens, demonstrating that these isolates may be spreading through food trade. In conclusion, both imported and locally produced chicken meats are potential

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

PubMed

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

2014-08-07

of the other potential pathogens identified in this study.

Novel royal jelly proteins identified by gel-based and gel-free proteomics.

PubMed

Han, Bin; Li, Chenxi; Zhang, Lan; Fang, Yu; Feng, Mao; Li, Jianke

2011-09-28

Royal jelly (RJ) plays an important role in caste determination of the honeybee; the genetically same female egg develops into either a queen or worker bee depending on the time and amount of RJ fed to the larvae. RJ also has numerous health-promoting properties for humans. Gel-based and gel-free proteomics approaches and high-performance liquid chromatography-chip quadruple time-of-flight tandem mass spectrometry were applied to comprehensively investigate the protein components of RJ. Overall, 37 and 22 nonredundant proteins were identified by one-dimensional gel electrophoresis and gel-free analysis, respectively, and 19 new proteins were found by these two proteomics approaches. Major royal jelly proteins (MRJPs) were identified as the principal protein components of RJ, and proteins related to carbohydrate metabolism such as glucose oxidase, α-glucosidase precursor, and glucose dehydrogenase were also successfully identified. Importantly, the 19 newly identified proteins were mainly classified into three functional categories: oxidation-reduction (ergic53 CG6822-PA isoform A isoform 1, Sec61 CG9539-PA, and ADP/ATP translocase), protein binding (regucalcin and translationally controlled tumor protein CG4800-PA isoform 1), and lipid transport (apolipophorin-III-like protein). These new findings not only significantly increase the RJ proteome coverage but also help to provide new knowledge of RJ for honeybee biology and potential use for human health promotion.

Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

PubMed Central

Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; Lovell, John T.; Moyers, Brook T.; Baraoidan, Marietta; Naredo, Maria Elizabeth B.; McNally, Kenneth L.; Poland, Jesse; Bush, Daniel R.; Leung, Hei; Leach, Jan E.; McKay, John K.

2017-01-01

To ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. Here we demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor-intensive measures of flowering time, height, biomass, grain yield, and harvest index. Genetic mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution. PMID:28220807

Identifying dissolved oxygen variability and stress in tidal freshwater streams of northern New Zealand.

PubMed

Wilding, Thomas K; Brown, Edmund; Collier, Kevin J

2012-10-01

Tidal streams are ecologically important components of lotic network, and we identify dissolved oxygen (DO) depletion as a potentially important stressor in freshwater tidal streams of northern New Zealand. Other studies have examined temporal DO variability within rivers and we build on this by examining variability between streams as a basis for regional-scale predictors of risk for DO stress. Diel DO variability in these streams was driven by: (1) photosynthesis by aquatic plants and community respiration which produced DO maxima in the afternoon and minima early morning (range, 0.6-4.7 g/m(3)) as a product of the solar cycle and (2) tidal variability as a product of the lunar cycle, including saline intrusions with variable DO concentrations plus a small residual effect on freshwater DO for low-velocity streams. The lowest DO concentrations were observed during March (early autumn) when water temperatures and macrophyte biomass were high. Spatial comparisons indicated that low-gradient tidal streams were at greater risk of DO depletions harmful to aquatic life. Tidal influence was stronger in low-gradient streams, which typically drain more developed catchments, have lower reaeration potential and offer conditions more suitable for aquatic plant proliferation. Combined, these characteristics supported a simple method based on the extent of low-gradient channel for identifying coastal streams at risk of DO depletion. High-risk streams can then be targeted for riparian planting, nutrient limits and water allocation controls to reduce potential ecological stress.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 ofmore » 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.« less

Combined expressional analysis, bioinformatics and targeted proteomics identify new potential therapeutic targets in glioblastoma stem cells.

PubMed

Stangeland, Biljana; Mughal, Awais A; Grieg, Zanina; Sandberg, Cecilie Jonsgar; Joel, Mrinal; Nygård, Ståle; Meling, Torstein; Murrell, Wayne; Vik Mo, Einar O; Langmoen, Iver A

2015-09-22

Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures. The expression of these genes was confirmed in clinical samples (TCGA and REMBRANDT). The first nine genes were highly co-expressed in all GBM subtypes and were part of the same protein-protein interaction network. Furthermore, their combined up-regulation correlated negatively with patient survival in the mesenchymal GBM subtype. Using targeted proteomics and the COGNOSCENTE database we linked these genes to GBM signalling pathways.Nine genes: PBK, CENPA, KIF15, DEPDC1, CDC6, DLG7, KIF18A, EZH2 and HMMR should be further explored as targets for treatment of GBM.

The use of lead isotope analysis to identify potential sources of lead toxicosis in a juvenile bald eagle (Haliaeetus leucocephalus) with ventricular foreign bodies

USGS Publications Warehouse

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.

Identifying the Potential Organizational Impact of an Educational Peer Review Program

ERIC Educational Resources Information Center

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…

A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer

PubMed Central

Lunardi, Andrea; Ala, Ugo; Epping, Mirjam T.; Salmena, Leonardo; Clohessy, John G.; Webster, Kaitlyn A.; Wang, Guocan; Mazzucchelli, Roberta; Bianconi, Maristella; Stack, Edward C.; Lis, Rosina; Patnaik, Akash; Cantley, Lewis C.; Bubley, Glenn; Cordon-Cardo, Carlos; Gerald, William L.; Montironi, Rodolfo; Signoretti, Sabina; Loda, Massimo; Nardella, Caterina; Pandolfi, Pier Paolo

2013-01-01

Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten-loss driven mouse model of prostate cancer through the induction of apoptosis and proliferation block. Conversely, this response is bypassed upon deletion of either Trp53 or Lrf together with Pten, leading to the development of castration resistant prostate cancer (CRPC). Mechanistically, the integrated acquisition of data from mouse models and patients identifies the expression patterns of XAF1-XIAP/SRD5A1 as a predictive and actionable signature for CRPC. Importantly, we show that combined inhibition of XIAP, SRD5A1, and AR pathways overcomes castration resistance. Thus, our co-clinical approach facilitates stratification of patients and the development of tailored and innovative therapeutic treatments. PMID:23727860

Temporal effects in trend prediction: identifying the most popular nodes in the future.

PubMed

Zhou, Yanbo; Zeng, An; Wang, Wei-Hong

2015-01-01

Prediction is an important problem in different science domains. In this paper, we focus on trend prediction in complex networks, i.e. to identify the most popular nodes in the future. Due to the preferential attachment mechanism in real systems, nodes' recent degree and cumulative degree have been successfully applied to design trend prediction methods. Here we took into account more detailed information about the network evolution and proposed a temporal-based predictor (TBP). The TBP predicts the future trend by the node strength in the weighted network with the link weight equal to its exponential aging. Three data sets with time information are used to test the performance of the new method. We find that TBP have high general accuracy in predicting the future most popular nodes. More importantly, it can identify many potential objects with low popularity in the past but high popularity in the future. The effect of the decay speed in the exponential aging on the results is discussed in detail.

Temporal Effects in Trend Prediction: Identifying the Most Popular Nodes in the Future

PubMed Central

Zhou, Yanbo; Zeng, An; Wang, Wei-Hong

2015-01-01

Prediction is an important problem in different science domains. In this paper, we focus on trend prediction in complex networks, i.e. to identify the most popular nodes in the future. Due to the preferential attachment mechanism in real systems, nodes’ recent degree and cumulative degree have been successfully applied to design trend prediction methods. Here we took into account more detailed information about the network evolution and proposed a temporal-based predictor (TBP). The TBP predicts the future trend by the node strength in the weighted network with the link weight equal to its exponential aging. Three data sets with time information are used to test the performance of the new method. We find that TBP have high general accuracy in predicting the future most popular nodes. More importantly, it can identify many potential objects with low popularity in the past but high popularity in the future. The effect of the decay speed in the exponential aging on the results is discussed in detail. PMID:25806810

Identifying Recent HIV Infections: From Serological Assays to Genomics.

PubMed

Moyo, Sikhulile; Wilkinson, Eduan; Novitsky, Vladimir; Vandormael, Alain; Gaseitsiwe, Simani; Essex, Max; Engelbrecht, Susan; de Oliveira, Tulio

2015-10-23

In this paper, we review serological and molecular based methods to identify HIV infection recency. The accurate identification of recent HIV infection continues to be an important research area and has implications for HIV prevention and treatment interventions. Longitudinal cohorts that follow HIV negative individuals over time are the current gold standard approach, but they are logistically challenging, time consuming and an expensive enterprise. Methods that utilize cross-sectional testing and biomarker information have become an affordable alternative to the longitudinal approach. These methods use well-characterized biological makers to differentiate between recent and established HIV infections. However, recent results have identified a number of limitations in serological based assays that are sensitive to the variability in immune responses modulated by HIV subtypes, viral load and antiretroviral therapy. Molecular methods that explore the dynamics between the timing of infection and viral evolution are now emerging as a promising approach. The combination of serological and molecular methods may provide a good solution to identify recent HIV infection in cross-sectional data. As part of this review, we present the advantages and limitations of serological and molecular based methods and their potential complementary role for the identification of HIV infection recency.

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

PubMed Central

Hofmann, Sarah; Elman, Tamar; Shenoy, Anjana; Geiger, Tamar; Elkon, Ran; Ehrlich, Marcelo

2017-01-01

Abstract 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. PMID:28460002

Dynamic spatiotemporal trends of imported dengue fever in Australia

PubMed Central

Huang, Xiaodong; Yakob, Laith; Devine, Gregor; Frentiu, Francesca D.; Fu, Shiu-Yun; Hu, Wenbiao

2016-01-01

Dengue fever (DF) epidemics in Australia are caused by infected international travellers and confined to Northern Queensland where competent vectors exist. Recent analyses suggest that global trade and climate change could lead to the re-establishment of Ae. aegypti across the country and promote the spread of dengue nationally. This study aimed to describe the dynamic spatiotemporal trends of imported DF cases and their origins, identify the current and potential future high-risk regions and locate areas that might be at particular risk of dengue transmission should competent mosquito vectors expand their range. Our results showed that the geographical distribution of imported DF cases has significantly expanded in mainland Australia over the past decade. In recent years, the geographical distribution of source countries of DF has expanded from the Pacific region and Asia to include Africa and the Americas. Australia is now exposed to dengue importations from all of the regions involved in the current global pandemic. The public health implications of a range expansion of dengue mosquito vectors are severe. Enhanced mosquito surveillance in those areas that have high imported cases is called for to reduce emerging threats from this globally expanding pathogen. PMID:27460696

The force exerted by the membrane potential during protein import into the mitochondrial matrix

NASA Technical Reports Server (NTRS)

Shariff, Karim; Ghosal, Sandip; Matouschek, Andreas

2004-01-01

The force exerted on a targeting sequence by the electrical potential across the inner mitochondrial membrane is calculated on the basis of continuum electrostatics. The force is found to vary from 3.0 pN to 2.2 pN (per unit elementary charge) as the radius of the inner membrane pore (assumed aqueous) is varied from 6.5 to 12 A, its measured range. In the present model, the decrease in force with increasing pore width arises from the shielding effect of water. Since the pore is not very much wider than the distance between water molecules, the full shielding effect of water may not be present; the extreme case of a purely membranous pore without water gives a force of 3.2 pN per unit charge, which should represent an upper limit. When applied to mitochondrial import experiments on the protein barnase, these results imply that forces between 11 +/- 2 pN and 13.5 +/- 2.5 pN catalyze the unfolding of barnase in those experiments. A comparison of these results with unfolding forces measured using atomic force microscopy is made.

Biodiversity of Aspergillus species in some important agricultural products.

PubMed

Perrone, G; Susca, A; Cozzi, G; Ehrlich, K; Varga, J; Frisvad, J C; Meijer, M; Noonim, P; Mahakarnchanakul, W; Samson, R A

2007-01-01

The genus Aspergillus is one of the most important filamentous fungal genera. Aspergillus species are used in the fermentation industry, but they are also responsible of various plant and food secondary rot, with the consequence of possible accumulation of mycotoxins. The aflatoxin producing A. flavus and A. parasiticus, and ochratoxinogenic A. niger, A. ochraceus and A. carbonarius species are frequently encountered in agricultural products. Studies on the biodiversity of toxigenic Aspergillus species is useful to clarify molecular, ecological and biochemical characteristics of the different species in relation to their different adaptation to environmental and geographical conditions, and to their potential toxigenicity. Here we analyzed the biodiversity of ochratoxin producing species occurring on two important crops: grapes and coffee, and the genetic diversity of A. flavus populations occurring in agricultural fields. Altogether nine different black Aspergillus species can be found on grapes which are often difficult to identify with classical methods. The polyphasic approach used in our studies led to the identification of three new species occurring on grapes: A. brasiliensis, A. ibericus, and A. uvarum. Similar studies on the Aspergillus species occurring on coffee beans have evidenced in the last five years that A. carbonarius is an important source of ochratoxin A in coffee. Four new species within the black aspergilli were also identified in coffee beans: A. sclerotioniger, A. lacticoffeatus, A. sclerotiicarbonarius, and A. aculeatinus. The genetic diversity within A. flavus populations has been widely studied in relation to their potential aflatoxigenicity and morphological variants L- and S-strains. Within A. flavus and other Aspergillus species capable of aflatoxin production, considerable diversity is found. We summarise the main recent achievements in the diversity of the aflatoxin gene cluster in A. flavus populations, A. parasiticus and the non

Evaluation and its importance for nursing practice.

PubMed

Moule, Pam; Armoogum, Julie; Douglass, Emma; Taylor, Dr Julie

2017-04-26

Evaluation of service delivery is an important aspect of nursing practice. Service evaluation is being increasingly used and led by nurses, who are well placed to evaluate service and practice delivery. This article defines evaluation of services and wider care delivery and its relevance in NHS practice and policy. It aims to encourage nurses to think about how evaluation of services or practice differs from research and audit activity and to consider why and how they should use evaluation in their practice. A process for planning and conducting an evaluation and disseminating findings is presented. Evaluation in the healthcare context can be a complicated activity and some of the potential challenges of evaluation are described, alongside possible solutions. Further resources and guidance on evaluation activity to support nurses' ongoing development are identified.

Identifying organic nitrogen compounds in Rocky Mountain National Park aerosols

NASA Astrophysics Data System (ADS)

Beem, K. B.; Desyaterik, Y.; Ozel, M. Z.; Hamilton, J. F.; Collett, J. L.

2010-12-01

Nitrogen deposition is an important issue in Rocky Mountain National Park (RMNP). While inorganic nitrogen contributions to the ecosystems in this area have been studied, the sources of organic nitrogen are still largely unknown. To better understand the potential sources of organic nitrogen, filter samples were collected and analyzed for organic nitrogen species. Samples were collected in RMNP using a Thermo Fisher Scientific TSP (total suspended particulate) high-volume sampler with a PM2.5 impactor plate from April - November of 2008. The samples presented the opportunity to compare two different methods for identification of individual organic nitrogen species. The first type of analysis was performed with a comprehensive two dimensional gas chromatography (GCxGC) system using a nitrogen chemiluminescence detector (NCD). The filter samples were spiked with propanil in dichloromethane to use as an internal standard and were then extracted in water followed by solid phase extraction. The GCxGC system was comprised of a volatility based separation (DB5 column) followed by a polarity based separation (RXI-17 column). A NCD was used to specifically detect nitrogen compounds and remove the complex background matrix. Individual standards were used to identify peaks by comparing retention times. This method has the added benefit of an equimolar response for nitrogen so only a single calibration is needed for all species. In the second analysis, a portion of the same filter samples were extracted in DI water and analyzed with liquid chromatography coupled with mass spectroscopy (LC/MS). The separation was performed using a C18 column and a water-methanol gradient elution. Electrospray ionization into a time of flight mass spectrometer was used for detection. High accuracy mass measurement allowed unambiguous assignments of elemental composition of resulting ions. Positive and negative polarities were used since amines tend to show up in positive mode and nitrates in

SCS-CN and GIS-based approach for identifying potential water harvesting sites in the Kali Watershed, Mahi River Basin, India

NASA Astrophysics Data System (ADS)

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%.

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

NASA Astrophysics Data System (ADS)

Crago, Patrick E.; Makowski, Nathaniel S.

2014-10-01

Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location.

PubMed

Crago, Patrick E; Makowski, Nathaniel S

2014-10-01

Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

PubMed Central

Crago, Patrick E; Makowski, Nathan S

2014-01-01

Objective Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main Results Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases.. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

Genetic regulation of gene expression in the lung identifies CST3 and CD22 as potential causal genes for airflow obstruction.

PubMed

Lamontagne, Maxime; Timens, Wim; Hao, Ke; Bossé, Yohan; Laviolette, Michel; Steiling, Katrina; Campbell, Joshua D; Couture, Christian; Conti, Massimo; Sherwood, Karen; Hogg, James C; Brandsma, Corry-Anke; van den Berge, Maarten; Sandford, Andrew; Lam, Stephen; Lenburg, Marc E; Spira, Avrum; Paré, Peter D; Nickle, David; Sin, Don D; Postma, Dirkje S

2014-11-01

COPD is a complex chronic disease with poorly understood pathogenesis. Integrative genomic approaches have the potential to elucidate the biological networks underlying COPD and lung function. We recently combined genome-wide genotyping and gene expression in 1111 human lung specimens to map expression quantitative trait loci (eQTL). To determine causal associations between COPD and lung function-associated single nucleotide polymorphisms (SNPs) and lung tissue gene expression changes in our lung eQTL dataset. We evaluated causality between SNPs and gene expression for three COPD phenotypes: FEV(1)% predicted, FEV(1)/FVC and COPD as a categorical variable. Different models were assessed in the three cohorts independently and in a meta-analysis. SNPs associated with a COPD phenotype and gene expression were subjected to causal pathway modelling and manual curation. In silico analyses evaluated functional enrichment of biological pathways among newly identified causal genes. Biologically relevant causal genes were validated in two separate gene expression datasets of lung tissues and bronchial airway brushings. High reliability causal relations were found in SNP-mRNA-phenotype triplets for FEV(1)% predicted (n=169) and FEV(1)/FVC (n=80). Several genes of potential biological relevance for COPD were revealed. eQTL-SNPs upregulating cystatin C (CST3) and CD22 were associated with worse lung function. Signalling pathways enriched with causal genes included xenobiotic metabolism, apoptosis, protease-antiprotease and oxidant-antioxidant balance. By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified CST3 and CD22 as potential causal genes for airflow obstruction. This study also augmented the understanding of previously described COPD pathways. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Generators of the brainstem auditory evoked potential in cat. III: Identified cell populations.

PubMed

Melcher, J R; Kiang, N Y

1996-04-01

This paper examines the relationship between different brainstem cell populations and the brainstem auditory evoked potential (BAEP). First, we present a mathematical model relating the BAEP to underlying cellular activity. Then, we identify specific cellular generators of the click-evoked BAEP in cats by combining model-derived insights with key experimental data. These data include (a) a correspondence between particular brainstem regions and specific extrema in the BAEP waveform, determined from lesion experiments, and (b) values for model parameters derived from published physiological and anatomical information. Ultimately, we conclude (with varying degrees of confidence) that: (1) the earliest extrema in the BAEP are generated by spiral ganglion cells, (2) P2 is mainly generated by cochlear nucleus (CN) globular cells, (3) P3 is partly generated by CN spherical cells and partly by cells receiving inputs from globular cells, (4) P4 is predominantly generated by medial superior olive (MSO) principal cells, which are driven by spherical cells, (5) the generators of P5 are driven by MSO principal cells, and (6) the BAEP, as a whole, is generated mainly by cells with characteristic frequencies above 2 kHz. Thus, the BAEP in cats mainly reflects cellular activity in two parallel pathways, one originating with globular cells and the other with spherical cells. Since the globular cell pathway is poorly represented in humans, we suggest that the human BAEP is largely generated by brainstem cells in the spherical cell pathway. Given our conclusions, it should now be possible to relate activity in specific cell populations to psychophysical performance since the BAEP can be recorded in behaving humans and animals.

Identifying core competencies for public health epidemiologists.

PubMed

Bondy, Susan J; Johnson, Ian; Cole, Donald C; Bercovitz, Kim

2008-01-01

Public health authorities have prioritized the identification of competencies, yet little empirical data exist to support decisions on competency selection among particular disciplines. We sought perspectives on important competencies among epidemiologists familiar with or practicing in public health settings (local to national). Using a sequential, qualitative-quantitative mixed method design, we conducted key informant interviews with 12 public health practitioners familiar with front-line epidemiologists' practice, followed by a web-based survey of members of a provincial association of public health epidemiologists (90 respondents of 155 eligible) and a consensus workshop. Competency statements were drawn from existing core competency lists and those identified by key informants, and ranked by extent of agreement in importance for entry-level practitioners. Competencies in quantitative methods and analysis, critical appraisal of scientific evidence and knowledge transfer of scientific data to other members of the public health team were all regarded as very important for public health epidemiologists. Epidemiologist competencies focused on the provision, interpretation and 'translation' of evidence to inform decision-making by other public health professionals. Considerable tension existed around some potential competency items, particularly in the areas of more advanced database and data-analytic skills. Empirical data can inform discussions of discipline-specific competencies as one input to decisions about competencies appropriate for epidemiologists in the public health workforce.

Physician Rating Websites: What Aspects Are Important to Identify a Good Doctor, and Are Patients Capable of Assessing Them? A Mixed-Methods Approach Including Physicians' and Health Care Consumers' Perspectives.

PubMed

Rothenfluh, Fabia; Schulz, Peter J

2017-05-01

Physician rating websites (PRWs) offer health care consumers the opportunity to evaluate their doctor anonymously. However, physicians' professional training and experience create a vast knowledge gap in medical matters between physicians and patients. This raises ethical concerns about the relevance and significance of health care consumers' evaluation of physicians' performance. To identify the aspects physician rating websites should offer for evaluation, this study investigated the aspects of physicians and their practice relevant for identifying a good doctor, and whether health care consumers are capable of evaluating these aspects. In a first step, a Delphi study with physicians from 4 specializations was conducted, testing various indicators to identify a good physician. These indicators were theoretically derived from Donabedian, who classifies quality in health care into pillars of structure, process, and outcome. In a second step, a cross-sectional survey with health care consumers in Switzerland (N=211) was launched based on the indicators developed in the Delphi study. Participants were asked to rate the importance of these indicators to identify a good physician and whether they would feel capable to evaluate those aspects after the first visit to a physician. All indicators were ordered into a 4×4 grid based on evaluation and importance, as judged by the physicians and health care consumers. Agreement between the physicians and health care consumers was calculated applying Holsti's method. In the majority of aspects, physicians and health care consumers agreed on what facets of care were important and not important to identify a good physician and whether patients were able to evaluate them, yielding a level of agreement of 74.3%. The two parties agreed that the infrastructure, staff, organization, and interpersonal skills are both important for a good physician and can be evaluated by health care consumers. Technical skills of a doctor and outcomes

Systemic analysis of genome-wide expression profiles identified potential therapeutic targets of demethylation drugs for glioblastoma.

PubMed

Ning, Tongbo; Cui, Hao; Sun, Feng; Zou, Jidian

2017-09-05

Glioblastoma represents one of the most aggressive malignant brain tumors with high morbidity and motility. Demethylation drugs have been developed for its treatment with little efficacy has been observed. The purpose of this study was to screen therapeutic targets of demethylation drugs or bioactive molecules for glioblastoma through systemic bioinformatics analysis. We firstly downloaded genome-wide expression profiles from the Gene Expression Omnibus (GEO) and conducted the primary analysis through R software, mainly including preprocessing of raw microarray data, transformation between probe ID and gene symbol and identification of differential expression genes (DEGs). Secondly, functional enrichment analysis was conducted via the Database for Annotation, Visualization and Integrated Discovery (DAVID) to explore biological processes involved in the development of glioblastoma. Thirdly, we constructed protein-protein interaction (PPI) network of interested genes and conducted cross analysis for multi datasets to obtain potential therapeutic targets for glioblastoma. Finally, we further confirmed the therapeutic targets through real-time RT-PCR. As a result, biological processes that related to cancer development, amino metabolism, immune response and etc. were found to be significantly enriched in genes that differential expression in glioblastoma and regulated by 5'aza-dC. Besides, network and cross analysis identified ACAT2, UFC1 and CYB5R1 as novel therapeutic targets of demethylation drugs which also confirmed by real time RT-PCR. In conclusions, our study identified several biological processes and genes that involved in the development of glioblastoma and regulated by 5'aza-dC, which would be helpful for the treatment of glioblastoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Identifying sites for elk restoration in Arkansas

USGS Publications Warehouse

Telesco, R.L.; Van Manen, F.T.; Clark, J.D.; Cartwright, Michael E.

2007-01-01

We used spatial data to identify potential areas for elk (Cervus elaphus) restoration in Arkansas. To assess habitat, we used locations of 239 elk groups collected from helicopter surveys in the Buffalo National River area of northwestern Arkansas, USA, from 1992 to 2002. We calculated the Mahalanobis distance (D2) statistic based on the relationship between those elk-group locations and a suite of 9 landscape variables to evaluate winter habitat in Arkansas. We tested model performance in the Buffalo National River area by comparing the D2 values of pixels representing areas with and without elk pellets along 19 fixed-width transects surveyed in March 2002. Pixels with elk scat had lower D2 values than pixels in which we found no pellets (logistic regression: Wald χ2 = 24.37, P < 0.001), indicating that habitat characteristics were similar to those selected by the aerially surveyed elk. Our D2 model indicated that the best elk habitat primarily occurred in northern and western Arkansas and was associated with areas of high landscape heterogeneity, heavy forest cover, gently sloping ridge tops and valleys, low human population density, and low road densities. To assess the potential for elk–human conflicts in Arkansas, we used the analytical hierarchy process to rank the importance of 8 criteria based on expert opinion from biologists involved in elk management. The biologists ranked availability of forage on public lands as having the strongest influence on the potential for elk–human conflict (33%), followed by human population growth rate (22%) and the amount of private land in row crops (18%). We then applied those rankings in a weighted linear summation to map the relative potential for elk–human conflict. Finally, we used white-tailed deer (Odocoileus virginianus) densities to identify areas where success of elk restoration may be hampered due to meningeal worm (Parelaphostrongylus tenuis) transmission. By combining results of the 3 spatial data layers

Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous‐cell carcinoma

PubMed Central

Syed, Nazia; Barbhuiya, Mustafa A.; Pinto, Sneha M.; Nirujogi, Raja Sekhar; Renuse, Santosh; Datta, Keshava K.; Khan, Aafaque Ahmad; Srikumar, Kotteazeth; Prasad, T. S. Keshava; Kumar, M. Vijaya; Kumar, Rekha Vijay; Chatterjee, Aditi; Pandey, Akhilesh

2015-01-01

Esophageal squamous‐cell carcinoma (ESCC) is one of the most common malignancies in Asia. Currently, surgical resection of early‐stage tumor is the best available treatment. However, most patients present late when surgery is not an option. Data suggest that chemotherapy regimens are inadequate for clinical management of advanced cancer. Targeted therapy has emerged as one of the most promising approaches to treat several malignancies. A prerequisite for developing targeted therapy is prior knowledge of proteins and pathways that drive proliferation in malignancies. We carried out phosphotyrosine profiling across four different ESCC cell lines and compared it to non‐neoplastic Het‐1A cell line to identify activated tyrosine kinase signaling pathways in ESCC. A total of 278 unique phosphopeptides were identified across these cell lines. This included several tyrosine kinases and their substrates that were hyperphosphorylated in ESCC. Ephrin receptor A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry‐based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA‐based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation. PMID:25366905

The reduction potential of nitric oxide (NO) and its importance to NO biochemistry

PubMed Central

Bartberger, Michael D.; Liu, Wei; Ford, Eleonora; Miranda, Katrina M.; Switzer, Christopher; Fukuto, Jon M.; Farmer, Patrick J.; Wink, David A.; Houk, Kendall N.

2002-01-01

A potential of about −0.8 (±0.2) V (at 1 M versus normal hydrogen electrode) for the reduction of nitric oxide (NO) to its one-electron reduced species, nitroxyl anion (3NO−) has been determined by a combination of quantum mechanical calculations, cyclic voltammetry measurements, and chemical reduction experiments. This value is in accord with some, but not the most commonly accepted, previous electrochemical measurements involving NO. Reduction of NO to 1NO− is highly unfavorable, with a predicted reduction potential of about −1.7 (±0.2) V at 1 M versus normal hydrogen electrode. These results represent a substantial revision of the derived and widely cited values of +0.39 V and −0.35 V for the NO/3NO− and NO/1NO− couples, respectively, and provide support for previous measurements obtained by electrochemical and photoelectrochemical means. With such highly negative reduction potentials, NO is inert to reduction compared with physiological events that reduce molecular oxygen to superoxide. From these reduction potentials, the pKa of 3NO− has been reevaluated as 11.6 (±3.4). Thus, nitroxyl exists almost exclusively in its protonated form, HNO, under physiological conditions. The singlet state of nitroxyl anion, 1NO−, is physiologically inaccessible. The significance of these potentials to physiological and pathophysiological processes involving NO and O2 under reductive conditions is discussed. PMID:12177417

Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

DOE PAGES

Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; ...

2017-02-21

In order to ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. We demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor- intensive measures of flowering time, height, biomass, grain yield, and harvest index. Furthermore, geneticmore » mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution.« less

Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanger, Paul; Klassen, Stephen; Mojica, Julius P.

In order to ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. We demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor- intensive measures of flowering time, height, biomass, grain yield, and harvest index. Furthermore, geneticmore » mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution.« less

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

PubMed

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.

Molecular Docking Studies to Explore Potential Binding Pockets and Inhibitors for Chikungunya Virus Envelope Glycoproteins.

PubMed

Nguyen, Phuong T V; Yu, Haibo; Keller, Paul A

2017-03-11

The chikungunya virus (CHIKV) envelope glycoproteins are considered important potential targets for anti-CHIKV drug discovery due to their crucial roles in virus attachment and virus entry. In this study, using two available crystal structures of the immature and mature forms of envelope glycoproteins, virtual screenings based on blind dockings and focused dockings were carried out to identify potential binding pockets and hit compounds for the virus. The chemical library database of compounds, NCI Diversity Set II, was used in these docking studies. In addition to reproducing previously reported examples, new binding pockets were identified, e.g., Pocket 2 in the 3N40, and Pocket 2 and Pocket 3 in the 3N42. Convergences in conformational sampling in docking using AutoDock Vina were evaluated. An analysis of docking results was carried out to understand interactions of the envelope glycoproteins complexes. Some key residues for interactions, for example Gly91 and His230, are identified as possessing important roles in the fusion process.

Neutronics Phenomena Important in Modeling and Simulation of Liquid-Fuel Molten Salt Reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diamond, David J.

This paper discusses liquid-fuel molten salt reactors, how they will operate under normal, transient, and accident conditions, and the results of an expert elicitation to determine the corresponding neutronic phenomena important to understanding their behavior. Identifying these phenomena will enable the U.S. Nuclear Regulatory Commission (NRC) to develop or identify modeling functionalities and tools required to carry out confirmatory analyses that examine the validity and accuracy of applicants’ calculations and help determine the margin of safety in plant design. NRC frequently does an expert elicitation using a Phenomena Identification and Ranking Table (PIRT) to identify and evaluate the state ofmore » knowledge of important modeling phenomena. However, few details about the design of these reactors and the sequence of events during accidents are known, so the process used was considered a preliminary PIRT. A panel met to define phenomena that would need to be modeled and considered the impact/importance of each phenomenon with respect to specific figures-of-merit (FoMs) (e.g., power distribution, fluence, kinetics parameters and reactivity). Each FoM reflected a potential impact on radionuclide release or loss of a barrier to release. The panel considered what the path forward might be with respect to being able to model the phenomenon in a simulation code. Results are explained for both thermal and fast spectrum designs.« less

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

PubMed

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 (p<0.01), and forest proximity (p<0.05). Using the model incorporating these locational parameters, we mapped the areas under the elevated risk of illegal C&D waste 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.

Biological soil crusts: Diminutive communities of potential global importance

USGS Publications Warehouse

Ferrenberg, Scott; Tucker, Colin; Reed, Sasha C.

2017-01-01

Biological soil crusts (biocrusts) are widespread, diverse communities of cyanobacteria, fungi, lichens, and mosses living on soil surfaces, primarily in drylands. Biocrusts can locally govern primary production, soil fertility, hydrology, and surface energy balance, with considerable variation in these functions across alternate community states. Further, these communities have been implicated in Earth system functioning via potential influences on global biogeochemistry and climate. Biocrusts are easily destroyed by disturbances and appear to be exceptionally vulnerable to warming temperatures and altered precipitation inputs, signaling possible losses of dryland functions with global change. Despite these concerns, we lack sufficient spatiotemporal data on biocrust function, cover, and community structure to confidently assess their ecological roles across the extensive dryland biome. Here, we present the case for cross-scale research and restoration efforts coupled with remote-sensing and modeling approaches that improve our collective understanding of biocrust responses to global change and the ecological roles of these diminutive communities at global scales.

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

PubMed

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.

Herbicidal potential of ophiobolins produced by Drechslera gigantea.

PubMed

Evidente, Antonio; Andolfi, Anna; Cimmino, Alessio; Vurro, Maurizio; Fracchiolla, Mariano; Charudattan, Raghavan

2006-03-08

Drechslera gigantea, a potential mycoherbicide of grass weeds, was isolated in Florida from naturally infected large crabgrass (Digitaria sanguinalis); it produces phytotoxic metabolites in liquid culture. The main metabolite was identified by spectroscopic methods and optical properties as ophiobolin A (1), a well-known phytotoxic sesterterpene produced by several phytopathogenic fungi of important crops and already extensively studied for its interesting biological activities. The other three minor metabolites proved to be related to ophiobolin A and were identified using the same techniques as 6-epi-ophiobolin A and 3-anhydro-6-epi-ophiobolin A (2 and 3) and ophiobolin I (4). Assayed on punctured detached leaves of several grass and dicotyledon weeds, ophiobolin A proved to be on average more phytotoxic as compared to the other related compounds. Some structural features appear to be important for the phytoxicity, such as the hydroxy group at C-3, the stereochemistry at C-6, and the aldehyde group at C-7. Furthermore, grass weeds usually proved to be more sensitive to the phytotoxins than dicotyledons, on which ophiobolin A caused the appearance of large necrosis even at the lowest concentration assayed. This is the first report about the production of ophiobolins from D. gigantea and of the proposed use as potential natural herbicides against grass weeds.

The study of trypanosome species circulating in domestic animals in two human African trypanosomiasis foci of Côte d'Ivoire identifies pigs and cattle as potential reservoirs of Trypanosoma brucei gambiense

PubMed Central

N’Djetchi, Martial Kassi; Ilboudo, Hamidou; Koffi, Mathurin; Kaboré, Jacques; Kaboré, Justin Windingoudi; Kaba, Dramane; Courtin, Fabrice; Coulibaly, Bamoro; Fauret, Pierre; Kouakou, Lingué; Ravel, Sophie; Deborggraeve, Stijn; Solano, Philippe; De Meeûs, Thierry; Bucheton, Bruno

2017-01-01

Background Important control efforts have led to a significant reduction of the prevalence of human African trypanosomiasis (HAT) in Côte d’Ivoire, but the disease is still present in several foci. The existence of an animal reservoir of Trypanosoma brucei gambiense may explain disease persistence in these foci where animal breeding is an important source of income but where the prevalence of animal African trypanosomiasis (AAT) is unknown. The aim of this study was to identify the trypanosome species circulating in domestic animals in both Bonon and Sinfra HAT endemic foci. Methodology/Principal findings 552 domestic animals (goats, pigs, cattle and sheep) were included. Blood samples were tested for trypanosomes by microscopic observation, species-specific PCR for T. brucei sl, T. congolense, T. vivax and subspecies-specific PCR for T. b. gambiense and T. b. gambiense immune trypanolysis (TL). Infection rates varied significantly between animal species and were by far the highest in pigs (30%). T. brucei s.l was the most prevalent trypanosome species (13.7%) followed by T. congolense. No T. b. gambiense was identified by PCR while high TL positivity rates were observed using T. b. gambiense specific variants (up to 27.6% for pigs in the Bonon focus). Conclusion This study shows that domestic animals are highly infected by trypanosomes in the studied foci. This was particularly true for pigs, possibly due to a higher exposure of these animals to tsetse flies. Whereas T. brucei s.l. was the most prevalent species, discordant results were obtained between PCR and TL regarding T. b. gambiense identification. It is therefore crucial to develop better tools to study the epidemiological role of potential animal reservoir for T. b. gambiense. Our study illustrates the importance of “one health” approaches to reach HAT elimination and contribute to AAT control in the studied foci. PMID:29045405

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

PubMed Central

Li, Ying; Wang, Jiaxing; Allingham, R. Rand; Hauser, Michael A.; Wiggs, Janey L.; Geisert, Eldon E.

2018-01-01

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 SNP

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

PubMed Central

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

2014-01-01

of the other potential pathogens identified in this study. PMID:24943374

Machine learning with naturally labeled data for identifying abbreviation definitions.

PubMed

Yeganova, Lana; Comeau, Donald C; Wilbur, W John

2011-06-09

The rapid growth of biomedical literature requires accurate text analysis and text processing tools. Detecting abbreviations and identifying their definitions is an important component of such tools. Most existing approaches for the abbreviation definition identification task employ rule-based methods. While achieving high precision, rule-based methods are limited to the rules defined and fail to capture many uncommon definition patterns. Supervised learning techniques, which offer more flexibility in detecting abbreviation definitions, have also been applied to the problem. However, they require manually labeled training data. In this work, we develop a machine learning algorithm for abbreviation definition identification in text which makes use of what we term naturally labeled data. Positive training examples are naturally occurring potential abbreviation-definition pairs in text. Negative training examples are generated by randomly mixing potential abbreviations with unrelated potential definitions. The machine learner is trained to distinguish between these two sets of examples. Then, the learned feature weights are used to identify the abbreviation full form. This approach does not require manually labeled training data. We evaluate the performance of our algorithm on the Ab3P, BIOADI and Medstract corpora. Our system demonstrated results that compare favourably to the existing Ab3P and BIOADI systems. We achieve an F-measure of 91.36% on Ab3P corpus, and an F-measure of 87.13% on BIOADI corpus which are superior to the results reported by Ab3P and BIOADI systems. Moreover, we outperform these systems in terms of recall, which is one of our goals.

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

NASA Astrophysics Data System (ADS)

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

Comparative genomics of biotechnologically important yeasts

PubMed Central

Riley, Robert; Haridas, Sajeet; Wolfe, Kenneth H.; Lopes, Mariana R.; Hittinger, Chris Todd; Göker, Markus; Salamov, Asaf A.; Wisecaver, Jennifer H.; Long, Tanya M.; Aerts, Andrea L.; Barry, Kerrie W.; Choi, Cindy; Clum, Alicia; Coughlan, Aisling Y.; Deshpande, Shweta; Douglass, Alexander P.; Hanson, Sara J.; Klenk, Hans-Peter; LaButti, Kurt M.; Lapidus, Alla; Lindquist, Erika A.; Lipzen, Anna M.; Meier-Kolthoff, Jan P.; Ohm, Robin A.; Otillar, Robert P.; Pangilinan, Jasmyn L.; Peng, Yi; Rosa, Carlos A.; Scheuner, Carmen; Sibirny, Andriy A.; Slot, Jason C.; Stielow, J. Benjamin; Sun, Hui; Kurtzman, Cletus P.; Blackwell, Meredith; Grigoriev, Igor V.

2016-01-01

Ascomycete yeasts are metabolically diverse, with great potential for biotechnology. Here, we report the comparative genome analysis of 29 taxonomically and biotechnologically important yeasts, including 16 newly sequenced. We identify a genetic code change, CUG-Ala, in Pachysolen tannophilus in the clade sister to the known CUG-Ser clade. Our well-resolved yeast phylogeny shows that some traits, such as methylotrophy, are restricted to single clades, whereas others, such as l-rhamnose utilization, have patchy phylogenetic distributions. Gene clusters, with variable organization and distribution, encode many pathways of interest. Genomics can predict some biochemical traits precisely, but the genomic basis of others, such as xylose utilization, remains unresolved. Our data also provide insight into early evolution of ascomycetes. We document the loss of H3K9me2/3 heterochromatin, the origin of ascomycete mating-type switching, and panascomycete synteny at the MAT locus. These data and analyses will facilitate the engineering of efficient biosynthetic and degradative pathways and gateways for genomic manipulation. PMID:27535936

Genomic analysis of adult B-ALL identifies potential markers of shorter survival.

PubMed

Patel, Shiven; Mason, Clinton C; Glenn, Martha J; Paxton, Christian N; South, Sara T; Cessna, Melissa H; Asch, Julie; Cobain, Erin F; Bixby, Dale L; Smith, Lauren B; Reshmi, Shalini; Gastier-Foster, Julie M; Schiffman, Joshua D; Miles, Rodney R

2017-05-01

B lymphoblastic leukemia (B-ALL) in adults has a higher risk of relapse and lower long-term survival than pediatric B-ALL, but data regarding genetic prognostic biomarkers are much more limited for adult patients. We identified 70 adult B-ALL patients from three institutions and performed genome-wide analysis via single nucleotide polymorphism (SNP) arrays on DNA isolated from their initial diagnostic sample and, when available, relapse bone marrow specimens to identify recurring copy number alterations (CNA). As B-cell developmental genes play a crucial role in this leukemia, we assessed such for recurrent deletions in diagnostic and relapse samples. We confirmed previous findings that the most prevalent deletions of these genes occur in CDKN2A, IKZF1, and PAX5, with several others at lower frequencies. Of the 16 samples having paired diagnostic and relapse samples, 5 showed new deletions in these recurrent B-cell related genes and 8 showed abolishment. Deletion of EBF1 heralded a significant negative prognostic impact on relapse free survival in univariate and multivariate analyses. The combination of both a CDKN2A/B deletion and an IKZF1 alteration (26% of cases) also showed a trend toward predicting worse overall survival compared to having only one or neither of these deletions. These findings add to the understanding of genomic influences on this comparably understudied disease cohort that upon further validation may help identify patients who would benefit from upfront treatment intensification. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identifying potential selective fluorescent probes for cancer-associated protein carbonic anhydrase IX using a computational approach.

PubMed

Kamstra, Rhiannon L; Floriano, Wely B

2014-11-01

Carbonic anhydrase IX (CAIX) is a biomarker for tumor hypoxia. Fluorescent inhibitors of CAIX have been used to study hypoxic tumor cell lines. However, these inhibitor-based fluorescent probes may have a therapeutic effect that is not appropriate for monitoring treatment efficacy. In the search for novel fluorescent probes that are not based on known inhibitors, a database of 20,860 fluorescent compounds was virtually screened against CAIX using hierarchical virtual ligand screening (HierVLS). The screening database contained 14,862 compounds tagged with the ATTO680 fluorophore plus an additional 5998 intrinsically fluorescent compounds. Overall ranking of compounds to identify hit molecular probe candidates utilized a principal component analysis (PCA) approach. Four potential binding sites, including the catalytic site, were identified within the structure of the protein and targeted for virtual screening. Available sequence information for 23 carbonic anhydrase isoforms was used to prioritize the four sites based on the estimated "uniqueness" of each site in CAIX relative to the other isoforms. A database of 32 known inhibitors and 478 decoy compounds was used to validate the methodology. A receiver-operating characteristic (ROC) analysis using the first principal component (PC1) as predictive score for the validation database yielded an area under the curve (AUC) of 0.92. AUC is interpreted as the probability that a binder will have a better score than a non-binder. The use of first component analysis of binding energies for multiple sites is a novel approach for hit selection. The very high prediction power for this approach increases confidence in the outcome from the fluorescent library screening. Ten of the top scoring candidates for isoform-selective putative binding sites are suggested for future testing as fluorescent molecular probe candidates. Copyright © 2014 Elsevier Inc. All rights reserved.

Potential mechanisms of resistance to venetoclax and strategies to circumvent it.

PubMed

Tahir, Stephen K; Smith, Morey L; Hessler, Paul; Rapp, Lisa Roberts; Idler, Kenneth B; Park, Chang H; Leverson, Joel D; Lam, Lloyd T

2017-06-02

Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges. In order to gain a more comprehensive insight into the nature of venetoclax resistance mechanisms, we evaluated the changes in the BCL-2 family members at the genetic and expression levels in seven different venetoclax-resistant derived leukemia and lymphoma cell lines. Gene and protein expression analyses identified a number of different alterations in the expression of pro- and anti-apoptotic BCL-2 family members. In the resistant derived cells, an increase in either or both the anti-apoptotic proteins BCL-X L or MCL-1, which are not targeted by venetoclax was observed, and either concomitant or exclusive with a decrease in one or more pro-apoptotic proteins. In addition, mutational analysis also revealed a mutation in the BH3 binding groove (F104L) that could potentially interfere with venetoclax-binding. Not all changes may be causally related to venetoclax resistance and may only be an epiphenomenon. For resistant cell lines showing elevations in BCL-X L or MCL-1, strong synergistic cell killing was observed when venetoclax was combined with either BCL-X L - or MCL-1-selective inhibitors, respectively. This highlights the importance of BCL-X L - and MCL-1 as causally contributing to venetoclax resistance. Overall our study identified numerous changes in multiple resistant lines; the changes were neither mutually exclusive nor universal across the cell lines tested, thus exemplifying the complexity

In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

PubMed Central

Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

2015-01-01

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. PMID:25569258

Non-specific effects of vaccines: plausible and potentially important, but implications uncertain.

PubMed

Pollard, Andrew J; Finn, Adam; Curtis, Nigel

2017-11-01

Non-specific effects (NSE) or heterologous effects of vaccines are proposed to explain observations in some studies that certain vaccines have an impact beyond the direct protection against infection with the specific pathogen for which the vaccines were designed. The importance and implications of such effects remain controversial. There are several known immunological mechanisms which could lead to NSE, since it is widely recognised that the generation of specific immunity is initiated by non-specific innate immune mechanisms that may also have wider effects on adaptive immune function. However, there are no published studies that demonstrate a mechanistic link between such immunological phenomena and clinically relevant NSE in humans. While it is highly plausible that some vaccines do have NSE, their magnitude and duration, and thus importance, remain uncertain. Although the WHO recently concluded that current evidence does not justify changes to immunisation policy, further studies of sufficient size and quality are needed to assess the importance of NSE for all-cause mortality. This could provide insights into vaccine immunobiology with important implications for infant health and survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical incidents involving students on placement: an analysis of incident reports to identify potential risk factors.

PubMed

Gaida, J E; Maloney, S; Lo, K; Morgan, P

2015-06-01

Students are sometimes involved in incidents during clinical training. To the authors' knowledge, no quantitative studies of incidents specifically involving physiotherapy students on clinical placement are available in the literature. A retrospective audit (2008 to 2011) of incident reports involving physiotherapy students was conducted to identify the nature and features of incidents. The study aimed to determine if injuries to a student or patient were more or less likely when the supervisor was in close proximity, and whether students with lower academic performance in their preclinical semester were more likely to be involved in an incident. There were 19 care-delivery-related and three equipment-related incidents. There were no incidents of violent, aggressive or demeaning behaviour towards students. The incident rate was 9.0/100,000 student-hours for third-year students and 6.8/100,000 student-hours for fourth-year students. The majority of incidents (55%) occurred from 11 am to 12-noon and from 3 pm to 3.30 pm. Incidents more often resulted in patient or student injury when the supervisor was not in close proximity (approximately 50% vs approximately 20%), although the difference was not significant (P=0.336). The academic results of students involved in incidents were equivalent to the whole cohort in their preclinical semester {mean 75 [standard deviation (SD) 6] vs 76 (SD 7); P=0.488}. The unexpected temporal clustering of incidents warrants further investigation. Student fatigue may warrant attention as a potential contributor; however, contextual factors, such as staff workload, along with organisational systems, structures and procedures may be more relevant. The potential relationship between supervisor proximity and injury also warrants further exploration. The findings of the present study should be integrated into clinical education curricula and communicated to clinical educators. Copyright © 2014 Chartered Society of Physiotherapy. Published by

Assessing the connection between health and education: identifying potential leverage points for public health to improve school attendance.

PubMed

Gase, Lauren N; Kuo, Tony; Coller, Karen; Guerrero, Lourdes R; Wong, Mitchell D

2014-09-01

We examined multiple variables influencing school truancy to identify potential leverage points to improve school attendance. A cross-sectional observational design was used to analyze inner-city data collected in Los Angeles County, California, during 2010 to 2011. We constructed an ordinal logistic regression model with cluster robust standard errors to examine the association between truancy and various covariates. The sample was predominantly Hispanic (84.3%). Multivariable analysis revealed greater truancy among students (1) with mild (adjusted odds ratio [AOR] = 1.57; 95% confidence interval [CI] = 1.22, 2.01) and severe (AOR = 1.80; 95% CI = 1.04, 3.13) depression (referent: no depression), (2) whose parents were neglectful (AOR = 2.21; 95% CI = 1.21, 4.03) or indulgent (AOR = 1.71; 95% CI = 1.04, 2.82; referent: authoritative parents), (3) who perceived less support from classes, teachers, and other students regarding college preparation (AOR = 0.87; 95% CI = 0.81, 0.95), (4) who had low grade point averages (AOR = 2.34; 95% CI = 1.49, 4.38), and (5) who reported using alcohol (AOR = 3.47; 95% CI = 2.34, 5.14) or marijuana (AOR = 1.59; 95% CI = 1.06, 2.38) during the past month. Study findings suggest depression, substance use, and parental engagement as potential leverage points for public health to intervene to improve school attendance.

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

NASA Astrophysics Data System (ADS)

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.

Human genetics as a tool to identify progranulin regulators.

PubMed

Nicholson, Alexandra M; Finch, NiCole A; Rademakers, Rosa

2011-11-01

Frontotemporal lobar degeneration (FTLD) is a common neurodegenerative disorder that predominantly affects individuals under the age of 65. It is known that the most common pathological subtype is FTLD with TAR DNA-binding protein 43 inclusions (FTLD-TDP). FTLD has a strong genetic component with about 50% of cases having a positive family history. Mutations identified in the progranulin gene (GRN) have been shown to cause FTLD-TDP as a result of progranulin haploinsufficiency. These findings suggest a progranulin-dependent mechanism in this pathological FTLD subtype. Thus, identifying regulators of progranulin levels is essential for new therapies and treatments for FTLD and related disorders. In this review, we discuss the role of genetic studies in identifying progranulin regulators, beginning with the discovery of pathogenic GRN mutations and additional GRN risk variants. We also cover more recent genetic advances, including the detection of variants in the transmembrane protein 106 B gene that increase FTLD-TDP risk presumably by modulating progranulin levels and the identification of a potential progranulin receptor, sortilin. This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases.

HUMAN GENETICS AS A TOOL TO IDENTIFY PROGRANULIN REGULATORS

PubMed Central

Nicholson, Alexandra M.; Finch, NiCole A.; Rademakers, Rosa

2012-01-01

Frontotemporal lobar degeneration (FTLD) is a common neurodegenerative disorder that predominantly affects individuals under the age of 65. It is known that the most common pathological subtype is FTLD with TAR DNA-binding protein 43 inclusions (FTLD-TDP). FTLD has a strong genetic component with about 50% of cases having a positive family history. Mutations identified in the progranulin gene (GRN) have been shown to cause FTLD-TDP as a result of progranulin haploinsufficiency. These findings suggest a progranulin-dependent mechanism in this pathological FTLD subtype. Thus, identifying regulators of progranulin levels is essential for new therapies and treatments for FTLD and related disorders. In this review, we discuss the role of genetic studies in identifying progranulin regulators, beginning with the discovery of pathogenic GRN mutations and additional GRN risk variants. We also cover more recent genetic advances, including the detection of variants in the transmembrane protein 106 B gene that increase FTLD-TDP risk presumably by modulating progranulin levels and the identification of a potential progranulin receptor, sortilin. This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases. PMID:21626010

Identifying stressed and potentially unstable trees by aerial photography on Ohio's highways.

DOT National Transportation Integrated Search

2002-10-01

Trees are valuable assets and potential liabilities in a man dominated situations such as : along Ohios highways. While trees are often long-lived, they must decline and die like : any other living thing. Decline may be nearly instantaneous as in ...

A targeted genotyping approach enhances identification of variants in taste receptor and appetite/reward genes of potential functional importance for obesity-related porcine traits.

PubMed

Cirera, S; Clop, A; Jacobsen, M J; Guerin, M; Lesnik, P; Jørgensen, C B; Fredholm, M; Karlskov-Mortensen, P

2018-04-01

Taste receptors (TASRs) and appetite and reward (AR) mechanisms influence eating behaviour, which in turn affects food intake and risk of obesity. In a previous study, we used next generation sequencing to identify potentially functional mutations in TASR and AR genes and found indications for genetic associations between identified variants and growth and fat deposition in a subgroup of animals (n = 38) from the UNIK resource pig population. This population was created for studying obesity and obesity-related diseases. In the present study we validated results from our previous study by investigating genetic associations between 24 selected single nucleotide variants in TASR and AR gene variants and 35 phenotypes describing obesity and metabolism in the entire UNIK population (n = 564). Fifteen variants showed significant association with specific obesity-related phenotypes after Bonferroni correction. Six of the 15 genes, namely SIM1, FOS, TAS2R4, TAS2R9, MCHR2 and LEPR, showed good correlation between known biological function and associated phenotype. We verified a genetic association between potentially functional variants in TASR/AR genes and growth/obesity and conclude that the combination of identification of potentially functional variants by next generation sequencing followed by targeted genotyping and association studies is a powerful and cost-effective approach for increasing the power of genetic association studies. © 2018 Stichting International Foundation for Animal Genetics.

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia

PubMed Central

Yamada, Kazuo; Gerber, David J.; Iwayama, Yoshimi; Ohnishi, Tetsuo; Ohba, Hisako; Toyota, Tomoko; Aruga, Jun; Minabe, Yoshio; Tonegawa, Susumu; Yoshikawa, Takeo

2007-01-01

The calcineurin cascade is central to neuronal signal transduction, and genes in this network are intriguing candidate schizophrenia susceptibility genes. To replicate and extend our previously reported association between the PPP3CC gene, encoding the calcineurin catalytic γ-subunit, and schizophrenia, we examined 84 SNPs from 14 calcineurin-related candidate genes for genetic association by using 124 Japanese schizophrenic pedigrees. Four of these genes (PPP3CC, EGR2, EGR3, and EGR4) showed nominally significant association with schizophrenia. In a postmortem brain study, EGR1, EGR2, and EGR3 transcripts were shown to be down-regulated in the prefrontal cortex of schizophrenic, but not bipolar, patients. These findings raise a potentially important role for EGR genes in schizophrenia pathogenesis. Because EGR3 is an attractive candidate gene based on its chromosomal location close to PPP3CC within 8p21.3 and its functional link to dopamine, glutamate, and neuregulin signaling, we extended our analysis by resequencing the entire EGR3 genomic interval and detected 15 SNPs. One of these, IVS1 + 607A→G SNP, displayed the strongest evidence for disease association, which was confirmed in 1,140 independent case-control samples. An in vitro promoter assay detected a possible expression-regulatory effect of this SNP. These findings support the previous genetic association of altered calcineurin signaling with schizophrenia pathogenesis and identify EGR3 as a compelling susceptibility gene. PMID:17360599

Proteomic profiling of human plasma exosomes identifies PPAR{gamma} as an exosome-associated protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Looze, Christopher; Yui, David; Leung, Lester

Exosomes are nanovesicles that are released from cells as a mechanism of cell-free intercellular communication. Only a limited number of proteins have been identified from the plasma exosome proteome. Here, we developed a multi-step fractionation scheme incorporating gel exclusion chromatography, rate zonal centrifugation through continuous sucrose gradients, and high-speed centrifugation to purify exosomes from human plasma. Exosome-associated proteins were separated by SDS-PAGE and 66 proteins were identified by LC-MS/MS, which included both cellular and extracellular proteins. Furthermore, we identified and characterized peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), a nuclear receptor that regulates adipocyte differentiation and proliferation, as well as immune and inflammatorymore » cell functions, as a novel component of plasma-derived exosomes. Given the important role of exosomes as intercellular messengers, the discovery of PPAR{gamma} as a component of human plasma exosomes identifies a potential new pathway for the paracrine transfer of nuclear receptors.« less

Domain-Specific QSAR Model for Identifying Potential Estrogenic Activity of Phenols (ASCCT annual meeting)

EPA Science Inventory

Humans are potentially exposed to tens of thousands of man-made chemicals in the environment, some of which may mimic natural endocrine hormones and thus have the potential to be endocrine disruptors. Predictive in silico tools can be used to quickly and efficiently evaluate thes...

[MALDI-TOF and SELDI-TOF analysis: "tandem" techniques to identify potential biomarker in fibromyalgia].

PubMed

Giacomelli, C; Bazzichi, L; Giusti, L; Ciregia, F; Baldini, C; Da Valle, Y; De Feo, F; Sernissi, F; Rossi, A; Bombardieri, S; Lucacchini, A

2011-11-09

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.

Identifying potential differences in ontogentic ages between modern and archaeological Nacella deaurata shells, Tierra del Fuego, Argentina

NASA Astrophysics Data System (ADS)

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.

Identifying Student Potential for ICT Entrepreneurship Using Myers-Briggs Personality Type Indicators

ERIC Educational Resources Information Center

Johnston, Kevin A.; Andersen, Barry K.; Davidge-Pitts, Jennifer; Ostensen-Saunders, Mark

2009-01-01

Literature relating to personality and entrepreneurship has focused primarily on personality characteristics of traditional entrepreneurs. The focus of this study was on personality characteristics and temperaments of potential Information and Communication Technology (ICT) entrepreneurs. The main objective of the study was to evaluate the…

Congregate retirement communities: exploring the importance of services and activities as viewed by residents, potential residents, and administrators.

PubMed

Cangelosi, J D; McAlhany, J W

1989-03-01

Given the demographic trends, which indicate a need for facilities to accommodate a rapidly increasing and healthier elderly population, our study provides relevant and timely information for builders and health care administrators who are considering the initial construction of or addition to a congregate retirement facility. Though a congregate retirement facility must satisfy the demands of its residents for services and activities, cost considerations make it equally important for builders and administrators to offer only those services that are essential to meet those demands successfully. A multitude of services and activities may seem attractive to the general population and to investors as they formulate plans for new congregate facilities, but there is little need to provide or fund services and activities that are not used or demanded. Our findings show that the elderly target market for congregate facilities is primarily concerned with "necessity" services such as transportation, shopping, security, health care, and appearance, rather than the availability of a multitude of nonessential recreational and cultural activities. In summary, congregate facilities currently offer numerous activities and services that are not being used and are not important to residents or potential residents. Our exploratory research examines an area that has not been studied extensively and the findings are important in planning for the future. By using these findings, administrators and planners of congregate facilities should be able to determine effectively the types of services and activities that will satisfy the demands of the elderly during their retirement.

Estimating the potential water reuse based on fuzzy reasoning.

PubMed

Almeida, Giovana; Vieira, José; Marques, Alfeu Sá; Kiperstok, Asher; Cardoso, Alberto

2013-10-15

Studies worldwide suggest that the risk of water shortage in regions affected by climate change is growing. Decision support tools can help governments to identify future water supply problems in order to plan mitigation measures. Treated wastewater is considered a suitable alternative water resource and it is used for non-potable applications in many dry regions around the world. This work describes a decision support system (DSS) that was developed to identify current water reuse potential and the variables that determine the reclamation level. The DSS uses fuzzy inference system (FIS) as a tool and multi-criteria decision making is the conceptual approach behind the DSS. It was observed that water reuse level seems to be related to environmental factors such as drought, water exploitation index, water use, population density and the wastewater treatment rate, among others. A dataset was built to analyze these features through water reuse potential with a FIS that considered 155 regions and 183 cities. Despite some inexact fit between the classification and simulation data for agricultural and urban water reuse potential it was found that the FIS was suitable to identify the water reuse trend. Information on the water reuse potential is important because it issues a warning about future water supply needs based on climate change scenarios, which helps to support decision making with a view to tackling water shortage. Copyright © 2013 Elsevier Ltd. All rights reserved.

Differentially Variable Component Analysis (dVCA): Identifying Multiple Evoked Components using Trial-to-Trial Variability

NASA Technical Reports Server (NTRS)

Knuth, Kevin H.; Shah, Ankoor S.; Truccolo, Wilson; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.

2003-01-01

Electric potentials and magnetic fields generated by ensembles of synchronously active neurons in response to external stimuli provide information essential to understanding the processes underlying cognitive and sensorimotor activity. Interpreting recordings of these potentials and fields is difficult as each detector records signals simultaneously generated by various regions throughout the brain. We introduce the differentially Variable Component Analysis (dVCA) algorithm, which relies on trial-to-trial variability in response amplitude and latency to identify multiple components. Using simulations we evaluate the importance of response variability to component identification, the robustness of dVCA to noise, and its ability to characterize single-trial data. Finally, we evaluate the technique using visually evoked field potentials recorded at incremental depths across the layers of cortical area VI, in an awake, behaving macaque monkey.

GREAM: A Web Server to Short-List Potentially Important Genomic Repeat Elements Based on Over-/Under-Representation in Specific Chromosomal Locations, Such as the Gene Neighborhoods, within or across 17 Mammalian Species

PubMed Central

Chandrashekar, Darshan Shimoga; Dey, Poulami; Acharya, Kshitish K.

2015-01-01

Background Genome-wide repeat sequences, such as LINEs, SINEs and LTRs share a considerable part of the mammalian nuclear genomes. These repeat elements seem to be important for multiple functions including the regulation of transcription initiation, alternative splicing and DNA methylation. But it is not possible to study all repeats and, hence, it would help to short-list before exploring their potential functional significance via experimental studies and/or detailed in silico analyses. Result We developed the ‘Genomic Repeat Element Analyzer for Mammals’ (GREAM) for analysis, screening and selection of potentially important mammalian genomic repeats. This web-server offers many novel utilities. For example, this is the only tool that can reveal a categorized list of specific types of transposons, retro-transposons and other genome-wide repetitive elements that are statistically over-/under-represented in regions around a set of genes, such as those expressed differentially in a disease condition. The output displays the position and frequency of identified elements within the specified regions. In addition, GREAM offers two other types of analyses of genomic repeat sequences: a) enrichment within chromosomal region(s) of interest, and b) comparative distribution across the neighborhood of orthologous genes. GREAM successfully short-listed a repeat element (MER20) known to contain functional motifs. In other case studies, we could use GREAM to short-list repetitive elements in the azoospermia factor a (AZFa) region of the human Y chromosome and those around the genes associated with rat liver injury. GREAM could also identify five over-represented repeats around some of the human and mouse transcription factor coding genes that had conserved expression patterns across the two species. Conclusion GREAM has been developed to provide an impetus to research on the role of repetitive sequences in mammalian genomes by offering easy selection of more interesting

Thermal-Hydraulics Phenomena Important in Modeling and Simulation of Liquid-Fuel Molten Salt Reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bajorek, Stephen; Diamond, David J.

This paper discusses liquid-fuel molten salt reactors, how they will operate under normal, transient, and accident conditions, and the results of an expert elicitation to determine the corresponding thermalhydraulic phenomena important to understanding their behavior. Identifying these phenomena will enable the U.S. Nuclear Regulatory Commission (NRC) to develop or identify modeling functionalities and tools required to carry out confirmatory analyses that examine the validity and accuracy of an applicant’s calculations and help determine the margin of safety in plant design. NRC frequently does an expert elicitation using a Phenomena Identification and Ranking Table (PIRT) to identify and evaluate the statemore » of knowledge of important modeling phenomena. However, few details about the design of these reactors and the sequence of events during accidents are known, so the process used was considered a preliminary PIRT. A panel met to define phenomena that would need to be modeled and considered the impact/importance of each phenomenon with respect to specific figures-of-merit (FoMs) (e.g., salt temperature, velocity, and composition). Each FoM reflected a potential impact on radionuclide release or loss of a barrier to release. The panel considered what the path forward might be with respect to being able to model the phenomenon in a simulation code. Results are explained for both thermal and fast spectrum designs.« less

Identifying potential areas for biofuel production and evaluating the environmental effects: a case study of the James River Basin in the Midwestern United States

USGS Publications Warehouse

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.

Oligomers, organosulfates, and nitroxy organosulfates identified in rainwater

NASA Astrophysics Data System (ADS)

Altieri, K. E.; Turpin, B. J.; Seitzinger, S. P.

2008-12-01

Wet deposition is an important removal mechanism for atmospheric organic matter, and a potentially important input for receiving ecosystems, yet less than 50 percent of rainwater organic matter is considered chemically characterized. Precipitation samples collected in New Jersey, USA, were analyzed by negative ion ultra-high resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). We document the presence of 552 unique compounds in the rainwater over a mass range of 50-500 Da, in four compound classes (i.e., CHO, CHOS, CHON, and CHONS). The presence of oligomers, organosulfates, nitroxy organosulfates, organic acids, and linear alkylbenzene sulfonates is reported. Some compounds detected have distinct primary sources; however, the composition of the bulk of this material suggests it is formed in the atmosphere and composed of known contributors to secondary organic aerosol. For example, eight oligomer series known to form through aqueous photooxidation of methylglyoxal and organosulfate compounds known to form from 4 precursors in smog chamber experiments were identified in the rainwater samples. The oligomers, organosulfates, and nitroxy organosulfates detected in the rainwater could all contribute to the HULIS fraction of atmospheric organic matter.

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

PubMed Central

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

2015-01-01

Objective We sought to employ an innovative tool based on common biological pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB), in order to enhance investigators' ability to identify to highlight common mechanisms and underlying genetic factors responsible for SPTB. Study Design 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 etiologies. A hierarchical 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 using VEGAS software. Results 1028 women with SPTB were assigned phenotypes. Hierarchical clustering of the phenotypes revealed five major clusters. Cluster 1 (N=445) was characterized by maternal stress, cluster 2 (N=294) by premature membrane rupture, cluster 3 (N=120) by familial factors, and cluster 4 (N=63) by maternal comorbidities. Cluster 5 (N=106) was multifactorial, characterized by infection (INF), decidual hemorrhage (DH) and placental dysfunction (PD). These three phenotypes were highly correlated by Chi-square analysis [PD and DH (p<2.2e-6); PD and INF (p=6.2e-10); INF and DH (p=0.0036)]. Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarchal clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors underlying SPTB. PMID:26070700

Cooperative Development of the Digital Library: Identifying and Working with Potential Partners.

ERIC Educational Resources Information Center

Poland, Jean

In a university environment, the library can benefit from interest in the digital future on the part of other concerned groups. Computer science departments are natural partners in the development of digital libraries. Professional societies, for-profit companies, and foundations are also potential sources of support. Cornell University Library…

Codling Moth (Lepidoptera: Tortricidae) Establishment in China: Stages of Invasion and Potential Future Distribution.

PubMed

Zhu, Hongyu; Kumar, Sunil; Neven, Lisa G

2017-07-01

Codling moth (Cydia pomonella L.) is an internal feeding pest of apples and can cause substantial economic losses to fruit growers due to larval feeding which in turn degrades fruit quality and can result in complete crop loss if left uncontrolled. Although this pest originally developed in central Asia, it was not known to occur in China until 1953. For the first three decades the spread of codling moth within China was slow. Within the last three decades, addition of new commercial apple orchards and improved transportation, this pest has spread to over 131 counties in seven provinces in China. We developed regional (China) and global ecological niche models using MaxEnt to identify areas at highest potential risk of codling moth establishment and spread. Our objectives were to 1) predict the potential distribution of codling moth in China, 2) identify the important environmental factors associated with codling moth distribution in China, and 3) identify the different stages of invasion of codling moth in China. Human footprint, annual temperature range, precipitation of wettest quarter, and degree days ≥10 °C were the most important predictors associated with codling moth distribution. Our analysis identified areas where codling moth has the potential to establish, and mapped the different stages of invasion (i.e., potential for population stabilization, colonization, adaptation, and sink) of codling moth in China. Our results can be used in effective monitoring and management to stem the spread of codling moth in China. Published by Oxford University Press on behalf of the Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

Selecting for Creativity and Innovation Potential: Implications for Practice in Healthcare Education

ERIC Educational Resources Information Center

Patterson, Fiona; Zibarras, Lara Dawn

2017-01-01

The ability to innovate is an important requirement in many organisations. Despite this pressing need, few selection systems in healthcare focus on identifying the potential for creativity and innovation and so this area has been vastly under-researched. As a first step towards understanding how we might select for creativity and innovation, this…

Using a distribution and conservation status weighted hotspot approach to identify areas in need of conservation action to benefit Idaho bird species

USGS Publications Warehouse

Haines, Aaron M.; Leu, Matthias; Svancara, Leona K.; Wilson, Gina; Scott, J. Michael

2010-01-01

Identification of biodiversity hotspots (hereafter, hotspots) has become a common strategy to delineate important areas for wildlife conservation. However, the use of hotspots has not often incorporated important habitat types, ecosystem services, anthropogenic activity, or consistency in identifying important conservation areas. The purpose of this study was to identify hotspots to improve avian conservation efforts for Species of Greatest Conservation Need (SGCN) in the state of Idaho, United States. We evaluated multiple approaches to define hotspots and used a unique approach based on weighting species by their distribution size and conservation status to identify hotspot areas. All hotspot approaches identified bodies of water (Bear Lake, Grays Lake, and American Falls Reservoir) as important hotspots for Idaho avian SGCN, but we found that the weighted approach produced more congruent hotspot areas when compared to other hotspot approaches. To incorporate anthropogenic activity into hotspot analysis, we grouped species based on their sensitivity to specific human threats (i.e., urban development, agriculture, fire suppression, grazing, roads, and logging) and identified ecological sections within Idaho that may require specific conservation actions to address these human threats using the weighted approach. The Snake River Basalts and Overthrust Mountains ecological sections were important areas for potential implementation of conservation actions to conserve biodiversity. Our approach to identifying hotspots may be useful as part of a larger conservation strategy to aid land managers or local governments in applying conservation actions on the ground.

Impact of legal regulations and administrative policies on persons with SCI: identifying potential research priorities through expert interviews.

PubMed

Trezzini, Bruno; Phillips, Barbara

2014-01-01

To identify research gaps and potential research priorities regarding the impact that legal regulations and administrative policies might have on people with spinal cord injury (SCI) living in Switzerland. We conducted semi-structured interviews with 14 healthcare professionals working for or being associated with the largest SCI clinic in Switzerland. The transcribed interviews were content analyzed, involving qualitative description, and thematic analysis techniques. Four interrelated clusters of issues were corroborated: (1) social insurance, (2) caregiving, (3) work integration, and (4) aging. In addition, two overarching themes were identified: (1) fairness considerations and (2) unavailability of systematic empirical evidence. Work capacity assessment and family caregiving were deemed to be the most pressing research priority areas. Legal frameworks do play both a direct and an indirect role in the lives of people with SCI in Switzerland. This is particularly true with regard to various issues related to the social insurance system, such as family caregiving and work capacity assessment. The salience of these topics is closely related to major sociodemographic and political driving forces, i.e. aging and social insurance reforms. Research directly involving people with SCI is needed to further substantiate and refine the findings of this study. When dealing with issues related to work reintegration, aging, social insurance, and caregiving, rehabilitation professionals should take existing legal frameworks into account. Eligibility criteria for disability benefits may influence the therapy motivation of rehabilitation clients.

Potential of calcium isotopes to identify fractionations in vegetation: experimental approach

NASA Astrophysics Data System (ADS)

Cobert, F.; Schmitt, A.; Bourgade, P.; Stille, P.; Chabaux, F. J.; Badot, P.; Jaegler, T.

2010-12-01

This study aims to better understand the role of vegetation on the Ca cycle at the level of the critical zone of the Earth, in order to specify the mechanisms controlling the Ca absorption by plants at the rock/plant interface. To do this, we performed experiments using hydroponic plant cultures in a way that we could control the cooccuring geochemical and biological processes and determine the impact of the nutritive solution on the Ca cycle within plants. A dicotyledon and calcicole plant with rapid growth, the French bean (Phaseolus vulgaris L.), has been chosen to have access to one complete growth cycle. Several experiments have been conducted with two Ca concentrations, 5 (L) and 60 (H) ppm and two pH values (4 and 6) in the nutritive solution, for which the Ca concentration was maintained constant, so its Ca content is considered to be infinite. We determined Ca concentrations and isotopic ratios in the nutritive solution and in different organs (main roots, secondary roots, old and young stems, old and young leaves and fruits) at two different growth stages (10 days and 6 weeks). Our results show, in accord with previously published field studies, that the bean organs are all enriched in the light 40Ca isotope compared to the nutritive solution (e.g. Wigand et al., 2005; Page et al., 2008; Cenki-Tok et al., 2009; Holmden and Bélanger, 2010). We identify two fractionation levels. The first occurs during the uptake of the nutrient elements by the lateral roots. This implies that the main mechanisms of light isotope enrichments in the plant are due to electrochemical gradient transport processes taking place at this interface. The second fractionation can be observed within the plant itself and is due to the nature of the considered organ itself. Indeed structural reservoirs (primary roots, stem, reproductive organs) incorporate more the light 40Ca isotope compared to the transfer reservoirs (lateral roots, xylem sap, leaves). This could be linked to ion

GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells.

PubMed

Nain, Minu; Mukherjee, Sriparna; Karmakar, Sonali Porey; Paton, Adrienne W; Paton, James C; Abdin, M Z; Basu, Anirban; Kalia, Manjula; Vrati, Sudhanshu

2017-03-15

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of viral encephalitis in Southeast Asia with potential to become a global pathogen. Here, we identify glucose-regulated protein 78 (GRP78) as an important host protein for virus entry and replication. Using the plasma membrane fractions from mouse neuronal (Neuro2a) cells, mass spectroscopy analysis identified GRP78 as a protein interacting with recombinant JEV envelope protein domain III. GRP78 was found to be expressed on the plasma membranes of Neuro2a cells, mouse primary neurons, and human epithelial Huh-7 cells. Antibodies against GRP78 significantly inhibited JEV entry in all three cell types, suggesting an important role of the protein in virus entry. Depletion of GRP78 by small interfering RNA (siRNA) significantly blocked JEV entry into Neuro2a cells, further supporting its role in virus uptake. Immunofluorescence studies showed extensive colocalization of GRP78 with JEV envelope protein in virus-infected cells. This interaction was also confirmed by immunoprecipitation studies. Additionally, GRP78 was shown to have an important role in JEV replication, as treatment of cells post-virus entry with subtilase cytotoxin that specifically cleaved GRP78 led to a substantial reduction in viral RNA replication and protein synthesis, resulting in significantly reduced extracellular virus titers. Our results indicate that GRP78, an endoplasmic reticulum chaperon of the HSP70 family, is a novel host factor involved at multiple steps of the JEV life cycle and could be a potential therapeutic target. IMPORTANCE Recent years have seen a rapid spread of mosquito-borne diseases caused by flaviviruses. The flavivirus family includes West Nile, dengue, Japanese encephalitis, and Zika viruses, which are major threats to public health with potential to become global pathogens. JEV is the major cause of viral encephalitis in several parts of Southeast Asia, affecting a predominantly pediatric

Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

PubMed Central

Rangel, Roberto; Lee, Song-Choon; Hon-Kim Ban, Kenneth; Guzman-Rojas, Liliana; Mann, Michael B.; Newberg, Justin Y.; McNoe, Leslie A.; Selvanesan, Luxmanan; Ward, Jerrold M.; Rust, Alistair G.; Chin, Kuan-Yew; Black, Michael A.; Jenkins, Nancy A.; Copeland, Neal G.

2016-01-01

Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1. Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC. PMID:27849608

Whole organism high content screening identifies stimulators of pancreatic beta-cell proliferation.

PubMed

Tsuji, Naoki; Ninov, Nikolay; Delawary, Mina; Osman, Sahar; Roh, Alex S; Gut, Philipp; Stainier, Didier Y R

2014-01-01

Inducing beta-cell mass expansion in diabetic patients with the aim to restore glucose homeostasis is a promising therapeutic strategy. Although several in vitro studies have been carried out to identify modulators of beta-cell mass expansion, restoring endogenous beta-cell mass in vivo has yet to be achieved. To identify potential stimulators of beta-cell replication in vivo, we established transgenic zebrafish lines that monitor and allow the quantification of cell proliferation by using the fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology. Using these new reagents, we performed an unbiased chemical screen, and identified 20 small molecules that markedly increased beta-cell proliferation in vivo. Importantly, these structurally distinct molecules, which include clinically-approved drugs, modulate three specific signaling pathways: serotonin, retinoic acid and glucocorticoids, showing the high sensitivity and robustness of our screen. Notably, two drug classes, retinoic acid and glucocorticoids, also promoted beta-cell regeneration after beta-cell ablation. Thus, this study establishes a proof of principle for a high-throughput small molecule-screen for beta-cell proliferation in vivo, and identified compounds that stimulate beta-cell proliferation and regeneration.

Flash visual evoked potentials are not specific enough to identify parieto-occipital lobe involvement in term neonates after significant hypoglycaemia.

PubMed

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.

Identifying organisational principles and management practices important to the quality of health care services for chronic conditions.

PubMed

Frølich, Anne

2012-02-01

effect of financial incentives and public performance reporting on the behaviour of professionals and quality of care. Using secondary data, KP and the Danish health care system were compared in terms of six central dimensions: population, health care professionals, health care organisations, utilization patterns, quality measurements, and costs. Differences existed between the two systems on all dimensions, complicating the interpretation of findings. For instance, observed differences might be due to similar tendencies in the two health care systems that were observed at different times, rather than true structural differences. The expenses in the two health care systems were corrected for differences in the populations served and the purchasing power of currencies. However, no validated methods existed to correct for observed differences in case-mixes of chronic conditions. Data from a population of about half a million patients with diabetes in a large U.S. integrated health care delivery system affiliated with 41 medical centers employing 15 different CCM management practices was the basis for identifying effective management practices. Through the use of statistical modelling, the management practice of provider alerts was identified as most effective for promoting screening for hemoglobin A1c and lipid profile. The CCM was used as a framework for implementing four rehabilitation programs. The model promoted continuity of care and quality of health care services. New management practices were developed in the study, and known practices were further developed. However, the observational nature of the study limited the generalisability of the findings. In a structured literature survey focusing on the effect of financial incentives and public performance reporting on the quality of health care services, few studies documenting an effect were identified. The results varied, and important program aspects or contextual variables were often omitted. A model describing

Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids.