Sample records for identify potential indicators

  1. Patient Safety Indicators: using administrative data to identify potential patient safety concerns.

    PubMed Central

    Miller, M R; Elixhauser, A; Zhan, C; Meyer, G S

    2001-01-01

    OBJECTIVE: To develop Patient Safety Indicators (PSI) to identify potential in-hospital patient safety problems for the purpose of quality improvement. DATA SOURCE/STUDY DESIGN: The data source was 2,400,000 discharge records in the 1997 New York State Inpatient Database. PSI algorithms were developed using systematic literature reviews of indicators and hand searches of the ICD-9-CM code book. The prevalence of PSI events and associations between PSI events and patient-level and hospital-level characteristics, length of stay, in-hospital mortality, and hospital charges were examined. PRINCIPAL FINDINGS: PSIs were developed for 12 distinct clinical situations and an overall summary measure. The 1997 event rates per 10,000 discharges varied from 1.1 for foreign bodies left during procedure to 84.7 for birth traumas. Discharge records with PSI events had twofold to threefold longer hospital stays, twofold to 20-fold higher rates of in-hospital mortality, and twofold to eightfold higher total charges than records without PSI events. Multivariate logistic regression revealed that PSI events were primarily associated with increasing age (p < .001), hospitals performing more inpatient surgery (p < .001), and hospitals with higher percentage of beds in intensive care units (p < .001). CONCLUSIONS: The PSIs provide an efficient and user-friendly tool to identify potential inhospital patient safety problems for targeted institution-level quality improvement efforts. Until better error-reporting systems are developed the PSIs can serve to shed light on the problem of medical errors not limited solely to mortality because of errors. PMID:16148964

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

    PubMed Central

    Parsons, Marsha B; Reid, Dennis H; 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

  3. Direct and indirect indicators to identify potential leakage of contaminants associated with unconventional oil and gas development based on conceptual geochemical and isotopic monitoring approaches

    NASA Astrophysics Data System (ADS)

    Humez, P.; Mayer, B.; Negrel, P. J.; Lions, J.; Lagneau, V.; Kloppmann, W.; Ing, J.; Becker, V.; Nightingale, M.

    2014-12-01

    The extraction of tightly bound natural gas and oil raises environmental concerns regarding shallow drinking water resources. These concerns include impacts of migration of contaminants through induced and natural fractures, drilling imperfections, wastewater discharge and accidental spills. Improved understanding of the fate and transport of contaminants through long-term monitoring, and sharing of data between industry, regulators and researchers will help to effectively manage risks for shallow water resources associated with the unconventional gas and oil industry. Based on the North-American experiences related to unconventional oil and gas resources and monitoring approaches developed in the Carbon Capture and Storage (CCS) context, we suggest conceptual models for monitoring the potential contamination of shallow aquifers overlying production zones. The strength of sensitive geochemical tracers is demonstrated based on conceptual approaches (e.g. diffusion model) and field and tracer studies (e.g. geochemical and isotopic monitoring) with three objectives: 1) characterize subsurface derived contaminants as direct geochemical and isotopic indicators; 2) assess geochemical processes enhanced by the fluid intrusion; 3) understand parameters and processes which could impact or alter the geochemical and isotopic signatures of the contaminants (e.g. microbial oxidation, migration or transport processes etc.) to determine indirect indicators of potential contaminant leakage. This comprehensive geochemical and isotope approach using direct and indirect indicators with the analyses of major and minor ions, trace elements, and ?11B, ?7Li, ?34SSO4, ?18OSO4, 87Sr/86Sr, ?18OH2O, and ?2HH2O values in the CO2FIELDLAB project (Humez et al., 2014) allowed discriminating reactive mechanisms from non-reactive mixing processes associated with gas leakage within a shallow aquifer. These and other results indicate that this conceptual approach is promising for monitoring strategies related to unconventional oil and gas resources. Humez et al., 2014. Chem. Geol., 368, 11-30.

  4. Forecasting potential project risks through leading indicators to project outcome

    E-print Network

    Choi, Ji Won

    2007-09-17

    tool was developed and validated. A screening process was conducted through industry surveys after identifying potential leading indicators. Each time, industry professionals were asked to evaluate the negative impact of leading indicators on project...

  5. Identifying novel drug indications through automated reasoning Authors and Affiliations

    E-print Network

    Baral, Chitta

    , and identifying new drug indications from large networks can be a time-consuming process. Methodology In this work the development process. Drug repurposing is the process of finding a new indication for existing drug compoundsTitle Identifying novel drug indications through automated reasoning Authors and Affiliations Luis

  6. Forecasting potential project risks through leading indicators to project outcome 

    E-print Network

    Choi, Ji Won

    2007-09-17

    , the Construction Industry Institute (CII) formed a research team to develop a new tool that can forecast the potential risk of not meeting specific project outcomes based on assessing leading indicators. Thus, the leading indicators were identified and then the new...

  7. Identifying the Potential Biosphere of Mars

    Microsoft Academic Search

    Eriita G. Jones; Charles H. Lineweaver

    2008-01-01

    Our current knowledge of life on Earth indicates a basic requirement for\\u000aliquid water. The locations of present liquid water are therefore the logical\\u000asites to search for current life on Mars. We develop a picture of where on Mars\\u000athe regions with the highest potential near-surface liquid water abundance can\\u000abe found through a study of gullies. We also

  8. Developing a Monitoring System for Indicators in Middle Childhood: Identifying Measures

    Microsoft Academic Search

    Kristin Anderson Moore; Sharon Vandivere; Astrid Atienza; Tatia Thiot

    2008-01-01

    This paper builds on an initial paper (Moore and Theokas, Child Indicators Research, 2008 DOI 10.1007\\/s12187-008-9011-9) that conceptualizes elements of well-being relevant for the middle childhood period, identifies potential constructs and\\u000a develops criteria for indicators. Here, we follow up by identifying a set of 20 indicator constructs, half positive and half\\u000a negative. Of these 20, half measure child well-being and

  9. Identifying indicators of laboratory management performance: a multiple constituency approach.

    PubMed

    Zinn, J; Zalokowski, A; Hunter, L

    2001-01-01

    The challenges for laboratory management posed by cost control, managed care, organizational restructuring, information networking and health system integration call for new measures to evaluate how effectively laboratories manage emerging performance expectations. This study identifies the Delphi panel method in achieving consensus on measures of effectiveness and considers a specific application, the identification of indicators of laboratory performance, from the perspective of key constituencies. PMID:11233353

  10. Identifying basketball performance indicators in regular season and playoff games.

    PubMed

    García, Javier; Ibáñez, Sergio J; De Santos, Raúl Martinez; Leite, Nuno; Sampaio, Jaime

    2013-03-01

    The aim of the present study was to identify basketball game performance indicators which best discriminate winners and losers in regular season and playoffs. The sample used was composed by 323 games of ACB Spanish Basketball League from the regular season (n=306) and from the playoffs (n=17). A previous cluster analysis allowed splitting the sample in balanced (equal or below 12 points), unbalanced (between 13 and 28 points) and very unbalanced games (above 28 points). A discriminant analysis was used to identify the performance indicators either in regular season and playoff games. In regular season games, the winning teams dominated in assists, defensive rebounds, successful 2 and 3-point field-goals. However, in playoff games the winning teams' superiority was only in defensive rebounding. In practical applications, these results may help the coaches to accurately design training programs to reflect the importance of having different offensive set plays and also have specific conditioning programs to prepare for defensive rebounding. PMID:23717365

  11. Identifying Basketball Performance Indicators in Regular Season and Playoff Games

    PubMed Central

    García, Javier; Ibáñez, Sergio J.; De Santos, Raúl Martinez; Leite, Nuno; Sampaio, Jaime

    2013-01-01

    The aim of the present study was to identify basketball game performance indicators which best discriminate winners and losers in regular season and playoffs. The sample used was composed by 323 games of ACB Spanish Basketball League from the regular season (n=306) and from the playoffs (n=17). A previous cluster analysis allowed splitting the sample in balanced (equal or below 12 points), unbalanced (between 13 and 28 points) and very unbalanced games (above 28 points). A discriminant analysis was used to identify the performance indicators either in regular season and playoff games. In regular season games, the winning teams dominated in assists, defensive rebounds, successful 2 and 3-point field-goals. However, in playoff games the winning teams’ superiority was only in defensive rebounding. In practical applications, these results may help the coaches to accurately design training programs to reflect the importance of having different offensive set plays and also have specific conditioning programs to prepare for defensive rebounding. PMID:23717365

  12. Identifying early indicators in bipolar disorder: a qualitative study.

    PubMed

    Benti, Liliane; Manicavasagar, Vijaya; Proudfoot, Judy; Parker, Gordon

    2014-06-01

    The identification of early markers has become a focus for early intervention in bipolar disorder. Using a retrospective, qualitative methodology, the present study compares the early experiences of participants with bipolar disorder to those with unipolar depression up until their first diagnosed episode. The study focuses on differences in early home and school environments as well as putative differences in personality characteristics between the two groups. Finally we a compare and contrast prodromal symptoms in these two populations. Thirty-nine participants, 20 diagnosed with unipolar depression and 19 diagnosed with bipolar disorder, took part in the study. A semi-structured interview was developed to elicit information about participants' experiences prior to their first episode. Participants with bipolar disorder reported disruptive home environments, driven personality features, greater emotion dysregulation and adverse experiences during the school years, whereas participants with depression tended to describe more supportive home environments, and more compliant and introvert personality traits. Retrospective data collection and no corroborative evidence from other family members. No distinction was made between bipolar I and bipolar II disorder nor between melancholic and non-melancholic depression in the sample. Finally the study spanned over a 12-month period which does not allow for the possibility of diagnostic reassignment of some of the bipolar participants to the unipolar condition. These findings indicate that there may be benefits in combining both proximal and distal indicators in identifying a bipolar disorder phenotype which, in turn, may be relevant to the development of early intervention programs for young people with bipolar disorder. PMID:24174009

  13. Identifying and Nurturing Potential Academic Leaders

    ERIC Educational Resources Information Center

    Hoppe, Sherry L.

    2003-01-01

    With a move away from rotational chairs and a reluctance to tackle the conflicting responsibilities inherent in the lower levels of academic leadership, how can those at the top of the pipeline identify faculty who have the ability and desire to move through the ranks? What characteristics will increase the probability of willingness, commitment,…

  14. Life Potential as a Basic Demographic Indicator

    ERIC Educational Resources Information Center

    Goerlich, Francisco J.; Soler, Angel

    2013-01-01

    This paper proposes an indicator that integrates life expectancy with the demographic structure of the population for a given society. By doing this, we have a simple indicator of mortality and aging combined, which could be very useful for developed societies. As is widely known, life expectancy at birth is independent of the demographic…

  15. Skin Potential as an Indicator of Emotion

    ERIC Educational Resources Information Center

    Seligman, Linda

    1975-01-01

    The skin-potential responses of six college students were monitored while each was seen for 10 counseling sessions. Negative skin-potential responses were accompanied by feelings described as pleasant and released; positive responses were associated with unpleasant and inhibited feelings; and neutral responses were often associated with unpleasant…

  16. Identifying Quality Indicators of SAE and FFA: A Delphi Approach

    ERIC Educational Resources Information Center

    Jenkins, Charles Cordell, III; Kitchel, Tracy

    2009-01-01

    The purpose of this study was to determine quality indicators for SAE and FFA according to 36 experts across the United States. This is a part of a larger study looking at all components of the traditional three-circle model. The study utilized the Delphi technique to garner expert opinion about quality indicators in Agricultural Education. For…

  17. Identifying mechanistic indicators of childhood asthma from blood gene expression

    EPA Science Inventory

    Asthmatic individuals have been identified as a susceptible subpopulation for air pollutants. However, asthma represents a syndrome with multiple probable etiologies, and the identification of these asthma endotypes is critical to accurately define the most susceptible subpopula...

  18. Identifying Value Indicators and Social Capital in Community Health Partnerships

    ERIC Educational Resources Information Center

    Hausman, Alice J.; Becker, Julie; Brawer, Rickie

    2005-01-01

    Increasingly, public health practice is turning to the application of community collaborative models to improve population health status. Despite the growth of these activities, however, evaluations of the national demonstrations have indicated that community health partnerships fail to achieve measurable results and struggle to maintain integrity…

  19. Selection indices to identify drought-tolerant grain sorghum cultivars.

    PubMed

    Menezes, C B; Ticona-Benavente, C A; Tardin, F D; Cardoso, M J; Bastos, E A; Nogueira, D W; Portugal, A F; Santos, C V; Schaffert, R E

    2014-01-01

    Twenty-five cultivars of grain sorghum [Sorghum bicolor (L.) Moench] were examined under both drought stress and normal conditions in 4 experiments. In each condition, genotypes were evaluated in a factorial experiment using a randomized complete block design with 3 replications. Eight drought tolerance indices including stability tolerance index, mean productivity (MP), geometric MP, harmonic mean, stress susceptibility index, tolerance index, yield index, and yield stability index were estimated for each genotype based on grain yield under drought (Ys) and irrigated conditions (Yp). The results indicated that there were positive and significant correlations among Yp and Ys with geometric MP, MP, harmonic mean, and stability tolerance index, indicating that these factors are better predictors of Yp and Ys than tolerance index, stress susceptibility index, yield stability index, and yield index. Based on adjusted means at Yp and Ys, indices geometric MP, MP, harmonic mean, and stability tolerance index, unweighted pair group method with arithmetic mean cluster and biplot analysis, the most tolerant cultivars were '9929020', '9929034', and 'N 95B'. PMID:25501191

  20. Chrysophyte cysts as potential environmental indicators.

    USGS Publications Warehouse

    Adam, D.P.; Mahood, A.D.

    1981-01-01

    Many chrysophyte algae produce morphologically distinctive, siliceous, microscopic cysts during a resting stage of their life cycles; these cysts are often preserved in sediments. Scanning electron microscopy and Nomarski optics permit much more detailed observation of these cysts than was heretofore possible. Many cyst types are found only in specific habitats, such as montane lakes, wet meadows, ephemeral ponds, and Sphagnum bogs. In the samples studied, cysts seem to be most common in fluctuating fresh-water habitats of low to moderate pH and some winter freezing. Chrysophyte cysts have the potential to be a useful tool for modern environmental assessments and paleoecological studies of Cenozoic fresh-water lacustrine deposits. -from Authors

  1. Amu-Daria liquids potential indicated

    SciTech Connect

    O'Connor, R.B. Jr. (WaveTech Geophysical Inc., Denver, CO (US)); Sonnenberg, S.

    1991-06-03

    The Amu-Daria basin is a large, primarily gas producing basin located in the Soviet Republics of Turkmen and Uzbek and in Afghanistan. It covers an area roughly three fourths that of Texas and has estimated gas reserves on a scale of several hundred trillion cubic feet. Of these, somewhat less that 50% have been produced, proven, or indicated as probable by drilling. The basin is of current interest because roughly 66,000 sq km of exploration and producing rights in its lightly explored southern part will be put up for foreign competitive bidding by the Turkmen government later this year. The purpose of this article is to present growing evidence that significant new oil and condensate reserves, in addition to large new gas reserves, are likely to be found in the subsalt carbonate reef complexes of Upper Jurassic age in the deeper part of the basin. In fact, there is a very real possibility, that a good portion of these reserves may be found in fields of giant or even supergiant size.

  2. Identifying indicators of illegal behaviour: carnivore killing in human-managed landscapes

    PubMed Central

    St John, Freya A. V.; Keane, Aidan M.; Edwards-Jones, Gareth; Jones, Lauren; Yarnell, Richard W.; Jones, Julia P. G.

    2012-01-01

    Managing natural resources often depends on influencing people's behaviour, however effectively targeting interventions to discourage environmentally harmful behaviours is challenging because those involved may be unwilling to identify themselves. Non-sensitive indicators of sensitive behaviours are therefore needed. Previous studies have investigated people's attitudes, assuming attitudes reflect behaviour. There has also been interest in using people's estimates of the proportion of their peers involved in sensitive behaviours to identify those involved, since people tend to assume that others behave like themselves. However, there has been little attempt to test the potential of such indicators. We use the randomized response technique (RRT), designed for investigating sensitive behaviours, to estimate the proportion of farmers in north-eastern South Africa killing carnivores, and use a modified logistic regression model to explore relationships between our best estimates of true behaviour (from RRT) and our proposed non-sensitive indicators (including farmers' attitudes, and estimates of peer-behaviour). Farmers' attitudes towards carnivores, question sensitivity and estimates of peers' behaviour, predict the likelihood of farmers killing carnivores. Attitude and estimates of peer-behaviour are useful indicators of involvement in illicit behaviours and may be used to identify groups of people to engage in interventions aimed at changing behaviour. PMID:21795272

  3. SELECTING INDICATORS OF BIODIVERSITY FOR CONSERVATION PLANNING: IDENTIFYING THE MECHANISMS BEHIND INDICATOR GROUP PERFORMANCE

    EPA Science Inventory

    Most conservation planning is constrained by time and funding. In particular, the selection of areas to protect biodiversity must often be completed with limited data on species distributions. Consequently, different groups of species have been proposed as indicators or surroga...

  4. Imaging, Diagnosis, Prognosis Gene Expression Analysis Identifies Potential Biomarkers of

    E-print Network

    Hammerton, James

    Imaging, Diagnosis, Prognosis Gene Expression Analysis Identifies Potential Biomarkers to verify NF1 diagnosis, monitor tumor burden, and/or detect transformation. Experimental Design: We used of transformation to MPNST. Clin Cancer Res; 16(20); 5048­57. ©2010 AACR. Neurofibromatosis type 1 (NF1

  5. Identifying Potential Kidney Donors Using Social Networking Websites

    PubMed Central

    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 U.S. 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. PMID:23600791

  6. COLIPHAGES AS POTENTIAL VIRAL INDICATORS OF FECAL POLLUTION

    EPA Science Inventory

    Friedman, Stephanie D. In press. Coliphages as Potential Viral Indicators of Fecal Pollution (Abstract). To be presented at the SWS/GERS Fall Joint Society Meeting: Communication and Collaboration: Coastal Systems of the Gulf of Mexico and Southeastern United States, 6-9 October ...

  7. ORIGINAL PAPER Soil enzyme activities as potential indicators

    E-print Network

    Paris-Sud XI, Université de

    with the activities of soil enzymes in natural secondary forest stands and adjacent larch plantation stands. & Methods a mountainous area, and the top 15 cm of the mineral soils were sampled from each field. & Results The soil on sampling time, and that the soil enzyme activities can be used as potential indicators of soil soluble

  8. Urinary peptidomics identifies potential biomarkers for major depressive disorder.

    PubMed

    Wang, Ying; Chen, Jianjun; Chen, Liang; Zheng, Peng; Xu, Hong-Bo; Lu, Jia; Zhong, Jiaju; Lei, Yang; Zhou, Chanjuan; Ma, Qingwei; Li, Yan; Xie, Peng

    2014-06-30

    Major depressive disorder (MDD) is a debilitating psychiatric illness with no available objective laboratory-based diagnostic test. In this study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based peptidomics was applied to identify potential urinary diagnostic biomarkers for MDD. A training set of 42 first-episode drug-naive MDD patients and 28 age- and gender-matched healthy controls (HC) was used to develop a peptide diagnostic pattern. Then, the diagnostic efficacy of this pattern was assessed in an independent blinded test set consisting of 24 MDD patients and 13 age- and gender-matched HC. A combination of five potential biomarkers was identified, yielding a sensitivity of 91.7% and specificity of 84.6% in the test set. Moreover, the protein precursors of four of the five peptides were identified by tandem mass spectrometric analysis: serum albumin, apolipoprotein A-I, protein AMBP, and basement membrane-specific heparan sulfate proteoglycan core protein. Taken together, the peptide pattern may be valuable for establishing an objective laboratory-based diagnostic test for MDD. PMID:24661976

  9. Identifying psychophysiological indices of expert vs. novice performance in deadly force judgment and decision making

    PubMed Central

    Johnson, Robin R.; Stone, Bradly T.; Miranda, Carrie M.; Vila, Bryan; James, Lois; James, Stephen M.; Rubio, Roberto F.; Berka, Chris

    2014-01-01

    Objective: To demonstrate that psychophysiology may have applications for objective assessment of expertise development in deadly force judgment and decision making (DFJDM). Background: Modern training techniques focus on improving decision-making skills with participative assessment between trainees and subject matter experts primarily through subjective observation. Objective metrics need to be developed. The current proof of concept study explored the potential for psychophysiological metrics in deadly force judgment contexts. Method: Twenty-four participants (novice, expert) were recruited. All wore a wireless Electroencephalography (EEG) device to collect psychophysiological data during high-fidelity simulated deadly force judgment and decision-making simulations using a modified Glock firearm. Participants were exposed to 27 video scenarios, one-third of which would have justified use of deadly force. Pass/fail was determined by whether the participant used deadly force appropriately. Results: Experts had a significantly higher pass rate compared to novices (p < 0.05). Multiple metrics were shown to distinguish novices from experts. Hierarchical regression analyses indicate that psychophysiological variables are able to explain 72% of the variability in expert performance, but only 37% in novices. Discriminant function analysis (DFA) using psychophysiological metrics was able to discern between experts and novices with 72.6% accuracy. Conclusion: While limited due to small sample size, the results suggest that psychophysiology may be developed for use as an objective measure of expertise in DFDJM. Specifically, discriminant function measures may have the potential to objectively identify expert skill acquisition. Application: Psychophysiological metrics may create a performance model with the potential to optimize simulator-based DFJDM training. These performance models could be used for trainee feedback, and/or by the instructor to assess performance objectively. PMID:25100966

  10. Identifying potential cancer driver genes by genomic data integration.

    PubMed

    Chen, Yong; Hao, Jingjing; Jiang, Wei; He, Tong; Zhang, Xuegong; Jiang, Tao; Jiang, Rui

    2013-01-01

    Cancer is a genomic disease associated with a plethora of gene mutations resulting in a loss of control over vital cellular functions. Among these mutated genes, driver genes are defined as being causally linked to oncogenesis, while passenger genes are thought to be irrelevant for cancer development. With increasing numbers of large-scale genomic datasets available, integrating these genomic data to identify driver genes from aberration regions of cancer genomes becomes an important goal of cancer genome analysis and investigations into mechanisms responsible for cancer development. A computational method, MAXDRIVER, is proposed here to identify potential driver genes on the basis of copy number aberration (CNA) regions of cancer genomes, by integrating publicly available human genomic data. MAXDRIVER employs several optimization strategies to construct a heterogeneous network, by means of combining a fused gene functional similarity network, gene-disease associations and a disease phenotypic similarity network. MAXDRIVER was validated to effectively recall known associations among genes and cancers. Previously identified as well as novel driver genes were detected by scanning CNAs of breast cancer, melanoma and liver carcinoma. Three predicted driver genes (CDKN2A, AKT1, RNF139) were found common in these three cancers by comparative analysis. PMID:24346768

  11. GIS-BASED SPATIAL INDICES FOR IDENTIFICATION OF POTENTIAL NUTRIENT EXPORT AT WATERSHED SCALE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Spatial indices for identifying potential pollution resulting from manure spread on agricultural lands were developed for evaluating lands in support of decision and policy-making. An existing nutrient delivery ratio was modified by calculating actual distance that water would have to travel to reac...

  12. Potentials for Soil Enzyme as Indicators of Ecological Management

    NASA Technical Reports Server (NTRS)

    Senwo, Z. N.; Manu, A.; Coleman, T. L.

    1997-01-01

    Activity measurements of selected soil enzymes (cellulase, glucosidase, amidohydrolase, phosphatase, arylsulfatase) involved in carbon, nitrogen, phosphorus, and sulfur cycling in the biosphere, hold potential as early and sensitive indicators of soil ecological stress and restoration, These measurements are advantageous because the procedures are simple, rapid, and reproducible over time. Enzyme activities are sensitive to short-term changes in soil and kind-use management. Enzyme activities have also been observed to be closely related to soil organic matter proposed as an index of soil quality.

  13. Paediatric tonsillotomy--an Irish perspective on potential evolving indications.

    PubMed

    Fitzgerald, C; Oosthuizen, J C; Colreavy, M

    2015-04-01

    Tonsillotomy is the preferred treatment of some otolaryngologists for younger patients (under 3 years) with low body weight (under 15 kgs) and a history of obstructive sleep apnoea. The use of the technique in the same patient cohort for recurrent tonsillitis remains controversial. The aim of this study was to evaluate the indications and outcomes of paediatric patients undergoing tonsillotomy (with or without adenoidectomy) at a paediatric ENT centre in Ireland. Patients were identified from a prospectively maintained database and chart review was completed. A total of 23 patients were identified who underwent tonsillotomy. The commonest indication was Obstructive Sleep Apnoea (OSA) in 15 patients (65%). Outcomes following tonsillotomy compared favourably with traditional tonsillectomy. No intra-operative or post-operative complications were recorded (0%). No patients required readmission or later tonsillectomy (0%). At follow-up 19/23 patients with OSA (82.6%) had complete symptom resolution. Tonsillotomy appears to represent a safe, effective treatment option in the paediatric population, however, its role in recurrent tonsillitis remains controversial. PMID:26016307

  14. A Method to Identify Estuarine Macroinvertebrate Pollution Indicator Species in the Virginian Biogeogarphic Province

    EPA Science Inventory

    Macroinvertebrates are commonly used as biomonitors to detect pollution impacts in estuaries. The goal of this research was to identify estuarine benthic invertebrates that could be used as indicator species to detect presence or absence of pollution in the Virginian Biogeograph...

  15. Identifying and Characterizing Dominant Plants as an Indicator of Community Condition

    Microsoft Academic Search

    Christin B. Frieswyk; Carol A. Johnston; Joy B. Zedler

    2007-01-01

    Dominant species play key roles in shaping community structure, but their behavior is far from uniform. We speculated that recognition of different behaviors (determined objectively) would be an indicator of the condition of plant communities. We developed a species dominance index (SDI) to identify dominant species and compare their behavior across multiple spatial scales. The SDI is based on three

  16. Potential anti-cancer drugs commonly used for other indications.

    PubMed

    Hanusova, Veronika; Skalova, Lenka; Kralova, Vera; Matouskova, Petra

    2015-01-01

    An increasing resistance of mammalian tumor cells to chemotherapy along with the severe side effects of commonly used cytostatics has raised the urgency in the search for new anti-cancer agents. Several drugs originally approved for indications other than cancer treatment have recently been found to have a cytostatic effect on cancer cells. These drugs could be expediently repurposed as anti-cancer agents, since they have already been tested for toxicity in humans and animals. The groups of newly recognized potential cytostatics discussed in this review include benzimidazole anthelmintics (albendazole, mebendazole, flubendazole), anti-hypertensive drugs (doxazosin, propranolol), psychopharmaceuticals (chlorpromazine, clomipramine) and antidiabetic drugs (metformin, pioglitazone). All these drugs have a definite potential to be used especially in combinations with other cytostatics; the chemotherapy targeting of multiple sites now represents a promising approach in cancer treatment. The present review summarizes recent information about the anti-cancer effects of selected drugs commonly used for other medical indications. Our aim is not to collect all the reported results, but to present an overview of various possibilities. Advantages, disadvantages and further perspectives regarding individual drugs are discussed and evaluated. PMID:25544649

  17. Barium as a potential indicator of phosphorus in agricultural runoff.

    PubMed

    Ahlgren, Joakim; Djodjic, Faruk; Wallin, Mats

    2012-01-01

    In many catchments, anthropogenic input of contaminants, and in particular phosphorus (P), into surface water is a mixture of agricultural and sewage runoff. Knowledge about the relative contribution from each of these sources is vital for mitigation of major environmental problems such as eutrophication. In this study, we investigated whether the distribution of trace elements in surface waters can be used to trace the contamination source. Water from three groups of streams was investigated: streams influenced only by agricultural runoff, streams influenced mainly by sewage runoff, and reference streams. Samples were collected at different flow regimes and times of year and analyzed for 62 elements using ICP-MS. Our results show that there are significant differences between the anthropogenic sources affecting the streams in terms of total element composition and individual elements, indicating that the method has the potential to trace anthropogenic impact on surface waters. The elements that show significant differences between sources are strontium (p < 0.001), calcium (p < 0.004), potassium (p < 0.001), magnesium (p < 0.001), boron (p < 0.001), rhodium (p = 0.001), and barium (p < 0.001). According to this study, barium shows the greatest potential as a tracer for an individual source of anthropogenic input to surface waters. We observed a strong relationship between barium and total P in the investigated samples (R(2) = 0.78), which could potentially be used to apportion anthropogenic sources of P and thereby facilitate targeting of mitigation practices. PMID:22218189

  18. Scavenging Rate Ecoassay: A Potential Indicator of Estuary Condition

    PubMed Central

    Porter, Augustine G.; Scanes, Peter R.

    2015-01-01

    Monitoring of estuary condition is essential due to the highly productive and often intensely impacted nature of these ecosystems. Assessment of the physico-chemical condition of estuaries is expensive and difficult due to naturally fluctuating water quality and biota. Assessing the vigour of ecosystem processes is an alternative method with potential to overcome much of the variability associated with physico-chemical measures. Indicators of estuary condition should have small spatial and temporal variability, have a predictable response to perturbation and be ecologically relevant. Here, we present tests of the first criterion, the spatio-temporal variability of a potential ecoassay measuring the rate of scavenging in estuaries. We hypothesised that the proposed scavenging ecoassay would not vary significantly among A) sites in an estuary, B) trips separated by weeks, or C) days in a trip. Because not all habitats are present in all estuaries, this test was undertaken in two habitats. When conducted over bare substrate there were occasional significant differences, but no discernible patterns, within levels of the experiment. When conducted over vegetated substrate, days within a trip did not vary significantly, but later trips experienced greater scavenging. This scavenging ecoassay shows potential as a tool for assessing the condition of estuarine ecosystems, and further exploration of this protocol is warranted by implementation in estuaries across a gradient of anthropogenic stress. PMID:26024225

  19. Redox potential: An indicator of site productivity in forest management

    NASA Astrophysics Data System (ADS)

    Sajedi, Toktam; Prescott, Cindy; Lavkulich, Les

    2010-05-01

    Redox potential (Eh) is an integrated soil measurement that reflects several environmental conditions in the soil associated with aeration, moisture and carbon (organic matter) dynamics. Its measurement can be related to water table fluctuations, precipitation and landscape gradients, organic matter decomposition rates, nutrient dynamics, biological diversity and plant species distribution. Redox is an excellent indicator of soil biological processes, as it is largely a reflection of microbial activities which to a large extent govern carbon dynamics and nutrient cycling. Redox thus serves as an ecological indicator of site productivity at the ecosystem scale and may be used for management purposes as its magnitude can be altered by activities such as harvesting and drainage. A threshold value of 300 mv has been documented as the critical value below which anaerobic conditions in the soil develop. However, redox measurements and its impacts on ecosystem processes such as nutrient cycling and productivity, especially in forest ecosystems, have not received the attention that this "master" variable deserves, On northern Vancouver Island, Canada, regenerating stands of western redcedar-western hemlock (CH) sites exhibit symptoms of nutrient deficiencies and slow growth, but this phenomenon does not occur on adjacent western hemlock- amabalis fir (HA) sites. We tested the hypothesis that differences in nutrient supply and distribution of plant species was caused by differences in moisture regime and redox potential. Redox potential, pH, soil aeration depth (steel rods), organic matter thickness, bulk density, soil carbon store, plant species distribution and richness were measured at five old-growth and five 10-year-old cutover blocks. Results of investigations confirmed that CH forests were wetter, had redox values lower than the critical 300mv and a shallower aerated zone, compared with adjacent regenerating HA sites. Fifty percent of the CH plots had redox values less than +300 mv in the forest floor; whereas only 15 percent of the HA plots had such low values. Composition of the forest understory species was related to soil moisture/aeration. Soil aeration was the most important soil variable influencing plant species composition, explaining 25% of the plant community variability. Eh was always greater than +300 mv in the mineral soil of old growth HA forests but below +300 mv in HA clearcuts, suggesting paludification; however it was below or at this threshold in both CH forests and clearcuts. The reduction in measured redox without a noticeable change in the watertable in HA sites suggests that harvesting HA forests shifts the ecosystem towards more anaerobic conditions more similar to CH sites. In a complimentary study, the significance of redox was assessed in a cedar swamp cutover by exploring the relationships between soil redox potential and tree growth, and mineralization of C and soil C store along a gradient of moisture caused by drainage. Drainage improved aeration in the rooting zone, expressed as redox, and above- and below ground C storage; however C mineralization measured as CO2 evolution was not affected. Tree growth was positively correlated with redox potential. Our results indicate that drainage could be a useful silvicultural practice for improving the productivity of these ecosystems and that it may be possible to improve tree growth without stimulating loss of soil C. This requires that drainage improve aeration in the rooting zone while maintaining redox levels of less than +300 mV in the bulk soil, indicating that redox measurements should be incorporated into silviculture interventions to improve productivity of these forests.

  20. Comparative analysis of viral pathogens and potential indicators in shellfish.

    PubMed

    Muniain-Mujika, I; Calvo, M; Lucena, F; Girones, R

    2003-05-25

    Shellfish can be responsible of outbreaks of infectious diseases and current health measures do not guarantee the absence of viral pathogens in this product. Here we examine the presence of pathogenic viruses and potential indicators in shellfish in a comparative analysis.Sixty shellfish samples collected in three areas with different levels of faecal contamination were analysed for Escherichia coli, total coliforms, Clostridium perfringens, somatic coliphages, F-specific phages of RNA (F-RNA), bacteriophages infecting Bacteroides fragilis RYC2056, human adenovirus, enterovirus and hepatitis A virus (HAV). Viruses were eluted in a glycine buffer at pH 10. The overall percentage of viral pathogens detected was 47% for human adenoviruses, 19% for enteroviruses and 24% for HAV. Since all the samples positive for enterovirus and HAV were also positives for human adenovirus, the latter may be considered useful as a molecular index of viral contamination in shellfish. No significant differences in the bioaccumulation of bacteria and bacteriophages for oysters or mussels were observed. It was found that the probability of detection of any of the pathogenic virus decreases as the temperature of shellfish growing waters increases. However, the probability of detecting viruses increases when phages of B. fragilis are found. Although more data are needed in order to fulfil the need of viral indicators for controlling the presence of human viruses in shellfish, the obtained results indicate that phages infecting B. fragilis RYC2056 could be a suitable group of bacteriophages to be used as an indicator of the presence of viruses in shellfish. PMID:12672594

  1. Rules for identifying potentially reactive or promiscuous compounds.

    PubMed

    Bruns, Robert F; Watson, Ian A

    2012-11-26

    This article describes a set of 275 rules, developed over an 18-year period, used to identify compounds that may interfere with biological assays, allowing their removal from screening sets. Reasons for rejection include reactivity (e.g., acyl halides), interference with assay measurements (fluorescence, absorbance, quenching), activities that damage proteins (oxidizers, detergents), instability (e.g., latent aldehydes), and lack of druggability (e.g., compounds lacking both oxygen and nitrogen). The structural queries were profiled for frequency of occurrence in druglike and nondruglike compound sets and were extensively reviewed by a panel of experienced medicinal chemists. As a means of profiling the rules and as a filter in its own right, an index of biological promiscuity was developed. The 584 gene targets with screening data at Lilly were assigned to 17 subfamilies, and the number of subfamilies at which a compound was active was used as a promiscuity index. For certain compounds, promiscuous activity disappeared after sample repurification, indicating interference from occult contaminants. Because this type of interference is not amenable to substructure search, a "nuisance list" was developed to flag interfering compounds that passed the substructure rules. PMID:23061697

  2. Kernel Density Surface Modelling as a Means to Identify Significant Concentrations of Vulnerable Marine Ecosystem Indicators

    PubMed Central

    Kenchington, Ellen; Murillo, Francisco Javier; Lirette, Camille; Sacau, Mar; Koen-Alonso, Mariano; Kenny, Andrew; Ollerhead, Neil; Wareham, Vonda; Beazley, Lindsay

    2014-01-01

    The United Nations General Assembly Resolution 61/105, concerning sustainable fisheries in the marine ecosystem, calls for the protection of vulnerable marine ecosystems (VME) from destructive fishing practices. Subsequently, the Food and Agriculture Organization (FAO) produced guidelines for identification of VME indicator species/taxa to assist in the implementation of the resolution, but recommended the development of case-specific operational definitions for their application. We applied kernel density estimation (KDE) to research vessel trawl survey data from inside the fishing footprint of the Northwest Atlantic Fisheries Organization (NAFO) Regulatory Area in the high seas of the northwest Atlantic to create biomass density surfaces for four VME indicator taxa: large-sized sponges, sea pens, small and large gorgonian corals. These VME indicator taxa were identified previously by NAFO using the fragility, life history characteristics and structural complexity criteria presented by FAO, along with an evaluation of their recovery trajectories. KDE, a non-parametric neighbour-based smoothing function, has been used previously in ecology to identify hotspots, that is, areas of relatively high biomass/abundance. We present a novel approach of examining relative changes in area under polygons created from encircling successive biomass categories on the KDE surface to identify “significant concentrations” of biomass, which we equate to VMEs. This allows identification of the VMEs from the broader distribution of the species in the study area. We provide independent assessments of the VMEs so identified using underwater images, benthic sampling with other gear types (dredges, cores), and/or published species distribution models of probability of occurrence, as available. For each VME indicator taxon we provide a brief review of their ecological function which will be important in future assessments of significant adverse impact on these habitats here and elsewhere. PMID:25289667

  3. Identifying and Quantifying Heterogeneity in High Content Analysis: Application of Heterogeneity Indices to Drug Discovery

    PubMed Central

    Gough, Albert H.; Chen, Ning; Shun, Tong Ying; Lezon, Timothy R.; Boltz, Robert C.; Reese, Celeste E.; Wagner, Jacob; Vernetti, Lawrence A.; Grandis, Jennifer R.; Lee, Adrian V.; Stern, Andrew M.; Schurdak, Mark E.; Taylor, D. Lansing

    2014-01-01

    One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology. PMID:25036749

  4. Sigma-2 Receptor as Potential Indicator of Stem Cell Differentiation

    PubMed Central

    Haller, Jodi L.; Panyutin, Irina; Chaudhry, Aneeka; Zeng, Chenbo; Mach, Robert H.; Frank, Joseph A.

    2011-01-01

    Purpose The sigma-2 (?2) receptor is a potential biomarker of proliferative status of solid tumors. Specific synthetic probes using N-substituted-9-azabicyclo[3.3.1]nonan-3?-yl carbamate analogs have been designed and implemented for experimental cancer diagnosis and therapy. Procedures We employed the fluorescently-labeled ?2 receptor probe, SW120, to evaluate ?2 receptor expression in human stem cells (SC), including: bone marrow stromal (BMSC), neural progenitor (NPC), amniotic fluid (AFSC), hematopoetic (HSC) and embryonic stem cells (ESC). We concurrently evaluated the intensity of SW120 and 5-ethynyl-2?-deoxyuridine (EdU) relative to passage number and multipotency. Results We substantiated significantly higher ?2 receptor density among proliferating SC relative to lineage-restricted cell types. Additionally, cellular internalization of the ?2 receptor in SC was consistent with receptor-mediated endocytosis and confocal microscopy indicated SW120 specific co-localization with a fluorescent marker of lysosomes in all SC imaged. Conclusion These results suggest that ?2 receptors may serve to monitor stem cell differentiation in future experimental studies. PMID:21614680

  5. Ultrastructural Changes in Endothelium during Apoptosis Indicate Low Microembolic Potential

    Microsoft Academic Search

    Wei Xu; Ross Boadle; Levina Dear; Mara Cvejic; Catherine Emmanuel; Hans Zoellner

    2005-01-01

    Background: Apoptotic endothelium has been suggested to have microthrombotic and microembolic potential. While some describe pro-coagulant activities and platelet binding, others demonstrate maintained fibrinolytic protein and anti-platelet aggregatory activity. Canalicular fragmentation is unique to apoptotic endothelium and is suggested to facilitate size reduction of apoptotic cells to reduce microembolic potential. Despite the potential importance of apoptotic microemboli, there are no

  6. 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...

  7. Using a geographic information system to identify areas with potential for off-target pesticide exposure.

    PubMed

    Pfleeger, Thomas G; Olszyk, David; Burdick, Connie A; King, George; Kern, Jeffrey; Fletcher, John

    2006-08-01

    In many countries, numerous tests are required as part of the risk assessment process before chemical registration to protect human health and the environment from unintended effects of chemical releases. Most of these tests are not based on ecological or environmental relevance but, rather, on consistent performance in the laboratory. A conceptual approach based on Geographic Information System (GIS) technology has been developed to identify areas that are vulnerable to nontarget chemical exposure. This GIS-based approach uses wind speed, frequency of those winds, pesticide application rates, and spatial location of agricultural crops to identify areas with the highest potential for pesticide exposure. A test scenario based on an incident in Idaho (USA) was used to identify the relative magnitude of risk from off-target movement of herbicides to plants in the conterminous United States. This analysis indicated that the western portion of the Corn Belt, the central California valley, southeastern Washington, the Willamette Valley of Oregon, and agricultural areas bordering the Great Lakes are among those areas in the United States that appear to have the greatest potential for off-target movement of herbicides via drift. Agricultural areas, such as the Mississippi River Valley and the southeastern United States, appears to have less potential, possibly due to lower average wind speeds. Ecological risk assessments developed for pesticide registration would be improved by using response data from species common to high-risk areas instead of extrapolating test data from species unrelated to those areas with the highest potential for exposure. PMID:16916045

  8. Baseline model for identifying the bioaccumulation potential of chemicals

    Microsoft Academic Search

    S. Dimitrov; N. Dimitrova; T. Parkerton; M. Comber; M. Bonnell; O. Mekenyan

    2005-01-01

    The base-line modeling concept presented in this work is based on the assumption of a maximum bioconcentration factor (BCF?) with mitigating factors that reduce the BCF. The maximum bioconcentration potential was described by the multi-compartment partitioning model for passive diffusion. The significance of different mitigating factors associated either with interactions with an organism or bioavailability were investigated. The most important

  9. ACCESSIBILITY INDICES: PILOT STUDY AND POTENTIAL USE IN STRATEGIC PLANNING

    Microsoft Academic Search

    John Schoon; Michael McDonald; Adrian Lee

    1999-01-01

    Accessibility indices (AIs) for public and private transport were estimated in a pilot study in northeast Hampshire, England. The AIs were based on a formulation relating travel time and cost between specified origins and destinations (O-Ds). Wider use of the role of the indices was examined, particularly for reducing car dependency as one element in improving sustainability within the North

  10. Hardness potential derivatives and their relation to Fukui indices.

    PubMed

    Saha, Soumen; Bhattacharjee, Rituparna; Roy, Ram Kinkar

    2013-03-30

    A simple as well as easy to compute formalism of hardness potential (originally defined by Parr and Gazquez, J. Phys. Chem., 1993, 97, 3939) is presented. Use of hardness potential formally resolves the N-dependence problem of local hardness. However, the hardness potential cannot describe the intra as well as intermolecular reactivity sequence satisfactorily of some chemical systems. The corresponding electrophilic [?(+)h(k)] and nucleophilic [?(-)h(k)] variants of the hardness potential are also developed, which measure the reactivity toward a nucleophilic (i.e., Nu(-)) and an electrophilic (i.e., El(+)) reagent, respectively. Interestingly, these two variants of the hardness potential lead to the right and left derivatives of Fukui potential. The proposed reactivity descriptors correctly predict the expected reactivity trends in the chosen systems. It has also been illustrated that the values of the variants of hardness potential (or Fukui potential) at the atomic nucleus have the ability to explain the intramolecular reactivity of biologically active indole derivatives. The future scope of applications as well as limitations of the proposed descriptors is also highlighted. PMID:23175426

  11. Nationwide Benthic Macroinvertebrate Assemblage Multimetric Indices: Identifying Inconsistencies and Limitations in Reporting Stream Impairment Status, USA

    NASA Astrophysics Data System (ADS)

    Lau, J. K.; Lauer, T. E.

    2015-07-01

    The objective of this study was to identify the current status of stream water-quality assessment and reporting methods for four states in the Ohio River basin (Indiana, Ohio, Tennessee, and Virginia), as required by the 305(b) section of the United States (US) Clean Water Act. Specifically, we clarified the discrepancies that exist among stream-impairment status classified by benthic macroinvertebrate multimetric indices (MMIs) and depicted using Geographic Information Systems shapefiles. In addition, we provided guidance in solving some of the comparability problems that arise when developing state-specific MMIs and depicting stream-impairment status using Geographic Information Systems technology. The MMI variation among states and differences in shapefile formats resulted in a nationwide dataset, which cannot be directly compared. Incorporating the changes suggested in this study allow for a uniform assessment and reporting method nationwide. Successful implementation of these changes would strengthen the US Environmental Protection Agency efforts to identify impaired streams and sources of those impairments without the limitations of state-by-state .developed assessment methods.

  12. Nationwide benthic macroinvertebrate assemblage multimetric indices: identifying inconsistencies and limitations in reporting stream impairment status, USA.

    PubMed

    Lau, J K; Lauer, T E

    2015-07-01

    The objective of this study was to identify the current status of stream water-quality assessment and reporting methods for four states in the Ohio River basin (Indiana, Ohio, Tennessee, and Virginia), as required by the 305(b) section of the United States (US) Clean Water Act. Specifically, we clarified the discrepancies that exist among stream-impairment status classified by benthic macroinvertebrate multimetric indices (MMIs) and depicted using Geographic Information Systems shapefiles. In addition, we provided guidance in solving some of the comparability problems that arise when developing state-specific MMIs and depicting stream-impairment status using Geographic Information Systems technology. The MMI variation among states and differences in shapefile formats resulted in a nationwide dataset, which cannot be directly compared. Incorporating the changes suggested in this study allow for a uniform assessment and reporting method nationwide. Successful implementation of these changes would strengthen the US Environmental Protection Agency efforts to identify impaired streams and sources of those impairments without the limitations of state-by-state .developed assessment methods. PMID:25832346

  13. Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer.

    PubMed

    Ema, Akira; Yamashita, Keishi; Ushiku, Hideki; Kojo, Ken; Minatani, Naoko; Kikuchi, Mariko; Mieno, Hiroaki; Moriya, Hiromitsu; Hosoda, Kei; Katada, Natsuya; Kikuchi, Shiro; Watanabe, Masahiko

    2014-12-01

    Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S-1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric cancer with standard treatment. Tumor tissues were obtained from 167 stage II/III advanced gastric cancer patients who underwent curative surgery and received postoperative S-1 chemotherapy from 2000 to 2010. Expression of the RTKs including EGFR, HER2, HER3, IGF-1R, and EphA2 was analyzed using immunohistochemistry (IHC). Analysis using a multivariate proportional hazard model identified the most significant RTKs that represented independent prognostic relevance. When tumor HER3 expression was classified into IHC 1+/2+ (n = 98) and IHC 0 (n = 69), the cumulative 5-year Relapse Free Survival (5y-RFS) was 56.5 and 82.9%, respectively (P = 0.0034). Significant prognostic relevance was similarly confirmed for IGF-1R (P = 0.014), and EGFR (P = 0.030), but not for EphA2 or HER2 expression. Intriguingly, HER3 expression was closely correlated with IGF-1R (P < 0.0001, R = 0.41), and EphA2 (P < 0.0001, R = 0.34) expression. Multivariate proportional hazard model analysis identified HER3 (IHC 1+/2+) (HR; 1.53, 95% CI, 1.11-2.16, P = 0.0078) as the sole RTK that was a poor prognostic factor independent of stage. Of the 53 patients who recurred, 40 patients (75.5%) were HER3-positive. Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment. PMID:25455899

  14. 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. PMID:21047057

  15. 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.

  16. Potential biochemical indicators of salinity tolerance in plants

    Microsoft Academic Search

    M. Ashraf; P. J. C. Harris

    2004-01-01

    Despite a wealth of published research on salinity tolerance of plants, neither the metabolic sites at which salt stress damages plants nor the adaptive mechanisms utilized by plants to survive under saline conditions are well understood. As a result, there are no well-defined indicators for salinity tolerance available to assist plant breeders in the improvement of salinity tolerance of important

  17. Identifying crater potential improves shallow gas kick control

    SciTech Connect

    Rocha, L.A. (Louisiana State Univ./Petrobras, Baton Rouge, LA (United States)); Bourgoyne, A.T. (Louisiana State Univ., Baton Rouge, LA (United States))

    1993-12-27

    An understanding of sea floor crater mechanisms can help drillers determine whether to divert or shut in a shallow gas kick. Proper well planning that considers potential shallow gas sources can eliminate some of the more common failure situations with both diverting and shutting in of a well. Current well control practice for land and bottom-supported marine rigs usually calls for shutting in the well when a kick is detected, providing sufficient casing has been set to keep any flow underground. The casing and surface equipment must have an adequately high working pressure to ensure that formation fracture occurs before the equipment fails. Even for high shut-in pressures, an underground blowout is preferable to a surface blowout. An operator may choose to divert the flow if the surface casing is not set deep enough to keep the underground flow outside the casing from breaking through the sediments to the surface. Once the flow reaches the surface, a crater may form at the sea bed, possibly sinking or damaging the rig. Craters increase the difficulty and time required to kill a blowout. The paper describes shallow gas environments, the decision to divert or shut in the well, fluid migration, cement bond failure, hydraulic fracture, shear failure, the effect of fault planes, crater mechanisms, formation liquefaction, piping, caving, historical cases, and a deepwater crater.

  18. Polymorphisms in canine platelet glycoproteins identify potential platelet antigens.

    PubMed

    Callan, Mary Beth; Werner, Petra; Mason, Nicola J; Meny, Geralyn M; Raducha, Michael G; Henthorn, Paula S

    2013-08-01

    Human alloimmune thrombocytopenic conditions caused by exposure to a platelet-specific alloantigen include neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness. More than 30 platelet-specific alloantigens have been defined in the human platelet antigen (HPA) system; however, there is no previous information on canine platelet-specific alloantigens. Using the HPA system as a model, we evaluated the canine ITGB3, ITGA2B, and GP1BB genes encoding GPIIIa (?3), GPIIb (?IIb), and GPIb?, respectively, which account for 21 of 27 HPA, to determine whether amino acid polymorphisms are present in the orthologous canine genes. A secondary objective was to perform a pilot study to assess possible association between specific alleles of these proteins and a diagnosis of idiopathic thrombocytopenic purpura (ITP) in dogs. By using genomic DNA from dogs of various breeds with and without ITP, sequencing of PCR products encompassing all coding regions and exon-intron boundaries for these 3 genes revealed 4 single-nucleotide polymorphisms in ITGA2B resulting in amino acid polymorphisms in the canine genome, 3 previously reported and 1 newly identified (Gly[GGG]/Arg[AGG] at amino acid position 576 of ITGA2B. Of 16 possible ITGA2B protein alleles resulting from unique combinations of the 4 polymorphic amino acids, 5 different protein isoforms were present in homozygous dogs and explain all of the genotype combinations in heterozygous dogs. There was no amino acid polymorphism or protein isoform that was specific for a particular breed or for the diagnosis of ITP. PMID:24209971

  19. Polymorphisms in Canine Platelet Glycoproteins Identify Potential Platelet Antigens

    PubMed Central

    Callan, Mary Beth; Werner, Petra; Mason, Nicola J; Meny, Geralyn M; Raducha, Michael G; Henthorn, Paula S

    2013-01-01

    Human alloimmune thrombocytopenic conditions caused by exposure to a platelet-specific alloantigen include neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness. More than 30 platelet-specific alloantigens have been defined in the human platelet antigen (HPA) system; however, there is no previous information on canine platelet-specific alloantigens. Using the HPA system as a model, we evaluated the canine ITGB3, ITGA2B, and GP1BB genes encoding GPIIIa (?3), GPIIb (?IIb), and GPIb?, respectively, which account for 21 of 27 HPA, to determine whether amino acid polymorphisms are present in the orthologous canine genes. A secondary objective was to perform a pilot study to assess possible association between specific alleles of these proteins and a diagnosis of idiopathic thrombocytopenic purpura (ITP) in dogs. By using genomic DNA from dogs of various breeds with and without ITP, sequencing of PCR products encompassing all coding regions and exon–intron boundaries for these 3 genes revealed 4 single-nucleotide polymorphisms in ITGA2B resulting in amino acid polymorphisms in the canine genome, 3 previously reported and 1 newly identified (Gly[GGG]/Arg[AGG] at amino acid position 576 of ITGA2B. Of 16 possible ITGA2B protein alleles resulting from unique combinations of the 4 polymorphic amino acids, 5 different protein isoforms were present in homozygous dogs and explain all of the genotype combinations in heterozygous dogs. There was no amino acid polymorphism or protein isoform that was specific for a particular breed or for the diagnosis of ITP. PMID:24209971

  20. Pb-Sn Alloy Microstructure: Potential Reliability Indicator for Interconnects

    Microsoft Academic Search

    GEORGE D. O'CLOCK; M. Peters; J. Pater; G. Kleese; R. Martini

    1987-01-01

    Investigation of the microstructure and chemistry of Pb-Sn alloy interconnects by scanning electron microscopy (SEM) and X-ray microanalysis shows that certain physical and chemical characteristics of the Pb-rich and Sn-rich phases are indicative of crack formation during temperature cycling. Those solder alloy interconnects that crack when temperature cycled exhibit significantly different microstructure patterns compared with solder interconnects that do not

  1. Geochemical Indicators and Diatoms Identify the Inundation Limit of the 2010 Maule Tsunami

    NASA Astrophysics Data System (ADS)

    Chague-Goff, C.; Goff, J. R.; Wong, H. K.; Cisternas, M.

    2013-05-01

    It has long been known that tsunamis inundate further than the limit of the sand deposit they leave behind, and that relying on the extent of the sandy sedimentary evidence is likely to result in an under-estimation of event magnitude and risk. However, the question remains about how to identify the real limit of tsunami inundation, particularly several months or more after the event. Here we report on a study carried out at a site on the Pacific coast of Chile south of Constitución in August 2010, nearly 6 months after the Mw 8.8 Maule tsunami. Eight pits were dug along a 480 m long shore-perpendicular transect, incorporating the area covered by tsunami sediment, a zone covered by a discontinuous and decomposing debris scatter up to the point of maximum inundation, and an area further landward from this point. The tsunami sand deposit extended from ~160 to 260 m inland and ranged in thickness from 22 to less than 1 cm at the limit of sediment deposition. It consisted of dark, generally well-sorted, coarse to medium sand. Logs, pumice and various organic debris were found up to a limit of tsunami inundation (380 m inland - confirmed by a local eye witness). New grass growth also covered the tsunami deposit and the field further inland. While the chemical composition of the tsunami deposit differed to that of the underlying soil, indicators of saltwater inundation were low in the sandy units, reflecting downward leaching and dilution by rainfall in the porous material in the 6 months since the tsunami. Concentrations of saltwater indicators (e.g. chloride, sulphate, bromide) were however elevated in the area covered by scattered debris up to the limit of tsunami inundation, suggesting preferential retention in organic-rich material. Marine and brackish-marine diatoms were found both in the sandy units and beyond, at the surface of the grass field, and occurred in higher concentrations than in the underlying soil. Both diatom assemblages and geochemical marine proxies are indicative of tsunami inundation well beyond the sediment limit. While sea spray and associated wind cannot be totally excluded as the source of soluble salts and wind-blown diatoms, chloride concentrations do not decrease landward within the area of tsunami inundation. A decrease in chloride would have been expected if it was solely due to sea spray. While further research is required to allow us to distinguish the effects of marine inundation from sea spray, the use of geochemical proxies and diatoms provides a means to identify the limit of tsunami inundation beyond the limit of sand deposition, and as previous studies have shown, even after debris marking it have decayed. This is of importance for tsunami risk assessment and mitigation.

  2. Identifying malaria vector breeding habitats with remote sensing data and terrain-based landscape indices in Zambia

    PubMed Central

    2010-01-01

    Background Malaria, caused by the parasite Plasmodium falciparum, is a significant source of morbidity and mortality in southern Zambia. In the Mapanza Chiefdom, where transmission is seasonal, Anopheles arabiensis is the dominant malaria vector. The ability to predict larval habitats can help focus control measures. Methods A survey was conducted in March-April 2007, at the end of the rainy season, to identify and map locations of water pooling and the occurrence anopheline larval habitats; this was repeated in October 2007 at the end of the dry season and in March-April 2008 during the next rainy season. Logistic regression and generalized linear mixed modeling were applied to assess the predictive value of terrain-based landscape indices along with LandSat imagery to identify aquatic habitats and, especially, those with anopheline mosquito larvae. Results Approximately two hundred aquatic habitat sites were identified with 69 percent positive for anopheline mosquitoes. Nine species of anopheline mosquitoes were identified, of which, 19% were An. arabiensis. Terrain-based landscape indices combined with LandSat predicted sites with water, sites with anopheline mosquitoes and sites specifically with An. arabiensis. These models were especially successful at ruling out potential locations, but had limited ability in predicting which anopheline species inhabited aquatic sites. Terrain indices derived from 90 meter Shuttle Radar Topography Mission (SRTM) digital elevation data (DEM) were better at predicting water drainage patterns and characterizing the landscape than those derived from 30 m Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) DEM. Conclusions The low number of aquatic habitats available and the ability to locate the limited number of aquatic habitat locations for surveillance, especially those containing anopheline larvae, suggest that larval control maybe a cost-effective control measure in the fight against malaria in Zambia and other regions with seasonal transmission. This work shows that, in areas of seasonal malaria transmission, incorporating terrain-based landscape models to the planning stages of vector control allows for the exclusion of significant portions of landscape that would be unsuitable for water to accumulate and for mosquito larvae occupation. With increasing free availability of satellite imagery such as SRTM and LandSat, the development of satellite imagery-based prediction models is becoming more accessible to vector management coordinators. PMID:21050496

  3. Fragmentation patterns of evergreen oak woodlands in Southwestern Iberia: identifying key spatial indicators.

    PubMed

    Costa, Augusta; Madeira, Manuel; Lima Santos, José; Plieninger, Tobias; Seixas, Júlia

    2014-01-15

    Mediterranean evergreen oak woodlands (composed of Quercus suber L. and Quercus rotundifolia Lam.) are becoming increasingly fragmented in the human-modified landscapes of Southwestern Portugal and Spain. Previous studies have largely neglected to assess the spatial changes of oak woodlands in relation to their surrounding landscape matrix, and to characterize and quantify woodland boundaries and edges. The present study aims to fill this gap by analyzing fragmentation patterns of oak woodlands over a 50-year period (1958-2007) in three landscapes. Using archived aerial imagery from 1958, 1995 and 2007, for two consecutive periods (1958-1995 and 1995-2007), we calculated a set of landscape metrics to compare woodland fragmentation over time. Our results indicated a continuous woodland fragmentation characterized by their edge dynamics. From 1958 to 2007, the replacement of open farmland by shrubland and by new afforestation areas in the oak woodland landscape surrounding matrix, led to the highest values for edge contrast length trends of 5.0 and 12.3, respectively. Linear discriminant analysis was performed to delineate fragmented woodland structures and identify metric variables that characterize woodland spatial configuration. The edge contrast length with open farmland showed a strong correlation with F1 (correlations ranging between 0.55 and 0.98) and may be used as a proxy for oak woodland mixedness in landscape matrix. The edge dynamics of oak woodlands may result in different patterns of oak recruitment and therefore, its study may be helpful in highlighting future baselines for the sustainable management of oak woodlands. PMID:24355688

  4. Self-Selection Patterns of College Roommates as Identified by the Myers-Briggs Type Indicator.

    ERIC Educational Resources Information Center

    Anchors, W. Scott; Hale, John, Jr.

    1985-01-01

    Investigated patterns and processes by which students (N=422) made unassisted roommate pairings within residence halls using the Myers-Briggs Type Indicator. Results indicated introverts, intuitives, feelers, and perceivers each tended to self-select. (BL)

  5. 7 CFR 170.6 - How are potential market participants identified for the USDA Farmers Market?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 false How are potential market participants identified for the USDA Farmers Market? 170.6 Section 170.6 Agriculture...AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market...

  6. 7 CFR 170.6 - How are potential market participants identified for the USDA Farmers Market?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 false How are potential market participants identified for the USDA Farmers Market? 170.6 Section 170.6 Agriculture...AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market...

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 false How are potential market participants identified for the USDA Farmers Market? 170.6 Section 170.6 Agriculture...AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market...

  8. A simple contact mapping algorithm for identifying potential peptide mimetics in protein–protein interaction partners

    PubMed Central

    Krall, Alex; Brunn, Jonathan; Kankanala, Spandana; Peters, Michael H

    2014-01-01

    A simple, static contact mapping algorithm has been developed as a first step at identifying potential peptide biomimetics from protein interaction partner structure files. This rapid and simple mapping algorithm, “OpenContact” provides screened or parsed protein interaction files based on specified criteria for interatomic separation distances and interatomic potential interactions. The algorithm, which uses all-atom Amber03 force field models, was blindly tested on several unrelated cases from the literature where potential peptide mimetics have been experimentally developed to varying degrees of success. In all cases, the screening algorithm efficiently predicted proposed or potential peptide biomimetics, or close variations thereof, and provided complete atom-atom interaction data necessary for further detailed analysis and drug development. In addition, we used the static parsing/mapping method to develop a peptide mimetic to the cancer protein target, epidermal growth factor receptor. In this case, secondary, loop structure for the peptide was indicated from the intra-protein mapping, and the peptide was subsequently synthesized and shown to exhibit successful binding to the target protein. The case studies, which all involved experimental peptide drug advancement, illustrate many of the challenges associated with the development of peptide biomimetics, in general. Proteins 2014; 82:2253–2262. © 2014 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. PMID:24756879

  9. A complementary approach to identifying and assessing the remediation potential of hydrocarbonoclastic bacteria.

    PubMed

    Kadali, Krishna K; Simons, Keryn L; Skuza, Pawel P; Moore, Robert B; Ball, Andrew S

    2012-03-01

    The isolation and assessment of hydrocarbonoclastic bacteria often represents a key strategy in the bioremediation of hydrocarbon-contaminated sites. However the isolation and assessment of such bacteria is often a lengthy and expensive procedure. The aim of this study was to identify potential isolates for use in the remediation of hydrocarbon contaminated sites using a combination of selective isolation plating, the Biolog system and subsequent multivariate analyses. The use of weathered oil as the main C source restricted the number of isolates growing to 5×10(2)CFUg soil(-1). Isolates (n=96) were then assessed individually using Biolog MT2 plates with seven different hydrocarbons (dodecane, tridecane, hexadecane, octadecane, eicosane, naphthalene and phenanthrene). The results indicated that all isolates were able to grow on at least one hydrocarbon from the seven chosen. This confirmed that the isolation media developed was selective in isolating hydrocarbonoclastic bacteria only. Cluster analysis of Biolog data separated the isolates into two discrete clusters with cluster 2 identifying hydrocarbonoclastic bacteria that are effective in degrading a variety of contaminants. Further study on the isolates from cluster 2 was carried out based on their phylogenetic analysis. Phylogenetic analysis of 28 bacterial isolates from cluster 2 based on the 1500bp sequences from 16S rDNA genes using MRBAYES confirmed all isolates as being hydrocarbonoclastic, providing supportive evidence that isolates from cluster 2 have a potential use in bioremediation. This approach could improve both the speed and efficiency of the commercial bioremediation process. PMID:22245375

  10. Research Questions to Identify Ecological Indicators Most Useful for Linking Ecosystems and Human Wellbeing

    EPA Science Inventory

    Background/Question/Methods While the desirability of ecological indicators that foster social science interpretation and use as well as public comprehension is well established, guidelines for developing indicators that meet these needs are not as well developed. In the past f...

  11. Using parasite databases to identify potential nontarget hosts of biological control organisms

    Microsoft Academic Search

    John M. McPartland; Judith Nicholson

    2003-01-01

    Biological control organisms undergo host range studies to identify potential nontarget hosts. The selection criterion for host range studies is primarily based on the target host's taxonomy. Thus, inaccuracies in host taxonomy may compromise the validity of host range studies. We propose that biocontrol researchers use internet?available databases to identify potential nontarget organisms that share parasites (biotrophic pathogens and pests)

  12. A Program Evaluation Model: Using Bloom's Taxonomy to Identify Outcome Indicators in Outcomes-Based Program Evaluations

    ERIC Educational Resources Information Center

    McNeil, Rita C.

    2011-01-01

    Outcomes-based program evaluation is a systematic approach to identifying outcome indicators and measuring results against those indicators. One dimension of program evaluation is assessing the level of learner acquisition to determine if learning objectives were achieved as intended. The purpose of the proposed model is to use Bloom's Taxonomy to…

  13. A Preliminary Examination to Identify the Presence of Quality Indicators in Single-Subject Research

    ERIC Educational Resources Information Center

    Tankersley, Melody; Cook, Bryan G.; Cook, Lysandra

    2008-01-01

    Scholars in the field of special education put forth a series of papers that proposed quality indicators for specific research designs that must be present for a study to be considered of high quality, as well as standards for evaluating a body of research to determine whether a practice is evidence-based. The purpose of this article was to pilot…

  14. A Preliminary Examination to Identify the Presence of Quality Indicators in Single-subject Research

    Microsoft Academic Search

    Melody Tankersley

    2008-01-01

    Scholars in the field of special education put forth a series of papers that proposed quality indicators for specific research designs that must be present for a study to be considered of high quality, as well as standards for evaluating a body of research to determine whether a practice is evidence-based. The purpose of this article was to pilot test

  15. 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 a second pilot testing with Spring 2012 graduates from 45 departments across the United States. These graduating students from undergraduate and graduate programs answered questions about their earth science education experiences at the high school, community college, and university levels; their quantitative skills; their research and internship experiences and their immediate plans after graduation. Out of the 294 complete responses to the survey, 233 were from undergraduate students. This presentation will focus on the responses of these undergraduate students. AGI hopes to fully deploy this survey broadly to geosciences departments across the country in Spring 2013. AGI will also begin longitudinally participants from the previous Exit Survey efforts in order to understand their progression through their chosen career paths.

  16. Heart Rate Variability as an Alternative Indicator for Identifying Cardiac Iron Status in Non-Transfusion Dependent Thalassemia Patients

    PubMed Central

    Wijarnpreecha, Karn; Siri-Angkul, Natthaphat; Shinlapawittayatorn, Krekwit; Charoenkwan, Pimlak; Silvilairat, Suchaya; Siwasomboon, Chate; Visarutratna, Pannee; Srichairatanakool, Somdet; Tantiworawit, Adisak; Phrommintikul, Arintaya; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2015-01-01

    Background Iron-overload cardiomyopathy is a major cause of death in thalassemia patients due to the lack of an early detection strategy. Although cardiac magnetic resonance (CMR) T2* is used for early detection of cardiac iron accumulation, its availability is limited. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and found to be depressed in thalassemia. However, its direct correlation with cardiac iron accumulation has never been investigated. We investigated whether HRV can be used as an alternative indicator for early identification of cardiac iron deposition in thalassemia patients. Methods Ninety-nine non-transfusion dependent thalassemia patients (23.00 (17.00, 32.75) years, 35 male) were enrolled. The correlation between HRV recorded using 24-hour Holter monitoring and non-transferrin bound iron (NTBI), hemoglobin (Hb), serum ferritin, LV ejection fraction (LVEF), and CMR-T2* were determined. Results The median NTBI value was 3.15 (1.11, 6.59) ?M. Both time and frequency domains of HRV showed a significant correlation with the NTBI level, supporting HRV as a marker of iron overload. Moreover, the LF/HF ratio showed a significant correlation with CMR-T2* with the receiver operating characteristic (ROC) curve of 0.684±0.063, suggesting that it could represent the cardiac iron deposit in thalassemia patients. HRV was also significantly correlated with serum ferritin and Hb. Conclusions This novel finding regarding the correlation between HRV and CMR-T2* indicates that HRV could be a potential marker in identifying early cardiac iron deposition prior to the development of LV dysfunction, and may be used as an alternative to CMR-T2* for screening cardiac iron status in thalassemia patients. PMID:26083259

  17. Identifying indicator species for post-release monitoring of genetically modified, herbicide resistant crops

    Microsoft Academic Search

    Angelika Hilbeck; Matthias Meier; Armin Benzler

    2008-01-01

    In Europe, regulations for release and placing-on-the-market of genetically modified (GM) crops require post-release monitoring\\u000a of their impact on the environment. Monitoring potential adverse effects of GM crops includes direct effects as well as indirect\\u000a effects, e.g. GM crop specific changes in land and pest management. Currently, there is a gap in the pre-release risk assessments\\u000a conducted for regulatory approval

  18. Identifying indicator plant species of habitat quality and invasibility as a guide for peri-urban forest management

    Microsoft Academic Search

    Sandrine Godefroid; Nico Koedam

    2003-01-01

    A floristic survey has been carried out in a peri-urban forest, the Sonian Forest in Brussels, to identify indicator plant species in the herbaceous layer, which could be used as an aid within the framework of a more sustainable management of the forest. Three hundred and seventy two (372) taxa have been identified, 33 of which are non-native (i.e. non-indigenous

  19. Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

    PubMed Central

    Rogers, Geraint B; Hoffman, Lucas R; Johnson, Matt W; Mayer-Hamblett, Nicole; Schwarze, Jürgen; Carroll, Mary P; Bruce, Kenneth D

    2011-01-01

    Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations. PMID:21405970

  20. Cluster analysis identifies aminoacid compositional features that indicate Toxoplasma gondii adhesin proteins

    PubMed Central

    Arenas, Ailan F; Salcedo, Gladys E; Moncada, Diego M; Erazo, Diego A; Osorio, Juan F; Gomez-Marin, Jorge E

    2012-01-01

    Toxoplasma gondii invade host cells using a multi-step process that depends on the regulated secretion of adhesions. To identify key primary sequence features of adhesins in this parasite, we analyze the relative frequency of individual amino acids, their dipeptide frequencies, and the polarity, polarizability and Van der Waals volume of the individual amino acids by using cluster analysis. This method identified cysteine as a key amino acid in the Toxoplasma adhesin group. The best vector algorithm of non-concatenated features was for 2 attributes: the single amino acid relative frequency and the dipeptide frequency. Polarity, polarizability and Van der Waals volume were not good classificatory attributes. Single amino acid attributes clustered unambiguously 67 apicomplexan hypothetical adhesins. This algorithm was also useful for clustering hypothetical Toxoplasma target host receptors. All of the cluster performances had over 70% sensitivity and 80% specificity. Compositional aminoacid data can be useful for improving machine learning-based prediction software when homology and structural data are not sufficient. PMID:23144551

  1. Cluster analysis identifies aminoacid compositional features that indicate Toxoplasma gondii adhesin proteins.

    PubMed

    Arenas, Ailan F; Salcedo, Gladys E; Moncada, Diego M; Erazo, Diego A; Osorio, Juan F; Gomez-Marin, Jorge E

    2012-01-01

    Toxoplasma gondii invade host cells using a multi-step process that depends on the regulated secretion of adhesions. To identify key primary sequence features of adhesins in this parasite, we analyze the relative frequency of individual amino acids, their dipeptide frequencies, and the polarity, polarizability and Van der Waals volume of the individual amino acids by using cluster analysis. This method identified cysteine as a key amino acid in the Toxoplasma adhesin group. The best vector algorithm of non-concatenated features was for 2 attributes: the single amino acid relative frequency and the dipeptide frequency. Polarity, polarizability and Van der Waals volume were not good classificatory attributes. Single amino acid attributes clustered unambiguously 67 apicomplexan hypothetical adhesins. This algorithm was also useful for clustering hypothetical Toxoplasma target host receptors. All of the cluster performances had over 70% sensitivity and 80% specificity. Compositional aminoacid data can be useful for improving machine learning-based prediction software when homology and structural data are not sufficient. PMID:23144551

  2. Researchers Identify Biological Markers that May Indicate Poor Breast Cancer Prognosis

    Cancer.gov

    A team of researchers has found an association between breast cancer survival and two proteins that, when present in the blood in high levels, are indicators of inflammation. Using data from the Health, Eating, Activity and Lifestyle (HEAL) study sponsored by the NCI, the researchers found that breast cancer patients with elevated levels of C-reactive protein (CRP) and serum amyloid A (SAA) were approximately two to three times more likely to die sooner or have their cancer return than those patients who had lower levels of these proteins, regardless of the patient's age, tumor stage, race, body mass index, or history of previous cardiovascular issues.

  3. Modal indices for identifying damage location in cable-stayed Kap Shui Mun Bridge

    NASA Astrophysics Data System (ADS)

    Sun, Zong G.; Ko, Jan Ming; Ni, Yi-Qing

    2001-08-01

    This paper presents a comparative study of using the modal curvature index and the modal flexibility index for damage localization in the cable-stayed Kap Shui Mun Bridge from the bridge global modal data before and after damage. Based on a precise and validated 3D finite element model of the bridge, a series of damage cases associated with the deck are introduced in the simulation study. They are the damage occurring at the members within deck segments and the damage occurring at the support and bearing system of the deck. The damage indices are applied to determine the specific deck segment that contains damaged member(s).

  4. Transcript and protein profiling identify candidate gene sets of potential adaptive significance in New Zealand Pachycladon

    PubMed Central

    2010-01-01

    Background Transcript profiling of closely related species provides a means for identifying genes potentially important in species diversification. However, the predictive value of transcript profiling for inferring downstream-physiological processes has been unclear. In the present study we use shotgun proteomics to validate inferences from microarray studies regarding physiological differences in three Pachycladon species. We compare transcript and protein profiling and evaluate their predictive value for inferring glucosinolate chemotypes characteristic of these species. Results Evidence from heterologous microarrays and shotgun proteomics revealed differential expression of genes involved in glucosinolate hydrolysis (myrosinase-associated proteins) and biosynthesis (methylthioalkylmalate isomerase and dehydrogenase), the interconversion of carbon dioxide and bicarbonate (carbonic anhydrases), water use efficiency (ascorbate peroxidase, 2 cys peroxiredoxin, 20 kDa chloroplastic chaperonin, mitochondrial succinyl CoA ligase) and others (glutathione-S-transferase, serine racemase, vegetative storage proteins, genes related to translation and photosynthesis). Differences in glucosinolate hydrolysis products were directly confirmed. Overall, prediction of protein abundances from transcript profiles was stronger than prediction of transcript abundance from protein profiles. Protein profiles also proved to be more accurate predictors of glucosinolate profiles than transcript profiles. The similarity of species profiles for both transcripts and proteins reflected previously inferred phylogenetic relationships while glucosinolate chemotypes did not. Conclusions We have used transcript and protein profiling to predict physiological processes that evolved differently during diversification of three Pachycladon species. This approach has also identified candidate genes potentially important in adaptation, which are now the focus of ongoing study. Our results indicate that protein profiling provides a valuable tool for validating transcript profiles in studies of adaptive divergence. PMID:20482888

  5. Metabolic profiling of human follicular fluid identifies potential biomarkers of oocyte developmental competence.

    PubMed

    O'Gorman, A; Wallace, M; Cottell, E; Gibney, M J; McAuliffe, F M; Wingfield, M; Brennan, L

    2013-10-01

    The use of metabolomic based techniques to aid oocyte and embryo selection has gained attention in recent years. Previous work from our laboratory has demonstrated that the (1)H NMR-based metabolic profile of follicular fluid correlates with oocyte developmental potential. Patients undergoing IVF at the Merrion Fertility Clinic had follicular fluid collected at the time of oocyte retrieval. The fatty acid composition of follicular fluid from follicles where oocytes fertilised and developed into multi-cell embryos (n=15) and from oocytes that fertilised normally but failed to cleave (n=9) (cleaved vs non-cleaved) was compared. Statistical analysis was performed on the data using univariate and multivariate techniques. Analysis of the fatty acid composition revealed that there were nine fatty acids significantly different between follicular fluid from the cleaved and the non-cleaved sample groups. Of particular interest were the higher concentration of total saturated (P=0.03) and the lower concentration of total polyunsaturated fatty acids in the non-cleaved sample group (P=0.001). Random forest classification models were used to predict successful cleavage in follicular fluid samples producing models with errors rates of <10%. Receiver operating characteristic analysis demonstrated that the model had good predictability with an area under the curve of 0.96. The panel of fatty acid biomarkers identified in this study indicates that the fatty acid composition of follicular fluid may be more predictive in comparison to other previously identified biomarkers. Following validation in a larger cohort, these biomarkers may have the potential to be used in fertility clinics to aid the selection of oocytes in the future. PMID:23886995

  6. 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.

  7. Evaluation of indicated suicide risk prevention approaches for potential high school dropouts.

    PubMed Central

    Thompson, E A; Eggert, L L; Randell, B P; Pike, K C

    2001-01-01

    OBJECTIVES: This study evaluated the efficacy of 2 indicated preventive interventions, postintervention and at 9-month follow-up. METHODS: Drawn from a pool of potential high school dropouts, 460 youths were identified as being at risk for suicide and participated in 1 of 3 conditions randomly assigned by school: (1) Counselors CARE (C-CARE) (n = 150), a brief one-to-one assessment and crisis intervention; (2) Coping and Support Training (CAST) (n = 155), a small-group skills-building and social support intervention delivered with C-CARE; and (3) usual-care control (n = 155). Survey instruments were administered pre-intervention, following C-CARE (4 weeks), following CAST (10 weeks), and at a 9-month follow-up. RESULTS: Growth curve analyses showed significant rates of decline in attitude toward suicide and suicidal ideation associated with the experimental interventions. C-CARE and CAST, compared with usual care, also were effective in reducing depression and hopelessness. Among females, reductions in anxiety and anger were greater in response to the experimental programs. CAST was most effective in enhancing and sustaining personal control and problem-solving coping for males and females. CONCLUSIONS: School-based, indicated prevention approaches are feasible and effective for reducing suicidal behaviors and related emotional distress and for enhancing protective factors. PMID:11344882

  8. Indication.

    PubMed

    Pust, Ronald E

    2012-01-01

    Should the indications for therapies differ from one nation to the next? What are the reasons behind controversial therapeutic variations? What roles do cultural history and authoritarian conflict among clinicians play in the adoption of therapies? When I worked at a rural hospital in Kenya, a woman experiencing obstructed labor made me ponder many questions-but only after our emergency ended in the death of her newborn son. In recounting and learning from this episode, I listened to the disparate Kenyan voices of the patient, the hospital's director, the consultant obstetrician, and to the even more controversial voices of evidence-based medicine. In reflecting on this process, I have learned at least 3 lessons-about the transmissibility of arrogance, the role of guests in other countries, and the nature of science. PMID:22230834

  9. Indication

    PubMed Central

    Pust, Ronald E.

    2012-01-01

    Should the indications for therapies differ from one nation to the next? What are the reasons behind controversial therapeutic variations? What roles do cultural history and authoritarian conflict among clinicians play in the adoption of therapies? When I worked at a rural hospital in Kenya, a woman experiencing obstructed labor made me ponder many questions—but only after our emergency ended in the death of her newborn son. In recounting and learning from this episode, I listened to the disparate Kenyan voices of the patient, the hospital’s director, the consultant obstetrician, and to the even more controversial voices of evidence-based medicine. In reflecting on this process, I have learned at least 3 lessons—about the transmissibility of arrogance, the role of guests in other countries, and the nature of science. PMID:22230834

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

    PubMed

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

    2015-02-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. PMID:25399920

  11. Transcriptome Profiling of Peripheral Blood Cells Identifies Potential Biomarkers for Doxorubicin Cardiotoxicity in a Rat Model

    PubMed Central

    Todorova, Valentina K.; Beggs, Marjorie L.; Delongchamp, Robert R.; Dhakal, Ishwori; Makhoul, Issam; Wei, Jeanne Y.; Klimberg, V. Suzanne

    2012-01-01

    Aims Doxorubicin (DOX), a widely used anticancer agent, can cause an unpredictable cardiac toxicity which remains a major limitation in cancer chemotherapy. There is a need for noninvasive, sensitive and specific biomarkers which will allow identifying patients at risk for DOX-induced cardiotoxicity to prevent permanent cardiac damage. The aim of this study was to investigate whether the expression of specific genes in the peripheral blood can be used as surrogate marker(s) for DOX-induced cardiotoxicity. Methods/Results Rats were treated with a single dose of DOX similar to one single dose that is often administered in humans. The cardiac and peripheral blood mononuclear cells (PBMCs) genome-wide expression profiling were examined using Illumina microarrays. The results showed 4,409 differentially regulated genes (DRG) in the hearts and 4,120 DRG in PBMC. Of these 2411 genes were similarly DRG (SDRG) in both the heart and PBMC. Pathway analysis of the three datasets of DRG using Gene Ontology (GO) enrichment analysis and Ingenuity Pathways Analysis (IPA) showed that most of the genes in these datasets fell into pathways related to oxidative stress response and protein ubiquination. IPA search for potential eligible biomarkers for cardiovascular disease within the SDRG list revealed 188 molecules. Conclusions We report the first in-depth comparison of DOX-induced global gene expression profiles of hearts and PBMCs. The high similarity between the gene expression profiles of the heart and PBMC induced by DOX indicates that the PBMC transcriptome may serve as a surrogate marker of DOX-induced cardiotoxicity. Future directions of this research will include analysis of PBMC expression profiles of cancer patients treated with DOX-based chemotherapy to identify the cardiotoxicity risk, predict DOX-treatment response and ultimately to allow individualized anti-cancer therapy. PMID:23209553

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

    USGS Publications Warehouse

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

    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.

  13. Calculation of a Toxic Potential Indicator Via Chinese-Language Material Safety Data Sheets

    Microsoft Academic Search

    Sheng-Bou Yen; Jahau Lewis Chen

    2009-01-01

    SummaryThis article presents an approach to evaluating the toxic potential for products or materials using Chinese-language material safety data sheets (MSDSs). The toxic potential indicator (TPI) is one of many simple methods used to evaluate the environmental impact of toxins in products and materials. According to actual application experience in Taiwan, difficulties and problems arise in the preliminary implementation of

  14. Identifying Women with Indicators of Subfertility in a Statewide Population Database: Operationalizing the Missing Link in ART Research

    PubMed Central

    Declercq, Eugene R; Belanoff, Candice; Diop, Hafsatou; Gopal, Daksha; Hornstein, Mark; Kotelchuck, Milton; Luke, Barbara; Stern, Judy E

    2014-01-01

    Objective To identify a group of deliveries to mothers with indicators of subfertility (SUBFERTILITY) Design Longitudinal cohort study Setting Massachusetts Patients 334,152 deliveries to Massachusetts mothers in a Massachusetts hospital between July 1, 2004-December 31, 2008 Interventions None Main Outcome Measure Subfertility was defined by an indication on current or past birth certificate or hospital utilization data of infertility or assisted reproductive technology (ART) cycle prior to index delivery and no indication of ART use with index delivery. Results Initially 12,367 deliveries met the inclusion criteria for SUBFERTILITY (8,019 from birth certificates; 2,777 from hospital data; 1,571 from prior ART treatment). Removing deliveries from more than one data source resulted in 10,764 unique deliveries. Removing deliveries resulting from ART treatments left 6,238 deliveries in the SUBFERTILITY category. Demographic analysis indicated that deliveries in SUBFERTILITY were more similar to ART than to the fertile population. Conclusions We have demonstrated the feasibility of using existing population based linked public health datasets to identify SUBFERTILITY deliveries and we have used ART data to distinguish ART and SUBFERTILITY births. The SUBFERTILITY category can serve as a comparison group of subfertile patients for studies of ART delivery and longitudinal health outcomes. PMID:24289994

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

    NASA Astrophysics Data System (ADS)

    German, Brian Joseph

    This research develops a technique for the solution of incompressible equivalents to planar steady subsonic potential flows. Riemannian geometric formalism is used to develop a gauge transformation of the length measure followed by a curvilinear coordinate transformation to map the given subsonic flow into a canonical Laplacian flow with the same boundary conditions. The effect of the transformation is to distort both the immersed profile shape and the domain interior nonuniformly as a function of local flow properties. The method represents the full nonlinear generalization of the classical methods of Prandtl-Glauert and Karman-Tsien. Unlike the classical methods which are "corrections," this method gives exact results in the sense that the inverse mapping produces the subsonic full potential solution over the original airfoil, up to numerical accuracy. The motivation for this research was provided by an observed analogy between linear potential flow and the special theory of relativity that emerges from the invariance of the d'Alembert wave equation under Lorentz transformations. This analogy is well known in an operational sense, being leveraged widely in linear unsteady aerodynamics and acoustics, stemming largely from the work of Kussner. Whereas elements of the special theory can be invoked for compressibility effects that are linear and global in nature, the question posed in this work was whether other mathematical techniques from the realm of relativity theory could be used to similar advantage for effects that are nonlinear and local. This line of thought led to a transformation leveraging Riemannian geometric methods common to the general theory of relativity. A gauge transformation is used to geometrize compressibility through the metric tensor of the underlying space to produce an equivalent incompressible flow that lives not on a plane but on a curved surface. In this sense, forces owing to compressibility can be ascribed to the geometry of space in 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.

  16. Bivalves as indicators of environmental variation and potential anthropogenic impacts in the southern Barents Sea

    PubMed Central

    Carroll, Michael L.; Johnson, Beverly J.; Henkes, Gregory A.; McMahon, Kelton W.; Voronkov, Andrey; Ambrose, William G.; Denisenko, Stanislav G.

    2009-01-01

    Identifying patterns and drivers of natural variability in populations is necessary to gauge potential effects of climatic change and the expected increases in commercial activities in the Arctic on communities and ecosystems. We analyzed growth rates and shell geochemistry of the circumpolar Greenland smooth cockle, Serripes groenlandicus, from the southern Barents Sea over almost 70 years between 1882 and 1968. The datasets were calibrated via annually-deposited growth lines, and growth, stable isotope (?18O, ?13C), and trace elemental (Mg, Sr, Ba, Mn) patterns were linked to environmental variations on weekly to decadal scales. Standardized growth indices revealed an oscillatory growth pattern with a multi-year periodicity, which was inversely related to the North Atlantic Oscillation Index (NAO), and positively related to local river discharge. Up to 60% of the annual variability in the Ba/Ca could be explained by variations in river discharge at the site closest to the rivers, but the relationship disappeared at a more distant location. Patterns of ?18O, ?13C, and Sr/Ca together provide evidence that bivalve growth ceases at elevated temperatures during the fall and recommences at the coldest temperatures in the early spring, with the implication that food, rather than temperature, is the primary driver of bivalve growth. The multi-proxy approach of combining the annually integrated information from the growth results and higher resolution geochemical results yielded a robust interpretation of biophysical coupling in the region over temporal and spatial scales. We thus demonstrate that sclerochronological proxies can be useful retrospective analytical tools for establishing a baseline of ecosystem variability in assessing potential combined impacts of climatic change and increasing commercial activities on Arctic communities. PMID:19394657

  17. Accelerometers identify inactive and potentially obese children (EarlyBird 3).

    PubMed

    Metcalf, B S; Voss, L D; Wilkin, T J

    2002-08-01

    Accelerometers revealed a fivefold variation in physical activity among healthy 5 year old children. They singled out habitually inactive children, most of them girls, who did little, whether at school or over the weekend. Accelerometers are of potential value in identifying, from an early age, children at risk of becoming obese. PMID:12138075

  18. Accelerometers identify inactive and potentially obese children (EarlyBird 3)

    Microsoft Academic Search

    B S Metcalf; L D Voss; T J Wilkin

    2002-01-01

    Accelerometers revealed a fivefold variation in physical activity among healthy 5 year old children. They singled out habitually inactive children, most of them girls, who did little, whether at school or over the weekend. Accelerometers are of potential value in identifying, from an early age, children at risk of becoming obese.

  19. Potential of Advanced Microwave Sounding Unit to identify precipitating systems and associated

    E-print Network

    Chaboureau, Jean-Pierre

    ) derived products and independent ground-based data. A more stringent condition based on differences] performed a climatology of cloud systems and upper level disturbances in the Mediterranean based on 8Potential of Advanced Microwave Sounding Unit to identify precipitating systems and associated

  20. An inverse docking approach for identifying new potential anti-cancer targets

    Microsoft Academic Search

    Sam Z. Grinter; Yayun Liang; Sheng-You Huang; Salman M. Hyder; Xiaoqin Zou

    2011-01-01

    Inverse docking is a relatively new technique that has been used to identify potential receptor targets of small molecules. Our docking software package MDock is well suited for such an application as it is both computationally efficient, yet simultaneously shows adequate results in binding affinity predictions and enrichment tests. As a validation study, we present the first stage results of

  1. ABSTRACT Genomics and bioinformatics have the vast potential to identify genes that cause disease by investigating

    E-print Network

    Hammock, Bruce D.

    ABSTRACT Genomics and bioinformatics have the vast potential to identify genes that cause disease by investigating whole-genome databases. Comparison of an individual's geno- type with a genomic database these metabolic profiles with genomic, expression, and proteomic databases. Application of the knowledge of indi

  2. Which anthropometric indicators identify a pregnant woman as acutely malnourished and predict adverse birth outcomes in the humanitarian context?

    PubMed

    Ververs, Mija-Tesse; Antierens, Annick; Sackl, Anita; Staderini, Nelly; Captier, Valerie

    2013-01-01

    Currently there is no consensus on how to identify pregnant women as acutely malnourished and when to enroll them in nutritional programmes. Médecins Sans Frontières Switzerland undertook a literature review with the purpose of determining values of anthropometric indicators for acute malnutrition that are associated with adverse birth outcomes (such as low birth weight (LBW)), pre-term birth and intra-uterine growth retardation (IUGR). A literature search in PUBMED was done covering 1 January 1995 to 12 September 2012 with the key terms maternal anthropometry and pregnancy. The review focused on the humanitarian context. Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age. The MUAC values below which most adverse effects were identified were <22 and <23 cm. A conservative cut-off of <23 cm is recommended to include most pregnant women at risk of LBW for their infants in the African and Asian contexts. PMID:23787989

  3. The rotifer fauna of Argentine Patagonia as a potential limnological indicator

    Microsoft Academic Search

    David Kuczynski; Ciencias Exactas

    1987-01-01

    Plankton samples of rivers, lakes, pools and minor water bodies were taken in the Patagonian Argentine provinces of Río Negro, Chubut, Neuquén and the Southern part of Buenos Aires. The relationship between physical and chemical characteristics of these waters and their rotifer fauna was analyzed. Sixty taxa were identified, and their value as indicators of temperature, pH, conductivity, total alkalinity

  4. Evaluating potential indicators of ecosystem processes across local gradients in a temperate grassland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Science-based information is needed to identify indicators of ecosystem services that may then be used to monitor natural resources and quantify effects of management. Here our aim was to perform a local gradient study to elucidate correlative associations between vegetation and multiple soil prope...

  5. Riverine threat indices to assess watershed condition and identify primary management capacity of agriculture natural resource management agencies.

    PubMed

    Fore, Jeffrey D; Sowa, Scott P; Galat, David L; Annis, Gust M; Diamond, David D; Rewa, Charles

    2014-03-01

    Managers can improve conservation of lotic systems over large geographies if they have tools to assess total watershed conditions for individual stream segments and can identify segments where conservation practices are most likely to be successful (i.e., primary management capacity). The goal of this research was to develop a suite of threat indices to help agriculture resource management agencies select and prioritize watersheds across Missouri River basin in which to implement agriculture conservation practices. We quantified watershed percentages or densities of 17 threat metrics that represent major sources of ecological stress to stream communities into five threat indices: agriculture, urban, point-source pollution, infrastructure, and all non-agriculture threats. We identified stream segments where agriculture management agencies had primary management capacity. Agriculture watershed condition differed by ecoregion and considerable local variation was observed among stream segments in ecoregions of high agriculture threats. Stream segments with high non-agriculture threats were most concentrated near urban areas, but showed high local variability. 60 % of stream segments in the basin were classified as under U.S. Department of Agriculture's Natural Resources Conservation Service (NRCS) primary management capacity and most segments were in regions of high agricultural threats. NRCS primary management capacity was locally variable which highlights the importance of assessing total watershed condition for multiple threats. Our threat indices can be used by agriculture resource management agencies to prioritize conservation actions and investments based on: (a) relative severity of all threats, (b) relative severity of agricultural threats, and (c) and degree of primary management capacity. PMID:24390081

  6. DRAR-CPI: a server for identifying drug repositioning potential and adverse drug reactions via the chemical–protein interactome

    PubMed Central

    Luo, Heng; Chen, Jian; Shi, Leming; Mikailov, Mike; Zhu, Huang; Wang, Kejian; He, Lin; Yang, Lun

    2011-01-01

    Identifying new indications for existing drugs (drug repositioning) is an efficient way of maximizing their potential. Adverse drug reaction (ADR) is one of the leading causes of death among hospitalized patients. As both new indications and ADRs are caused by unexpected chemical–protein interactions on off-targets, it is reasonable to predict these interactions by mining the chemical–protein interactome (CPI). Making such predictions has recently been facilitated by a web server named DRAR-CPI. This server has a representative collection of drug molecules and targetable human proteins built up from our work in drug repositioning and ADR. When a user submits a molecule, the server will give the positive or negative association scores between the user’s molecule and our library drugs based on their interaction profiles towards the targets. Users can thus predict the indications or ADRs of their molecule based on the association scores towards our library drugs. We have matched our predictions of drug–drug associations with those predicted via gene-expression profiles, achieving a matching rate as high as 74%. We have also successfully predicted the connections between anti-psychotics and anti-infectives, indicating the underlying relevance of anti-psychotics in the potential treatment of infections, vice versa. This server is freely available at http://cpi.bio-x.cn/drar/. PMID:21558322

  7. Identifying DNA-binding proteins using structural motifs and the electrostatic potential

    Microsoft Academic Search

    Hugh P. Shanahan; Mario A. Garcia; Susan Jones; Janet M. Thornton

    2004-01-01

    Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA- binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix-turn-helix (HTH), helix- hairpin-helix

  8. A novel fault-tree approach for identifying potential causes of satellite reaction wheel failure

    Microsoft Academic Search

    A. Barua; P. Sinha; K. Khorasani; S. Tafazoli

    2005-01-01

    Due to unforeseen circumstances and naturally occurring faults, it is desired that an on-board fault-diagnosis system of a space vehicle be capable of detecting, isolating, identifying or classifying faults in the system. In this paper, a novel approach is proposed which strengthens existing efficient fault-detection mechanisms with an additional ability to classify different types of faults to effectively determine potential

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

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

    PubMed

    Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric; Alexandrov, Ludmil B; Calderaro, Julien; Rebouissou, Sandra; Couchy, Gabrielle; Meiller, Clément; Shinde, Jayendra; Soysouvanh, Frederic; Calatayud, Anna-Line; Pinyol, Roser; Pelletier, Laura; Balabaud, Charles; Laurent, Alexis; Blanc, Jean-Frederic; Mazzaferro, Vincenzo; Calvo, Fabien; Villanueva, Augusto; Nault, Jean-Charles; Bioulac-Sage, Paulette; Stratton, Michael R; Llovet, Josep M; Zucman-Rossi, Jessica

    2015-05-01

    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. Analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereas FGF3, FGF4, FGF19 or CCND1 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. In conclusion, 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. PMID:25822088

  11. 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. PMID:16933080

  12. The dissolved organic matter as a potential soil quality indicator in arable soils of Hungary.

    PubMed

    Filep, Tibor; Draskovits, Eszter; Szabó, József; Koós, Sándor; László, Péter; Szalai, Zoltán

    2015-07-01

    Although several authors have suggested that the labile fraction of soils could be a potential soil quality indicator, the possibilities and limitations of using the dissolved organic matter (DOM) fraction for this purpose have not yet been investigated. The objective of this study was to evaluate the hypothesis that DOM is an adequate indicator of soil quality. To test this, the soil quality indices (SQI) of 190 arable soils from a Hungarian dataset were estimated, and these values were compared to DOM parameters (DOC and SUVA254). A clear difference in soil quality was found between the soil types, with low soil quality for arenosols (average SQI 0.5) and significantly higher values for gleysols, vertisols, regosols, solonetzes and chernozems. The SQI-DOC relationship could be described by non-linear regression, while a linear connection was observed between SQI and SUVA. The regression equations obtained for the dataset showed only one relatively weak significant correlation between the variables, for DOC (R (2) = 0.157(***); n = 190), while non-significant relationships were found for the DOC and SUVA254 values. However, an envelope curve operated with the datasets showed the robust potential of DOC to indicate soil quality changes, with a high R (2) value for the envelope curve regression equation. The limitations to using the DOM fraction of soils as a quality indicator are due to the contradictory processes which take place in soils in many cases. PMID:26130245

  13. Developing consensus on hospital prescribing indicators of potential harms amenable to decision support

    PubMed Central

    Thomas, Sarah K; McDowell, Sarah E; Hodson, James; Nwulu, Ugochi; Howard, Rachel L; Avery, Anthony J; Slee, Ann; Coleman, Jamie J

    2013-01-01

    Aims To develop a list of prescribing indicators specific for the hospital setting that would facilitate the prospective collection of high-severity and/or high-frequency prescribing errors, which are also amenable to electronic clinical decision support. Methods A two-stage consensus technique (electronic Delphi) was carried out with 20 experts across England. Participants were asked to score prescribing errors using a five-point Likert scale for their likelihood of occurrence and the severity of the most likely outcome. These were combined to produce risk scores, from which median scores were calculated for each indicator across the participants in the study. The degree of consensus between the participants was defined as the proportion that gave a risk score in the same category as the median. Indicators were included if a consensus of 80% or more was achieved. Results A total of 80 prescribing errors were identified by consensus as being high or extreme risk. The most common drug classes named within the indicators were antibiotics (n = 13), antidepressants (n = 8), nonsteroidal anti-inflammatory drugs (n = 6) and opioid analgesics (n = 6). The most frequent error type identified as high or extreme risk were those classified as clinical contraindications (n = 29 of 80). Conclusions Eighty high-risk prescribing errors in the hospital setting have been identified by an expert panel. These indicators can serve as a standardized, validated tool for the collection of prescribing data in both paper-based and electronic prescribing processes. This can assess the impact of safety improvement initiatives, such as the implementation of electronic clinical decision support. PMID:23362926

  14. Sural sensory action potential identifies diabetic peripheral neuropathy responders to therapy.

    PubMed

    Vinik, Aaron I; Bril, Vera; Litchy, William J; Price, Karen L; Bastyr, Edward J

    2005-11-01

    Identifying patients with diabetic peripheral neuropathy (DPN) amenable to therapy is a challenge. To determine whether the amplitude of the sural sensory nerve action potential (sural SNAP) reflects the severity of DPN, an analysis was performed on 205 patients with DPN, identified by an abnormal vibration detection threshold (VDT), who were enrolled in a multinational clinical trial investigating ruboxistaurin (RBX) mesylate. Nerve conduction velocity and response amplitude and latency were measured and compared. VDT was significantly lower in those with preserved sural SNAPs (n = 128) than in those in whom they were absent (n = 77; 21.5 vs. 22.7 JND units, P = 0.002). Thus, preserved sural SNAP denoted less severe DPN. Logistic regression analyses evaluating baseline characteristics, HbA(1c), and baseline symptom scores identified only DPN duration as a factor that might contribute to the presence of sural SNAP (P = 0.004; OR = 0.896). For patients with abnormal VDT, preserved sural SNAP identifies a patient population with less severe DPN who may respond to therapeutic intervention in clinical trials. PMID:16116628

  15. Identifying a potential receptor for the antibacterial peptide of sponge Axinella donnani endosymbiont.

    PubMed

    Vimala, A; Ramakrishnan, C; Gromiha, M Michael

    2015-07-25

    Marine sponges and their associated bacteria are rich sources of novel secondary metabolites with therapeutic usefulness. In our earlier work, we have identified a novel antibacterial peptide from the marine sponge Axinella donnani endosymbiotic bacteria. In this work, we have carried out a comparative genomic analysis and identified a set of 60 proteins as probable receptor which is common in all the strains. The analysis on binding substrate showed that ? barrel assembly machinery (BamA) of the outer membrane protein 85 (omp85) superfamily is a potential receptor protein for the antibacterial peptide. It plays a central role in OMP biogenesis, especially in cell viability. Further, the triplet and quartet motifs RGF and YGDG, respectively in L6 loop are conserved over all the strains and these conserved residues interact with antibacterial peptide to inhibit the BamA function, which is essential for OMP biogenesis. PMID:25939848

  16. Intraoperative radiotherapy in early stage breast cancer: potential indications and evidence to date.

    PubMed

    Hanna, G G; Kirby, A M

    2015-05-01

    Following early results of recent studies of intraoperative radiotherapy (IORT) in the adjuvant treatment of patients with early breast cancer, the clinical utility of IORT is a subject of much recent debate within the breast oncology community. This review describes the intraoperative techniques available, the potential indications and the evidence to date pertaining to local control and toxicity. We also discuss any implications for current practice and future research. PMID:25734489

  17. Mandatory reporting of “imminent” death to identify organ donors: History, controversy, and potential solutions

    Microsoft Academic Search

    Peter Dodek

    2003-01-01

    Purpose  To review the history of mandatory reporting for the purpose of identifying potential organ and tissue donors, and the controversy\\u000a around the terms, “imminent” or “impending” death, and to suggest a solution to this controversy.\\u000a \\u000a \\u000a \\u000a Source  In this narrative review, published papers were retrieved based on a Medline search using the terms, “mandatory reporting”\\u000a and “organ donation.” In addition, unpublished data

  18. The Potential for Spatial Distribution Indices to Signal Thresholds in Marine Fish Biomass

    PubMed Central

    Reuchlin-Hugenholtz, Emilie

    2015-01-01

    The frequently observed positive relationship between fish population abundance and spatial distribution suggests that changes in distribution can be indicative of trends in abundance. If contractions in spatial distribution precede declines in spawning stock biomass (SSB), spatial distribution reference points could complement the SSB reference points that are commonly used in marine conservation biology and fisheries management. When relevant spatial distribution information is integrated into fisheries management and recovery plans, risks and uncertainties associated with a plan based solely on the SSB criterion would be reduced. To assess the added value of spatial distribution data, we examine the relationship between SSB and four metrics of spatial distribution intended to reflect changes in population range, concentration, and density for 10 demersal populations (9 species) inhabiting the Scotian Shelf, Northwest Atlantic. Our primary purpose is to assess their potential to serve as indices of SSB, using fisheries independent survey data. We find that metrics of density offer the best correlate of spawner biomass. A decline in the frequency of encountering high density areas is associated with, and in a few cases preceded by, rapid declines in SSB in 6 of 10 populations. Density-based indices have considerable potential to serve both as an indicator of SSB and as spatially based reference points in fisheries management. PMID:25789624

  19. The potential for spatial distribution indices to signal thresholds in marine fish biomass.

    PubMed

    Reuchlin-Hugenholtz, Emilie; Shackell, Nancy L; Hutchings, Jeffrey A

    2015-01-01

    The frequently observed positive relationship between fish population abundance and spatial distribution suggests that changes in distribution can be indicative of trends in abundance. If contractions in spatial distribution precede declines in spawning stock biomass (SSB), spatial distribution reference points could complement the SSB reference points that are commonly used in marine conservation biology and fisheries management. When relevant spatial distribution information is integrated into fisheries management and recovery plans, risks and uncertainties associated with a plan based solely on the SSB criterion would be reduced. To assess the added value of spatial distribution data, we examine the relationship between SSB and four metrics of spatial distribution intended to reflect changes in population range, concentration, and density for 10 demersal populations (9 species) inhabiting the Scotian Shelf, Northwest Atlantic. Our primary purpose is to assess their potential to serve as indices of SSB, using fisheries independent survey data. We find that metrics of density offer the best correlate of spawner biomass. A decline in the frequency of encountering high density areas is associated with, and in a few cases preceded by, rapid declines in SSB in 6 of 10 populations. Density-based indices have considerable potential to serve both as an indicator of SSB and as spatially based reference points in fisheries management. PMID:25789624

  20. Rapid, Computer Vision-Enabled Murine Screening System Identifies Neuropharmacological Potential of Two New Mechanisms

    PubMed Central

    Roberds, Steven L.; Filippov, Igor; Alexandrov, Vadim; Hanania, Taleen; Brunner, Dani

    2011-01-01

    The lack of predictive in vitro models for behavioral phenotypes impedes rapid advancement in neuropharmacology and psychopharmacology. In vivo behavioral assays are more predictive of activity in human disorders, but such assays are often highly resource-intensive. Here we describe the successful application of a computer vision-enabled system to identify potential neuropharmacological activity of two new mechanisms. The analytical system was trained using multiple drugs that are used clinically to treat depression, schizophrenia, anxiety, and other psychiatric or behavioral disorders. During blinded testing the PDE10 inhibitor TP-10 produced a signature of activity suggesting potential antipsychotic activity. This finding is consistent with TP-10’s activity in multiple rodent models that is similar to that of clinically used antipsychotic drugs. The CK1? inhibitor PF-670462 produced a signature consistent with anxiolytic activity and, at the highest dose tested, behavioral effects similar to that of opiate analgesics. Neither TP-10 nor PF-670462 was included in the training set. Thus, computer vision-based behavioral analysis can facilitate drug discovery by identifying neuropharmacological effects of compounds acting through new mechanisms. PMID:21927596

  1. Transcript Profiling and RNA Interference as Tools to Identify Small Molecule Mechanisms and Therapeutic Potential

    PubMed Central

    Palchaudhuri, Rahul; Hergenrother, Paul J.

    2011-01-01

    Summary The identification of the mechanism-of-action and therapeutic potential of bioactive small molecules remain considerable challenges in the field of drug discovery and chemical biology. Apart from traditional target identification techniques, new tools have emerged that can significantly aid mechanism elucidation efforts. The development of pattern matching algorithms that compare transcription profile data to analogous data on compounds with known cellular targets allows for mechanistic insights without the need to synthesize chemically modified probes. In addition, such methods can be used to connect small molecules to particular disease states, thus aiding the rational identification of candidate therapeutics. Another method with considerable potential is whole-genome RNAi screening, a technique that can identify critical upstream proteins involved in a small molecule’s mechanism-of-action. Several proof-of-concept studies using compounds with known cellular targets suggest this tool will enable mechanistic characterization of bioactive small molecules with unknown mechanisms. This review highlights recent successes in using these pattern matching and chemical genetic tools, with the goal of uncovering small molecule mechanisms and identifying therapeutic candidates for disease treatment. PMID:21105689

  2. Development of biological indices for identifying and evaluating impacts of pollutants on freshwater ecosystems. Final report, June 1975-October 1980

    SciTech Connect

    Cairns, J. Jr.; Cherry, D.S.

    1980-09-30

    The ten Research Areas reported included: (1) the development of functional indices for identifying and evaluating impacts of pollutants on Aufwuchs communities, (2) relationship of protozoan colonization rates to the eutrophication process, (3) testing of methods to determine the functioning of zooplankton communities subjected to entrainment stress, (4) the use of the first steps of detritus processing (microbial decomposition) as a technique for assessing pollutional stress on aquatic communities in a river system, (5) relationship of protozoan invasion and extinction rate to the eutrophication process, (6) extension of present early colonization studies to the simultaneous evaluation of natural environmental parameters and power plant effluents and application of the early colonization approach to microbial communities in streams of the New River drainage, (7) testing of single species-community responses of protozoans from selected heavy metals, (8) the effects of selected power plant pollutants on grazer utilization of Aufwuchs, (9) investigation of bioconcentration and bioaccumulation mechanisms of the Asiatic clam (Corbicula fluminea) populations in field artificial streams and laboratory microcosms with reference to physical chemistry and diet alterations, and (10) investigation of the homeostatic regulation in bluegill sunfish following acute hypothermal shock and to other power plant related effluents.

  3. 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-exchange reactions with the pectins in the cell walls of the conducting xylem. However, we also observe that bean organs from L4 experiment growing in nutrient solutions with lower Ca concentrations and low pH behave slightly differently and show reduced Ca isotopic fractionations compared with beans from the other experiments. All these results indicate that there is no simple correlation between Ca isotopic variations, Ca content and pH of the nutrient solution, and that also biological effects have to be involved. The data confirm the potential of the Ca isotopic system for tracing biological fractionations in natural ecosystems. Wiegand et al., (2005). Geophys. Res. Lett., 32, L11404 Page et al., (2008). Biogeochemistry, 88, 1-13 Cenki-Tok et al,. (2009). Geochim. Cosmochim. Acta, 73, 2215-2228 Holmden and Bélanger(2010). Geochim. Cosmochim. Acta, 74, 995-1015

  4. 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

  5. An Empirical Comparison of Key Statistical Attributes Among Potential ICU Quality Indicators*

    PubMed Central

    Brown, Sydney E. S.; Ratcliffe, Sarah J.; Halpern, Scott D.

    2014-01-01

    Objective Good quality indicators should have face validity, relevance to patients, and be able to be measured reliably. Beyond these general requirements, good quality indicators should also have certain statistical properties, including sufficient variability to identify poor performers, relative insensitivity to severity adjustment, and the ability to capture what providers do rather than patients' characteristics. We assessed the performance of candidate indicators of ICU quality on these criteria. Indicators included ICU readmission, mortality, several length of stay outcomes, and the processes of venous-thromboembolism and stress ulcer prophylaxis provision. Design Retrospective cohort study Setting One hundred thirty-eight U.S. ICUs from 2001-2008 in the Project IMPACT database. Patients Two hundred sixty-eight thousand eight hundred twenty-four patients discharged from U.S. ICUs. Interventions None. Measurements and Main Results We assessed indicators' (1) variability across ICU-years; (2) degree of influence by patient vs. ICU and hospital characteristics using the Omega statistic; (3) sensitivity to severity adjustment by comparing the area under the receiver operating characteristic curve (AUC) between models including vs. excluding patient variables, and (4) correlation between risk adjusted quality indicators using a Spearman correlation. Large ranges of among-ICU variability were noted for all quality indicators, particularly for prolonged length of stay (4.7–71.3%) and the proportion of patients discharged home (30.6–82.0%), and ICU and hospital characteristics outweighed patient characteristics for stress ulcer prophylaxis (?, 0.43; 95% CI, 0.34–0.54), venous thromboembolism prophylaxis (?, 0.57; 95% CI, 0.53–0.61), and ICU readmissions (?, 0.69; 95% CI, 0.52–0.90). Mortality measures were the most sensitive to severity adjustment (area under the receiver operating characteristic curve % difference, 29.6%); process measures were the least sensitive (area under the receiver operating characteristic curve % differences: venous thromboembolism prophylaxis, 3.4%; stress ulcer prophylaxis, 2.1%). None of the 10 indicators was clearly and consistently correlated with a majority of the other nine indicators. Conclusions No indicator performed optimally across assessments. Future research should seek to define and operationalize quality in a way that is relevant to both patients and providers. PMID:24717464

  6. 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

    ...VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63...VHAP of Potential Concern Identified by Industry CAS No. Chemical name EPA de minimis... 0.2 75092 Methylene chloride 4.0 79469 2-Nitropropane 1.0...

  7. 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

    ...VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63...VHAP of Potential Concern Identified by Industry CAS No. Chemical name EPA de minimis... 0.2 75092 Methylene chloride 4.0 79469 2-Nitropropane 1.0...

  8. 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

    ...VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63...VHAP of Potential Concern Identified by Industry CAS No. Chemical name EPA de minimis... 0.2 75092 Methylene chloride 4.0 79469 2-Nitropropane 1.0...

  9. 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

    ...VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63...VHAP of Potential Concern Identified by Industry CAS No. Chemical name EPA de minimis... 0.2 75092 Methylene chloride 4.0 79469 2-Nitropropane 1.0...

  10. 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

    ...VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63...VHAP of Potential Concern Identified by Industry CAS No. Chemical name EPA de minimis... 0.2 75092 Methylene chloride 4.0 79469 2-Nitropropane 1.0...

  11. Assessment of potential indicators for protein-energy malnutrition in the algorithm for integrated management of childhood illness.

    PubMed Central

    Bern, C.; Zucker, J. R.; Perkins, B. A.; Otieno, J.; Oloo, A. J.; Yip, R.

    1997-01-01

    Potential indicators were assessed for the two classifications of protein-energy malnutrition in the guidelines for integrated management of childhood illness: severe malnutrition, which requires immediate referral to hospital, and very low weight, which calls for feeding assessment, nutritional counselling and follow-up. Children aged < 2 years require feeding assessment and counselling as a preventive intervention. For severe malnutrition, we examined 1202 children admitted to a Kenyan hospital for any association of the indicators with mortality within one month. Bipedal oedema indicating kwashiorkor, and two marasmus indicators (visible severe wasting and weight-for-height (WFH) Z-score of < -3) were associated with a significantly increased mortality risk (odds ratios, 3.1-3.9). Very low weight-for-age (WFA) (Z-score of < -4.4) was not associated with an increased risk of mortality. Because first-level health facilities generally lack length-boards, bipedal oedema and visible severe wasting were chosen as indicators of severe malnutrition. To assess potential WFA thresholds for the very low weight classification, our primary source of data came from 1785 Kenyan outpatient children, but we also examined data from surveys in Nepal, Bolivia, and Togo. We examined the performance of WFA at various thresholds to identify children with low WFH and, for children aged < or = 2 years, low height-for-age (HFA). Use of a WFA threshold Z-score of < -2 identified a considerable proportion of children (from 13% in Bolivia to 68% in Nepal) which, in most settings, would pose an enormous burden on the health facility. Among ill children in Kenya, a threshold WFA Z-score of < -3 had a sensitivity of 89-100% to detect children with WFH Z-scores of < -3, and, with an identification rate of 9%, would avoid overburdening the clinics. Potential modifications include use of a more restrictive cut-off in countries with high rates of stunting, or the elimination of the WFA screen in order to concentrate efforts on intervention for all children below the 2-year age cut-off. Key issues in every country include the capacity to provide counselling for many children and linkage to nutritional improvement programmes in the community. PMID:9529721

  12. Groundwater baseline sampling programs designed to identify potential leakage from unconventional gas plays in Alberta, Canada

    NASA Astrophysics Data System (ADS)

    Mayer, B.; Humez, P.; Ing, J.; Nightingale, M.

    2014-12-01

    With the rapid expansion of natural gas exploitation from unconventional reservoirs including coalbed methane and shale gas plays, there is significant public concern about potential future contamination of shallow potable groundwater with stray gases, formation waters or chemicals used during hydraulic fracturing. In order to enable a scientifically sound assessment of potential future deterioration of freshwater resources in shallow aquifers, it is essential to first establish and understand the current baseline of groundwater quality including its dissolved or free gases. Since 2006, we have conducted monitoring programs determining the chemical and isotopic compositions of water, its dissolved constituents, and of gases obtained from shallow groundwater and formation fluids collected from coalbed methane and shale gas plays in Western Canada. For groundwater samples, we placed special emphasis on determining the sources of dissolved and free gases using isotope techniques to assess whether gases produced from shale gas plays or potentially leaking from the intermediate zone are isotopically distinct from those in shallow aquifers. Methane and ethane in free gas samples obtained from shallow aquifers (n = 24) were found to have mean ?13C values of -72.4 ‰ and -50.2 ‰, respectively. These values are markedly different from the much higher ?13C values of methane and ethane in deeper portions of the Western Canadian Sedimentary Basin and in shale gas plays. Therefore, it appears highly feasible to identify potential gas leakage from unconventional gas plays provided that baseline data for shallow groundwater have been determined. Repeat baseline sampling of free gas from selected wells revealed a comparatively low variability of ?13C values of methane and ethane of usually < 2 ‰ over periods of several years, suggesting that it is not necessary to conduct baseline analyses more than three times. Also, ?13C values of methane in free gas samples and dissolved gas samples typically agreed within 1 ‰ suggesting that both sampling approaches are suitable for determining baseline carbon isotope ratios in case that methane occurs in shallow aquifers.

  13. Sphagnum ?13C Values as Potential Indicators of Palaeohydrological Changes in Peat Bogs

    NASA Astrophysics Data System (ADS)

    Loisel, J.; Garneau, M.; Hélie, J.

    2007-12-01

    Late-Holocene peat stratigraphy of a Canadian boreal peat bog was examined in order to evaluate the potential of Sphagnum ?13C values as a surface wetness proxy indicator. Carbon isotope-inferred past moisture levels were compared to testate amoebae-inferred water table depths, and to past decomposition levels inferred by colorimetric analyses, bulk density and carbon to nitrogen ratio measurements. Analyses were carried out at the same levels, allowing relations between the different proxies. In order to establish peat chronology, six AMS radiocarbon dates were coupled with ten 210Pb dates. Proxy records were combined and compared, and since a strong correlation was found among proxies, a valuable high-resolution surface- moisture reconstruction was obtained from the core. Although the mechanisms underlying carbon fractionation processes in peatlands are not well understood, we demonstrate that Sphagnum ?13C values have a great potential for palaeohydrological reconstructions by providing a complementary source of information.

  14. Event-related potential indices of workload in a single task paradigm

    NASA Technical Reports Server (NTRS)

    Horst, R. L.; Munson, R. C.; Ruchkin, D. S.

    1984-01-01

    Many previous studies of both behavioral and physiological correlates of cognitive workload have burdened subjects with a contrived secondary task in order to assess the workload of a primary task. The present study investigated event-related potential (ERP) indices of workload in a single task paradigm. Subjects monitored changing digital readouts for values that went 'out-of-bounds'. The amplitude of a long-latency positivity in the ERPs elicited by readout changes increased with the number of readouts being monitored. This effect of workload on ERPs is reported, along with plans for additional analyses to address theoretical implications.

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

    PubMed

    Wang, Degao; Tian, Fulin; Yang, Meng; Liu, Chenlin; Li, Yi-Fan

    2009-05-01

    Soil derived sources of polycyclic aromatic hydrocarbons (PAHs) in the region of Dalian, China were investigated using positive matrix factorization (PMF). Three factors were separated based on PMF for the statistical investigation of the datasets both in summer and winter. These factors were dominated by the pattern of single sources or groups of similar sources, showing seasonal and regional variations. The main sources of PAHs in Dalian soil in summer were the emissions from coal combustion average (46%), diesel engine (30%), and gasoline engine (24%). In winter, the main sources were the emissions from coal-fired boiler (72%), traffic average (20%), and gasoline engine (8%). These factors with strong seasonality indicated that coal combustion in winter and traffic exhaust in summer dominated the sources of PAHs in soil. These results suggested that PMF model was a proper approach to identify the sources of PAHs in soil. PMID:19201072

  16. Identifying At-Risk Employees: Modeling Psychosocial Precursors of Potential Insider Threats

    SciTech Connect

    Greitzer, Frank L.; Kangas, Lars J.; Noonan, Christine F.; Dalton, Angela C.; Hohimer, Ryan E.

    2012-01-04

    In many insider crimes, managers and other coworkers observed that the offenders had exhibited signs of stress, disgruntlement, or other issues, but no alarms were raised. Barriers to using such psychosocial indicators include the inability to recognize the signs and the failure to record the behaviors so that they can be assessed. A psychosocial model was developed to assess an employee's behavior associated with an increased risk of insider abuse. The model is based on case studies and research literature on factors/correlates associated with precursor behavioral manifestations of individuals committing insider crimes. To test the model's agreement with human resources and management professionals, we conducted an experiment with positive results. If implemented in an operational setting, the model would be part of a set of management tools for employee assessment to identify employees who pose a greater insider threat.

  17. 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.

  18. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets

    PubMed Central

    Turner, Nicholas; Lambros, Maryou B; Horlings, Hugo M.; Pearson, Alex; Sharpe, Rachel; Natrajan, Rachael; Geyer, Felipe C; van Kouwenhove, Marieke; Kreike, Bas; Mackay, Alan; Ashworth, Alan; van de Vijver, Marc J; Reis-Filho, Jorge S

    2009-01-01

    Triple negative breast cancers (TNBCs) have a relatively poor prognosis and cannot be effectively treated with current targeted therapies. We searched for genes that have the potential to be therapeutic targets by identifying genes consistently over-expressed when amplified. Fifty-six TNBCs were subjected to high-resolution microarray-based comparative genomic hybridisation (aCGH), of which 24 were subjected to genome-wide gene expression analysis. TNBCs were genetically heterogeneous; no individual focal amplification was present at high frequency, although 78.6% of TNBCs harboured at least one focal amplification. Integration of aCGH and expression data revealed 40 genes significantly overexpressed when amplified, including the known oncogenes and potential therapeutic targets, FGFR2 (10q26.3), BUB3 (10q26.3), RAB20 (13q34), PKN1 (19p13.12), and NOTCH3 (19p13.12). We identified two TNBC cell lines with FGFR2 amplification, which both had constitutive activation of FGFR2. Amplified cell lines were highly sensitive to FGFR inhibitor PD173074, and to RNAi silencing of FGFR2. Treatment with PD173074 induced apoptosis resulting partly from inhibition of PI3K-AKT signalling. Independent validation using publicly available aCGH datasets revealed FGFR2 gene was amplified in 4% (6/165) of TNBC, but not in other subtypes (0/214, p=0.0065). Our analysis demonstrates that TNBCs are heterogeneous tumours with amplifications of FGFR2 in a subgroup of tumours. PMID:20101236

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

    SciTech Connect

    Wendt, Jeremy Daniel

    2013-07-01

    We present the results of a two year project focused on a common social engineering attack method called %22spear phishing%22. In a spear phishing attack, the user receives an email with information specifically focused on the user. This email contains either a malware-laced attachment or a link to download the malware that has been disguised as a useful program. Spear phishing attacks have been one of the most effective avenues for attackers to gain initial entry into a target network. This project focused on a proactive approach to spear phishing. To create an effective, user-specific spear phishing email, the attacker must research the intended recipient. We believe that much of the information used by the attacker is provided by the target organization's own external website. Thus when researching potential targets, the attacker leaves signs of his research in the webserver's logs. We created tools and visualizations to improve cybersecurity analysts' abilities to quickly understand a visitor's visit patterns and interests. Given these suspicious visitors and log-parsing tools, analysts can more quickly identify truly suspicious visitors, search for potential spear-phishing targeted users, and improve security around those users before the spear phishing email is sent.

  20. Structured methods for identifying and correcting potential human errors in space operations.

    PubMed

    Nelson, W R; Haney, L N; Ostrom, L T; Richards, R E

    1998-01-01

    Human performance plays a significant role in the development and operation of any complex system, and human errors are significant contributors to degraded performance, incidents, and accidents for technologies as diverse as medical systems, commercial aircraft, offshore oil platforms, nuclear power plants, and space systems. To date, serious accidents attributed to human error have fortunately been rare in space operations. However, as flight rates go up and the duration of space missions increases, the accident rate could increase unless proactive action is taken to identity and correct potential human errors in space operations. The Idaho National Engineering and Environmental Laboratory (INEEL) has developed and applied structured methods of human error analysis to identify potential human errors, assess their effects on system performance, and develop strategies to prevent the errors or mitigate their consequences. These methods are being applied in NASA-sponsored programs to the domain of commercial aviation, focusing on airplane maintenance and air traffic management. The application of human error analysis to space operations could contribute to minimize the risks associated with human error in the design and operation of future space systems. PMID:11541925

  1. Evaluation of Potential Indicators of Viral Contamination in Shellfish and Their Applicability to Diverse Geographical Areas

    PubMed Central

    Formiga-Cruz, M.; Allard, A. K.; Conden-Hansson, A.-C.; Henshilwood, K.; Hernroth, B. E.; Jofre, J.; Lees, D. N.; Lucena, F.; Papapetropoulou, M.; Rangdale, R. E.; Tsibouxi, A.; Vantarakis, A.; Girones, R.

    2003-01-01

    The distribution of the concentration of potential indicators of fecal viral pollution in shellfish was analyzed under diverse conditions over 18 months in diverse geographical areas. These microorganisms have been evaluated in relation to contamination by human viral pathogens detected in parallel in the analyzed shellfish samples. Thus, significant shellfish-growing areas from diverse countries in the north and south of Europe (Greece, Spain, Sweden, and the United Kingdom) were defined and studied by analyzing different physicochemical parameters in the water and the levels of Escherichia coli, F-specific RNA bacteriophages, and phages infecting Bacteroides fragilis strain RYC2056 in the shellfish produced, before and after depuration treatments. A total of 475 shellfish samples were studied, and the results were statistically analyzed. According to statistical analysis, the presence of human viruses seems to be related to the presence of all potential indicators in the heavily contaminated areas, where E. coli would probably be suitable as a fecal indicator. The F-RNA phages, which are present in higher numbers in Northern Europe, seem to be significantly related to the presence of viral contamination in shellfish, with a very weak predictive value for hepatitis A virus, human adenovirus, and enterovirus and a stronger one for Norwalk-like virus. However, it is important to note that shellfish produced in A or clean B areas can sporadically contain human viruses even in the absence of E. coli or F-RNA phages. The data presented here will be useful in defining microbiological parameters for improving the sanitary control of shellfish consumed raw or barely cooked. PMID:12620843

  2. Identifiers Identifiers

    E-print Network

    Brass, Stefan

    , July 1998. . Tim Berners­Lee: Cool URIs don't change. [http://www.w3.org/Provider/Style/URI] . Uniform://archive.ncsa.uiuc.edu/demoweb/url­primer.html] . T. Berners­Lee, R. Fielding, L. Masinter: Uniform Resource Identifiers (URI): Generic Syntax. RFC Names. RFC 1737, December 1994, 7 pages. . T. Berners­Lee, L. Masinter, M. McCahill: Uniform Resource

  3. Identifiers Identifiers

    E-print Network

    Brass, Stefan

    , July 1998. . Tim Berners­Lee: Cool URIs don't change. [http://www.w3.org/Provider/Style/URI] Stefan://archive.ncsa.uiuc.edu/demoweb/url­primer.html] . T. Berners­Lee, R. Fielding, L. Masinter: Uniform Resource Identifiers (URI): Generic Syntax. RFC Names. RFC 1737, December 1994, 7 pages. . T. Berners­Lee, L. Masinter, M. McCahill: Uniform Resource

  4. An indicator of probable semicircular canal dehiscence: ocular vestibular evoked myogenic potentials to high frequencies.

    PubMed

    Manzari, Leonardo; Burgess, Ann M; McGarvie, Leigh A; Curthoys, Ian S

    2013-07-01

    The n10 component of the ocular vestibular evoked myogenic potential (oVEMP) to sound and vibration stimuli is a crossed response that has enhanced amplitude and decreased threshold in patients with CT-verified superior semicircular canal dehiscence (SSCD). However, demonstrating enhanced VEMP amplitude and reduced VEMP thresholds requires multiple trials and can be very time consuming and tiring for patients, so a specific indicator of probable SCD that is fast and not tiring would be preferred. Here we report a 1-trial indicator: that the oVEMP n10 in response to a very high frequency stimulus (4000 Hz), either air-conducted sound (ACS) or bone conducted vibration (BCV), is such a fast indicator of probable SCD. In 22 healthy subjects, oVEMP n10 at 4000 Hz was not detectable; however, in all 22 CT-verified SSCD patients tested, oVEMP n10 responses were clearly present to 4000 Hz to either ACS or BCV stimuli. PMID:23674567

  5. Polyphenols as potential indicators for drought tolerance in tea (Camellia sinensis L.).

    PubMed

    Cheruiyot, Erick K; Mumera, Louis M; Ng'etich, Wilson K; Hassanali, Ahmed; Wachira, Francis

    2007-09-01

    Plant polyphenols have gained prominence in quality of plant products and in human health. An experiment was conducted to determine the association of tea polyphenols with water stress and their suitability as indicators for drought tolerance. The experiment was conducted in a 'rain-out' shelter, and consisted of six tea clones (BBK 35, TRFK 6/8, TRFK 76/1, TRFK 395/2, TRFK 31/30, and TRFK 311/287) and four levels of soil water contents (38, 30, 22, and 14% v/v), which were maintained for a period of 12 weeks. The treatments were arranged in a completely randomized design and replicated three times. Plant growth was monitored over 6 weeks, and a water stress index was calculated to determine water-stress tolerant clones. Total polyphenols in tea shoots was analyzed and a regression analysis done. The results indicate that declining soil water content (SWC) reduced both growth and content of polyphenols in tea. Tolerant clones maintained a high polyphenol content at low SWC, and also showed less fluctuation in phenolics when subjected to changes in SWC. There was significant (P<0.001) correlation of total polyphenol content with shoot growth and WSI of tea, and a linear relationship (r2=0.97) between SWC for tea and both, water stress index and shoot polyphenol content. We report that there is a potential to use polyphenols as indicators for selection of drought-tolerant tea cultivars. PMID:17827703

  6. High-magnification selection of spermatozoa prior to oocyte injection: confirmed and potential indications.

    PubMed

    Boitrelle, F; Guthauser, B; Alter, L; Bailly, M; Bergere, M; Wainer, R; Vialard, F; Albert, M; Selva, J

    2014-01-01

    Intracytoplasmic morphologically selected sperm injection (IMSI) involves the use of differential interference contrast microscopy at high magnification (at least ·6300) to improve the observation of live human spermatozoa (particularly by showing sperm head vacuoles that are not necessarily seen at lower magnifications) prior to intracytoplasmic sperm injection (ICSI) into the oocyte. However, a decade after IMSI’s introduction, the technique’s indications and ability to increase pregnancy and/or birth rates (relative to conventional ICSI) are subject to debate. In an attempt to clarify this debate, this work performed a systematic literature review according to the PRISMA guidelines. The PubMed database was searched from 2001 onwards with the terms ‘IMSI’, ‘MSOME’ and ‘high-magnification, sperm’. Out of 168 search results, 22 relevant studies reporting IMSI outcomes in terms of blastocyst, pregnancy, delivery and/or birth rates were selected and reviewed. The studies’ methodologies and results are described and discussed herein. In view of the scarcity of head-to-head IMSI versus ICSI studies, the only confirmed indication for IMSI is recurrent implantation failure following ICSI. All other potential indications of IMSI require further investigation. PMID:24268730

  7. Evaluation of potential sources and transport mechanisms of fecal indicator bacteria to beach water, Murphy Park Beach, Door County, Wisconsin

    USGS Publications Warehouse

    Juckem, Paul F.; Corsi, Steven R.; McDermott, Colleen; Kleinheinz, Gregory; Fogarty, Lisa R.; Haack, Sheridan K.; Johnson, Heather E.

    2013-01-01

    Fecal Indicator Bacteria (FIB) concentrations in beach water have been used for many years as a criterion for closing beaches due to potential health concerns. Yet, current understanding of sources and transport mechanisms that drive FIB occurrence remains insufficient for accurate prediction of closures at many beaches. Murphy Park Beach, a relatively pristine beach on Green Bay in Door County, Wis., was selected for a study to evaluate FIB sources and transport mechanisms. Although the relatively pristine nature of the beach yielded no detection of pathogenic bacterial genes and relatively low FIB concentrations during the study period compared with other Great Lakes Beaches, its selection limited the number of confounding FIB sources and associated transport mechanisms. The primary sources of FIB appear to be internal to the beach rather than external sources such as rivers, storm sewer outfalls, and industrial discharges. Three potential FIB sources were identified: sand, swash-zone groundwater, and Cladophora mats. Modest correlations between FIB concentrations in these potential source reservoirs and FIB concentrations at the beach from the same day illustrate the importance of understanding transport mechanisms between FIB sources and the water column. One likely mechanism for transport and dispersion of FIB from sand and Cladophora sources appears to be agitation of Cladophora mats and erosion of beach sand due to storm activity, as inferred from storm indicators including turbidity, wave height, current speed, wind speed, sky visibility, 24-hour precipitation, and suspended particulate concentration. FIB concentrations in beach water had a statistically significant relation (p-value ‹0.05) with the magnitude of these storm indicators. In addition, transport of FIB in swash-zone groundwater into beach water appears to be driven by groundwater recharge associated with multiday precipitation and corresponding increased swash-zone groundwater discharge at the beach, as indicated by an increase in the specific conductance of beach water. Understanding the dynamics of FIB sources (sand, swash-zone groundwater, and Cladophora) and transport mechanisms (dispersion and erosion from storm energy, and swash-zone groundwater discharge) is important for improving predictions of potential health risks from FIB in beach water.

  8. Characterizing the successful student in general chemistry and physical science classes in terms of Jung's personality types as identified by the Myers-Briggs Type Indicator

    NASA Astrophysics Data System (ADS)

    Riley, Wayne David

    1998-11-01

    A student's success in a science class can depend upon previous experiences, motivation, and the level of interest in the subject. Since psychological type is intrinsic to a person's whole being, it can be influential upon the student's motivation and interests. Thus, a study of student psychological types versus the level of success in a class, as measured by a percentage, has potential to uncover certain personality characteristics which may be helpful to or which may hinder a student's learning environment. This study was initiated, using the Myers-Briggs Type Indicator, to evaluate any correlation between a student's personality type and his/her performance in a science class. A total of 1041 students from three classes: Chemistry 121/122, Chemistry 112, Physical Science 100, volunteered for the study. An analysis of variance (ANOVA) was used to determine the levels of significance among sixteen personality types' averages. The results reveal that for the Chemistry 1121/122 course, the average score of the INTJ personality type was 5.1 to 12.6 points higher than every other personality type. The ANOVA identifies 3 personality types with averages significantly below the INTJ at the p < 0.05 significance level. The ANOVA analysis for the Chemistry 112 course identified significances between student scores at p = 0.08. The significance level for the differences among scores for the Physical Science 100 course was determined at a level of p = 0.02. Significance levels for p < 0.05 and <0.01 were identified between several groups in this course. The data suggest, that although personality type may not predict a particular student's success in a science class, students with certain personality traits may be favored in a chemistry class due the structure of the instruction and the presentation of the subject matter.

  9. Dipole potentials indicate restructuring of the membrane interface induced by gadolinium and beryllium ions.

    PubMed Central

    Ermakov, Y A; Averbakh, A Z; Yusipovich, A I; Sukharev, S

    2001-01-01

    The dipole component of the membrane boundary potential, phi(d), is an integral parameter that may report on the conformational state of the lipid headgroups and their hydration. In this work, we describe an experimental approach to measurements of the dipole potential changes, Deltaphi(d), and apply it in studies of Be(2+) and Gd(3+) interactions with membranes composed of phosphatidylserine (PS), phosphatidylcholine (PC), and their mixtures. Deltaphi(d) is determined as the difference between the changes of the total boundary potential, phi(b), measured by the IFC method in planar lipid membranes and the surface potential, phi(s), determined from the electrophoretic mobility of liposomes. The Gouy-Chapman-Stern formalism, combined with the condition of mass balance, well describes the ion equilibria for these high-affinity cations. For the adsorption of Be(2+) and Gd(3+) to PC membranes, and of Mg(2+) to PS membranes, the values of Deltaphi(b) and Deltaphi(s) are the same, indicative of no change of phi(d). Binding of Gd(3+) to PS-containing membranes induces changes of phi(d) of opposite signs depending on the density of ionized PS headgroups in the bilayer. At low density, the induced Deltaphi(d) is negative (-30 mV), consistent with the effect of dehydration of the surface. At maximal density (pure PS, neutral pH), adsorption of Be(2+) or Gd(3+) induces an increase of phi(d) of 35 or 140 mV, respectively. The onset of the strong positive dipole effect on PS membranes with Gd(3+) is observed near the zero charge point and correlates with a six-fold increase of membrane tension. The observed phenomena may reflect concerted reorientation of dipole moments of PS headgroups as a result of ion adsorption and lipid condensation. Their possible implications to in-vivo effects of these high-affinity ions are discussed. PMID:11259298

  10. Measuring Quality in Higher Education: Can a Performance Indicator Approach Be Extended to Identifying the Quality of Students' Union Provision?

    ERIC Educational Resources Information Center

    Rodgers, Timothy

    2008-01-01

    The desire to enhance the quality of the services provided by higher education institutions in the UK has led to the development of a series of benchmarking performance indicators to aid the quality management process. This paper examines whether or not similar indicators could be developed for use as tools in the management of quality within…

  11. Systemic Approach to Identify Serum microRNAs as Potential Biomarkers for Acute Myocardial Infarction

    PubMed Central

    Chen, Shu-Jen; Chang, Yu-Sun; Chu, Pao-Hsien

    2014-01-01

    Background. Recent studies have revealed the role of microRNAs (miRNAs) in a variety of biological and pathological processes, including acute myocardial infarction (AMI). We hypothesized that ST-segment elevation myocardial infarction (STEMI) may be associated with an alteration of miRNAs and that circulating miRNAs may be used as diagnostic markers for STEMI. Methods. Expression levels of 270 serum miRNAs were analyzed in 8 STEMI patients and 8 matched healthy controls to identify miRNAs differentially expressed in the sera of patients with AMI. The differentially expressed miRNAs were evaluated in a separate cohort of 62 subjects, including 31 STEMI patients and 31 normal controls. Results. The initial profiling study identified 12 upregulated and 13 downregulated serum miRNAs in the AMI samples. A subsequent validation study confirmed that serum miR-486-3p and miR-150-3p were upregulated while miR-126-3p, miR-26a-5p, and miR-191-5p were significantly downregulated in the sera of patients with AMI. Ratios between the level of upregulated and downregulated miRNAs were also significantly different in those with AMI. Receiver operator characteristics curve analysis using the expression ratio of miR-486-3p and miR-191-5p showed an area under the curve of 0.863. Conclusion. Our results suggest that serum miRNAs may be used as potential diagnostic biomarkers for STEMI. PMID:24900964

  12. A proton current drives action potentials in genetically identified sour taste cells

    PubMed Central

    Chang, Rui B.; Waters, Hang; Liman, Emily R.

    2010-01-01

    Five tastes have been identified, each of which is transduced by a separate set of taste cells. Of these sour, which is associated with acid stimuli, is the least understood. Genetic ablation experiments have established that sour is detected by a subset of taste cells that express the TRP channel PKD2L1 and its partner PKD1L3, however the mechanisms by which this subset of cells detects acids remain unclear. Previous efforts to understand sour taste transduction have been hindered because sour responsive cells represent only a small fraction of cells in a taste bud, and numerous ion channels with no role in sour sensing are sensitive to acidic pH. To identify acid-sensitive conductances unique to sour cells, we created genetically modified mice in which sour cells were marked by expression of YFP under the control of the PKD2L1 promoter. To measure responses to sour stimuli we developed a method in which suction electrode recording is combined with UV photolysis of NPE-caged proton. Using these methods, we report that responses to sour stimuli are not mediated by Na+ permeable channels as previously thought, but instead are mediated by a proton conductance specific to PKD2L1-expressing taste cells. This conductance is sufficient to drive action potential firing in response to acid stimuli, is enriched in the apical membrane of PKD2L1-expressing taste cells and is not affected by targeted deletion of the PKD1L3 gene. We conclude that, during sour transduction, protons enter through an apical proton conductance to directly depolarize the taste cell membrane. PMID:21098668

  13. On the use of the resting potential and level set methods for identifying ischemic heart disease: An inverse problem

    NASA Astrophysics Data System (ADS)

    Nielsen, Bjørn Fredrik; Lysaker, Marius; Tveito, Aslak

    2007-01-01

    The electrical activity in the heart is modeled by a complex, nonlinear, fully coupled system of differential equations. Several scientists have studied how this model, referred to as the bidomain model, can be modified to incorporate the effect of heart infarctions on simulated ECG (electrocardiogram) recordings. We are concerned with the associated inverse problem; how can we use ECG recordings and mathematical models to identify the position, size and shape of heart infarctions? Due to the extreme CPU efforts needed to solve the bidomain equations, this model, in its full complexity, is not well-suited for this kind of problems. In this paper we show how biological knowledge about the resting potential in the heart and level set techniques can be combined to derive a suitable stationary model, expressed in terms of an elliptic PDE, for such applications. This approach leads to a nonlinear ill-posed minimization problem, which we propose to regularize and solve with a simple iterative scheme. Finally, our theoretical findings are illuminated through a series of computer simulations for an experimental setup involving a realistic heart in torso geometry. More specifically, experiments with synthetic ECG recordings, produced by solving the bidomain model, indicate that our method manages to identify the physical characteristics of the ischemic region(s) in the heart. Furthermore, the ill-posed nature of this inverse problem is explored, i.e. several quantitative issues of our scheme are explored.

  14. A mixture of odorant molecules potentially indicating oestrus in mammals elicits penile erections in male rats.

    PubMed

    Nielsen, Birte L; Jerôme, Nathalie; Saint-Albin, Audrey; Thonat, Catherine; Briant, Christine; Boué, Franck; Rampin, Olivier; Maurin, Yves

    2011-12-01

    A common set of odorous molecules may indicate female receptiveness across species, as male rats display sexual arousal when exposed to the odour of oestrous faeces from rats, vixens and mares. More than 900 different compounds were identified by GC-MS analyses performed on faeces samples from di-oestrous and oestrous females and from males of the three species. Five carboxylic acids were found in lower concentrations in faeces from all oestrous females. We subjected 12 sexually trained male rats to a 30 min exposure to different dilutions of a mixture of these five molecules in the same proportions as found in female oestrous faeces. The behavioural responses of the rats were compared to those displayed when exposed to water (negative control) and faeces from oestrous female rats (positive control). Frequency of penile erections were found to be significantly dependent on mixture dilution, with two intermediate dilutions eliciting frequencies of penile erections that did not differ from those obtained during exposure to oestrous female rat faeces. Higher and lower dilutions did not elicit more penile erections than observed with water. These results support our hypothesis that a small set of odorous molecules may indicate sexual receptiveness in mammalian females. PMID:21884731

  15. Use of EMCS Recorded Data to Identify Potential Savings Due to Improved HVAC Operations & Maintenance (O&M)

    E-print Network

    Liu, M.; Zhu, Y.; Claridge, D. E.

    1996-01-01

    In most chiller and boiler central plants, the energy management and control systems (EMCS) monitor and record key operation parameters and energy production continuously. A method was developed to identify potential O&M savings by using the EMCS...

  16. 49 CFR 192.917 - How does an operator identify potential threats to pipeline integrity and use the threat...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...operator identify potential threats to pipeline integrity and use the threat identification...Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION...DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL...

  17. Correlation Analysis between SNP and Expression Arrays in Gliomas Identify Potentially Relevant Targets Genes1

    PubMed Central

    Kotliarov, Yuri; Kotliarova, Svetlana; Charong, Nurdina; Li, Aiguo; Walling, Jennifer; Aquilanti, Elisa; Ahn, Susie; Steed, Mary Ellen; Su, Qin; Center, Angela; Zenklusen, Jean C; Fine, Howard A.

    2008-01-01

    Primary brain tumors are a major cause of cancer mortality in the United States. Therapy for gliomas, the most common type of primary brain tumors, remains suboptimal. The development of improved therapeutics will require greater knowledge of the biology of gliomas at both the genomic and transcriptional levels. We have previously reported whole genome profiling of chromosome copy number alterations (CNA) in gliomas, and now present our findings on how those changes may affect transcription of genes that may be involved in tumor induction and progression. By calculating correlation values of mRNA expression vs. DNA copy number average in a moving window around a given RNA probeset, biologically relevant information can be gained that is obscured by the analysis of a single data type. Correlation coefficients ranged from ?0.6 to 0.7; highly significant when compared to previously studies. Most correlated genes are located on chromosomes 1, 7, 9, 10, 13, 14, 19, 20 and 22, chromosomes known to have genomic alterations in gliomas. Additionally, we were able to identify CNAs whose gene expression correlation suggests possible epigenetic regulation. This analysis revealed a number of interesting candidates such as CXCL12, PTER, LRRN6C, among others. The results have been verified using real-time PCR and methylation sequencing assays. These data will further help differentiate genes involved in the induction and/or maintenance of the tumorigenic process from those that are mere passenger mutations, thereby enriching for a population of potentially new therapeutic molecular targets. PMID:19190341

  18. 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.

  19. In silico analysis for identifying potential vaccine candidates against Staphylococcus aureus

    PubMed Central

    Sedighian, Hamid

    2015-01-01

    Purpose Staphylococcus aureus is one of the most important causes of nosocomial and community-acquired infections. The increasing incidence of multiple antibiotic-resistant S. aureus strains and the emergence of vancomycin resistant S. aureus strains have placed renewed interest on alternative means of prevention and control of infection. S. aureus produces a variety of virulence factors, so a multi-subunit vaccine will be more successful for preventing S. aureus infections than a mono-subunit vaccine. Materials and Methods We selected three important virulence factors of S. aureus, clumping factor A (ClfA), iron-regulated surface determinant (IsdB), and gamma hemolysin (Hlg) that are potential candidates for vaccine development. We designed synthetic genes encoding the clfA, isdB, and hlg and used bioinformatics tools to predict structure of the synthetic construct and its stabilities. VaxiJen analysis of the protein showed a high antigenicity. Linear and conformational B-cell epitopes were identified. Results The proteins encoded by these genes were useful as vaccine candidates against S. aureus infections. Conclusion In silico tools are highly suited to study, design, and evaluate vaccine strategies. PMID:25649548

  20. 2D-DIGE proteomic analysis identifies new potential therapeutic targets for adrenocortical carcinoma

    PubMed Central

    Armignacco, Roberta; Ercolino, Tonino; Canu, Letizia; Baroni, Gianna; Nesi, Gabriella; Galli, Andrea; Mannelli, Massimo; Luconi, Michaela

    2015-01-01

    Adrenocortical carcinoma (ACC) is a rare aggressive tumor with poor prognosis when metastatic at diagnosis. The tumor biology is still mostly unclear, justifying the limited specificity and efficacy of the anti-cancer drugs currently available. This study reports the first proteomic analysis of ACC by using two-dimensional-differential-in-gel-electrophoresis (2D-DIGE) to evaluate a differential protein expression profile between adrenocortical carcinoma and normal adrenal. Mass spectrometry, associated with 2D-DIGE analysis of carcinomas and normal adrenals, identified 22 proteins in 27 differentially expressed 2D spots, mostly overexpressed in ACC. Gene ontology analysis revealed that most of the proteins concurs towards a metabolic shift, called the Warburg effect, in adrenocortical cancer. The differential expression was validated by Western blot for Aldehyde-dehydrogenase-6-A1,Transferrin, Fascin-1,Lamin A/C,Adenylate-cyclase-associated-protein-1 and Ferredoxin-reductase. Moreover, immunohistochemistry performed on paraffin-embedded ACC and normal adrenal specimens confirmed marked positive staining for all 6 proteins diffusely expressed by neoplastic cells, compared with normal adrenal cortex. In conclusion, our preliminary findings reveal a different proteomic profile in adrenocortical carcinoma compared with normal adrenal cortex characterized by overexpression of mainly metabolic enzymes, thus suggesting the Warburg effect also occurs in ACC. These proteins may represent promising novel ACC biomarkers and potential therapeutic targets if validated in larger cohorts of patients. PMID:25691058

  1. Plasma sphingolipids as potential indicators of hepatic necroinflammation in patients with chronic hepatitis C and normal alanine aminotransferase level.

    PubMed

    Li, Jun-Feng; Qu, Feng; Zheng, Su-Jun; Ren, Jin-Yu; Wu, Hui-Li; Liu, Mei; Liu, Hui; Ren, Feng; Chen, Yu; Zhang, Jin-Lan; Duan, Zhong-Ping

    2014-01-01

    Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C (CHC) is crucial for prediction of prognosis and design of therapeutic strategy, which is particularly true for CHC patients with normal alanine aminotransferase (ALT) level. Recent studies have shown that sphingolipids have a close relationship with hepatitis C virus infection. The present study aimed to identify plasma sphingolipids related to hepatic necroinflammation. We included 120 treatment-naïve CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC patients who underwent liver biopsies were subjected to Scheuer scoring analysis for scope of hepatic inflammation. Plasma sphingolipids were detected by high-performance liquid chromatography tandem mass spectrometry. Our results showed 44 plasma sphingolipids were detected altogether. Of all detected sphingolipids, hexosylceramide (HexCer) (d18?1/22?0) and HexCer (d18?1/24?0) showed a significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying hepatic necroinflammation (G?2), after adjusting other factors, the odds ratio (OR) of HexCer (d18?1/22?0) reached 1.01 (95% confidence interval [CI]: 1.00-1.02). Furthermore, the area under the curve (AUC) of HexCer (d18?1/22?0) was 0.7 (P?=?0.01) and approached that of ALT (AUC?=?0.78). However, in CHC patients with normal ALT, HexCer (d18?1/22?0) was an independent factor (OR: 1.02, 95% CI: 1.01-1.03) to identify the hepatic necroinflammation (G?2). HexCer (d18?1/22?0) not only showed the largest AUC (0.78, P?=?0.001), but also exhibited the highest specificity of all indicators. These results indicate that plasma HexCer (d18?1/22?0) is a potential indicator to distinguish hepatic necroinflammation in CHC patients. For CHC with normal ALT, the ability of HexCer (d18?1/22?0) to distinguish hepatic necroinflammation might be superior to conventional serum indicators. PMID:24736528

  2. Identifying Individual Changes in Performance with Composite Quality Indicators while Accounting for Regression-to-the-Mean

    PubMed Central

    Gajewski, Byron J.; Dunton, Nancy

    2012-01-01

    Almost a decade ago Morton & Torgerson (p. 1084) indicated that perceived medical benefits could be due to “…regression-to-the-mean.” Despite this caution, the regression-to-the-mean “…effects on the identification of changes in institutional performance do not seem to have been considered previously in any depth.” (Jones & Spiegelhalter, p. 1646). As a response, Jones & Spiegelhalter provide a methodology to adjust for regression-to-the-mean when modeling recent changes in institutional performance for one variable quality indicators (QIs). Therefore, in our view, Jones & Spiegelhalter provide a breakthrough methodology for performance measures. At the same time, in the interests of parsimony, it is useful to aggregate individual QIs into a composite score. Our question is: Can we develop and demonstrate a methodology that extends the ‘regression-to-the-mean’ literature to allow for composite quality indicators? Using a latent variable modeling approach, we extend the methodology to the composite indicator case. We demonstrate the approach on four indicators collected by the National Database of Nursing Quality Indicators® (NDNQI®). A simulation study further demonstrates its “proof of concept.” PMID:23035127

  3. National valuation of monarch butterflies indicates an untapped potential for incentive-based conservation

    USGS Publications Warehouse

    Diffendorfer, Jay E.; Loomis, John B.; Ries, Leslie; Oberhauser, Karen; Semmens, Darius; Semmens, Brice; Butterfield, Bruce; Bagstad, Ken; Goldstein, Josh; Wiederholt, Ruscena; Mattsson, Brady; Thogmartin, Wayne E.

    2013-01-01

    The annual migration of monarch butterflies (Danaus plexippus) has high cultural value and recent surveys indicate monarch populations are declining. Protecting migratory species is complex because they cross international borders and depend on multiple regions. Understanding how much, and where, humans place value on migratory species can facilitate market-based conservation approaches. We performed a contingent valuation study of monarchs to understand the potential for such approaches to fund monarch conservation. The survey asked U.S. respondents about the money they would spend, or have spent, growing monarch-friendly plants, and the amount they would donate to monarch conservation organizations. Combining planting payments and donations, the survey indicated U.S. households valued monarchs as a total one-time payment of $4.78–$6.64 billion, levels similar to many endangered vertebrate species. The financial contribution of even a small percentage of households through purchases or donations could generate new funding for monarch conservation through market-based approaches.

  4. Antioxidant Potential of a Polyherbal Antimalarial as an Indicator of Its Therapeutic Value

    PubMed Central

    Arrey Tarkang, Protus; Nwachiban Atchan, Achille Parfait; Kuiate, Jules-Roger; Okalebo, Faith Apoelot; Guantai, Anastasia Nkatha; Agbor, Gabriel Agbor

    2013-01-01

    Nefang is a polyherbal product composed of Mangifera indica (bark and leaf), Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum (leaves), used for the treatment of malaria. Compounds with antioxidant activity are believed to modulate plasmodial infection. Antioxidant activity of the constituent aqueous plants extracts, in vitro, was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic content (TPC), and ferric reducing antioxidant power (FRAP) methods and, in vivo, Nefang (100 and 500?mg?kg?1) activity was evaluated in carbon tetrachloride-induced oxidative stressed Wistar rats. Superoxide dismutase, catalase activities, and lipid peroxidation by the malondialdehyde and total proteins assays were carried out. P. guajava, M. indica leaf, and bark extracts had the highest antioxidant properties in all three assays, with no statistically significant difference. Rats treated with the carbon tetrachloride had a statistically significant decrease in levels of triglycerides, superoxide dismutase, and catalase (P < 0.05) and increase in malondialdehyde activity, total protein levels, and liver and renal function markers, whereas rats treated with Nefang showed increased levels in the former and dose-dependent decrease towards normal levels in the later. These results reveal the constituent plants of Nefang that contribute to its in vivo antioxidant potential. This activity is a good indication of the therapeutic potential of Nefang. PMID:24454347

  5. Phenology of Dasineura oxycoccana (Diptera: Cecidomyiidae) on cranberry and blueberry indicates potential for gene flow.

    PubMed

    Cook, Melissa A; Fitzpatrick, Sheila M; Roitberg, Bernard D

    2012-08-01

    Dasineura oxycoccana (Johnson) (Diptera: Cecidomyiidae) is a pest of cranberry, Vaccinium macrocarpon (Aiton) (Ericales: Ericaceae), and highbush blueberry, Vaccinium corymbosum (L.) (Ericales: Ericaceae), in North America. In British Columbia, Canada, D. oxycoccana was first found on highbush blueberry in 1991 and then on cranberry seven years later. Because many cranberry and highbush blueberry farms are adjacent to one another, we hypothesized that D. oxycoccana was moving from highbush blueberry onto cranberry. Cranberry and highbush blueberry differ in phenology, and adaptation to these different phenologies may result in host races or cryptic species on these two crops. We recognized the alternative hypothesis that D. oxycoccana had arrived as immature stages with cranberry vines imported from another region of North America. During spring and summer, we recorded the phenology of D. oxycoccana and the development of plant shoots from three cranberry and three highbush blueberry farms to determine whether the opportunity exists for successful movement of D. oxycoccana between the two crops. Our results show that D. oxycoccana from cranberry and highbush blueberry overlap in phenology for much of the season, indicating a high potential for movement and gene flow. However, differences were seen in number of larvae per shoot, location of pupae, and heat unit accumulation during larval development suggesting that instead there may be the potential for host race or cryptic species formation. PMID:22928299

  6. Potential for early warning of maalria in India using NOAA-AVHRR based vegetation health indices

    NASA Astrophysics Data System (ADS)

    Dhiman, R. C.; Kogan, Felix; Singh, Neeru; Singh, R. P.; Dash, A. P.

    Malaria is still a major public health problem in India with about 1 82 million cases annually and 1000 deaths As per World Health Organization WHO estimates about 1 3 million Disability Adjusted Life Years DALYs are lost annually due to malaria in India Central peninsular region of India is prone to malaria outbreaks Meteorological parameters changes in ecological conditions development of resistance in mosquito vectors development of resistance in Plasmodium falciparum parasite and lack of surveillance are the likely reasons of outbreaks Based on satellite data and climatic factors efforts have been made to develop Early Warning System EWS in Africa but there is no headway in this regard in India In order to find out the potential of NOAA satellite AVHRR derived Vegetation Condition Index VCI Temperature Condition Index TCI and a cumulative indicator Vegetation Health Index VHI were attempted to find out their potential for development of EWS Studies were initiated by analysing epidemiological data of malaria vis-a-vis VCI TCI and VHI from Bikaner and Jaisalmer districts of Rajasthan and Tumkur and Raichur districts of Karnataka Correlation coefficients between VCI and monthly malaria cases for epidemic years were computed Positive correlation 0 67 has been found with one-month lag between VCI and malaria incidence in respect of Tumkur while a negative correlation with TCI -0 45 is observed In Bikaner VCI is found to be negatively related -0 71 with malaria cases in epidemic year of 1994 Weekly

  7. The Potential Use of DNA Methylation Biomarkers to Identify Risk and Progression of Type 2 Diabetes

    PubMed Central

    Gillberg, Linn; Ling, Charlotte

    2015-01-01

    Type 2 diabetes mellitus (T2D) is a slowly progressive disease that can be postponed or even avoided through lifestyle changes. Recent data demonstrate highly significant correlations between DNA methylation and the most important risk factors of T2D, including age and body mass index, in blood and human tissues relevant to insulin resistance and T2D. Also, T2D patients and individuals with increased risk of the disease display differential DNA methylation profiles and plasticity compared to controls. Accordingly, the novel clues to DNA methylation fingerprints in blood and tissues with deteriorated metabolic capacity indicate that blood-borne epigenetic biomarkers of T2D progression might become a reality. This Review will address the most recent associations between DNA methylation and diabetes-related traits in human tissues and blood. The overall focus is on the potential of future epigenome-wide studies, carried out across tissues and populations with correlations to pre-diabetes and T2D risk factors, to build up a library of epigenetic markers of risk and early progression of T2D. These markers may, tentatively in combination with other predictors of T2D development, increase the possibility of individual-based lifestyle prevention of T2D and associated metabolic diseases. PMID:25870586

  8. 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 co-orbitals, but also gives their mass distributions. Although our technique provides only the statistical properties, it indicates where high resolution optical surveys should be obtained in order to identify and track specific hazardous bodies.

  9. Identifying populations potentially exposed to agricultural pesticides using remote sensing and a Geographic Information System.

    PubMed Central

    Ward, M H; Nuckols, J R; Weigel, S J; Maxwell, S K; Cantor, K P; Miller, R S

    2000-01-01

    Pesticides used in agriculture may cause adverse health effects among the population living near agricultural areas. However, identifying the populations most likely to be exposed is difficult. We conducted a feasibility study to determine whether satellite imagery could be used to reconstruct historical crop patterns. We used historical Farm Service Agency records as a source of ground reference data to classify a late summer 1984 satellite image into crop species in a three-county area in south central Nebraska. Residences from a population-based epidemiologic study of non-Hodgkin lymphoma were located on the crop maps using a geographic information system (GIS). Corn, soybeans, sorghum, and alfalfa were the major crops grown in the study area. Eighty-five percent of residences could be located, and of these 22% had one of the four major crops within 500 m of the residence, an intermediate distance for the range of drift effects from pesticides applied in agriculture. We determined the proximity of residences to specific crop species and calculated crop-specific probabilities of pesticide use based on available data. This feasibility study demonstrated that remote sensing data and historical records on crop location can be used to create historical crop maps. The crop pesticides that were likely to have been applied can be estimated when information about crop-specific pesticide use is available. Using a GIS, zones of potential exposure to agricultural pesticides and proximity measures can be determined for residences in a study. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:10622770

  10. Quantification of Impervious Surfaces Along the Wasatch Front, Utah: AN Object-Based Image Analysis Approach to Identifying AN Indicator for Wetland Stress

    NASA Astrophysics Data System (ADS)

    Leydsman-McGinty, E. I.; Ramsey, R. D.; McGinty, C.

    2013-12-01

    The Remote Sensing/GIS Laboratory at Utah State University, in cooperation with the United States Environmental Protection Agency, is quantifying impervious surfaces for three watershed sub-basins in Utah. The primary objective of developing watershed-scale quantifications of impervious surfaces is to provide an indicator of potential impacts to wetlands that occur within the Wasatch Front and along the Great Salt Lake. A geospatial layer of impervious surfaces can assist state agencies involved with Utah's Wetlands Program Plan (WPP) in understanding the impacts of impervious surfaces on wetlands, as well as support them in carrying out goals and actions identified in the WPP. The three watershed sub-basins, Lower Bear-Malad, Lower Weber, and Jordan, span the highly urbanized Wasatch Front and are consistent with focal areas in need of wetland monitoring and assessment as identified in Utah's WPP. Geospatial layers of impervious surface currently exist in the form of national and regional land cover datasets; however, these datasets are too coarse to be utilized in fine-scale analyses. In addition, the pixel-based image processing techniques used to develop these coarse datasets have proven insufficient in smaller scale or detailed studies, particularly when applied to high-resolution satellite imagery or aerial photography. Therefore, object-based image analysis techniques are being implemented to develop the geospatial layer of impervious surfaces. Object-based image analysis techniques employ a combination of both geospatial and image processing methods to extract meaningful information from high-resolution imagery. Spectral, spatial, textural, and contextual information is used to group pixels into image objects and then subsequently used to develop rule sets for image classification. eCognition, an object-based image analysis software program, is being utilized in conjunction with one-meter resolution National Agriculture Imagery Program (NAIP) aerial photography from 2011.

  11. Intrasample REE variability in Pacific Ocean Fe-Mn crusts: A potential paleoceanographic indicator

    SciTech Connect

    De Carlo, E.H. (Hawaii Institute of Geophysics, Honolulu (USA))

    1990-06-01

    Recent studies of the microscale chemistry and morphology of marine Fe-Mn crusts suggest that prevailing oceanographic conditions at the time of formation are recorded in individual layers of the deposits. Using current radiometric crust growth-rate estimates of 1 to 5 mm per million years, thick Fe-Mn oxide accumulations may represent a growth record ranging from 10 to 100 million years. Detailed chemical and mineralogical analyses were performed on 5 mm layers of selected thick (5-10 cm) crusts from our collection. The analyses reveal significant variations in the distribution and abundance of the REE as a function of depth within the crusts. The trivalent REE generally exhibit sympathetic concentration changes in pure Fe-Mn oxides but display a greater degree of fractionation between the light and heavy REE in layers enriched in phosphatic matter. The compositional variability and the extent of REE fractionation can be explained partially by mineralogical control but are also believed to reflect differing depositional conditions and the composition of the seawater from which the deposits formed. Changes in the Ce anomaly throughout the crust correlates with Pt and Ir anomalies observed by other workers and appears to be a very promising indicator of major events. The potential use of Ce as a paleoceanographic tracer stems from its electronic structure, which leads to a preference for the highly insoluble tetravalent CeO{sub 2}, whereas other REE exist principally in the trivalent oxidation state. Because Fe-Mn crusts accrete primarily under oxidizing conditions, variations in the Ce anomaly of crusts may be useful as a paleoredox indicator as previously suggested by other investigators. The REE patterns observed in this study will be discussed in terms of their relation to the major element composition and mineralogy of the crusts.

  12. An improved genetically encoded red fluorescent Ca2+ indicator for detecting optically evoked action potentials.

    PubMed

    Ohkura, Masamichi; Sasaki, Takuya; Kobayashi, Chiaki; Ikegaya, Yuji; Nakai, Junichi

    2012-01-01

    Genetically encoded Ca(2+) indicators (GECIs) are powerful tools to image activities of defined cell populations. Here, we developed an improved red fluorescent GECI, termed R-CaMP1.07, by mutagenizing R-GECO1. In HeLa cell assays, R-CaMP1.07 exhibited a 1.5-2-fold greater fluorescence response compared to R-GECO1. In hippocampal pyramidal neurons, R-CaMP1.07 detected Ca(2+) transients triggered by single action potentials (APs) with a probability of 95% and a signal-to-noise ratio >7 at a frame rate of 50 Hz. The amplitudes of Ca(2+) transients linearly correlated with the number of APs. The expression of R-CaMP1.07 did not significantly alter the electrophysiological properties or synaptic activity patterns. The co-expression of R-CaMP1.07 and channelrhodpsin-2 (ChR2), a photosensitive cation channel, in pyramidal neurons demonstrated that R-CaMP1.07 was applicable for the monitoring of Ca(2+) transients in response to optically evoked APs, because the excitation light for R-CaMP1.07 hardly activated ChR2. These technical advancements provide a novel strategy for monitoring and manipulating neuronal activity with single cell resolution. PMID:22808076

  13. Identifying and reducing potentially wrong immunoassay results even when plausible and "not-unreasonable".

    PubMed

    Ismail, Adel A A

    2014-01-01

    The primary role of the clinical laboratory is to report accurate results for diagnosis of disease and management of illnesses. This goal has, to a large extent been achieved for routine biochemical tests, but not for immunoassays which remained susceptible to interference from endogenous immunoglobulin antibodies, causing false, and clinically misleading results. Clinicians regard all abnormal results including false ones as "pathological" necessitating further investigations, or concluding iniquitous diagnosis. Even more seriously, "false-negative" results may wrongly exclude pathology, thus denying patients' necessary treatment. Analytical error rate in immunoassays is relatively high, ranging from 0.4% to 4.0%. Because analytical interference from endogenous antibodies is confined to individuals' sera, it can be inconspicuous, pernicious, sporadic, and insidious because it cannot be detected by internal or external quality assessment procedures. An approach based on Bayesian reasoning can enhance the robustness of clinical validation in highlighting potentially erroneous immunoassay results. When this rational clinical/statistical approach is followed by analytical affirmative follow-up tests, it can help identifying inaccurate and clinically misleading immunoassay data even when they appear plausible and "not-unreasonable." This chapter is largely based on peer reviewed articles associated with and related to this approach. The first section underlines (without mathematical equations) the dominance and misuse of conventional statistics and the underuse of Bayesian paradigm and shows that laboratorians are intuitively (albeit unwittingly) practicing Bayesians. Secondly, because interference from endogenous antibodies is method's dependent (with numerous formats and different reagents), it is almost impossible to accurately assess its incidence in all differently formulated immunoassays and for each analytes/biomarkers. However, reiterating the basic concepts underpinning interference from endogenous antibodies can highlight why interference will remain analytically pernicious, sporadic, and an inveterate problem. The following section discuses various stratagems to reduce this source of inaccuracy in current immunoassay results including the role of Bayesian reasoning. Finally, the role of three commonly used follow-up affirmative tests and their interpretation in confirming analytical interference is discussed. PMID:25344990

  14. Epigenetic screen identifies genotype- specific promoter DNA methylation and oncogenic potential of CHRNB4

    PubMed Central

    Scherf, David B; Sarkisyan, Narek; Jacobsson, Hanna; Claus, Rainer; Bermejo, Justo L; Peil, Barbara; Gu, Lei; Muley, Thomas; Meister, Michael; Dienemann, Hendrik; Plass, Christoph; Risch, Angela

    2012-01-01

    Genome-wide association studies have highlighted three major lung cancer susceptibility regions at 15q25.1, 5p15.33 and 6p21.33. To gain insight into the possible mechanistic relevance of the genes in these regions, we investigated the regulation of candidate susceptibility gene expression by epigenetic alterations in healthy and lung tumor tissues. For genes up- or downregulated in lung tumors the influence of genetic variants on DNA methylation was investigated and in vitro studies were performed. We analyzed 394 CpG units within 19 CpG islands in the susceptibility regions in a screening set of 34 patients. Significant findings were validated in an independent patient set (n=50) with available DNA and RNA. The most consistent overall DNA methylation difference between tumor and adjacent normal tissue on 15q25 was tumor hypomethylation in the promoter region of CHRNB4 with a median difference of 8% (p<0.001) which resulted in overexpression of the transcript in tumors (p<0.001). Confirming previous studies we also found hypermethylation in CHRNA3 and TERT with significant expression changes. Decitabine treatment of H1299 cells resulted in reduced methylation levels in gene promoters, elevated transcript levels of CHRNB4 and CHRNA3 and a slight downregulation of TERT demonstrating epigenetic regulation of lung cancer cells. SNPs rs421629 on 5p15.33 and rs1948, rs660652, rs8040868 and rs2036527 on 15q25.1, previously identified as lung cancer risk or nicotine addiction modifiers were associated with tumor DNA methylation levels in the promoters of TERT and CHRNB4 (p<0.001) respectively in two independent sample sets (n=82; n=150). In addition, CHRNB4 knock down in two different cell lines (A549 and H1299) resulted in reduced proliferation (pA549<0.05;pH1299L<0.001) and propensity to form colonies in H1299 cells. These results suggest epigenetic deregulation of nicotinic acetylcholinereceptor subunit (nAChR) genes which in the case of CHRNB4 is strongly associated with genetic lung cancer susceptibility variants and a functional impact on tumorigenic potential. PMID:22945651

  15. Multiple Indices of Diffusion Identifies White Matter Damage in Mild Cognitive Impairment and Alzheimer’s Disease

    PubMed Central

    O'Dwyer, Laurence; Lamberton, Franck; Bokde, Arun L. W.; Ewers, Michael; Faluyi, Yetunde O.; Tanner, Colby; Mazoyer, Bernard; O'Neill, Des; Bartley, Máiréad; Collins, D. Rónán; Coughlan, Tara; Prvulovic, David; Hampel, Harald

    2011-01-01

    The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa. PMID:21738785

  16. Combined single channel and single molecule detection identifies subunit composition of STIM1-activated transient receptor potential canonical (TRPC) channels.

    PubMed

    Asanov, Alexander; Sampieri, Alicia; Moreno, Claudia; Pacheco, Jonathan; Salgado, Alfonso; Sherry, Ryan; Vaca, Luis

    2015-01-01

    Depletion of intracellular calcium ion stores initiates a rapid cascade of events culminating with the activation of the so-called Store-Operated Channels (SOC) at the plasma membrane. Calcium influx via SOC is essential in the initiation of calcium-dependent intracellular signaling and for the refilling of internal calcium stores, ensuring the regeneration of the signaling cascade. In spite of the significance of this evolutionary conserved mechanism, the molecular identity of SOC has been the center of a heated controversy spanning over the last 20 years. Initial studies positioned some members of the transient receptor potential canonical (TRPC) channel superfamily of channels (with the more robust evidence pointing to TRPC1) as a putative SOC. Recent evidence indicates that Stromal Interacting Molecule 1 (STIM1) activates some members from the TRPC family of channels. However, the exact subunit composition of TRPC channels remains undetermined to this date. To identify the subunit composition of STIM1-activated TRPC channels, we developed novel method, which combines single channel electrophysiological measurements based on the patch clamp technique with single molecule fluorescence imaging. We termed this method Single ion Channel Single Molecule Detection technique (SC-SMD). Using SC-SMD method, we have obtained direct evidence of the subunit composition of TRPC channels activated by STIM1. Furthermore, our electrophysiological-imaging SC-SMD method provides evidence at the molecular level of the mechanism by which STIM1 and calmodulin antagonize to modulate TRPC channel activity. PMID:25465892

  17. Multi-Analytical Approach Reveals Potential Microbial Indicators in Soil for Sugarcane Model Systems

    PubMed Central

    Navarrete, Acacio Aparecido; Diniz, Tatiana Rosa; Braga, Lucas Palma Perez; Silva, Genivaldo Gueiros Zacarias; Franchini, Julio Cezar; Rossetto, Raffaella; Edwards, Robert Alan; Tsai, Siu Mui

    2015-01-01

    This study focused on the effects of organic and inorganic amendments and straw retention on the microbial biomass (MB) and taxonomic groups of bacteria in sugarcane-cultivated soils in a greenhouse mesocosm experiment monitored for gas emissions and chemical factors. The experiment consisted of combinations of synthetic nitrogen (N), vinasse (V; a liquid waste from ethanol production), and sugarcane-straw blankets. Increases in CO2-C and N2O-N emissions were identified shortly after the addition of both N and V to the soils, thus increasing MB nitrogen (MB-N) and decreasing MB carbon (MB-C) in the N+V-amended soils and altering soil chemical factors that were correlated with the MB. Across 57 soil metagenomic datasets, Actinobacteria (31.5%), Planctomycetes (12.3%), Deltaproteobacteria (12.3%), Alphaproteobacteria (12.0%) and Betaproteobacteria (11.1%) were the most dominant bacterial groups during the experiment. Differences in relative abundance of metagenomic sequences were mainly revealed for Acidobacteria, Actinobacteria, Gammaproteobacteria and Verrucomicrobia with regard to N+V fertilization and straw retention. Differential abundances in bacterial groups were confirmed using 16S rRNA gene-targeted phylum-specific primers for real-time PCR analysis in all soil samples, whose results were in accordance with sequence data, except for Gammaproteobacteria. Actinobacteria were more responsive to straw retention with Rubrobacterales, Bifidobacteriales and Actinomycetales related to the chemical factors of N+V-amended soils. Acidobacteria subgroup 7 and Opitutae, a verrucomicrobial class, were related to the chemical factors of soils without straw retention as a surface blanket. Taken together, the results showed that MB-C and MB-N responded to changes in soil chemical factors and CO2-C and N2O-N emissions, especially for N+V-amended soils. The results also indicated that several taxonomic groups of bacteria, such as Acidobacteria, Actinobacteria and Verrucomicrobia, and their subgroups acted as early-warning indicators of N+V amendments and straw retention in sugarcane-cultivated soils, which can alter the soil chemical factors. PMID:26057123

  18. Multi-Analytical Approach Reveals Potential Microbial Indicators in Soil for Sugarcane Model Systems.

    PubMed

    Navarrete, Acacio Aparecido; Diniz, Tatiana Rosa; Braga, Lucas Palma Perez; Silva, Genivaldo Gueiros Zacarias; Franchini, Julio Cezar; Rossetto, Raffaella; Edwards, Robert Alan; Tsai, Siu Mui

    2015-01-01

    This study focused on the effects of organic and inorganic amendments and straw retention on the microbial biomass (MB) and taxonomic groups of bacteria in sugarcane-cultivated soils in a greenhouse mesocosm experiment monitored for gas emissions and chemical factors. The experiment consisted of combinations of synthetic nitrogen (N), vinasse (V; a liquid waste from ethanol production), and sugarcane-straw blankets. Increases in CO2-C and N2O-N emissions were identified shortly after the addition of both N and V to the soils, thus increasing MB nitrogen (MB-N) and decreasing MB carbon (MB-C) in the N+V-amended soils and altering soil chemical factors that were correlated with the MB. Across 57 soil metagenomic datasets, Actinobacteria (31.5%), Planctomycetes (12.3%), Deltaproteobacteria (12.3%), Alphaproteobacteria (12.0%) and Betaproteobacteria (11.1%) were the most dominant bacterial groups during the experiment. Differences in relative abundance of metagenomic sequences were mainly revealed for Acidobacteria, Actinobacteria, Gammaproteobacteria and Verrucomicrobia with regard to N+V fertilization and straw retention. Differential abundances in bacterial groups were confirmed using 16S rRNA gene-targeted phylum-specific primers for real-time PCR analysis in all soil samples, whose results were in accordance with sequence data, except for Gammaproteobacteria. Actinobacteria were more responsive to straw retention with Rubrobacterales, Bifidobacteriales and Actinomycetales related to the chemical factors of N+V-amended soils. Acidobacteria subgroup 7 and Opitutae, a verrucomicrobial class, were related to the chemical factors of soils without straw retention as a surface blanket. Taken together, the results showed that MB-C and MB-N responded to changes in soil chemical factors and CO2-C and N2O-N emissions, especially for N+V-amended soils. The results also indicated that several taxonomic groups of bacteria, such as Acidobacteria, Actinobacteria and Verrucomicrobia, and their subgroups acted as early-warning indicators of N+V amendments and straw retention in sugarcane-cultivated soils, which can alter the soil chemical factors. PMID:26057123

  19. Potential risk indicators of retained placenta and other diseases in multiparous cows.

    PubMed

    Qu, Y; Fadden, A N; Traber, M G; Bobe, G

    2014-07-01

    Retained placenta (RP), defined as fetal membranes not being expelled within 24 h after calving, is a costly disease in multiparous dairy cows that has been linked to immune suppression, infections, elevated lipid mobilization, and depleted status of antioxidants including ?-tocopherol, and that increases the risk of other diseases (OD) in early lactation. Early detection of cows at increased risk of developing RP, OD, or both in early lactation could improve treatment success and result in improved milk production and reproductive performance. To identify risk indicators of RP, OD, or both, we used a nested case-control design and compared multiparous dairy cows that developed RP (n=32) with cows that remained healthy (H; n=32) or cows that developed OD (n=32) in early lactation. We compared peripartal body condition score (BCS) as well as serum concentrations of ?-tocopherol, metabolites [?-hydroxybutyrate (BHBA), cholesterol, glucose, nonesterified fatty acids (NEFA), and urea N], haptoglobin, and macrominerals (i.e., calcium, magnesium, and phosphorus) on d -21, -14, -7, -3, -1, 0, 1, 3, 7, 14, 21, 28, 35, 42, and 49 postpartum. In addition, average serum concentrations were calculated for each cow for the last 3 wk prepartum, for 3 and 2 wk prepartum combined, for the last week prepartum, and for the morning after calving and compared between groups. The RP cows had lower BCS than the H or OD cows until 2 wk postpartum. During the prepartal periods, RP and OD cows had lower ?-tocopherol concentrations (corrected or not for cholesterol concentration) and higher NEFA and BHBA concentrations than H cows. Thus, lower prepartal BCS could be an early predictor for RP risk, and lower ?-tocopherol concentrations and higher NEFA and BHBA concentrations could be early predictors for disease. PMID:24792789

  20. Investigating the Potential of Bevacizumab in Other Indications: Metastatic Renal Cell, Non-Small Cell Lung, Pancreatic and Breast Cancer

    Microsoft Academic Search

    2005-01-01

    Bevacizumab (Avastin®) has unprecedented survival benefit in patients with metastatic colorectal cancer. Trials are already in progress to investigate the potential of bevacizumab in indications including metastatic renal cell cancer (RCC), non-small cell lung cancer (NSCLC), pancreatic cancer, breast and ovarian cancer. Bevacizumab offers the potential to increase survival without substantially altering the toxicity profile in these tumor types. Bevacizumab

  1. Evaluation of potential health risk of arsenic-affected groundwater using indicator kriging and dose response model

    Microsoft Academic Search

    Jin-Jing Lee; Cheng-Shin Jang; Sheng-Wei Wang; Chen-Wuing Liu

    2007-01-01

    This study analyzed the potential health risk associated with the ingestion of arsenic-affected groundwater in the arseniasis-endemic Lanyang plain of northeastern Taiwan. Indicator kriging was used to estimate arsenic concentrations in groundwater. Target cancer risk (TR) and dose response functions were adopted to evaluate the potential health risk based on the estimated arsenic concentration distributions. The estimated arsenic concentrations in

  2. Cortical EEG oscillations and network connectivity as efficacy indices for assessing drugs with cognition enhancing potential.

    PubMed

    Ahnaou, A; Huysmans, H; Jacobs, T; Drinkenburg, W H I M

    2014-11-01

    Synchronization of electroencephalographic (EEG) oscillations represents a core mechanism for cortical and subcortical networks, and disturbance in neural synchrony underlies cognitive processing deficits in neurological and neuropsychiatric disorders. Here, we investigated the effects of cognition enhancers (donepezil, rivastigmine, tacrine, galantamine and memantine), which are approved for symptomatic treatment of dementia, on EEG oscillations and network connectivity in conscious rats chronically instrumented with epidural electrodes in different cortical areas. Next, EEG network indices of cognitive impairments with the muscarinic receptor antagonist scopolamine were modeled. Lastly, we examined the efficacy of cognition enhancers to normalize those aberrant oscillations. Cognition enhancers elicited systematic ("fingerprint") enhancement of cortical slow theta (4.5-6 Hz) and gamma (30.5-50 Hz) oscillations correlated with lower activity levels. Principal component analysis (PCA) revealed a compact cluster that corresponds to shared underlying mechanisms as compared to different drug classes. Functional network connectivity revealed consistent elevated coherent slow theta activity in parieto-occipital and between interhemispheric cortical areas. In rats instrumented with depth hippocampal CA1-CA3 electrodes, donepezil elicited similar oscillatory and coherent activities in cortico-hippocampal networks. When combined with scopolamine, the cognition enhancers attenuated the leftward shift in coherent slow delta activity. Such a consistent shift in EEG coherence into slow oscillations associated with altered slow theta and gamma oscillations may underlie cognitive deficits in scopolamine-treated animals, whereas enhanced coherent slow theta and gamma activity may be a relevant mechanism by which cognition enhancers exert their beneficial effect on plasticity and cognitive processes. The findings underscore that PCA and network connectivity are valuable tools to assess efficacy of novel therapeutic drugs with cognition enhancing potential. PMID:25181033

  3. Trehalose as an indicator of desiccation stress in Drosophila melanogaster larvae: A potential marker of anhydrobiosis

    SciTech Connect

    Thorat, Leena J. [Centre for Advanced Studies, Department of Zoology, University of Pune, Pune 411007 (India)] [Centre for Advanced Studies, Department of Zoology, University of Pune, Pune 411007 (India); Gaikwad, Sushama M. [Division of Biochemical Sciences, National Chemical Laboratory, Pune 411008 (India)] [Division of Biochemical Sciences, National Chemical Laboratory, Pune 411008 (India); Nath, Bimalendu B., E-mail: bbnath@unipune.ac.in [Centre for Advanced Studies, Department of Zoology, University of Pune, Pune 411007 (India)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer First report confirming anhydrobiosis in Drosophila melanogaster larvae. Black-Right-Pointing-Pointer Trehalose synthesis and accumulation in larvae that hydrolyzed on rehydration. Black-Right-Pointing-Pointer Trehalose synthesis in concert with the enzymes involved in trehalose metabolism. Black-Right-Pointing-Pointer Inhibition of trehalose hydrolysis in presence of a specific trehalase inhibitor. Black-Right-Pointing-Pointer Trehalose proposed as a reliable marker for biomonitoring of climate change studies. -- Abstract: In the current scenario of global climate change, desiccation is considered as one of the major environmental stressors for the biota exposed to altered levels of ambient temperature and humidity. Drosophila melanogaster, a cosmopolitan terrestrial insect has been chosen as a humidity-sensitive bioindicator model for the present study since its habitat undergoes frequent stochastic and/or seasonally aggravated dehydration regimes. We report here for the first time the occurrence of anhydrobiosis in D. melanogaster larvae by subjecting them to desiccation stress under laboratory conditions. Larvae desiccated for ten hours at <5% relative humidity could enter anhydrobiosis and could revive upon rehydration followed by resumption of active metabolism. As revealed by FTIR and HPLC analyzes, our findings strongly indicated the synthesis and accumulation of trehalose in the desiccating larvae. Biochemical measurements pointed out the desiccation-responsive trehalose metabolic pathway that was found to be coordinated in concert with the enzymes trehalose 6-phosphate synthase and trehalase. Further, an inhibitor-based experimental approach using deoxynojirimycin, a specific trehalase inhibitor, demonstrated the pivotal role of trehalose in larval anhydrobiosis of D. melanogaster. We therefore propose trehalose as a potential marker for the assessment of anhydrobiosis in Drosophila. The present findings thus add to the growing list of novel biochemical markers in specific bioindicator organisms for fulfilling the urgent need of environmental biomonitoring of climate change.

  4. Version soumise Agricultural System le 8/09/08 Identifying indicators of the spatial variation of agricultural practices by a tree

    E-print Network

    Paris-Sud XI, Université de

    requirements for sustainable development, such as preservation of water resources, soil conservation, and geneVersion soumise à Agricultural System le 8/09/08 Identifying indicators of the spatial variation of agricultural practices by a tree partitioning method: the case of weed control practices in a vine growing

  5. Relevant magnetic and soil parameters as potential indicators of soil conservation status of Mediterranean agroecosystems

    NASA Astrophysics Data System (ADS)

    Quijano, Laura; Chaparro, Marcos A. E.; Marié, Débora C.; Gaspar, Leticia; Navas, Ana

    2014-09-01

    The main sources of magnetic minerals in soils unaffected by anthropogenic pollution are iron oxides and hydroxides derived from parent materials through soil formation processes. Soil magnetic minerals can be used as indicators of environmental factors including soil forming processes, degree of pedogenesis, weathering processes and biological activities. In this study measurements of magnetic susceptibility are used to detect the presence and the concentration of soil magnetic minerals in topsoil and bulk samples in a small cultivated field, which forms a hydrological unit that can be considered to be representative of the rainfed agroecosystems of Mediterranean mountain environments. Additional magnetic studies such as isothermal remanent magnetization (IRM), anhysteretic remanent magnetization (ARM) and thermomagnetic measurements are used to identify and characterize the magnetic mineralogy of soil minerals. The objectives were to analyse the spatial variability of the magnetic parameters to assess whether topographic factors, soil redistribution processes, and soil properties such as soil texture, organic matter and carbonate contents analysed in this study, are related to the spatial distribution pattern of magnetic properties. The medians of mass specific magnetic susceptibility at low frequency (?lf) were 36.0 and 31.1 × 10-8 m3 kg-1 in bulk and topsoil samples respectively. High correlation coefficients were found between the ?lf in topsoil and bulk core samples (r = 0.951, p < 0.01). In addition, volumetric magnetic susceptibility was measured in situ in the field (?is) and values varied from 13.3 to 64.0 × 10-5 SI. High correlation coefficients were found between ?lf in topsoil measured in the laboratory and volumetric magnetic susceptibility field measurements (r = 0.894, p < 0.01). The results obtained from magnetic studies such as IRM, ARM and thermomagnetic measurements show the presence of magnetite, which is the predominant magnetic carrier, and hematite. The predominance of superparamagnetic minerals in upper soil layers suggests enrichment in pedogenic minerals. The finer soil particles, the organic matter content and the magnetic susceptibility values are statistically correlated and their spatial variability is related to similar physical processes. Runoff redistributes soil components including magnetic minerals and exports fine particles out the field. This research contributed to further knowledge on the application of soil magnetic properties to derive useful information on soil processes in Mediterranean cultivated soils.

  6. Identifying putative drug targets and potential drug leads: starting points for virtual screening and docking.

    PubMed

    Wishart, David S

    2015-01-01

    The availability of 3D models of both drug leads (small molecule ligands) and drug targets (proteins) is essential to molecular docking and computational drug discovery. This chapter describes a simple approach that can be used to identify both drug leads and drug targets using two popular Web-accessible databases: (1) DrugBank and (2) The Human Metabolome Database. First, it is illustrated how putative drug targets and drug leads for exogenous diseases (i.e., infectious diseases) can be readily identified and their 3D structures selected using only the genomic sequences from pathogenic bacteria or viruses as input. The second part illustrates how putative drug targets and drug leads for endogenous diseases (i.e., noninfectious diseases or chronic conditions) can be identified using similar databases and similar sequence input. This chapter is intended to illustrate how bioinformatics and cheminformatics can work synergistically to help provide the necessary inputs for computer-aided drug design. PMID:25330974

  7. Identifying Carcinogenic Potentials of Drinking Water Disinfection Byproducts using Normal Human Colonocyte Cultures

    EPA Science Inventory

    Epidemiological studies have linked the consumption of disinfected surface waters to an increased risk of colorectal cancer. Approximately 600 byproducts (DBPs) have been identified for the major disinfectants currently in use and represent less than half of the total organic car...

  8. Development of Normal Human Colonocyte Cultures to Identify a Carcinogenic Potential for Priority Disinfection Byproducts

    EPA Science Inventory

    Epidemiological studies have linked the consumption of disinfected surface waters to an increased risk of colorectal cancer. Of the approximately >600 disinfection byproducts (DBPs) identified, the US EPA regulates 11 DBPS for an increased risk of cancer. An in-depth mechanism-ba...

  9. Identifying chemical carcinogens and assessing potential risk in short-term bioassays using transgenic mouse models.

    PubMed Central

    Tennant, R W; French, J E; Spalding, J W

    1995-01-01

    Cancer is a worldwide public health concern. Identifying carcinogens and limiting their exposure is one approach to the problem of reducing risk. Currently, epidemiology and rodent bioassays are the means by which putative human carcinogens are identified. Both methods have intrinsic limitations: they are slow and expensive processes with many uncertainties. The development of methods to modify specific genes in the mammalian genome has provided promising new tools for identifying carcinogens and characterizing risk. Transgenic mice may provide advantages in shortening the time required for bioassays and improving the accuracy of carcinogen identification; transgenic mice might now be included in the testing armamentarium without abandoning the two-year bioassay, the current standard. We show that mutagenic carcinogens can be identified with increased sensitivity and specificity using hemizygous p53 mice in which one allele of the p53 gene has been inactivated. Furthermore, the TG.AC transgenic model, carrying a v-Ha-ras construct, has developed papillomas and malignant tumors in response to a number of mutagenic and nonmutagenic carcinogens and tumor promoters, but not to noncarcinogens. We present a decision-tree approach that permits, at modest extra cost, the testing of more chemicals with improved ability to extrapolate from rodents to humans. Images Figure 1. Figure 2. Figure 3. PMID:8529591

  10. Six-Item Screener to Identify Cognitive Impairment Among Potential Subjects for Clinical Research

    Microsoft Academic Search

    CHRISTOPHER M. CALLAHAN; FREDERICK W. UNVERZAGT; SIU L. HUI; ANTHONY J. PERKINS; HUGH C. HENDRIE

    OBJECTIVE. To design a brief cognitive screener with acceptable sensitivity and speci- ficity for identifying subjects with cognitive impairment DESIGN. Cohort one is assembled from a community-based survey coupled with a second-stage diagnostic evaluation using for- mal diagnostic criteria for dementia. Cohort two is assembled from referrals to a specialty clinic for dementing disorders that completed the same diagnostic evaluation.

  11. DRAFT MANUSCRIPT IN REVIEW DO NOT CITE Coastal Flooding and Environmental Justice: Identifying Potential Strategies for

    E-print Network

    Douglas, Ellen M.

    to be exposed to increasing risks, including coastal erosion, due to climate change and sea-level riseDRAFT MANUSCRIPT IN REVIEW DO NOT CITE 1 Coastal Flooding and Environmental Justice: Identifying MANUSCRIPT IN REVIEW DO NOT CITE 2 Abstract We explored the possible future impacts of increased coastal

  12. Exploiting Literature-derived Knowledge and Semantics to Identify Potential Prostate Cancer Drugs

    PubMed Central

    Zhang, Rui; Cairelli, Michael J; Fiszman, Marcelo; Kilicoglu, Halil; Rindflesch, Thomas C; Pakhomov, Serguei V; Melton, Genevieve B

    2014-01-01

    In this study, we report on the performance of an automated approach to discovery of potential prostate cancer drugs from the biomedical literature. We used the semantic relationships in SemMedDB, a database of structured knowledge extracted from all MEDLINE citations using SemRep, to extract potential relationships using knowledge of cancer drugs pathways. Two cancer drugs pathway schemas were constructed using these relationships extracted from SemMedDB. Through both pathway schemas, we found drugs already used for prostate cancer therapy and drugs not currently listed as the prostate cancer medications. Our study demonstrates that the appropriate linking of relevant structured semantic relationships stored in SemMedDB can support the discovery of potential prostate cancer drugs. PMID:25392688

  13. 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...

  14. Gene expression profiling and real-time PCR analyses identify novel potential cancer-testis antigens in multiple myeloma1

    E-print Network

    Paris-Sud XI, Université de

    1 Gene expression profiling and real-time PCR analyses identify novel potential cancer-testis Tumorerkrankungen, INF350, D-69115 Heidelberg, Germany; Running title: Novel cancer-testis genes in multiple myeloma manuscript, published in "J Immunol 2009;183(2):832-40" DOI : 10.4049/jimmunol.0803298 #12;2 Abstract Cancer-testis

  15. Genetic Analysis of White-tailed Deer Population Structure in Iowa: Identifying Potential Patterns and Rates of Disease Spread

    E-print Network

    Koford, Rolf R.

    Genetic Analysis of White-tailed Deer Population Structure in Iowa: Identifying Potential Patterns and Objectives: o Conduct a statewide assessment of deer population genetic structure in Iowa to determine the degree of genetic connectivity between free-ranging deer populations in Iowa and free-ranging deer

  16. Video Games and Mathematics Education: Studying Commercial Sports Video Games to Identify the Potential for Learning and Thinking About

    E-print Network

    Spagnolo, Filippo

    Video Games and Mathematics Education: Studying Commercial Sports Video Games to Identify What happens when commercial sports video games, designed for entertainment, are used in an effort is an attempt to examine the potential for connecting digital media (sports video games) to learning various

  17. Computer simulations indicate that electrical field effects contribute to the shape of the epileptiform field potential.

    PubMed

    Traub, R D; Dudek, F E; Snow, R W; Knowles, W D

    1985-08-01

    In the presence of convulsant drugs such as picrotoxin, neurons in the hippocampal-slice preparation generate synchronized depolarizing bursts. This synchrony occurs on a time scale of tens of milliseconds and is produced by excitatory synaptic interactions between neurons. The synaptic interactions themselves occur on a time scale of tens of milliseconds. The "epileptiform" local-field potential during such synchronized bursts is comb-shaped ("ringing"), whereas the field potential expected if action potentials in neighboring neurons were uncorrelated is noisy and not comb-shaped. This suggests that individual action potentials are locally synchronized on a time scale of 1 ms. We have previously shown, using computer simulations, that electrical interactions--mediated by currents flowing in the extracellular medium--can plausibly explain action-potential synchronization in experiments where chemical synapses are blocked. The present simulations demonstrate that electrical interactions can also account for action-potential synchronization--and thus the "ringing" shape of the field potential--during epileptiform bursts, where excitatory synapses are functional. The field potential is thus a modulating influence on, as well as a reflection of, underlying neuronal transmembrane events. PMID:4047402

  18. IDENTIFYING POTENTIAL ENVIRONMENTAL AND BEHAVIORAL STRESSORS THROUGH BLOOD CORTISOL IN THE BLACK RHINOCEROS (DICER OS BICOILVIS)

    Microsoft Academic Search

    Christine M. Bobko; Rhino Keeper

    Environmental and behavioral stressors have potentially negative effects on the captive management of the black rhinoceros. Overcrowding, pair incompatibility, and poor nutrition are just a few of the factors facing this species in a zoological setting. The black rhino is considered to be the most nervous and stress-susceptible of the 5 rhino species (Carlstead, 1999). There are several disease syndromes

  19. A Comparison between Survey and Verbal Choice Methods of Identifying Potential Reinforcers among Employees

    ERIC Educational Resources Information Center

    Wilder, David A; Therrien, Kelly; Wine, Byron

    2006-01-01

    Two methods of assessing preference for stimuli (i.e., potential reinforcers) were compared for adult administrative assistant employees. During Phase 1, a survey method and a verbal choice method of assessing preference for 6 stimuli were administered. During Phase 2, a coupon system was used to determine which categories of stimuli actually…

  20. Identifying potential environmental impacts of large-scale deployment of dedicated bioenergy crops in the UK

    Microsoft Academic Search

    Rebecca L. Rowe; Gail Taylor

    2009-01-01

    There is momentum, globally, to increase the use of plant biomass for the production of heat, power and liquid transport fuels. This review assesses the evidence base for potential impacts of large-scale bioenergy crop deployment principally within the UK context, but with wider implications for Europe, the USA and elsewhere. We focus on second generation, dedicated lignocellulosic crops, but where

  1. Diversity and Biocatalytic Potential of Epoxide Hydrolases Identified by Genome Analysis

    Microsoft Academic Search

    Dick B. Janssen; Marcel G. Wubbolts; Michael Arand; Jaap Kingma; Bert van Loo

    2006-01-01

    Epoxide hydrolases play an important role in the biodegradation of organic compounds and are potentially useful in enantioselective biocatalysis. An analysis of various genomic databases revealed that about 20% of sequenced organisms contain one or more putative epoxide hydrolase genes. They were found in all domains of life, and many fungi and actinobacteria contain several putative epoxide hydrolase-encoding genes. Multiple

  2. UNAIDS 'multiple sexual partners' core indicator: promoting sexual networks to reduce potential biases.

    PubMed

    Dimbuene, Zacharie Tsala; Emina, Jacques B O; Sankoh, Osman

    2014-01-01

    UNAIDS proposed a set of core indicators for monitoring changes in the worldwide AIDS epidemic. This paper explores the validity and effectiveness of the 'multiple sexual partners' core indicator, which is only partially captured with current available data. The paper also suggests an innovative approach for collecting more informative data that can be used to provide an accurate measure of the UNAIDS's 'multiple sexual partners' core indicator. Specifically, the paper addresses three major limitations associated with the indicator when it is measured with respondents' sexual behaviors. First, the indicator assumes that a person's risk of contracting HIV/AIDS/STIs is merely a function of his/her own sexual behavior. Second, the indicator does not account for a partner's sexual history, which is very important in assessing an individual's risk level. Finally, the 12-month period used to define a person's risks can be misleading, especially because HIV/AIDS theoretically has a period of latency longer than a year. The paper concludes that, programmatically, improvements in data collection are a top priority for reducing the observed bias in the 'multiple sexual partners' core indicator. PMID:24647127

  3. UNAIDS ‘multiple sexual partners’ core indicator: promoting sexual networks to reduce potential biases

    PubMed Central

    Dimbuene, Zacharie Tsala; Emina, Jacques B.O.; Sankoh, Osman

    2014-01-01

    UNAIDS proposed a set of core indicators for monitoring changes in the worldwide AIDS epidemic. This paper explores the validity and effectiveness of the ‘multiple sexual partners’ core indicator, which is only partially captured with current available data. The paper also suggests an innovative approach for collecting more informative data that can be used to provide an accurate measure of the UNAIDS’s ‘multiple sexual partners’ core indicator. Specifically, the paper addresses three major limitations associated with the indicator when it is measured with respondents’ sexual behaviors. First, the indicator assumes that a person’s risk of contracting HIV/AIDS/STIs is merely a function of his/her own sexual behavior. Second, the indicator does not account for a partner’s sexual history, which is very important in assessing an individual’s risk level. Finally, the 12-month period used to define a person’s risks can be misleading, especially because HIV/AIDS theoretically has a period of latency longer than a year. The paper concludes that, programmatically, improvements in data collection are a top priority for reducing the observed bias in the ‘multiple sexual partners’ core indicator. PMID:24647127

  4. A quantitative high-throughput screen identifies potential epigenetic modulators of gene expression

    Microsoft Academic Search

    Ronald L. Johnson; Wenwei Huang; Ajit Jadhav; Christopher P. Austin; James Inglese; Elisabeth D. Martinez

    2008-01-01

    Epigenetic regulation of gene expression is essential in embryonic development and contributes to cancer pathology. We used a cell-based imaging assay that measures derepression of a silenced green fluorescent protein (GFP) reporter to identify novel classes of compounds involved in epigenetic regulation. This locus derepression (LDR) assay was screened against a 69,137-member chemical library using quantitative high-throughput screening (qHTS), a

  5. Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet Syndrome treatment

    PubMed Central

    Baraban, Scott C.; Dinday, Matthew T.; Hortopan, Gabriela A.

    2013-01-01

    Dravet syndrome (DS) is a catastrophic pediatric epilepsy with severe intellectual disability, impaired social development and persistent drug-resistant seizures. One of its primary monogenic causes are mutations in Nav1.1 (SCN1A), a voltage-gated sodium channel. Here we characterise zebrafish Nav1.1 (scn1Lab) mutants originally identified in a chemical mutagenesis screen. Mutants exhibit spontaneous abnormal electrographic activity, hyperactivity and convulsive behaviors. Although scn1Lab expression is reduced, microarray analysis is remarkable for the small fraction of differentially expressed genes (~3%) and lack of compensatory expression changes in other scn subunits. Ketogenic diet, diazepam, valproate, potassium bromide and stiripentol attenuate mutant seizure activity; seven other antiepileptic drugs have no effect. A phenotype-based screen of 320 compounds identifies a US Food and Drug Administration-approved compound (clemizole) that inhibits convulsive behaviors and electrographic seizures. This approach represents a new direction in modeling pediatric epilepsy and could be used to identify novel therapeutics for any monogenic epilepsy disorder. PMID:24002024

  6. Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment.

    PubMed

    Baraban, Scott C; Dinday, Matthew T; Hortopan, Gabriela A

    2013-01-01

    Dravet syndrome is a catastrophic pediatric epilepsy with severe intellectual disability, impaired social development and persistent drug-resistant seizures. One of its primary monogenic causes are mutations in Nav1.1 (SCN1A), a voltage-gated sodium channel. Here we characterize zebrafish Nav1.1 (scn1Lab) mutants originally identified in a chemical mutagenesis screen. Mutants exhibit spontaneous abnormal electrographic activity, hyperactivity and convulsive behaviours. Although scn1Lab expression is reduced, microarray analysis is remarkable for the small fraction of differentially expressed genes (~3%) and lack of compensatory expression changes in other scn subunits. Ketogenic diet, diazepam, valproate, potassium bromide and stiripentol attenuate mutant seizure activity; seven other antiepileptic drugs have no effect. A phenotype-based screen of 320 compounds identifies a US Food and Drug Administration-approved compound (clemizole) that inhibits convulsive behaviours and electrographic seizures. This approach represents a new direction in modelling pediatric epilepsy and could be used to identify novel therapeutics for any monogenic epilepsy disorder. PMID:24002024

  7. Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma

    PubMed Central

    McKay, Siobhan C; Unger, Kristian; Pericleous, Stephanos; Stamp, Gordon; Thomas, Gerry; Hutchins, Robert R; Spalding, Duncan R C

    2011-01-01

    Background Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets. Methods DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment. Results DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained. Conclusions We identified CN gains in the region of 11 useful molecular targets. Findings of variable gains in some regions in this and other studies support the argument for molecular stratification before treatment for CC so that treatment can be tailored to the individual patient. PMID:21492330

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

    PubMed

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

    2014-08-26

    Abstract Background: Previous research has paid little to no attention towards exploring methods of identifying existing medical student leaders. Aim: Focusing on the role of influence and employing the tenets of the engaging leadership model, this study examines demographic and academic performance-related differences of positive influencers and if students who have been peer-identified as positive influencers also demonstrate high levels of genuine concern for others. Methods: Three separate fourth-year classes were asked to designate classmates that had significant positive influences on their professional and personal development. The top 10% of those students receiving positive influence nominations were compared with the other students on demographics, academic performance, and genuine concern for others. Results: Besides age, no demographic differences were found between positive influencers and other students. High positive influencers were not found to have higher standardized exam scores but did receive significantly higher clinical clerkship ratings. High positive influencers were found to possess a higher degree of genuine concern for others. Conclusion: The findings lend support to (a) utilizing the engaging model to explore leaders and leadership within medical education, (b) this particular method of identifying existing medical student leaders, and (c) return the focus of leadership research to the power of influence. PMID:25155553

  9. Antibody microarray profiling of osteosarcoma cell serum for identifying potential biomarkers.

    PubMed

    Zhu, Zi-Qiang; Tang, Jin-Shan; Gang, Duan; Wang, Ming-Xing; Wang, Jian-Qiang; Lei, Zhou; Feng, Zhou; Fang, Ming-Liang; Yan, Lin

    2015-07-01

    The aim of the present study was to identify biomarkers in osteosarcoma (OS) cell serum by antibody microarray profiling, which may be used for OS diagnosis and therapy. An antibody microarray was used to detect the expression levels of cytokines in serum samples from 20 patients with OS and 20 healthy individuals. Significantly expressed cytokines in OS serum were selected when P<0.05 and fold change >2. An enzyme-linked immunosorbent assay (ELISA) was used to validate the antibody microarray results. Finally, classification accuracy was calculated by cluster analysis. Twenty one cytokines were significantly upregulated in OS cell serum samples compared with control samples. Expression of interleukin-6, monocyte chemoattractant protein-1, tumor growth factor-?, growth-related oncogene, hepatocyte growth factor, chemokine ligand 16, Endoglin, matrix metalloproteinase-9 and platelet-derived growth factor-AA was validated by ELISAs. OS serum samples and control samples were distinguished by significantly expressed cytokines with an accuracy of 95%. The results demonstrated that expressed cytokines identified by antibody microarray may be used as biomarkers for OS diagnosis and therapy. PMID:25815525

  10. Development of recovery indicators to be used during product design process: method, potentialities and limits

    Microsoft Academic Search

    Fabrice Mathieux; Daniel Froelich; Pierre Moszkowicz

    2001-01-01

    The paper presents a recently developed comprehensive design for recycling methodology. The goal of this method is to assess product design alternatives regarding their suitability for trecovery system performance. The ability of a product to be recovered is evaluated through three types of indicators according to the following criteria: technical, economical and environmental. The method to model a product, the

  11. Assessing indices for predicting potential N mineralization in pedogenically distinct soils under different tillage management systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A reliable laboratory index of nitrogen availability would be useful for making N recommendations but no single approach has received broad acceptance across a wide range of soils. We compared several indices over a range of soil conditions to test the possibility of determining the best combination...

  12. The potential of soil protein-based methods to indicate metal contamination

    Microsoft Academic Search

    I. Singleton; G. Merrington; S. Colvan; J. S. Delahunty

    2003-01-01

    Soil metal contamination is an international problem and there is a recognised need for methods to detect the effects of such pollution. To this end, we investigated the use of soil protein extraction, quantification and expression as indicators of cadmium contamination of soil. A variety of methods to extract total soil protein were examined and the effects of cadmium and

  13. Indication of the Side of Delayed Endolymphatic Hydrops by Vestibular Evoked Myogenic Potential and Caloric Test

    Microsoft Academic Search

    Naoya Egami; Munetaka Ushio; Tatsuya Yamasoba; Toshihisa Murofushi; Shinichi Iwasaki

    2010-01-01

    Objective: Delayed endolymphatic hydrops (DEH) can be clinically classified into ipsi- and contralateral types. This study aims to investigate the relationship between the results of vestibular evoked myogenic potential (VEMP) and caloric testing and the clinical type of DEH. Methods: The data of 33 patients with DEH who underwent both VEMPs and caloric testing were retrospectively examined. The type of

  14. Electrophysiological (Event-Related Potentials) Indices of Cognitive Processing in Autistic Learners.

    ERIC Educational Resources Information Center

    Shibley, Ralph, Jr.; And Others

    Event-related Potentials (ERPs) were recorded to both auditory and visual stimuli from the scalps of nine autistic males and nine normal controls (all Ss between 12 and 22 years of age) to examine the differences in information processing strategies. Ss were tested on three different tasks: an auditory missing stimulus paradigm, a visual color…

  15. Transcranial electrical motor evoked potentials as a prognostic indicator for motor recovery in stroke patients

    Microsoft Academic Search

    M Dominkus; W Grisold; V Jelinek

    1990-01-01

    Transcranial electrical motor evoked potentials (MEP) were examined in 33 patients within three days after stroke. Normal values for MEP and motor central conduction time (CCT) were obtained in 46 healthy controls whose MEPs were evaluated during slight voluntary muscle contraction and at rest. Two months later 23 patients were re-examined clinically and electrophysiologically. Motor function change was correlated with

  16. MACROCLIMATIC INDICES TO DEFINE POTENTIAL SOIL ORGANIC CARBON STORAGE WITH NO TILLAGE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    No tillage has become an accepted cropping practice throughout the USA. Potential climate change has prompted great interest in conservation tillage as a practice to help sequester CO2 from the atmosphere into the soil. Numerous reports published in recent years about the effect of no tillage compar...

  17. Gene Expression-Based Chemical Genomics Identifies Potential Therapeutic Drugs in Hepatocellular Carcinoma

    PubMed Central

    Chang, Peter Mu-Hsin; Lai, Jin-Mei; Hsu, Chun-Nan; Chao, Kun-Mao; Kao, Cheng-Yan; Huang, Chi-Ying F.

    2011-01-01

    Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the “Encyclopedia of Hepatocellular Carcinoma genes Online 2”, dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap), which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment. PMID:22087264

  18. On the Potential of Surfers to Monitor Environmental Indicators in the Coastal Zone

    PubMed Central

    Brewin, Robert J. W.; de Mora, Lee; Jackson, Thomas; Brewin, Thomas G.; Shutler, Jamie

    2015-01-01

    The social and economic benefits of the coastal zone make it one of the most treasured environments on our planet. Yet it is vulnerable to increasing anthropogenic pressure and climate change. Coastal management aims to mitigate these pressures while augmenting the socio-economic benefits the coastal region has to offer. However, coastal management is challenged by inadequate sampling of key environmental indicators, partly due to issues relating to cost of data collection. Here, we investigate the use of recreational surfers as platforms to improve sampling coverage of environmental indicators in the coastal zone. We equipped a recreational surfer, based in the south west United Kingdom (UK), with a temperature sensor and Global Positioning System (GPS) device that they used when surfing for a period of one year (85 surfing sessions). The temperature sensor was used to derive estimates of sea-surface temperature (SST), an important environmental indicator, and the GPS device used to provide sample location and to extract information on surfer performance. SST data acquired by the surfer were compared with data from an oceanographic station in the south west UK and with satellite observations. Our results demonstrate: (i) high-quality SST data can be acquired by surfers using low cost sensors; and (ii) GPS data can provide information on surfing performance that may help motivate data collection by surfers. Using recent estimates of the UK surfing population, and frequency of surfer participation, we speculate around 40 million measurements on environmental indicators per year could be acquired at the UK coastline by surfers. This quantity of data is likely to enhance coastal monitoring and aid UK coastal management. Considering surfing is a world-wide sport, our results have global implications and the approach could be expanded to other popular marine recreational activities for coastal monitoring of environmental indicators. PMID:26154173

  19. On the Potential of Surfers to Monitor Environmental Indicators in the Coastal Zone.

    PubMed

    Brewin, Robert J W; de Mora, Lee; Jackson, Thomas; Brewin, Thomas G; Shutler, Jamie

    2015-01-01

    The social and economic benefits of the coastal zone make it one of the most treasured environments on our planet. Yet it is vulnerable to increasing anthropogenic pressure and climate change. Coastal management aims to mitigate these pressures while augmenting the socio-economic benefits the coastal region has to offer. However, coastal management is challenged by inadequate sampling of key environmental indicators, partly due to issues relating to cost of data collection. Here, we investigate the use of recreational surfers as platforms to improve sampling coverage of environmental indicators in the coastal zone. We equipped a recreational surfer, based in the south west United Kingdom (UK), with a temperature sensor and Global Positioning System (GPS) device that they used when surfing for a period of one year (85 surfing sessions). The temperature sensor was used to derive estimates of sea-surface temperature (SST), an important environmental indicator, and the GPS device used to provide sample location and to extract information on surfer performance. SST data acquired by the surfer were compared with data from an oceanographic station in the south west UK and with satellite observations. Our results demonstrate: (i) high-quality SST data can be acquired by surfers using low cost sensors; and (ii) GPS data can provide information on surfing performance that may help motivate data collection by surfers. Using recent estimates of the UK surfing population, and frequency of surfer participation, we speculate around 40 million measurements on environmental indicators per year could be acquired at the UK coastline by surfers. This quantity of data is likely to enhance coastal monitoring and aid UK coastal management. Considering surfing is a world-wide sport, our results have global implications and the approach could be expanded to other popular marine recreational activities for coastal monitoring of environmental indicators. PMID:26154173

  20. Urban liveability: emerging lessons from Australia for exploring the potential for indicators to measure the social determinants of health.

    PubMed

    Badland, Hannah; Whitzman, Carolyn; Lowe, Melanie; Davern, Melanie; Aye, Lu; Butterworth, Iain; Hes, Dominique; Giles-Corti, Billie

    2014-06-01

    It has long been recognised that urban form impacts on health outcomes and their determinants. There is growing interest in creating indicators of liveability to measure progress towards achieving a wide range of policy outcomes, including enhanced health and wellbeing, and reduced inequalities. This review aimed to: 1) bring together the concepts of urban 'liveability' and social determinants of health; 2) synthesise the various liveability indicators developed to date; and 3) assess their quality using a health and wellbeing lens. Between 2011 and 2013, the research team reviewed 114 international academic and policy documents, as well as reports related to urban liveability. Overall, 233 indicators were found. Of these, 61 indicators were regarded as promising, 57 indicators needed further development, and 115 indicators were not useful for our purposes. Eleven domains of liveability were identified that likely contribute to health and wellbeing through the social determinants of health. These were: crime and safety; education; employment and income; health and social services; housing; leisure and culture; local food and other goods; natural environment; public open space; transport; and social cohesion and local democracy. Many of the indicators came from Australian sources; however most remain relevant from a 'global north' perspective. Although many indicators were identified, there was inconsistency in how these domains were measured. Few have been validated to assess their association with health and wellbeing outcomes, and little information was provided for how they should be applied to guide urban policy and practice. There is a substantial opportunity to further develop these measures to create a series of robust and evidence-based liveability indices, which could be linked with existing health and wellbeing data to better inform urban planning policies within Australia and beyond. PMID:24762261

  1. Using self-organizing maps to identify potential halo white dwarfs.

    PubMed

    García-Berro, Enrique; Torres, Santiago; Isern, Jordi

    2003-01-01

    We present the results of an unsupervised classification of the disk and halo white dwarf populations in the solar neighborhood. The classification is done by merging the results of detailed Monte Carlo (MC) simulations, which reproduce very well the characteristics of the white dwarf populations in the solar neighborhood, with a catalogue of real stars. The resulting composite catalogue is analyzed using a competitive learning algorithm. In particular we have used the so-called self-organized map. The MC simulated stars are used as tracers and help in identifying the resulting clusters. The results of such an strategy turn out to be quite satisfactory, suggesting that this approach can provide an useful framework for analyzing large databases of white dwarfs with well determined kinematical, spatial and photometric properties once they become available in the next decade. Moreover, the results are of astrophysical interest as well, since a straightforward interpretation of several recent astronomical observations, like the detected microlensing events in the direction of the Magellanic Clouds, the possible detection of high proper motion white dwarfs in the Hubble Deep Field and the discovery of high velocity white dwarfs in the solar neighborhood, suggests that a fraction of the baryonic dark matter component of our galaxy could be in the form of old and dim halo white dwarfs. PMID:12672435

  2. Yeast model identifies ENTPD6 as a potential non-obstructive azoospermia pathogenic gene

    PubMed Central

    Wang, Qian; Liu, Chao; Tang, Chaoming; Guo, Huiping; Liu, Yujiao; Wang, Lina; Zhao, Haichao; Shang, Yongliang; Wen, Yang; Lin, Yuan; Zhou, Tao; Zhou, Zuomin; Dong, Wen; Hu, Zhibin; Guo, Xuejiang; Sha, Jiahao; Li, Wei

    2015-01-01

    Approximately ten percent of male infertility is caused by non-obstructive azoospermia (NOA), but the etiologies of many NOA remain elusive. Recently, a genome-wide association study (GWAS) of NOA in Han Chinese men was conducted, and only a few genetic variants associated with NOA were found, which might have resulted from genetic heterogeneity. However, those variants that lack genome-wide significance might still be essential for fertility. Functional analysis of genes surrounding these variants in Drosophila identified some spermatogenesis-essential genes. As a complementary method of Drosophila screening, SK1 background Saccharomvces cerevisiae was used as a model to screen meiosis-related genes from the NOA GWAS data in this study. After functional screening, GDA1 (orthologous to humanENTPD6) was found to be a novel meiosis-related gene. The deletion of GDA1 resulted in the failure of yeast sporulation. Further investigations showed that Gda1p was important for pre-meiotic S phase entry. Interestingly, the meiotic role of Gda1p was dependent on its guanosine diphosphatase activity, but not it’s cytoplasmic, transmembrane or stem domains. These yeast data suggest that ENTPD6 may be a novel meiosis-associated NOA-related gene, and the yeast model provides a good approach to analyze GWAS results of NOA. PMID:26152596

  3. Gene Expression Profiling in a Mouse Model Identifies Fetal Liver and Placenta-Derived Potential Biomarkers for Down Syndrome Screening

    Microsoft Academic Search

    Jeroen L. A. Pennings; Wendy Rodenburg; Sandra Imholz; Maria P. H. Koster; Conny T. M. van Oostrom; Timo M. Breit; Peter C. J. I. Schielen; Annemieke de Vries; Gisela Nogales-Gadea

    2011-01-01

    BackgroundAs a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues were chosen as target.Methodology\\/Principal FindingsPlacenta and fetal liver at 15.5 days gestation were analyzed by

  4. Identifying Academic Potential in Students from Underrepresented Populations: Is Using the Ravens Progressive Matrices a Good Idea?

    Microsoft Academic Search

    Carol J. Mills; Sherri L. Tissot

    1995-01-01

    Increasing concern has been focused on the under-representation of African-American and Hispanic students in programs for the academically talented. The Raven's Progressive Matrices (RPM) has been suggested as a possible instrument to help remedy this situation, although little research has been conducted about its viability in identifying academic potential in minority populations. A sample of low-income minority students was given

  5. An assessment indicator for air ventilation and pollutant dispersion potential in an urban canopy with complex natural terrain and significant wind variations

    NASA Astrophysics Data System (ADS)

    Yim, S. H. L.; Fung, J. C. H.; Ng, E. Y. Y.

    2014-09-01

    In an urban planning context, an assessment indicator for evaluating a city's dispersion potential is beneficial, especially if the city has a complex natural terrain and significant wind variations. A study was conducted to implement an urban canopy drag indicator, taking site wind variation into account by involving both wind speed and direction in the calculations. Hong Kong (HK) was taken as an example due to its complicated natural topography and wind characteristics. A spatial distribution of an urban canopy drag over HK was determined based on wind data from 2004. The urban canopy drag values in three highly urbanized areas in HK, including Kowloon West, Kowloon East and Hong Kong Island North, were obtained and are discussed in detail. A fluid particle tracking program was developed and applied to identify the major wind paths in Kowloon West, with an area of approximately 5.5 × 6 km as an example. We analyzed the diurnal variation in the dispersion times and the major wind paths in the region during both summer and winter. Our results estimated that the horizontal dispersion times of Kowloon West during both winter and summer were approximately 20 min. By combining the wind paths from both seasons, we identified several major wind paths and critical ventilation areas in Kowloon West. This paper demonstrates the potential use of an urban canopy drag indicator for assessing air ventilation and pollutant dispersion in a city planning context.

  6. Effect of cooking on meat proteins: mapping hydrothermal protein modification as a potential indicator of bioavailability.

    PubMed

    Deb-Choudhury, Santanu; Haines, Stephen; Harland, Duane; Clerens, Stefan; van Koten, Chikako; Dyer, Jolon

    2014-08-13

    Thermal treatment of meat proteins induces a range of observable and molecular-level changes. In order to understand and track these heat-induced modifications at the amino acid level, various analytical techniques were used. Changes were observed both in the soluble and in the insoluble fractions after hydrothermal treatment of minced beef samples. Redox proteomics clearly indicated increasing oxidative modification of proteins with increased heat exposure. Collagens in the soluble fraction and myosin in the insoluble fraction were found to be highly susceptible to such modifications. Maillard reaction products in the insoluble and pyrrolidone formation in the soluble fraction steadily increased with increased heat exposure. Fluorescence studies indicated a rapid increase in fluorescence with heat, suggesting the formation of advanced glycation end products. Overall these results provide a deeper understanding of the effect of cooking on meat proteins and the possible relationship to processing conditions in meat-derived food. PMID:25033321

  7. Abnormal Indices of Cell Cycle Activity in Schizophrenia and their Potential Association with Oligodendrocytes

    Microsoft Academic Search

    Pavel Katsel; Kenneth L Davis; Celeste Li; Weilun Tan; Elizabeth Greenstein; Lisa B Kleiner Hoffman; Vahram Haroutunian

    2008-01-01

    The goal of this study was to determine what signaling pathways may elicit myelin-specific gene expression deficits in schizophrenia (SZ). Microarray analyses indicated that genes associated with canonical cell cycle pathways were significantly affected in the anterior cingulate gyrus (ACG), the region exhibiting the most profound myelin-specific gene expression changes, in persons with SZ (N=16) as compared with controls (N=19).

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

    PubMed

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

    2014-04-01

    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

  9. GAS6 expression identifies high-risk adult AML patients: potential implications for therapy

    PubMed Central

    Whitman, Susan P.; Kohlschmidt, Jessica; Maharry, Kati; Volinia, Stefano; Mrózek, Krzysztof; Nicolet, Deedra; Schwind, Sebastian; Becker, Heiko; Metzeler, Klaus H.; Mendler, Jason H.; Eisfeld, Ann-Kathrin; Carroll, Andrew J.; Powell, Bayard L.; Carter, Thomas H.; Baer, Maria R.; Kolitz, Jonathan E.; Park, Il-Kyoo; Stone, Richard M.

    2014-01-01

    Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in 270 adults (n=71 aged <60 years; n=199 aged ?60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged ?60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6?). After adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02), shorter DFS (P=0.004) and OS (P=0.04). To gain further biologic insights, we derived a GAS6-associated gene-expression signature (P<0.001) that in GAS6+ patients included overexpressed BAALC and MN1, known to confer adverse prognosis in CN-AML, and overexpressed CXCL12, encoding stromal cell-derived factor, and its receptor genes, CXCR4 and CXCR7. This study reports for the first time that GAS6 expression is an adverse prognostic marker in CN-AML. Although GAS6 decoy receptors are not yet available in the clinic for GAS6+ CN-AML therapy, potential alternative therapies targeting GAS6+-associated pathways, e.g., CXCR4 antagonists may be considered for GAS6+ patients to sensitize them to chemotherapy. PMID:24326683

  10. A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs.

    PubMed

    Cao, Jianzhong; Forrest, J Craig; Zhang, Xuming

    2015-02-01

    With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8log10 in virus titer) with an IC50 ranging from 11nM to 1.2?M. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs. PMID:25451075

  11. Identifying Potential Clinical Syndromes of Hepatocellular Carcinoma Using PSO-Based Hierarchical Feature Selection Algorithm

    PubMed Central

    Ji, Zhiwei; Wang, Bing

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Clinical symptoms attributable to HCC are usually absent, thus often miss the best therapeutic opportunities. Traditional Chinese Medicine (TCM) plays an active role in diagnosis and treatment of HCC. In this paper, we proposed a particle swarm optimization-based hierarchical feature selection (PSOHFS) model to infer potential syndromes for diagnosis of HCC. Firstly, the hierarchical feature representation is developed by a three-layer tree. The clinical symptoms and positive score of patient are leaf nodes and root in the tree, respectively, while each syndrome feature on the middle layer is extracted from a group of symptoms. Secondly, an improved PSO-based algorithm is applied in a new reduced feature space to search an optimal syndrome subset. Based on the result of feature selection, the causal relationships of symptoms and syndromes are inferred via Bayesian networks. In our experiment, 147 symptoms were aggregated into 27 groups and 27 syndrome features were extracted. The proposed approach discovered 24 syndromes which obviously improved the diagnosis accuracy. Finally, the Bayesian approach was applied to represent the causal relationships both at symptom and syndrome levels. The results show that our computational model can facilitate the clinical diagnosis of HCC. PMID:24745007

  12. Identifying potential clinical syndromes of hepatocellular carcinoma using PSO-based hierarchical feature selection algorithm.

    PubMed

    Ji, Zhiwei; Wang, Bing

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Clinical symptoms attributable to HCC are usually absent, thus often miss the best therapeutic opportunities. Traditional Chinese Medicine (TCM) plays an active role in diagnosis and treatment of HCC. In this paper, we proposed a particle swarm optimization-based hierarchical feature selection (PSOHFS) model to infer potential syndromes for diagnosis of HCC. Firstly, the hierarchical feature representation is developed by a three-layer tree. The clinical symptoms and positive score of patient are leaf nodes and root in the tree, respectively, while each syndrome feature on the middle layer is extracted from a group of symptoms. Secondly, an improved PSO-based algorithm is applied in a new reduced feature space to search an optimal syndrome subset. Based on the result of feature selection, the causal relationships of symptoms and syndromes are inferred via Bayesian networks. In our experiment, 147 symptoms were aggregated into 27 groups and 27 syndrome features were extracted. The proposed approach discovered 24 syndromes which obviously improved the diagnosis accuracy. Finally, the Bayesian approach was applied to represent the causal relationships both at symptom and syndrome levels. The results show that our computational model can facilitate the clinical diagnosis of HCC. PMID:24745007

  13. Heavy metal indicator potential of the Asiatic clam ( Corbicula fluminea ) in artificial stream systems

    Microsoft Academic Search

    Robert L. Graney; Donald S. Cherry; John Cairns

    1983-01-01

    The potential of the Asiatic clam, Corbicula fluminea, as a bioindicator of cadmium, copper, and zinc was studied during 28-day exposures in field artificial streams receiving river water on a once-through basis. Copper, at aquatic concentrations of 0.016 and 0.057 mg l-1, showed the greatest degree of tissue uptake and had bioconcentration factors (BCF) of 22 571 and 17 720,

  14. 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. PMID:25572526

  15. GAS6 expression identifies high-risk adult AML patients: potential implications for therapy.

    PubMed

    Whitman, S P; Kohlschmidt, J; Maharry, K; Volinia, S; Mrózek, K; Nicolet, D; Schwind, S; Becker, H; Metzeler, K H; Mendler, J H; Eisfeld, A-K; Carroll, A J; Powell, B L; Carter, T H; Baer, M R; Kolitz, J E; Park, I-K; Stone, R M; Caligiuri, M A; Marcucci, G; Bloomfield, C D

    2014-06-01

    Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in 270 adults (n=71 aged<60 years; n=199 aged ?60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged ?60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6-). After adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02), shorter DFS (P=0.004) and OS (P=0.04). To gain further biological insights, we derived a GAS6-associated gene-expression signature (P<0.001) that in GAS6+ patients included overexpressed BAALC and MN1, known to confer adverse prognosis in CN-AML, and overexpressed CXCL12, encoding stromal cell-derived factor, and its receptor genes, chemokine (C-X-C motif) receptor 4 (CXCR4) and CXCR7. This study reports for the first time that GAS6 expression is an adverse prognostic marker in CN-AML. Although GAS6 decoy receptors are not yet available in the clinic for GAS6+ CN-AML therapy, potential alternative therapies targeting GAS6+-associated pathways, for example, CXCR4 antagonists, may be considered for GAS6+ patients to sensitize them to chemotherapy. PMID:24326683

  16. A protocol for a scoping and qualitative study to identify and evaluate indications for damage control surgery and damage control interventions in civilian trauma patients

    PubMed Central

    Roberts, Derek J; Zygun, David A; Kirkpatrick, Andrew W; Ball, Chad G; Faris, Peter D; Bobrovitz, Niklas; Robertson, Helen Lee; Stelfox, H Thomas

    2014-01-01

    Introduction Initial abbreviated surgery with planned reoperation (damage control surgery) is frequently used for major trauma patients to rapidly control haemorrhage while limiting surgical stress. Although damage control surgery may decrease mortality risk among the severely injured, it may also be associated with several complications when inappropriately applied. We seek to scope the literature on trauma damage control surgery, identify its proposed indications, map and clarify their definitions, and examine the content and evidence on which they are based. We also seek to generate a comprehensive list of unique indications to inform an appropriateness rating process. Methods and analysis We will search 11 electronic bibliographic databases, included article bibliographies and grey literature sources for citations involving civilian trauma patients that proposed one or more indications for damage control surgery or a damage control intervention. Indications will be classified into a predefined conceptual framework and categorised and described using qualitative content analysis. Constant comparative methodology will be used to create, modify and test codes describing principal findings or injuries (eg, bilobar liver injury) and associated decision variables (eg, coagulopathy) that comprise the reported indications. After a unique list of codes have been developed, we will use the organisational system recommended by the RAND/University of California, Los Angeles (RAND-UCLA) Appropriateness Rating Method to group principal findings or injuries into chapters (subdivided by associated decision variables) according to broader clinical findings encountered during surgical practice (eg, major liver injury). Ethics and dissemination This study will constitute the first step in a multistep research programme aimed at developing appropriate, evidence-informed indications for damage control in civilian trauma patients. With use of an integrated knowledge translation intervention that includes collaboration with surgical practice leaders, this research may allow for development of indications that are more likely to be relevant to and used by surgeons. Ethics approval is not required for this study. PMID:25001397

  17. Brachial arterial temperature as an indicator of core temperature: proof of concept and potential applications.

    PubMed

    Pawley, Matthew D M; Martinsen, Paul; Mitchell, Simon J; Cheeseman, James F; Merry, Alan F; Willcox, Timothy; Grieve, Robert; Nand, Parma; Davies, Elaine; Warman, Guy R

    2013-06-01

    There is potential for heat loss and hypothermia during anesthesia and also for hyperthermia if heat conservation and active warming measures are not accurately titrated. Accurate temperature monitoring is particularly important in procedures in which the patient is actively cooled and then rewarmed such as during cardiopulmonary bypass surgery (CPB). We simultaneously measured core, nasopharyngeal, and brachial artery temperatures to investigate the last named as a potential peripheral temperature monitoring site. Ten patients undergoing hypothermic CPB were instrumented for simultaneous monitoring of temperatures in the pulmonary artery (PA), aortic arterial inflow (AI), nasopharynx (NP), and brachial artery (BA). Core temperature was defined as PA temperature before and after CPB and the AI temperature during CPB. Mean deviations of BA and NP temperatures from core temperature were calculated for three steady-state periods (before, during, and after CPB). Mean deviation of BA and NP temperatures from AI temperature was also calculated during active rewarming. A total of 1862 measurements were obtained and logged from eight patients. Mean BA and NP deviations from core temperature across the steady-state periods (before, during, and after CBP) were, respectively: .23 +/- .25, -.26 +/- .3, and -.09 +/- .05 degrees C (BA), and .11 +/- .19, -.1 +/- .47, and -.04 +/- .3 degrees C (NP). During steady-state periods, there was no evidence of a difference between the mean BA and NP deviation. During active rewarming, the mean difference between the BA and AI temperatures was .14 +/- .36 degrees C. During this period, NP temperature lagged behind AI and BA temperatures by up to 41 minutes and was up to 5.3 degres C lower than BA (mean difference between BA and NP temperatures was 1.22 +/- .58 degrees C). The BA temperature is an adequate surrogate for core temperature. It also accurately tracks the changing AI temperature during rewarming and is therefore potentially useful in detecting a hyperthermic perfusate, which might cause cerebral hyperthermia. PMID:23930377

  18. Lysergic acid diethylamide. Photoelectron ionization potentials as indices of behavioral activity.

    PubMed

    Domelsmith, L N; Munchausen, L L; Houk, K N

    1977-10-01

    The photoelectron spectrum of lysergic acid diethylamide (LSD) reveals five ionization potentials (IP's) between 7.25 and 9.75 eV arising from the aromatic (pi) portion of the molecule and IP's of 8.4 eV arising from the tertiary amine and 8.5-9.0 and 9.1 eV arising from the amide group. Comparisons of the IP's of LSD, and of phenethylamines and tryptamines reported by us elsewhere, with activities of these compounds in rat and human behavioral tests show that increasing activity is paralleled by decreasing IP. PMID:903923

  19. Sedimentary ladderane core lipids as potential indicators of hypoxia in the East China Sea

    NASA Astrophysics Data System (ADS)

    Zhao, Zongshan; Cao, Yali; Li, Li; Song, Guodong; Yang, Hongmei; Liu, Sumei; Zhao, Meixun

    2013-01-01

    Anammox (anaerobic ammonium oxidation) is an important process in many suboxic to anoxic marine environments for converting fixed nitrogen to N2, and has a major impact on the marine nitrogen cycle. Ladderane core lipids have been utilized as an indicator of the contribution of anammox to the marine nitrogen cycles. However, such studies have not been reported for the China seas and little is known about the importance of anammox within the nitrogen cycle of these marginal seas. In the research reported here, the ladderane core lipid contents of 17 surface sediment samples from the East China Sea are reported, and their spatial distribution is investigated. C18 -[5]-ladderane FAME, C20-[5]-ladderane FAME and C20-[3]-ladderane FAME have all been detected, suggesting that the anammox bacteria are widely present within the study area. The total contents of the three ladderane lipids (?FAMEs) range from 24-355 ng/g (weight of dry sediments), with higher contents occurring in the Minzhe Mud Zone and broadly coincident with the spatial distribution of hypoxia. It is suggested that the sedimentary ladderane core lipids are mainly produced in the water column and their sedimentary contents can be used as indicators of water column hypoxia.

  20. Personality traits of endodontic residents indicate potential for becoming endodontic faculty.

    PubMed

    O'Neill, Paula N; Svec, Timothy A; Ludington, John R; Suchina, John A

    2007-04-01

    Dental schools across America are challenged by the shortage of qualified faculty to fill vacant positions. This project, conducted through survey methodology, focused on obtaining a basic understanding of the personality types that seek out and maintain positions as full-time endodontic educators and compared those educators with endodontic residents to define similarities and differences that could lead to strategies to recruit those residents into academic endodontic education to assist in alleviating the faculty shortage in dentistry. All full-time endodontic faculty and residents were invited to participate. The Myers Briggs type indicator form M was administered electronically to faculty and postgraduates/residents. A 38.8% faculty and 21.3% resident response rate was achieved. Survey results were analyzed by using description statistics and chi-square tests. Results of the study indicate that there are parallel personality preferences of residents and faculty resulting in recommendations of early identification of academic interest, structured mentoring, faculty development of residents, and the implementation of debt-reduction strategies to ease entry into academic dentistry. PMID:17368332

  1. Sensory shelf life determination of a processed meat product 'rullepølse' and microbial metabolites as potential indicators.

    PubMed

    Stolzenbach, Sandra; Leisner, Jørgen J; Byrne, Derek V

    2009-10-01

    Sensory profiling was performed for a Danish lightly fermented heat-processed cold cut pork product termed 'rullepølse'. Product samples were stored under modified atmosphere (MAP, 30% CO(2)/70% N(2)) for 0, 28 and 34days and with subsequent aerobic storage for 4days (MAP-OPEN) at temperatures of 4°C and 8°C. Microbial growth and metabolism was also measured with a focus on lactic acid bacteria (LAB) and their organic acid metabolites including lactic acid, acetic acid and ?-ketoisocaproic acid. These acids were examined for sensory shelf life indexing potential for the 'rullepølse'. Storage temperature exerted distinct impacts on the sensory characterised shelf life of 'rullepølse' stored under MAP and MAP-OPEN conditions. The MAP stored 'rullepølse' with subsequent 4days storage in air (MAP-OPEN) could be stored for at least 28days at 4°C without a decrease in the sensory quality when opened. Whilst MAP stored 'rullepølse' at 8°C with subsequent open storage (MAP-OPEN), compared to the lower temperature displayed a reduced shelf life of less than 28days if sensory quality of the 'rullepølse' was to be maintained. The stage of sensory deterioration was correlated with high bacterial counts exceeding 10(6)CFUg(-1). With respect to indexing ability of the examined organic acids none were found to have clear potential for prediction of the sensory deterioration. PMID:20416734

  2. Using new dynamical indicators to distinguish between order and chaos in a galactic potential producing exact periodic orbits and chaotic components

    E-print Network

    Zotos, Euaggelos E

    2013-01-01

    The theory of the inverse problem is used in order to find a two dimensional galactic potential generating a mono-parametric family of elliptic periodic orbits. The potential is made up of a two-dimensional harmonic oscillator with perturbing terms of third and fourth degree and can be considered to describe local motion in the central parts of a barred galaxy. Our numerical calculations indicate that the potential produces also other families of orbits and there are cases, where distinct chaotic components are also observed. The numerical experiments suggest that there are regular as well as chaotic orbits supporting the barred structure. We use a variety of dynamical indicators, in order to determine the character of motion. Of significant interest, is the S(g) dynamical spectrum, which is used in order to identify the islandic motion of resonant orbits and also proves to be a very useful and fast indicator, in order to distinguish between regular and chaotic motion. Comparison with other methods for detect...

  3. Using new dynamical indicators to distinguish between order and chaos in a galactic potential producing exact periodic orbits and chaotic components

    E-print Network

    Euaggelos E. Zotos

    2013-03-03

    The theory of the inverse problem is used in order to find a two dimensional galactic potential generating a mono-parametric family of elliptic periodic orbits. The potential is made up of a two-dimensional harmonic oscillator with perturbing terms of third and fourth degree and can be considered to describe local motion in the central parts of a barred galaxy. Our numerical calculations indicate that the potential produces also other families of orbits and there are cases, where distinct chaotic components are also observed. The numerical experiments suggest that there are regular as well as chaotic orbits supporting the barred structure. We use a variety of dynamical indicators, in order to determine the character of motion. Of significant interest, is the S(g) dynamical spectrum, which is used in order to identify the islandic motion of resonant orbits and also proves to be a very useful and fast indicator, in order to distinguish between regular and chaotic motion. Comparison with other methods for detecting chaos is also discussed. The present results are compared with outcomes from earlier work.

  4. Mid-infrared prediction of lactoferrin content in bovine milk: potential indicator of mastitis.

    PubMed

    Soyeurt, H; Bastin, C; Colinet, F G; Arnould, V M-R; Berry, D P; Wall, E; Dehareng, F; Nguyen, H N; Dardenne, P; Schefers, J; Vandenplas, J; Weigel, K; Coffey, M; Théron, L; Detilleux, J; Reding, E; Gengler, N; McParland, S

    2012-11-01

    Lactoferrin (LTF) is a milk glycoprotein favorably associated with the immune system of dairy cows. Somatic cell count is often used as an indicator of mastitis in dairy cows, but knowledge on the milk LTF content could aid in mastitis detection. An inexpensive, rapid and robust method to predict milk LTF is required. The aim of this study was to develop an equation to quantify the LTF content in bovine milk using mid-infrared (MIR) spectrometry. LTF was quantified by enzyme-linked immunosorbent assay (ELISA), and all milk samples were analyzed by MIR. After discarding samples with a coefficient of variation between 2 ELISA measurements of more than 5% and the spectral outliers, the calibration set consisted of 2499 samples from Belgium (n = 110), Ireland (n = 1658) and Scotland (n = 731). Six statistical methods were evaluated to develop the LTF equation. The best method yielded a cross-validation coefficient of determination for LTF of 0.71 and a cross-validation standard error of 50.55 mg/l of milk. An external validation was undertaken using an additional dataset containing 274 Walloon samples. The validation coefficient of determination was 0.60. To assess the usefulness of the MIR predicted LTF, four logistic regressions using somatic cell score (SCS) and MIR LTF were developed to predict the presence of mastitis. The dataset used to build the logistic regressions consisted of 275 mastitis records and 13 507 MIR data collected in 18 Walloon herds. The LTF and the interaction SCS × LTF effects were significant (P < 0.001 and P = 0.02, respectively). When only the predicted LTF was included in the model, the prediction of the presence of mastitis was not accurate despite a moderate correlation between SCS and LTF (r = 0.54). The specificity and the sensitivity of models were assessed using Walloon data (i.e. internal validation) and data collected from a research herd at the University of Wisconsin - Madison (i.e. 5886 Wisconsin MIR records related to 93 mastistis events - external validation). Model specificity was better when LTF was included in the regression along with SCS when compared with SCS alone. Correct classification of non-mastitis records was 95.44% and 92.05% from Wisconsin and Walloon data, respectively. The same conclusion was formulated from the Hosmer and Lemeshow test. In conclusion, this study confirms the possibility to quantify an LTF indicator from milk MIR spectra. It suggests the usefulness of this indicator associated to SCS to detect the presence of mastitis. Moreover, the knowledge of milk LTF could also improve the milk nutritional quality. PMID:22717388

  5. The potential to reconstruct broadscale climate indices associated with southeast Australian droughts from Athrotaxis species, Tasmania

    NASA Astrophysics Data System (ADS)

    Allen, K. J.; Ogden, J.; Buckley, B. M.; Cook, E. R.; Baker, P. J.

    2011-11-01

    Occurrence of drought and dry periods in southeastern Australia has been linked to broad scale climate phenomena including the Southern Oscillation, Interdecadal Pacific Oscillation (IPO), Indian Ocean Dipole (IOD), Southern Annular Mode (SAM) and persistence of blocking high pressure in the Tasman Sea. We examine relationships between Athrotaxis tree ring chronologies from southern Australia extending over much of the past millennia and these broad scale indices. We also examine relationships between the chronologies, temperature, precipitation and a standardised precipitation and evapotranspiration index. Timing of significant correlations with maximum temperature varies between species. The responses of the species with broadscale indices vary with location: northern Athrotaxis cupressoides (Pencil Pine) are more strongly related to the Interdecadal Pacific Oscillation (IPO) and Southern Oscillation Index (SOI) than southern sites. As an exception to this, a site in the far south had significant correlations with both the SOI and IPO, opposite in sign to those observed for the northern sites. Significant spectral power at frequencies consistent with the SOI and IPO occur in all chronologies. Western and southern sites are more strongly related to a seasonalised index of SAM. These three systems have played important roles in determining moisture conditions in southeastern Australia over the past millennium. Results suggest that reconstructions of the SOI, IPO or SAM are unlikely based solely on this Athrotaxis network. The Athrotaxis network of tree ring sites, is however, likely to be an important input to multi-proxy models reconstructing the SOI, IPO or SAM in the Australian sector. The Athrotaxis network of sites is also an important extension of the existing network of Australian tree ring sites that could be used to reconstruct historical drought in southeastern Australia.

  6. RARE EARTH ELEMENTS IN FLY ASHES AS POTENTIAL INDICATORS OF ANTHROPOGENIC SOIL CONTAMINATION

    SciTech Connect

    Mattigod, Shas V.

    2003-08-01

    Studies of rare earth element (REE) content of disposed fly ashes and their potential mobility were neglected for decades because these elements were believed to be environmentally benign. A number of recent studies have now shown that REE may pose a long-term risk to the biosphere. Therefore, there is a critical need to study the REE concentrations in fly ash and their potential mobilization and dispersal upon disposal in the environment. We analyzed the REE content of bulk, size fractionated, and density separated fractions of three fly ash samples derived from combustion of sub bituminous coals from the western United States and found that the concentrations of these elements in bulk ashes were within the range typical of fly ashes derived from coals from the North American continent. The concentrations of light rare earth elements (LREE) such as La, Ce, and Nd, however, tended towards the higher end of the concentration range whereas, the concentrations of middle rare earth elements (MREE) (Sm and Eu) and heavy rare earth elements (HREE) (Lu) were closer to the lower end of the observed range for North American fly ashes. The concentrations of REE did not show any significant enrichment with decreasing particle size, this is typical of nonvolatile lithophilic element behavior during the combustion process. The lithophilic nature of REE was also confirmed by their concentrations in heavy density fractions of these fly ashes being on average about two times more enriched than the concentrations in the light density fractions. Shale normalized average of REE concentrations of fly ashes and coals revealed significant positive anomalies for Eu and Dy. Because of these distinctive positive anomalies of Eu and Dy, we believe that fly ash contamination of soils can be fingerprinted and distinguished from other sources of anthropogenic REE inputs in to the environment.

  7. Potential impact of climate change and reindeer density on tundra indicator species in the Barents Sea region

    Microsoft Academic Search

    Christoph Zöckler; Lera Miles; Lucy Fish; Annett Wolf; Gareth Rees; Fiona Danks

    2008-01-01

    Climate change is expected to alter the distribution of habitats and thus the distribution of species connected with these\\u000a habitats in the terrestrial Barents Sea region. It was hypothesised that wild species connected with the tundra and open-land\\u000a biome may be particularly at risk as forest area expands. Fourteen species of birds were identified as useful indicators for\\u000a the biodiversity

  8. 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. PMID:26076036

  9. Complex forest dynamics indicate potential for slowing carbon accumulation in the southeastern United States

    PubMed Central

    Coulston, John W.; Wear, David N.; Vose, James M.

    2015-01-01

    Over the past century forest regrowth in Europe and North America expanded forest carbon (C) sinks and offset C emissions but future C accumulation is uncertain. Policy makers need insights into forest C dynamics as they anticipate emissions futures and goals. We used land use and forest inventory data to estimate how forest C dynamics have changed in the southeastern United States and attribute changes to land use, management, and disturbance causes. From 2007-2012, forests yielded a net sink of C because of net land use change (+6.48?Tg C yr?1) and net biomass accumulation (+75.4?Tg C yr?1). Forests disturbed by weather, insect/disease, and fire show dampened yet positive forest C changes (+1.56, +1.4, +5.48?Tg C yr?1, respectively). Forest cutting caused net decreases in C (?76.7?Tg C yr?1) but was offset by forest growth (+143.77?Tg C yr?1). Forest growth rates depend on age or stage of development and projected C stock changes indicate a gradual slowing of carbon accumulation with anticipated forest aging (a reduction of 9.5% over the next five years). Additionally, small shifts in land use transitions consistent with economic futures resulted in a 40.6% decrease in C accumulation. PMID:25614123

  10. Complex forest dynamics indicate potential for slowing carbon accumulation in the southeastern United States

    NASA Astrophysics Data System (ADS)

    Coulston, John W.; Wear, David N.; Vose, James M.

    2015-01-01

    Over the past century forest regrowth in Europe and North America expanded forest carbon (C) sinks and offset C emissions but future C accumulation is uncertain. Policy makers need insights into forest C dynamics as they anticipate emissions futures and goals. We used land use and forest inventory data to estimate how forest C dynamics have changed in the southeastern United States and attribute changes to land use, management, and disturbance causes. From 2007-2012, forests yielded a net sink of C because of net land use change (+6.48 Tg C yr-1) and net biomass accumulation (+75.4 Tg C yr-1). Forests disturbed by weather, insect/disease, and fire show dampened yet positive forest C changes (+1.56, +1.4, +5.48 Tg C yr-1, respectively). Forest cutting caused net decreases in C (-76.7 Tg C yr-1) but was offset by forest growth (+143.77 Tg C yr-1). Forest growth rates depend on age or stage of development and projected C stock changes indicate a gradual slowing of carbon accumulation with anticipated forest aging (a reduction of 9.5% over the next five years). Additionally, small shifts in land use transitions consistent with economic futures resulted in a 40.6% decrease in C accumulation.

  11. The relationship between poor sleep and inhibitory functions indicated by event-related potentials.

    PubMed

    Breimhorst, Markus; Falkenstein, Michael; Marks, Anke; Griefahn, Barbara

    2008-06-01

    The present study focused on the relationship between normal variations of sleep and inhibitory functions as reflected in event-related potentials. For this reason one night of 21 healthy participants was analysed. After waking up all participants completed a visual Go/Nogo task. On the basis of a sleep disturbance index (SDI) the participants were separated into 8 SDI-good and 13 SDI-poor sleepers using a cluster analysis. The results showed that Nogo-N2 amplitude was smaller and Nogo-P3 latency longer in SDI-poor sleepers. Moreover, Go-P3 amplitude was smaller in SDI-poor sleepers. Performance parameters were not influenced by poor sleep. We concluded that poor sleep specifically affects the intensity of pre-motor inhibitory processes (Nogo-N2 amplitude), the speed to inhibit a motor response (Nogo-P3 latency) and the intensity of task-relevant information processing (Go-P3 amplitude). In further studies, it should be explored under which conditions such subliminal deficits also become relevant for overt behaviour. PMID:18324392

  12. Parasites of the grouper fish Epinephelus coioides (Serranidae) as potential environmental indicators in Indonesian coastal ecosystems.

    PubMed

    Kleinertz, S; Palm, H W

    2013-09-10

    A total of 195 Epinephelus coioides (Hamilton, 1822) were studied for fish parasites from Javanese (Segara Anakan lagoon) and Balinese waters. Up to 25 different parasite species belonging to the following taxa: one Ciliata, one Microsporea, five Digenea, one Monogenea, four Cestoda, four Nematoda, one Acanthocephala, one Hirudinea and seven Crustacea were identified with four new host and locality records. The dominant parasites included the monogenean Pseudorhabdosynochus lantauensis (53.3-97.1%), the nematode Spirophilometra endangae (23.3-42.9%), the digenean Didymodiclinus sp. (2.9-40.0%), the nematodes Philometra sp. (22.6-34.3%) and Raphidascaris sp. (2.9-28.6%), and the isopod Alcirona sp. (6.7-31.4%). Regional differences for E. coioides were found in terms of endoparasite diversity, total diversity according to Shannon-Wiener, Simpson index and Evenness. A comparison with published data from Sumatera revealed highest endoparasite diversity (Shannon-Wiener: 1.86/1.67-2.04) and lowest ectoparasite/endoparasite ratio (0.73/0.57-0.88) off the Balinese coast, followed by Lampung Bay, Sumatera (1.84; 0.67), off the coast of Segara Anakan lagoon (1.71; 0.71), and in the lagoon (0.30/0.19-0.66; 0.85/0.67-1.00). The presented data demonstrate the natural range of these parameters and parasite prevalences according to habitat and region, allowing adjustment of the scale that has been used in the visual integration of the parasite parameters into a star graph. The parasite fauna of E. coioides in Segara Anakan lagoon 'improved' from 2004 until 2008/09, possibly related to earlier oil spill events in 2002 and 2004. The use of grouper fish parasites as an early warning system for environmental change in Indonesian coastal ecosystems is discussed. PMID:24018181

  13. Dissolved Organic Carbon and Optical Properties as Indicators of Trihalomethane Formation Potential in an Agricultural Watershed

    NASA Astrophysics Data System (ADS)

    Pellerin, B. A.; Bergamaschi, B. A.; Spencer, R. G.

    2006-12-01

    Elevated concentrations of dissolved organic carbon (DOC) in the Sacramento-San Joaquin Delta waters may result in the formation of high levels of carcinogenic disinfection byproducts such as trihalomethane during drinking water treatment. The importance of Central Valley agricultural lands as sources of DOC and THM- precursors upstream of the Delta is presently unknown. We are quantifying contributions of DOC and THM- precursors from the Willow Slough watershed, a 425 km2 agriculturally-dominated catchment. During 2006, water samples were collected weekly at the mouth of the watershed and analyzed for DOC concentrations, optical properties (UV absorbance and fluorescence), and trihalomethane formation potential (THMFP). Additional synoptic samples were collected seasonally (winter, spring, summer) from 16 watershed locations and analyzed for optical properties, DOC concentrations, and THMFP. DOC concentrations generally ranged from approximately 2 to 4 mg/L at the watershed outlet during winter and spring, but increased weekly to 8 mg/L following the onset of irrigation. The THMFP at the mouth of the water was correlated with DOC concentration (r2 = 0.87), with higher concentrations during high discharge events and lower concentrations during summer and prolonged rain-free periods. In addition, the species of THM varied between high and low-flow periods, with THM formation dominated by brominated species during low- flow periods and chlorinated species during rainfall-runoff events. Optical characterization of DOC via UV absorbance and fluorescence suggests changes in DOC composition between high- and low-flow periods, likely reflective of changing sources and flowpaths of runoff.

  14. Secretome analysis identifies potential virulence factors of Diplodia corticola, a fungal pathogen involved in cork oak (Quercus suber) decline.

    PubMed

    Fernandes, Isabel; Alves, Artur; Correia, António; Devreese, Bart; Esteves, Ana Cristina

    2014-01-01

    The characterisation of the secretome of phytopathogenic fungi may contribute to elucidate the molecular mechanisms of pathogenesis. This is particularly relevant for Diplodia corticola, a fungal plant pathogen belonging to the family Botryosphaeriaceae, whose genome remains unsequenced. This phytopathogenic fungus is recognised as one of the most important pathogens of cork oak, being related to the decline of cork oak forests in the Iberian Peninsula. Unfortunately, secretome analysis of filamentous fungi is limited by the low protein concentration and by the presence of many interfering substances, such as polysaccharides, which affect the separation and analysis by 1D and 2D gel electrophoresis. We compared six protein extraction protocols concerning their suitability for further application with proteomic workflows. The protocols involving protein precipitation were the most efficient, with emphasis on TCA-acetone protocol, allowing us to identify the most abundant proteins on the secretome of this plant pathogen. Approximately 60% of the spots detected were identified, all corresponding to extracellular proteins. Most proteins identified were carbohydrate degrading enzymes and proteases that may be related to D. corticola pathogenicity. Although the secretome was assessed in a noninfection environment, potential virulence factors such as the putative glucan-?-glucosidase, neuraminidase, and the putative ferulic acid esterase were identified. The data obtained forms a useful basis for a deeper understanding of the pathogenicity and infection biology of D. corticola. Moreover, it will contribute to the development of proteomics studies on other members of the Botryosphaeriaceae. PMID:24863480

  15. Indicators and optical configuration for simultaneous high-resolution recording of membrane potential and intracellular calcium using laser scanning microscopy.

    PubMed

    Bullen, A; Saggau, P

    1998-10-01

    The instrumental design and experimental conditions for high-speed, simultaneous optical recording of membrane potential and intracellular Ca2+ with subcellular resolution are presented. This method employs an extended version of a high-speed, random-access, laser-scanning fluorescence microscope designed to record fast physiological signals from small neuronal structures with high spatiotemporal resolution (Bullen, Patel, Saggau, Biophys J 73:477-491, 1997). With this instrument, imaging and optical recording functions are conducted separately allowing frame rates up to 3 kHz. Individual scanning points are selected interactively from a reference image collected with differential interference contrast (DIC) optics. At each recording site, fluorescence from two indicators is measured simultaneously by independent photodetectors. To optimize signal strength, spectral separation and the achievable signal-to-noise ratio, several combinations of voltage-sensitive dye, Ca2+ indicator and optical elements (dichroic mirrors, filters, etc.) were considered. The best results were achieved from the combination of the intracellular voltage-sensitive dye Di-2-ANEPEQ and the Ca2+ indicator Calcium Green-1. These indicators have overlapping absorption spectra allowing simultaneous excitation with a single laser line (488 nm). Spectral separation of the fluorescence from these two indicators was accomplished using a secondary dichroic mirror (DCLP580) and emission filters (535/45 and OG590). Representative records obtained with this instrument and this combination of indicators demonstrate the feasibility of simultaneous high fidelity measurements of membrane potential and intracellular Ca2+ from the same point at high spatial (2 micrometer) and temporal (

  16. Mycobacterium growth indicator tube testing in conjunction with the AccuProbe or the AMPLICOR-PCR assay for detecting and identifying mycobacteria from sputum samples.

    PubMed Central

    Ichiyama, S; Iinuma, Y; Yamori, S; Hasegawa, Y; Shimokata, K; Nakashima, N

    1997-01-01

    We have compared the ability of the Mycobacterium Growth Indicator Tube (MGIT) system, a new culture method with an oxygen-sensitive fluorescent sensor, to recover mycobacteria from sputum samples with the abilities of egg-based medium and the Septi-Chek AFB system. We have also assessed the clinical utility of the AccuProbe or the AMPLICOR-PCR assay to directly identify Mycobacterium tuberculosis complex and M. avium-M. intracellulare complex (MAC) from positive MGITs. From 382 sputum samples, 99 isolates of M. tuberculosis complex and 20 isolates of MAC were recovered. The MGIT system had the highest recovery rates for M. tuberculosis complex (97.0%) and MAC (100%), compared to recovery rates of 51.5 and 65.0%, respectively, with the egg-based medium and 81.8 and 85.0%, respectively, with the Septi-Chek AFB system. The shortest recovery times were also achieved with the MGIT system: 16.6 days for M. tuberculosis complex and 12.0 days for MAC, compared to 27.1 and 20.1 days, respectively, with the egg-based medium and 21.4 and 13.2 days, respectively, with the Septi-Chek AFB system. The AccuProbe identified 74 (77.1%) of the 96 M. tuberculosis complex-positive MGITs and 17 (85.0%) of the 20 MAC-positive vials. The AMPLICOR system correctly identified 94 (97.9%) of the 96 M. tuberculosis complex-positive MGITs and all 20 MAC-positive vials. Therefore, the MGIT system used in conjunction with the AMPLICOR system is a rapid and sensitive method for detecting and identifying M. tuberculosis complex and MAC isolates from sputum samples. PMID:9230374

  17. 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. PMID:25875632

  18. Transcriptome analysis identifies novel responses and potential regulatory genes involved in seasonal dormancy transitions of leafy spurge (Euphorbia esula L.)

    PubMed Central

    Horvath, David P; Chao, Wun S; Suttle, Jeffrey C; Thimmapuram, Jyothi; Anderson, James V

    2008-01-01

    Background Dormancy of buds is a critical developmental process that allows perennial plants to survive extreme seasonal variations in climate. Dormancy transitions in underground crown buds of the model herbaceous perennial weed leafy spurge were investigated using a 23 K element cDNA microarray. These data represent the first large-scale transcriptome analysis of dormancy in underground buds of an herbaceous perennial species. Crown buds collected monthly from August through December, over a five year period, were used to monitor the changes in the transcriptome during dormancy transitions. Results Nearly 1,000 genes were differentially-expressed through seasonal dormancy transitions. Expected patterns of gene expression were observed for previously characterized genes and physiological processes indicated that resolution in our analysis was sufficient for identifying shifts in global gene expression. Conclusion Gene ontology of differentially-expressed genes suggests dormancy transitions require specific alterations in transport functions (including induction of a series of mitochondrial substrate carriers, and sugar transporters), ethylene, jasmonic acid, auxin, gibberellic acid, and abscisic acid responses, and responses to stress (primarily oxidative and cold/drought). Comparison to other dormancy microarray studies indicated that nearly half of the genes identified in our study were also differentially expressed in at least two other plant species during dormancy transitions. This comparison allowed us to identify a particular MADS-box transcription factor related to the DORMANCY ASSOCIATED MADS-BOX genes from peach and hypothesize that it may play a direct role in dormancy induction and maintenance through regulation of FLOWERING LOCUS T. PMID:19014493

  19. A chemical biology approach identified PI3K as a potential therapeutic target for neurofibromatosis type 2

    PubMed Central

    Petrilli, Alejandra M; Fuse, Marisa A; Donnan, Mathew S; Bott, Marga; Sparrow, Nicklaus A; Tondera, Daniel; Huffziger, Julia; Frenzel, Corina; Malany, C Siobhan; Echeverri, Christophe J; Smith, Layton; Fernández-Valle, Cristina

    2014-01-01

    Mutations in the merlin tumor suppressor gene cause Neurofibromatosis type 2 (NF2), which is a disease characterized by development of multiple benign tumors in the nervous system. The current standard of care for NF2 calls for surgical resection of the characteristic tumors, often with devastating neurological consequences. There are currently no approved non-surgical therapies for NF2. In an attempt to identify much needed targets and therapeutically active compounds for NF2 treatment, we employed a chemical biology approach using ultra-high-throughput screening. To support this goal, we created a merlin-null mouse Schwann cell (MSC) line to screen for compounds that selectively decrease their viability and proliferation. We optimized conditions for 384-well plate assays and executed a proof-of-concept screen of the Library of Pharmacologically Active Compounds. Further confirmatory and selectivity assays identified phosphatidylinositol 3-kinase (PI3K) as a potential NF2 drug target. Notably, loss of merlin function is associated with activation of the PI3K/Akt pathway in human schwannomas. We report that AS605240, a PI3K inhibitor, decreased merlin-null MSC viability in a dose-dependent manner without significantly decreasing viability of control Schwann cells. AS605240 exerted its action on merlin-null MSCs by promoting caspase-dependent apoptosis and inducing autophagy. Additional PI3K inhibitors tested also decreased viability of merlin-null MSCs in a dose-dependent manner. In summary, our chemical genomic screen and subsequent hit validation studies have identified PI3K as potential target for NF2 therapy. PMID:25360213

  20. Zebrafish: an emerging technology for in vivo pharmacological assessment to identify potential safety liabilities in early drug discovery

    PubMed Central

    Barros, T P; Alderton, W K; Reynolds, H M; Roach, A G; Berghmans, S

    2008-01-01

    The zebrafish is a well-established model organism used in developmental biology. In the last decade, this technology has been extended to the generation of high-value knowledge on safety risks of novel drugs. Indeed, the larval zebrafish appear to combine advantages of whole organism phenotypic assays and those (rapid production of results with minimal resource engagement) of in vitro high-throughput screening techniques. Thus, if appropriately evaluated, it can offer undeniable advantages in drug discovery for identification of target and off-target effects. Here, we review some applications of zebrafish to identify potential safety liabilities, particularly before lead/candidate selection. For instance, zebrafish cardiovascular system can be used to reveal decreases in heart rate and atrial–ventricular dissociation, which may signal human ether-a-go-go-related gene (hERG) channel blockade. Another main area of interest is the CNS, where zebrafish behavioural assays have been and are further being developed into screening platforms for assessment of locomotor activity, convulsant and proconvulsant liability, cognitive impairment, drug dependence potential and impaired visual and auditory functions. Zebrafish also offer interesting possibilities for evaluating effects on bone density and gastrointestinal function. Furthermore, available knowledge of the renal system in larval zebrafish can allow identification of potential safety issues of drug candidates on this often neglected area in early development platforms. Although additional validation is certainly needed, the zebrafish is emerging as a versatile in vivo animal model to identify off-target effects that need investigation and further clarification early in the drug discovery process to reduce the current, high degree of attrition in development. PMID:18552866

  1. Meta-analysis indicates that the European GWAS-identified risk SNP rs1344706 within ZNF804A is not associated with schizophrenia in Han Chinese population.

    PubMed

    Li, Ming; Zhang, Hui; Luo, Xiong-jian; Gao, Lei; Qi, Xue-bin; Gourraud, Pierre-Antoine; Su, Bing

    2013-01-01

    Recent genetic association studies have implicated several candidate susceptibility variants for schizophrenia among general populations. Rs1344706, an intronic SNP within ZNF804A, was identified as one of the most compelling candidate risk SNPs for schizophrenia in Europeans through genome-wide association studies (GWASs) and replications as well as large-scale meta-analyses. However, in Han Chinese, the results for rs1344706 are inconsistent, and whether rs1344706 is an authentic risk SNP for schizophrenia in Han Chinese is inconclusive. Here, we conducted a systematic meta-analysis of rs1344706 with schizophrenia in Chinese population by combining all available case-control samples (N?=?12), including a total of 8,982 cases and 12,342 controls. The results of our meta-analysis were not able to confirm an association of rs1344706 A-allele with schizophrenia (p?=?0.10, odds ratio?=?1.06, 95% confidence interval?=?0.99-1.13). Such absence of association was further confirmed by the non-superiority test (p?=?0.0003), suggesting that rs1344706 is not a risk SNP for schizophrenia in Han Chinese. Detailed examinations of individual samples revealed potential sampling bias in previous replication studies in Han Chinese. The absence of rs1344706 association in Han Chinese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating genome-wide association findings of schizophrenia across different ethnic populations. PMID:23776546

  2. Heat tolerance around flowering in wheat identified as a key trait for increased yield potential in Europe under climate change.

    PubMed

    Stratonovitch, Pierre; Semenov, Mikhail A

    2015-06-01

    To deliver food security for the 9 billon population in 2050, a 70% increase in world food supply will be required. Projected climatic and environmental changes emphasize the need for breeding strategies that delivers both a substantial increase in yield potential and resilience to extreme weather events such as heat waves, late frost, and drought. Heat stress around sensitive stages of wheat development has been identified as a possible threat to wheat production in Europe. However, no estimates have been made to assess yield losses due to increased frequency and magnitude of heat stress under climate change. Using existing experimental data, the Sirius wheat model was refined by incorporating the effects of extreme temperature during flowering and grain filling on accelerated leaf senescence, grain number, and grain weight. This allowed us, for the first time, to quantify yield losses resulting from heat stress under climate change. The model was used to optimize wheat ideotypes for CMIP5-based climate scenarios for 2050 at six sites in Europe with diverse climates. The yield potential for heat-tolerant ideotypes can be substantially increased in the future (e.g. by 80% at Seville, 100% at Debrecen) compared with the current cultivars by selecting an optimal combination of wheat traits, e.g. optimal phenology and extended duration of grain filling. However, at two sites, Seville and Debrecen, the grain yields of heat-sensitive ideotypes were substantially lower (by 54% and 16%) and more variable compared with heat-tolerant ideotypes, because the extended grain filling required for the increased yield potential was in conflict with episodes of high temperature during flowering and grain filling. Despite much earlier flowering at these sites, the risk of heat stress affecting yields of heat-sensitive ideotypes remained high. Therefore, heat tolerance in wheat is likely to become a key trait for increased yield potential and yield stability in southern Europe in the future. PMID:25750425

  3. Heat tolerance around flowering in wheat identified as a key trait for increased yield potential in Europe under climate change

    PubMed Central

    Stratonovitch, Pierre; Semenov, Mikhail A.

    2015-01-01

    To deliver food security for the 9 billon population in 2050, a 70% increase in world food supply will be required. Projected climatic and environmental changes emphasize the need for breeding strategies that delivers both a substantial increase in yield potential and resilience to extreme weather events such as heat waves, late frost, and drought. Heat stress around sensitive stages of wheat development has been identified as a possible threat to wheat production in Europe. However, no estimates have been made to assess yield losses due to increased frequency and magnitude of heat stress under climate change. Using existing experimental data, the Sirius wheat model was refined by incorporating the effects of extreme temperature during flowering and grain filling on accelerated leaf senescence, grain number, and grain weight. This allowed us, for the first time, to quantify yield losses resulting from heat stress under climate change. The model was used to optimize wheat ideotypes for CMIP5-based climate scenarios for 2050 at six sites in Europe with diverse climates. The yield potential for heat-tolerant ideotypes can be substantially increased in the future (e.g. by 80% at Seville, 100% at Debrecen) compared with the current cultivars by selecting an optimal combination of wheat traits, e.g. optimal phenology and extended duration of grain filling. However, at two sites, Seville and Debrecen, the grain yields of heat-sensitive ideotypes were substantially lower (by 54% and 16%) and more variable compared with heat-tolerant ideotypes, because the extended grain filling required for the increased yield potential was in conflict with episodes of high temperature during flowering and grain filling. Despite much earlier flowering at these sites, the risk of heat stress affecting yields of heat-sensitive ideotypes remained high. Therefore, heat tolerance in wheat is likely to become a key trait for increased yield potential and yield stability in southern Europe in the future. PMID:25750425

  4. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions

    PubMed Central

    Kraft, Robert; Kahn, Allon; Medina-Franco, José L.; Orlowski, Mikayla L.; Baynes, Cayla; López-Vallejo, Fabian; Barnard, Kobus; Maggiora, Gerald M.; Restifo, Linda L.

    2013-01-01

    SUMMARY The actin-bundling protein fascin is a key mediator of tumor invasion and metastasis and its activity drives filopodia formation, cell-shape changes and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency might underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bidirectional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the ‘filagree’ phenotype. Taking a repurposing approach, we screened a library of 1040 known compounds, many of them FDA-approved drugs, for filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity) and 48 fascin-pathway enhancers (with potential cognitive-enhancer activity). The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably the ‘beads-on-a-string’ defect, which is induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function, bidirectional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose strategy for drug discovery. PMID:22917928

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

    PubMed Central

    2011-01-01

    The recent publication of the draft genome sequences of the Neanderthal and a ~50,000-year-old archaic hominin from Denisova Cave in southern Siberia has ushered in a new age in molecular archaeology. We previously cross-compared the human, chimpanzee and Neanderthal genome sequences with respect to a set of disease-causing/disease-associated missense and regulatory mutations (Human Gene Mutation Database) and succeeded in identifying genetic variants which, although apparently pathogenic in humans, may represent a 'compensated' wild-type state in at least one of the other two species. Here, in an attempt to identify further 'potentially compensated mutations' (PCMs) of interest, we have compared our dataset of disease-causing/disease-associated mutations with their corresponding nucleotide positions in the Denisovan hominin, Neanderthal and chimpanzee genomes. Of the 15 human putatively disease-causing mutations that were found to be compensated in chimpanzee, Denisovan or Neanderthal, only a solitary F5 variant (Val1736Met) was specific to the Denisovan. In humans, this missense mutation is associated with activated protein C resistance and an increased risk of thromboembolism and recurrent miscarriage. It is unclear at this juncture whether this variant was indeed a PCM in the Denisovan or whether it could instead have been associated with disease in this ancient hominin. PMID:21807602

  6. Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma.

    PubMed

    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; Gowda, Harsha

    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

  7. Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome

    PubMed Central

    Gatto, S.; Gagliardi, M.; Crujeiras, A. B.; Matarazzo, M. R.; Esteller, M.; Sandoval, J.

    2015-01-01

    Introduction and Results Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues. Conclusions In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers with the aim to facilitate the identification of ICF patients. PMID:26161907

  8. 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

    2014-08-01

    Coral diseases have been increasingly reported over the past few decades and are a major contributor to coral decline worldwide. The Caribbean, in particular, has been noted as a hotspot for coral disease, and the aptly named white syndromes have caused the decline of the dominant reef building corals throughout their range. White band disease (WBD) has been implicated in the dramatic loss of Acropora cervicornis and Acropora palmata since the 1970s, resulting in both species being listed as critically endangered on the International Union for Conservation of Nature Red list. The causal agent of WBD remains unknown, although recent studies based on challenge experiments with filtrate from infected hosts concluded that the disease is probably caused by bacteria. Here, we report an experiment using four different antibiotic treatments, targeting different members of the disease-associated microbial community. Two antibiotics, ampicillin and paromomycin, arrested the disease completely, and by comparing with community shifts brought about by treatments that did not arrest the disease, we have identified the likely candidate causal agent or agents of WBD. Our interpretation of the experimental treatments is that one or a combination of up to three specific bacterial types, detected consistently in diseased corals but not detectable in healthy corals, are likely causal agents of WBD. In addition, a histophagous ciliate (Philaster lucinda) identical to that found consistently in association with white syndrome in Indo-Pacific acroporas was also consistently detected in all WBD samples and absent in healthy coral. Treatment with metronidazole reduced it to below detection limits, but did not arrest the disease. However, the microscopic disease signs changed, suggesting a secondary role in disease causation for this ciliate. In future studies to identify a causal agent of WBD via tests of Henle-Koch's postulates, it will be vital to experimentally control for populations of the other potential pathogens identified in this study. PMID:24943374

  9. Potential shortcomings of output:input ratios as indicators of economic efficiency in commercial beef breed evaluations.

    PubMed

    Melton, B E; Colette, W A

    1993-03-01

    In recent years animal breeders have increasingly made use of output:input ratios and simple measures of economic efficiency, such as annual profits, as a basis for comparisons and evaluations of the commercial applicability of alternative beef breeds. In many instances, however, output:input ratios may produce fallacious indications of economic efficiency that may, in turn, lead to erroneous conclusions regarding the true commercial applicability of the breeds evaluated. Errors potentially arising from the use of output:input ratios in breed evaluations may be attributed to a combination of 1) a narrow range of input use values under which most breeds are evaluated and 2) the inability of output:input ratios, including average annual profitability, to reflect consistently the economic objectives of commercial cow-calf producers. An alternative basis for breed comparison and evaluation is, therefore, developed from economic theories related to optimal investment and asset replacement. Comparison of the results obtained with this alternative to those obtained from output:input ratio evaluation, including annual profitability, indicate that potential value differences of as much as 33% may result from the use of output:input ratios as a primary basis of commercial breed evaluation. PMID:8463143

  10. A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential therapeutic treatments

    PubMed Central

    Zhao, Min; Kong, Lei; Qu, Hong

    2014-01-01

    Although the intelligence quotient (IQ) is the most popular intelligence test in the world, little is known about the underlying biological mechanisms that lead to the differences in human. To improve our understanding of cognitive processes and identify potential biomarkers, we conducted a comprehensive investigation of 158 IQ-related genes selected from the literature. A genomic distribution analysis demonstrated that IQ-related genes were enriched in seven regions of chromosome 7 and the X chromosome. In addition, these genes were enriched in target lists of seven transcription factors and sixteen microRNAs. Using a network-based approach, we further reconstructed an IQ-related pathway from known human pathway interaction data. Based on this reconstructed pathway, we incorporated enriched drugs and described the importance of dopamine and norepinephrine systems in IQ-related biological process. These findings not only reveal several testable genes and processes related to IQ scores, but also have potential therapeutic implications for IQ-related mental disorders. PMID:24566931

  11. Disappointing reliability of pulsatility indices to identify candidates for magnetic resonance imaging screening in population-based studies assessing prevalence of cerebral small vessel disease

    PubMed Central

    Del Brutto, Oscar H.; Mera, Robertino M.; Andrade, María de la Luz; Castillo, Pablo R.; Zambrano, Mauricio; Nader, Juan A.

    2015-01-01

    Background: Diagnosis of cerebral small vessel disease (SVD) is a challenge in remote areas where magnetic resonance imaging (MRI) is not available. Hospital-based studies in high-risk or stroke patients have found an association between the pulsatility index (PI) of intracranial arteries – as derived from transcranial Doppler (TCD) – and white matter hyperintensities (WMH) of presumed vascular origin. We aimed to assess the reliability of cerebral pulsatility indices to identify candidates for MRI screening in population-based studies assessing prevalence of SVD. Methods: A representative sample of stroke-free Atahualpa residents aged ?65 years investigated with MRI underwent TCD. Using generalized linear models, we evaluated whether the PI of major intracranial arteries correlate with WMH (used as a proxy of diffuse SVD), after adjusting for demographics and cardiovascular risk factors. Results: Out of 70 participants (mean age 70.6 ± 4.6 years, 57% women), 28 (40%) had moderate-to-severe WMH. In multivariate models, there were no differences across categories of WMH in the mean PI of middle cerebral arteries (1.10 ± 0.16 vs. 1.22 ± 0.24, ?: 0.065, 95% confidence interval (CI): ?0.084–0.177, P = 0.474) or vertebrobasilar arteries (1.11 ± 0.16 vs. 1.29 ± 0.27, ?: 0.066, 95% CI: ?0.0024–0.156, P = 0.146). Conclusions: Cerebral PI should not be used to identify candidates for MRI screening in population-based studies assessing the burden of SVD.

  12. A Genome-Wide Aberrant RNA Splicing in Patients with Acute Myeloid Leukemia Identifies Novel Potential Disease Markers and Therapeutic Targets

    PubMed Central

    Adamia, Sophia; Haibe-Kains, Benjamin; Pilarski, Patrick M.; Bar-Natan, Michal; Pevzner, Samuel; Avet-Loiseau, Herve; Lode, Laurence; Verselis, Sigitas; Fox, Edward A.; Burke, John; Galinsky, Ilene; Dagogo-Jack, Ibiayi; Wadleigh, Martha; Steensma, David P.; Motyckova, Gabriela; Deangelo, Daniel J.; Quackenbush, John; Stone, Richard; Griffin, James D.

    2015-01-01

    Purpose Despite new treatments, acute myeloid leukemia (AML) remains an incurable disease. More effective drug design requires an expanded view of the molecular complexity that underlies AML. Alternative splicing of RNA is used by normal cells to generate protein diversity. Growing evidence indicates that aberrant splicing of genes plays a key role in cancer. We investigated genome-wide splicing abnormalities in AML and based on these abnormalities, we aimed to identify novel potential biomarkers and therapeutic targets. Experimental Design We used genome-wide alternative splicing screening to investigate alternative splicing abnormalities in two independent AML patient cohorts [Dana-Farber Cancer Institute (DFCI) (Boston, MA) and University Hospital de Nantes (UHN) (Nantes, France)] and normal donors. Selected splicing events were confirmed through cloning and sequencing analysis, and than validated in 193 patients with AML. Results Our results show that approximately 29% of expressed genes genome-wide were differentially and recurrently spliced in patients with AML compared with normal donors bone marrow CD34+ cells. Results were reproducible in two independent AML cohorts. In both cohorts, annotation analyses indicated similar proportions of differentially spliced genes encoding several oncogenes, tumor suppressor proteins, splicing factors, and heterogeneous-nuclear-ribonucleoproteins, proteins involved in apoptosis, cell proliferation, and spliceosome assembly. Our findings are consistent with reports for other malignances and indicate that AML-specific aberrations in splicing mechanisms are a hallmark of AML pathogenesis. Conclusions Overall, our results suggest that aberrant splicing is a common characteristic for AML. Our findings also suggest that splice variant transcripts that are the result of splicing aberrations create novel disease markers and provide potential targets for small molecules or antibody therapeutics for this disease. PMID:24284058

  13. Indicators of hydrological, biogeochemical and ecological integrity for estimating potential loss of ecosystem services from wetlands on domesticated landscapes

    NASA Astrophysics Data System (ADS)

    Creed, I. F.; Aldred, D.; Spargo, A.; Bayley, S.

    2012-12-01

    Wetlands are being lost at an alarming rate in the prairie pothole landscape of North America. The full consequence of this loss is not fully understood or recognized due to (1) inadequate or incomplete wetland inventories (with mapping emphasizing permanent and not ephemeral wetlands, and only capturing "easy to observe" wetland area defined by open water and not the true dynamic wetland extent defined by saturated soils), and (2) lack of appropriate theoretical frameworks to assess the functions and benefits of these wetlands. We present a theoretical framework that integrates indicators to estimate functions and benefits of wetland integrity in central Alberta. We establish indicators using the principles that are representative of the dominant processes operating on the landscape, are simple and are scalable. While some of these indicators may be widely recognized, their implementation is often not comprehensive or complete. First, we develop an automated method for fine scale mapping of permanent and ephemeral wetlands from a fusion of high-resolution elevation data and aerial photography. Second, we estimate historic wetland loss over the past 50 years during which intensive domestication of the landscape occurred by modeling the distribution of wetlands in an undisturbed landscape using area-frequency power functions and calculating the difference in the actual wetland inventory. Third, we define relative wetland assessment units using cluster analysis of hydrological and ecological variables, including climate, geology, topography, soils and land use/land covers. Fourth, for each assessment unit we define indicators of functions and benefits of aquatic ecosystem services including water storage (surface and subsurface), phosphorus retention, nitrate removal, sediment retention, ecological health/biodiversity and human use, and then use practical strategies rooted in the fusion of digital terrain analysis and remote sensing techniques to measure and monitor these indicators over the past years. For a time series of wetlands loss we derive these indicators of functions and benefits to estimate changes in the provision of specific aquatic ecosystem services on the landscape. Last, we develop formulae for integrating these indicators to determine whether a specific wetland or wetland complex should be prioritized for conservation, exemplifying potential trade-offs among ecosystem services in setting conservation targets on this wetland dominated landscapes. The proposed theoretical framework evolved from close collaboration between scientists and resource managers, and will inform those engaged in developing wetland policies for a broad range of jurisdictions.

  14. ECOLOGICAL INDICATORS

    EPA Science Inventory

    An international symposium on ecological indicators was developed to explore both the potential of ecological indicators and the issues surrounding their development and implementation. his symposium presented state-of-the-science information on the identification, application re...

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

    For infrastructure design, operations, and maintenance requirements in the North the ability to accurately and efficiently detect the presence (or absence) of ground ice in permafrost terrains is a serious challenge. Ground ice features including ice wedges, thermokarst cave-ice, and segregation ice are present in a variety of spatial scales and patterns. Currently, most engineering applications use borehole logging and sampling to extrapolate conditions at the point scale. However, there is high risk of over or under estimating the presence of frozen or unfrozen features when relying on borehole information alone. In addition, boreholes are costly, especially for planning linear structures like roads or runways. Predicted climate warming will provide further challenges for infrastructure development and transportation operations where permafrost degradation occurs. Accurately identifying the subsurface character in permafrost terrains will allow engineers and planners to cost effectively create novel infrastructure designs to withstand the changing environment. There is thus a great need for a low cost rapidly deployable, spatially extensive means of 'measuring' subsurface conditions. Geophysical measurements, both terrestrial and airborne, have strong potential to revolutionize our way of mapping subsurface conditions. Many studies in continuous and discontinuous permafrost have used geophysical measurements to identify discrete features and repeatable patterns in the subsurface. The most common measurements include galvanic and capacitive coupled resistivity, ground penetrating radar, and multi frequency electromagnetic induction techniques. Each of these measurements has strengths, weaknesses, and limitations. By combining horizontal geophysical measurements, downhole geophysics, multispectral remote sensing images, LiDAR measurements, and soil and vegetation mapping we can start to assemble a holistic view of how surface conditions and standoff measurements can be used to delineate subsurface permafrost geomorphology. This presentation will include examples of projects in Alaska and Greenland where a combination of geophysical and other measurement techniques have been used to identify subsurface conditions. These include projects at multiple locations around Interior Alaska where a variety of ground based and standoff measurements are being used to identify subsurface conditions, and infrastructure projects at Thule, Greenland, where geophysical measurements are being used to cut costs for new construction and maintenance. The expansion of the Cold Regions Research and Engineering Laboratories' Fox Permafrost Tunnel is to provide a three dimensional test bed for geophysical measurements, and construction is aided by geophysical measurements. The array of geophysical research tools used to interrogate the subsurface in permafrost terrains can likely provide worthwhile information in non-frozen ground terrains to support sensor development and geomorphological interpretation.

  16. Naphthenic acids in coastal sediments after the Hebei Spirit oil spill: a potential indicator for oil contamination.

    PubMed

    Wan, Yi; Wang, Beili; Khim, Jong Seong; Hong, Seongjin; Shim, Won Joon; Hu, Jianying

    2014-04-01

    Naphthenic acids (NAs) as toxic components in most petroleum sources are suspected to be one of the major pollutants in the aquatic environment following oil spills, and the polarity and persistence of NAs make it a potential indicator for oil contamination. However, the contamination and potential effects of pollutants in oil spill affected areas remain unknown. To investigate NAs in oil spill affected areas, a sensitive method was first established for analysis of NAs, together with oxy-NAs in sediment samples by UPLC-QTOF-MS. Then the method was applied to determine the NA mixtures in crude oil, weathered oil, and sediments from the spilled sites after the Hebei Spirit oil spill, Taean, South Korea (Dec. 2007). Concentrations of NAs, O3-NAs, and O4-NAs were found to be 7.8-130, 3.6-44, and 0.8-20 mg kg(-1) dw in sediments from the Taean area, respectively, which were much greater than those measured in the reference sites of Manlipo and Anmyundo beaches. Concentrations of NAs were 50-100 times greater than those (0.077-2.5 mg kg(-1) dw) of PAHs in the same sediment samples, thus the ecological risk of NAs in oil spill affected areas deserves more attention. The sedimentary profiles of oil-derived NAs and background NAs centered around compounds with 21-35 and 12-21 carbons, respectively, indicating that the crude-derived NA mixtures originating from the 2007 oil spill were persistent. Acyclic NAsn=5-20 were easily degraded compared to cyclic NAsn=21-41 during the oil weathering processes, and the ratio of oxy-NAsn=21-41 relative to NAsn=21-41 could be a novel index to estimate the degree of oil weathering in sediments. Altogether, the persistent oil-derived NAsn=21-41 could be used as a potential indicator for oil-specific contamination, as such compounds would not be much affected by the properties of coastal sediments possibly due to the high sorption of the negatively charged compounds (NAs) in sediment. PMID:24579908

  17. Subtractive Phage Display Selection from Canine Visceral Leishmaniasis Identifies Novel Epitopes That Mimic Leishmania infantum Antigens with Potential Serodiagnosis Applications

    PubMed Central

    Costa, Lourena E.; Lima, Mayara I. S.; Chávez-Fumagalli, Miguel A.; Menezes-Souza, Daniel; Martins, Vivian T.; Duarte, Mariana C.; Lage, Paula S.; Lopes, Eliane G. P.; Lage, Daniela P.; Ribeiro, Tatiana G.; Andrade, Pedro H. R.; de Magalhães-Soares, Danielle F.; Soto, Manuel; Tavares, Carlos A. P.; Goulart, Luiz R.

    2014-01-01

    Visceral leishmaniasis (VL) is a zoonotic disease that is endemic to Brazil, where dogs are the main domestic parasite reservoirs, and the percentages of infected dogs living in regions where canine VL (CVL) is endemic have ranged from 10% to 62%. Despite technological advances, some problems have been reported with CVL serodiagnosis. The present study describes a sequential subtractive selection through phage display technology from polyclonal antibodies of negative and positive sera that resulted in the identification of potential bacteriophage-fused peptides that were highly sensitive and specific to antibodies of CVL. A negative selection was performed in which phage clones were adhered to purified IgGs from healthy and Trypanosoma cruzi-infected dogs to eliminate cross-reactive phages. The remaining supernatant nonadhered phages were submitted to positive selection against IgG from the blood serum of dogs that were infected with Leishmania infantum. Phage clones that adhered to purified IgGs from the CVL-infected serum samples were selected. Eighteen clones were identified and their reactivities tested by a phage enzyme-linked immunosorbent assay (phage-ELISA) against the serum samples from infected dogs (n = 31) compared to those from vaccinated dogs (n = 21), experimentally infected dogs with cross-reactive parasites (n = 23), and healthy controls (n = 17). Eight clones presented sensitivity, specificity, and positive and negative predictive values of 100%, and they showed no cross-reactivity with T. cruzi- or Ehrlichia canis-infected dogs or with dogs vaccinated with two different commercial CVL vaccines in Brazil. Our study identified eight mimotopes of L. infantum antigens with 100% accuracy for CVL serodiagnosis. The use of these mimotopes by phage-ELISA proved to be an excellent assay that was reproducible, simple, fast, and inexpensive, and it can be applied in CVL-monitoring programs. PMID:24256622

  18. 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 situation could be improved by the development of molecular databases. PMID:25993342

  19. Managing the Risk of Triggered Seismicity: Can We Identify (and Avoid) Potentially Active Faults? - A Practical Case Study in Oklahoma

    NASA Astrophysics Data System (ADS)

    Zoback, M. D.; Alt, R. C., II; Walsh, F. R.; Walters, R. J.

    2014-12-01

    It is well known that throughout the central and eastern U.S. there has been a marked increase in seismicity since 2009, at least some of which appears to increased wastewater injection. No area has seen a greater increase in seismicity than Oklahoma. In this paper, we utilize newly available information on in situ stress orientation and relative magnitudes, the distribution of high volume injection wells and knowledge of the intervals used for waste water disposal to identify the factors potentially contributing to the occurrence of triggered seismicity. While there are a number of sites where in situ stress data has been successfully used to identify potentially active faults, we are investigating whether this methodology can be implemented throughout a state utilizing the types of information frequently available in areas of oil and gas development. As an initial test of this concept, we have been compiling stress orientation data from wells throughout Oklahoma provided by private industry. Over fifty new high quality data points, principally drilling-induced tensile fractures observed in image logs, result in a greatly improved understanding of the stress field in much of the state. A relatively uniform ENE direction of maximum compressive stress is observed, although stress orientations (and possibly relative stress magnitudes) differ in the southern and southwestern parts of the state. The proposed methodology can be tested in the area of the NE-trending fault that produced the M 5+ earthquakes in the Prague, OK sequence in 2011, and the Meers fault in southwestern OK, that produced a M~7 reverse faulting earthquake about 1100 years ago. This methodology can also be used to essentially rule out slip on other major faults in the area, such as the ~N-S trending Nemaha fault system. Additional factors leading to the occurrence of relatively large triggered earthquakes in Oklahoma are 1) the overall increase in injection volumes throughout the state in recent years (especially in some particular areas) 2) the injection of waste water in a geologic formation laying directly above crystalline basement rocks and 3) the widespread distribution of injection wells.

  20. Spatial prediction of habitat overlap of introduced and native thistles to identify potential areas of nontarget activity of biological control agents.

    PubMed

    Wiggins, G J; Grant, J F; Lambdin, P L; Ranney, Jack W; Wilkerson, J B; van Manen, F T

    2010-12-01

    Nontarget feeding of Rhinocyllus conicus Fröelich and Trichosirocalus horridus (Panzer) on native North American thistles in the genus Cirsium has been documented. Some species of these native thistles have shown greater infestation levels of R. conicus in populations that are in close proximity to the target plant species, Carduus nutans L. In 2005 a study was initiated to identify areas of potential nontarget feeding by R. conicus and T. horridus on thistle species by predicting habitats of two known introduced hosts [C. nutans and Cirsium vulgare (Savi) Tenore] and two native species [Cirsium carolinianum (Walter) Fernald and Schubert and C. discolor (Muhlenberg ex Willdenow) Sprengel] using Mahalanobis distance (D(2)). Cumulative frequency graphs showed that the D(2) models for all four plant species effectively identified site conditions that contribute to the presence of the respective species. Poisson regression showed an association between D(2) values and plant counts at field-test sites for C. nutans and C. carolinianum. However, negative binomial regression detected no association between D(2) values and plant counts for C. discolor or C. vulgare. Chi-square analysis indicated associations between both weevil species and sites where C. vulgare and Carduus nutans were found, but not between the weevil and native thistle species. Habitats of C. nutans and Cirsium carolinianum overlapped in ?12% of the study area. Data-based habitat models may provide a powerful tool for land managers and scientists to monitor native plant populations for nontarget feeding by introduced biological control agents. PMID:22182552

  1. Tissue phosphoproteomics with PolyMAC identifies potential therapeutic targets in a transgenic mouse model of HER2 positive breast cancer.

    PubMed

    Searleman, Adam C; Iliuk, Anton B; Collier, Timothy S; Chodosh, Lewis A; Tao, W Andy; Bose, Ron

    2014-12-01

    Altered protein phosphorylation is a feature of many human cancers that can be targeted therapeutically. Phosphopeptide enrichment is a critical step for maximizing the depth of phosphoproteome coverage by MS, but remains challenging for tissue specimens because of their high complexity. We describe the first analysis of a tissue phosphoproteome using polymer-based metal ion affinity capture (PolyMAC), a nanopolymer that has excellent yield and specificity for phosphopeptide enrichment, on a transgenic mouse model of HER2-driven breast cancer. By combining phosphotyrosine immunoprecipitation with PolyMAC, 411 unique peptides with 139 phosphotyrosine, 45 phosphoserine, and 29 phosphothreonine sites were identified from five LC-MS/MS runs. Combining reverse phase liquid chromatography fractionation at pH 8.0 with PolyMAC identified 1571 unique peptides with 1279 phosphoserine, 213 phosphothreonine, and 21 phosphotyrosine sites from eight LC-MS/MS runs. Linear motif analysis indicated that many of the phosphosites correspond to well-known phosphorylation motifs. Analysis of the tyrosine phosphoproteome with the Drug Gene Interaction database uncovered a network of potential therapeutic targets centered on Src family kinases with inhibitors that are either FDA-approved or in clinical development. These results demonstrate that PolyMAC is well suited for phosphoproteomic analysis of tissue specimens. PMID:24723360

  2. 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 populations and potentially in the future for Indochinese tigers, given adequate prey and protection. PMID:23077476

  3. Volatile fingerprint of Brazilian defective coffee seeds: corroboration of potential marker compounds and identification of new low quality indicators.

    PubMed

    Toci, Aline T; Farah, Adriana

    2014-06-15

    In the present work, the volatile profiles of green and roasted Brazilian defective coffee seeds and their controls were characterised, totalling 159 compounds. Overall, defective seeds showed higher number and concentration of volatile compounds compared to those of control seeds, especially pyrazines, pyrroles and phenols. Corroborating our previous results, butyrolactone and hexanoic acid, previously considered as potential defective seeds' markers, were observed only in raw and roasted defective seeds, respectively, and not in control seeds. New compounds were suggested as potential defective seeds' markers: hexanoic acid (for raw and roasted defective seeds in general), butyrolactone (for raw defective seeds in general), and 3-ethyl-2-methyl-1,3-hexadiene (for raw black seeds); ?-linalool and 2-butyl-3,5-dimethylpyrazine (for roasted defective seeds in general), and 2-pentylfuran (for roasted black seeds). Additional compounds suggested as low quality indicators were 2,3,5,6-tetramethylpyrazine,2,3-butanediol and 4-ethylguaiacol, ?-linalool, 2-,3-dimethylbutyl butanoate, 2-phenylethyl acetate, 2,3-butanedione, hexanedioic acid, guaiacol, 2,3-dihydro-2-methyl-1H-benzopyrrol, 3-methylpiperidine, 2-pentylpiperidine, 3-octen-2-one, 2-octenal, 2-pentylfuran and 2-butyl-3-methylpyrazine. PMID:24491734

  4. A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor.

    PubMed

    Chung, C-M; Wang, R-Y; Chen, J-W; Fann, C S J; Leu, H-B; Ho, H-Y; Ting, C-T; Lin, T-H; Sheu, S-H; Tsai, W-C; Chen, J-H; Jong, Y-S; Lin, S-J; Chen, Y-T; Pan, W-H

    2010-12-01

    Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight single nucleotide polymorphisms (SNPs) of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (P=3.0 x 10?²?), rs495828 (P=3.5 x 10??) and rs8176746 (P=9.3 x 10??) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and showed a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE-activity-raising alleles. These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACEI. PMID:20066004

  5. 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

  6. Dual optical recordings for action potentials and calcium handling in induced pluripotent stem cell models of cardiac arrhythmias using genetically encoded fluorescent indicators.

    PubMed

    Song, LouJin; Awari, Daniel W; Han, Elizabeth Y; Uche-Anya, Eugenia; Park, Seon-Hye E; Yabe, Yoko A; Chung, Wendy K; Yazawa, Masayuki

    2015-05-01

    Reprogramming of human somatic cells to pluripotency has been used to investigate disease mechanisms and to identify potential therapeutics. However, the methods used for reprogramming, in vitro differentiation, and phenotyping are still complicated, expensive, and time-consuming. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from patients with Timothy syndrome into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared with the controls. The results are consistent with previous reports using a retroviral method for reprogramming and an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording the action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and that these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to investigate mechanisms underlying cardiac arrhythmias and to test potential therapeutics. PMID:25769651

  7. Predictors of 30 Day Readmission after Intracerebral Hemorrhage: A single-center approach for identifying potentially modifiable associations with readmission

    PubMed Central

    Liotta, Eric M.; Singh, Mandeep; Kosteva, Adam R.; Beaumont, Jennifer L.; Guth, James C.; Bauer, Rebecca M.; Prabhakaran, Shyam; Rosenberg, Neil F.; Maas, Matthew B.; Naidech, Andrew M.

    2013-01-01

    Objective To determine if patient demographics or severity of illness predict hospital readmission within 30 days following spontaneous intracerebral hemorrhage (ICH), to identify readmission associations that may be modifiable at the single center level, and to determine the impact of readmission on outcomes. Design We collected demographic, clinical, and hospital course data for consecutive patients with spontaneous ICH enrolled in an observational study. Readmission within 30 days was determined retrospectively by an automated query with manual confirmation. We identified the reason for readmission and tested for associations between readmission and functional outcomes using modified Rankin Scale (mRS, a validated functional outcome measure from 0, no symptoms to 6, death) scores before ICH and at 14 days, 28 days, and three months after ICH. Setting Neurologic intensive care unit of a tertiary care hospital. Patients Critically ill patients with spontaneous ICH. Interventions Patients received standard critical care management for ICH. Measurements and Main Results Of 246 patients (mean age 65 years, 51% female), 193 (78%) survived to discharge. Of these, 22 (11%) were re-admitted at a median of 9 [interquartile range (IQR) 4–15] days. The most common readmission diagnoses were infections after discharge (N=10) and vascular events (N=6). Age, history of stroke and hypertension, severity of neurologic deficit at admission, APACHE acute physiology score, ICU and hospital length of stay, ventilator free days, days febrile, and surgical procedures were not predictors of readmission. History of coronary artery disease was associated with readmission (p=0.03). Readmitted patients had similar mRS and severity of neurologic deficit at 14 days but higher (worse) mRS scores at three months (median [IQR], 5 [3–6] vs. 3 [1–4], p=0.01). Conclusions Severity of illness and hospital complications were not associated with 30-day readmission. The most common indication for readmission was infection after discharge, and readmission was associated with worse functional outcomes at three months. Preventing readmission after ICH may depend primarily on optimizing care after discharge and improve functional outcomes at three months. PMID:23963121

  8. RNA Interference Screen Identifies VEGFR1 as Potentially Synthetic Lethal to Aberrant Wnt/?-catenin Activation in Colon Cancer

    PubMed Central

    Naik, Snehal; Dothager, Robin S.; Marasa, Jayne; Lewis, Cory L.; Piwnica-Worms, David

    2009-01-01

    Purpose: The Wnt/?-catenin (?-cat) signaling cascade is a key regulator of development, and dysregulation of Wnt/?-cat contributes to selected cancers, such as colorectal, breast and hepatocellular carcinoma, through abnormal activation of Wnt target genes. To identify novel modulators of the Wnt/?-cat pathway which may emerge as therapeutic targets, we performed an unbiased high-throughput RNA interference screen. Experimental Design: A synthetic oligonucleotide siRNA library targeting 691 known and predicted human kinases was screened in Wnt3a-stimulated human cells in a live cell luciferase assay for modulation of Wnt/?-cat-dependent transcription. Follow-up studies of a selected high-confidence “hit” were conducted. Results: A robust quartile-based statistical analysis and secondary screen yielded several kinases worthy of further investigation, including Cdc2L1, Lmtk3, Pank2, ErbB3, and of note, vascular endothelial growth factor receptor-1 (VEGFR1/Flt1), a receptor tyrosine kinase with putative weak kinase activity conventionally believed to be a negative regulator of angiogenesis. A series of loss-of-function, genetic null, and VEGFR tyrosine kinase inhibitor assays further revealed that VEGFR1 is a positive regulator of Wnt signaling that functions in a glycogen synthase kinase-3? (GSK3?)-independent manner as a potential synthetic lethal target in Wnt/?-cat-addicted colon carcinoma cells. Conclusion: This unanticipated non-endothelial link between VEGFR1 tyrosine kinase activity and Wnt/?-cat signaling may refine our understanding of aberrant Wnt signaling in colon carcinoma and points to new combinatorial therapeutics targeted to the tumor cell compartment, rather than angiogenesis, in the context of colon cancer. PMID:20008853

  9. The IGF-1 Receptor Identifies a Pool of Human Cardiac Stem Cells with Superior Therapeutic Potential for Myocardial Regeneration

    PubMed Central

    D’Amario, Domenico; Cabral-Da-Silva, Mauricio; Zheng, Hanqiao; Fiorini, Claudia; Goichberg, Polina; Steadman, Elisabeth; Ferreira-Martins, João; Sanada, Fumihiro; Piccoli, Marco; Cappetta, Donato; D’Alessandro, David A.; Michler, Robert E.; Hosoda, Toru; Anastasia, Luigi; Rota, Marcello; Leri, Annarosa; Anversa, Piero; Kajstura, Jan

    2012-01-01

    Rationale Age and coronary artery disease may negatively affect the function of human cardiac stem cells (hCSCs) and their potential therapeutic efficacy for autologous cell transplantation in the failing heart. Objective Insulin-like growth factor 1 (IGF-1) and 2 (IGF-2), and angiotensin II (Ang II) and their receptors, IGF-1R, IGF-2R and AT1R, were characterized in c-kit-positive-hCSCs to establish whether these systems would allow us to separate hCSC classes with different growth reserve in the aging and diseased myocardium. Methods and Results C-kit-positive-hCSCs were collected from myocardial samples obtained from 24 patients, 48 to 86 years of age, undergoing elective cardiac surgery for coronary artery disease. The expression of IGF-1R in hCSCs recognized a young cell phenotype defined by long telomeres, high telomerase activity, enhanced cell proliferation and attenuated apoptosis. In addition to IGF-1, IGF-1R-positive-hCSCs secreted IGF-2 that promoted myocyte differentiation. Conversely, the presence of IGF-2R and AT1R, in the absence of IGF-1R, identified senescent hCSCs with impaired growth reserve and increased susceptibility to apoptosis. The ability of IGF-1R-positive-hCSCs to regenerate infarcted myocardium was then compared with that of unselected c-kit-positive-hCSCs. IGF-1R-positive-hCSCs improved cardiomyogenesis and vasculogenesis. Pretreatment of IGF-1R-positive-hCSCs with IGF-2 resulted in the formation of more mature myocytes and superior recovery of ventricular structure. Conclusions hCSCs expressing only IGF-1R synthesize both IGF-1 and IGF-2, which are potent modulators of stem cell replication, commitment to the myocyte lineage and myocyte differentiation, pointing to this hCSC subset as the ideal candidate cell for the management of human heart failure. PMID:21546606

  10. Identifying potentially active volcanoes in the Andes: Radiometric evidence for late Pleistocene-early Holocene eruptions at Volcán Imbabura, Ecuador

    NASA Astrophysics Data System (ADS)

    Le Pennec, J. L.; Ruiz, A. G.; Eissen, J. P.; Hall, M. L.; Fornari, M.

    2011-09-01

    Recent eruptions from volcanoes with no previously known historical activity in Chile and Indonesia have raised the importance of the early identification of potentially active centers for the purpose of hazard assessment. Here we bring radiometric evidence ( 14 C, 39Ar- 40Ar) of previously unrecognized but significant magmatic activity at partly eroded Imbabura volcano (Ecuador) in late Pleistocene to early Holocene times, on whose perimeter live more than 300,000 persons. Following an effusive stage from 50 to 30 ka with the emplacement of andesitic lava flows on different flanks of its edifice, the activity became explosive with the generation of andesitic block-and-ash flows on its eastern side, beginning at ~ 35 ka cal BP. Subsequently a flank collapse associated with a volcanic blast occurred on the volcano's SW flank at ~ 30 ka cal BP. The resulting debris avalanche and blast breccias cover an area now heavily populated around San Pablo Lake and its source was later concealed by successive dome building episodes at Huarmi which produced ~ 2.8 km 3 of silicic andesite. Renewed dome activity at the edifice's Taita summit occurred at ~ 17 ka cal BP and continued intermittently into early Holocene times, as indicated by pyroclastic flow deposits overlying a palaeosoil dated at ~ 9 ka cal BP. In summary, this study reveals an eruptive behavior characterized by a low recurrence rate but with quite large eruptions, a pattern which is also observed at other silicic volcanoes of Ecuador's Western Cordillera. It is now imperative to reconsider the origin and source of the many tephra layers catalogued in Holocene lacustrine sediments in the Imbabura area. Tephra and lava volume estimates for Imbabura volcano converted to Dense Rock Equivalent values yield a minimum magmatic output rate of 0.13 km 3/ka in the past 35,000 years, which argues for sustained magma production for this volcano in recent geological times. The Imbabura example thus raises the question of how to improve population preparedness for volcanoes with infrequent eruptions, and how to guide authorities' decisions concerning the development of urban areas and infrastructures near presently inactive but potentially highly dangerous volcanoes.

  11. Why are people with "poor lung function" at increased atherothrombotic risk? A critical review with potential therapeutic indications.

    PubMed

    Fimognari, Filippo Luca; Scarlata, Simone; Antonelli-Incalzi, Raffaele

    2010-07-01

    Patients classified as having a "poor lung function" in large populations studies are at increased risk of atherothrombosis, but potential mechanisms are unclear. A large proportion of these people are affected by chronic obstructive pulmonary disease (COPD), a recognized risk factor for vascular events. Systemic inflammation is the main atherothrombotic abnormality in COPD, but hypoxia-related platelet activation, pro-coagulant status and oxidative stress may play a role. Systemic inflammation is presumably a leading mechanism of atherothrombosis also in people who have a "restrictive" spirometric dysfunction, rather than the classic obstructive pattern of COPD. Many persons with "poor lung function" are affected by diabetes and their cardiovascular risk is therefore linked to the diabetic status. Patients affected by diabetes tend to have a "restrictive" dysfunction, rather than COPD. Recent studies show that restriction at spirometry precedes the onset of diabetes, thereby representing a marker of mechanisms involved in the pre-diabetic, insulin-resistant state. This is also proved by the fact that most patients with metabolic syndrome, a pre-diabetic condition, have a restrictive ventilatory pattern at spirometry. A significant proportion of people with "poor lung function" have visceral obesity, a cardiovascular risk factor. By hampering lung expansion, visceral obesity causes a restrictive ventilatory pattern. In conclusion, the term "poor lung function" includes various chronic illnesses with different mechanisms of atherothrombosis. Research is needed for better understanding why persons with lung dysfunctions have higher cardiovascular risk, and for identifying adequate preventive strategies. PMID:19485925

  12. QRS complex duration enhancement as ventricular late potential indicator by signal-averaged ECG using time-amplitude alignments.

    PubMed

    Avitia, Roberto L; Reyna, Marco A; Bravo-Zanoguera, Miguel E; Cetto, Lucio A

    2013-04-01

    Ventricular late potentials (VLPs) are small-amplitude waves with a short duration that appear at the end part of the QRS complex, making a QRS complex duration larger. The signal-averaged electrocardiography (ECG) technique enhances VLPs and beats, assuming noise as the only random variable. However, ECG signals are not completely stationary and different elongations appear in both time and amplitude in each beat. This research proposes to use piecewise linear approximation to segment each beat and performs the alignment of the beats using the technique known as derivative dynamic time-warping to have beats better aligned and consequently enhance the presence of VLPs. We recorded high-resolution ECGs (HRECGs) from 50 subjects in supine position with no heart-stroke antecedents. VLPs were created synthetically and added to the HRECGs. Two cases were evaluated: (i) duration of the QRS complexes with VLPs without beats alignment, and (ii) duration of QRS complexes with VLPs using beats alignment in time and amplitude. Considering QRS duration as an indicative of VLP presence, results show that when using beats alignment in time and amplitude it is possible to reach a sensitivity of 0.96 and a specificity of 0.52, as opposed to 0.72 and 0.40, respectively, when using only averaging without beats alignment in time and amplitude. PMID:23446922

  13. Histopathological and ultrastructural perturbations in tilapia liver as potential indicators of pollution in Lake Al-Asfar, Saudi Arabia.

    PubMed

    Abdel-Moneim, Ashraf M

    2014-03-01

    Lake Al-Asfar (Al-Hassa, Saudi Arabia) is under threat from contaminants released through human activities such as agriculture and urban and industrial developments. In the present study, histopathologic and ultrastructural changes in liver of tilapia Oreochromis niloticus were analyzed to monitor the possible impact of pollution in Al-Asfar estuary. Heavy metals such as Ni, Fe, Zn, Co, Ba, Pb, and Cd were predominant in the lake water and far exceeded the international permissible limits. In fish samples, high prevalences of preneoplastic changes (50 %) and one case of cholangiocarcinoma were revealed in liver tissues. Cytological damage in fish hepatocytes included glycogen exhaustion, deformation of nuclear envelope, heterochromatin condensation, mitochondrial degeneration, vesiculation of rough endoplasmic reticulum, augmentation of smooth endoplasmic reticulum, and lysosomal proliferation. In conclusion, the observed biomarker responses were potential indicators of health impairment or disease in field fish populations, although there was no direct proof of a simple cause-effect relationship. This is the first biological effect assessment in Lake Al-Asfar using tilapia as suitable target species. PMID:24323321

  14. 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

    ...HEALTH AND HUMAN SERVICES Evaluation of In Vitro Tests for Identifying Eye Injury Hazard...to assess the validation status of in vitro tests and integrated non-animal testing...submission of data from substances tested in in vitro tests for identifying eye injury...

  15. IDENTIFYING SUITABLE INDICATORS FOR MEASURING SUSTAINABILITY OF BIOENERGY PRODUCTS DERIVED FROM PINE FORESTS IN THE U.S. SOUTH (PHASE-1)

    EPA Science Inventory

    In this phase of the project, a sustainability framework was developed for four sustainability indices namely: 1) economic; 2) biodiversity; 3) greenhouse gas emission reduction and net energy ratio; and 4) soil and water quali...

  16. Different methanotrophic potentials in stratified polar fjord waters (Storfjorden, Spitsbergen) identified by using a combination of methane oxidation techniques

    NASA Astrophysics Data System (ADS)

    Mau, S.; Blees, J.; Helmke, E.; Niemann, H.; Damm, E.

    2013-04-01

    The bacterially mediated aerobic methane oxidation (MOx) is a key mechanism in controlling methane (CH4) emissions from the world's oceans to the atmosphere. In this study, we investigated MOx in the Arctic fjord Storfjorden (Spitsbergen) by applying a combination of radio-tracer based incubation assays (3H-CH4 and 14H-CH4), stable C-CH4 isotope measurements, and molecular tools (16S rRNA DGGE-fingerprinting, pmoA- and mxaF gene analyses). Strofjorden is stratified in the summertime with melt water (MW) in the upper 60 m of the water column, Arctic water (ArW) between 60-100 m and brine-enriched shelf water (BSW) down to 140 m. CH4 concentrations were supersaturated with respect to the atmospheric equilibrium (∼3 nM) throughout the water column, increasing from ∼20 nM at the surface to a maximum of 72 nM at 60 m and decreasing below. MOx rate measurements at near in situ CH4 concentrations (here measured with 3H-CH4 raising the ambient CH4 pool by <2 nM) showed a similar trend: low rates at the sea surface increasing to a maximum of ∼2.3 nM d-1 at 60 m followed by a decrease in the deeper ArW/BSW. In contrast, rate measurements with 14H-CH4 at elevated CH4 concentrations (incubations were spiked with ∼450 nM of 14H-CH4, providing an estimate of the CH4 oxidation potential) showed comparably low turnover rates (<1 nMd-1) at 60 m, but peaked in ArW/BSW at ∼100 m water depth, concomitant with increasing 14C-values in the residual CH4 pool. Our results indicate that the MOx community in the surface MW is adapted to relatively low CH4 concentrations. In contrast, the activity of the deep water MOx community is relatively low at the ambient, summertime CH4 concentrations but has the potential to increase rapidly in response to CH4 availability. A similar distinction between surface and deep water MOx is also suggested by our molecular analyses. Although, we found pmoA and maxF gene sequences throughout the water column attesting the ubiquitous presence of MOx communities in Storfjorden, deep water amplicons of pmoA and maxF were unusually long. Also a DGGE band related to the known Type I MOx Mehtylosphera was observed in deep BWS, but absent in surface MW. Apparently, different MOx communities have developed in the stratified water masses in Storfjorden, which is possibly related to the spatiotemporal variability in CH4 supply to the distinct water masses.

  17. Differential transcript regulation in Arabidopsis thaliana and the halotolerant Lobularia maritima indicates genes with potential function in plant salt adaptation.

    PubMed

    Popova, Olga V; Yang, Oksoon; Dietz, Karl-Josef; Golldack, Dortje

    2008-11-01

    Salt stress is an environmental factor that severely impairs plant growth and productivity. Salinity-induced transcript accumulation was monitored in the salt-sensitive Arabidopsis thaliana and the related salt-tolerant Lobularia maritima using cDNA-arrays with expressed sequence tags derived from a cDNA subtraction library of salt-stressed L. maritima. The expression profiles revealed differences of the steady state transcript regulation in A. thaliana and L. maritima in response to salt stress. The differentially expressed transcripts include those involved in the control of gene expression as a transcription factor II homologue as well as signal transduction elements such as a serine/threonine protein kinase, a SNF1-related protein kinase AKIN10 homologue, and protein phosphatase 2C. Other ESTs with differential regulation patterns included transcripts encoding proteins with function in general stress responses and defense and included a peroxidase, dehydrins, enzymes of lipid and nitrogen metabolism, and functionally unclassified proteins. In a more detailed analysis the basic leucine zipper transcription factor AtbZIP24 showed differential transcript abundance in A. thaliana and L. maritima in response to salt stress. Transgenic AtbZIP24-RNAi lines showed improved growth and development under salt stress that was correlated with changed Cl(-) accumulation. The data indicate that AtbZIP24 functions as a transcriptional repressor in salt-stressed A. thaliana that negatively regulates growth and development under salinity in context of controlling Cl(-) homeostasis. Monitoring the differential and tissue specific global regulation of gene expression during adaptation to salinity in salt-sensitive and halotolerant plants is a promising and powerful approach to identify novel elements of plant salt stress adaptation. PMID:18703123

  18. An assessment of potential hydro-political tensions in transboundary river basins using environmental, political, and economic indicators

    NASA Astrophysics Data System (ADS)

    De Stefano, Lucia; Petersen-Perlman, Jacob; Sproles, Eric; Eynard, James; Wolf, Aaron T.

    2015-04-01

    Globally 286 river basins extend across international borders, covering over 61.9 million km2 of the earth's surface and hosting a total of approximately 2.7 billion people. In these basins, transboundary water resources support an interdependent web of environmental, political, and economic systems that can enhance or destabilize a region. We present an integrated global-scale assessment of transboundary watersheds to identify regions more likely to experience hydro-political tensions over the next decade and beyond based upon environmental, political, and economic indicators. We combine NASA's Gravity Recovery and Climate Experiment (GRACE) measurements of changes in terrestrial water storage with metrics of projected climate change impacts on water variability, the institutional capacity of countries to manage shared water resources, the development of new water infrastructure, per capita gross national income, domestic and international armed conflicts, and recent history of disputes over transboundary waters. The construction of new water-related infrastructure is on-going or planned in many basins worldwide. New water infrastructure is foreseen also in areas where instruments of international cooperation are still absent or limited in scope, e.g. in Southeast Asia, South Asia, Central America, the northern part of the South American continent, and the southern Balkans as well as in different parts of Africa. Moreover, in Central and Eastern Africa, the Middle East, and Central, South and South-East Asia there is a concomitance of several political, environmental and socioeconomic factors that could exacerbate hydropolitical tensions. Our analysis integrates political, economic and environmental metrics and is part of the United Nation's Transboundary Waters Assessment Programme to provide the first global-scale assessment of its type.

  19. 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, Shuguang; 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.

  20. Distribution of the C 37 tetra-unsaturated alkenone in Lake Qinghai, China: A potential lake salinity indicator

    NASA Astrophysics Data System (ADS)

    Liu, Weiguo; Liu, Zhonghui; Fu, Mingyi; An, Zhisheng

    2008-02-01

    The alkenone unsaturation index U K'37 has been applied to reconstruct past temperature changes in both marine and lacustrine systems. However, few studies have addressed whether the relative abundance of the C 37:4 alkenone to the total C 37 production (%C 37:4) can reflect surface salinity changes in lacustrine systems. Here we present long-chain C 37 alkenone distribution patterns in surface sediments from Lake Qinghai, China. Surface sediments were sampled over a large range of surface salinity changes (1.7-25 g/l) within Lake Qinghai and its surrounding lakes, while temperature differences at these sampling locations should be relatively small. We have found that %C 37:4 varies from 15% to 49% as surface salinity decreases. We tentatively describe this %C 37:4-salinity link with a general linear regression: %C 37:4 = 53.4 (±7.8) - 1.73 (±0.45) × S ( n = 28, r2 = 0.62), although step-wise %C 37:4 changes in response to salinity variation may exist. U K'37 values vary between 0.10 and 0.16 at these sites and the inferred range of lake water temperature changes is ˜2-3 °C, suggesting that U K'37 largely reflects temperature signal across a large salinity range, consistent with previous findings that U K'37 can indicate temperature changes over a large diversity of environmental settings. We have also found that U K'37 values are correlated with salinity changes ( r2 = 0.4), and thus cannot exclude potential temperature effect on %C 37:4 and salinity effect on U K'37 in this study. However, even extreme estimates of temperature differences within the lake are still unable to explain the observed %C 37:4 changes. We therefore suggest that %C 37:4 could be used to infer past lake salinity changes at a regional scale.

  1. Aqueous and lipid nuclear magnetic resonance metabolomic profiles of the earthworm Aporrectodea caliginosa show potential as an indicator species for environmental metabolomics.

    PubMed

    Brown, Jeffrey N; Samuelsson, Linda; Bernardi, Giuliana; Gooneratne, Ravi; Larsson, D G Joakim

    2014-10-01

    The common pasture earthworm Aporrectodea caliginosa has often been neglected in environmental metabolomics in favor of species easily bred in the laboratory. The present study assigns aqueous metabolites in A. caliginosa using high-resolution 1- and 2-dimensional nuclear magnetic resonance (NMR) spectroscopy. In total, 51 aqueous metabolites were identified, including typical amino acids (alanine, leucine, asparagine, phenylalanine), sugars (maltose, glucose), the dominant earthworm-specific 2-hexyl-5-ethyl-furansulfonate, and several previously unreported metabolites (oxoglutarate, putrescine). Examining the lesser-known earthworm lipid metabolome showed various lipid fatty acyl chains, cholesterol, and phosphatidylcholine. To briefly test if the NMR metabolomic techniques could differentiate A. caliginosa from different sites, earthworms were collected from 2 adjacent farms. Orthogonal partial least squares discriminant analysis detected metabolomic differences, suggesting the worms from the 2 sites differed in their energy metabolism, as indicated by altered levels of alanine, glutamine, glutamate, malate, fumarate, and lipids. Evidence of greater utilization of lipid energy reserves and onset of protein catabolism was also present. While the precise cause of the metabolomic differences could not be determined, the results show the potential of this species for further environmental metabolomic studies. PMID:24995628

  2. Identifying the potential for irrigation development in Mozambique: Capitalizing on the drivers behind farmer-led irrigation expansion

    NASA Astrophysics Data System (ADS)

    Beekman, W.; Veldwisch, G. J.; Bolding, A.

    Smallholder irrigation in Central Mozambique predominantly takes place in an informal setting. This renders these smallholders and their activities invisible for policy purposes. Identification efforts of smallholder irrigation as well as the potential for new irrigation development are often the basis for policy setting. But the potential is often approached technocratically: the technical availability of water and land with the assumption that smallholder irrigation is not happening and should be developed. Although more and more effort is done to include social economical aspects into the identification as well, it remains a GIS exercise, based on incomplete data using large pixel sizes, analyzing countries or continents as a whole. This study describes and presents the methodology and the results of an irrigation potential identification exercise carried out in two studies in Central Mozambique. Apart from describing the identification methods used, this study highlights the extent of farmer-led irrigation development, its drivers and the potential for farmer-led smallholder irrigation development. This study demonstrates the prolific nature of smallholder irrigation, arguing for the recognition that smallholder farmers are already developing irrigation and that this should lead to changing the focus of identification efforts towards the drivers behind farmer-led irrigation development. Using these context-specific drivers to define the potential for new irrigation development should result in a better response in policy to both the technical and socio-economical potential of smallholder irrigation development.

  3. Persistence of somatic and F-specific coliphages, potential indicators of fecal contamination, on spinach foliar tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent outbreaks of foodborne illness have been linked to consumption of fresh leafy greens. E. coli is commonly used as the indicator microorganism for fecal contamination on leafy greens. However, alternative microorganisms, such as coliphages, may deserve consideration as indicators of fecal cont...

  4. Point to a Referent, and Say, "What Is This?" Gesture as a Potential Cue to Identify Referents in a Discourse

    ERIC Educational Resources Information Center

    So, Wing Chee; Lim, Jia Yi

    2012-01-01

    This study explored whether caregivers' gestures followed the discourse-pragmatic principle of information status of referents (given vs. new) and how their children responded to those gestures when identifying referents. Ten Chinese-speaking and eight English-speaking caregivers were videotaped while interacting spontaneously with their children.…

  5. Virtual Reality and Its Potential Use in Special Education. Identifying Emerging Issues and Trends in Technology for Special Education.

    ERIC Educational Resources Information Center

    Woodward, John

    As part of a 3-year study to identify emerging issues and trends in technology for special education, this paper addresses the possible contributions of virtual reality technology to educational services for students with disabilities. An example of the use of virtual reality in medical imaging introduces the paper and leads to a brief review of…

  6. Development of Normal Human Colon Cell Cultures to Identify Unregulated Disiinfection By-products (DBPs) with a Carcinogenic Potential - GEMS.

    EPA Science Inventory

    Epidemiological studies have linked the consumption of chlorinated surface waters to an increased risk of colorectal cancer. Approximately 600 DBPs, less that half of the total organic carbon in drinking water, have been identified of which 50 unregulated DBPs have received the ...

  7. Predatory Online Behavior: Modus Operandi of Convicted Sex Offenders in Identifying Potential Victims and Contacting Minors over the Internet

    ERIC Educational Resources Information Center

    Malesky, L. Alvin, Jr.

    2007-01-01

    Sex offenders have used the Internet to identify and contact minors for sexual exploitation (Armagh, 1998; Hernandez, 2000; Lamb, 1998; Lanning, 1998). Yet little is known about how these individuals select their online victims. In order to gain a better understanding of this behavior, the online activity of 31 men who perpetrated or attempted to…

  8. Reading at the Instructional Level with Children Identified as Learning Disabled: Potential Implications for Response-to-Intervention

    ERIC Educational Resources Information Center

    Burns, Matthew K.

    2007-01-01

    Curriculum-based assessment assesses the match between curriculum and student skill by computing the percentage of known words in a reading task and comparing it to the instructional level criterion of 93% to 97% known. The current study examined the effect of preteaching unknown words to 29 third-grade children identified as learning disabled…

  9. Development of Normal Human Colonocyte Cultures to Identify the Carcinogenic Potential of Priorty Disinfection By-products

    EPA Science Inventory

    Epidemiological studies have linked the consumption of disinfected surface waters to an increased risk of colorectal cancer. Of the approximately >600 disinfection byproducts (DBPs) identified, the US EPA regulates 11 DBPs for an increased risk of cancer. An in-depth mechanism-...

  10. DEVELOPMENT OF NORMAL HUMAN COLON CELL CULTURES TO IDENTIFY UNREGULATED DISINFECTION BY-PRODUCTS (DBPS) WITH CARCINOGENIC POTENTIAL.

    EPA Science Inventory

    Epidemiological studies have linked the consumption of chlorinated surface waters to an increased risk of colorectal cancer. Approximately 600 DBPs, less than half of the total organic carbon in drinking water have been identified. We are developing an in vitro system to i...

  11. A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of ?1-antitrypsin deficiency.

    PubMed

    O'Reilly, Linda P; Long, Olivia S; Cobanoglu, Murat C; Benson, Joshua A; Luke, Cliff J; Miedel, Mark T; Hale, Pamela; Perlmutter, David H; Bahar, Ivet; Silverman, Gary A; Pak, Stephen C

    2014-10-01

    ?1-Antitrypsin deficiency (ATD) is a common genetic disorder that can lead to end-stage liver and lung disease. Although liver transplantation remains the only therapy currently available, manipulation of the proteostasis network (PN) by small molecule therapeutics offers great promise. To accelerate the drug-discovery process for this disease, we first developed a semi-automated high-throughput/content-genome-wide RNAi screen to identify PN modifiers affecting the accumulation of the ?1-antitrypsin Z mutant (ATZ) in a Caenorhabditis elegans model of ATD. We identified 104 PN modifiers, and these genes were used in a computational strategy to identify human ortholog-ligand pairs. Based on rigorous selection criteria, we identified four FDA-approved drugs directed against four different PN targets that decreased the accumulation of ATZ in C. elegans. We also tested one of the compounds in a mammalian cell line with similar results. This methodology also proved useful in confirming drug targets in vivo, and predicting the success of combination therapy. We propose that small animal models of genetic disorders combined with genome-wide RNAi screening and computational methods can be used to rapidly, economically and strategically prime the preclinical discovery pipeline for rare and neglected diseases with limited therapeutic options. PMID:24838285

  12. Genetic Analysis of Fin Development in Zebrafish Identifies Furin and Hemicentin1 as Potential Novel Fraser Syndrome Disease Genes

    Microsoft Academic Search

    Thomas J. Carney; Natália Martins Feitosa; Carmen Sonntag; Krasimir Slanchev; Johannes Kluger; Daiji Kiyozumi; Jan M. Gebauer; Jared Coffin Talbot; Charles B. Kimmel; Kiyotoshi Sekiguchi; Raimund Wagener; Heinz Schwarz; Phillip W. Ingham; Matthias Hammerschmidt

    2010-01-01

    Using forward genetics, we have identified the genes mutated in two classes of zebrafish fin mutants. The mutants of the first class are characterized by defects in embryonic fin morphogenesis, which are due to mutations in a Laminin subunit or an Integrin alpha receptor, respectively. The mutants of the second class display characteristic blistering underneath the basement membrane of the

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

    Microsoft Academic Search

    Yogeswaran Lokanathan; Adura Mohd-Adnan; Kiew-Lian Wan; Sheila Nathan

    2010-01-01

    BACKGROUND: Cryptocaryon irritans is a parasitic ciliate that causes cryptocaryonosis (white spot disease) in marine fish. Diagnosis of cryptocaryonosis often depends on the appearance of white spots on the surface of the fish, which are usually visible only during later stages of the disease. Identifying suitable biomarkers of this parasite would aid the development of diagnostic tools and control strategies

  14. Identifying Academic Potential in Students from Under-Represented Populations: Is Using the Ravens Progressive Matrices a Good Idea?

    ERIC Educational Resources Information Center

    Mills, Carol J.; Tissot, Sherri L.

    1995-01-01

    The Raven's Progressive Matrices (RPM) and the Raven's Advanced Progressive Matrices (APM) were evaluated as possible instruments for identifying academically talented students in minority populations. A significantly higher proportion of minority children scored well on the RPM than on a traditional measure. Issues and concerns about using the…

  15. Potential nitrification as an indicator of preferential uptake of ammonium or nitrate by plants in an oak woodland understorey

    Microsoft Academic Search

    M. O. Olsson; U. Falkengren-Grerup

    2000-01-01

    The preferences of some woodland understorey species for ammonium and nitrate were investigated by measuring the potential nitrification (conversion of ammonium to nitrate) in the rhizosphere compared with the bulk soil. Less acid-tolerant species, which usually prefer nitrate or a mixture of ammonium and nitrate in hydroponic culture, should have a higher potential nitrification in the rhizosphere compared to the

  16. Circulating MiR-16-5p and MiR-19b-3p as Two Novel Potential Biomarkers to Indicate Progression of Gastric Cancer

    PubMed Central

    Zhang, Jingpu; Song, Yang; Zhang, Chunlei; Zhi, Xiao; Fu, Hualin; Ma, Yue; Chen, Yunsheng; Pan, Fei; Wang, Kan; Ni, Jian; Jin, Weilin; He, Xianli; Su, Haichuan; Cui, Daxiang

    2015-01-01

    Gastric cancer (GC) is the second most common cancer in China and the second leading cause of cancer-related death in the world. Identifying circulating biomarkers is helpful to improve theranostics of gastric cancer. Herein, we are for the first time to report miR-16-5p and miR-19b-3p were identified to be the novel potential plasma biomarkers to detect gastric cancer. Differentially expressed miRNAs were initially screened out by genome-wide miRNA profiling microarrays between 16 plasma samples of gastric cancer and 18 matched normal controls, and then were quantified and validated by quantitative reverse transcription-PCR method between 155 gastric cancer cases and 111 normal controls. Additionally, 30 plasma samples from precancerous lesions and 18 paired samples from gastric cancer patients with gastrectomy were further detected. Results showed that based on two normalization methods, miR-16-5p and miR-19b-3p in plasma were found to be capable of distinguishing normal population from GC cases with different TNM stages and differentiation grades, particularly including the early cancer cases (P<0.05). And the two miRNAs were down-regulated in GC cases (FC<0.5). Especially, the down-regulation degree was correlated with the progression of the GC cases from the early stage to the advanced stage (0.2< rs<0.3, P<0.01). And the same weak down-regulation of the two biomarkers as the early GC occurred initially in the precancerous diseases (P<0.05). The corresponding performance of the two miRNAs to detect GC in ROC analysis gradually performed better with the disease progression from the earlier stages or lower grades to the advanced stages (TNM ? stage: AUC=0.832 for miR-16-5p; TNM ? stage: AUC=0.822 for miR-19b-3p) or high grade (Poorly differentiated: AUC=0.801, 0.791 respectively for miR-16-5p and miR-19b-3p). Additionally, miR-19b-3p remained down-regulated in patient plasma within 9 days after gastrectomy. In conclusion, miR-19b-3p and miR-16-5p maybe prospective biomarkers to detect gastric cancer and indicate its progression, and thus may own great potential in applications such as early screening and progression evaluation of gastric cancer in the near future. PMID:25897338

  17. A novel cell-cycle-indicator, mVenus-p27K-, identifies quiescent cells and visualizes G0-G1 transition.

    PubMed

    Oki, Toshihiko; Nishimura, Koutarou; Kitaura, Jiro; Togami, Katsuhiro; Maehara, Akie; Izawa, Kumi; Sakaue-Sawano, Asako; Niida, Atsushi; Miyano, Satoru; Aburatani, Hiroyuki; Kiyonari, Hiroshi; Miyawaki, Atsushi; Kitamura, Toshio

    2014-01-01

    The quiescent (G0) phase of the cell cycle is the reversible phase from which the cells exit from the cell cycle. Due to the difficulty of defining the G0 phase, quiescent cells have not been well characterized. In this study, a fusion protein consisting of mVenus and a defective mutant of CDK inhibitor, p27 (p27K(-)) was shown to be able to identify and isolate a population of quiescent cells and to effectively visualize the G0 to G1 transition. By comparing the expression profiles of the G0 and G1 cells defined by mVenus-p27K(-), we have identified molecular features of quiescent cells. Quiescence is also an important feature of many types of stem cells, and mVenus-p27K(-)-transgenic mice enabled the detection of the quiescent cells with muscle stem cell markers in muscle in vivo. The mVenus-p27K(-) probe could be useful in investigating stem cells as well as quiescent cells. PMID:24500246

  18. A novel cell-cycle-indicator, mVenus-p27K-, identifies quiescent cells and visualizes G0-G1 transition

    NASA Astrophysics Data System (ADS)

    Oki, Toshihiko; Nishimura, Koutarou; Kitaura, Jiro; Togami, Katsuhiro; Maehara, Akie; Izawa, Kumi; Sakaue-Sawano, Asako; Niida, Atsushi; Miyano, Satoru; Aburatani, Hiroyuki; Kiyonari, Hiroshi; Miyawaki, Atsushi; Kitamura, Toshio

    2014-02-01

    The quiescent (G0) phase of the cell cycle is the reversible phase from which the cells exit from the cell cycle. Due to the difficulty of defining the G0 phase, quiescent cells have not been well characterized. In this study, a fusion protein consisting of mVenus and a defective mutant of CDK inhibitor, p27 (p27K-) was shown to be able to identify and isolate a population of quiescent cells and to effectively visualize the G0 to G1 transition. By comparing the expression profiles of the G0 and G1 cells defined by mVenus-p27K-, we have identified molecular features of quiescent cells. Quiescence is also an important feature of many types of stem cells, and mVenus-p27K--transgenic mice enabled the detection of the quiescent cells with muscle stem cell markers in muscle in vivo. The mVenus-p27K- probe could be useful in investigating stem cells as well as quiescent cells.

  19. A Comparison of Canopy Evapotranspiration for Maize and Two Perennial Grass Species Identified as Potential Bioenergy Crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perennial rhizomatous grasses (PRGs) that utilize the C4 photosynthetic pathway are considered one of the most promising vegetation types to accommodate a cellulosic feedstock for renewable energy production. The potential widespread use of biomass crops for renewable energy production has sparked n...

  20. Identifying food proteins with allergenic potential: Evolution of approaches to safety assessment and research to provide additional tools

    Microsoft Academic Search

    Gregory S. Ladics; MaryJane K. Selgrade

    2009-01-01

    A safety assessment process exists for genetically engineered crops that includes the evaluation of the expressed protein for allergenic potential. The objectives of this evaluation are twofold: (1) to protect allergic consumers from exposure to known allergenic or cross-reactive proteins, and (2) protect the general population from risks associated with the introduction of genes encoding proteins that are likely to

  1. A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor

    Microsoft Academic Search

    C-M Chung; R-Y Wang; J-W Chen; C S J Fann; H-B Leu; H-Y Ho; C-T Ting; T-H Lin; S-H Sheu; W-C Tsai; J-H Chen; Y-S Jong; S-J Lin; Y-T Chen; W-H Pan

    2010-01-01

    Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects.

  2. Linking molecular biomarkers with higher level condition indicators to identify effects of copper exposures on the endangered delta smelt (Hypomesus transpacificus).

    PubMed

    Connon, Richard E; Beggel, Sebastian; D'Abronzo, Leandro S; Geist, Juergen P; Pfeiff, Janice; Loguinov, Alexander V; Vulpe, Christopher D; Werner, Inge

    2011-02-01

    The delta smelt (Hypomesus transpacificus) is an endangered pelagic fish species endemic to the Sacramento-San Joaquin estuary (CA, USA), and considered an indicator of ecosystem health. Copper is a contaminant of concern in Californian waterways that may affect the development and survival of this endangered species. The experimental combination of molecular biomarkers with higher level effects may allow for interpretation of responses in a functional context that can be used to predict detrimental outcomes caused by exposure. A delta smelt microarray was developed and applied to screen for candidate molecular biomarkers that may be used in monitoring programs. Functional classifications of microarray responses were used along with quantitative polymerase chain reaction determining effects upon neuromuscular, digestive, and immune responses in Cu-exposed delta smelt. Differences in sensitivity were measured between juveniles and larvae (median lethal concentration = 25.2 and 80.4 µg/L Cu(2+), respectively). Swimming velocity declined with higher exposure concentrations in a dose-dependent manner (r = ?-0.911, p < 0.05), though was not statistically significant to controls. Genes encoding for aspartoacylase, hemopexin, ?-actin, and calcium regulation proteins were significantly affected by exposure and were functionally interpreted with measured swimming responses. Effects on digestion were measured by upregulation of chitinase and downregulation of amylase, whereas downregulation of tumor necrosis factor indicated a probable compromised immune system. Results from this study, and many others, support the use of functionally characterized molecular biomarkers to assess effects of contaminants in field scenarios. We thus propose that to attribute environmental relevance to molecular biomarkers, research should concentrate on their application in field studies with the aim of assisting monitoring programs. PMID:21072851

  3. Vibrational stark effects to identify ion-pairing and determine reduction potentials in electrolyte-free environments

    DOE PAGESBeta

    Mani, Tomoyasu [Brookhaven National Lab. (BNL), Upton, NY (United States); Grills, David C. [Brookhaven National Lab. (BNL), Upton, NY (United States); Miller, John R. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-01-28

    A recently-developed instrument for time-resolved infrared detection following pulse radiolysis has been used to measure the ?(C?N) IR band of the radical anion of a CN-substituted fluorene in tetrahydrofuran. Specific vibrational frequencies can exhibit distinct frequency shifts due to ion-pairing, which can be explained in the framework of the vibrational Stark effect. Measurements of the ratio of free ions and ion-pairs in different electrolyte concentrations allowed us to obtain an association constant and free energy change for ion-pairing. This new method has the potential to probe the geometry of ion-pairing and allows the reduction potentials of molecules to be determined in the absence of electrolyte in an environment of low dielectric constant.

  4. Vibrational stark effects to identify ion-pairing and determine reduction potentials in electrolyte-free environments

    DOE PAGESBeta

    Mani, Tomoyasu; Grills, David C.; Miller, John R.

    2015-01-28

    A recently-developed instrument for time-resolved infrared detection following pulse radiolysis has been used to measure the ?(C?N) IR band of the radical anion of a CN-substituted fluorene in tetrahydrofuran. Specific vibrational frequencies can exhibit distinct frequency shifts due to ion-pairing, which can be explained in the framework of the vibrational Stark effect. Measurements of the ratio of free ions and ion-pairs in different electrolyte concentrations allowed us to obtain an association constant and free energy change for ion-pairing. This new method has the potential to probe the geometry of ion-pairing and allows the reduction potentials of molecules to be determinedmore »in the absence of electrolyte in an environment of low dielectric constant.« less

  5. Identifying potential RNAi targets in grain aphid (Sitobion avenae F.) based on transcriptome profiling of its alimentary canal after feeding on wheat plants

    PubMed Central

    2013-01-01

    Background The grain aphid (Sitobion avenae F.) is a major agricultural pest which causes significant yield losses of wheat in China, Europe and North America annually. Transcriptome profiling of the grain aphid alimentary canal after feeding on wheat plants could provide comprehensive gene expression information involved in feeding, ingestion and digestion. Furthermore, selection of aphid-specific RNAi target genes would be essential for utilizing a plant-mediated RNAi strategy to control aphids via a non-toxic mode of action. However, due to the tiny size of the alimentary canal and lack of genomic information on grain aphid as a whole, selection of the RNAi targets is a challenging task that as far as we are aware, has never been documented previously. Results In this study, we performed de novo transcriptome assembly and gene expression analyses of the alimentary canals of grain aphids before and after feeding on wheat plants using Illumina RNA sequencing. The transcriptome profiling generated 30,427 unigenes with an average length of 664 bp. Furthermore, comparison of the transcriptomes of alimentary canals of pre- and post feeding grain aphids indicated that 5490 unigenes were differentially expressed, among which, diverse genes and/or pathways were identified and annotated. Based on the RPKM values of these unigenes, 16 of them that were significantly up or down-regulated upon feeding were selected for dsRNA artificial feeding assay. Of these, 5 unigenes led to higher mortality and developmental stunting in an artificial feeding assay due to the down-regulation of the target gene expression. Finally, by adding fluorescently labelled dsRNA into the artificial diet, the spread of fluorescence signal in the whole body tissues of grain aphid was observed. Conclusions Comparison of the transcriptome profiles of the alimentary canals of pre- and post-feeding grain aphids on wheat plants provided comprehensive gene expression information that could facilitate our understanding of the molecular mechanisms underlying feeding, ingestion and digestion. Furthermore, five novel and effective potential RNAi target genes were identified in grain aphid for the first time. This finding would provide a fundamental basis for aphid control in wheat through plant mediated RNAi strategy. PMID:23957588

  6. The useful potential of using existing data to uniquely identify predictable wind events and regimes, part 1

    NASA Technical Reports Server (NTRS)

    Trettel, D. W.; Aquino, J. T.; Piazza, T. R.; Taylor, L. E.; Trask, D. C.

    1982-01-01

    Correlations between standard meteorological data and wind power generation potential were developed. Combined with appropriate wind forecasts, these correlations can be useful to load dispatchers to supplement conventional energy sources. Hourly wind data were analyzed for four sites, each exhibiting a unique physiography. These sites are Amarillo, Texas; Ludington, Michigan; Montauk Point, New York; and San Gorgonio, California. Synoptic weather maps and tables are presented to illustrate various wind 'regimes' at these sites.

  7. Big data in chemical toxicity research: the use of high-throughput screening assays to identify potential toxicants.

    PubMed

    Zhu, Hao; Zhang, Jun; Kim, Marlene T; Boison, Abena; Sedykh, Alexander; Moran, Kimberlee

    2014-10-20

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound's ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

  8. Comparative Proteomics of Colon Cancer Stem Cells and Differentiated Tumor Cells Identifies BIRC6 as a Potential Therapeutic Target*

    PubMed Central

    Van Houdt, WJ; Emmink, BL; Pham, TV; Piersma, SR; Verheem, A; Vries, RG; Fratantoni, SA; Pronk, A; Clevers, H; Borel Rinkes, IHM; Jimenez, CR; Kranenburg, O

    2011-01-01

    Patients with liver metastases from colon carcinoma show highly variable responses to chemotherapy and tumor recurrence is frequently observed. Therapy-resistant cancer stem cells have been implicated in drug resistance and tumor recurrence. However, the factors determining therapy resistance and tumor recurrence are poorly understood. The aim of this study was to gain insight into these mechanisms by comparing the proteomes of patient-derived cancer stem cell cultures and their differentiated isogenic offspring. We established colonosphere cultures derived from resection specimens of liver metastases in patients with colon cancer. These colonospheres, enriched for colon cancer stem cells, were used to establish isogenic cultures of stably differentiated nontumorigenic progeny. Proteomics based on one-dimensional gel electrophoresis coupled to nano liquid chromatography tandem MS was used to identify proteome differences between three of these paired cultures. The resulting data were analyzed using Ingenuity Pathway Software. Out of a total data set of 3048 identified proteins, 32 proteins were at least twofold up-regulated in the colon cancer stem cells when compared with the differentiated cells. Pathway analysis showed that “cell death ” regulation is strikingly different between the two cell types. Interestingly, one of the top-up-regulated proteins was BIRC6, which belongs to the class of Inhibitor of Apoptosis Proteins. Knockdown of BIRC6 sensitized colon cancer stem cells against the chemotherapeutic drugs oxaliplatin and cisplatin. This study reveals that differentiation of colon cancer stem cells is accompanied by altered regulation of cell death pathways. We identified BIRC6 as an important mediator of cancer stem cell resistance against cisplatin and oxaliplatin. Targeting BIRC6, or other Inhibitors of Apoptosis Proteins, may help eradicating colon cancer stem cells. PMID:21788403

  9. Quantifying the relative importance and potential interactive effects of multiple indices when predicting fire risk and severity in the Western US

    Microsoft Academic Search

    A. Keyser; A. L. Westerling

    2010-01-01

    A long history of fire suppression in the western United States has interrupted the fire regimes of many forest types. This interruption has significantly changed forest structure and ecological function and led to increasingly uncharacteristic fires in terms of size and severity. This project investigated the potential for predicting forest fire severity across the Western US. Identifying areas at risk

  10. Stable isotopes as indicators of water and salinity sources in a southeast Australian coastal wetland: identifying relict marine water, and implications for future change

    NASA Astrophysics Data System (ADS)

    Currell, Matthew J.; Dahlhaus, Peter; , Hiroyuki, Ii

    2015-03-01

    The Lake Connewarre Complex is an internationally protected wetland in southeast Australia, undergoing increasing environmental change due to urbanisation. Stable isotopes of water (?18O and ?2H) and other geochemical indicators were used to assess sources of water and salinity in the shallow groundwater and surface-water systems, and to better understand groundwater/surface-water interactions. While much of the shallow groundwater is saline (from 1.27 to 50.3 g/L TDS) with overlapping salinities across water groups, stable isotopes allow clear delineation of two distinct sources of water and salinity: marine water with ?18O between -1.4 and +1.3 ‰ and ion ratios characteristic of seawater; and meteoric water with ?18O between -6.1 and -3.6 ‰ containing cyclic salts, probably concentrated by plant transpiration. Groundwater bodies in shallow sediments beneath the wetlands have salinities and stable isotopic compositions intermediate between fresh wetland surface water and a marine water end-member. This marine-type water is likely relict seawater emplaced when the wetlands were connected to the estuary, prior to modern river regulation. Freshwater input to underlying groundwater is a recent consequence of this regulation. Future predicted changes such as increased stormwater inflow, will increase rates of freshwater leakage to shallow groundwater, favouring the proliferation of exotic reed species.

  11. 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.

  12. Rapid, potentially automatable, method extract biomarkers for HPLC/ESI/MS/MS to detect and identify BW agents

    SciTech Connect

    White, D.C. [Univ. of Tennessee, Knoxville, TN (United States). Center for Environmental Biotechnology]|[Oak Ridge National Lab., TN (United States). Environmental Science Div.; Burkhalter, R.S.; Smith, C. [Univ. of Tennessee, Knoxville, TN (United States). Center for Environmental Biotechnology; Whitaker, K.W. [Microbial Insights, Inc., Rockford, TN (United States)

    1997-12-31

    The program proposes to concentrate on the rapid recovery of signature biomarkers based on automated high-pressure, high-temperature solvent extraction (ASE) and/or supercritical fluid extraction (SFE) to produce lipids, nucleic acids and proteins sequentially concentrated and purified in minutes with yields especially from microeukaryotes, Gram-positive bacteria and spores. Lipids are extracted in higher proportions greater than classical one-phase, room temperature solvent extraction without major changes in lipid composition. High performance liquid chromatography (HPLC) with or without derivatization, electrospray ionization (ESI) and highly specific detection by mass spectrometry (MS) particularly with (MS){sup n} provides the detection, identification and because the signature lipid biomarkers are both phenotypic as well as genotypic biomarkers, insights into potential infectivity of BW agents. Feasibility has been demonstrated with detection, identification, and determination of infectious potential of Cryptosporidium parvum at the sensitivity of a single oocyst (which is unculturable in vitro) and accurate identification and prediction, pathogenicity, and drug-resistance of Mycobacteria spp.

  13. 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

  14. Persistence of somatic and F-specific coliphages, potential indicators of fecal contamination, on spinach foliar tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Recent outbreaks of foodborne illness have been linked to consumption of fresh leafy greens. E. coli is commonly used as the indicator microorganism for fecal contamination on growing leafy greens. However, alternative microorganisms, such as coliphages, may be an alternative indicat...

  15. Use of identical assay conditions for cocaine analog binding and dopamine uptake to identify potential cocaine antagonists.

    PubMed

    Slusher, B S; Tiffany, C W; Olkowski, J L; Jackson, P F

    1997-10-25

    The addictive and euphorogenic properties of cocaine are thought to result from inhibition of the dopamine transporter (DAT). Recent evidence suggests that dopamine and cocaine bind to distinct sites on the transporter protein. Therefore it should be possible to design drugs which specifically inhibit cocaine recognition by the DAT while permitting the transporter to maintain its function of accumulating dopamine. One way to monitor such activity is to compare the inhibition constants of test agents for inhibition of radiolabelled dopamine uptake (Kiuptake) and inhibition of the binding of a cocaine ligand such as [3H]2 beta-carbomethoxy-3 beta-3 beta-(fluorophenyl)tropane (CFT; Kibind) and select for compounds with Kiuptake/Kibind ratios greater than unity. Because others have shown that compounds can exhibit Kiuptake/Kibind ratios greater than unity when the assays are performed under non-identical conditions, we have established these assays under identical conditions of time, temperature and buffer using a Chinese hamster ovary (CHO) cell line which stably expresses the human DAT. Kinetic and saturation analyses were performed on both assay and over 200 structurally diverse compounds were screened. Using identical assay parameters, several series of compounds having Kiuptake/Kibind ratios significantly greater than unity were identified. Such compounds include local anesthetics (procaine, dibucaine, tolperisone, dyclonine, diperodone), antipsychotic agents (10-(diethylaminopropionyl)phenothiazine), antidepressants (desipramine, imipramine, protriptyline), a diuretic (5-N-methyl-N-isobutyl-amilioride), an anticholinergic agent (prindinol), a PKC inhibitor (H-8), a calcium channel antagonist (loperamide) and an antimalarial compound (chloroquine). To our knowledge, even though these compounds exhibit low binding affinities (3-24 microM), they represent some of the most cocaine site-selective compounds identified to date using identical assay parameters. PMID:9330920

  16. Event-Related Potential (ERP) Indices of Infants' Recognition of Familiar and Unfamiliar Objects in Two and Three Dimensions

    ERIC Educational Resources Information Center

    Carver, Leslie J.; Meltzoff, Andrew N.; Dawson, Geraldine

    2006-01-01

    We measured infants' recognition of familiar and unfamiliar 3-D objects and their 2-D representations using event-related potentials (ERPs). Infants differentiated familiar from unfamiliar objects when viewing them in both two and three dimensions. However, differentiation between the familiar and novel objects occurred more quickly when infants…

  17. Airborne laser scanning: Exploratory data analysis indicates potential variables for classification of individual trees or forest stands according to species

    Microsoft Academic Search

    T. Moffiet; K. Mengersen; C. Witte; R. King; R. Denham

    2005-01-01

    Understanding your data through exploratory data analysis is a necessary first stage of data analysis particularly for observational data. The checking of data integrity and understanding the distributions, correlations and relationships between potentially important variables is a fundamental part of the analysis process prior to model development and hypothesis testing. In this paper, exploratory data analysis is used to assess

  18. Recycled water: Potential health risks from volatile organic compounds and use of 1,4-dichlorobenzene as treatment performance indicator

    Microsoft Academic Search

    Clemencia Rodriguez; Kathryn Linge; Palenque Blair; Francesco Busetti; Brian Devine; Paul Van Buynder; Philip Weinstein; Angus Cook

    Characterisation of the concentrations and potential health risks of chemicals in recycled water is important if this source of water is to be safely used to supplement drinking water sources. This research was conducted to: (i) determine the concentration of volatile organic compounds (VOCs) in secondary treated effluent (STE) and, post-reverse osmosis (RO) treatment and to; (ii) assess the health

  19. Koenigia Islandica (Iceland Purslane) — A Case Study of a Potential Indicator of Climate Change in the UK

    Microsoft Academic Search

    Barry Meatyard

    Koenigia islandica (Iceland purslane) is an annual arctic-subarctic species that is found in only two locations in the UK. On the Isle of Mull, Argyll, Scotland, it grows at the southerly limit of its W.European distribution. The habitat requirements of Koenigia are specialised. It is predicted that an annual species at the limit of its geographical range is potentially sensitive

  20. MicroRNA-224 is Readily Detectable in Urine of Individuals with Diabetes Mellitus and is a Potential Indicator of Beta-Cell Demise.

    PubMed

    Bacon, Siobhán; Engelbrecht, Britta; Schmid, Jasmin; Pfeiffer, Shona; Gallagher, Ross; McCarthy, Ailbhe; Burke, Marie; Concannon, Caoimhín; Prehn, Jochen H M; Byrne, Maria M

    2015-01-01

    MicroRNA (miRNA) are a class of non-coding, 19-25 nucleotide RNA critical for network-level regulation of gene expression. miRNA serve as paracrine signaling molecules. Using an unbiased array approach, we previously identified elevated levels of miR-224 and miR-103 to be associated with a monogenic form of diabetes; HNF1A-MODY. miR-224 is a novel miRNA in the field of diabetes. We sought to explore the role of miR-224 as a potential biomarker in diabetes, and whether such diabetes-associated-miRNA can also be detected in the urine of patients. Absolute levels of miR-224 and miR-103 were determined in the urine of n = 144 individuals including carriers of a HNF1A mutation, participants with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and normal controls. Expression levels were correlated with clinical and biochemical parameters. miR-224 was significantly elevated in the urine of carriers of a HNF1A mutation and participants with T1DM. miR-103 was highly expressed in urine across all diabetes cohorts when compared to controls. For both miR-224 and-103, we found a significant correlation between serum and urine levels (p < 0.01). We demonstrate that miRNA can be readily detected in the urine independent of clinical indices of renal dysfunction. We surmise that the differential expression levels of miR-224 in both HNF1A-MODY mutation carriers and T1DM may be an attempt to compensate for beta-cell demise. PMID:26110317

  1. MicroRNA-224 is Readily Detectable in Urine of Individuals with Diabetes Mellitus and is a Potential Indicator of Beta-Cell Demise

    PubMed Central

    Bacon, Siobhán; Engelbrecht, Britta; Schmid, Jasmin; Pfeiffer, Shona; Gallagher, Ross; McCarthy, Ailbhe; Burke, Marie; Concannon, Caoimhín; Prehn, Jochen H. M.; Byrne, Maria M.

    2015-01-01

    MicroRNA (miRNA) are a class of non-coding, 19–25 nucleotide RNA critical for network-level regulation of gene expression. miRNA serve as paracrine signaling molecules. Using an unbiased array approach, we previously identified elevated levels of miR-224 and miR-103 to be associated with a monogenic form of diabetes; HNF1A-MODY. miR-224 is a novel miRNA in the field of diabetes. We sought to explore the role of miR-224 as a potential biomarker in diabetes, and whether such diabetes-associated-miRNA can also be detected in the urine of patients. Absolute levels of miR-224 and miR-103 were determined in the urine of n = 144 individuals including carriers of a HNF1A mutation, participants with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and normal controls. Expression levels were correlated with clinical and biochemical parameters. miR-224 was significantly elevated in the urine of carriers of a HNF1A mutation and participants with T1DM. miR-103 was highly expressed in urine across all diabetes cohorts when compared to controls. For both miR-224 and-103, we found a significant correlation between serum and urine levels (p < 0.01). We demonstrate that miRNA can be readily detected in the urine independent of clinical indices of renal dysfunction. We surmise that the differential expression levels of miR-224 in both HNF1A-MODY mutation carriers and T1DM may be an attempt to compensate for beta-cell demise. PMID:26110317

  2. Efficacy of Quality Criteria to Identify Potentially Harmful Information: A Cross-sectional Survey of Complementary and Alternative Medicine Web Sites

    PubMed Central

    Walji, Muhammad; Sagaram, Smitha; Sagaram, Deepak; Meric-Bernstam, Funda; Johnson, Craig; Mirza, Nadeem Q

    2004-01-01

    Background Many users search the Internet for answers to health questions. Complementary and alternative medicine (CAM) is a particularly common search topic. Because many CAM therapies do not require a clinician's prescription, false or misleading CAM information may be more dangerous than information about traditional therapies. Many quality criteria have been suggested to filter out potentially harmful online health information. However, assessing the accuracy of CAM information is uniquely challenging since CAM is generally not supported by conventional literature. Objective The purpose of this study is to determine whether domain-independent technical quality criteria can identify potentially harmful online CAM content. Methods We analyzed 150 Web sites retrieved from a search for the three most popular herbs: ginseng, ginkgo and St. John's wort and their purported uses on the ten most commonly used search engines. The presence of technical quality criteria as well as potentially harmful statements (commissions) and vital information that should have been mentioned (omissions) was recorded. Results Thirty-eight sites (25%) contained statements that could lead to direct physical harm if acted upon. One hundred forty five sites (97%) had omitted information. We found no relationship between technical quality criteria and potentially harmful information. Conclusions Current technical quality criteria do not identify potentially harmful CAM information online. Consumers should be warned to use other means of validation or to trust only known sites. Quality criteria that consider the uniqueness of CAM must be developed and validated. PMID:15249270

  3. Identifying potential receptors and routes of contaminant exposure in the traditional territory of the Ouje-Bougoumou Cree: land use and a geographical information system.

    PubMed

    Tsuji, Leonard J S; Manson, Harry; Wainman, Bruce C; Vanspronsen, Eric P; Shecapio-Blacksmith, Joseph; Rabbitskin, Tommy

    2007-04-01

    Great concern has been raised with respect to the 13 traplines that constitute the traditional territory of the Ouje-Bougoumou Cree located in the James Bay region of northern Quebec, Canada, with respect to mine wastes originating from three local mines. As a result, an "Integrative Risk Assessment" was initiated consisting of three interrelated components: a comprehensive human health study, an assessment of the existing ecological/environmental database, and a land use/potential sites of concern study. In this paper, we document past and present land use in the traditional territory of the Ouje-Bougoumou Cree for 72 heads of households, including 13 tallymen, and use a Geographic Information System (GIS) to layer harvest/hunting and gathering/collecting data over known mining areas and potential sites of concern. In this way, potential receptors of contamination and routes of human exposure were identified. Areas of overlap with respect to land use activity and mining operations were relatively extensive for certain harvesting activities (e.g., beaver, Castor canadensis and various species of game birds), less so for fish harvesting (all species) and water collection, and relatively restrictive for large mammal harvesting and collection of fire wood (and other collection activities). Potential receptors of contaminants associated with mining activity (e.g., fish and small mammals) and potential routes of exposure (e.g., ingestion of contaminated game and drinking of contaminated water) were identified. PMID:16897501

  4. Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure.

    PubMed

    Bourdon, Julie A; Williams, Andrew; Kuo, Byron; Moffat, Ivy; White, Paul A; Halappanavar, Sabina; Vogel, Ulla; Wallin, Håkan; Yauk, Carole L

    2013-01-01

    New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 ?g Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose-response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment. PMID:23146762

  5. The stability of adenosine deaminase and adenosine monophosphate (AMP) deaminase as potential spoilage indicators for postmortem ice stored shrimp 

    E-print Network

    Cheuk, Wai Lun

    1978-01-01

    indicated the impor- tance of bacterial ammonia production. ACKNOWLEDGMENTS Sincere gratitude is expressed to Dr. Ranzell Nickelson, II and Dr. Gunner Finne for suggesting the research program. I am greatly indebted to them for their generous support.... The bacteriology of Gulf coast shrimp. 4. Bacteriological, chemical and organoleptical changes with ice storage. Food Technol. 6:125. Cobb III, B. F. , Alaniz, I. and Thompson, C. A. , Jr. 1973a. Biochemical and microbial studies on shrimp: Voltile nitrogen...

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

    PubMed

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

    2013-03-01

    Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)]. PMID:23065025

  7. Proteomics of Genetically Engineered Mouse Mammary Tumors Identifies Fatty Acid Metabolism Members as Potential Predictive Markers for Cisplatin Resistance*

    PubMed Central

    Warmoes, Marc; Jaspers, Janneke E.; Xu, Guotai; Sampadi, Bharath K.; Pham, Thang V.; Knol, Jaco C.; Piersma, Sander R.; Boven, Epie; Jonkers, Jos; Rottenberg, Sven; Jimenez, Connie R.

    2013-01-01

    In contrast to various signatures that predict the prognosis of breast cancer patients, markers that predict chemotherapy response are still elusive. To detect such predictive biomarkers, we investigated early changes in protein expression using two mouse models for distinct breast cancer subtypes who have a differential knock-out status for the breast cancer 1, early onset (Brca1) gene. The proteome of cisplatin-sensitive BRCA1-deficient mammary tumors was compared with that of cisplatin-resistant mammary tumors resembling pleomorphic invasive lobular carcinoma. The analyses were performed 24 h after administration of the maximum tolerable dose of cisplatin. At this time point, drug-sensitive BRCA1-deficient tumors showed DNA damage, but cells were largely viable. By applying paired statistics and quantitative filtering, we identified highly discriminatory markers for the sensitive and resistant model. Proteins up-regulated in the sensitive model are involved in centrosome organization, chromosome condensation, homology-directed DNA repair, and nucleotide metabolism. Major discriminatory markers that were up-regulated in the resistant model were predominantly involved in fatty acid metabolism, such as fatty-acid synthase. Specific inhibition of fatty-acid synthase sensitized resistant cells to cisplatin. Our data suggest that exploring the functional link between the DNA damage response and cancer metabolism shortly after the initial treatment may be a useful strategy to predict the efficacy of cisplatin. PMID:23397111

  8. Gene expression profiling and real-time PCR analyses identify novel potential cancer-testis antigens in multiple myeloma

    PubMed Central

    Condomines, Maud; Hose, Dirk; Rème, Thierry; Requirand, Guilhem; Hundemer, Michael; Schoenhals, Matthieu; Goldschmidt, Hartmut; Klein, Bernard

    2009-01-01

    Cancer-testis (CT) antigens are attractive targets for immunotherapeutic strategies since they are aberrantly expressed in malignant cells and not, or in limited number, in somatic tissues, except germ cells. To identify novel CT genes in multiple myeloma, we used Affymetrix HG-U133 gene expression profiles of 5 testis, 64 primary myeloma cell (MMC) and 24 normal tissue (NT) samples. A 5-filter method was developed to keep known CT genes while deleting non-CT genes. Starting from 44928 probe sets, including probe sets for 18 previously-described CT genes, we have obtained 82 genes expressed in MMC and testis and not detected in more than 6 NT. This list includes 14 of the 18 known CT genes and 68 novel putative CT genes. Real-time RT-PCR was performed for 34 genes in 12 NT, 5 MMC samples and one sample of 5 pooled testes. It has validated the CT status of 23/34 genes (67%). We found one novel “testis-restricted” gene (expression in testis and tumor only) – TEX14 –, 8 “tissue-restricted” (mRNA detected in 1 or 2 non-gametogenic tissues), and 7 “differentially expressed” (mRNA detected in three to six non-gametogenic tissues) CT genes. Further studies are warranted to determine the immunogenicity of these novel CT antigen candidates. PMID:19542363

  9. Global biochemical profiling identifies ?-hydroxypyruvate as a potential mediator of type 2 diabetes in mice and humans.

    PubMed

    Zhang, Sheng; Wang, Songyan; Puhl, Matthew D; Jiang, Xuntian; Hyrc, Krzysztof L; Laciny, Erin; Wallendorf, Michael J; Pappan, Kirk L; Coyle, Joseph T; Wice, Burton M

    2015-04-01

    Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are incretins secreted by respective K and L enteroendocrine cells after eating and amplify glucose-stimulated insulin secretion (GSIS). This amplification has been termed the "incretin response." To determine the role(s) of K cells for the incretin response and type 2 diabetes mellitus (T2DM), diphtheria toxin-expressing (DT) mice that specifically lack GIP-producing cells were backcrossed five to eight times onto the diabetogenic NONcNZO10/Ltj background. As in humans with T2DM, DT mice lacked an incretin response, although GLP-1 release was maintained. With high-fat (HF) feeding, DT mice remained lean but developed T2DM, whereas wild-type mice developed obesity but not diabetes. Metabolomics identified biochemicals reflecting impaired glucose handling, insulin resistance, and diabetes complications in prediabetic DT/HF mice. ?-Hydroxypyruvate and benzoate levels were increased and decreased, respectively, suggesting ?-hydroxypyruvate production from d-serine. In vitro, ?-hydroxypyruvate altered excitatory properties of myenteric neurons and reduced islet insulin content but not GSIS. ?-Hydroxypyruvate-to-d-serine ratios were lower in humans with impaired glucose tolerance compared with normal glucose tolerance and T2DM. Earlier human studies unmasked a neural relay that amplifies GIP-mediated insulin secretion in a pattern reciprocal to ?-hydroxypyruvate-to-d-serine ratios in all groups. Thus, K cells may maintain long-term function of neurons and ?-cells by regulating ?-hydroxypyruvate levels. PMID:25368100

  10. Indicators and optical configuration for simultaneous high-resolution recording of membrane potential and intracellular calcium using laser scanning microscopy

    Microsoft Academic Search

    Andrew Bullen; Peter Saggau

    1998-01-01

    The instrumental design and experimental conditions for high-speed, simultaneous optical recording of membrane potential\\u000a and intracellular Ca2+ with subcellular resolution are presented. This method employs an extended version of a high-speed, random-access, laser-scanning\\u000a fluorescence microscope designed to record fast physiological signals from small neuronal structures with high spatiotemporal\\u000a resolution (Bullen, Patel, Saggau, Biophys J 73:477–491, 1997). With this instrument, imaging

  11. A thermal profile method to identify potential ground-water discharge areas and preferred salmonid habitats for long river reaches

    USGS Publications Warehouse

    Vaccaro, J.J.; Maloy, K.J.

    2006-01-01

    The thermal regime of riverine systems is a major control on aquatic ecosystems. Ground water discharge is an important abiotic driver of the aquatic ecosystem because it provides preferred thermal structure and habitat for different types of fish at different times in their life history. In large diverse river basins with an extensive riverine system, documenting the thermal regime and ground-water discharge is difficult and problematic. A method was developed to thermally profile long (5-25 kilometers) river reaches by towing in a Lagrangian framework one or two probes that measure temperature, depth, and conductivity. One probe is towed near the streambed and, if used, a second probe is towed near the surface. The probes continuously record data at 1-3-second intervals while a Global Positioning System logs spatial coordinates. The thermal profile provides valuable information about spatial and temporal variations in habitat, and, notably, indicates ground-water discharge areas. This method was developed and tested in the Yakima River Basin, Washington, in summer 2001 during low flows in an extreme drought year. The temperature profile comprehensively documents the longitudinal distribution of a river's temperature regime that cannot be captured by fixed station data. The example profile presented exhibits intra-reach diversity that reflects the many factors controlling the temperature of a parcel of water as it moves downstream. Thermal profiles provide a new perspective on riverine system temperature regimes that represent part of the aquatic habitat template for lotic community patterns.

  12. Biochemical and transcription analysis of acetohydroxyacid synthase isoforms in Mycobacterium tuberculosis identifies these enzymes as potential targets for drug development.

    PubMed

    Singh, Vinayak; Chandra, Deepak; Srivastava, Brahm S; Srivastava, Ranjana

    2011-01-01

    Acetohydroxyacid synthase (AHAS) is a biosynthetic enzyme essential for de novo synthesis of branched-chain amino acids. The genome sequence of Mycobacterium tuberculosis revealed genes encoding four catalytic subunits, ilvB1 (Rv3003c), ilvB2 (Rv3470c), ilvG (Rv1820) and ilvX (Rv3509c), and one regulatory subunit, ilvN (Rv3002c), of AHAS. All these genes were found to be expressed in M. tuberculosis growing in vitro. Each AHAS subunit gene was cloned and expressed in Escherichia coli. AHAS activity of IlvB1 and IlvG was found in cell-free lysates and with recombinant purified proteins. Kinetic studies with purified IlvG revealed positive cooperativity towards substrate and cofactors. To understand the role of the catalytic subunits in the biology of M. tuberculosis, expression of AHAS genes was analysed in different physiological conditions. ilvB1, ilvB2 and ilvG were differentially expressed. The role of ilvB1 in persistence is known, but the upregulation of ilvB2 and ilvG in extended stationary phase, ex vivo, and in acid stress and hypoxic environments, suggests the relevance of AHAS enzymes in the metabolism and survival of M. tuberculosis by functioning as catabolic AHAS. These enzymes are therefore potential targets for drug development. PMID:20884690

  13. Aldosterone receptor antagonists in cardiovascular disease: a review of the recent literature and insight into potential future indications.

    PubMed

    Markowitz, Mindy; Messineo, Frank; Coplan, Neil L

    2012-10-01

    Randomized controlled trials demonstrate the efficacy of aldosterone receptor antagonists (spironolactone and eplerenone) as a useful pharmacologic intervention specifically in patients with New York Heart Association (NYHA) class III and IV heart failure, in patients with an ejection fraction <40% after myocardial infarction, and most recently in patients with mildly symptomatic heart failure. However, aldosterone receptor antagonists may be beneficial in a broader patient population. Aldosterone receptor antagonists can potentially serve as an antiarrhythmic pharmacologic agent for atrial and ventricular arrhythmias, an anti-ischemic medication in coronary artery disease through prevention of myocardial fibrosis and vascular damage, and as an agent in people with asymptomatic and mild heart failure (NYHA classes I and II) and diastolic heart failure. However, many clinicians remain reluctant to prescribe this highly efficacious pharmacologic therapy for a variety of reasons, including concerns about polypharmacy and hyperkalemia. Recent observational analysis demonstrates that less than one-third of eligible patients hospitalized with heart failure actually received aldosterone antagonist therapy. This article will review the current and potential future uses of aldosterone receptor antagonists across the entire spectrum of cardiovascular disease. The authors have no funding, financial relationships, or conflicts of interest to disclose. PMID:22778046

  14. Global Health Education: a cross-sectional study among German medical students to identify needs, deficits and potential benefits (Part 2 of 2: Knowledge gaps and potential benefits)

    PubMed Central

    2010-01-01

    Background In Germany, educational deficits or potential benefits involved in global health education have not been analysed till now. Objective We assess the importance medical students place on learning about social determinants of health (SDH) and assess their knowledge of global health topics in relation to (i) mobility patterns, their education in (ii) tropical medicine or (iii) global health. Methods Cross-sectional study among medical students from all 36 medical schools in Germany using a web-based, semi-structured questionnaire. Participants were recruited via mailing-lists of students' unions, all medical students registered in 2007 were eligible to participate in the study. We captured international mobility patterns, exposure to global health learning opportunities and attitudes to learning about SDH. Both an objective and subjective knowledge assessment were performed. Results 1126 online-replies were received and analysed. International health electives in developing countries correlated significantly with a higher importance placed on all provided SDH (p ? 0.006). Participation in tropical medicine (p < 0.03) and global health courses (p < 0.02) were significantly associated with a higher rating of 'culture, language and religion' and the 'economic system'. Global health trainings correlated with significantly higher ratings of the 'educational system' (p = 0.007) and the 'health system structure' (p = 0.007), while the item 'politics' was marginally significant (p = 0.053). In the knowledge assessment students achieved an average score of 3.6 (SD 1.5; Mdn 4.0), 75% achieved a score of 4.0 or less (Q25 = 3.0; Q75 = 4.0) from a maximum achievable score of 8.0. A better performance was associated with international health electives (p = 0.032), participation in tropical medicine (p = 0.038) and global health (p = 0.258) courses. Conclusion The importance medical students in our sample placed on learning about SDH strongly interacts with students' mobility, and participation in tropical medicine and global health courses. The knowledge assessment revealed deficits and outlined needs to further analyse education gaps in global health. Developing concerted educational interventions aimed at fostering students' engagement with SDH could make full use of synergy effects inherent in student mobility, tropical medicine and global health education. PMID:20932278

  15. [The significance of glucose positive coliform bacteria and potentially pathogenic bacteria as an indicator of epidemiological safety of tap water].

    PubMed

    Zhuravlev, P V; Aleshnya, V V; Panasovets, O P; Morozova, A A; Artemova, T Z; Talaeva, Yu G; Zagaynova, A V

    2013-01-01

    Due to intensive anthropogenic pollution of water environment generally accepted indicators of epidemic security of water bodies--common bacteria (CB) and thermotolerant coliform bacteria (TCB) do not always permit to obtain an objective characterization of bacterial contamination of tap water. From the point of view of authors the integral index--glucose positive coliform bacteria most adequately reflect the sanitary-hygienic and epidemiological situation of water bodies. In monitoring for bacterial quality of tap water it is advisable to determine glucose positive coliform bacteria, that will provide the relevance of estimation of the epidemiological safety of water use. According to the method developed by the authors the calculation of the index of population risk of acute intestinal infections (AHI) occurrence in dependence on the quality of tap water in Azov and Tsimlyansk towns. PMID:23805697

  16. [The value of glucose-positive coliform bacteria and potentially pathogenic bacteria as indicators of epidemiological safety of tap water].

    PubMed

    Zhuravlev, P V; Aleshnia, V V; Panasovets, O P; Morozova, A A; Artemova, T Z; Talaeva, Iu G; Zaga?nova, A V; Gipp, E K

    2012-01-01

    Due to intensive anthropogenic pollution of water environment generally accepted indicators of epidemic security of water bodies - common bacteria and thermotolerant coliform bacteria do not always permit to obtain an objective characterization of bacterial contamination of tap water. From the point of view of authors the integral index - glucose positive coliform bacteria most adequately reflect the sanitary-hygienic and epidemiological situation of water bodies. In monitoring for bacterial quality of tap water it is advisable to determine glucose positive coliform bacteria, that will provide the relevance of estimation of the epidemiological safety of water use. According to the method developed by the authors the calculation of the index of population risk of acute intestinal infections occurrence in dependence on the quality of tap water in Azov and Tsimlyansk towns. PMID:23458011

  17. Increased serum proMMP-3 in inflammatory arthritides: a potential indicator of synovial inflammatory monokine activity.

    PubMed Central

    Taylor, D J; Cheung, N T; Dawes, P T

    1994-01-01

    OBJECTIVE--To investigate if the increased concentrations of stromelysin (MMP-3) found in the synovial fluid (SF) of patients with various arthritides reflect the concentrations in the circulation. METHODS--Using a double antibody ELISA, we have measured proMMP-3 concentrations in sera from these patient groups and in others with a heightened acute phase response (APR) as a result of multiple organ failure. RESULTS--The median serum concentration of proMMP-3 was increased by up to ninefold in the inflammatory arthritides, but not in osteoarthritis or in patients with a heightened APR resulting from a non-chronic inflammatory condition. CONCLUSION--In chronic inflammatory diseases such as rheumatoid arthritis, serum proMMP-3 may prove to be a more specific indicator of monokine activity than currently available serum markers. PMID:7826140

  18. Evaluating the Response of Biological Assemblages as Potential Indicators for Restoration Measures in an Intermittent Mediterranean River

    NASA Astrophysics Data System (ADS)

    Hughes, Samantha Jane; Santos, Jose; Ferreira, Teresa; Mendes, Ana

    2010-08-01

    Bioindicators are essential for detecting environmental degradation and for assessing the success of river restoration initiatives. River restoration projects require the identification of environmental and pressure gradients that affect the river system under study and the selection of suitable indicators to assess habitat quality before, during and after restoration. We assessed the response of benthic macroinvertebrates, fish, bird and macrophyte assemblages to environmental and pressure gradients from sites situated upstream and downstream of a cofferdam on the River Odelouca, an intermittent Mediterranean river in southwest Portugal. The Odelouca will be permanently dammed in 2010. Principal Component Analyses (PCA) of environmental and pressure variables revealed that most variance was explained by environmental factors that clearly separated sites upstream and downstream of the partially built cofferdam. The pressure gradient describing physical impacts to the banks and channel as a result of land use change was less distinct. Redundancy Analysis revealed significant levels of explained variance to species distribution patterns in relation to environmental and pressure variables for all 4 biological assemblages. Partial Redundancy analyses revealed high levels of redundancy for pH between groups and that the avifauna was best associated with pressures acting upon the system. Patterns in invertebrates and fish were associated with descriptors of habitat quality, although fish distribution patterns were affected by reduced connectivity. Procrustean and RELATE (Mantel test) analyses gave broadly similar results and supported these findings. We give suggestions on the suitability of key indicator groups such as benthic macroinvertebrates and endemic fish species to assess in stream habitat quality and appropriate restoration measures, such as the release of peak flow patterns that mimic intermittent Mediterranean systems to combat habitat fragmentation and reduced connectivity.

  19. Evaluating the response of biological assemblages as potential indicators for restoration measures in an intermittent Mediterranean river.

    PubMed

    Hughes, Samantha Jane; Santos, Jose; Ferreira, Teresa; Mendes, Ana

    2010-08-01

    Bioindicators are essential for detecting environmental degradation and for assessing the success of river restoration initiatives. River restoration projects require the identification of environmental and pressure gradients that affect the river system under study and the selection of suitable indicators to assess habitat quality before, during and after restoration. We assessed the response of benthic macroinvertebrates, fish, bird and macrophyte assemblages to environmental and pressure gradients from sites situated upstream and downstream of a cofferdam on the River Odelouca, an intermittent Mediterranean river in southwest Portugal. The Odelouca will be permanently dammed in 2010. Principal Component Analyses (PCA) of environmental and pressure variables revealed that most variance was explained by environmental factors that clearly separated sites upstream and downstream of the partially built cofferdam. The pressure gradient describing physical impacts to the banks and channel as a result of land use change was less distinct. Redundancy Analysis revealed significant levels of explained variance to species distribution patterns in relation to environmental and pressure variables for all 4 biological assemblages. Partial Redundancy analyses revealed high levels of redundancy for pH between groups and that the avifauna was best associated with pressures acting upon the system. Patterns in invertebrates and fish were associated with descriptors of habitat quality, although fish distribution patterns were affected by reduced connectivity. Procrustean and RELATE (Mantel test) analyses gave broadly similar results and supported these findings. We give suggestions on the suitability of key indicator groups such as benthic macroinvertebrates and endemic fish species to assess in stream habitat quality and appropriate restoration measures, such as the release of peak flow patterns that mimic intermittent Mediterranean systems to combat habitat fragmentation and reduced connectivity. PMID:20640421

  20. 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 highlighting attractive objects of interest for future ground-based observation opportunities.

  1. 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.; Benner, L. A. M.; Drake, B. G.; Friedensen, V. P.

    2012-01-01

    Over the past several years, much attention has been focused on the human exploration of near-Earth asteroids (NEAs). Two independent NASA studies examined the feasibility of sending piloted missions to NEAs [1, 2], and in 2009, the Augustine Commission identified NEAs as high profile destinations for human exploration missions beyond the Earth-Moon system [3]. More recently the current U.S. presidential administration directed NASA to include NEAs as destinations for future human exploration with the goal of sending astronauts to a NEA in the mid to late 2020s. This directive became part of the official National Space Policy of the United States of America as of June 28, 2010 [4]. Detailed planning for such deep space exploration missions and identifying potential NEAs as targets for human spaceflight requires selecting objects from the ever growing list of newly discovered NEAs. Hence NASA developed and implemented the Near-Earth Object (NEO) Human Space Flight (HSF) Accessible Target Study (NHATS), which identifies potential candidate objects on the basis of defined dynamical trajectory performance constraints.

  2. Description and evaluation of imposex in Strombus canarium Linnaeus, 1758 (Gastropoda, Strombidae): a potential bio-indicator of tributyltin pollution.

    PubMed

    Cob, Zaidi Che; Arshad, Aziz; Bujang, Japar Sidik; Abd Ghaffar, Mazlan

    2011-07-01

    Strombus canarium Linnaeus, 1758 is an important gastropod species within the study area and was traditionally collected for food by the locals. The objective of the present study is to assess the incidence of imposex and its severity in this species. Adult conchs were sampled during their main reproductive period, from October 2005 to January 2006, at Sungai Pulai estuary, Johor Straits, Malaysia. A total of 32.81% of adult females showed imposex characteristics, with varying degrees of severity though. The relative penis size (RPS) index ranged from 1.74 to 33.29 (mean = 13.40 ± 2.27, n = 21), while the relative penis length (RPL) index ranged from 6.28 to 55.19 (mean = 25.83 ± 3.33, n = 21). The use of vas deferens sequence (VDS) index was however cannot be applied as the presence of egg groove obscured any vas deferens development in affected females. Sequence of imposex (male penis) development in female conch, from merely a small stump to an advance male penis homologous was therefore carefully analyzed and described, and an alternative imposex classification scheme was proposed. S. canarium can be a good indicator for monitoring of organotin pollution within the study area. However, more studies are needed in order to further develop and test its validity and application, such as its correlation with levels of pollutant within the tissues and the environment, as well as its application on other Strombus species. PMID:20824325

  3. Integrated use of biomarkers and condition indices in mussels (Mytilus galloprovincialis) for monitoring pollution and development of biomarker index to assess the potential toxic of coastal sites.

    PubMed

    Benali, Imene; Boutiba, Zitouni; Merabet, Amina; Chèvre, Nathalie

    2015-06-15

    In this study, we are interested in spatial and temporal variations of the biological and physiological responses of mussels collected from contrasting marine sites regarding their levels of pollution. We measured both the conditions indices and the enzymatic biomarker expression: acetylcholinesterase (AChE), catalase (CAT) and glutathione S-transferase (GST) activity. The enzymatic biomarkers were chosen because they respond to environmental stress. Results show a significant interactions between biomarker variations and conditions indices in the industrial harbor site throughout the seasons. But no significant changes in the reference site. Furthermore, we classified the sites along the seasons according to their potential ecotoxicity, calculated based on the sum of the normalised values of the biomarkers. The results show a very high biomarker index in the impacted site with irregular changes between seasons. This biomarker index is therefore a valuable tool that could be used to classify the toxic potential of coastal sites. PMID:25865346

  4. Highly efficient, selective, sensitive and stability indicating RP-HPLC-UV method for the quantitative determination of potential impurities and characterization of four novel impurities in eslicarbazepine acetate active pharmaceutical ingredient by LC/ESI-IT/MS/MS.

    PubMed

    Thomas, Saji; Bharti, Amber; Maddhesia, Pawan Kumar; Shandilya, Sanjeev; Agarwal, Ashutosh; Dharamvir; Biswas, Sujay; Bhansal, Vikas; Gupta, Ashish Kumar; Tewari, Praveen Kumar; Mathela, Chandra S

    2012-03-01

    A novel, sensitive, selective and stability indicating LC-UV method was developed for the determination of potential impurities of eslicarbazepine acetate. High performance liquid chromatographic investigation of eslicarbazepine acetate laboratory sample revealed the presence of several impurities. Three impurities were characterized rapidly and four impurities were found to be unknown. The unknown impurities were identified by liquid chromatography coupled with electrospray ionization, ion trap mass spectrometry (LC/ESI-IT/MS/MS). Structural confirmation of these impurities was unambiguously carried out by synthesis followed by characterization using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (FT-IR) and mass spectrometry (MS). Based on the spectroscopic, spectrometric and elemental analysis data unknown impurities were characterized as 5-acetyl-5,11-dihydro-10H-dibenzo [b,f]azepin-10-one, N-acetyl-5H-dibenzo[b,f]azepine-5-carboxamide, 5-acetyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate and 5-acetyl-5H-dibenzo[b,f]azepin-10-yl acetate. The newly developed LC-UV method was validated according to ICH guidelines considering eleven potential impurities and four new impurities to demonstrate specificity, precision, linearity, accuracy and stability indicating nature of the method. The newly developed method was found to be highly efficient, selective, sensitive and stability indicating. A plausible pathway for the formation of four new impurities is proposed. PMID:22178334

  5. Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion

    PubMed Central

    Gallardo, Viviana E.; Varshney, Gaurav K.; Lee, Minnkyong; Bupp, Sujata; Xu, Lisha; Shinn, Paul; Crawford, Nigel P.; Inglese, James; Burgess, Shawn M.

    2015-01-01

    ABSTRACT In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, high-throughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds. PMID:25810455

  6. Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion.

    PubMed

    Gallardo, Viviana E; Varshney, Gaurav K; Lee, Minnkyong; Bupp, Sujata; Xu, Lisha; Shinn, Paul; Crawford, Nigel P; Inglese, James; Burgess, Shawn M

    2015-06-01

    In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, high-throughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds. PMID:25810455

  7. Subtractive hybridization analysis of gastric diseases-associated Helicobacter pylori identifies peptidyl-prolyl isomerase as a potential marker for gastric cancer.

    PubMed

    Gong, Yue-Hua; Chen, Moye; Xu, Ying; Dong, Nannan; Sang, Zhikun; Liu, Jun; Yuan, Yuan

    2011-07-01

    Helicobacter pylori, a microaerophilic Gram-negative bacterium, is known to cause chronic gastritis, peptic ulcer and gastric cancer. Genes that are present in certain isolates may determine strain-specific traits such as disease association and drug resistance. In order to understand the pathogenic mechanisms of gastric diseases, identify molecular markers of the diseases associated with H. pylori strains and provide clues for target treatment of H. pylori-related diseases, a subtracted DNA library was constructed from a gastric cancer-associated H. pylori strain and a superficial gastritis-associated H. pylori strain by suppression subtractive hybridization. The presence of gastric cancer-specific genes was identified by dot blot hybridization, DNA sequencing and PCR-based screening. Twelve gastric cancer-specific high-copy genes and nine low-copy genes were found in gastric cancer compared with the superficial gastritis strain. These genes were confirmed by PCR analysis of H. pylori isolates. Notably, peptidyl-prolyl cis-trans isomerase (PPIase) was detected positively in 11 out of 22 (50%) gastric cancer-associated H. pylori strains. In contrast, <24% of the H. pylori strains from superficial gastritis showed positive results. Given the potential role of PPIases in cell growth, apoptosis and oncogenic transformation, our results suggest that PPIase may represent a novel marker and potential therapeutic target for gastric cancer. PMID:21535099

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

    SciTech Connect

    Coteron, Jose M.; Marco, Maria; Esquivias, Jorge; Deng, Xiaoyi; White, Karen L.; White, John; Koltun, Maria; El Mazouni, Farah; Kokkonda, Sreekanth; Katneni, Kasiram; Bhamidipati, Ravi; Shackleford, David M.; Angulo-Barturen, Inigo; Ferrer, Santiago B.; Jimenez-Diaz, Maria Belen; Gamo, Francisco-Javier; Goldsmith, Elizabeth J.; Charman, William N.; Bathurst, Ian; Floyd, David; Matthews, David; Burrows, Jeremy N.; Rathod, Pradipsinh K.; Charman, Susan A.; Phillips, Margaret A. (UWASH); (MMV, Switzerland); (GSK); (Monash); (UW); (UTSMC)

    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, 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.

  9. 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

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

    PubMed

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

    2015-08-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. PMID:25933445

  11. ECOLOGICAL PERFORMANCE INDICATORS

    EPA Science Inventory

    EMAP has traditionally relied on indicators of ecological condition to report on the extent to which coastal waters are impaired. Correlations between biological indicators and physical or chemical indicators may generate hypotheses about potential causes of impairment but are n...

  12. Object-based classification as an alternative approach to the traditional pixel-based classification to identify potential habitat of the grasshopper sparrow.

    PubMed

    Jobin, Benoît; Labrecque, Sandra; Grenier, Marcelle; Falardeau, Gilles

    2008-01-01

    The traditional method of identifying wildlife habitat distribution over large regions consists of pixel-based classification of satellite images into a suite of habitat classes used to select suitable habitat patches. Object-based classification is a new method that can achieve the same objective based on the segmentation of spectral bands of the image creating homogeneous polygons with regard to spatial or spectral characteristics. The segmentation algorithm does not solely rely on the single pixel value, but also on shape, texture, and pixel spatial continuity. The object-based classification is a knowledge base process where an interpretation key is developed using ground control points and objects are assigned to specific classes according to threshold values of determined spectral and/or spatial attributes. We developed a model using the eCognition software to identify suitable habitats for the Grasshopper Sparrow, a rare and declining species found in southwestern Québec. The model was developed in a region with known breeding sites and applied on other images covering adjacent regions where potential breeding habitats may be present. We were successful in locating potential habitats in areas where dairy farming prevailed but failed in an adjacent region covered by a distinct Landsat scene and dominated by annual crops. We discuss the added value of this method, such as the possibility to use the contextual information associated to objects and the ability to eliminate unsuitable areas in the segmentation and land cover classification processes, as well as technical and logistical constraints. A series of recommendations on the use of this method and on conservation issues of Grasshopper Sparrow habitat is also provided. PMID:17985180

  13. Assessing upper extremity capacity as a potential indicator of needs related to household activities for rehabilitation services in people with myotonic dystrophy type 1.

    PubMed

    Raymond, Kateri; Auger, Louis-Pierre; Cormier, Marie-France; Vachon, Christine; St-Onge, Sabrina; Mathieu, Jean; Noreau, Luc; Gagnon, Cynthia

    2015-06-01

    This study aimed to assess upper extremity capacity as a potential indicator of needs related to household activities for rehabilitation services in people with myotonic dystrophy type 1 (DM1). A cross-sectional study was set in an outpatient neuromuscular clinic where 200 adults with a confirmed diagnosis of DM1 (121 women; mean age: 47?y) were selected from the registry of a neuromuscular clinic to participate. Housing-related activities were assessed using the "housing" section of the Assessment of Life Habits Questionnaire (LIFE-H). The upper extremity assessment included grip strength (Jamar dynamometer), lateral pinch strength (pinch gauge), gross dexterity (Box and Block Test) and fine dexterity (Purdue Pegboard Test). Correlations with the LIFE-H item "housing" were stronger for grip and lateral strength (r?=?0.62; 0.61). When difficulties were present in "housing", the cut-off score associated with lateral pinch strength was 4.8?kg (sensitivity: 75.6%; specificity: 79.2%). Grip strength presented cut-off scores that clinically differed by gender. In conclusion, potential indicator of needs related to household activities for rehabilitation services with valid assessment tools were developed for people with DM1 who experience difficulties in housing-related activities. These criteria will assist health professionals in their attempt to refer DM1 patients to rehabilitation services at the appropriate time. PMID:25953319

  14. Immuno-proteomic analysis of human immune responses to experimental Neisseria meningitidis outer membrane vesicle vaccines identifies potential cross-reactive antigens.

    PubMed

    Williams, Jeannette N; Weynants, Vincent; Poolman, Jan T; Heckels, John E; Christodoulides, Myron

    2014-03-01

    Human volunteers were vaccinated with experimental Neisseria meningitidis serogroup B vaccines based on strain H44/76 detoxified L3 lipooligosaccharide (LOS)-derived outer membrane vesicles (OMV) or the licensed Cuban vaccine, VA-MENGOC-BC. Some volunteers were able to elicit cross-bactericidal antibodies against heterologous L2-LOS strain (760676). An immuno-proteomic approach was used to identify potential targets of these cross-bactericidal antibodies using an L2-LOS derived OMV preparation. A total of nine immuno-reactive spots were detected in this proteome: individuals vaccinated with the detoxified OMVs showed an increase in post-vaccination serum reactivity with Spots 2-8, but not with Spots 1 and 9. Vaccination with VA-MENGOC-BC induced sera that showed increased reactivity with all of the protein spots. Vaccinees showed increases in serum bactericidal activity (SBA) against the heterologous L2-LOS expressing strain 760676, which correlated, in general, with immunoblot reactivity. The identities of proteins within the immuno-reactive spots were determined. These included not only well-studied antigens such as Rmp, Opa, PorB and FbpA (NMB0634), but also identified novel antigens such as exopolyphosphatase (NMB1467) and ?-glutamyltranspeptidase (NMB1057) enzymes and a putative cell binding factor (NMB0345) protein. Investigating the biological properties of such novel antigens may provide candidates for the development of second generation meningococcal vaccines. PMID:24486354

  15. Imaging-Based High-Throughput Screening Assay To Identify New Molecules with Transmission-Blocking Potential against Plasmodium falciparum Female Gamete Formation.

    PubMed

    Miguel-Blanco, Celia; Lelièvre, Joël; Delves, Michael J; Bardera, Ana I; Presa, Jesús L; López-Barragán, María José; Ruecker, Andrea; Marques, Sara; Sinden, Robert E; Herreros, Esperanza

    2015-06-01

    In response to a call for the global eradication of malaria, drug discovery has recently been extended to identify compounds that prevent the onward transmission of the parasite, which is mediated by Plasmodium falciparum stage V gametocytes. Lately, metabolic activity has been used in vitro as a surrogate for gametocyte viability; however, as gametocytes remain relatively quiescent at this stage, their ability to undergo onward development (gamete formation) may be a better measure of their functional viability. During gamete formation, female gametocytes undergo profound morphological changes and express translationally repressed mRNA. By assessing female gamete cell surface expression of one such repressed protein, Pfs25, as the readout for female gametocyte functional viability, we developed an imaging-based high-throughput screening (HTS) assay to identify transmission-blocking compounds. This assay, designated the P. falciparum female gametocyte activation assay (FGAA), was scaled up to a high-throughput format (Z' factor, 0.7 ± 0.1) and subsequently validated using a selection of 50 known antimalarials from diverse chemical families. Only a few of these agents showed submicromolar 50% inhibitory concentrations in the assay: thiostrepton, methylene blue, and some endoperoxides. To determine the best conditions for HTS, a robustness test was performed with a selection of the GlaxoSmithKline Tres Cantos Antimalarial Set (TCAMS) and the final screening conditions for this library were determined to be a 2 ?M concentration and 48 h of incubation with gametocytes. The P. falciparum FGAA has been proven to be a robust HTS assay faithful to Plasmodium transmission-stage cell biology, and it is an innovative useful tool for antimalarial drug discovery which aims to identify new molecules with transmission-blocking potential. PMID:25801574

  16. High-Throughput Transcriptomic and RNAi Analysis Identifies AIM1, ERGIC1, TMED3 and TPX2 as Potential Drug Targets in Prostate Cancer

    PubMed Central

    Vainio, Paula; Mpindi, John-Patrick; Kohonen, Pekka; Fey, Vidal; Mirtti, Tuomas; Alanen, Kalle A.; Perälä, Merja; Kallioniemi, Olli; Iljin, Kristiina

    2012-01-01

    Prostate cancer is a heterogeneous group of diseases and there is a need for more efficient and targeted methods of treatment. In this study, the potential of gene expression data and RNA interference technique were combined to advance future personalized prostate cancer therapeutics. To distinguish the most promising in vivo prevalidated prostate cancer drug targets, a bioinformatic analysis was carried out using genome-wide gene expression data from 9873 human tissue samples. In total, 295 genes were selected for further functional studies in cultured prostate cancer cells due to their high mRNA expression in prostate, prostate cancer or in metastatic prostate cancer samples. Second, RNAi based cell viability assay was performed in VCaP and LNCaP prostate cancer cells. Based on the siRNA results, gene expression patterns in human tissues and novelty, endoplasmic reticulum function associated targets AIM1, ERGIC1 and TMED3, as well as mitosis regulating TPX2 were selected for further validation. AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression. ERGIC1 silencing specifically regulated the proliferation of ERG oncogene positive prostate cancer cells and inhibited ERG mRNA expression in these cells, indicating that it is a potent drug target in ERG positive subgroup of prostate cancers. TPX2 expression associated with PSA failure and TPX2 silencing reduced PSA expression, indicating that TPX2 regulates androgen receptor mediated signaling. In conclusion, the combinatorial usage of microarray and RNAi techniques yielded in a large number of potential novel biomarkers and therapeutic targets, for future development of targeted and personalized approaches for prostate cancer management. PMID:22761906

  17. Axinopsida serricata shell encrustation: a potential indicator of organic enrichment conditions in sediments in the southern Strait of Georgia, British Columbia, Canada.

    PubMed

    Burd, Brenda; Macdonald, Robie; van Roodselaar, Albert; Wright, Cindy

    2008-12-01

    We evaluate the potential of the geographic and within-sediment distribution patterns of rust-coloured shell encrustations on an abundant subtidal bivalve, Axinopsida serricata (Carpenter, 1864) as geochemical indicators of organic enrichment from marine municipal outfalls. The progressive development of shell encrustation over the life of the animals is suggested by heavier encrustations on large shells compared to smaller shells regardless of the geochemical conditions of the habitat. Heavy encrustations decline in an exponential manner at sediment acid volatile sulphide (AVS) levels>7 micromol/g. Analyses show that the reddish shell encrustations are from an amorphous iron oxide or hydroxy-oxide likely micro-biologically mediated; the oxides appear to be embedded within the inner matrix of an organic layer, with a chemically distinct outer layer. A schematic model is proposed which shows how enrichment of labile organic carbon around outfalls affects the availability of dissolved iron in sediments and leads to less extensive encrustations on bivalve shells. Predominantly sandy sediments with low organic loading have much less potential for iron oxide deposition than silty sediments due to greater oxygen penetration into the surface sediment. Shell encrustation appears to be relatively persistent and indicative of long-term conditions, regardless of spatial and temporal fluctuations in sediment geochemistry. With more research on development over the life-cycle of the animal, the pattern of A. serricata shell encrustation has the potential to rapidly provide a map of cumulative labile organic loading and oxygen penetration of sediments around municipal outfalls on the west coast of North America where this species is common. However, caution must be used in interpreting results, since background sediment characteristics (substrate type, bottom currents and sediment transport) can affect encrustation patterns. PMID:18954901

  18. A Molecular Approach to Identifying the Natural Prey of the African Creeping Water Bug Naucoris, A Potential Reservoir of Mycobacterium ulcerans

    PubMed Central

    Gamboa, Maribet; Kimbirauskas, Ryan K.; Merritt, Richard W.; Monaghan, Michael T.

    2012-01-01

    The extra-oral digestion of creeping water bugs (Naucoridae: Hemiptera) hinders the study of their diet using the standard method of identifying prey body parts in the gut. Genetic methods are available, but rely on PCR tests or similar diagnostics to confirm suspected prey. Where the potential prey is unknown and a broad search for all possible prey is desirable, methods that can potentially capture any prey item are required. Naucoris sp. is known to harbor Mycobacterium ulcerans (Actinomycetales: Mycobacteriaceae), the causative bacterium of Buruli ulcer. Outbreaks of Buruli ulcer have been associated with disturbed freshwater habitats, but the mode of transmission to humans remains unclear. Here we examine the diet of Naucoris sp., a dominant aquatic predator in water bodies in Ghana where the prevalence of Buruli ulcer is high. We cloned and sequenced 576 PCR products (mtDNA rrnL, cox1) isolated from the gut of 60 Naucoris sp. individuals to determining diet composition as broadly as possible. Using phylogenetic analysis of newly sequenced clones and 6 potential prey taxa collected from the site, sequences isolated from Naucoris sp. guts matched locally collected Coleoptera (Hydrophilidae). Blastn queries to GenBank of other clone sequences produced matches to (Anura) (n = 1), Rotifera (n = 5), and fungi (n = 4) as additional components of the diet. Our results suggest that sp. in this Buruli ulcer-endemic area feeds on a wide range of prey and body sizes, and that the approach could be successfully applied to studies of aquatic food webs where morphological identification of prey is impossible and where little or no a priori knowledge is available. PMID:22934669

  19. A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries

    PubMed Central

    Li, Xiaohui; Bykhovskaya, Yelena; Haritunians, Talin; Siscovick, David; Aldave, Anthony; Szczotka-Flynn, Loretta; Iyengar, Sudha K.; Rotter, Jerome I.; Taylor, Kent D.; Rabinowitz, Yaron S.

    2012-01-01

    Keratoconus is a condition in which the cornea progressively thins over time, and is a major cause for cornea transplantation. To identify keratoconus susceptibility regions, we performed a comprehensive genome-wide association study (GWAS) using a discovery and replication design. A discovery panel of 222 keratoconus Caucasian patients and 3324 Caucasian controls was genotyped using Illumina 370K beadchips. Further associated and fine-mapping single nucleotide polymorphisms (SNPs) (n= 4905) were genotyped in an independent replication case–control panel of 304 cases and 518 controls and a family panel of 307 subjects in 70 families. Logistic regression models implemented in PLINK were performed to test associations in case–control samples with and without principal component (PC) adjustments. Generalized estimation equation models accounting for familial correlations implemented in GWAF were used for association testing in families. No genome-wide associations were identified in the discovery GWAS panel. From the initial testing without adjustments for PCs, the top three SNPs located at 3p26 (rs6442925), 2q21.3 (rs4954218) and 19q13.3 (rs1428642) were identified with unadjusted P-values of 6.5 × 10?8, 2.4 × 10?7 and 3.1 × 10?7, respectively. After adjustments for PCs, rs1428642 became the most significant through the genome with a P-value of 1.4 × 10?6, while rs6442925 and rs4954218 were less significant (P= 1.9 × 10?5 and 2.6 × 10?4). SNP rs4954218 was confirmed in two independent replication panels with P-values of 0.004 and 0.009, respectively. Meta-analysis revealed a highest association at rs4954218 with adjusted P= 1.6 × 10?7 (unadjusted P= 1.2 × 10?9). These findings suggest SNP rs4954218, located near the RAB3GAP1 gene, previously reported to be associated with corneal malformation, is a potential susceptibility locus for keratoconus. PMID:21979947

  20. The use of transformed IMR90 cell model to identify the potential extra-telomeric effects of hTERT in cell migration and DNA damage response

    PubMed Central

    2014-01-01

    Background Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomesase, is responsible for telomere maintenance and its reactivation is implicated in almost 90% human cancers. Recent evidences show that hTERT is essential for neoplastic transformation independent of its canonical function. However, the roles of hTERT in the process remain elusive. In the current work, we explore the extra-telomeric role of hTERT in the neoplastic transformation of fibroblast IMR90. Results Here we established transformed IMR90 cells by co-expression of three oncogenic factors, namely, H-Ras, SV40 Large-T antigen and hTERT (RSH). The RSH-transformed cells acquired hallmarks of cancer, such as they can grow under anchorage independent conditions; self-sufficient in growth signals; attenuated response to apoptosis; and possessed recurrent chromosomal abnormalities. Furthermore, the RSH-transformed cells showed enhanced migration capability which was also observed in IMR90 cells expressing hTERT alone, indicating that hTERT plays a role in cell migration, and thus possibly contribute to their metastatic potential during tumor transformation. This notion was further supported by our microarray analysis. In addition, we found that Ku70 were exclusively upregulated in both RSH-transformed IMR90 cells and hTERT-overexpressing IMR90 cells, suggesting the potential role of hTERT in DNA damage response (DDR). Conclusions Collectively, our study revealed the extra-telomeric effects of hTERT in cell migration and DDR during neoplastic transformation. PMID:25098897

  1. A molecular dynamics study of catestatin docked on nicotinic acetylcholine receptors to identify amino acids potentially involved in the binding of chromogranin A fragments.

    PubMed

    Kraszewski, Sebastian; Drabik, Dominik; Langner, Marek; Ramseyer, Christophe; Kembubpha, Sineenat; Yasothornsrikul, Sukkid

    2015-06-24

    Catestatin, a cationic and hydrophobic 21-amino acid fragment of chromogranin A, is known to be a non-competitive nicotinic antagonist acting through nicotinic acetylcholine receptors (nAChRs) to inhibit catecholamine release. Since this receptor is the target of several neuronal and non-neuronal disorder prophylaxes and treatments, this study aims at the elucidation of the binding of human catestatin to the entire nAChR reconstructed in lipid bilayers by means of docking followed by full atomistic molecular dynamics simulations. The obtained results show that the minimum free energy for the binding of the peptide and the receptor attains minimal values for locations at the pore site and in the outer beta subunit. This result is consistent with previous studies showing that catestatin occludes the pore opening. A new finding is an additional even stronger binding seat at the beta subunit and that membrane presence could be an important factor. Specific amino acids involved in catestatin binding have been identified, indicating targets for point mutation studies. In addition to improving the understanding of the interaction between the peptide and muscle-type and even other nAChR subtypes, the results of this study provide directions for future peptidomimetic research. PMID:26079001

  2. A Drug-Repositioning Screening Identifies Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-Mediated Virulence of Pseudomonas aeruginosa

    PubMed Central

    Gi, Mia; Jeong, Junhui; Lee, Keehoon; Lee, Kang-Mu; Toyofuku, Masanori; Yong, Dong Eun

    2014-01-01

    Pseudomonas aeruginosa, a Gram-negative bacterium of clinical significance, produces elastase as a predominant exoprotease. Here, we screened a library of chemical compounds currently used for human medication and identified diethylene triamine penta-acetic acid (DTPA, pentetic acid) as an agent that suppresses the production of elastase. Elastase activity found in the prototype P. aeruginosa strain PAO1 was significantly decreased when grown with a concentration as low as 20 ?M DTPA. Supplementation with Zn2+ or Mn2+ ions restored the suppressive effect of DTPA, suggesting that the DTPA-mediated decrease in elastase activity is associated with ion-chelating activity. In DTPA-treated PAO1 cells, transcription of the elastase-encoding lasB gene and levels of the Pseudomonas quinolone signal (PQS), a molecule that mediates P. aeruginosa quorum sensing (QS), were significantly downregulated, reflecting the potential involvement of the PQS QS system in DTPA-mediated elastase suppression. Biofilm formation was also decreased by DTPA treatment. When A549 alveolar type II-like adenocarcinoma cells were infected with PAO1 cells in the presence of DTPA, A549 cell viability was substantially increased. Furthermore, the intranasal delivery of DTPA to PAO1-infected mice alleviated the pathogenic effects of PAO1 cells in the animals. Together, our results revealed a novel function for a known molecule that may help treat P. aeruginosa airway infection. PMID:25246397

  3. 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, P. A.; 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.

    2012-03-01

    The Near-Earth Object Human Space Flight Accessible Target Study (NHATS) identifies NEAs for human exploration. An updated list of NEAs identified under the NHATS criteria will be made available to the international community via a NASA website.

  4. A novel highly divergent protein family identified from a viviparous insect by RNA-seq analysis: a potential target for tsetse fly-specific abortifacients.

    PubMed

    Benoit, Joshua B; Attardo, Geoffrey M; Michalkova, Veronika; Krause, Tyler B; Bohova, Jana; Zhang, Qirui; Baumann, Aaron A; Mireji, Paul O; Taká?, Peter; Denlinger, David L; Ribeiro, Jose M; Aksoy, Serap

    2014-04-01

    In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1-3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4-10). The genes encoding mgp2-10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2-10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2-10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2-10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2-10 to tsetse and their critical role during lactation suggests that these proteins may be an excellent target for tsetse-specific population control approaches. PMID:24763277

  5. A Novel Highly Divergent Protein Family Identified from a Viviparous Insect by RNA-seq Analysis: A Potential Target for Tsetse Fly-Specific Abortifacients

    PubMed Central

    Benoit, Joshua B.; Attardo, Geoffrey M.; Michalkova, Veronika; Krause, Tyler B.; Bohova, Jana; Zhang, Qirui; Baumann, Aaron A.; Mireji, Paul O.; Taká?, Peter; Denlinger, David L.; Ribeiro, Jose M.; Aksoy, Serap

    2014-01-01

    In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1–3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4–10). The genes encoding mgp2–10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2–10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2–10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2–10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2–10 to tsetse and their critical role during lactation suggests that these proteins may be an excellent target for tsetse-specific population control approaches. PMID:24763277

  6. Comparative Secretome Analysis of Epithelial and Mesenchymal Subpopulations of Head and Neck Squamous Cell Carcinoma Identifies S100A4 as a Potential Therapeutic Target*

    PubMed Central

    Rasanen, Kati; Sriswasdi, Sira; Valiga, Alexander; Tang, Hsin-Yao; Zhang, Gao; Perego, Michela; Somasundaram, Rajasekharan; Li, Ling; Speicher, Kaye; Klein-Szanto, Andres J.; Basu, Devraj; Rustgi, Anil K.; Speicher, David W.; Herlyn, Meenhard

    2013-01-01

    Epithelial-mesenchymal transition (EMT) is a key contributor in tumor progression and metastasis. EMT produces cellular heterogeneity within head and neck squamous cell carcinomas (HNSCC) by creating a phenotypically distinct mesenchymal subpopulation that is resistant to conventional therapies. In this study, we systematically characterized differences in the secretomes of E-cadherin high epithelial-like and E-cadherin low mesenchymal-like subpopulations using unbiased and targeted proteomics. A total 1765 proteins showed significant changes with 177 elevated in the epithelial subpopulation and 173 elevated in the mesenchymal cells. Key nodes in affected networks included NF?B, Akt, and ERK, and most implicated cellular components involved various aspects of the extracellular matrix. In particular, large changes were observed in multiple collagens with most affected collagens at much higher abundance levels in the mesenchymal subpopulation. These cells also exhibited a secretome profile resembling that of cancer-associated fibroblastic cells (CAF). S100A4, a commonly used marker for cancer-associated fibroblastic cells, was elevated more than 20-fold in the mesenchymal cells and this increase was further verified at the transcriptome level. S100A4 is a known mediator of EMT, leading to metastasis and EMT has been proposed as a potential source of cancer-associated fibroblastic cells in solid tumors. S100A4 knockdown by small interfering RNA led to decreased expression, secretion and activity of matrix metalloproteinase 2, as verified by quantitative PCR, multiple reaction monitoring and zymography analyses, and reduced invasion in collagen-embedded spheroids. Further confirmation in three-dimensional organotypic reconstructs showed less invasion and advanced differentiation in the S100A4 RNA interference samples. Orthotopic metastasis model, developed to validate the findings in vivo, demonstrated a decrease in spontaneous metastasis and augmented differentiation in the primary tumor in siS100A4 xenografts. These results demonstrate the value of secretome profiling to evaluate phenotypic conversion and identify potential novel therapeutic targets such as S100A4. PMID:24037664

  7. Comparative secretome analysis of epithelial and mesenchymal subpopulations of head and neck squamous cell carcinoma identifies S100A4 as a potential therapeutic target.

    PubMed

    Rasanen, Kati; Sriswasdi, Sira; Valiga, Alexander; Tang, Hsin-Yao; Zhang, Gao; Perego, Michela; Somasundaram, Rajasekharan; Li, Ling; Speicher, Kaye; Klein-Szanto, Andres J; Basu, Devraj; Rustgi, Anil K; Speicher, David W; Herlyn, Meenhard

    2013-12-01

    Epithelial-mesenchymal transition (EMT) is a key contributor in tumor progression and metastasis. EMT produces cellular heterogeneity within head and neck squamous cell carcinomas (HNSCC) by creating a phenotypically distinct mesenchymal subpopulation that is resistant to conventional therapies. In this study, we systematically characterized differences in the secretomes of E-cadherin high epithelial-like and E-cadherin low mesenchymal-like subpopulations using unbiased and targeted proteomics. A total 1765 proteins showed significant changes with 177 elevated in the epithelial subpopulation and 173 elevated in the mesenchymal cells. Key nodes in affected networks included NF?B, Akt, and ERK, and most implicated cellular components involved various aspects of the extracellular matrix. In particular, large changes were observed in multiple collagens with most affected collagens at much higher abundance levels in the mesenchymal subpopulation. These cells also exhibited a secretome profile resembling that of cancer-associated fibroblastic cells (CAF). S100A4, a commonly used marker for cancer-associated fibroblastic cells, was elevated more than 20-fold in the mesenchymal cells and this increase was further verified at the transcriptome level. S100A4 is a known mediator of EMT, leading to metastasis and EMT has been proposed as a potential source of cancer-associated fibroblastic cells in solid tumors. S100A4 knockdown by small interfering RNA led to decreased expression, secretion and activity of matrix metalloproteinase 2, as verified by quantitative PCR, multiple reaction monitoring and zymography analyses, and reduced invasion in collagen-embedded spheroids. Further confirmation in three-dimensional organotypic reconstructs showed less invasion and advanced differentiation in the S100A4 RNA interference samples. Orthotopic metastasis model, developed to validate the findings in vivo, demonstrated a decrease in spontaneous metastasis and augmented differentiation in the primary tumor in siS100A4 xenografts. These results demonstrate the value of secretome profiling to evaluate phenotypic conversion and identify potential novel therapeutic targets such as S100A4. PMID:24037664

  8. Methods to Identify Changes in Background Water-Quality Conditions Using Dissolved-Solids Concentrations and Loads as Indicators, Arkansas River and Fountain Creek, in the Vicinity of Pueblo, Colorado

    USGS Publications Warehouse

    Ortiz, Roderick F.

    2004-01-01

    Effective management of existing water-storage capacity in the Arkansas River Basin is anticipated to help satisfy the need for water in southeastern Colorado. A strategy to meet these needs has been developed, but implementation could affect the water quality of the Arkansas River and Fountain Creek in the vicinity of Pueblo, Colorado. Because no known methods are available to determine what effects future changes in operations will have on water quality, the U.S. Geological Survey, in cooperation with the Southeastern Colorado Water Activity Enterprise, began a study in 2002 to develop methods that could identify if future water-quality conditions have changed significantly from background (preexisting) water-quality conditions. A method was developed to identify when significant departures from background (preexisting) water-quality conditions occur in the lower Arkansas River and Fountain Creek in the vicinity of Pueblo, Colorado. Additionally, the methods described in this report provide information that can be used by various water-resource agencies for an internet-based decision-support tool. Estimated dissolved-solids concentrations at five sites in the study area were evaluated to designate historical background conditions and to calculate tolerance limits used to identify statistical departures from background conditions. This method provided a tool that could be applied with defined statistical probabilities associated with specific tolerance limits. Drought data from 2002 were used to test the method. Dissolved-solids concentrations exceeded the tolerance limits at all four sites on the Arkansas River at some point during 2002. The number of exceedances was particularly evident when streamflow from Pueblo Reservoir was reduced, and return flows and ground-water influences to the river were more prevalent. No exceedances were observed at the site on Fountain Creek. These comparisons illustrated the need to adjust the concentration data to account for varying streamflow. As such, similar comparisons between flow-adjusted data were done. At the site Arkansas River near Avondale, nearly all the 2002 flow-adjusted concentration data were less than the flow-adjusted tolerance limit which illustrated the effects of using flow-adjusted concentrations. Numerous exceedances of the flow-adjusted tolerance limits, however, were observed at the sites Arkansas River above Pueblo and Arkansas River at Pueblo. These results indicated that the method was able to identify a change in the ratio of source waters under drought conditions. Additionally, tolerance limits were calculated for daily dissolved-solids load and evaluated in a similar manner. Several other mass-load approaches were presented to help identify long-term changes in water quality. These included comparisons of cumulative mass load at selected sites and comparisons of mass load contributed at the Arkansas River near Avondale site by measured and unmeasured sources.

  9. THP-1 monocytes but not macrophages as a potential alternative for CD34{sup +} dendritic cells to identify chemical skin sensitizers

    SciTech Connect

    Lambrechts, Nathalie [Flemish Institute for Technological Research (VITO N.V.), Centre of Expertise in Environmental Toxicology, Mol (Belgium)], E-mail: nathalie.lambrechts@vito.be; Verstraelen, Sandra [Flemish Institute for Technological Research (VITO N.V.), Centre of Expertise in Environmental Toxicology, Mol (Belgium)], E-mail: sandra.verstraelen@vito.be; Lodewyckx, Hanne; Felicio, Ana; Hooyberghs, Jef; Witters, Hilda [Flemish Institute for Technological Research (VITO N.V.), Centre of Expertise in Environmental Toxicology, Mol (Belgium); Tendeloo, Viggo van [University of Antwerp (Ukraine), Vaccine and Infectious Disease Institute, Laboratory of Experimental Hematology (Belgium); Cauwenberge, Paul van [University of Ghent (UGhent), Department of Otolaryngology (Belgium); Nelissen, Inge; Heuvel, Rosette van den [Flemish Institute for Technological Research (VITO N.V.), Centre of Expertise in Environmental Toxicology, Mol (Belgium); Schoeters, Greet [Flemish Institute for Technological Research (VITO N.V.), Centre of Expertise in Environmental Toxicology, Mol (Belgium); University of Antwerp (Ukraine), Department of Biomedical Sciences (Belgium)

    2009-04-15

    Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34{sup +} progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (L-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.

  10. Method to identify potential phosphorus rate-limiting conditions in post-denitrification biofilm reactors within systems designed for simultaneous low-level effluent nitrogen and phosphorus concentrations.

    PubMed

    Boltz, Joshua P; Morgenroth, Eberhard; Daigger, Glen T; deBarbadillo, Christine; Murthy, Sudhir; Sørensen, Kim H; Stinson, Beverly

    2012-12-01

    Water-quality standards requiring simultaneous low level effluent N and P concentrations are increasingly common in Europe and the United States of America. Moving bed biofilm reactors (MBBRs) and biologically active filters (BAFs) have been used as post-denitrification biofilm reactors in processes designed and operated for this purpose (Boltz et al., 2010a). There is a paucity of information describing systematic design and operational protocols that will minimize the potential for phosphorus rate-limited conditions as well as a lack of information describing the interaction between these post-denitrification biofilm reactors and unit processes that substantially alter phosphorus speciation (e.g., chemically enhanced clarification). In this paper, a simple mathematical model for estimating the threshold below which P becomes rate-limiting, and the model is presented and evaluated by comparing its predictions with operational data from post-denitrification MBBRs and BAFs. Ortho-phosphorus (PO(4)-P), which is the dissolved reactive component of total phosphorus, was a primary indicator of P rate-limiting conditions in the evaluated post-denitrification biofilm reactors. The threshold below which PO(4)-P becomes the rate-limiting substrate is defined: S(PO4-P):S(NOx-N) = 0.0086 g P/g N and S(PO4-P):S(M) = 0.0013 g P/g COD. Additional analyses indicate J(NOx-N)(avg) =0.48 g/m2/d when S(PO4-P):S(NOx-N) > 0.0086, and J(NOx-N)(avg) = 0.06 g/m2/d when S(PO4-P):S(NOx-N) < 0.0086. Effluent nitrate-nitrogen plus nitrite-nitrogen concentration (S(NOx-N)) from the evaluated post-denitrification biofilm reactors began to rapidly increase when S(PO4-P):S(NOx-N) was 0.01, approximately (consistent with the rate-limitation threshold of S(PO4-P):S(NOx-N) < 0.0086 predicted by the mathematical model described in this paper). Depending on the processes used at a given WWTP, optimizing chemically enhanced clarification to increase the amount of PO(4)-P that remains in the clarifiers effluent stream, dosing phosphoric acid in the MBBR or BAF influent stream, and/or optimizing secondary process EBPR may overcome phosphorus rate-limitations in the biofilm-based post-denitrification process. PMID:23058109

  11. Barium variation in Pagrus auratus (Sparidae) otoliths: A potential indicator of migration between an embayment and ocean waters in south-eastern Australia

    NASA Astrophysics Data System (ADS)

    Hamer, Paul A.; Jenkins, Gregory P.; Coutin, Patrick

    2006-07-01

    Chronological variation in otolith chemistry can be used to reconstruct migration histories of fish. The use of otolith chemistry to study migration, however, requires knowledge of relationships between the chemical properties of the water and elemental incorporation into otoliths, and how water chemistry varies in space and time. We explored the potential for otolith chemistry of snapper, Pagrus auratus, to provide information on movement history between a large semi-enclosed bay, Port Phillip, and coastal waters in south-eastern Australia. Comparisons of water chemistry across two years demonstrated that ambient barium (Ba) levels in Port Phillip Bay were approximately double those in coastal waters (11 ?g L -1 versus 6 ?g L -1). Ba levels in otolith margins of wild juvenile snapper were highly positively correlated with ambient levels across 17 sampling locations, and levels in otolith margins of adult snapper collected from Port Phillip Bay were approximately double those of snapper collected in coastal waters. Mean partition coefficients for Ba ( DBa) were similar for juvenile (0.43) and adult (0.46) otoliths, suggesting that otolith Ba incorporation relative to ambient levels was similar across life-stages. Low Ba variation across otoliths from adult snapper maintained in tanks for three years indicated that annual temperature and/or growth cycles did not strongly influence otolith Ba variation. We concluded that chronological Ba variation in snapper otoliths would be a reliable proxy for life-history exposure to variable ambient Ba. We used water chemistry data and Ba levels across otoliths of ocean resident snapper to estimate otolith Ba levels indicative of residence in Port Phillip Bay (>10 ?g g -1) or coastal waters (<6 ?g g -1). Peaks in Ba exceeding 10 ?g g -1 were common across otoliths of snapper collected in Port Phillip Bay and a nearby coastal region. The location of strong Ba peaks within otoliths was consistent with residence in Port Phillip Bay during the spring/summer when snapper move into the Bay from coastal waters to spawn. Our results for snapper support the use of otolith Ba as a proxy for ambient levels throughout the life-history, however, confident interpretation of migration history from otolith Ba chronologies will most likely require matching time series of ambient Ba in the water bodies of interest.

  12. Station Identifier

    Microsoft Academic Search

    J. Stepan

    1968-01-01

    This paper describes an end office tributary identifier which sends to a toll center the calling subscriber's directory number. It is arranged to interface with the Bell System's centralized automatic message accounting (CAMA) centers. The electronic identifier operates on either a terminal per line, a terminal per station, or mixed basis. In operating, it feeds an ac signal on the

  13. Construction of a GeogDetector-based model system to indicate the potential occurrence of grasshoppers in Inner Mongolia steppe habitats.

    PubMed

    Shen, J; Zhang, N; Gexigeduren; He, B; Liu, C-Y; Li, Y; Zhang, H-Y; Chen, X-Y; Lin, H

    2015-06-01

    Grasshopper plagues have seriously disturbed grassland ecosystems in Inner Mongolia, China. The accurate prediction of grasshopper infestations and control of grasshopper plagues have become urgent needs. We sampled 234, 342, 335, and 369 plots in Xianghuangqi County of Xilingol League in 2010, 2011, 2012, and 2013, respectively, and measured the density of the most dominant grasshopper species, Oedaleus decorus asiaticus, and the latitude, longitude, and associated relatively stable habitat factors at each plot. We used Excel-GeogDetector software to explore the effects of individual habitat factors and the two-factor interactions on grasshopper density. We estimated the membership of each grasshopper density rank and determined the weights of each habitat category. These results were used to construct a model system evaluating grasshopper habitat suitability. The results showed that our evaluation system was reliable and the fuzzy evaluation scores of grasshopper habitat suitability were good indicators of potential occurrence of grasshoppers. The effects of the two-factor interactions on grasshopper density were greater than the effects of any individual factors. O. d. asiaticus was most likely to be found at elevations of 1300-1400 m, flat terrain or slopes of 4-6°, typical chestnut soil with 70-80% sand content in the top 5 cm of soil, and medium-coverage grassland. The species preferred temperate bunchgrass steppe dominated by Stipa krylovii and Cleistogenes squarrosa. These findings may be used to improve models to predict grasshopper occurrence and to develop management guidelines to control grasshopper plagues by changing habitats. PMID:25779652

  14. Quantifying the Relative Importance and Potential Interactive Effects of Multiple Indices When Predicting Fire Risk and Severity in the Western US.

    NASA Astrophysics Data System (ADS)

    Keyser, A. R.; Westerling, A.

    2007-12-01

    The national fire plan was implemented after the landmark fire season of 2000 as a response to a perceived increasing threat of severe wildfires. Subsequently, the Landfire project was initiated to develop a national dataset comprising vegetation condition, wildland fuels and fire regimes, and ecosystem status to support the national fire plan. A key product in this dataset to predict areas at risk for severe fires is the fire regime condition class (FRCC). The FRCC is an index of the degree of departure from the historical fire regime. This departure is a metric of the difference between current landscape vegetation composition and the range of historical reference vegetation characteristics; this difference can result from changes in vegetation characteristics and/or the spatial fire regime. The FRCC index is derived relative to simulated reference conditions, which in turn are based on Landsum, a landscape fire succession model. In addition to land management decisions, factors such as nitrogen deposition, ozone and climate affect both reference and current vegetation characteristics. It is an open question as to whether FRCC is sensitive enough to capture the full suite of potential effects on fire regimes. We are interested in examining vegetation change (via FRCC), nitrogen deposition, ozone concentration and climate variability in terms of their utility in predicting spatial variability in fire regime characteristics. Our analysis includes statistical examination of the multiple effects of nitrogen deposition, ozone, climate indices, and FRCC on fire frequency, size, and severity in California and the Western United States. We will assess how these four factors might act alone to influence fire, and their relative importance as co-determinants of fire risks. Our results will quantify how distinct FRCC is from climate and its efficacy as a predictor of fire risk and severity. Of particular interest is the extent to which FRCC predicts spatial variability in fire activity, and the extent to which climate and pollution patterns predict or influence the FRCC.

  15. Evolution of a Genome-Encoded Bias in Amino Acid Biosynthetic Pathways Is a Potential Indicator of Amino Acid Dynamics in the Environment

    PubMed Central

    Fasani, Rick A.; Savageau, Michael A.

    2014-01-01

    Overcoming the stress of starvation is one of an organism’s most challenging phenotypic responses. Those organisms that frequently survive the challenge, by virtue of their fitness, will have evolved genomes that are shaped by their specific environments. Understanding this genotype–environment–phenotype relationship at a deep level will require quantitative predictive models of the complex molecular systems that link these aspects of an organism’s existence. Here, we treat one of the most fundamental molecular systems, protein synthesis, and the amino acid biosynthetic pathways involved in the stringent response to starvation. These systems face an inherent logical dilemma: Building an amino acid biosynthetic pathway to synthesize its product—the cognate amino acid of the pathway—may require that very amino acid when it is no longer available. To study this potential “catch-22,” we have created a generic model of amino acid biosynthesis in response to sudden starvation. Our mathematical analysis and computational results indicate that there are two distinctly different outcomes: Partial recovery to a new steady state, or full system failure. Moreover, the cell’s fate is dictated by the cognate bias, the number of cognate amino acids in the corresponding biosynthetic pathway relative to the average number of that amino acid in the proteome. We test these implications by analyzing the proteomes of over 1,800 sequenced microbes, which reveals statistically significant evidence of low cognate bias, a genetic trait that would avoid the biosynthetic quandary. Furthermore, these results suggest that the pattern of cognate bias, which is readily derived by genome sequencing, may provide evolutionary clues to an organism’s natural environment. PMID:25118252

  16. Comparative Analysis of Mafriwal (Bos taurus × Bos indicus) and Kedah Kelantan (Bos indicus) Sperm Proteome Identifies Sperm Proteins Potentially Responsible for Higher Fertility in a Tropical Climate

    PubMed Central

    Ashrafzadeh, Ali; Nathan, Sheila; Karsani, Saiful Anuar

    2013-01-01

    The fertility of zebu cattle (Bos indicus) is higher than that of the European purebred (Bos taurus) and crossbred (Bos taurus × Bos indicus) cattle in tropical areas. To identify proteins related to the higher thermo-tolerance and fertility of Zebu cattle, this study was undertaken to identify differences in sperm proteome between the high fertile Malaysian indigenous zebu cattle (Kedah Kelantan) and the sub-fertile crossbred cattle (Mafriwal). Frozen semen from three high performance bulls from each breed were processed to obtain live and pure sperm. Sperm proteins were then extracted, and two-dimensional gel electrophoresis performed to compare proteome profiles. Gel image analysis identified protein spots of interest which were then identified by liquid chromatography mass spectrometry quadrupole time-of-flight (LC MS/MS Q-TOF). STRING network analysis predicted interactions between at least 20 of the identified proteins. Among the identified proteins, a number of motility and energy related proteins were present in greater abundance in Kedah Kelantan. Sperm motility evaluation by Computer Assisted Semen Analysis (CASA) confirmed significantly higher motility in Kedah Kelantan. While results from this study do identify proteins that may be responsible for the higher fertility of Kedah Kelantan, functional characterization of these proteins is warranted to reinforce our understanding of their roles in sperm fertility. PMID:23903046

  17. Environmental Indicators

    NSDL National Science Digital Library

    Environment Canada has developed a set of environmental indicators that are easily measurable and provide useful clues on the state of the environment. This Web site provides a listing of those indicators that Environment Canada monitors. For each indicator, there is a detailed description of the environmental indicator, how it relates to larger environmental problems, and what is being done to reduce the threat. A number of Web links are provided for further information on each indicator.

  18. Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 11,087 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 2004 - 2008 -- based on BCSC data through 2009 -- All Diagnostic Examinations

    Cancer.gov

    Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 11,087 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 2004 - 2008 -- based on BCSC data through 2009

  19. Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 21,109 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 1996 - 2005 --- based on BCSC data as of 2007 -- All Diagnostic Examinations

    Cancer.gov

    Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 21,109 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 1996 - 2005 --- based on BCSC data as of 2007

  20. Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 11,087 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 2004 - 2008 -- based on BCSC data through 2009 -- Evaluation of Breast Problem/Palpable Lump

    Cancer.gov

    Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 11,087 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 2004 - 2008 -- based on BCSC data through 2009

  1. Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 11,087 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 2004 - 2008 -- based on BCSC data through 2009 -- Evaluation of Breast Problem/No Lump or Lump Unknown

    Cancer.gov

    Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 11,087 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 2004 - 2008 -- based on BCSC data through 2009

  2. Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 11,087 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 2004 - 2008 -- based on BCSC data through 2009 -- Work-up of Abnormal Screen

    Cancer.gov

    Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 11,087 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 2004 - 2008 -- based on BCSC data through 2009

  3. Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 21,109 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 1996 - 2005 --- based on BCSC data as of 2007 -- Evaluation of Breast Problem/No Lump or Lump Unknown

    Cancer.gov

    Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 21,109 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 1996 - 2005 --- based on BCSC data as of 2007

  4. Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 21,109 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 1996 - 2005 --- based on BCSC data as of 2007 -- Evaluation of Breast Problem/Palpable Lump

    Cancer.gov

    Text Description of Figure: Smoothed Plots of Sensitivity by Indication for Examination for 21,109 Cancers That Were Identified at Diagnostic Mammography (Among Radiologists Finding Five or More Cancers), 1996 - 2005 --- based on BCSC data as of 2007

  5. Using Cl/Br ratios and other indicators to assess potential impacts on groundwater quality from septic systems: A review and examples from principal aquifers in the United States

    USGS Publications Warehouse

    Katz, B.G.; Eberts, S.M.; Kauffman, L.J.

    2011-01-01

    A detailed review was made of chemical indicators used to identify impacts from septic tanks on groundwater quality. Potential impacts from septic tank leachate on groundwater quality were assessed using the mass ratio of chloride-bromide (Cl/Br), concentrations of selected chemical constituents, and ancillary information (land use, census data, well depth, soil characteristics) for wells in principal aquifers of the United States. Chemical data were evaluated from 1848 domestic wells in 19 aquifers, 121 public-supply wells in 6 aquifers, and associated monitoring wells in four aquifers and their overlying hydrogeologic units. Based on previously reported Cl/Br ratios, statistical comparisons between targeted wells (where Cl/Br ratios range from 400 to 1100 and Cl concentrations range from 20 to 100 mg/L) and non-targeted wells indicated that shallow targeted monitoring and domestic wells (0.5. mg/L) shallow groundwater from target domestic wells, relative to non-target wells (1.5. mg/L), corresponded to significantly higher potassium, boron, chloride, dissolved organic carbon, and sulfate concentrations, which may also indicate the influence of septic-tank effluent. Impacts on groundwater quality from septic systems were most evident for the Eastern Glacial Deposits aquifer and the Northern High Plains aquifer that were associated with the number of housing units using septic tanks, high permeability of overlying sediments, mostly oxic conditions, and shallow wells. Overall, little or no influence from septic systems were found for water samples from the deeper public-supply wells.The Cl/Br ratio is a useful first-level screening tool for assessing possible septic tank influence in water from shallow wells (<20 m) with the range of 400-1100. The use of this ratio would be enhanced with information on other chloride sources, temporal variability of chloride and bromide concentrations in shallow groundwater, knowledge of septic-system age and maintenance, and the use of multiple tracers (combination of additional chemical and microbiological indicators). ?? 2010.

  6. Using Cl/Br ratios and other indicators to assess potential impacts on groundwater quality from septic systems: A review and examples from principal aquifers in the United States

    NASA Astrophysics Data System (ADS)

    Katz, Brian G.; Eberts, Sandra M.; Kauffman, Leon J.

    2011-02-01

    SummaryA detailed review was made of chemical indicators used to identify impacts from septic tanks on groundwater quality. Potential impacts from septic tank leachate on groundwater quality were assessed using the mass ratio of chloride-bromide (Cl/Br), concentrations of selected chemical constituents, and ancillary information (land use, census data, well depth, soil characteristics) for wells in principal aquifers of the United States. Chemical data were evaluated from 1848 domestic wells in 19 aquifers, 121 public-supply wells in 6 aquifers, and associated monitoring wells in four aquifers and their overlying hydrogeologic units. Based on previously reported Cl/Br ratios, statistical comparisons between targeted wells (where Cl/Br ratios range from 400 to 1100 and Cl concentrations range from 20 to 100 mg/L) and non-targeted wells indicated that shallow targeted monitoring and domestic wells (<20 m depth below land surface) had a significantly ( p < 0.05) higher median percentage of houses with septic tanks (1990 census data) than non-targeted wells. Higher ( p = 0.08) median nitrate-N concentration (3.1 mg/L) in oxic (dissolved oxygen concentrations >0.5 mg/L) shallow groundwater from target domestic wells, relative to non-target wells (1.5 mg/L), corresponded to significantly higher potassium, boron, chloride, dissolved organic carbon, and sulfate concentrations, which may also indicate the influence of septic-tank effluent. Impacts on groundwater quality from septic systems were most evident for the Eastern Glacial Deposits aquifer and the Northern High Plains aquifer that were associated with the number of housing units using septic tanks, high permeability of overlying sediments, mostly oxic conditions, and shallow wells. Overall, little or no influence from septic systems were found for water samples from the deeper public-supply wells. The Cl/Br ratio is a useful first-level screening tool for assessing possible septic tank influence in water from shallow wells (<20 m) with the range of 400-1100. The use of this ratio would be enhanced with information on other chloride sources, temporal variability of chloride and bromide concentrations in shallow groundwater, knowledge of septic-system age and maintenance, and the use of multiple tracers (combination of additional chemical and microbiological indicators).

  7. Sequential strategy to identify a susceptibility gene for schizophrenia: Report of potential linkage on chromosome 22q12-q13.1: Part 1

    Microsoft Academic Search

    Ann E. Pulver; P. S. Wolyniec; V. K. Lasseter; Laura Kasch; Gerald Nestadt; Stylianos Antonarakis; David Housman; Haig H. Kazazian; Deborah Meyers; Jurg Ott; Malgorzata Lamacz; Kung-Yee Liang; John Hanfelt; Gail Ullrich; Nicola DeMarchi; Elango Ramu; Paul R. McHugh; Lawrence Adler; Marion Thomas; William T. Carpenter; Theo Manschreck; C. T. Gordon; Michelle Kimberland; Robert Babb; Jennifer Puck; Barton Childs

    1994-01-01

    To identify genes responsible for the susceptibility for schizophrenia, and to test the hypothesis that schizophrenia is etiologically heterogeneous, we have studied 39 multiplex families from a systematic sample of schizophrenic patients. Using a complex autosomal dominant model, which considers only those with a diagnosis of schizophrenia or schizoaffective disorder as affected, a random search of the genome for detection

  8. ENVIRONMENTAL PUBLIC HEALTH INDICATORS

    EPA Science Inventory

    Environmental Public Health Indicators (EPHIs), quantitative measures of health factors and environmental influences tracked over time, can be used to identify specific areas and populations for intervention and prevention efforts and to evaluate the outcomes of implemented polic...

  9. Quantifying the relative importance and potential interactive effects of multiple indices when predicting fire risk and severity in the Western US

    NASA Astrophysics Data System (ADS)

    Keyser, A.; Westerling, A. L.

    2010-12-01

    A long history of fire suppression in the western United States has interrupted the fire regimes of many forest types. This interruption has significantly changed forest structure and ecological function and led to increasingly uncharacteristic fires in terms of size and severity. This project investigated the potential for predicting forest fire severity across the Western US. Identifying areas at risk for fires whose severity is outside the natural fire regime will allow for targeted fuel reduction and mitigation to preserve ecosystem integrity. Our objective was to examine fire regime change, vegetation, fuels, and climate in terms of their utility in predicting forest fire severity in the Western US. How do these factors act separately to influence fire severity and what is their relative importance as co-determinants of fire severity? Is fire severity controlled more by bottom-up (vegetation and fuels) or top-down (climate) factors? We have a mapped fire severity dataset of 4591 large fires spanning twenty-four years (1984-2007) for eleven western states (AZ, CA, CO, ID, MT, NM, NV, OR, UT, WA, WY) as well as a suite of topographic and vegetation data layers from the Landfire project. Our hydro-climate dataset was developed using the VIC hydrologic model with the LDAS parameterization; we thus used the LDAS 1/8° grid to sample our fire severity, topographic, and vegetation datasets. Over our entire dataset, high severity fires make up a small percentage of the overall record. More than 75% of large fires have < 17% of the total fire area classified as high severity. Few years stand out with large fractions of high fire severity across multiple western states; 2002 is one where 6/11 states had significantly more high severity fire area than usual. Regional similarities in inter-annual high severity fire fraction and overall magnitude of high severity fraction occur. For instance, mean annual high severity fraction in large fires in the Southwestern US never reaches 20%. However, mean annual high severity for the Northern Rocky Mountains regularly reaches 30-50%. Initial analyses of the relationship between hydro-climate variables and high fractional fire severity show a number of strong relationships. High severity fraction is positively correlated to topographic complexity, Spring snowpack, and cumulative precipitation for the 12-month prior period and the 12-month period ending 6-months prior to the month of the fire. High severity fraction is negatively correlated to summer moisture deficit, average spring temperature, and cumulative adjusted moisture deficit for 12 months prior to the month of fire and the 12-month period ending 6 months prior to the fire. These initial correlations counter our hypothesis that high severity fire would be positively correlated to drier conditions. This hypothesis is based the importance of fuel moisture to fire severity and also previous results for California. We will present a final predictive model of fire severity as well as analysis as to whether patterns observed are driven more by bottom-up or top-down controls.

  10. What helps children in a pupil referral unit (PRU)? An exploration into the potential protective factors of a PRU as identified by children and staff

    Microsoft Academic Search

    Natalie Hart

    2012-01-01

    Previous studies have focused on the views of excluded children or those finding themselves in Pupil Referral Units (PRUs). Few, however, have focused on exploring views from a resilience perspective. Studies linked to resilience have tended to focus on exploring factors through quantitative rather than qualitative measures. This piece of research aimed to explore the potential protective factors of one

  11. Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy

    Microsoft Academic Search

    C M NUTTING; C M CORBISHLEY; B SANCHEZ; V P COSGROVE; S WEBB; D P DEARNALEY

    The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential

  12. Object-Based Classification as an Alternative Approach to the Traditional Pixel-Based Classification to Identify Potential Habitat of the Grasshopper Sparrow

    Microsoft Academic Search

    Benoît Jobin; Sandra Labrecque; Marcelle Grenier; Gilles Falardeau

    2008-01-01

    The traditional method of identifying wildlife habitat distribution over large regions consists of pixel-based classification\\u000a of satellite images into a suite of habitat classes used to select suitable habitat patches. Object-based classification is\\u000a a new method that can achieve the same objective based on the segmentation of spectral bands of the image creating homogeneous\\u000a polygons with regard to spatial or

  13. Expression Profiling in Medicago truncatula Identifies More Than 750 Genes Differentially Expressed during Nodulation, Including Many Potential Regulators of the Symbiotic Program1[w

    PubMed Central

    El Yahyaoui, Fikri; Küster, Helge; Amor, Besma Ben; Hohnjec, Natalija; Pühler, Alfred; Becker, Anke; Gouzy, Jérôme; Vernié, Tatiana; Gough, Clare; Niebel, Andreas; Godiard, Laurence; Gamas, Pascal

    2004-01-01

    In this study, we describe a large-scale expression-profiling approach to identify genes differentially regulated during the symbiotic interaction between the model legume Medicago truncatula and the nitrogen-fixing bacterium Sinorhizobium meliloti. Macro- and microarrays containing about 6,000 probes were generated on the basis of three cDNA libraries dedicated to the study of root symbiotic interactions. The experiments performed on wild-type and symbiotic mutant material led us to identify a set of 756 genes either up- or down-regulated at different stages of the nodulation process. Among these, 41 known nodulation marker genes were up-regulated as expected, suggesting that we have identified hundreds of new nodulation marker genes. We discuss the possible involvement of this wide range of genes in various aspects of the symbiotic interaction, such as bacterial infection, nodule formation and functioning, and defense responses. Importantly, we found at least 13 genes that are good candidates to play a role in the regulation of the symbiotic program. This represents substantial progress toward a better understanding of this complex developmental program. PMID:15466239

  14. Plants as regional indicators of Great Lakes coastal wetland health

    Microsoft Academic Search

    D. A. Albert; L. D. Minc

    2004-01-01

    In this paper we explore the potential for developing plant-based indicators for key dimensions of wetland stress, including 1) hydrologic flow modification (through water-level regulation and diking), 2) water quality degradation (through nutrient loading and sedimentation), and 3) ecological structural breakdown or physical degradation. Based on a review of the literature, we identify species or species groups that potentially function

  15. Identifying Erosion

    NSDL National Science Digital Library

    COSI

    2009-01-01

    In this environmental science activity (page 3 of the PDF), leaners will identify and explain the causes of erosion. They will observe the effects of erosion on the surrounding area and further explore examples of erosion online. An extension activity allows learners to make a hands-on model of soil erosion. Though this was created as a pre-visit activity for a workshop about water flow and erosion, it makes a great stand-alone activity as well!

  16. Identify Symmetry

    NSDL National Science Digital Library

    Mrs. Neubert

    2011-03-03

    This unit will teach you how to identify symmetry in everyday objects and mathematical shapes in lines and rotational symmetry. What is line symmetry? Click on the link to find out: Line Symmetry Here is a line activity to see if you understand it: Line Symmetry Class Zone See if you understand the concepts by doing the following quiz: Line Symmetry Work Now for rotational symmetry: Rotational Symmetry See if you understand rotational symmetry by taking this quiz: Rotational Symmetry Work ...

  17. Implementing a Real-time Complex Event Stream Processing System to Help Identify Potential Participants in Clinical and Translational Research Studies.

    PubMed

    Weber, Susan; Lowe, Henry J; Malunjkar, Sanjay; Quinn, James

    2010-01-01

    Event Stream Processing is a computational approach to the problem of how to infer the occurrence of an event from a data stream in real time without reference to a database. This paper describes how we implemented this technology on the STRIDE platform to address the challenge of real time notification of patients presenting in the Emergency Department (ED) who potentially meet eligibility criteria for a clinical study. The system was evaluated against a standalone legacy alerting system and found to perform adequately. While our initial use of this technology was focused on relatively simple alerts, the system is extensible and has the potential to provide enterprise-level research alerting services supporting more complex scenarios. PMID:21347023

  18. Use of a comparative approach to identify allelopathic potential and relationship between allelopathy bioassays and “competition” experiments for ten grassland and plant species

    Microsoft Academic Search

    D. A. Wardle; K. S. Nicholson; A. Rahman

    1996-01-01

    Various allelopathy bioassays were used to evaluate the allelopathic potential of 10 grassland forage species against a common test (phytometer) species,Carduus nutans L. Aqueous extracts did not influenceC. nutans germination, although radicle elongation was often severely inhibited.C. nutans was strongly affected by shoot, but not root, leachates. Decomposing ground tissue had mixed effects, and often stimulated shoot production ofC. nutans.

  19. SCS-CN and GIS-based approach for identifying potential water harvesting sites in the Kali Watershed, Mahi River Basin, India

    Microsoft Academic Search

    D. Ramakrishnan; A. Bandyopadhyay; K. N. Kusuma

    2009-01-01

    The Kali sub-watershed is situated in the semi-arid region of Gujarat, India and forms a part of the Mahi River Watershed.\\u000a This watershed receives an average annual rainfall of 900mm mainly between July and September. Due to high runoff potential,\\u000a evapo-transpiration and poor infiltration, drought like situation prevails in this area from December to June almost every\\u000a year. In this

  20. An ShRNA Based Genetic Screen Identified Sesn2 as a Potential Tumor Suppressor in Lung Cancer via Suppression of Akt-mTOR-p70S6K Signaling

    PubMed Central

    Zhang, Haiyuan; Liu, Jiawei; Fan, Fangfang; Li, Yilan; Ning, Xuelian; Sun, Yue; Dai, Shaochun; Liu, Baogang; Gao, Min; Fu, Songbin; Zhou, Chunshui

    2015-01-01

    Background Lung cancer is emerging rapidly as the leading death cause in Chinese cancer patients. The causal factors for Chinese lung cancer development remain largely unclear. Here we employed an shRNA library-based loss-of-function screen in a genome-wide and unbiased manner to interrogate potential tumor suppressor candidates in the immortalized human lung epithelial cell line BEAS-2B. Methods/Results Soft agar assays were conducted for screening BEAS-2B cells infected with the retroviral shRNA library with the acquired feature of anchorage-independent growth, large (>0.5mm in diameter) and well—separated colonies were isolated for proliferation. PCRs were performed to amplify the integrated shRNA fragment from individual genomic DNA extracted from each colony, and each PCR product is submitted for DNA sequencing to reveal the integrated shRNA and its target gene. A total of 6 candidate transformation suppressors including INPP4B, Sesn2, TIAR, ACRC, Nup210, LMTK3 were identified. We validated Sesn2 as the candidate of lung cancer tumor suppressor. Knockdown of Sesn2 by an shRNA targeting 3’ UTR of Sesn2 transcript potently stimulated the proliferation and malignant transformation of lung bronchial epithelial cell BEAS-2B via activation of Akt-mTOR-p70S6K signaling, whereas ectopic expression of Sens2 re-suppressed the malignant transformation elicited by the Sesn2 shRNA. Moreover, knockdown of Sesn2 in BEAS-2B cells promoted the BEAS-2B cell-transplanted xenograft tumor growth in nude mice. Lastly, DNA sequencing indicated mutations of Sesn2 gene are rare, the protein levels of Sesn2 of 77 Chinese lung cancer patients varies greatly compared to their adjacent normal tissues, and the low expression level of Sesn2 associates with the poor survival in these examined patients by Kaplan Meier analysis. Conclusions Our shRNA-based screen has demonstrated Sesn2 is a potential tumor suppressor in lung epithelial cells. The expression level of Sesn2 may serve as a prognostic marker for Chinese lung cancer patients in the clinic. PMID:25962159

  1. Operculoinsular cortex encodes pain intensity at the earliest stages of cortical processing as indicated by amplitude of laser-evoked potentials in humans

    Microsoft Academic Search

    G. D. Iannetti; L. Zambreanu; G. Cruccu; I. Tracey

    2005-01-01

    Converging evidence from different functional imaging studies indicates that the intensity of activation of different nociceptive areas (including the operculoinsular cortex, the primary somatosensory cortex, and the anterior cingulate gyrus) correlates with perceived pain intensity in the human brain. Brief radiant laser pulses excite selectively A? and C nociceptors in the superficial skin layers, provide a purely nociceptive input, and

  2. Isolation and characterization of potential indicator bacteria to be used for validation of Escherichia coli O157:H7 reduction in beef slaughter plant critical control points

    E-print Network

    Magana Yepez, Maria Belem

    2005-11-01

    are in beef slaughter processing. Since E. coli O157:H7 has been shown to have some acid resistance, the ability of typical indicator organisms to accurately predict the reduction of this pathogen by carcass decontamination procedures has been a concern...

  3. Effects of Exercise Intervention on Event-Related Potential and Task Performance Indices of Attention Networks in Children with Developmental Coordination Disorder

    ERIC Educational Resources Information Center

    Tsai, Chia-Liang; Wang, Chun-Hao; Tseng, Yu-Ting

    2012-01-01

    The study investigated whether 10-week soccer training can benefit the inhibitory control and neuroelectric indices in children with developmental coordination disorder (DCD). Fifty-one children were divided into groups of typically developing (TD, n = 21), DCD-training (n = 16), and DCD non-training (n=14) individuals using the for Children test,…

  4. RBC indices

    MedlinePLUS

    ... corpuscular hemoglobin concentration (MCHC); Mean corpuscular volume (MCV); Red blood cell indices ... and hemoglobin. The MCV reflects the size of red blood cells. The MCH and MCHC reflect the ...

  5. Regional differences in species composition and toxigenic potential among Fusarium head blight isolates from Uruguay indicate a risk of nivalenol contamination in new wheat production areas

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Members of the Fusarium graminearum species complex (FGSC) are the primary cause of Fusarium head blight (FHB) of wheat, and frequently contaminate grain with trichothecene mycotoxins that pose a serious threat to food safety and animal health. The species identity and trichothecene toxin potential...

  6. Spatial association as an indicator of the potential for future interactions between wind energy developments and golden eagles Aquila chrysaetos in Scotland

    Microsoft Academic Search

    Alan H. Fielding; D. Philip Whitfield; David R. A. McLeod

    2006-01-01

    Despite their environmental benefits in generating electricity without emission of ‘greenhouse’ gases, wind farms have attracted controversy with regard to their impacts on birds, especially golden eagles Aquila chrysaetos. Evidence from USA studies suggest eagle fatalities through collision with turbines may be the main potential impact whereas for breeding eagles in Scotland, displacement from wind farm areas (indirect habitat loss)

  7. Phosphorylation within the cysteine-rich region of dystrophin enhances its association with ?-dystroglycan and identifies a potential novel therapeutic target for skeletal muscle wasting.

    PubMed

    Swiderski, Kristy; Shaffer, Scott A; Gallis, Byron; Odom, Guy L; Arnett, Andrea L; Scott Edgar, J; Baum, Dale M; Chee, Annabel; Naim, Timur; Gregorevic, Paul; Murphy, Kate T; Moody, James; Goodlett, David R; Lynch, Gordon S; Chamberlain, Jeffrey S

    2014-12-20

    Mutations in dystrophin lead to Duchenne muscular dystrophy, which is among the most common human genetic disorders. Dystrophin nucleates assembly of the dystrophin-glycoprotein complex (DGC), and a defective DGC disrupts an essential link between the intracellular cytoskeleton and the basal lamina, leading to progressive muscle wasting. In vitro studies have suggested that dystrophin phosphorylation may affect interactions with actin or syntrophin, yet whether this occurs in vivo or affects protein function remains unknown. Utilizing nanoflow liquid chromatography mass spectrometry, we identified 18 phosphorylated residues within endogenous dystrophin. Mutagenesis revealed that phosphorylation at S3059 enhances the dystrophin-dystroglycan interaction and 3D modeling utilizing the Rosetta software program provided a structural model for how phosphorylation enhances this interaction. These findings demonstrate that phosphorylation is a key mechanism regulating the interaction between dystrophin and the DGC and reveal that posttranslational modification of a single amino acid directly modulates the function of dystrophin. PMID:25082828

  8. Energy transport corridors: the potential role of Federal lands in states identified by the Energy Policy Act of 2005, section 368(b).

    SciTech Connect

    Krummel, J.; Hlohowskyj, I.; Kuiper, J.; Kolpa, R.; Moore, R.; May, J.; VanKuiken, J.C.; Kavicky, J.A.; McLamore, M.R.; Shamsuddin, S. (Decision and Information Sciences); ( EVS)

    2011-09-01

    On August 8, 2005, the President signed the Energy Policy Act of 2005 (EPAct) into law. In Subtitle F of EPAct, Congress set forth various provisions that would change the way certain federal agencies (Agencies) coordinate to authorize the use of land for a variety of energy-related purposes. As part of Subtitle F of EPAct, Section 368 addresses the issue of energy transportation corridors on federal land for oil, gas, and hydrogen pipelines, as well as electricity transmission and distribution facilities. Because of the critical importance of improving the nation's electrical transmission grid, Congress recognized that electricity transmission issues should receive added attention when the Agencies address corridor location and analysis issues. In Section 368, Congress specifically directed the Agencies to consider the need for upgraded and new facilities to deliver electricity: In carrying out [Section 368], the Secretaries shall take into account the need for upgraded and new electricity transmission and distribution facilities to (1) improve reliability; (2) relieve congestion; and (3) enhance capability of the national grid to deliver electricity. Section 368 does not require the Agencies to consider or approve specific projects, applications for rights-of-way (ROWs), or other permits within designated energy corridors. Importantly, Section 368 does not direct, license, or otherwise permit any on-the-ground activity of any sort. If an applicant is interested in obtaining an authorization to develop a project within any corridor designated under Section 368, the applicant would have to apply for a ROW authorization and applicable permits. The Agencies would consider each application by applying appropriate project-specific reviews under requirements of laws and related regulations, including, but not limited to, the National Environmental Policy Act (NEPA), the Clean Water Act, the Clean Air Act, Section 7 of the Endangered Species Act (ESA), and Section 106 of the National Historic Preservation Act (NHPA). Under Section 368, Congress divided the United States into two groups of states: the 11 contiguous western states and the remaining states. Direction for energy transportation corridor analysis and selection in the 11 western states was addressed in Section 368(a) of EPAct, while direction for energy transportation corridor analysis and selection in all other states was addressed under Section 368(b) of EPAct. It was clearly the priority of Congress to conduct corridor location studies and designation first on federal lands in the western states. Under Section 368(a), the Agencies produced a programmatic environmental impact statement (EIS), Designation of Energy Corridors on Federal Land in the 11 Western States (DOE and DOI 2008), that was used in part as the basis for designating more than 6,000 mi (9,656 km) of energy transportation corridors on federal land in 11 western states. Under Section 368(a) of EPAct, Congress clearly stated the Agencies needed to (1) designate energy transportation corridors on federal land, (2) conduct the necessary environmental review of the designated corridors, and (3) incorporate the designated corridors into the appropriate land use plans. Congressional direction under Section 368(b) of EPAct differs from that provided under Section 368(a). Specifically, Section 368(b) requires the secretaries of the Agencies, in consultation with the Federal Energy Regulatory Commission (FERC), affected utility industries, and other interested persons, to jointly: (1) Identify corridors for oil, gas, and hydrogen pipelines and electricity transmission and distribution facilities on federal land in states other than the 11 western states identified under Section 368(a) of EPAct, and (2) Schedule prompt action to identify, designate, and incorporate the corridors into the applicable land use plans. While Section 368(a) clearly directs designation as a necessary first step for energy transportation corridors in the 11 western states, Section 368(b) directs the Agencies to first identify corridor

  9. Twitter as a Potential Disaster Risk Reduction Tool. Part II: Descriptive Analysis of Identified Twitter Activity during the 2013 Hattiesburg F4 Tornado

    PubMed Central

    Cooper, Guy Paul; Yeager, Violet; Burkle, Frederick M.; Subbarao, Italo

    2015-01-01

    Background: This article describes a novel triangulation methodological approach for identifying twitter activity of regional active twitter users during the 2013 Hattiesburg EF-4 Tornado. Methodology: A data extraction and geographically centered filtration approach was utilized to generate Twitter data for 48 hrs pre- and post-Tornado. The data was further validated using six sigma approach utilizing GPS data. Results: The regional analysis revealed a total of 81,441 tweets, 10,646 Twitter users, 27,309 retweets and 2637 tweets with GPS coordinates. Conclusions: Twitter tweet activity increased 5 fold during the response to the Hattiesburg Tornado.  Retweeting activity increased 2.2 fold. Tweets with a hashtag increased 1.4 fold. Twitter was an effective disaster risk reduction tool for the Hattiesburg EF-4 Tornado 2013. 

  10. Small ncRNA Expression-Profiling of Blood from Hemophilia A Patients Identifies miR-1246 as a Potential Regulator of Factor 8 Gene

    PubMed Central

    Sarachana, Tewarit; Dahiya, Neetu; Simhadri, Vijaya L.; Pandey, Gouri Shankar; Saini, Surbhi; Guelcher, Christine; Guerrera, Michael F.; Kimchi-Sarfaty, Chava; Sauna, Zuben E.; Atreya, Chintamani D.

    2015-01-01

    Hemophilia A (HA) is a bleeding disorder caused by deficiency of functional plasma clotting factor VIII (FVIII). Genetic mutations in the gene encoding FVIII (F8) have been extensively studied. Over a thousand different mutations have been reported in the F8 gene. These span a diverse range of mutation types, namely, missense, splice-site, deletions of single and multiple exons, inversions, etc. There is nonetheless evidence that other molecular mechanisms, in addition to mutations in the gene encoding the FVIII protein, may be involved in the pathobiology of HA. In this study, global small ncRNA expression profiling analysis of whole blood from HA patients, and controls, was performed using high-throughput ncRNA microarrays. Patients were further sub-divided into those that developed neutralizing-anti-FVIII antibodies (inhibitors) and those that did not. Selected differentially expressed ncRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. We identified several ncRNAs, and among them hsa-miR-1246 was significantly up-regulated in HA patients. In addition, miR-1246 showed a six-fold higher expression in HA patients without inhibitors. We have identified an miR-1246 target site in the noncoding region of F8 mRNA and were able to confirm the suppressory role of hsa-miR-1246 on F8 expression in a stable lymphoblastoid cell line expressing FVIII. These findings suggest several testable hypotheses vis-à-vis the role of nc-RNAs in the regulation of F8 expression. These hypotheses have not been exhaustively tested in this study as they require carefully curated clinical samples. PMID:26176629

  11. Robust process capability indices

    Microsoft Academic Search

    Sameer Prasad; Tom Bramorski

    1998-01-01

    Many organizations are mandating the use of process capability indices to measure and reduce variability. Managers may find the use of such indices as unreliable when the interaction of the dependency structure and outliers mask potential assignable causes of variation. A monitoring procedure is proposed that effectively classifies a series' variability into three components: (1) the underlying correlation structure, (2)

  12. Fragmentation patterns in the diatom genus Rouxia and their potential for identifying latent depositional hiatuses in the early Pliocene diatomite of the ANDRILL AND-1B core

    NASA Astrophysics Data System (ADS)

    Konfirst, M. A.; Scherer, R. P.; Winter, D.; Sjunneskog, C.; Warnock, J.; Kuhn, G.; Niessen, F.; Helling, D.; Magens, D.

    2009-04-01

    Diatom genera have traditionally been split into two primary groupings based upon the symmetry of the siliceous frustule. Diatoms symmetric about a point are classified as centrics, while those symmetric about a line are classified as pennates. This fundamental difference in shape has consequences for preservation in ice proximal settings, where an overriding ice sheet can create shearing in the upper meters of the sediment column. This leads to preferential breakage in pennate forms, and results in a higher ratio of undamaged centric to pennate frustules (Scherer et al., 2004). Similarly, an ice sheet grounded over highly porous diatomite results in significant diatom fragmentation resulting from normal load compaction. The diatom genus Rouxia is a pennate form with a relatively wide raphe, making it particularly susceptible to breakage during ice advance and retreat, and offering the opportunity to evaluate ice advance stages in sedimentary units where glacial erosion may have removed upper depositional units. In the ANDRILL AND-1B core, a long interval of nearly pure diatomite was recovered from 382.98-459.24 mbsf. Construction of an age model during this interval has relied primarily on age ranges provided by presence or absence of key diatom species. However, questions still remain as to the continuity of deposition. In this study, samples were collected at an average of 50-cm spacing for the length of the long diatom unit as well as for 20 meters of the silica-rich diamictite unit directly overlaying the diatomite. Fragments of specimens from the genus Rouxia were counted and classified into categories based on the size of the fragment in relation to total frustule length. These data were then used to develop a quantitative index, which was examined for changes in fragmentation through time. Preliminary data are presented that indicate increased fragmentation at the top of the section under study, which we interpret to indicate evidence for increased glacial shearing. Below this (401.11-373.61 mbsf), fragmentation levels remain virtually constant, which is taken to indicate a relatively long interval of continuous deposition and evenly distributed effects of normal load compaction. A sharp increase in the fragmentation index at 401.35 mbsf is interpreted as evidence for a depositional hiatus and corresponds to a peak in abundance of the silicoflagelate genus Distephanus. More sporadic fragmentation occurs below 401.35. Future work will include comparing these results to sediment texture and physical properties of the core.

  13. Use of a comparative approach to identify allelopathic potential and relationship between allelopathy bioassays and "competition" experiments for ten grassland and plant species.

    PubMed

    Wardle, D A; Nicholson, K S; Rahman, A

    1996-05-01

    Various allelopathy bioassays were used to evaluate the allelopathic potential of 10 grassland forage species against a common test (phytometer) species,Carduus nutans L. Aqueous extracts did not influenceC. nutans germination, although radicle elongation was often severely inhibited.C. nutans was strongly affected by shoot, but not root, leachates. Decomposing ground tissue had mixed effects, and often stimulated shoot production ofC. nutans. Calculation ofR (2) (coefficient of determination) values between these results, and the results of previous experiments investigating the effects of the same 10 species onC. nutans emergence and development in field plots and glasshouse competition experiments frequently revealed strong, statistically significant relationships. Our results therefore provide correlative evidence for the importance of allelopathy in field conditions. PMID:24227616

  14. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study.

    PubMed

    Wu, Jing; Lu, Chanyi; Diao, Ni; Zhang, Shu; Wang, Sen; Wang, Feifei; Gao, Yan; Chen, Jiazhen; Shao, Lingyun; Lu, Jingning; Zhang, Xuelian; Weng, Xinhua; Wang, Honghai; Zhang, Wenhong; Huang, Yuxian

    2012-01-01

    To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p < 0.0001); miR-155* exhibited a fold change of 1.9 in the HC and 4.6 in the ATB group (p < 0.005). In ROC plots, the area under the curve was 0.8972 for miR-155 and 0.7945 for miR-155*. The background expression of these 2 microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. PMID:22037148

  15. Identifying Species

    NSDL National Science Digital Library

    Michael DiSpezio

    This two part activity will allow students to investigate biological diversity in the area of their school. They will first prepare a taxonomic key to distinguish between the four insects or spiders that they have selected. All of the keys are combined and students then perform a transect study of a neighborhood field or school playing ground. Finally as a class students will compile a list of the animals and plants that are found within a mile of their school. They may need to use field guides, local resources, taxonomic keys, and species lists to help identify these organisms. Once they have compiled their list they will organize the species into the taxonomic groups they have studied.

  16. Extended x-ray absorption fine-structure indication of a double-well potential for oxygen vibration in Ba1 - xKxBiO3

    NASA Astrophysics Data System (ADS)

    Menushenkov, A. P.; Klementev, K. V.

    2000-04-01

    X-ray absorption spectra of the oxide systems Ba1 - x Kx BiO3 and BaPbO3 above the Bi and Pb L3 absorption edges were investigated. It was shown that oxygen ions move in a double-well potential and their oscillations are correlated with the charge-carrier movement. The observed breathing-like oxygen vibration in the double-well potential with large amplitude and low frequency causes the strong electron-phonon coupling and high Tc -values for doped BaBiO3 . Based on the experimental data, a model of the relationship of the electronic and local crystal structures is proposed that is in good agreement with the results from transport measurements, and inelastic neutron and electron scattering, Raman scattering, and photoemission spectroscopy. In the framework of the model, the possible reasons for the superconductivity in perovskite-like oxides are discussed.

  17. Position indicator

    DOEpatents

    Tanner, David E. (Poway, CA)

    1981-01-01

    A nuclear reactor system is described in which a position indicator is provided for detecting and indicating the position of a movable element inside a pressure vessel. The movable element may be a valve element or similar device which moves about an axis. Light from a light source is transmitted from a source outside the pressure vessel to a first region inside the pressure vessel in alignment with the axis of the movable element. The light is redirected by a reflector prism to a second region displaced radially from the first region. The reflector prism moves in response to movement of the movable element about its axis such that the second region moves arcuately with respect to the first region. Sensors are arrayed in an arc corresponding to the arc of movement of the second region and signals are transmitted from the sensors to the exterior of the reactor vessel to provide indication of the position of the movable element.

  18. Rapid, non-invasive imaging of alphaviral brain infection: Reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals

    PubMed Central

    Patterson, Michael; Poussard, Allison; Taylor, Katherine; Seregin, Alexey; Smith, Jeanon; Peng, Bi-Hung; Walker, Aida; Linde, Jenna; Smith, Jennifer; Salazar, Milagros; Paessler, Slobodan

    2011-01-01

    Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume’s 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion. PMID:22001884

  19. Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention

    PubMed Central

    Zambrowicz, Brian P.; Abuin, Alejandro; Ramirez-Solis, Ramiro; Richter, Lizabeth J.; Piggott, James; BeltrandelRio, Hector; Buxton, Eric C.; Edwards, Joel; Finch, Rick A.; Friddle, Carl J.; Gupta, Anupma; Hansen, Gwenn; Hu, Yi; Huang, Wenhu; Jaing, Crystal; Key, Billie Wayne; Kipp, Peter; Kohlhauff, Buckley; Ma, Zhi-Qing; Markesich, Diane; Payne, Robert; Potter, David G.; Qian, Ny; Shaw, Joseph; Schrick, Jeff; Shi, Zheng-Zheng; Sparks, Mary Jean; Van Sligtenhorst, Isaac; Vogel, Peter; Walke, Wade; Xu, Nianhua; Zhu, Qichao; Person, Christophe; Sands, Arthur T.

    2003-01-01

    The availability of both the mouse and human genome sequences allows for the systematic discovery of human gene function through the use of the mouse as a model system. To accelerate the genetic determination of gene function, we have developed a sequence-tagged gene-trap library of >270,000 mouse embryonic stem cell clones representing mutations in ?60% of mammalian genes. Through the generation and phenotypic analysis of knockout mice from this resource, we are undertaking a functional screen to identify genes regulating physiological parameters such as blood pressure. As part of this screen, mice deficient for the Wnk1 kinase gene were generated and analyzed. Genetic studies in humans have shown that large intronic deletions in WNK1 lead to its overexpression and are responsible for pseudohypoaldosteronism type II, an autosomal dominant disorder characterized by hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Consistent with the human genetic studies, Wnk1 heterozygous mice displayed a significant decrease in blood pressure. Mice homozygous for the Wnk1 mutation died during embryonic development before day 13 of gestation. These results demonstrate that Wnk1 is a regulator of blood pressure critical for development and illustrate the utility of a functional screen driven by a sequence-based mutagenesis approach. PMID:14610273

  20. Potential gastrointestinal tumor suppressor locus at the 3p14.2 FRA3B site identified by homozygous deletions in tumor cell lines.

    PubMed

    Kastury, K; Baffa, R; Druck, T; Ohta, M; Cotticelli, M G; Inoue, H; Negrini, M; Rugge, M; Huang, D; Croce, C M; Palazzo, J; Huebner, K

    1996-03-01

    A number of DNA fragments, identified by representational difference analysis, which were homozygously deleted in various cancer cell lines were previously mapped to human chromosomal arms. One of these, BE758-6, which was homozygously deleted in a number of colon carcinoma cell lines, had been mapped to chromosome region 3p. We have further localized the probe to 3p14.2, approximately 350kbp telomeric to the 3p14.2 break of the t(3;8) hereditary renal cell carcinoma chromosome translocation, within or near the 3p14.2 FRA3B, the most common human fragile site. We determined the sizes of the homozygous deletions in a number of cancer cell lines after isolation of a yeast artificial chromosome contig and development of STS markers which fall between D3S1234 and D2S1481, which flank the deletions. Homozygous deletions were observed and sized not only in the cell lines originally reported but also in a number of nasopharyngeal carcinoma cell lines and a gastric carcinoma cell line. About 50% of uncultured stomach and colon carcinomas were then shown to lose heterozygosity for alleles in the same region, with a common region of loss between the D3S1234 and D3S1481 markers. Thus, it is likely that the homozygous deletion observed in these cancer cell lines harbors an important tumor suppressor gene for several tumor types. PMID:8640789

  1. Rapid, non-invasive imaging of alphaviral brain infection: reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals.

    PubMed

    Patterson, Michael; Poussard, Allison; Taylor, Katherine; Seregin, Alexey; Smith, Jeanon; Peng, Bi-Hung; Walker, Aida; Linde, Jenna; Smith, Jennifer; Salazar, Milagros; Paessler, Slobodan

    2011-11-21

    Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume's 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion. PMID:22001884

  2. Shotgun metabolomic profiles in maternal urine identify potential mass spectral markers of abnormal fetal biochemistry - dihydrouracil and progesterone in the metabolism of Down syndrome.

    PubMed

    Trivedi, Drupad K; Iles, Ray K

    2015-08-01

    In Down syndrome (DS) in particular, the precise cellular mechanisms linking genotype to phenotype is not straightforward despite a clear mapping of the genetic cause. Metabolomic profiling might be more revealing in understanding molecular-cellular mechanisms of inborn errors of metabolism/syndromes than genomics alone and also result in new prenatal screening approaches. The urinary metabolome of 122 maternal urine from women with and without an aneuploid pregnancy (predominantly Down syndrome) were compared by both zwitterionic hydrophilic interaction chromatography (ZIC-HILIC) and reversed-phase liquid chromatography (RPLC) coupled to hybrid ion trap time of flight mass spectral analysis. ZIC-HILIC mass spectrometry resolved 10-fold more unique molecular ions than RPLC mass spectrometry, of which molecules corresponding to ions of m/z 114.07 and m/z 314.20 showed maternal urinary level changes that significantly coincided with the presence of a DS fetus. The ion of m/z 314.20 was identified as progesterone and m/z 114.07 as dihydrouracil. A metabolomics profiling-based maternal urinary screening test modelled from this separation data would detect approximately 87 and 60.87% (using HILIC-MS and RPLC-MS, respectively) of all DS pregnancies between 9 and 23?weeks of gestation with no false positives. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25545476

  3. Analysis of BH3-only proteins upregulated in response to oxygen/glucose deprivation in cortical neurons identifies Bmf but not Noxa as potential mediator of neuronal injury

    PubMed Central

    Pfeiffer, S; Anilkumar, U; Chen, G; Ramírez-Peinado, S; Galindo-Moreno, J; Muñoz-Pinedo, C; Prehn, J H M

    2014-01-01

    Stress signaling in response to oxygen/glucose deprivation (OGD) and ischemic injury activates a group of pro-apoptotic genes, the Bcl-2 homology domain 3 (BH3)-only proteins, which are capable of activating the mitochondrial apoptosis pathway. Targeted studies previously identified the BH3-only proteins Puma, Bim and Bid to have a role in ischemic/hypoxic neuronal injury. We here investigated the transcriptional activation of pro-apoptotic BH3-only proteins after OGD-induced injury in murine neocortical neurons. We observed a potent and early upregulation of noxa at mRNA and protein level, and a significant increase in Bmf protein levels during OGD in neocortical neurons and in the ipsilateral cortex of mice subjected to transient middle cerebral artery occlusion (tMCAO). Surprisingly, gene deficiency in noxa reduced neither OGD- nor glutamate-induced neuronal injury in cortical neurons and failed to influence infarct size or neurological deficits after tMCAO. In contrast, bmf deficiency induced significant protection against OGD- or glutamate-induced injury in cultured neurons, and bmf-deficient mice showed reduced neurological deficits after tMCAO in vivo. Collectively, our data not only point to a role of Bmf as a BH3-only protein contributing to excitotoxic and ischemic neuronal injury but also demonstrate that the early and potent induction of noxa does not influence ischemic neuronal injury. PMID:25299781

  4. Gonad RNA-specific qRT-PCR analyses identify genes with potential functions in schistosome reproduction such as SmFz1 and SmFGFRs

    PubMed Central

    Hahnel, Steffen; Quack, Thomas; Parker-Manuel, Sophia J.; Lu, Zhigang; Vanderstraete, Mathieu; Morel, Marion; Dissous, Colette; Cailliau, Katia; Grevelding, Christoph G.

    2014-01-01

    In the search for new strategies to fight schistosomiasis, the unique reproductive biology of Schistosoma mansoni has come into the focus of research. The development of the gonads and the ability of egg production are fundamental not only for continuing the life cycle but also for pathogenicity. Previous studies of schistosome biology demonstrated an influence of pairing on gonad development of the female and on gene expression profiles in both genders. Due to the limited access to specific tissues, however, most of these studies were done at the level of whole worms neglecting individual tissues that may be targets of pairing-dependent processes. Recently, we established a protocol allowing the isolation of testes and ovaries from adult S. mansoni. Here, we describe tissue-specific qRT-PCR analyses comparing transcript levels of selected genes on the basis of RNA from gonads and whole worms. Gene expression in ovary and testes was in some cases found to be significantly influenced by pairing, which was not traceable in whole worms. Among the candidate genes identified as regulated by pairing in gonads were the frizzled homolog SmFz1 and the two fibroblast growth factor receptor homologs SmFGFR-A and SmFGFR-B. First functional characterizations were done, including comparative qRT-PCR analyses, in situ-localization experiments, heterologous expression in Xenopus oocytes (SmFGFR-A/B), and inhibitor studies using the Fz/Dvl-pathway inhibitor 3289-8625, or BIBF1120 blocking FGFR-signaling. Besides confirming gonad localization and receptor functions, inhibitor-induced phenotypes were observed in vitro such as decreased egg production as well as drastic effects on gonad differentiation, morphology, embryogenesis, and survival of adult worms. In summary, these results emphasise the usefulness of tissue-specific qRT-PCRs for selection of candidate genes with important roles in reproduction, allowing subsequent studies to determine their suitability as drug targets. PMID:24959172

  5. A high-throughput screen identifies PARP1/2 inhibitors as a potential therapy for ERCC1-deficient non-small cell lung cancer.

    PubMed

    Postel-Vinay, S; Bajrami, I; Friboulet, L; Elliott, R; Fontebasso, Y; Dorvault, N; Olaussen, K A; André, F; Soria, J-C; Lord, C J; Ashworth, A

    2013-11-21

    Excision repair cross-complementation group 1 (ERCC1) is a DNA repair enzyme that is frequently defective in non-small cell lung cancer (NSCLC). Although low ERCC1 expression correlates with platinum sensitivity, the clinical effectiveness of platinum therapy is limited, highlighting the need for alternative treatment strategies. To discover new mechanism-based therapeutic strategies for ERCC1-defective tumours, we performed high-throughput drug screens in an isogenic NSCLC model of ERCC1 deficiency and dissected the mechanism underlying ERCC1-selective effects by studying molecular biomarkers of tumour cell response. The high-throughput screens identified multiple clinical poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors, such as olaparib (AZD-2281), niraparib (MK-4827) and BMN 673, as being selective for ERCC1 deficiency. We observed that ERCC1-deficient cells displayed a significant delay in double-strand break repair associated with a profound and prolonged G?/M arrest following PARP1/2 inhibitor treatment. Importantly, we found that ERCC1 isoform 202, which has recently been shown to mediate platinum sensitivity, also modulated PARP1/2 sensitivity. A PARP1/2 inhibitor-synthetic lethal siRNA screen revealed that ERCC1 deficiency was epistatic with homologous recombination deficiency. However, ERCC1-deficient cells did not display a defect in RAD51 foci formation, suggesting that ERCC1 might be required to process PARP1/2 inhibitor-induced DNA lesions before DNA strand invasion. PARP1 silencing restored PARP1/2 inhibitor resistance in ERCC1-deficient cells but had no effect in ERCC1-proficient cells, supporting the hypothesis that PARP1 might be required for the ERCC1 selectivity of PARP1/2 inhibitors. This study suggests that PARP1/2 inhibitors as a monotherapy could represent a novel therapeutic strategy for NSCLC patients with ERCC1-deficient tumours. PMID:23934192

  6. Chemical Indicators.

    ERIC Educational Resources Information Center

    Prombain, Dorothy R.; And Others

    This science sourcebook was written for intermediate grade teachers to provide guidance in teaching a specially developed unit on chemical indicators. Directions and suggestions for guiding student science activities are given. Some of the activities concern soil testing, crystals, and household powders such as sugar and salt. A list of necessary…

  7. Cumulative ventilation air drying potential as an indication of dry mass content in wastewater sludge in a thin-layer solar drying facility

    NASA Astrophysics Data System (ADS)

    Krawczyk, Piotr

    2013-12-01

    Controlling low-temperature drying facilities which utilise nonprepared air is quite difficult, due to very large variability of ventilation air parameters - both in daily and seasonal cycles. The paper defines the concept of cumulative drying potential of ventilation air and presents experimental evidence that there is a relation between this parameter and condition of the dried matter (sewage sludge). Knowledge on current dry mass content in the dried matter (sewage sludge) provides new possibilities for controlling such systems. Experimental data analysed in the paper was collected in early 2012 during operation of a test solar drying facility in a sewage treatment plant in B?onie near Warsaw, Poland.

  8. Identifying the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) as a potential target for hypericin--a theoretical study.

    PubMed

    Eriksson, Emma S E; Eriksson, Leif A

    2012-09-28

    The exact cellular target for the potent anti-cancer agent hypericin has not yet been determined; this thus encourages the application of computational chemistry tools to be employed in order to provide insights that can be employed in further drug development studies. In the present study computational docking and molecular dynamics simulations are applied to investigate possible interactions between hypericin and the Ca(2+) pump SERCA as proposed in the literature. Hypericin was found to bind strongly both in pockets within the transmembrane region and in the cytosolic region of the protein, although the two studied isoforms of SERCA differ slightly in their preferred binding sites. The calculated binding energies for hypericin in the four investigated sites were of the same magnitude as for thapsigargin (TG), the most potent SERCA inhibitor, or in the range between TG and di-tert-butylhydroquinone (BHQ), which is also known to possess inhibitory activity. The hydrophobic character of hypericin indicates that the molecule initially binds in the ER membrane from which it diffuses into the transmembrane region of the protein and to binding pockets therein. The transmembrane TG and BHQ binding pockets provide suitable locations for hypericin as they allow for favourable interactions with the lipid tails that surround these. High binding energies were noted for hypericin in these pockets and are expected to constitute highly possible binding sites due to their accessibility from the ER membrane. Hypericin most likely binds to both isoforms of SERCA and acts as an inhibitor or, under light irradiation, as a singlet oxygen generator that in turn degrades the protein or induces lipid peroxidation. PMID:22892582

  9. Compound library screening identified Akt/PKB kinase pathway inhibitors as potential key molecules for the development of new chemotherapeutics against schistosomiasis

    PubMed Central

    Morel, Marion; Vanderstraete, Mathieu; Cailliau, Katia; Lescuyer, Arlette; Lancelot, Julien; Dissous, Colette

    2014-01-01

    Protein kinases (PKs) are one of the largest protein families in most eukaryotic organisms. These enzymes are involved in the control of cell proliferation, differentiation and metabolism and a large number of the anticancer drugs currently used are directed against PKs. The structure and function of PKs are well conserved throughout evolution. In schistosome parasites, PKs were shown to be involved in essential functions at every stage of the parasite life cycle, making these enzymes promising anti-parasite drug targets. In this study, we tested a panel of commercial inhibitors for various PKs and analyzed their effects on pairing and egg production by schistosomes as well as their toxicity towards schistosomula larvae. Results obtained confirmed the deleterious effect of PK targeting on Schistosoma mansoni physiology and the important function of different tyrosine and serine/threonine kinases in the biology and reproduction of this parasite. They also indicated for the first time that the Protein kinase B (also called Akt) which is a major downstream target of many receptor tyrosine kinases and a central player at the crossroads of signal transduction pathways activated in response to growth factors and insulin, can constitute a novel target for anti-schistosome chemotherapy. Structural and functional studies have shown that SmAkt is a conserved kinase and that its activity can be inhibited by commercially available Akt inhibitors. In treated adult worms, Akt/PKB kinase pathway inhibitors induced profound alterations in pairing and egg laying and they also greatly affected the viability of schistosomula larvae. PMID:25516836

  10. Expression of Erk5 in Early Stage Breast Cancer and Association with Disease Free Survival Identifies this Kinase as a Potential Therapeutic Target

    PubMed Central

    Abad, Mar; Ortiz-Ruiz, María Jesús; Pandiella, Atanasio; Esparís-Ogando, Azucena

    2009-01-01

    Background Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improved disease outcome, some patients relapse. Therefore, attempts to better define the molecular determinants that drive breast cancer cell proliferation may help in defining potential therapeutic targets. Mitogen-activated protein kinases (MAPK) play important roles in tumorigenesis. One of them, Erk5, has been linked to the proliferation of breast cancer cells in vitro. Here we have investigated the expression and prognostic value of Erk5 in human breast cancer. Methodology/Principal Findings Animal and cellular models were used to study Erk5 expression and function in breast cancer. In 84 human breast tumours the expression of Erk5 was analyzed by immunohistochemistry. Active Erk5 (pErk5) was studied by Western blotting. Correlation of Erk5 with clinicopathological parameters and with disease-free survival in early stage breast cancer patients was analyzed. Expression of Erk5 was detected in most patients, and overexpression was found in 20%. Active Erk5 was present in a substantial number of samples, as well as in tumours from an animal breast cancer model. Overexpression of Erk5 was associated with a decrease in disease-free survival time, which was independent of other clinicopathological parameters of prognosis. Transient transfection of a short hairpin RNA (shRNA) targeting Erk5, and a stable cell line expressing a dominant negative form of Erk5 (Erk5AEF), were used to investigate the influence of Erk5 on drugs used in the clinic to treat breast tumours. We found that inhibition of Erk5 decreased cancer cell proliferation and also sensitized these cells to the action of anti-HER2 therapies. Conclusions/Significance Overexpression of Erk5 is an independent predictor of disease-free survival in breast cancer, and may represent a future therapeutic target. PMID:19440538

  11. The relationship between uric acid and its oxidative product allantoin: a potential indicator for the evaluation of oxidative stress in birds.

    PubMed

    Tsahar, Ella; Arad, Zeev; Izhaki, Ido; Guglielmo, Christopher G

    2006-09-01

    Uric acid is the main nitrogenous waste product in birds but it is also known to be a potent antioxidant. Hominoid primates and birds lack the enzyme urate oxidase, which oxidizes uric acid to allantoin. Consequently, the presence of allantoin in their plasma results from non-enzymatic oxidation. In humans, the allantoin to uric acid ratio in plasma increases during oxidative stress, thus this ratio has been suggested to be an in vivo marker for oxidative stress in humans. We measured the concentrations of uric acid and allantoin in the plasma and ureteral urine of white-crowned sparrows (Zonotrichia leucophrys gambelii) at rest, immediately after 30 min of exercise in a hop/hover wheel, and after 1 h of recovery. The plasma allantoin concentration and the allantoin to uric acid ratio did not increase during exercise but we found a positive relationship between the concentrations of uric acid and allantoin in the plasma and in the ureteral urine in the three activity phases. In the plasma, the slope of the regression describing the above positive relationships was significantly higher immediately after activity. We suggest that the slope indicates the rate of uric acid oxidation and that during activity this rate increases as a result of higher production of free radicals. The present study demonstrates that allantoin is present in the plasma and in the ureteral urine of white-crowned sparrows and therefore might be useful as an indicator of oxidative stress in birds. PMID:16705445

  12. THE VIOLOGEN INDICATORS

    PubMed Central

    Michaelis, L.; Hill, Edgar S.

    1933-01-01

    The tabulation gives the normal potentials of the various indicators at 30°C.; referred to the normal hydrogen electrode, the accuracy is estimated to be ±0.002 volt. Normal potentials of the viologens at 30°C.: Methyl viologen –0.446 volts Ethyl viologen –0.449 volts Betaine viologen –0.444 volts Benzyl viologen –0.359 volts Supposing some solution brings about a coloration of one of these indicators to the extent of A per cent of the maximum color, the oxidation-reduction potential of this solution is E = Eo – 0.06 log See PDF for Equation where Eo is the normal potential according to the above tabulation. This normal potential is independent of pH. PMID:19872744

  13. Monitoring of coastal coral reefs near Dahab (Gulf of Aqaba, Red Sea) indicates local eutrophication as potential cause for change in benthic communities.

    PubMed

    Naumann, Malik S; Bednarz, Vanessa N; Ferse, Sebastian C A; Niggl, Wolfgang; Wild, Christian

    2015-02-01

    Coral reef ecosystems fringing the coastline of Dahab (South Sinai, Egypt) have experienced increasing anthropogenic disturbance as an emergent international tourism destination. Previous reports covering tourism-related impacts on coastal environments, particularly mechanical damage and destructive fishing, have highlighted the vital necessity for regular ecosystem monitoring of coral reefs near Dahab. However, a continuous scientific monitoring programme of permanent survey sites has not been established to date. Thus, this study conducted in situ monitoring surveys to investigate spatio-temporal variability of benthic reef communities and selected reef-associated herbivores along with reef health indicator organisms by revisiting three of the locally most frequented dive sites during expeditions in March 2010, September 2011 and February 2013. In addition, inorganic nutrient concentrations in reef-surrounding waters were determined to evaluate bottom-up effects of key environmental parameters on benthic reef community shifts in relation to grazer-induced top-down control. Findings revealed that from 2010 to 2013, live hard coral cover declined significantly by 12 % at the current-sheltered site Three Pools (TP), while showing negative trends for the Blue Hole (BH) and Lighthouse (LH) sites. Hard coral cover decline was significantly and highly correlated to a substantial increase in turf algae cover (up to 57 % at TP) at all sites, replacing hard corals as dominant benthic space occupiers in 2013. These changes were correlated to ambient phosphate and ammonium concentrations that exhibited highest values (0.64?±?0.07 ?mol PO4 (3-)?l(-1), 1.05?±?0.07 ?mol NH4 (+)?l(-1)) at the degraded site TP. While macroalgae appeared to respond to both bottom-up and top-down factors, change in turf algae was consistent with expected indications for bottom-up control. Temporal variability measured in herbivorous reef fish stocks reflected seasonal impacts by local fisheries, with concomitant changes in macroalgal cover. These findings represent the first record of rapid, localised change in benthic reef communities near Dahab, consistent with indications for bottom-up controlled early-stage phase shifts, underlining the necessity for efficient regional wastewater management for coastal facilities. PMID:25637388

  14. Multicenter dizygotic twin cohort study confirms two linkage susceptibility loci for body mass index at 3q29 and 7q36 and identifies three further potential novel loci

    PubMed Central

    Kettunen, J; Perola, M; Martin, NG; Cornes, BK; Wilson, SG; Montgomery, GW; Benyamin, B; Harris, JR; Boomsma, D; Willemsen, G; Hottenga, J-J; Slagboom, PE; Christensen, K; Kyvik, KO; Sørensen, TIA; Pedersen, NL; Magnusson, PKE; Andrew, T; Spector, TD; Widen, E; Silventoinen, K; Kaprio, J; Palotie, A; Peltonen, L

    2010-01-01

    Objective To identify common loci and potential genetic variants affecting body mass index (BMI, kg m?2) in study populations originating from Europe. Design We combined genome-wide linkage scans of six cohorts from Australia, Denmark, Finland, the Netherlands, Sweden and the United Kingdom with an ~10-cM microsatellite marker map. Variance components linkage analysis was carried out with age, sex and country of origin as covariates. Subjects The GenomEUtwin consortium consists of twin cohorts from eight countries (Australia, Denmark, the Netherlands, Finland, Italy, Norway, Sweden and the United Kingdom) with a total data collection of more than 500 000 monozygotic and dizygotic (DZ) twin pairs. Variance due to early-life events and the environment is reduced within twin pairs, which makes DZ pairs highly valuable for linkage studies of complex traits. This study totaled 4401 European-originated twin families (10 535 individuals) from six countries (Australia, Denmark, the Netherlands, Finland, Sweden and the United Kingdom). Results We found suggestive evidence for a quantitative trait locus on 3q29 and 7q36 in the combined sample of DZ twins (multipoint logarithm of odds score (MLOD) 2.6 and 2.4, respectively). Two individual cohorts showed strong evidence independently for three additional loci: 16q23 (MLOD = 3.7) and 2p24 (MLOD = 3.4) in the Dutch cohort and 20q13 (MLOD = 3.2) in the Finnish cohort. Conclusion Linkage analysis of the combined data in this large twin cohort study provided evidence for suggestive linkage to BMI. In addition, two cohorts independently provided significant evidence of linkage to three new loci. The results of our study suggest a smaller environmental variance between DZ twins than full siblings, with a corresponding increase in heritability for BMI as well as an increase in linkage signal in well-replicated regions. The results are consistent with the possibility of locus heterogeneity for some genomic regions, and indicate a lack of major common quantitative trait locus variants affecting BMI in European populations. PMID:19721450

  15. Social Indicators

    NSDL National Science Digital Library

    Bolton, Paul.

    The House of Commons Library Research Papers are published for the benefit of Parliament members, but this one should be of interest to both researchers and general readers wanting to learn more about contemporary British social issues. Social Indicators is the first paper in a new series that will be published three times a year. The 71-page paper includes a wide range of topic pages that present social statistics on a variety of issues, from the prison population to defense expenses to agricultural outputs. Each Social Indicator paper will also offer feature articles that give a closer look at specific subjects (in this instance,, election turnout and adult literacy) and an article on statistical sources for a particular issue (in this paper, social security statistics). The last few pages are devoted to a list of important, recent governmental statistical publications.

  16. Potential indicator species of climate changes occurring in Québec, Part 1: the small brown lacewing fly Micromus posticus (Walker) (Neuroptera: Hemerobiidae)

    PubMed Central

    2013-01-01

    Abstract Micromus posticus (Walker) is a small brown lacewing fly rarely collected in Canada and represented in collections by only a limited number of specimens. Indeed, fewer than 50 specimens were captured in Québec and Ontario over the last century, all within a small area delimited by the northern shore of Lake Erie, Ottawa and Montréal. Aylmer, located on the north shore of the Ottawa River, northwest of Ottawa, is a new, most southwestern locality record of this species for Québec. The Aylmer specimens were collected 1-7 days later than any of the known specimens collected elsewhere in Québec or in Ontario, and 16-22 days later than in the neighbouring localities, indicating an apparent phenological shift. PMID:24723766

  17. A sensitive crude oil bioassay indicates that oil spills potentially induce a change of major nitrifying prokaryotes from the archaea to the bacteria.

    PubMed

    Urakawa, Hidetoshi; Garcia, Juan C; Barreto, Patricia D; Molina, Gabriela A; Barreto, Jose C

    2012-05-01

    The sensitivity of nitrifiers to crude oil released by the BP Deepwater Horizon oil spill in Gulf of Mexico was examined using characterized ammonia-oxidizing bacteria and archaea to develop a bioassay and to gain further insight into the ecological response of these two groups of microorganisms to marine oil spills. Inhibition of nitrite production was observed among all the tested ammonia-oxidizing organisms at 100 ppb crude oil. Nitrosopumilus maritimus, a cultured representative of the abundant Marine Group I Archaea, showed 20% inhibition at 1 ppb, a much greater degree of sensitivity to petroleum than the tested ammonia-oxidizing and heterotrophic bacteria. The differing susceptibility may have ecological significance since a shift to bacterial dominance in response to an oil spill could potentially persist and alter trophic interactions influenced by availability of different nitrogen species. PMID:22327114

  18. Differences between mild cognitive impairment subtypes as indicated by event-related potential correlates of cognitive and motor processes in a Simon task.

    PubMed

    Cespón, Jesús; Galdo-Álvarez, Santiago; Pereiro, Arturo X; Díaz, Fernando

    2015-01-01

    Mild cognitive impairment (MCI) may represent a prodromal stage of Alzheimer's disease (AD), although the clinical manifestations of MCI are heterogeneous. Consequently, MCI subtypes are differentiated since amnestic decline (particularly when combined with decline on multiple cognitive domains) increases the probability of progression to AD. In the present study, event-related potential (ERP) correlates of stimulus evaluation (N2), visuospatial attention (negativity posterior-contralateral, N2pc), stimulus categorization (P3b), executive control (pre-response positivity, PP, and medial frontal negativity), and motor (lateralized readiness potential, LRP) processes were studied in 53 participants while they performed a Simon task. Participants were divided into control group (CG), multiple-domain non-amnestic MCI (mdnaMCI), single-domain amnestic MCI (sdaMCI), and multiple-domain amnesic MCI (mdaMCI). Although there were no differences in reaction times and percentage of errors in the performed Simon-type task, a differential pattern of electrophysiological correlates was observed in MCI compared to CG. Concretely, amnestic MCI (sdaMCI and mdaMCI) showed reduced motor activity (LRP amplitude; AUC: 0.84); impairment in executive control (PP amplitude; AUC: 0.80) was observed in multiple-domain MCI (mdaMCI and mdnaMCI); finally, stimulus evaluation (N2 latency; AUC: 0.86) and visuospatial attention (N2pc amplitude; AUC: 0.78) was affected in mdaMCI. Overall, results linked the poorer prognosis of the mdaMCI subtype with a greater number of differences in ERP correlates regarding CG. Therefore, the present results enable us to suggest possible ERP biomarkers for specific MCI subtypes. PMID:25125461

  19. Selenium Bioaccumulation in Stocked Fish as an Indicator of Fishery Potential in Pit Lakes on Reclaimed Coal Mines in Alberta, Canada

    NASA Astrophysics Data System (ADS)

    Miller, L. L.; Rasmussen, J. B.; Palace, V. P.; Sterling, G.; Hontela, A.

    2013-07-01

    Pit lakes are a common reclamation strategy for open pit mines; however, there is a concern about their water quality and suitability as fish habitat because they are often contaminated by metals or metalloids. This study assessed the exposure of fish and invertebrates to selenium (Se) and other metals and metalloids in pit lakes formed by open pit coal mining in Tertiary (thermal coal) and in Cretaceous (metallurgical coal) bedrock. Juvenile hatchery rainbow trout, Oncorhynchus mykiss, and brook trout, Salvelinus fontinalis, were stocked into two thermal coal pit lakes (water Se < 2 ?g/L, low water Se) and two metallurgical coal pit lakes (water Se > 15 ?g/L, high water Se). Se accumulation in stocked fish and concentrations in invertebrates were characterized over a period of 2 years. In the metallurgical pits, invertebrates had higher Se concentrations and fish accumulated Se to higher levels (exceeding USEPA tissue Se guidelines) than biota in the thermal pits. Rainbow and brook trout accumulated similar concentrations of Se in their muscle and exhibited a similar relationship between whole-body and muscle Se concentrations. These results may be used by resource managers to assess compliance with whole-body tissue Se guidelines and to determine if pit lakes in coal mining areas pose a significant Se risk to wildlife or human health. The high Se exposure in metallurgical coal pits indicates that under the current mining and reclamation strategy, these lakes are not suitable for management as recreational "put and take" fisheries.

  20. Diffuse light reflectance signals as potential indicators of loss of viability in brain tissue due to hypoxia: charge-coupled-device-based imaging and fiber-based measurement

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Nishidate, Izumi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Sato, Shunichi

    2013-01-01

    Brain tissue is highly vulnerable to ischemia/hypoxia, and real-time monitoring of its viability is important. By fiber-based measurements for rat brain, we previously observed a unique triphasic reflectance change (TRC) after a certain period of time after hypoxia. After TRC, rats could not be rescued, suggesting that TRC can be used as an indicator of loss of brain tissue viability. In this study, we investigated this diffuse-reflectance change due to hypoxia in three parts. First, we developed and validated a theoretical method to quantify changes in the absorption and reduced scattering coefficients involved in TRC. Second, we performed charge-coupled-device-based reflectance imaging of the rat brain during hypoxia followed by reoxygenation to examine spatiotemporal characteristics of the reflectance and its correlation with reversibility of brain tissue damage. Third, we made simultaneous imaging and fiber-based measurement of the reflectance for the rat to compare signals obtained by these two modalities. We observed a nontriphasic reflectance change by the imaging, and it was associated with brain tissue viability. We found that TRC measured by the fibers preceded the reflectance-signal change captured by the imaging. This time difference is attributable to the different observation depths in the brain with these two methods.

  1. Recolonization patterns of ants in a rehabilitated lignite mine in central Italy: Potential for the use of Mediterranean ants as indicators of restoration processes

    SciTech Connect

    Ottonetti, L.; Tucci, L.; Santini, G. [University of Florence, Florence (Italy)

    2006-03-15

    Ant (Hymenoptera: Formicidae) assemblages were sampled with pitfall traps in three different habitats associated with a rehabilitated mine district and in undisturbed forests in Tuscany, Italy. The four habitats were (1) open fields (3-4 years old); (2) a middle-age mixed plantation (10 years); (3) an old-age mixed plantation (20 years); and (4) an oak woodland (40 years) not directly affected by mining activities. The aim of the study was to analyze ant recolonization patterns in order to provide insights on the use of Mediterranean ant fauna as indicators of restoration processes. Species richness and diversity were not significantly different among the four habitats. However, multivariate analyses showed that the assemblages in the different habitats were clearly differentiated, with similarity relationships reflecting a successional gradient among rehabilitated sites. The observed patterns of functional group changes along the gradient broadly accord with those of previous studies in other biogeographic regions. These were (1) a decrease of dominant Dolichoderinae and opportunists; (2) an increase in the proportion of cold-climate specialists; and (3) the appearance of the Cryptic species in the oldest plantations, with a maximum of abundance in the woodland. In conclusion, the results of our study supported the use of Mediterranean ants as a suitable tool for biomonitoring of restoration processes, and in particular, the functional group approach proved a valuable framework to better interpret local trends in terms of global ecological patterns. Further research is, however, needed in order to obtain a reliable classification of Mediterranean ant functional groups.

  2. Characterization of a potential medium for 'biorelevant' in vitro release testing of a naltrexone implant, employing a validated stability-indicating HPLC method.

    PubMed

    Iyer, Sunil S; Barr, William H; Karnes, H Thomas

    2007-02-19

    A variety of factors have been recognized that influence media optimization for drug release studies of implant dosage forms. Of primary importance is selection of a medium that physiologically mimics the milieu at the site of administration (a condition termed 'biorelevance'). We describe in this paper, the characterization of Hanks' balanced salts solution, with necessary modification, for application as a 'biorelevant' medium for in vitro release studies of a biodegradable, subcutaneous implant of naltrexone. A detailed investigation of changes in pH, osmolality and ultraviolet (UV) spectrum as a function of time and temperature was conducted. Variation in the parameters evaluated was found to be within acceptable limits. Validation of a simple and selective, high performance liquid chromatography (HPLC) assay method for naltrexone was carried out to evaluate stability. The calibration curves were linear from 0.16 to 20.00 microg ml(-1). Imprecision and inaccuracy were less than 2% and no interference was observed from degradation peaks. Stability studies of naltrexone indicated the media should be replaced every 7-8 days for real-time testing. This was applied to an investigation of in vitro drug release. The method has been proven to be suitable for investigation of naltrexone released from the implant. PMID:17045445

  3. 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

  4. Selection of the Australian indicator region

    NASA Technical Reports Server (NTRS)

    Reed, C. R. (principal investigator)

    1981-01-01

    Each Australian state was examined for the availability of LANDSAT data, area, yield, and production characteristics, statistics, crop calendars, and other ancillary data. Agrophysical conditions that could influence labeling and classification accuracies were identified in connection with the highest producing states as determined from available Australian crop statistics. Based primarily on these production statistics, Western Australia and New South Wales were selected as the wheat indicator region for Australia. The general characteristics of wheat in the indicator region, with potential problems anticipated for proportion estimation are considered. The varieties of wheat, the diseases and pests common to New South Wales, and the wheat growing regions of both states are examined.

  5. Is asymptomatic bronchial hyperresponsiveness an indication of potential asthma? A two-year follow-up of young students with bronchial hyperresponsiveness.

    PubMed

    Zhong, N S; Chen, R C; Yang, M O; Wu, Z Y; Zheng, J P; Li, Y F

    1992-10-01

    To determine the possibility that asymptomatic bronchial hyperresponsiveness (BHR) develops into symptomatic asthma, a two-year follow-up study was conducted in 81 students (48 male, 33 female; 11 to 17 years) who were found to have BHR in a 3,067 population survey (BHR group). Eighty-eight age-matched students (48 male, 40 female) with normal bronchial responsiveness served as control subjects. Daily symptom cards were recorded. Peak expiratory flow rate was measured for 24 h when symptoms occurred. Histamine inhalation tests were performed at the beginning of the study and at the end of the first and the second year. In the BHR group, 58 students remained bronchial hyperresponsive at the end of follow-up. Nine of 31 students with initially diagnosed bronchial asthma had their symptoms relieved entirely, but ten asymptomatic students developed asthma. The incidence of newly diagnosed asthma (12.5 percent in the BHR group or 20 percent in the asymptomatic BHR group) and the total percentage of diagnosed asthma (39.5 percent) in the BHR group were significantly higher than those (2.27 percent, 2.27 percent) in the control group. FVC and FEV1 showed no significant difference between two groups. PD20 FEV1 values in newly diagnosed asthmatics were significantly lower than those in asymptomatic students both at the beginning (3.05 +/- 1.56 mumol vs 6.14 +/- 1.60 mumol, p < 0.05) or the end (3.47 +/- 1.73 mumol vs 6.55 +/- 1.51 mumol, p < 0.05). The percentage of early respiratory illness was significantly higher in those with newly diagnosed asthma (80 percent) than in asymptomatic students (22.3 percent), but atopic index and the percentage of parental asthma showed no difference between two groups. In nine asthmatics whose symptoms were relieved entirely in the two-year follow-up, PD20 FEV1 was undetectable within the cumulative dose of 7.8 mumol of histamine in three students and rose from 4.58 +/- 1.85 mumol to 7.62 +/- 1.02 mumol in the remaining six. The higher the BHR, the more likely the students developed asthma. About 45 percent of asymptomatic students with PD20 < or = 3.2 mumol developed asthma in the following two years and 80 percent of them had a history of early respiratory illness, suggesting that they may have subclinical or potential asthma. PMID:1395752

  6. Cabbage Juice Indicator

    NSDL National Science Digital Library

    The Science House

    2014-01-28

    In this chemistry activity, learners make indicator solution from red cabbage. Then, learners test everyday foods and household substances using the cabbage juice indicator. Learners will record the color change, approximate pH (using the pH scale), and identify if it is an acid or base. As an extension, learners can make pH paper strips to conduct an "at home" pH test of other household items. The indicator solution can be frozen in ice trays and when mixed with alcohol, can last for months. For safety reasons, adult supervision is recommended.

  7. Country Indicators for Foreign Policy

    NSDL National Science Digital Library

    Created and maintained by the Department of Foreign Affairs and International Trade and Norman Paterson School of International Affairs, Country Indicators for Foreign Policy (CIFP) "represents an on-going effort to identify and assemble statistical information conveying the key features of the economic, political, social and cultural environments of countries around the world." Started in 1997, this flexible database project is intended to serve the needs of NGOs, government departments, and the private sector, and can potentially be used to aid in strategic decision-making, for risk analysis, and to monitor countries for possible "peacebuilding intervention." The database may be searched by region, regional and global organization, or by issue area. New users will want to visit the Users Guide, which offers detailed instructions for searching the database. Registration by email is required, and a user name and password will be emailed within two days.

  8. Potential New Indications of Topical Calcineurin Inhibitors

    Microsoft Academic Search

    Thomas Luger; Carle Paul

    2007-01-01

    The topical calcineurin inhibitors pimecrolimus (Elidel®) and tacrolimus (Protopic®) were initially developed for the treatment of atopic eczema (atopic dermatitis), a chronic or chronically relapsing skin condition most prevalent in infants and children. Their main advantages compared with conventional topical corticosteroid therapy are that they are more selective in their mode of action, do not induce skin atrophy and are

  9. Identifying Early Indicators for Autism in Self-Regulation Difficulties

    ERIC Educational Resources Information Center

    Gomez, Caroline R.; Baird, Samera

    2005-01-01

    Researchers have suggested that individuals with autism have difficulties with self-regulation in early infancy, which may represent an early risk factor for autism. In this study, the authors explored self-regulatory behavior in young children who were later diagnosed with autism. Parents of children diagnosed with autism (n = 65) retrospectively…

  10. How to Identify leading indicators for scenario monitoring

    E-print Network

    Xu, Xia, M. Eng. Massachusetts Institute of Technology

    2014-01-01

    Being able to quickly adapt to changes in the business environment has been widely acknowledged as essential for sustainable success by business leaders. Scenario planning is recognized as an effective tool used to explore ...

  11. Identifying indicators that connect streams to human well being

    EPA Science Inventory

    Background Ecosystems provide services that benefit diverse human users. Identification of the ecosystem features providing these benefits is one of the fundamental prerequisites for wisely monitoring and managing ecosystems and their support for human well being. Because soc...

  12. Indicator Variables for Optimal Policy

    Microsoft Academic Search

    Lars E. O. Svensson; Michael Woodford

    1999-01-01

    The optimal weights on indicators in models with partial information about the state of the economy and forward-looking variables are derived and interpreted, both for equilibria under discretion and under commitment. An example of optimal monetary policy with a partially observable potential output and a forward-looking indicator is examined. The optimal response to the optimal estimate of potential output displays

  13. Should researchers use single indicators, best indicators, or multiple indicators in structural equation models?

    PubMed Central

    2012-01-01

    Background Structural equation modeling developed as a statistical melding of path analysis and factor analysis that obscured a fundamental tension between a factor preference for multiple indicators and path modeling’s openness to fewer indicators. Discussion Multiple indicators hamper theory by unnecessarily restricting the number of modeled latents. Using the few best indicators – possibly even the single best indicator of each latent – encourages development of theoretically sophisticated models. Additional latent variables permit stronger statistical control of potential confounders, and encourage detailed investigation of mediating causal mechanisms. Summary We recommend the use of the few best indicators. One or two indicators are often sufficient, but three indicators may occasionally be helpful. More than three indicators are rarely warranted because additional redundant indicators provide less research benefit than single indicators of additional latent variables. Scales created from multiple indicators can introduce additional problems, and are prone to being less desirable than either single or multiple indicators. PMID:23088287

  14. Auction markets for specialty food products with geographical indications

    Microsoft Academic Search

    Günter Schamel

    2007-01-01

    We present a first analysis of online auction markets for specialty food products. We identify auction prices, trade volume, and value for domestic and foreign-origin specialty ham with geographical indications (GIs) that were sold in online auctions in Germany within a 1-month period. Applying hedonic modeling, we examine potential factors that may influence online bidding behavior and final auction prices.

  15. Indicators for Inquiry

    NSDL National Science Digital Library

    Jeffery Townsend

    2006-02-01

    Fifth-grade students use homemade plant-based acid/base indicators to learn about matter at an age-appropriate level and develop process skills. As a result of completing this lesson sequence the students should be able to perform many tasks using process skills such as observing chemical changes; identifying acids and bases by performing tests; classifying common household substances as acidic, basic (alkaline), or neutral; and developing a scheme for solving a performance-based scenario.

  16. Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer.

    PubMed

    Yeh, Chao-Chi; Hsu, Chih-Hung; Shao, Yu-Yun; Ho, Wen-Ching; Tsai, Mong-Hsun; Feng, Wen-Chi; Chow, Lu-Ping

    2015-06-01

    Sorafenib has become the standard therapy for patients with advanced hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop acquired resistance. Therefore, it is important to identify potential biomarkers that could predict the efficacy of sorafenib. To identify target proteins associated with the development of sorafenib resistance, we applied stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomic approach to analyze differences in protein expression levels between parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7(R)) cells in vitro, combined with an isobaric tags for relative and absolute quantitation (iTRAQ) quantitative analysis of HuH-7 and HuH-7(R) tumors in vivo. In total, 2,450 quantified proteins were identified in common in SILAC and iTRAQ experiments, with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75 showing decreased expression (<0.5-fold). In silico analyses of these differentially expressed proteins predicted that 10 proteins were related to cancer with involvements in cell adhesion, migration, and invasion. Knockdown of one of these candidate proteins, galectin-1, decreased cell proliferation and metastasis in HuH-7(R) cells and restored sensitivity to sorafenib. We verified galectin-1 as a predictive marker of sorafenib resistance and a downstream target of the AKT/mTOR/HIF-1? signaling pathway. In addition, increased galectin-1 expression in HCC patients' serum was associated with poor tumor control and low response rate. We also found that a high serum galectin-1 level was an independent factor associated with poor progression-free survival and overall survival. In conclusion, these results suggest that galectin-1 is a possible biomarker for predicting the response of HCC patients to treatment with sorafenib. As such, it may assist in the stratification of HCC and help direct personalized therapy. PMID:25850433

  17. Quality Indicators of Online Programs

    Microsoft Academic Search

    Leo Hirner; Thomas Kochtanek

    2012-01-01

    The continued growth of online programs in higher education has resulted in concerns about how institutions monitor the quality of their online programs. These concerns indicate a need for a process by which online programs may be evaluated and compared. They provided the impetus for this study, the goals of which were to identify quality indicators specific to community college

  18. Indicators for Transboundary River Management

    Microsoft Academic Search

    CAROLIN M. LORENZ; ALISON J. GILBERT; WIM P. COFINO

    2001-01-01

    The aim of this paper is to analyze the potential of indicators for integrated river basin management and to develop a set\\u000a of indicators for the management of transboundary river basins. An indicator, comprising a variable or some aggregation of\\u000a variables, describes a system or process such that it has significance beyond the face value of its components. Integrated\\u000a river

  19. Selection of an Aquatic Indicator Species to Monitor Organic Contaminants in Trophically Simple Lotic Food Webs

    Microsoft Academic Search

    G. J. Scrimgeour; D. Wicklum; S. D. Pruss

    1998-01-01

    .   A four-step procedure was used to identify an aquatic macroinvertebrate with which to monitor organic contaminant burdens\\u000a in trophically simple lake food webs of Alberta, Canada. We identified leeches (Oligochaeta: Hirudinea) as the potential indicator\\u000a assemblage (Step 1), and then documented their abundance and distribution in 16 lakes to identify a species-level bioindicator\\u000a (Step 2). The latter two steps

  20. Inference for identifiable parameters in partially identified econometric models

    Microsoft Academic Search

    Joseph P. Romano; Azeem M. Shaikh

    2008-01-01

    This paper considers the problem of inference for partially identified econometric models. The class of models studied are defined by a population objective function Q(?,P) for ???. The second argument indicates the dependence of the objective function on P, the distribution of the observed data. Unlike the classical extremum estimation framework, it is not assumed that Q(?,P) has a unique

  1. Purification of the 70-kDa heat-shock protein from catfish liver: Immunological comparison of the protein in different fish species and its potential use as a stress indicator

    SciTech Connect

    Abukhalaf, I.K.; Zimmerman, E.G.; Dickson, K.L.; Masaracchia, R.A.; Donahue, M.J. (Univ. of North Texas, Denton, TX (United States)); Covington, S. (Cadmus Group, Inc., Laramie, WY (United States))

    1994-08-01

    The heat-shock protein or stress-70 family was isolated from catfish liver. The homogeneity of the purified protein was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Fish subjected to whole-body hyperthermia contained the constitutive and the heat-inducible stress-70 with approximate molecular weights of 70 and 68 kDa, respectively. The final purification product from livers of catfish raised under normal temperature was only the constitutive stress-70. Western blot analysis with rabbit antiserum prepared against purified catfish (Ictalurus punctatus) liver stress-70 showed that the antibody cross-reacted with liver, muscle, and gill tissue homogenates of fathead minnows (Pimephales promelas), red shiners (Cyprinella lutrensis), black bass (Micropterus salmoides), and bluegill (Lepomis macrochirus), with various intensities suggesting that stress-70s from different tissues of various fish species share common antigenic determinants of the protein. This substantiates that the antigen/antibody approach of stress-70 is useful as a stress indicator and, consequently, as a potential biomarker for water quality.

  2. The masticatory normative indicator.

    PubMed

    Woda, A; Nicolas, E; Mishellany-Dutour, A; Hennequin, M; Mazille, M-N; Veyrune, J-L; Peyron, M-A

    2010-03-01

    There is no established quantitative, objective method to differentiate individuals with good masticatory function from those lacking this attribute. The aim of this study was to specify a normal range of median particle size values for masticated raw carrots collected just before being swallowed. The masticatory normative indicator (MNI) value thus obtained was based on seven studies carried out by different investigators using different methods for measuring particle size in carrot boluses. A simple mathematical transformation of variables and the choice of an interval of +/-1.96 times the standard deviation gave 4.0 mm as the upper limit of normal median particle size for carrots in a population of young persons with good oral health. This value identifies boluses that may be considered as resulting from impaired mastication, as illustrated in healthy individuals with experimentally hampered mastication, denture wearers, and individuals presenting with obesity or Down syndrome. PMID:20118433

  3. Identifying Lagrangian fronts with favourable fishery conditions

    NASA Astrophysics Data System (ADS)

    Prants, S. V.; Budyansky, M. V.; Uleysky, M. Yu.

    2014-08-01

    Lagrangian fronts (LFs) in the ocean are defined as boundaries between surface waters with strongly different Lagrangian properties. They can be accurately detected in a given velocity field by computing synoptic maps for displacements of synthetic tracers and other Lagrangian indicators. We use Pacific saury catch and location data for a number of commercial fishery seasons in the region of the northwest Pacific with one of the richest fishery in the world. It is shown statistically that the saury fishing grounds with maximal catches are not randomly distributed over the region but located mainly along the sharp LFs where productive cold waters of the Oyashio Current, warmer waters of the southern branch of the Soya Current, and waters of warm-core Kuroshio rings converge. Computation of those fronts in altimetric geostrophic velocity fields both in the years with the First and Second Oyashio Intrusions shows that in spite of different oceanographic conditions LF locations may serve as good indicators of potential fishing grounds. Possible biophysical reasons for saury aggregation near sharp LFs are discussed. We propose a mechanism for effective export of nutrient rich waters based on stretching of material lines in the vicinity of hyperbolic objects in the ocean. The developed method, based on identifying LFs in any velocity fields, is quite general and may be applied to find potential fishing grounds for the other pelagic fish.

  4. Dynamic Process Capability Indices

    Microsoft Academic Search

    Jing Sun

    2002-01-01

    Process capability indices as an important kind of indices are intended to provide single-number assessments of the inherent process capability to meet specification limits on quality characteristic(s) of interest. In this paper the condition for the application of process capability indices is analyzed. On the basis of process capability indices, dynamic process capability indices as a new kind of indices

  5. Tamper indicating packaging

    SciTech Connect

    Baumann, M.J.; Bartberger, J.C.; Welch, T.D.

    1994-08-01

    Protecting sensitive items from undetected tampering in an unattended environment is crucial to the success of non-proliferation efforts relying on the verification of critical activities. Tamper Indicating Packaging (TIP) technologies are applied to containers, packages, and equipment that require an indication of a tamper attempt. Examples include: the transportation and storage of nuclear material, the operation and shipment of surveillance equipment and monitoring sensors, and the retail storage of medicine and food products. The spectrum of adversarial tampering ranges from attempted concealment of a pin-hole sized penetration to the complete container replacement, which would involve counterfeiting efforts of various degrees. Sandia National Laboratories (SNL) has developed a technology base for advanced TIP materials, sensors, designs, and processes which can be adapted to various future monitoring systems. The purpose of this technology base is to investigate potential new technologies, and to perform basic research of advanced technologies. This paper will describe the theory of TIP technologies and recent investigations of TIP technologies at SNL.

  6. Indicators of the appropriateness of long-term prescribing in general practice in the United Kingdom: consensus development, face and content validity, feasibility, and reliability

    Microsoft Academic Search

    J. A. Cantrill; B. Sibbald; S. Buetow

    1998-01-01

    OBJECTIVES: To develop valid, reliable indicators of the appropriateness of long-term prescribing in general practice medical records in the United Kingdom. DESIGN: A nominal group was used to identify potential indicators of appropriateness of prescribing. Their face and content validity were subsequently assessed in a two round Delphi exercise. Feasibility and reliability between raters were evaluated for the indicators for

  7. Geochemical indicators of intrinsic bioremediation

    Microsoft Academic Search

    Robert C. Borden; Carlos A. Gomez; Mark T. Becker

    1995-01-01

    A detailed field investigation has been completed at a gasoline-contaminated aquifer near Rocky Point, NC, to examine possible indicators of intrinsic bioremediation and identify factors that may significantly influence the rae and extent of bioremediation. The dissolved plume of benzene, toluene, ethylbenzene, and xylene (BTEX) in ground water is naturally degrading. Toluene and o-xylene are most rapidly degraded followed by

  8. Quality Indicators of Online Programs

    ERIC Educational Resources Information Center

    Hirner, Leo; Kochtanek, Thomas

    2012-01-01

    The continued growth of online programs in higher education has resulted in concerns about how institutions monitor the quality of their online programs. These concerns indicate a need for a process by which online programs may be evaluated and compared. They provided the impetus for this study, the goals of which were to identify quality…

  9. Do We Know Whom To Serve? Issues in Using Risk Factors To Identify Dropouts.

    ERIC Educational Resources Information Center

    Gleason, Philip; Dynarski, Mark

    2002-01-01

    Analyzes the effectiveness of widely used risk factors for identifying potential dropouts, using data from the School Dropout Demonstration Assistance Program. Findings indicate that most risk factors are not effective predictors of dropping out, and that dropout prevention programs often serve students who would not have dropped out and do not…

  10. Terrestrial Indicators and Measurements

    E-print Network

    jurisdictions. General Approach. Indicators were selected through a five-step participatory process involving in at least one national monitoring program, was used for the core indicators. Core Indicators and/or vegetation trend monitoring: (1)

  11. Cepheids as Distance Indicators

    E-print Network

    N. R. Tanvir

    1996-11-04

    We review the use of Cepheids as distance indicators with particular emphasis on the methods which have been applied to HST observations of Cepheids. The calibration of the period-luminosity relations is examined in detail and we identify possible problems with the existing calibrations. New V- and I-band period luminosity relations are presented based on a sample of 53 Cepheids in the LMC with photometry drawn from the literature. These revised PL relations result in a systematic decrease of approx 0.1 magnitudes in distance moduli derived using the standard method of extinction correction. Hence estimates of the Hubble constant based on such distances should be increased by $\\sim5%$. Other aspects of Cepheid distance determination, specifically incompleteness bias, metallicity dependence, the effects of crowding and contamination of samples by non-Cepheids are also discussed. We conclude that current HST distance estimates to individual galaxies are probably good to about 10%, but that much of this error is systematic. Efforts to reduce the systematics, therefore, for example by improving the photometric calibration, refining the distance to the LMC, and reobserving the Cepheid galaxies in the infrared with NICMOS, will give large returns.

  12. Molecular Models of Indicators

    NSDL National Science Digital Library

    The article by Nicholas C. Thomas and Stephen Faulk on "Colorful Chemical Fountains" (1) reminds us that color—the colors of acid–base indicators or of metal complexes—is responsible for many of us developing an interest in chemistry. The featured molecules this month are the acid and base forms of three common indicators–phenolphthalein, methyl orange, and methyl red. These three substances display interesting structural features as the pH-induced transformation from one form to another takes place in three different ways. In the case of phenolphthalein, the lactam ring is cleaved on deprotonation to produce a carboxyl group with the concomitant removal of a proton from a phenolic group. In methyl orange, one of the nitrogen atoms is protonated in the acid form, and that proton is lost in the base form. In methyl red, a carboxylic acid function is deprotonated. There are many other interesting aspects of acid–base indicators. Since most plants and fruits contain pigments that show a color change in some pH range, it is difficult to state with any degree of certainty when these changes were first put to use in a systematic fashion. The Spanish alchemist Arnaldus de Villa Nova (Arnold of Villanova) is purported to have used litmus in the early 14th century. In general systematic use of indicators is traced to the latter half of the nineteenth century with the development of the three synthetic indicators described above. Many students will be familiar with the use of phenolphthalein to identify blood—often shown on the various forensic chemistry TV dramas by dropping some solution on a cotton swab that has been used to pick up some of the sample in question. If the swab turns red we frequently hear "It's blood". The reality of using phenolphthalein in this way is more complicated. The test is presumptive for the presence of blood, but not conclusive. It is not an acid–base reaction but rather, in the presence of hydrogen peroxide, relies on hemoglobin to catalyze the oxidation of phenolphthalein. An interesting assignment for students in a high-school or non-majors course would be to have them explore the details of this Kastle–Meyers test to see just what is involved in the correct application of the test, and what factors complicate the process. For example, would tomato juice infused with asparagus juice give a positive Kastle–Meyers test? Historically phenolphthalein was used in a variety of laxatives. Recently that usage has been discontinued due to concern about the carcinogenic nature of the substance. A review of the history of the controversy surrounding the use of phenolphthalein in laxatives would make a good research paper at the high-school level. Lastly, students with some practice building structures and performing calculations might wish to explore the structures of two other forms of phenolphthalein—one found in very acidic solutions, having an orange color, and one found in very basic solutions that is colorless.

  13. PIBEA: Prospect Indicator Based Evolutionary Algorithm for Multiobjective Optimization Problems

    E-print Network

    Suzuki, Jun

    PIBEA: Prospect Indicator Based Evolutionary Algorithm for Multiobjective Optimization Problems multiobjective optimization algorithm (EMOA) that uses a new quality indicator, called the prospect indicator, for parent selection and environmental selection operators. The prospect indicator measures the potential

  14. Global Health Education: a cross-sectional study among German medical students to identify needs, deficits and potential benefits (Part 1 of 2: Mobility patterns & educational needs and demands)

    Microsoft Academic Search

    Kayvan Bozorgmehr; Kirsten Schubert; Johannes Menzel-Severing; Peter Tinnemann

    2010-01-01

    BACKGROUND: In recent years, education and training in global health has been the subject of recurring debate in many countries. However, in Germany, there has been no analysis of the educational needs or demands of medical students, or the educational deficits or potential benefits involved in global health education. Our purpose is to analyse international health elective patterns of medical

  15. RAPID HEALTH-BASED METHOD FOR MEASURING MICROBIAL INDICATORS OF RECREATIONAL WATER QUALITY

    EPA Science Inventory

    Because the currently approved cultural methods for monitoring indicator bacteria in recreational water require 24 hours to produce results, the public may be exposed to potentially contaminated water before the water has been identified as hazardous. This project was initiated t...

  16. Technology and indications.

    PubMed

    Sunada, Keijiro; Yamamoto, Hironori

    2009-07-01

    Double-balloon endoscopy (DBE) was developed based on the principle of preventing stretching of the intestinal tract by anchoring the convoluted intestinal tract with an endoscope and overtube fitted with inflatable balloons. The DBE system includes the main body of the endoscope with a built-in air channel, a balloon attached to the tip of the endoscope, an overtube with a hydrophilic coating equipped with an inflatable balloon, and a balloon controller that safely inflates/deflates the two balloons. At present, there are three different types of endoscopes for DBE. The indications for DBE include the diagnosis or treatment of various small intestinal conditions such as obscure gastrointestinal bleeding, Crohn's disease, and benign and malignant tumors. In addition, DBE can be used to approach the surgically modified intestinal tract; conventional endoscopes have difficulty in that situation. DBE can be used for colonoscopy in cases in which it is difficult to insert a conventional colonoscope. In the future, DBE will have the potential for wider use in routine colonoscopy because the insertion technique is easy and reliable. PMID:19647642

  17. Positive Indicators of Child Well-Being: A Conceptual Framework, Measures, and Methodological Issues

    Microsoft Academic Search

    Laura H. Lippman; Kristin Anderson Moore; Hugh McIntosh

    2009-01-01

    This article suggests a comprehensive conceptual framework which identifies constructs for positive well-being as well as\\u000a potential indicators and extant measures that fit with those constructs. In addition, the article reviews existing data sources\\u000a for examples of positive measures that are found in the proposed framework as well as research studies that have been successful\\u000a in measuring these indicators. The

  18. Gang Identifiers and Terminology.

    ERIC Educational Resources Information Center

    Cantrell, Mary Lynn

    1992-01-01

    Provides lists of gang identifiers and terminology. Suggests that, to find out names and associated identifiers of local gangs, readers should talk to their local police. Included in listing are descriptions of gang-related symbols, physical signals, graffiti, slogans, right-left rules, colors, clothing, jewelry, hair styles, and fingernails. Also…

  19. [Performance in