Factors Influencing the Implementation of Training and Learning in the Workplace.

ERIC Educational Resources Information Center

Ridoutt, Lee; Dutneall, Ralph; Hummel, Kevin; Smith, Chris Selby

The quantitative relationship between factors previously identified as affecting the extent and intensity of training within organizations was explored through a survey of companies in Australia's entertainment and process manufacturing sectors. A self-completion questionnaire was mailed first to a sample of 446 companies across Australia (112 of…

A Learner Perspective on Barriers to E-Learning

ERIC Educational Resources Information Center

Becker, Karen; Newton, Cameron; Sawang, Sukanlaya

2013-01-01

This study aims to identify and categorize barriers to e-learning adoption and the relative impact of those barriers on learners. It contributes to the understanding of learner perceptions of barriers, the different types of barriers and their relative importance. This study used a quantitative methodology grounded in previous literature. The…

Teachers' (Mis)Understandings of Resilience

ERIC Educational Resources Information Center

Green, Deborah; Oswald, Murray; Spears, Barbara

2007-01-01

This study aimed to extend previous studies into resilience, by identifying the roles that teachers played in fostering resilience (N=57: females n=43; and males n=14). A quantitative scale was administered to teachers in South Australia's Catholic education sector to determine the extent to which they were involved in fostering resilience. A…

Aligning Person-Centred Methods and Young People's Conceptualizations of Diversity

ERIC Educational Resources Information Center

Waite, Sue; Boyask, Ruth; Lawson, Hazel

2010-01-01

Many existing studies of diversity are concerned with social groups identified by externally determined factors, for example, ethnicity, gender, or educational attainment, and examine, either quantitatively or qualitatively, issues delineated by these. In evaluating methods used in previous research, we consider ways in which the adoption of…

Management Approaches to Stomal and Peristomal Complications: A Narrative Descriptive Study.

PubMed

Beitz, Janice M; Colwell, Janice C

2016-01-01

The purpose of this study was to identify optimal interventions for selected complications based on WOC nurse experts' judgment/expertise. A cross-sectional quantitative descriptive design with qualitative, narrative-type components was used for this study. Following validation rating of appropriateness of interventions and quantitative rankings of first-, second-, and third-line approaches, participants provided substantive handwritten narrative comments about listed interventions. Comments were organized and prioritized using frequency count. Narrative comments reflected the quantitative rankings of efficacy of approaches. Clinicians offered further specific suggestions regarding product use and progression of care for selected complications. Narrative analysis using descriptive quantitative frequency count supported the rankings of most preferred treatments of selected stomal and peristomal complications. Findings add to the previous research on prioritized approaches and evidence-based practice in ostomy care.

Quantitative methylene blue decolourisation assays as rapid screening tools for assessing the efficiency of catalytic reactions.

PubMed

Kruid, Jan; Fogel, Ronen; Limson, Janice Leigh

2017-05-01

Identifying the most efficient oxidation process to achieve maximum removal of a target pollutant compound forms the subject of much research. There exists a need to develop rapid screening tools to support research in this area. In this work we report on the development of a quantitative assay as a means for identifying catalysts capable of decolourising methylene blue through the generation of oxidising species from hydrogen peroxide. Here, a previously described methylene blue test strip method was repurposed as a quantitative, aqueous-based spectrophotometric assay. From amongst a selection of metal salts and metallophthalocyanine complexes, monitoring of the decolourisation of the cationic dye methylene blue (via Fenton-like and non-Fenton oxidation reactions) by the assay identified the following to be suitable oxidation catalysts: CuSO 4 (a Fenton-like catalyst), iron(II)phthalocyanine (a non-Fenton oxidation catalyst), as well as manganese(II) phthalocyanine. The applicability of the method was examined for the removal of bisphenol A (BPA), as measured by HPLC, during parallel oxidation experiments. The order of catalytic activity was identified as FePc > MnPc > CuSO 4 for both BPA and MB. The quantitative MB decolourisation assay may offer a rapid method for screening a wide range of potential catalysts for oxidation processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection and quantitation of HPV in genital and oral tissues and fluids by real time PCR

PubMed Central

2010-01-01

Background Human papillomaviruses (HPVs) remain a serious world health problem due to their association with anogenital/oral cancers and warts. While over 100 HPV types have been identified, a subset is associated with malignancy. HPV16 and 18 are the most prevalent oncogenic types, while HPV6 and 11 are most commonly responsible for anogenital warts. While other quantitative PCR (qPCR) assays detect oncogenic HPV, there is no single tube assay distinguishing the most frequent oncogenic types and the most common types found in warts. Results A Sybr Green-based qPCR assay was developed utilizing degenerate primers to the highly conserved HPV E1 theoretically detecting any HPV type. A single tube multiplex qPCR assay was also developed using type-specific primer pairs and TaqMan probes that allowed for detection and quantitation of HPV6,11,16,18. Each HPV type was detected over a range from 2 × 101 to 2 × 106copies/reaction providing a reliable method of quantitating type-specific HPV in 140 anogenital/cutaneous/oral benign and malignant specimens. 35 oncogenic and low risk alpha genus HPV types were detected. Concordance was detected in previously typed specimens. Comparisons to the gold standard detected an overall sensitivity of 89% (95% CI: 77% - 96%) and specificity of 90% (95%CI: 52% - 98%). Conclusion There was good agreement between the ability of the qPCR assays described here to identify HPV types in malignancies previously typed using standard methods. These novel qPCR assays will allow rapid detection and quantitation of HPVs to assess their role in viral pathogenesis. PMID:20723234

Supplemental Hazard Analysis and Risk Assessment - Hydrotreater

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

Lowry, Peter P.; Wagner, Katie A.

A supplemental hazard analysis was conducted and quantitative risk assessment performed in response to an independent review comment received by the Pacific Northwest National Laboratory (PNNL) from the U.S. Department of Energy Pacific Northwest Field Office (PNSO) against the Hydrotreater/Distillation Column Hazard Analysis Report issued in April 2013. The supplemental analysis used the hazardous conditions documented by the previous April 2013 report as a basis. The conditions were screened and grouped for the purpose of identifying whether additional prudent, practical hazard controls could be identified, using a quantitative risk evaluation to assess the adequacy of the controls and establish amore » lower level of concern for the likelihood of potential serious accidents. Calculations were performed to support conclusions where necessary.« less

Comparative Study of School Principals' Leadership Practices: Lessons for Chile from a Cross-Country Analysis

ERIC Educational Resources Information Center

Marfan, Javiera; Pascual, Javier

2018-01-01

The article reports the results of a cross-country educational research project that uses quantitative methods to identify school leadership practices and contextual characteristics that contribute to explain student achievement in Chile, considering international comparisons. The results question previous evidence about a common repertoire of…

Identification of single nucleotide polymorphism markers associated with bacterial cold water disease resistance and spleen size in rainbow trout

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) is one of the frequent causes of elevated mortality in salmonid aquaculture. Previously, we identified and validated microsatellites associated with QTL (quantitative trait loci) for BCWD resistance and spleen size in rainbow trout. The objective of this study was...

Identification of single nucleotide polymorphism markers associated with bacterial cold water disease resistance and spleen size in rainbow trout

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) is one of the frequent causes of elevated mortality in salmonid aquaculture. Previously, we identified and validated microsatellite markers associated with QTL (quantitative trait loci) for BCWD resistance and spleen size in rainbow trout. The objective of this st...

Concordance of transcriptional and apical benchmark dose levels for conazole-ind uced liver effects in mice

EPA Science Inventory

The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time can inform mode of action and improve quantitative risk assessment. Previous research identified a 330-gene cluster commonly resp...

Synthesis of quantitative and qualitative research: an example using Critical Interpretive Synthesis.

PubMed

Flemming, Kate

2010-01-01

This paper is a report of a Critical Interpretive Synthesis to synthesize quantitative research, in the form of an effectiveness review and a guideline, with qualitative research to examine the use of morphine to treat cancer-related pain. Critical Interpretive Synthesis is a new method of reviewing, developed from meta-ethnography, which integrates systematic review methodology with a qualitative tradition of enquiry. It has not previously been used specifically to synthesize effectiveness and qualitative literature. Data sources. An existing systematic review of quantitative research and a guideline examining the effectiveness of oral morphine to treat cancer pain were identified. Electronic searches of Medline, CINAHL, Embase, PsychINFO, Health Management Information Consortium database and the Social Science Citation Index to identify qualitative research were carried out in May 2008. Qualitative research papers reporting on the use of morphine to treat cancer pain were identified. The findings of the effectiveness research were used as a framework to guide the translation of findings from qualitative research using an integrative grid. A secondary translation of findings from the qualitative research, not specifically mapped to the effectiveness literature, was guided by the framework. Nineteen qualitative papers were synthesized with the quantitative effectiveness literature, producing 14 synthetic constructs. These were developed into four synthesizing arguments which drew on patients', carers' and healthcare professionals' interpretations of the meaning and context of the use of morphine to treat cancer pain. Critical Interpretive Synthesis can be adapted to synthesize reviews of quantitative research into effectiveness with qualitative research and fits into an existing typology of approaches to synthesizing qualitative and quantitative research.

Linkage Analysis of Quantitative Refraction and Refractive Errors in the Beaver Dam Eye Study

PubMed Central

Duggal, Priya; Lee, Kristine E.; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E.; Klein, Barbara E. K.

2011-01-01

Purpose. Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Methods. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Results. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10−4), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10−3 and 1.48 × 10−3, respectively) and to 7p15 of refraction (empiric P = 9.43 × 10−4). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10−3), a region previously linked to high myopia. Conclusions. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11. PMID:21571680

Donation of peripheral blood stem cells to unrelated strangers: A thematic analysis

PubMed Central

Billen, Annelies; Madrigal, J. Alejandro; Scior, Katrina; Shaw, Bronwen E.; Strydom, Andre

2017-01-01

Background Donation of haematopoietic stem cells, either through bone marrow (BM) or peripheral blood stem cell (PBSC) collection, is a generally safe procedure for healthy donors, although side effects are a known risk. Previous research, including our recent quantitative study, has shown that the psychosocial response to donating is usually a positive one and most donors would be willing to donate again in the future. This is often despite experiencing significant side effects during the donation process. Due to the relative recent introduction of PBSC, a comprehensive understanding of the range of physical and emotional issues donors may experience is lacking, as well as an understanding of specific donor characteristics Qualitative research can provide rich narrative data into these areas. This study was set up in order to identify specific donor characteristics and to further explore the relationship between pre-donation physical health and the donation experience, as previously identified in our quantitative study. Methods It involved in-depth telephone interviews with 14 PBSC donors who participated in our original quantitative study. Thematic analysis was used to analyse the findings and the results provide a summary of participants’ characteristics using themes and constituent codes. Results We identified several donor characteristics, including strong intrinsic motivation, altruism, sense of duty, determination, low levels of ambivalence and the ability to develop a strong emotional relationship with an (unknown/anonymous) recipient whilst being able to manage strong feelings and emotions. Conclusions These personality traits may explain the resilience that has been observed previously in haematopoietic stem cells donors. Significant feelings of grief were reported after a recipient’s death. Possibilities to alleviate these symptoms may include raising awareness of potential poor outcomes in the recipient and offering improved counselling services if the recipient dies. We acknowledge several limitations including the sampling frame. PMID:29069088

Genome-wide association study identified three major QTL for carcass weight including the PLAG1-CHCHD7 QTN for stature in Japanese Black cattle

PubMed Central

2012-01-01

Background Significant quantitative trait loci (QTL) for carcass weight were previously mapped on several chromosomes in Japanese Black half-sib families. Two QTL, CW-1 and CW-2, were narrowed down to 1.1-Mb and 591-kb regions, respectively. Recent advances in genomic tools allowed us to perform a genome-wide association study (GWAS) in cattle to detect associations in a general population and estimate their effect size. Here, we performed a GWAS for carcass weight using 1156 Japanese Black steers. Results Bonferroni-corrected genome-wide significant associations were detected in three chromosomal regions on bovine chromosomes (BTA) 6, 8, and 14. The associated single nucleotide polymorphisms (SNP) on BTA 6 were in linkage disequilibrium with the SNP encoding NCAPG Ile442Met, which was previously identified as a candidate quantitative trait nucleotide for CW-2. In contrast, the most highly associated SNP on BTA 14 was located 2.3-Mb centromeric from the previously identified CW-1 region. Linkage disequilibrium mapping led to a revision of the CW-1 region within a 0.9-Mb interval around the associated SNP, and targeted resequencing followed by association analysis highlighted the quantitative trait nucleotides for bovine stature in the PLAG1-CHCHD7 intergenic region. The association on BTA 8 was accounted for by two SNP on the BovineSNP50 BeadChip and corresponded to CW-3, which was simultaneously detected by linkage analyses using half-sib families. The allele substitution effects of CW-1, CW-2, and CW-3 were 28.4, 35.3, and 35.0 kg per allele, respectively. Conclusion The GWAS revealed the genetic architecture underlying carcass weight variation in Japanese Black cattle in which three major QTL accounted for approximately one-third of the genetic variance. PMID:22607022

Novel Autism Subtype-Dependent Genetic Variants Are Revealed by Quantitative Trait and Subphenotype Association Analyses of Published GWAS Data

PubMed Central

Hu, Valerie W.; Addington, Anjene; Hyman, Alexander

2011-01-01

The heterogeneity of symptoms associated with autism spectrum disorders (ASDs) has presented a significant challenge to genetic analyses. Even when associations with genetic variants have been identified, it has been difficult to associate them with a specific trait or characteristic of autism. Here, we report that quantitative trait analyses of ASD symptoms combined with case-control association analyses using distinct ASD subphenotypes identified on the basis of symptomatic profiles result in the identification of highly significant associations with 18 novel single nucleotide polymorphisms (SNPs). The symptom categories included deficits in language usage, non-verbal communication, social development, and play skills, as well as insistence on sameness or ritualistic behaviors. Ten of the trait-associated SNPs, or quantitative trait loci (QTL), were associated with more than one subtype, providing partial replication of the identified QTL. Notably, none of the novel SNPs is located within an exonic region, suggesting that these hereditary components of ASDs are more likely related to gene regulatory processes (or gene expression) than to structural or functional changes in gene products. Seven of the QTL reside within intergenic chromosomal regions associated with rare copy number variants that have been previously reported in autistic samples. Pathway analyses of the genes associated with the QTL identified in this study implicate neurological functions and disorders associated with autism pathophysiology. This study underscores the advantage of incorporating both quantitative traits as well as subphenotypes into large-scale genome-wide analyses of complex disorders. PMID:21556359

Genetic dissection of the maize (Zea mays L.) MAMP response.

PubMed

Zhang, Xinye; Valdés-López, Oswaldo; Arellano, Consuelo; Stacey, Gary; Balint-Kurti, Peter

2017-06-01

Loci associated with variation in maize responses to two microbe-associated molecular patterns (MAMPs) were identified. MAMP responses were correlated. No relationship between MAMP responses and quantitative disease resistance was identified. Microbe-associated molecular patterns (MAMPs) are highly conserved molecules commonly found in microbes which can be recognized by plant pattern recognition receptors. Recognition triggers a suite of responses including production of reactive oxygen species (ROS) and nitric oxide (NO) and expression changes of defense-related genes. In this study, we used two well-studied MAMPs (flg22 and chitooctaose) to challenge different maize lines to determine whether there was variation in the level of responses to these MAMPs, to dissect the genetic basis underlying that variation and to understand the relationship between MAMP response and quantitative disease resistance (QDR). Naturally occurring quantitative variation in ROS, NO production, and defense genes expression levels triggered by MAMPs was observed. A major quantitative traits locus (QTL) associated with variation in the ROS production response to both flg22 and chitooctaose was identified on chromosome 2 in a recombinant inbred line (RIL) population derived from the maize inbred lines B73 and CML228. Minor QTL associated with variation in the flg22 ROS response was identified on chromosomes 1 and 4. Comparison of these results with data previously obtained for variation in QDR and the defense response in the same RIL population did not provide any evidence for a common genetic basis controlling variation in these traits.

Similar genetic architecture with shared and unique quantitative trait loci for bacterial cold water disease resistance in two rainbow trout breeding populations

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a 57K SNP array and a genome phys...

"Inject-mix-react-separate-and-quantitate" (IMReSQ) method for screening enzyme inhibitors.

PubMed

Wong, Edmund; Okhonin, Victor; Berezovski, Maxim V; Nozaki, Tomoyoshi; Waldmann, Herbert; Alexandrov, Kirill; Krylov, Sergey N

2008-09-10

Many regulatory enzymes are considered attractive therapeutic targets, and their inhibitors are potential drug candidates. Screening combinatorial libraries for enzyme inhibitors is pivotal to identifying hit compounds for the development of drugs targeting regulatory enzymes. Here, we introduce the first inhibitor screening method that consumes only nanoliters of the reactant solutions and is applicable to regulatory enzymes. The method is termed inject-mix-react-separate-and-quantitate (IMReSQ) and includes five steps. First, nanoliter volumes of substrate, candidate inhibitor, and enzyme solutions are injected by pressure into a capillary as separate plugs. Second, the plugs are mixed inside this capillary microreactor by transverse diffusion of laminar flow profiles. Third, the reaction mixture is incubated to form the enzymatic product. Fourth, the product is separated from the substrate inside the capillary by electrophoresis. Fifth, the amounts of the product and substrate are quantitated. In this proof-of-principle work, we applied IMReSQ to study inhibition of recently cloned protein farnesyltransferase from parasite Entamoeba histolytica. This enzyme is a potential therapeutic target for antiparasitic drugs. We identified three previously unknown inhibitors of this enzyme and proved that IMReSQ could be used for quantitatively ranking the potencies of inhibitors.

Cloning of DOG1, a quantitative trait locus controlling seed dormancy in Arabidopsis.

PubMed

Bentsink, Leónie; Jowett, Jemma; Hanhart, Corrie J; Koornneef, Maarten

2006-11-07

Genetic variation for seed dormancy in nature is a typical quantitative trait controlled by multiple loci on which environmental factors have a strong effect. Finding the genes underlying dormancy quantitative trait loci is a major scientific challenge, which also has relevance for agriculture and ecology. In this study we describe the identification of the DELAY OF GERMINATION 1 (DOG1) gene previously identified as a quantitative trait locus involved in the control of seed dormancy. This gene was isolated by a combination of positional cloning and mutant analysis and is absolutely required for the induction of seed dormancy. DOG1 is a member of a small gene family of unknown molecular function, with five members in Arabidopsis. The functional natural allelic variation present in Arabidopsis is caused by polymorphisms in the cis-regulatory region of the DOG1 gene and results in considerable expression differences between the DOG1 alleles of the accessions analyzed.

[Advantages and disadvantages of incorporating qualitative methodology in the evaluation of health services. A practical case: evaluation of a high-resolution clinic].

PubMed

Alvarez Del Arco, D; Rodríguez Rieiro, C; Sanchidrián De Blás, C; Alejos, B; Plá Mestre, R

2012-01-01

We examined the usefulness of incorporating a qualitative phase in the evaluation of the quality of care in a high-resolution medical service carried out with quantitative methods. A quantitative research was performed using a structured questionnaire and selecting interviewees by systematic randomized sampling methods (n=320). In addition, a qualitative research was carried on through semi-structured interviews with patients selected by convenience criteria (n=11), observations in the care assistance circuit, and a group interview with health professionals working in the service. A multidisciplinary research team conducted an individual analysis of the information collected in both quantitative and qualitative phases. Subsequently, three meetings based on group brainstorming techniques were held to identify the diverse contributions of each of the methodologies employed to the research, using affinity graphs to analyse the different results obtained in both phases and evaluate possible bias arising from the use of qualitative methods. Qualitative research allowed examining specific aspects of the health care service that had been collected in the quantitative phase, harmonizing the results obtained in the previous phase, giving in-depth data on the reasons for patient dissatisfaction with specific aspects, such as waiting times and available infrastructures, and identifying emerging issues of the service which had not been previously assessed. Overall, the qualitative phase enriched the results of the research. It is appropriate and recommendable to incorporate this methodological approach in research aimed at evaluating the quality of the service in specific health care settings, since it is provided first hand, by the voice of the customer. Copyright © 2011 SECA. Published by Elsevier Espana. All rights reserved.

The ACCE method: an approach for obtaining quantitative or qualitative estimates of residual confounding that includes unmeasured confounding

PubMed Central

Smith, Eric G.

2015-01-01

Background:  Nonrandomized studies typically cannot account for confounding from unmeasured factors.  Method:  A method is presented that exploits the recently-identified phenomenon of  “confounding amplification” to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors.  Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure.  Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome. Results:  Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method’s requirements and assumptions are met.  Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding. Limitations:  Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method’s estimates (although bootstrapping is one plausible approach). Conclusions:  To this author’s knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is straightforward.  The method's routine usefulness, however, has not yet been established, nor has the method been fully validated. Rapid further investigation of this novel method is clearly indicated, given the potential value of its quantitative or qualitative output. PMID:25580226

Quantitative label-free proteomic analysis of human urine to identify novel candidate protein biomarkers for schistosomiasis.

PubMed

Onile, Olugbenga Samson; Calder, Bridget; Soares, Nelson C; Anumudu, Chiaka I; Blackburn, Jonathan M

2017-11-01

Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity. A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers. A total of 1306 proteins and 9701 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70). These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis.

How Does Mindfulness Training Change the Narratives of Young People Identified as Having Behavioural Difficulties? An Exploratory Study

ERIC Educational Resources Information Center

Ardern, Catherine

2016-01-01

Previous research investigating the use of Mindfulness as an intervention has generally taken a quantitative approach, focusing on outcomes rather than processes. The purpose of this research was to develop an understanding of how and why Mindfulness training might influence young people. The study explored the changes in narratives that occur in…

Factors Mediating the Interactions between Adviser and Advisee during the Master's Thesis Project: A Quantitative Approach

ERIC Educational Resources Information Center

Rodrigues Jr., Jose Florencio; Lehmann, Angela Valeria Levay; Fleith, Denise De Souza

2005-01-01

Building on previous studies centred on the interaction between adviser and advisee in masters thesis projects, in which a qualitative approach was used, the present study uses factor analysis to identify the factors that determine either a successful or unsuccessful outcome for the masters thesis project. There were five factors relating to the…

Identifying haplotypes for flowering and QTLs for fruit quality in the RosBREED Michigan and Oregon strawberry (Fragaria ×ananassa) breeding sets using pedigree-based analysis [abstract

USDA-ARS?s Scientific Manuscript database

Strawberry (Fragaria ×ananassa) is consumed for its flavor and health benefits. Over the last two decades, several quantitative trait loci (QTL) analysis studies for consumer traits were conducted using low-density genetic maps. The previous studies utilized low-throughput genotyping methodologies. ...

The Bicoid Class Homeodomain Factors ceh-36/OTX and unc-30/PITX Cooperate in C. elegans Embryonic Progenitor Cells to Regulate Robust Development

PubMed Central

Walton, Travis; Preston, Elicia; Nair, Gautham; Zacharias, Amanda L.; Raj, Arjun; Murray, John Isaac

2015-01-01

While many transcriptional regulators of pluripotent and terminally differentiated states have been identified, regulation of intermediate progenitor states is less well understood. Previous high throughput cellular resolution expression studies identified dozens of transcription factors with lineage-specific expression patterns in C. elegans embryos that could regulate progenitor identity. In this study we identified a broad embryonic role for the C. elegans OTX transcription factor ceh-36, which was previously shown to be required for the terminal specification of four neurons. ceh-36 is expressed in progenitors of over 30% of embryonic cells, yet is not required for embryonic viability. Quantitative phenotyping by computational analysis of time-lapse movies of ceh-36 mutant embryos identified cell cycle or cell migration defects in over 100 of these cells, but most defects were low-penetrance, suggesting redundancy. Expression of ceh-36 partially overlaps with that of the PITX transcription factor unc-30. unc-30 single mutants are viable but loss of both ceh-36 and unc-30 causes 100% lethality, and double mutants have significantly higher frequencies of cellular developmental defects in the cells where their expression normally overlaps. These factors are also required for robust expression of the downstream developmental regulator mls-2/HMX. This work provides the first example of genetic redundancy between the related yet evolutionarily distant OTX and PITX families of bicoid class homeodomain factors and demonstrates the power of quantitative developmental phenotyping in C. elegans to identify developmental regulators acting in progenitor cells. PMID:25738873

A high-resolution genetic map of yellow monkeyflower identifies chemical defense QTLs and recombination rate variation.

PubMed

Holeski, Liza M; Monnahan, Patrick; Koseva, Boryana; McCool, Nick; Lindroth, Richard L; Kelly, John K

2014-03-13

Genotyping-by-sequencing methods have vastly improved the resolution and accuracy of genetic linkage maps by increasing both the number of marker loci as well as the number of individuals genotyped at these loci. Using restriction-associated DNA sequencing, we construct a dense linkage map for a panel of recombinant inbred lines derived from a cross between divergent ecotypes of Mimulus guttatus. We used this map to estimate recombination rate across the genome and to identify quantitative trait loci for the production of several secondary compounds (PPGs) of the phenylpropanoid pathway implicated in defense against herbivores. Levels of different PPGs are correlated across recombinant inbred lines suggesting joint regulation of the phenylpropanoid pathway. However, the three quantitative trait loci identified in this study each act on a distinct PPG. Finally, we map three putative genomic inversions differentiating the two parental populations, including a previously characterized inversion that contributes to life-history differences between the annual/perennial ecotypes. Copyright © 2014 Holeski et al.

Identification of Salmonella Typhimurium deubiquitinase SseL substrates by immunoaffinity enrichment and quantitative proteomic analysis

DOE PAGES

Nakayasu, Ernesto S.; Sydor, Michael A.; Brown, Roslyn N.; ...

2015-07-06

Ubiquitination is a key protein post-translational modification that regulates many important cellular pathways and whose levels are regulated by equilibrium between the activities of ubiquitin ligases and deubiquitinases. Here we present a method to identify specific deubiquitinase substrates based on treatment of cell lysates with recombinant enzymes, immunoaffinity purification and global quantitative proteomic analysis. As model system to identify substrates, we used a virulence-related deubiquitinase secreted by Salmonella enterica serovar Typhimurium into the host cells, SseL. By using this approach two SseL substrates were identified in RAW 264.7 murine macrophage-like cell line, S100A6 and het-erogeneous nuclear ribonuclear protein K, inmore » addition to the previously reported K63-linked ubiquitin chains. These substrates were further validated by a combination of enzymatic and binding assays. Finally, this method can be used for the systematic identification of substrates of deubiquitinases from other organisms and applied to study their functions in physiology and disease.« less

Identification of Salmonella Typhimurium deubiquitinase SseL substrates by immunoaffinity enrichment and quantitative proteomic analysis

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

Nakayasu, Ernesto S.; Sydor, Michael A.; Brown, Roslyn N.

Ubiquitination is a key protein post-translational modification that regulates many important cellular pathways and whose levels are regulated by equilibrium between the activities of ubiquitin ligases and deubiquitinases. Here we present a method to identify specific deubiquitinase substrates based on treatment of cell lysates with recombinant enzymes, immunoaffinity purification and global quantitative proteomic analysis. As model system to identify substrates, we used a virulence-related deubiquitinase secreted by Salmonella enterica serovar Typhimurium into the host cells, SseL. By using this approach two SseL substrates were identified in RAW 264.7 murine macrophage-like cell line, S100A6 and het-erogeneous nuclear ribonuclear protein K, inmore » addition to the previously reported K63-linked ubiquitin chains. These substrates were further validated by a combination of enzymatic and binding assays. Finally, this method can be used for the systematic identification of substrates of deubiquitinases from other organisms and applied to study their functions in physiology and disease.« less

The quantitative and condition-dependent Escherichia coli proteome

PubMed Central

Schmidt, Alexander; Kochanowski, Karl; Vedelaar, Silke; Ahrné, Erik; Volkmer, Benjamin; Callipo, Luciano; Knoops, Kèvin; Bauer, Manuel; Aebersold, Ruedi; Heinemann, Matthias

2016-01-01

Measuring precise concentrations of proteins can provide insights into biological processes. Here, we use efficient protein extraction and sample fractionation and state-of-the-art quantitative mass spectrometry techniques to generate a comprehensive, condition-dependent protein abundance map of Escherichia coli. We measure cellular protein concentrations for 55% of predicted E. coli genes (>2300 proteins) under 22 different experimental conditions and identify methylation and N-terminal protein acetylations previously not known to be prevalent in bacteria. We uncover system-wide proteome allocation, expression regulation, and post-translational adaptations. These data provide a valuable resource for the systems biology and broader E. coli research communities. PMID:26641532

Quantitative spatial frequency fluorescence imaging in the sub-diffusive domain for image-guided glioma resection

PubMed Central

Sibai, Mira; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Wilson, Brian C.

2015-01-01

Intraoperative 5- aminolevulinic acid induced-Protoporphyrin IX (PpIX) fluorescence guidance enables maximum safe resection of glioblastomas by providing surgeons with real-time tumor optical contrast. However, visual assessment of PpIX fluorescence is subjective and limited by the distorting effects of light attenuation and tissue autofluorescence. We have previously shown that non-invasive point measurements of absolute PpIX concentration identifies residual tumor that is otherwise non-detectable. Here, we extend this approach to wide-field quantitative fluorescence imaging by implementing spatial frequency domain imaging to recover tissue optical properties across the field-of-view in phantoms and ex vivo tissue. PMID:26713206

Agency Problems and Airport Security: Quantitative and Qualitative Evidence on the Impact of Security Training.

PubMed

de Gramatica, Martina; Massacci, Fabio; Shim, Woohyun; Turhan, Uğur; Williams, Julian

2017-02-01

We analyze the issue of agency costs in aviation security by combining results from a quantitative economic model with a qualitative study based on semi-structured interviews. Our model extends previous principal-agent models by combining the traditional fixed and varying monetary responses to physical and cognitive effort with nonmonetary welfare and potentially transferable value of employees' own human capital. To provide empirical evidence for the tradeoffs identified in the quantitative model, we have undertaken an extensive interview process with regulators, airport managers, security personnel, and those tasked with training security personnel from an airport operating in a relatively high-risk state, Turkey. Our results indicate that the effectiveness of additional training depends on the mix of "transferable skills" and "emotional" buy-in of the security agents. Principals need to identify on which side of a critical tipping point their agents are to ensure that additional training, with attached expectations of the burden of work, aligns the incentives of employees with the principals' own objectives. © 2016 Society for Risk Analysis.

Quantitative trait locus analysis of plasma cholesterol levels and body weight by controlling the effects of the Apoa2 allele in mice.

PubMed

Suto, Jun-ichi

2007-04-01

Colleagues and I previously performed quantitative trait locus (QTL) analysis on plasma total-cholesterol (T-CHO) levels in C57BL/6J (B6) x RR F2 mice. We identified only one significant QTL (Cq6) on chromosome 1 in a region containing the Apoa2 gene locus, a convincing candidate gene for Cq6. Because Cq6 was a highly significant QTL, we considered that the detection of other potential QTLs might be hindered. In the present study, QTL analysis was performed in B6.KK-Apoa2b N(8) x RR F2 mice [B6.KK-Apoa2b N(8) is a partial congenic strain carrying the Apoa2b allele from the KK strain, and RR also has the Apoa2b allele] by controlling of the effects of the Apoa2 allele, for identifying additional QTLs. Although no significant QTLs were identified, 2 suggestive QTLs were found on chromosomes 2 and 3 in place of the effects of the Apoa2 allele. A significant body weight QTL was identified on chromosome 3 (Bwq7, peak LOD score 5.2); its effect on body weight was not significant in previously analyzed B6 x RR F2 mice. Suggestive body weight QTL that had been identified in B6 x RR F2 mice on chromosome 4 (LOD score 3.8) was not identified in B6.KK-Apoa2b N(8) x RR F2 mice. Thus, contrary to expectation, the genetic control of body weight was also altered significantly by controlling of the effects of the Apoa2 allele. The QTL mapping strategy by controlling of the effects of a major QTL facilitated the identification of additional QTLs.

Quantitative Measures of Swallowing Deficits in Patients With Parkinson's Disease.

PubMed

Ellerston, Julia K; Heller, Amanda C; Houtz, Daniel R; Kendall, Katherine A

2016-05-01

Dysphagia and associated aspiration pneumonia are commonly reported sequelae of Parkinson's disease (PD). Previous studies of swallowing in patients with PD have described prolonged pharyngeal transit time, delayed onset of pharyngeal transit, cricopharyngeal (CP) achalasia, reduced pharyngeal constriction, and slowed hyolaryngeal elevation. These studies were completed using inconsistent evaluation methodology, reliance on qualitative analysis, and a lack of a large control group, resulting in concerns regarding diagnostic precision. The purpose of this study was to investigate swallowing function in patients with PD using a norm-referenced, quantitative approach. This retrospective study includes 34 patients with a diagnosis of PD referred to a multidisciplinary voice and swallowing clinic. Modified barium swallow studies were performed using quantitative measures of pharyngeal transit time, hyoid displacement, CP sphincter opening, area of the pharynx at maximal constriction, and timing of laryngeal vestibule closure relative to bolus arrival at the CP sphincter. Reduced pharyngeal constriction was found in 30.4%, and a delay in airway closure relative to arrival of the bolus at the CP sphincter was the most common abnormality, present in 62% of patients. Previously reported findings of prolonged pharyngeal transit, poor hyoid elevation, and CP achalasia were not identified as prominent features. © The Author(s) 2015.

Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

DTIC Science & Technology

2008-09-01

12]. Another interesting gene ; monoamine oxidase A ( MAOA ) was upregulated in patients with PSA relapse (Figure 8A). Quantitative real-time PCR (qRT...from prostate. After excluding genes previously shown to be influenced by the radical prostatectomy procedure, we identified 51 genes with significant...analyses confirmed overexpression of GDF15 may confer resistance to chemotherapy in prostate cancer cells. Gene expression changes after

[Profile of adolescents with repeated pregnancies attended at a prenatal clinic].

PubMed

Persona, Lia; Shimo, Antonieta Keiko Kakuda; Tarallo, Maria Celina

2004-01-01

This study identified the biopsychosocial profile of adolescent with repeated pregnancies, who were attended at a prenatal clinic. Data were collected through patient records and interviews and were subject to quantitative analysis. Based on the obtained results and in accordance with literature, factors that are strongly associated with the occurrence of pregnancy repetition were selected in the adolescents' profiles. These are: early menarche; first sexual intercourse shortly after menarche; school repetition; school dropout; non remunerated occupation; low family income; involvement with older partners; living with the partner; consensual union with the partner; one partner; low condom use; family history of adolescent pregnancy; father's absence because of death or abandonment; positive family reaction to previous pregnancy; previous abortion; adolescent's positive concepts about previous delivery; and absence from previous postpartum consultations.

Quantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis.

PubMed

Stoletov, Konstantin; Willetts, Lian; Paproski, Robert J; Bond, David J; Raha, Srijan; Jovel, Juan; Adam, Benjamin; Robertson, Amy E; Wong, Francis; Woolner, Emma; Sosnowski, Deborah L; Bismar, Tarek A; Wong, Gane Ka-Shu; Zijlstra, Andries; Lewis, John D

2018-06-14

Metastasis is the most lethal aspect of cancer, yet current therapeutic strategies do not target its key rate-limiting steps. We have previously shown that the entry of cancer cells into the blood stream, or intravasation, is highly dependent upon in vivo cancer cell motility, making it an attractive therapeutic target. To systemically identify genes required for tumor cell motility in an in vivo tumor microenvironment, we established a novel quantitative in vivo screening platform based on intravital imaging of human cancer metastasis in ex ovo avian embryos. Utilizing this platform to screen a genome-wide shRNA library, we identified a panel of novel genes whose function is required for productive cancer cell motility in vivo, and whose expression is closely associated with metastatic risk in human cancers. The RNAi-mediated inhibition of these gene targets resulted in a nearly total (>99.5%) block of spontaneous cancer metastasis in vivo.

Quantitative Proteomic Analysis Reveals That Anti-Cancer Effects of Selenium-Binding Protein 1 In Vivo Are Associated with Metabolic Pathways

PubMed Central

Ying, Qi; Ansong, Emmanuel; Diamond, Alan M.; Lu, Zhaoxin; Yang, Wancai; Bie, Xiaomei

2015-01-01

Previous studies have shown the tumor-suppressive role of selenium-binding protein 1 (SBP1), but the underlying mechanisms are unclear. In this study, we found that induction of SBP1 showed significant inhibition of colorectal cancer cell growth and metastasis in mice. We further employed isobaric tags for relative and absolute quantitation (iTRAQ) to identify proteins that were involved in SBP1-mediated anti-cancer effects in tumor tissues. We identified 132 differentially expressed proteins, among them, 53 proteins were upregulated and 79 proteins were downregulated. Importantly, many of the differentially altered proteins were associated with lipid/glucose metabolism, which were also linked to Glycolysis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT) signaling pathways. These results have revealed a novel mechanism that SBP1-mediated cancer inhibition is through altering lipid/glucose metabolic signaling pathways. PMID:25974208

Time series regression-based pairs trading in the Korean equities market

NASA Astrophysics Data System (ADS)

Kim, Saejoon; Heo, Jun

2017-07-01

Pairs trading is an instance of statistical arbitrage that relies on heavy quantitative data analysis to profit by capitalising low-risk trading opportunities provided by anomalies of related assets. A key element in pairs trading is the rule by which open and close trading triggers are defined. This paper investigates the use of time series regression to define the rule which has previously been identified with fixed threshold-based approaches. Empirical results indicate that our approach may yield significantly increased excess returns compared to ones obtained by previous approaches on large capitalisation stocks in the Korean equities market.

Critical Appraisal of Emergency Medicine Education Research: The Best Publications of 2014.

PubMed

Yarris, Lalena M; Juve, Amy Miller; Coates, Wendy C; Fisher, Jonathan; Heitz, Corey; Shayne, Philip; Farrell, Susan E

2015-11-01

The objective was to critically appraise and highlight rigorous education research study articles published in 2014 whose outcomes advance the science of emergency medicine (EM) education. A search of the English language literature in 2014 querying Education Resources Information Center (ERIC), PsychINFO, PubMed, and Scopus identified 243 EM-related articles using either quantitative (hypothesis-testing or observational investigations of educational interventions) or qualitative (exploring important phenomena in EM education) methods. Two reviewers independently screened all of the publications using previously established exclusion criteria. Six reviewers then independently scored the 25 selected publications using either a qualitative or a quantitative scoring system. Each scoring system consisted of nine criteria. Selected criteria were based on accepted educational review literature and chosen a priori. Both scoring systems use parallel scoring metrics and have been used previously within this annual review. Twenty-five medical education research papers (22 quantitative, three qualitative) met the criteria for inclusion and were reviewed. Five quantitative and two qualitative studies were ranked most highly by the reviewers as exemplary and are summarized in this article. This annual critical appraisal series highlights seven excellent EM education research studies, meeting a priori criteria and published in 2014. Methodologic strengths in the 2014 papers are noted, and current trends in medical education research in EM are discussed. © 2015 by the Society for Academic Emergency Medicine.

Automated detection of solar eruptions

NASA Astrophysics Data System (ADS)

Hurlburt, N.

2015-12-01

Observation of the solar atmosphere reveals a wide range of motions, from small scale jets and spicules to global-scale coronal mass ejections (CMEs). Identifying and characterizing these motions are essential to advancing our understanding of the drivers of space weather. Both automated and visual identifications are currently used in identifying Coronal Mass Ejections. To date, eruptions near the solar surface, which may be precursors to CMEs, have been identified primarily by visual inspection. Here we report on Eruption Patrol (EP): a software module that is designed to automatically identify eruptions from data collected by the Atmospheric Imaging Assembly on the Solar Dynamics Observatory (SDO/AIA). We describe the method underlying the module and compare its results to previous identifications found in the Heliophysics Event Knowledgebase. EP identifies eruptions events that are consistent with those found by human annotations, but in a significantly more consistent and quantitative manner. Eruptions are found to be distributed within 15 Mm of the solar surface. They possess peak speeds ranging from 4 to 100 km/s and display a power-law probability distribution over that range. These characteristics are consistent with previous observations of prominences.

Methodological exemplar of integrating quantitative and qualitative evidence - supportive care for men with prostate cancer: what are the most important components?

PubMed

Huntley, Alyson L; King, Anna J L; Moore, Theresa H M; Paterson, Charlotte; Persad, Raj; Sharp, Debbie; Evans, Maggie

2017-01-01

To present a methodological exemplar of integrating findings from a quantitative and qualitative review on the same topic to provide insight into components of care that contribute to supportive care that is acceptable to men with prostate cancer. Men with prostate cancer are likely to live a long time with the disease, experience side effects from treatment and therefore have ongoing supportive care needs. Quantitative and qualitative reviews have been published but the findings have yet to be integrated. Integration of quantitative and qualitative synthesized evidence. Two previously published systematic reviews. Synthesized evidence on supportive care for men with prostate cancer was integrated from two previously published systematic reviews: a narrative quantitative review and a qualitative review with thematic synthesis. These two streams of synthesized evidence were synthesized using concurrent narrative summary. Data from both reviews were used to develop a set of propositions from which a summary of components of care that likely to contribute to supportive care acceptable to men with prostate cancer were identified. Nine propositions were developed which covered men's supportive care focusing on the role of health professionals. These propositions were used to compose nine components of care likely to lead to supportive care that is acceptable to men with prostate cancer. Some of these components are no/low cost such as developing a more empathic personalized approach, but more specific approaches need further investigation in randomized controlled trials, for example, online support. This methodological exemplar demonstrates the integration of quantitative and qualitative synthesized data to determine components of care likely to lead to provision of supportive care acceptable to men with prostate cancer. © 2016 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

Durable resistance: A key to sustainable management of pathogens and pests

PubMed Central

Mundt, Christopher C.

2014-01-01

This review briefly addresses what has been learned about resistance durability in recent years, as well as the questions that still remain. Molecular analyses of major gene interactions have potential to contribute to both breeding for resistance and improved understanding of virulence impacts on pathogen fitness. Though the molecular basis of quantitative resistance is less clear substantial evidence has accumulated for the relative simplicity of inheritance. There is increasing evidence for specific interactions with quantitative resistance, though implications o this for durability are still unknown. Mechanisms by which resistance gene pyramids contribute to durability remain elusive, though ideas have been generated for identifying gene combinations that may be more durable. Though cultivar mixtures and related approaches have been used successfully, identifying the diseases and conditions that are most conducive to the use of diversity has been surprisingly difficult, and the selective influence of diversity on pathogen populations is complex. The importance of considering resistance durability in a landscape context has received increasing emphasis and is an important future area of research. Experimental systems are being developed to test resistance gene deployment strategies that previously could be addressed only with logic and observation. The value of molecular markers for identifying and pyramiding major genes is quite clear, but the successful use of quantitative trait loci (QTL) for marker-assisted selection of quantitative resistance will depend greatly on the degree to which the identified QTL are expressed in different genetic backgrounds. Transgenic approaches will likely provide opportunities for control of some recalcitrant pathogens, though issues of durability for transgenes are likely to be no different than other genes for resistance. The need for high quality phenotypic analysis and screening methodologies is a priority, and field-based studies are likely to remain of signal importance in the foreseeable future. PMID:24486735

Faculty Grading of Quantitative Problems: A Mismatch between Values and Practice

NASA Astrophysics Data System (ADS)

Petcovic, Heather L.; Fynewever, Herb; Henderson, Charles; Mutambuki, Jacinta M.; Barney, Jeffrey A.

2013-04-01

Grading practices can send a powerful message to students about course expectations. A study by Henderson et al. (American Journal of Physics 72:164-169, 2004) in physics education has identified a misalignment between what college instructors say they value and their actual scoring of quantitative student solutions. This work identified three values that guide grading decisions: (1) a desire to see students' reasoning, (2) a readiness to deduct points from solutions with obvious errors and a reluctance to deduct points from solutions that might be correct, and (3) a tendency to assume correct reasoning when solutions are ambiguous. These authors propose that when values are in conflict, the conflict is resolved by placing the burden of proof on either the instructor or the student. Here, we extend the results of the physics study to earth science ( n = 7) and chemistry ( n = 10) instructors in a think-aloud interview study. Our results suggest that both the previously identified three values and the misalignment between values and grading practices exist among science faculty more generally. Furthermore, we identified a fourth value not previously recognized. Although all of the faculty across both studies stated that they valued seeing student reasoning, the combined effect suggests that only 49% of faculty across the three disciplines graded work in such a way that would actually encourage students to show their reasoning, and 34% of instructors could be viewed as penalizing students for showing their work. This research may contribute toward a better alignment between values and practice in faculty development.

Comprehensive analysis of "bath salts" purchased from California stores and the internet.

PubMed

Schneir, A; Ly, B T; Casagrande, K; Darracq, M; Offerman, S R; Thornton, S; Smollin, C; Vohra, R; Rangun, C; Tomaszewski, C; Gerona, R R

2014-08-01

To analyze the contents of "bath salt" products purchased from California stores and the Internet qualitatively and quantitatively in a comprehensive manner. A convenience sample of "bath salt" products were purchased in person by multiple authors at retail stores in six California cities and over the Internet (U.S. sites only), between August 11, 2011 and December 15, 2011. Liquid chromatography-time-of-flight mass spectrometry was utilized to identify and quantify all substances in the purchased products. Thirty-five "bath salt" products were purchased and analyzed. Prices ranged from $9.95 to 49.99 (U.S. dollars). Most products had a warning against use. The majority (32/35, 91%) had one (n = 15) or multiple cathinones (n = 17) present. Fourteen different cathinones were identified, 3,4-methylenedioxypyrovalerone (MDPV) being the most common. Multiple drugs found including cathinones (buphedrone, ethcathinone, ethylone, MDPBP, and PBP), other designer amines (ethylamphetamine, fluoramphetamine, and 5-IAI), and the antihistamine doxylamine had not been previously identified in U.S. "bath salt" products. Quantification revealed high stimulant content and in some cases dramatic differences in either total cathinone or synthetic stimulant content between products with the same declared weight and even between identically named and outwardly appearing products. Comprehensive analysis of "bath salts" purchased from California stores and the Internet revealed the products to consistently contain cathinones, alone, or in different combinations, sometimes in high quantity. Multiple cathinones and other drugs found had not been previously identified in U.S. "bath salt" products. High total stimulant content in some products and variable qualitative and quantitative composition amongst products were demonstrated.

A peptide-retrieval strategy enables significant improvement of quantitative performance without compromising confidence of identification.

PubMed

Tu, Chengjian; Shen, Shichen; Sheng, Quanhu; Shyr, Yu; Qu, Jun

2017-01-30

Reliable quantification of low-abundance proteins in complex proteomes is challenging largely owing to the limited number of spectra/peptides identified. In this study we developed a straightforward method to improve the quantitative accuracy and precision of proteins by strategically retrieving the less confident peptides that were previously filtered out using the standard target-decoy search strategy. The filtered-out MS/MS spectra matched to confidently-identified proteins were recovered, and the peptide-spectrum-match FDR were re-calculated and controlled at a confident level of FDR≤1%, while protein FDR maintained at ~1%. We evaluated the performance of this strategy in both spectral count- and ion current-based methods. >60% increase of total quantified spectra/peptides was respectively achieved for analyzing a spike-in sample set and a public dataset from CPTAC. Incorporating the peptide retrieval strategy significantly improved the quantitative accuracy and precision, especially for low-abundance proteins (e.g. one-hit proteins). Moreover, the capacity of confidently discovering significantly-altered proteins was also enhanced substantially, as demonstrated with two spike-in datasets. In summary, improved quantitative performance was achieved by this peptide recovery strategy without compromising confidence of protein identification, which can be readily implemented in a broad range of quantitative proteomics techniques including label-free or labeling approaches. We hypothesize that more quantifiable spectra and peptides in a protein, even including less confident peptides, could help reduce variations and improve protein quantification. Hence the peptide retrieval strategy was developed and evaluated in two spike-in sample sets with different LC-MS/MS variations using both MS1- and MS2-based quantitative approach. The list of confidently identified proteins using the standard target-decoy search strategy was fixed and more spectra/peptides with less confidence matched to confident proteins were retrieved. However, the total peptide-spectrum-match false discovery rate (PSM FDR) after retrieval analysis was still controlled at a confident level of FDR≤1%. As expected, the penalty for occasionally incorporating incorrect peptide identifications is negligible by comparison with the improvements in quantitative performance. More quantifiable peptides, lower missing value rate, better quantitative accuracy and precision were significantly achieved for the same protein identifications by this simple strategy. This strategy is theoretically applicable for any quantitative approaches in proteomics and thereby provides more quantitative information, especially on low-abundance proteins. Published by Elsevier B.V.

Quantitative Assessment of In-solution Digestion Efficiency Identifies Optimal Protocols for Unbiased Protein Analysis*

PubMed Central

León, Ileana R.; Schwämmle, Veit; Jensen, Ole N.; Sprenger, Richard R.

2013-01-01

The majority of mass spectrometry-based protein quantification studies uses peptide-centric analytical methods and thus strongly relies on efficient and unbiased protein digestion protocols for sample preparation. We present a novel objective approach to assess protein digestion efficiency using a combination of qualitative and quantitative liquid chromatography-tandem MS methods and statistical data analysis. In contrast to previous studies we employed both standard qualitative as well as data-independent quantitative workflows to systematically assess trypsin digestion efficiency and bias using mitochondrial protein fractions. We evaluated nine trypsin-based digestion protocols, based on standard in-solution or on spin filter-aided digestion, including new optimized protocols. We investigated various reagents for protein solubilization and denaturation (dodecyl sulfate, deoxycholate, urea), several trypsin digestion conditions (buffer, RapiGest, deoxycholate, urea), and two methods for removal of detergents before analysis of peptides (acid precipitation or phase separation with ethyl acetate). Our data-independent quantitative liquid chromatography-tandem MS workflow quantified over 3700 distinct peptides with 96% completeness between all protocols and replicates, with an average 40% protein sequence coverage and an average of 11 peptides identified per protein. Systematic quantitative and statistical analysis of physicochemical parameters demonstrated that deoxycholate-assisted in-solution digestion combined with phase transfer allows for efficient, unbiased generation and recovery of peptides from all protein classes, including membrane proteins. This deoxycholate-assisted protocol was also optimal for spin filter-aided digestions as compared with existing methods. PMID:23792921

A novel iterative mixed model to remap three complex orthopedic traits in dogs

PubMed Central

Huang, Meng; Hayward, Jessica J.; Corey, Elizabeth; Garrison, Susan J.; Wagner, Gabriela R.; Krotscheck, Ursula; Hayashi, Kei; Schweitzer, Peter A.; Lust, George; Boyko, Adam R.; Todhunter, Rory J.

2017-01-01

Hip dysplasia (HD), elbow dysplasia (ED), and rupture of the cranial (anterior) cruciate ligament (RCCL) are the most common complex orthopedic traits of dogs and all result in debilitating osteoarthritis. We reanalyzed previously reported data: the Norberg angle (a quantitative measure of HD) in 921 dogs, ED in 113 cases and 633 controls, and RCCL in 271 cases and 399 controls and their genotypes at ~185,000 single nucleotide polymorphisms. A novel fixed and random model with a circulating probability unification (FarmCPU) function, with marker-based principal components and a kinship matrix to correct for population stratification, was used. A Bonferroni correction at p<0.01 resulted in a P< 6.96 ×10−8. Six loci were identified; three for HD and three for RCCL. An associated locus at CFA28:34,369,342 for HD was described previously in the same dogs using a conventional mixed model. No loci were identified for RCCL in the previous report but the two loci for ED in the previous report did not reach genome-wide significance using the FarmCPU model. These results were supported by simulation which demonstrated that the FarmCPU held no power advantage over the linear mixed model for the ED sample but provided additional power for the HD and RCCL samples. Candidate genes for HD and RCCL are discussed. When using FarmCPU software, we recommend a resampling test, that a positive control be used to determine the optimum pseudo quantitative trait nucleotide-based covariate structure of the model, and a negative control be used consisting of permutation testing and the identical resampling test as for the non-permuted phenotypes. PMID:28614352

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

PubMed

Law, Matthew H; Bishop, D Timothy; Lee, Jeffrey E; Brossard, Myriam; Martin, Nicholas G; Moses, Eric K; Song, Fengju; Barrett, Jennifer H; Kumar, Rajiv; Easton, Douglas F; Pharoah, Paul D P; Swerdlow, Anthony J; Kypreou, Katerina P; Taylor, John C; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A; Andresen, Per A; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M; Dębniak, Tadeusz; Duffy, David L; Elder, David E; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M; Goldstein, Alisa M; Gruis, Nelleke A; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A; Chen, Wei V; Landi, Maria Teresa; Lang, Julie; Lathrop, G Mark; Lubiński, Jan; Mackie, Rona M; Mann, Graham J; Molven, Anders; Montgomery, Grant W; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A; Radford-Smith, Graham L; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C; Craig, Jamie E; Schadendorf, Dirk; Simms, Lisa A; Burdon, Kathryn P; Nyholt, Dale R; Pooley, Karen A; Orr, Nick; Stratigos, Alexander J; Cust, Anne E; Ward, Sarah V; Hayward, Nicholas K; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M; Bishop, Julia A Newton; Demenais, Florence; Amos, Christopher I; MacGregor, Stuart; Iles, Mark M

2015-09-01

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma

PubMed Central

Law, Matthew H.; Bishop, D. Timothy; Martin, Nicholas G.; Moses, Eric K.; Song, Fengju; Barrett, Jennifer H.; Kumar, Rajiv; Easton, Douglas F.; Pharoah, Paul D. P.; Swerdlow, Anthony J.; Kypreou, Katerina P.; Taylor, John C.; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A.; Andresen, Per A.; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M.; Dębniak, Tadeusz; Duffy, David L.; Elder, David E.; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M.; Goldstein, Alisa M.; Gruis, Nelleke A.; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A.; Chen, Wei V.; Landi, Maria Teresa; Lang, Julie; Lathrop, G. Mark; Lubiński, Jan; Mackie, Rona M.; Mann, Graham J.; Molven, Anders; Montgomery, Grant W.; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A.; Radford-Smith, Graham L.; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C.; Craig, Jamie E.; Schadendorf, Dirk; Simms, Lisa A.; Burdon, Kathryn P.; Nyholt, Dale R.; Pooley, Karen A.; Orr, Nick; Stratigos, Alexander J.; Cust, Anne E.; Ward, Sarah V.; Hayward, Nicholas K.; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M.; Bishop, Julia A. Newton; MacGregor, Stuart; Iles, Mark M.

2015-01-01

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5×10–8), as did two previously-reported but un-replicated loci and all thirteen established loci. Novel SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes including one involved in telomere biology. PMID:26237428

Hydro-geomorphological characterization and classification of Chilean river networks using horizontal, vertical and climatological properties

NASA Astrophysics Data System (ADS)

Pereira, A. A.; Gironas, J. A.; Passalacqua, P.; Mejia, A.; Niemann, J. D.

2017-12-01

Previous work has shown that lithological, tectonic and climatic processes have a major influence in shaping the geomorphology of river networks. Accordingly, quantitative classification methods have been developed to identify and characterize network types (dendritic, parallel, pinnate, rectangular and trellis) based solely on the self-affinity of their planform properties, computed from available Digital Elevation Model (DEM) data. In contrast, this research aim is to include both horizontal and vertical properties to evaluate a quantitative classification method for river networks. We include vertical properties to consider the unique surficial conditions (e.g., large and steep height drops, volcanic activity, and complexity of stream networks) of the Andes Mountains. Furthermore, the goal of the research is also to explain the implications and possible relations between the hydro-geomorphological properties and climatic conditions. The classification method is applied to 42 basins in the southern Andes in Chile, ranging in size from 208 Km2 to 8,000 Km2. The planform metrics include the incremental drainage area, stream course irregularity and junction angles, while the vertical metrics include the hypsometric curve and the slope-area relationship. We introduce new network structures (Brush, Funnel and Low Sinuosity Rectangular), possibly unique to the Andes, that can be quantitatively differentiated from previous networks identified in other geographic regions. Then, this research evaluates the effect that excluding different Strahler order streams has on the horizontal properties and therefore in the classification. We found that climatic conditions are not only linked to horizontal parameters, but also to vertical ones, finding significant correlation between climatic variables (average near-surface temperature and rainfall) and vertical measures (parameters associated with the hypsometric curve and slope-area relation). The proposed classification shows differences among basins previously classified as the same type, which are not noticeable in their horizontal properties and helps reduce misclassifications within the old clusters. Additional hydro-geomorphological metrics are to be considered in the classification method to improve the effectiveness of it.

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

ERIC Educational Resources Information Center

Hart, Natalie

2013-01-01

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…

Application of targeted quantitative proteomics analysis in human cerebrospinal fluid using a liquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (LC MALDI TOF/TOF) platform.

PubMed

Pan, Sheng; Rush, John; Peskind, Elaine R; Galasko, Douglas; Chung, Kathryn; Quinn, Joseph; Jankovic, Joseph; Leverenz, James B; Zabetian, Cyrus; Pan, Catherine; Wang, Yan; Oh, Jung Hun; Gao, Jean; Zhang, Jianpeng; Montine, Thomas; Zhang, Jing

2008-02-01

Targeted quantitative proteomics by mass spectrometry aims to selectively detect one or a panel of peptides/proteins in a complex sample and is particularly appealing for novel biomarker verification/validation because it does not require specific antibodies. Here, we demonstrated the application of targeted quantitative proteomics in searching, identifying, and quantifying selected peptides in human cerebrospinal spinal fluid (CSF) using a matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF)-based platform. The approach involved two major components: the use of isotopic-labeled synthetic peptides as references for targeted identification and quantification and a highly selective mass spectrometric analysis based on the unique characteristics of the MALDI instrument. The platform provides high confidence for targeted peptide detection in a complex system and can potentially be developed into a high-throughput system. Using the liquid chromatography (LC) MALDI TOF/TOF platform and the complementary identification strategy, we were able to selectively identify and quantify a panel of targeted peptides in the whole proteome of CSF without prior depletion of abundant proteins. The effectiveness and robustness of the approach associated with different sample complexity, sample preparation strategies, as well as mass spectrometric quantification were evaluated. Other issues related to chromatography separation and the feasibility for high-throughput analysis were also discussed. Finally, we applied targeted quantitative proteomics to analyze a subset of previously identified candidate markers in CSF samples of patients with Parkinson's disease (PD) at different stages and Alzheimer's disease (AD) along with normal controls.

Social workers and workplace bullying: perceptions, responses and implications.

PubMed

Whitaker, Tracy

2012-01-01

This non-experimental, cross-sectional study examined social workers' perceptions of bullying work relationships and their ability to construct effective coping responses to perceived workplace bullying. Quantitative data were gathered through the use of a mailed questionnaire, and qualitative data resulted from semi-structured individual interviews. The quantitative sample consisted of 111 social workers from the metropolitan, Washington, DC area, who were employed in organizations. Two self-identified targets of bullying participated in the interviews. Nearly three of five social workers (58%) in the sample reported being the targets of demeaning, rude, and hostile workplace interactions more than once in the previous year. Targets were more likely to work in government agencies/military and mental health outpatient organizations (19% and 18% respectively). More than a third of targets (35%) held a direct service role (clinical/direct practice), whereas almost a third (29%) identified their role as administration or management. The findings from this study suggest that workplace bullying may be a problem for social workers and that the social work profession may need to develop tools and guidelines to help practitioners identify, confront and extinguish these behaviors.

Comparative mapping reveals quantitative trait loci that affect spawning time in coho salmon (Oncorhynchus kisutch)

PubMed Central

Araneda, Cristian; Díaz, Nelson F.; Gomez, Gilda; López, María Eugenia; Iturra, Patricia

2012-01-01

Spawning time in salmonids is a sex-limited quantitative trait that can be modified by selection. In rainbow trout (Oncorhynchus mykiss), various quantitative trait loci (QTL) that affect the expression of this trait have been discovered. In this study, we describe four microsatellite loci associated with two possible spawning time QTL regions in coho salmon (Oncorhynchus kisutch). The four loci were identified in females from two populations (early and late spawners) produced by divergent selection from the same base population. Three of the loci (OmyFGT34TUF, One2ASC and One19ASC) that were strongly associated with spawning time in coho salmon (p < 0.0002) were previously associated with QTL for the same trait in rainbow trout; a fourth loci (Oki10) with a suggestive association (p = 0.00035) mapped 10 cM from locus OmyFGT34TUF in rainbow trout. The changes in allelic frequency observed after three generations of selection were greater than expected because of genetic drift. This work shows that comparing information from closely-related species is a valid strategy for identifying QTLs for marker-assisted selection in species whose genomes are poorly characterized or lack a saturated genetic map. PMID:22888302

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

PubMed Central

2014-01-01

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

A quantitative analysis of naiad mollusks from the Prairie du Chien, Wisconsin dredge material site on the Mississippi River

USGS Publications Warehouse

Havlik, M.E.; Marking, L.L.

1980-01-01

The Prairie du Chien dredge material site contains about 100,000 cubic meters of material dredged from the East Channel of the Mississippi Riverin1976. Previous studies in that area suggested a rich molluscan fauna, but most studies were only qualitative or simply observations. Our study of this material was designed to determine the density and diversity of molluscan fauna, to assess changes in the fauna, to identify endemic species previously unreported, and to evaluate the status of the endangered Lampsilis higginsi. Ten cubic meters of dredge material were sieved to recover shells. Molluscan fauna at the site contained38 species of naiades and up to 1,737 identifiable valves per cubic meter. The endangered L. higginsi ranked18th In occurrence, accounted for only 0.52% of the identifiable shells, and averaged about three valves per cubic meter. From a total of 813 kg of naiades and gastropods, 6,339 naiad valves were identified. Five naiad species were collected at the site for the first time, and Eploblasma triquetra had not been reported previously in the Prairie du Chien area. Although the molluscan fauna has changed, the East Channel at Prairie du Chien is obviously suitable for L. higginsi.

Use of Genome Sequence Information for Meat Quality Trait QTL Mining for Causal Genes and Mutations on Pig Chromosome 17

PubMed Central

Hu, Zhi-Liang; Ramos, Antonio M.; Humphray, Sean J.; Rogers, Jane; Reecy, James M.; Rothschild, Max F.

2011-01-01

The newly available pig genome sequence has provided new information to fine map quantitative trait loci (QTL) in order to eventually identify causal variants. With targeted genomic sequencing efforts, we were able to obtain high quality BAC sequences that cover a region on pig chromosome 17 where a number of meat quality QTL have been previously discovered. Sequences from 70 BAC clones were assembled to form an 8-Mbp contig. Subsequently, we successfully mapped five previously identified QTL, three for meat color and two for lactate related traits, to the contig. With an additional 25 genetic markers that were identified by sequence comparison, we were able to carry out further linkage disequilibrium analysis to narrow down the genomic locations of these QTL, which allowed identification of the chromosomal regions that likely contain the causative variants. This research has provided one practical approach to combine genetic and molecular information for QTL mining. PMID:22303339

Quantitative perceptual differences among over-the-counter vaginal products using a standardized methodology: implications for microbicide development☆

PubMed Central

Mahan, Ellen D.; Morrow, Kathleen M.; Hayes, John E.

2015-01-01

Background Increasing prevalence of HIV infection among women worldwide has motivated the development of female-initiated prevention methods, including gel-based microbicides. User acceptability is vital for microbicide success; however, varying cultural vaginal practices indicate multiple formulations must be developed to appeal to different populations. Perceptual attributes of microbicides have been identified as primary drivers of acceptability; however, previous studies do not allow for direct comparison of these qualities between multiple formulations. Study Design Six vaginal products were analyzed ex vivo using descriptive analysis. Perceptual attributes of samples were identified by trained participants (n=10) and rated quantitatively using scales based on a panel-developed lexicon. Data were analyzed using two-way ANOVAs for each attribute; product differences were assessed via Tukey’s honestly significant difference test. Results Significant differences were found between products for multiple attributes. Patterns were also seen for attributes across intended product usage (i.e., contraceptive, moisturizer or lubricant). For example, Options© Gynol II® (Caldwell Consumer Health, LLC) was significantly stickier and grainier than other products. Conclusions Descriptive analysis, a quantitative approach that is based on consensus lexicon usage among participants, successfully quantified perceptual differences among vaginal products. Since perceptual attributes of products can be directly compared quantitatively, this study represents a novel approach that could be used to inform rational design of microbicides. PMID:21757061

Quantitative perceptual differences among over-the-counter vaginal products using a standardized methodology: implications for microbicide development.

PubMed

Mahan, Ellen D; Morrow, Kathleen M; Hayes, John E

2011-08-01

Increasing prevalence of HIV infection among women worldwide has motivated the development of female-initiated prevention methods, including gel-based microbicides. User acceptability is vital for microbicide success; however, varying cultural vaginal practices indicate multiple formulations must be developed to appeal to different populations. Perceptual attributes of microbicides have been identified as primary drivers of acceptability; however, previous studies do not allow for direct comparison of these qualities between multiple formulations. Six vaginal products were analyzed ex vivo using descriptive analysis. Perceptual attributes of samples were identified by trained participants (n=10) and rated quantitatively using scales based on a panel-developed lexicon. Data were analyzed using two-way ANOVAs for each attribute; product differences were assessed via Tukey's honestly significant difference test. Significant differences were found between products for multiple attributes. Patterns were also seen for attributes across intended product usage (i.e., contraceptive, moisturizer or lubricant). For example, Options© Gynol II® (Caldwell Consumer Health, LLC) was significantly stickier and grainier than other products. Descriptive analysis, a quantitative approach that is based on consensus lexicon usage among participants, successfully quantified perceptual differences among vaginal products. Since perceptual attributes of products can be directly compared quantitatively, this study represents a novel approach that could be used to inform rational design of microbicides. Copyright © 2011 Elsevier Inc. All rights reserved.

Correlations of Genotype with Climate Parameters Suggest Caenorhabditis elegans Niche Adaptations

PubMed Central

Evans, Kathryn S.; Zhao, Yuehui; Brady, Shannon C.; Long, Lijiang; McGrath, Patrick T.; Andersen, Erik C.

2016-01-01

Species inhabit a variety of environmental niches, and the adaptation to a particular niche is often controlled by genetic factors, including gene-by-environment interactions. The genes that vary in order to regulate the ability to colonize a niche are often difficult to identify, especially in the context of complex ecological systems and in experimentally uncontrolled natural environments. Quantitative genetic approaches provide an opportunity to investigate correlations between genetic factors and environmental parameters that might define a niche. Previously, we have shown how a collection of 208 whole-genome sequenced wild Caenorhabditis elegans can facilitate association mapping approaches. To correlate climate parameters with the variation found in this collection of wild strains, we used geographic data to exhaustively curate daily weather measurements in short-term (3 month), middle-term (one year), and long-term (three year) durations surrounding the date of strain isolation. These climate parameters were used as quantitative traits in association mapping approaches, where we identified 11 quantitative trait loci (QTL) for three climatic variables: elevation, relative humidity, and average temperature. We then narrowed the genomic interval of interest to identify gene candidates with variants potentially underlying phenotypic differences. Additionally, we performed two-strain competition assays at high and low temperatures to validate a QTL that could underlie adaptation to temperature and found suggestive evidence supporting that hypothesis. PMID:27866149

Detection of Low-Level Cardinium and Wolbachia Infections in Culicoides

PubMed Central

Mee, Peter T.; Weeks, Andrew R.; Walker, Peter J.; Hoffmann, Ary A.

2015-01-01

Bacterial endosymbionts have been identified as potentially useful biological control agents for a range of invertebrate vectors of disease. Previous studies of Culicoides (Diptera: Ceratopogonidae) species using conventional PCR assays have provided evidence of Wolbachia (1/33) and Cardinium (8/33) infections. Here, we screened 20 species of Culicoides for Wolbachia and Cardinium, utilizing a combination of conventional PCR and more sensitive quantitative PCR (qPCR) assays. Low levels of Cardinium DNA were detected in females of all but one of the Culicoides species screened, and low levels of Wolbachia were detected in females of 9 of the 20 Culicoides species. Sequence analysis based on partial 16S rRNA gene and gyrB sequences identified “Candidatus Cardinium hertigii” from group C, which has previously been identified in Culicoides from Japan, Israel, and the United Kingdom. Wolbachia strains detected in this study showed 98 to 99% sequence identity to Wolbachia previously detected from Culicoides based on the 16S rRNA gene, whereas a strain with a novel wsp sequence was identified in Culicoides narrabeenensis. Cardinium isolates grouped to geographical regions independent of the host Culicoides species, suggesting possible geographical barriers to Cardinium movement. Screening also identified Asaia bacteria in Culicoides. These findings point to a diversity of low-level endosymbiont infections in Culicoides, providing candidates for further characterization and highlighting the widespread occurrence of these endosymbionts in this insect group. PMID:26150447

A genome-wide association study of seed protein and oil content in soybean

PubMed Central

2014-01-01

Background Association analysis is an alternative to conventional family-based methods to detect the location of gene(s) or quantitative trait loci (QTL) and provides relatively high resolution in terms of defining the genome position of a gene or QTL. Seed protein and oil concentration are quantitative traits which are determined by the interaction among many genes with small to moderate genetic effects and their interaction with the environment. In this study, a genome-wide association study (GWAS) was performed to identify quantitative trait loci (QTL) controlling seed protein and oil concentration in 298 soybean germplasm accessions exhibiting a wide range of seed protein and oil content. Results A total of 55,159 single nucleotide polymorphisms (SNPs) were genotyped using various methods including Illumina Infinium and GoldenGate assays and 31,954 markers with minor allele frequency >0.10 were used to estimate linkage disequilibrium (LD) in heterochromatic and euchromatic regions. In euchromatic regions, the mean LD (r 2 ) rapidly declined to 0.2 within 360 Kbp, whereas the mean LD declined to 0.2 at 9,600 Kbp in heterochromatic regions. The GWAS results identified 40 SNPs in 17 different genomic regions significantly associated with seed protein. Of these, the five SNPs with the highest associations and seven adjacent SNPs were located in the 27.6-30.0 Mbp region of Gm20. A major seed protein QTL has been previously mapped to the same location and potential candidate genes have recently been identified in this region. The GWAS results also detected 25 SNPs in 13 different genomic regions associated with seed oil. Of these markers, seven SNPs had a significant association with both protein and oil. Conclusions This research indicated that GWAS not only identified most of the previously reported QTL controlling seed protein and oil, but also resulted in narrower genomic regions than the regions reported as containing these QTL. The narrower GWAS-defined genome regions will allow more precise marker-assisted allele selection and will expedite positional cloning of the causal gene(s). PMID:24382143

A genome-wide association study of seed protein and oil content in soybean.

PubMed

Hwang, Eun-Young; Song, Qijian; Jia, Gaofeng; Specht, James E; Hyten, David L; Costa, Jose; Cregan, Perry B

2014-01-02

Association analysis is an alternative to conventional family-based methods to detect the location of gene(s) or quantitative trait loci (QTL) and provides relatively high resolution in terms of defining the genome position of a gene or QTL. Seed protein and oil concentration are quantitative traits which are determined by the interaction among many genes with small to moderate genetic effects and their interaction with the environment. In this study, a genome-wide association study (GWAS) was performed to identify quantitative trait loci (QTL) controlling seed protein and oil concentration in 298 soybean germplasm accessions exhibiting a wide range of seed protein and oil content. A total of 55,159 single nucleotide polymorphisms (SNPs) were genotyped using various methods including Illumina Infinium and GoldenGate assays and 31,954 markers with minor allele frequency >0.10 were used to estimate linkage disequilibrium (LD) in heterochromatic and euchromatic regions. In euchromatic regions, the mean LD (r2) rapidly declined to 0.2 within 360 Kbp, whereas the mean LD declined to 0.2 at 9,600 Kbp in heterochromatic regions. The GWAS results identified 40 SNPs in 17 different genomic regions significantly associated with seed protein. Of these, the five SNPs with the highest associations and seven adjacent SNPs were located in the 27.6-30.0 Mbp region of Gm20. A major seed protein QTL has been previously mapped to the same location and potential candidate genes have recently been identified in this region. The GWAS results also detected 25 SNPs in 13 different genomic regions associated with seed oil. Of these markers, seven SNPs had a significant association with both protein and oil. This research indicated that GWAS not only identified most of the previously reported QTL controlling seed protein and oil, but also resulted in narrower genomic regions than the regions reported as containing these QTL. The narrower GWAS-defined genome regions will allow more precise marker-assisted allele selection and will expedite positional cloning of the causal gene(s).

A General Method for Targeted Quantitative Cross-Linking Mass Spectrometry.

PubMed

Chavez, Juan D; Eng, Jimmy K; Schweppe, Devin K; Cilia, Michelle; Rivera, Keith; Zhong, Xuefei; Wu, Xia; Allen, Terrence; Khurgel, Moshe; Kumar, Akhilesh; Lampropoulos, Athanasios; Larsson, Mårten; Maity, Shuvadeep; Morozov, Yaroslav; Pathmasiri, Wimal; Perez-Neut, Mathew; Pineyro-Ruiz, Coriness; Polina, Elizabeth; Post, Stephanie; Rider, Mark; Tokmina-Roszyk, Dorota; Tyson, Katherine; Vieira Parrine Sant'Ana, Debora; Bruce, James E

2016-01-01

Chemical cross-linking mass spectrometry (XL-MS) provides protein structural information by identifying covalently linked proximal amino acid residues on protein surfaces. The information gained by this technique is complementary to other structural biology methods such as x-ray crystallography, NMR and cryo-electron microscopy[1]. The extension of traditional quantitative proteomics methods with chemical cross-linking can provide information on the structural dynamics of protein structures and protein complexes. The identification and quantitation of cross-linked peptides remains challenging for the general community, requiring specialized expertise ultimately limiting more widespread adoption of the technique. We describe a general method for targeted quantitative mass spectrometric analysis of cross-linked peptide pairs. We report the adaptation of the widely used, open source software package Skyline, for the analysis of quantitative XL-MS data as a means for data analysis and sharing of methods. We demonstrate the utility and robustness of the method with a cross-laboratory study and present data that is supported by and validates previously published data on quantified cross-linked peptide pairs. This advance provides an easy to use resource so that any lab with access to a LC-MS system capable of performing targeted quantitative analysis can quickly and accurately measure dynamic changes in protein structure and protein interactions.

Development of an SRM method for absolute quantitation of MYDGF/C19orf10 protein.

PubMed

Dwivedi, Ravi C; Krokhin, Oleg V; El-Gabalawy, Hani S; Wilkins, John A

2016-06-01

To develop a MS-based selected reaction monitoring (SRM) assay for quantitation of myeloid-derived growth factor (MYDGF) formerly chromosome 19 open reading frame (C19orf10). Candidate reporter peptides were identified in digests of recombinant MYDGF. Isotopically labeled forms of these reporter peptides were employed as internal standards for assay development. Two reference peptides were selected SYLYFQTFFK and GAEIEYAMAYSK with respective LOQ of 42 and 380 attomole per injection. Application of the assay to human serum and synovial fluid determined that the assay sensitivity was reduced and quantitation was not achievable. However, the partial depletion of albumin and immunoglobulin from synovial fluids provided estimates of 300-650 femtomoles per injection (0.7-1.6 nanomolar (nM) fluid concentrations) in three of the six samples analyzed. A validated sensitive assay for the quantitation of MYDGF in biological fluids was developed. However, the endogenous levels of MYDGF in such fluids are at or below the current levels of quantitation. The levels of MYDGF are lower than those previously reported using an ELISA. The current results suggest that additional steps may be required to remove high abundance proteins or to enrich MYDGF for SRM-based quantitation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Management of natural resources through automatic cartographic inventory. [Spanish Catalonia and Landes of Gascony (France)

NASA Technical Reports Server (NTRS)

Rey, P. A.; Gourinard, Y.; Cambou, F. (Principal Investigator); Guyader, J. C.; Gouaux, P.; Letoan, T.; Monchant, M.; Donville, B.; Loubet, D.

1973-01-01

The author has identified the following significant results. Significant results of the ARNICA program (February - December 1973) were: (1) The quantitative processing of ERTS-1 data was developed along two lines: the study of geological structures and lineaments of Spanish Catalonia, and the phytogeographical study of the forest region of the Landes of Gascony (France). In both cases it is shown that the ERTS-1 imagery can be used in establishing zonings of equal quantitative interpretation value. (2) In keeping with the operational transfer program proposed in previous reports between exploration of the imagery and charting of the object, a precise data processing method was developed, concerning more particularly the selection of digital equidensity samples computer display and rigorous referencing.

T2* Mapping Provides Information That Is Statistically Comparable to an Arthroscopic Evaluation of Acetabular Cartilage.

PubMed

Morgan, Patrick; Nissi, Mikko J; Hughes, John; Mortazavi, Shabnam; Ellerman, Jutta

2017-07-01

Objectives The purpose of this study was to validate T2* mapping as an objective, noninvasive method for the prediction of acetabular cartilage damage. Methods This is the second step in the validation of T2*. In a previous study, we established a quantitative predictive model for identifying and grading acetabular cartilage damage. In this study, the model was applied to a second cohort of 27 consecutive hips to validate the model. A clinical 3.0-T imaging protocol with T2* mapping was used. Acetabular regions of interest (ROI) were identified on magnetic resonance and graded using the previously established model. Each ROI was then graded in a blinded fashion by arthroscopy. Accurate surgical location of ROIs was facilitated with a 2-dimensional map projection of the acetabulum. A total of 459 ROIs were studied. Results When T2* mapping and arthroscopic assessment were compared, 82% of ROIs were within 1 Beck group (of a total 6 possible) and 32% of ROIs were classified identically. Disease prediction based on receiver operating characteristic curve analysis demonstrated a sensitivity of 0.713 and a specificity of 0.804. Model stability evaluation required no significant changes to the predictive model produced in the initial study. Conclusions These results validate that T2* mapping provides statistically comparable information regarding acetabular cartilage when compared to arthroscopy. In contrast to arthroscopy, T2* mapping is quantitative, noninvasive, and can be used in follow-up. Unlike research quantitative magnetic resonance protocols, T2* takes little time and does not require a contrast agent. This may facilitate its use in the clinical sphere.

The application of quantitative methods for identifying and exploring the presence of bias in systematic reviews: PDE-5 inhibitors for erectile dysfunction.

PubMed

Bekkering, G E; Abou-Setta, A M; Kleijnen, J

2008-01-01

A systematic review of PDE-5 inhibitors for erectile dysfunction was performed to evaluate the utility of quantitative methods for identifying and exploring the influence of bias and study quality on pooled outcomes from meta-analyses. We included 123 randomized controlled trials (RCTs). Methodological quality was poorly reported. All three drugs appeared highly effective. Indirect adjusted analyses showed no differences between the three drugs. Funnel plots and statistical tests showed no evidence of small-study effects for sildenafil whereas there was evidence of such bias for tadalafil and vardenafil. Adjustment for missing studies using trim and fill techniques did not alter the pooled estimates substantially. The exclusion of previous sildenafil nonresponders was associated with larger treatment effects for tadalafil. This investigation was hampered by poor reporting of methodological quality, a low number of studies, heterogeneity and large effect sizes. Despite such limitations, a comprehensive assessment of biases should be a routine in systematic reviews.

Pair correlation functions for identifying spatial correlation in discrete domains

NASA Astrophysics Data System (ADS)

Gavagnin, Enrico; Owen, Jennifer P.; Yates, Christian A.

2018-06-01

Identifying and quantifying spatial correlation are important aspects of studying the collective behavior of multiagent systems. Pair correlation functions (PCFs) are powerful statistical tools that can provide qualitative and quantitative information about correlation between pairs of agents. Despite the numerous PCFs defined for off-lattice domains, only a few recent studies have considered a PCF for discrete domains. Our work extends the study of spatial correlation in discrete domains by defining a new set of PCFs using two natural and intuitive definitions of distance for a square lattice: the taxicab and uniform metric. We show how these PCFs improve upon previous attempts and compare between the quantitative data acquired. We also extend our definitions of the PCF to other types of regular tessellation that have not been studied before, including hexagonal, triangular, and cuboidal. Finally, we provide a comprehensive PCF for any tessellation and metric, allowing investigation of spatial correlation in irregular lattices for which recognizing correlation is less intuitive.

Statistical thermodynamics unveils the dissolution mechanism of cellobiose.

PubMed

Nicol, Thomas W J; Isobe, Noriyuki; Clark, James H; Shimizu, Seishi

2017-08-30

In the study of the cellulose dissolution mechanism opinion is still divided. Here, the solution interaction components of the most prominent hypotheses for the driving force of cellulose dissolution were evaluated quantitatively. Combining a rigorous statistical thermodynamic theory and cellobiose solubility data in the presence of chloride salts, whose cations progress in the Hofmeister series (KCl, NaCl, LiCl and ZnCl 2 ), we have shown that cellobiose solubilization is driven by the preferential accumulation of salts around the solutes which is stronger than cellobiose hydration. Yet contrary to the classical chaotropy hypothesis, increasing salt concentration leads to cellobiose dehydration in the presence of the strongest solubilizer ZnCl 2 . However, thanks to cellobiose dehydration, cellobiose-salt interaction still remains preferential despite weakening salt accumulation. Based on such insights, the previous hypotheses based on hydrophobicity and polymer charging have also been evaluated quantitatively. Thus, our present study successfully paved a way towards identifying the basic driving forces for cellulose solubilization in a quantitative manner for the first time. When combined with unit additivity methods this quantitative information could lead to a full understanding of cellulose solubility.

Protein isoform-specific validation defines multiple chloride intracellular channel and tropomyosin isoforms as serological biomarkers of ovarian cancer.

PubMed

Tang, Hsin-Yao; Beer, Lynn A; Tanyi, Janos L; Zhang, Rugang; Liu, Qin; Speicher, David W

2013-08-26

New serological biomarkers for early detection and clinical management of ovarian cancer are urgently needed, and many candidates have been reported. A major challenge frequently encountered when validating candidates in patients is establishing quantitative assays that distinguish between highly homologous proteins. The current study tested whether multiple members of two recently discovered ovarian cancer biomarker protein families, chloride intracellular channel (CLIC) proteins and tropomyosins (TPM), were detectable in ovarian cancer patient sera. A multiplexed, label-free multiple reaction monitoring (MRM) assay was established to target peptides specific to all detected CLIC and TPM family members, and their serum levels were quantitated for ovarian cancer patients and non-cancer controls. In addition to CLIC1 and TPM1, which were the proteins initially discovered in a xenograft mouse model, CLIC4, TPM2, TPM3, and TPM4 were present in ovarian cancer patient sera at significantly elevated levels compared with controls. Some of the additional biomarkers identified in this homolog-centric verification and validation approach may be superior to the previously identified biomarkers at discriminating between ovarian cancer and non-cancer patients. This demonstrates the importance of considering all potential protein homologs and using quantitative assays for cancer biomarker validation with well-defined isoform specificity. This manuscript addresses the importance of distinguishing between protein homologs and isoforms when identifying and validating cancer biomarkers in plasma or serum. Specifically, it describes the use of targeted in-depth LC-MS/MS analysis to determine the members of two protein families, chloride intracellular channel (CLIC) and tropomyosin (TPM) proteins that are detectable in sera of ovarian cancer patients. It then establishes a multiplexed isoform- and homology-specific MRM assay to quantify all observed gene products in these two protein families as well as many of the closely related tropomyosin isoforms. Using this assay, levels of all detected CLICs and TPMs were quantified in ovarian cancer patient and control subject sera. These results demonstrate that in addition to the previously known CLIC1, multiple tropomyosins and CLIC4 are promising new ovarian cancer biomarkers. Based on these initial validation studies, these new ovarian cancer biomarkers appear to be superior to most previously known ovarian cancer biomarkers. Copyright © 2013 Elsevier B.V. All rights reserved.

Fine-mapping diabetes-related traits, including insulin resistance, in heterogeneous stock rats

PubMed Central

Holl, Katie L.; Oreper, Daniel; Xie, Yuying; Tsaih, Shirng-Wern; Valdar, William

2012-01-01

Type 2 diabetes (T2D) is a disease of relative insulin deficiency resulting from both insulin resistance and beta cell failure. We have previously used heterogeneous stock (HS) rats to fine-map a locus for glucose tolerance. We show here that glucose intolerance in the founder strains of the HS colony is mediated by different mechanisms: insulin resistance in WKY and an insulin secretion defect in ACI, and we demonstrate a high degree of variability for measures of insulin resistance and insulin secretion in HS rats. As such, our goal was to use HS rats to fine-map several diabetes-related traits within a region on rat chromosome 1. We measured blood glucose and plasma insulin levels after a glucose tolerance test in 782 male HS rats. Using 97 SSLP markers, we genotyped a 68 Mb region on rat chromosome 1 previously implicated in glucose and insulin regulation. We used linkage disequilibrium mapping by mixed model regression with inferred descent to identify a region from 198.85 to 205.9 that contains one or more quantitative trait loci (QTL) for fasting insulin and a measure of insulin resistance, the quantitative insulin sensitivity check index. This region also encompasses loci identified for fasting glucose and Insulin_AUC (area under the curve). A separate <3 Mb QTL was identified for body weight. Using a novel penalized regression method we then estimated effects of alternative haplotype pairings under each locus. These studies highlight the utility of HS rats for fine-mapping genetic loci involved in the underlying causes of T2D. PMID:22947656

Quantitative fetal fibronectin and cervical length to predict preterm birth in asymptomatic women with previous cervical surgery.

PubMed

Vandermolen, Brooke I; Hezelgrave, Natasha L; Smout, Elizabeth M; Abbott, Danielle S; Seed, Paul T; Shennan, Andrew H

2016-10-01

Quantitative fetal fibronectin testing has demonstrated accuracy for prediction of spontaneous preterm birth in asymptomatic women with a history of preterm birth. Predictive accuracy in women with previous cervical surgery (a potentially different risk mechanism) is not known. We sought to compare the predictive accuracy of cervicovaginal fluid quantitative fetal fibronectin and cervical length testing in asymptomatic women with previous cervical surgery to that in women with 1 previous preterm birth. We conducted a prospective blinded secondary analysis of a larger observational study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women measured with a Hologic 10Q system (Hologic, Marlborough, MA). Prediction of spontaneous preterm birth (<30, <34, and <37 weeks) with cervicovaginal fluid quantitative fetal fibronectin concentration in primiparous women who had undergone at least 1 invasive cervical procedure (n = 473) was compared with prediction in women who had previous spontaneous preterm birth, preterm prelabor rupture of membranes, or late miscarriage (n = 821). Relationship with cervical length was explored. The rate of spontaneous preterm birth <34 weeks in the cervical surgery group was 3% compared with 9% in previous spontaneous preterm birth group. Receiver operating characteristic curves comparing quantitative fetal fibronectin for prediction at all 3 gestational end points were comparable between the cervical surgery and previous spontaneous preterm birth groups (34 weeks: area under the curve, 0.78 [95% confidence interval 0.64-0.93] vs 0.71 [95% confidence interval 0.64-0.78]; P = .39). Prediction of spontaneous preterm birth using cervical length compared with quantitative fetal fibronectin for prediction of preterm birth <34 weeks of gestation offered similar prediction (area under the curve, 0.88 [95% confidence interval 0.79-0.96] vs 0.77 [95% confidence interval 0.62-0.92], P = .12 in the cervical surgery group; and 0.77 [95% confidence interval 0.70-0.84] vs 0.74 [95% confidence interval 0.67-0.81], P = .32 in the previous spontaneous preterm birth group). Prediction of spontaneous preterm birth using cervicovaginal fluid quantitative fetal fibronectin in asymptomatic women with cervical surgery is valid, and has comparative accuracy to that in women with a history of spontaneous preterm birth. Copyright © 2016 Elsevier Inc. All rights reserved.

High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial Sulfate Reduction.

PubMed

Carlson, Hans K; Mullan, Mark R; Mosqueda, Lorraine A; Chen, Steven; Arkin, Michelle R; Coates, John D

2017-06-20

The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive, and corrosive. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to identify potent and selective inhibitors of SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Zinc pyrithione is the most potent inhibitor of sulfidogenesis that we identified, and is several orders of magnitude more potent than commonly used industrial biocides. Both zinc and copper pyrithione are also moderately selective against SRM. The high-throughput (HT) approach we present can be readily adapted to target SRM in diverse environments and similar strategies could be used to quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant to efforts to engineer environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space.

Protein isoform-specific validation defines multiple chloride intracellular channel and tropomyosin isoforms as serological biomarkers of ovarian cancer

PubMed Central

Tang, Hsin-Yao; Beer, Lynn A.; Tanyi, Janos L.; Zhang, Rugang; Liu, Qin; Speicher, David W.

2013-01-01

New serological biomarkers for early detection and clinical management of ovarian cancer are urgently needed, and many candidates have been reported. A major challenge frequently encountered when validating candidates in patients is establishing quantitative assays that distinguish between highly homologous proteins. The current study tested whether multiple members of two recently discovered ovarian cancer biomarker protein families, chloride intracellular channel (CLIC) proteins and tropomyosins (TPM), were detectable in ovarian cancer patient sera. A multiplexed, label-free multiple reaction monitoring (MRM) assay was established to target peptides specific to all detected CLIC and TPM family members, and their serum levels were quantitated for ovarian cancer patients and non-cancer controls. In addition to CLIC1 and TPM1, which were the proteins initially discovered in a xenograft mouse model, CLIC4, TPM2, TPM3, and TPM4 were present in ovarian cancer patient sera at significantly elevated levels compared with controls. Some of the additional biomarkers identified in this homolog-centric verification and validation approach may be superior to the previously identified biomarkers at discriminating between ovarian cancer and non-cancer patients. This demonstrates the importance of considering all potential protein homologs and using quantitative assays for cancer biomarker validation with well-defined isoform specificity. PMID:23792823

Direct Standard-Free Quantitation of Tamiflu® and Other Pharmaceutical Tablets using Clustering Agents with Electrospray Ionization Mass Spectrometry

PubMed Central

Flick, Tawnya G.; Leib, Ryan D.; Williams, Evan R.

2010-01-01

Accurate and rapid quantitation is advantageous to identify counterfeit and substandard pharmaceutical drugs. A standard-free electrospray ionization mass spectrometry method is used to directly determine the dosage in the prescription and over-the-counter drugs, Tamiflu®, Sudafed®, and Dramamine®. A tablet of each drug was dissolved in aqueous solution, filtered, and introduced into solutions containing a known concentration of either L-tryptophan, L-phenylalanine or prednisone as clustering agents. The active ingredient(s) incorporates statistically into large clusters of the clustering agent where effects of differential ionization/detection are substantially reduced. From the abundances of large clusters, the dosages of the active ingredients in each of the tablets were determined to typically better than 20% accuracy even when the ionization/detection efficiency of the individual components differed by over 100×. Although this unorthodox method for quantitation is not as accurate as using conventional standards, it has the advantages that it is fast, it can be applied to mixtures where the identities of the analytes are unknown, and it can be used when suitable standards may not be readily available, such as schedule I or II controlled substances or new designer drugs that have not previously been identified. PMID:20092258

Technique for Determination of Rational Boundaries in Combining Construction and Installation Processes Based on Quantitative Estimation of Technological Connections

NASA Astrophysics Data System (ADS)

Gusev, E. V.; Mukhametzyanov, Z. R.; Razyapov, R. V.

2017-11-01

The problems of the existing methods for the determination of combining and technologically interlinked construction processes and activities are considered under the modern construction conditions of various facilities. The necessity to identify common parameters that characterize the interaction nature of all the technology-related construction and installation processes and activities is shown. The research of the technologies of construction and installation processes for buildings and structures with the goal of determining a common parameter for evaluating the relationship between technologically interconnected processes and construction works are conducted. The result of this research was to identify the quantitative evaluation of interaction construction and installation processes and activities in a minimum technologically necessary volume of the previous process allowing one to plan and organize the execution of a subsequent technologically interconnected process. The quantitative evaluation is used as the basis for the calculation of the optimum range of the combination of processes and activities. The calculation method is based on the use of the graph theory. The authors applied a generic characterization parameter to reveal the technological links between construction and installation processes, and the proposed technique has adaptive properties which are key for wide use in organizational decisions forming. The article provides a written practical significance of the developed technique.

Common and distinct neural correlates of personal and vicarious reward: A quantitative meta-analysis

PubMed Central

Morelli, Sylvia A.; Sacchet, Matthew D.; Zaki, Jamil

2015-01-01

Individuals experience reward not only when directly receiving positive outcomes (e.g., food or money), but also when observing others receive such outcomes. This latter phenomenon, known as vicarious reward, is a perennial topic of interest among psychologists and economists. More recently, neuroscientists have begun exploring the neuroanatomy underlying vicarious reward. Here we present a quantitative whole-brain meta-analysis of this emerging literature. We identified 25 functional neuroimaging studies that included contrasts between vicarious reward and a neutral control, and subjected these contrasts to an activation likelihood estimate (ALE) meta-analysis. This analysis revealed a consistent pattern of activation across studies, spanning structures typically associated with the computation of value (especially ventromedial prefrontal cortex) and mentalizing (including dorsomedial prefrontal cortex and superior temporal sulcus). We further quantitatively compared this activation pattern to activation foci from a previous meta-analysis of personal reward. Conjunction analyses yielded overlapping VMPFC activity in response to personal and vicarious reward. Contrast analyses identified preferential engagement of the nucleus accumbens in response to personal as compared to vicarious reward, and in mentalizing-related structures in response to vicarious as compared to personal reward. These data shed light on the common and unique components of the reward that individuals experience directly and through their social connections. PMID:25554428

Quantitative interaction screen of telomeric repeat-containing RNA reveals novel TERRA regulators

PubMed Central

Scheibe, Marion; Arnoult, Nausica; Kappei, Dennis; Buchholz, Frank; Decottignies, Anabelle; Butter, Falk; Mann, Matthias

2013-01-01

Telomeres are actively transcribed into telomeric repeat-containing RNA (TERRA), which has been implicated in the regulation of telomere length and heterochromatin formation. Here, we applied quantitative mass spectrometry (MS)–based proteomics to obtain a high-confidence interactome of TERRA. Using SILAC-labeled nuclear cell lysates in an RNA pull-down experiment and two different salt conditions, we distinguished 115 proteins binding specifically to TERRA out of a large set of background binders. While TERRA binders identified in two previous studies showed little overlap, using quantitative mass spectrometry we obtained many candidates reported in these two studies. To test whether novel candidates found here are involved in TERRA regulation, we performed an esiRNA-based interference analysis for 15 of them. Knockdown of 10 genes encoding candidate proteins significantly affected total cellular levels of TERRA, and RNAi of five candidates perturbed TERRA recruitment to telomeres. Notably, depletion of SRRT/ARS2, involved in miRNA processing, up-regulated both total and telomere-bound TERRA. Conversely, knockdown of MORF4L2, a component of the NuA4 histone acetyltransferase complex, reduced TERRA levels both globally and for telomere-bound TERRA. We thus identified new proteins involved in the homeostasis and telomeric abundance of TERRA, extending our knowledge of TERRA regulation. PMID:23921659

Confirmatory and quantitative analysis of beta-lactam antibiotics in bovine kidney tissue by dispersive solid-phase extraction and liquid chromatography-tandem mass spectrometry.

PubMed

Fagerquist, Clifton K; Lightfield, Alan R; Lehotay, Steven J

2005-03-01

A simple, rapid, rugged, sensitive, and specific method for the confirmation and quantitation of 10 beta-lactam antibiotics in fortified and incurred bovine kidney tissue has been developed. The method uses a simple solvent extraction, dispersive solid-phase extraction (dispersive-SPE) cleanup, and liquid chromatography-tandem mass spectrometry (LC/MS/MS) for confirmation and quantitation. Dispersive-SPE greatly simplifies and accelerates sample cleanup and improves overall recoveries compared with conventional SPE cleanup. The beta-lactam antibiotics tested were as follows: deacetylcephapirin (an antimicrobial metabolite of cephapirin), amoxicillin, desfuroylceftiofur cysteine disulfide (DCCD, an antimicrobial metabolite of ceftiofur), ampicillin, cefazolin, penicillin G, oxacillin, cloxacillin, naficillin, and dicloxacillin. Average recoveries of fortified samples were 70% or better for all beta-lactams except DCCD, which had an average recovery of 58%. The LC/MS/MS method was able to demonstrate quantitative recoveries at established tolerance levels and provide confirmatory data for unambiguous analyte identification. The method was also tested on 30 incurred bovine kidney samples obtained from the USDA Food Safety and Inspection Service, which had previously tested the samples using the approved semiquantitative microbial assay. The results from the quantitative LC/MS/MS analysis were in general agreement with the microbial assay for 23 samples although the LC/MS/MS method was superior in that it could specifically identify which beta-lactam was present and quantitate its concentration, whereas the microbial assay could only identify the type of beta-lactam present and report a concentration with respect to the microbial inhibition of a penicillin G standard. In addition, for 6 of the 23 samples, LC/MS/MS analysis detected a penicillin and a cephalosporin beta-lactam, whereas the microbial assay detected only a penicillin beta-lactam. For samples that do not fall into the "general agreement" category, the most serious discrepancy involves two samples where the LC/MS/MS method detected a violative level of a cephalosporin beta-lactam (deacetylcephapirin) in the first sample and a possibly violative level of desfuroylceftiofur in the second, whereas the microbial assay identified the two samples as having only violative levels of a penicillin beta-lactam.

Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.

PubMed

Sabatti, Chiara; Service, Susan K; Hartikainen, Anna-Liisa; Pouta, Anneli; Ripatti, Samuli; Brodsky, Jae; Jones, Chris G; Zaitlen, Noah A; Varilo, Teppo; Kaakinen, Marika; Sovio, Ulla; Ruokonen, Aimo; Laitinen, Jaana; Jakkula, Eveliina; Coin, Lachlan; Hoggart, Clive; Collins, Andrew; Turunen, Hannu; Gabriel, Stacey; Elliot, Paul; McCarthy, Mark I; Daly, Mark J; Järvelin, Marjo-Riitta; Freimer, Nelson B; Peltonen, Leena

2009-01-01

Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

Variation in seed dormancy quantitative trait loci in Arabidopsis thaliana originating from one site.

PubMed

Silady, Rebecca A; Effgen, Sigi; Koornneef, Maarten; Reymond, Matthieu

2011-01-01

A Quantitative Trait Locus (QTL) analysis was performed using two novel Recombinant Inbred Line (RIL) populations, derived from the progeny between two Arabidopsis thaliana genotypes collected at the same site in Kyoto (Japan) crossed with the reference laboratory strain Landsberg erecta (Ler). We used these two RIL populations to determine the genetic basis of seed dormancy and flowering time, which are assumed to be the main traits controlling life history variation in Arabidopsis. The analysis revealed quantitative variation for seed dormancy that is associated with allelic variation at the seed dormancy QTL DOG1 (for Delay Of Germination 1) in one population and at DOG6 in both. These DOG QTL have been previously identified using mapping populations derived from accessions collected at different sites around the world. Genetic variation within a population may enhance its ability to respond accurately to variation within and between seasons. In contrast, variation for flowering time, which also segregated within each mapping population, is mainly governed by the same QTL.

Criteria for quantitative and qualitative data integration: mixed-methods research methodology.

PubMed

Lee, Seonah; Smith, Carrol A M

2012-05-01

Many studies have emphasized the need and importance of a mixed-methods approach for evaluation of clinical information systems. However, those studies had no criteria to guide integration of multiple data sets. Integrating different data sets serves to actualize the paradigm that a mixed-methods approach argues; thus, we require criteria that provide the right direction to integrate quantitative and qualitative data. The first author used a set of criteria organized from a literature search for integration of multiple data sets from mixed-methods research. The purpose of this article was to reorganize the identified criteria. Through critical appraisal of the reasons for designing mixed-methods research, three criteria resulted: validation, complementarity, and discrepancy. In applying the criteria to empirical data of a previous mixed methods study, integration of quantitative and qualitative data was achieved in a systematic manner. It helped us obtain a better organized understanding of the results. The criteria of this article offer the potential to produce insightful analyses of mixed-methods evaluations of health information systems.

Identification of hydrologic indicators related to fish diversity and abundance: A data mining approach for fish community analysis

NASA Astrophysics Data System (ADS)

Yang, Yi-Chen E.; Cai, Ximing; Herricks, Edwin E.

2008-04-01

This paper develops a new approach to identify hydrologic indicators related to fish community and generate a quantitative function between an ecological target index and the identified hydrologic indicators. The approach is based on genetic programming (GP), a data mining method. Using the Shannon Index (a fish community diversity index) or the number of individuals (total abundance) of a fish community, as an ecological target, the GP identified the most ecologically relevant hydrologic indicators (ERHIs) from 32 indicators of hydrologic alteration, for the case study site, the upper Illinois River. Robustness analysis showed that different GP runs found a similar set of ERHIs; each of the identified ERHI from different GP runs had a consistent relationship with the target index. By comparing the GP results with those from principal component analysis and autecology matrix, the three approaches identified a small number (six) of common ERHIs. Particularly, the timing of low flow (Dmin) seems to be more relevant to the diversity of the fish community, while the magnitude of the low flow (Qb) is more relevant to the total fish abundance; large rising rates result in a significant improvement of fish diversity, which is counterintuitive and against previous findings. The quantitative function developed by GP was further used to construct an indicator impact matrix (IIM), which was demonstrated as a potentially useful tool for streamflow restoration design.

Genome-wide study of the adaptation of Saccharomyces cerevisiae to the early stages of wine fermentation.

PubMed

Novo, Maite; Mangado, Ana; Quirós, Manuel; Morales, Pilar; Salvadó, Zoel; Gonzalez, Ramon

2013-01-01

This work was designed to identify yeast cellular functions specifically affected by the stress factors predominating during the early stages of wine fermentation, and genes required for optimal growth under these conditions. The main experimental method was quantitative fitness analysis by means of competition experiments in continuous culture of whole genome barcoded yeast knockout collections. This methodology allowed the identification of haploinsufficient genes, and homozygous deletions resulting in growth impairment in synthetic must. However, genes identified as haploproficient, or homozygous deletions resulting in fitness advantage, were of little predictive power concerning optimal growth in this medium. The relevance of these functions for enological performance of yeast was assessed in batch cultures with single strains. Previous studies addressing yeast adaptation to winemaking conditions by quantitative fitness analysis were not specifically focused on the proliferative stages. In some instances our results highlight the importance of genes not previously linked to winemaking. In other cases they are complementary to those reported in previous studies concerning, for example, the relevance of some genes involved in vacuolar, peroxisomal, or ribosomal functions. Our results indicate that adaptation to the quickly changing growth conditions during grape must fermentation require the function of different gene sets in different moments of the process. Transport processes and glucose signaling seem to be negatively affected by the stress factors encountered by yeast in synthetic must. Vacuolar activity is important for continued growth during the transition to stationary phase. Finally, reduced biogenesis of peroxisomes also seems to be advantageous. However, in contrast to what was described for later stages, reduced protein synthesis is not advantageous for the early (proliferative) stages of the fermentation process. Finally, we found adenine and lysine to be in short supply for yeast growth in some natural grape musts.

Whole genome re-sequencing identifies a mutation in an ABC transporter (mdr2) in a Plasmodium chabaudi clone with altered susceptibility to antifolate drugs☆

PubMed Central

Martinelli, Axel; Henriques, Gisela; Cravo, Pedro; Hunt, Paul

2011-01-01

In malaria parasites, mutations in two genes of folate biosynthesis encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) modify responses to antifolate therapies which target these enzymes. However, the involvement of other genes which modify the availability of exogenous folate, for example, has been proposed. Here, we used short-read whole-genome re-sequencing to determine the mutations in a clone of the rodent malaria parasite, Plasmodium chabaudi, which has altered susceptibility to both sulphadoxine and pyrimethamine. This clone bears a previously identified S106N mutation in dhfr and no mutation in dhps. Instead, three additional point mutations in genes on chromosomes 2, 13 and 14 were identified. The mutated gene on chromosome 13 (mdr2 K392Q) encodes an ABC transporter. Because Quantitative Trait Locus analysis previously indicated an association of genetic markers on chromosome 13 with responses to individual and combined antifolates, MDR2 is proposed to modulate antifolate responses, possibly mediated by the transport of folate intermediates. PMID:20858498

Application of satellite data for snow mapping in Norway

NASA Technical Reports Server (NTRS)

Odegaard, H. A.; Andersen, T.; Ostrem, G. (Principal Investigator)

1980-01-01

The author has identified the following significant results. A close quantitative relationship was found between snow covered areas and subsequent runoff for different parts of the country despite climate differences. Digital LANDSAT data can be used for areas down to approximately 10 sq km to 20 sq km for accurate measurement of snow cover extent. On large watersheds (more than 500 sq km), digital NOAA/TIROS imagery can be used for snow mapping if the area/runoff relationship is determined by using observations from previous years.

Spontaneous Focusing on Quantitative Relations: Towards a Characterization

ERIC Educational Resources Information Center

Degrande, Tine; Verschaffel, Lieven; Van Dooren, Wim

2017-01-01

In contrast to previous studies on Spontaneous Focusing on Quantitative Relations (SFOR), the present study investigated not only the "extent" to which children focus on (multiplicative) quantitative relations, but also the "nature" of children's quantitative focus (i.e., the types of quantitative relations that children focus…

Methanotrophic bacteria in warm geothermal spring sediments identified using stable-isotope probing.

PubMed

Sharp, Christine E; Martínez-Lorenzo, Azucena; Brady, Allyson L; Grasby, Stephen E; Dunfield, Peter F

2014-10-01

We investigated methanotrophic bacteria in sediments of several warm geothermal springs ranging in temperature from 22 to 45 °C. Methane oxidation was measured at potential rates up to 141 μmol CH4 d(-1) g(-1) sediment. Active methanotrophs were identified using (13) CH4 stable-isotope probing (SIP) incubations performed at close to in situ temperatures for each site. Quantitative (q) PCR of pmoA genes identified the position of the heavy ((13) C-labelled) DNA fractions in density gradients, and 16S rRNA gene pyrotag sequencing of the heavy fractions was performed to identify the active methanotrophs. Methanotroph communities identified in heavy fractions of all samples were predominated by species similar (≥ 95% 16S rRNA gene identities) to previously characterized Gammaproteobacteria and Alphaproteobacteria methanotrophs. Among the five hottest samples (45 °C), members of the Gammaproteobacteria genus Methylocaldum dominated in two cases, while three others were dominated by an OTU closely related (96.8% similarity) to the Alphaproteobacteria genus Methylocapsa. These results suggest that diverse methanotroph groups are adapted to warm environments, including the Methylocapsa-Methylocella-Methyloferula group, which has previously only been detected in cooler sites. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Bone Mineral Density Variation in Men is influenced by Sex-Specific and Non Sex-Specific Quantitative Trait Loci

PubMed Central

Peacock, Munro; Koller, Daniel L.; Lai, Dongbing; Hui, Siu; Foroud, Tatiana; Econs, Michael J.

2009-01-01

Introduction A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. Methods aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). Results A genome wide scan identified significant QTL (LOD>3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosome 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. Conclusions This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to spine and five were linked to hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis. PMID:19427925

Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

PubMed Central

Martin, Timothy M.; Concel, Vincent J.; Upadhyay, Swapna; Bein, Kiflai; Brant, Kelly A.; George, Leema; Mitra, Ankita; Thimraj, Tania A.; Fabisiak, James P.; Vuga, Louis J.; Fattman, Cheryl; Kaminski, Naftali; Schulz, Holger; Leikauf, George D.

2014-01-01

Secreted phosphoprotein 1 (Spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting C3H/HeJ and JF1/Msf mouse strains that have extremely divergent lung function. JF1/Msf mice with diminished lung function had reduced lung SPP1 transcript and protein during the peak stage of alveologenesis (postnatal day [P]14–P28) as compared with C3H/HeJ mice. In addition to a previously identified genetic variant that altered runt-related transcription factor 2 (RUNX2) binding in the Spp1 promoter, we identified another promoter variant in a putative RUNX2 binding site that increased the DNA protein binding. SPP1 induced dose-dependent mouse lung epithelial-15 cell proliferation. Spp1(−/−) mice have decreased specific total lung capacity/body weight, higher specific compliance, and increased mean airspace chord length (Lm) compared with Spp1(+/+) mice. Microarray analysis revealed enriched gene ontogeny categories, with numerous genes associated with lung development and/or respiratory disease. Insulin-like growth factor 1, Hedgehog-interacting protein, wingless-related mouse mammary tumor virus integration site 5A, and NOTCH1 transcripts decreased in the lung of P14 Spp1(−/−) mice as determined by quantitative RT-PCR analysis. SPP1 promotes pneumocyte growth, and mice lacking SPP1 have smaller, more compliant lungs with enlarged airspace (i.e., increased Lm). Microarray analysis suggests a dysregulation of key lung developmental transcripts in gene-targeted Spp1(−/−) mice, particularly during the peak phase of alveologenesis. In addition to its known roles in lung disease, this study supports SPP1 as a determinant of lung development in mice. PMID:24816281

The use of children's drawings in the evaluation and treatment of child sexual, emotional, and physical abuse.

PubMed

Peterson, L W; Hardin, M; Nitsch, M J

1995-05-01

Primary care physicians can be instrumental in the initial identification of potential sexual, emotional, and physical abuse of children. We reviewed the use of children's artwork as a method of communicating individual and family functioning. A quantitative method of analyzing children's artwork provides more reliability and validity than some methods used previously. A new scoring system was developed that uses individual human figure drawings and kinetic family drawings. This scoring system was based on research with 842 children (341 positively identified as sexually molested, 252 positively not sexually molested but having emotional or behavioral problems, and 249 "normal" public school children). This system is more comprehensive than previous systems of assessment of potential abuse.

What’s in a Prerequisite? A Mixed-Methods Approach to Identifying the Impact of a Prerequisite Course

PubMed Central

Sato, Brian K.; Lee, Amanda K.; Alam, Usman; Dang, Jennifer V.; Dacanay, Samantha J.; Morgado, Pedro; Pirino, Giorgia; Brunner, Jo Ellen; Castillo, Leanne A.; Chan, Valerie W.; Sandholtz, Judith H.

2017-01-01

Despite the ubiquity of prerequisites in undergraduate science, technology, engineering, and mathematics curricula, there has been minimal effort to assess their value in a data-driven manner. Using both quantitative and qualitative data, we examined the impact of prerequisites in the context of a microbiology lecture and lab course pairing. Through interviews and an online survey, students highlighted a number of positive attributes of prerequisites, including their role in knowledge acquisition, along with negative impacts, such as perhaps needlessly increasing time to degree and adding to the cost of education. We also identified a number of reasons why individuals do or do not enroll in prerequisite courses, many of which were not related to student learning. In our particular curriculum, students did not believe the microbiology lecture course impacted success in the lab, which agrees with our analysis of lab course performance using a previously established “familiarity” scale. These conclusions highlight the importance of soliciting and analyzing student feedback, and triangulating these data with quantitative performance metrics to assess the state of science, technology, engineering, and mathematics curricula. PMID:28232587

Deep Learning for Brain MRI Segmentation: State of the Art and Future Directions.

PubMed

Akkus, Zeynettin; Galimzianova, Alfiia; Hoogi, Assaf; Rubin, Daniel L; Erickson, Bradley J

2017-08-01

Quantitative analysis of brain MRI is routine for many neurological diseases and conditions and relies on accurate segmentation of structures of interest. Deep learning-based segmentation approaches for brain MRI are gaining interest due to their self-learning and generalization ability over large amounts of data. As the deep learning architectures are becoming more mature, they gradually outperform previous state-of-the-art classical machine learning algorithms. This review aims to provide an overview of current deep learning-based segmentation approaches for quantitative brain MRI. First we review the current deep learning architectures used for segmentation of anatomical brain structures and brain lesions. Next, the performance, speed, and properties of deep learning approaches are summarized and discussed. Finally, we provide a critical assessment of the current state and identify likely future developments and trends.

A methodological analysis of chaplaincy research: 2000-2009.

PubMed

Galek, Kathleen; Flannelly, Kevin J; Jankowski, Katherine R B; Handzo, George F

2011-01-01

The present article presents a comprehensive review and analysis of quantitative research conducted in the United States on chaplaincy and closely related topics published between 2000 and 2009. A combined search strategy identified 49 quantitative studies in 13 journals. The analysis focuses on the methodological sophistication of the studies, compared to earlier research on chaplaincy and pastoral care. Cross-sectional surveys of convenience samples still dominate the field, but sample sizes have increased somewhat over the past three decades. Reporting of the validity and reliability of measures continues to be low, although reporting of response rates has improved. Improvements in the use of inferential statistics and statistical controls were also observed, compared to previous research. The authors conclude that more experimental research is needed on chaplaincy, along with an increased use of hypothesis testing, regardless of the research designs that are used.

Strigolactone-regulated proteins revealed by iTRAQ-based quantitative proteomics in Arabidopsis.

PubMed

Li, Zhou; Czarnecki, Olaf; Chourey, Karuna; Yang, Jun; Tuskan, Gerald A; Hurst, Gregory B; Pan, Chongle; Chen, Jin-Gui

2014-03-07

Strigolactones (SLs) are a new class of plant hormones. In addition to acting as a key inhibitor of shoot branching, SLs stimulate seed germination of root parasitic plants and promote hyphal branching and root colonization of symbiotic arbuscular mycorrhizal fungi. They also regulate many other aspects of plant growth and development. At the transcription level, SL-regulated genes have been reported. However, nothing is known about the proteome regulated by this new class of plant hormones. A quantitative proteomics approach using an isobaric chemical labeling reagent, iTRAQ, to identify the proteome regulated by SLs in Arabidopsis seedlings is presented. It was found that SLs regulate the expression of about three dozen proteins that have not been previously assigned to SL pathways. These findings provide a new tool to investigate the molecular mechanism of action of SLs.

The emotional coaching model: quantitative and qualitative research into relationships, communication and decisions in physical and sports rehabilitation

PubMed Central

RESPIZZI, STEFANO; COVELLI, ELISABETTA

2015-01-01

The emotional coaching model uses quantitative and qualitative elements to demonstrate some assumptions relevant to new methods of treatment in physical rehabilitation, considering emotional, cognitive and behavioral aspects in patients, whether or not they are sportsmen. Through quantitative tools (Tampa Kinesiophobia Scale, Emotional Interview Test, Previous Re-Injury Test, and reports on test scores) and qualitative tools (training contracts and relationships of emotional alliance or “contagion”), we investigate initial assumptions regarding: the presence of a cognitive and emotional mental state of impasse in patients at the beginning of the rehabilitation pathway; the curative value of the emotional alliance or “emotional contagion” relationship between healthcare provider and patient; the link between the patient’s pathology and type of contact with his own body and emotions; analysis of the psychosocial variables for the prediction of possible cases of re-injury for patients who have undergone or are afraid to undergo reconstruction of the anterior cruciate ligament (ACL). Although this approach is still in the experimental stage, the scores of the administered tests show the possibility of integrating quantitative and qualitative tools to investigate and develop a patient’s physical, mental and emotional resources during the course of his rehabilitation. Furthermore, it seems possible to identify many elements characterizing patients likely to undergo episodes of re-injury or to withdraw totally from sporting activity. In particular, such patients are competitive athletes, who fear or have previously undergone ACL reconstruction. The theories referred to (the transactional analysis theory, self-determination theory) and the tools used demonstrate the usefulness of continuing this research in order to build a shared coaching model treatment aimed at all patients, sportspeople or otherwise, which is not only physical but also emotional, cognitive and behavioral. PMID:26904525

Characterization of Sensory Differences in Mixing and Premium Rums Through the Use of Descriptive Sensory Analysis.

PubMed

Ickes, Chelsea M; Cadwallader, Keith R

2017-11-01

This study identified and quantitated perceived sensory differences between 7 premium rums and 2 mixing rums using a hybrid of the Quantitative Descriptive Analysis and Spectrum methods. In addition, the results of this study validated the previously developed rum flavor wheel created from web-based materials. Results showed that the use of the rum flavor wheel aided in sensory term generation, as 17 additional terms were generated after the wheel was provided to panelists. Thirty-eight sensory terms encompassing aroma, aroma-by-mouth, mouthfeel, taste and aftertaste modalities, were generated and evaluated by the panel. Of the finalized terms, only 5 did not exist previously on the rum flavor wheel. Twenty attributes were found to be significantly different among rums. The majority of rums showed similar aroma profiles with the exception of 2 rums, which were characterized by higher perceived intensities of brown sugar, caramel, vanilla, and chocolate aroma, caramel, maple, and vanilla aroma-by-mouth and caramel aftertaste. These results demonstrate the previously developed rum flavor wheel can be used to adequately describe the flavor profile of rum. Additionally, results of this study document the sensory differences among premium rums and may be used to correlate with analytical data to better understand how changes in chemical composition of the product affect sensory perception. © 2017 Institute of Food Technologists®.

Construction of a high-density linkage map and mapping quantitative trait loci for somatic embryogenesis using leaf petioles as explants in upland cotton (Gossypium hirsutum L.).

PubMed

Xu, Zhenzhen; Zhang, Chaojun; Ge, Xiaoyang; Wang, Ni; Zhou, Kehai; Yang, Xiaojie; Wu, Zhixia; Zhang, Xueyan; Liu, Chuanliang; Yang, Zuoren; Li, Changfeng; Liu, Kun; Yang, Zhaoen; Qian, Yuyuan; Li, Fuguang

2015-07-01

The first high-density linkage map was constructed to identify quantitative trait loci (QTLs) for somatic embryogenesis (SE) in cotton ( Gossypium hirsutum L.) using leaf petioles as explants. Cotton transformation is highly limited by only a few regenerable genotypes and the lack of understanding of the genetic and molecular basis of somatic embryogenesis (SE) in cotton (Gossypium hirsutum L.). To construct a more saturated linkage map and further identify quantitative trait loci (QTLs) for SE using leaf petioles as explants, a high embryogenesis frequency line (W10) from the commercial Chinese cotton cultivar CRI24 was crossed with TM-1, a genetic standard upland cotton with no embryogenesis frequency. The genetic map spanned 2300.41 cM in genetic distance and contained 411 polymorphic simple sequence repeat (SSR) loci. Of the 411 mapped loci, 25 were developed from unigenes identified for SE in our previous study. Six QTLs for SE were detected by composite interval mapping method, each explaining 6.88-37.07% of the phenotypic variance. Single marker analysis was also performed to verify the reliability of QTLs detection, and the SSR markers NAU3325 and DPL0209 were detected by the two methods. Further studies on the relatively stable and anchoring QTLs/markers for SE in an advanced population of W10 × TM-1 and other cross combinations with different SE abilities may shed light on the genetic and molecular mechanism of SE in cotton.

Epistatic Effects Contribute to Variation in BMD in Fischer 344 × Lewis F2 Rats

PubMed Central

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

To further delineate the factors underlying the complex genetic architecture of BMD in the rat model, a genome screen for epistatic interactions was conducted. Several significant interactions were identified, involving both previously identified and novel QTLs. Introduction The variation in several of the risk factors for osteoporotic fracture, including BMD, has been shown to be caused largely by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We have previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 595 female F2 progeny of Fischer 344 and Lewis rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Materials and Methods Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted BMD (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine a genome-wide significance threshold for the epistasis or interaction LOD score corresponding to an α level of 0.01. Results and Conclusions Novel loci on chromosomes 12 and 15 showed a strong epistatic effect on total BMD at the femoral midshaft by pQCT (LOD = 5.4). A previously reported QTL on chromosome 7 was found to interact with a novel locus on chromosome 20 to affect whole lumbar BMD by pQCT (LOD = 6.2). These results provide new information regarding the mode of action of previously identified rat QTLs, as well as identifying novel loci that act in combination with known QTLs or with other novel loci to contribute to the risk factors for osteoporotic fracture. PMID:17907919

Epistatic effects contribute to variation in BMD in Fischer 344 x Lewis F2 rats.

PubMed

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

To further delineate the factors underlying the complex genetic architecture of BMD in the rat model, a genome screen for epistatic interactions was conducted. Several significant interactions were identified, involving both previously identified and novel QTLs. The variation in several of the risk factors for osteoporotic fracture, including BMD, has been shown to be caused largely by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We have previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 595 female F(2) progeny of Fischer 344 and Lewis rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted BMD (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine a genome-wide significance threshold for the epistasis or interaction LOD score corresponding to an alpha level of 0.01. Novel loci on chromosomes 12 and 15 showed a strong epistatic effect on total BMD at the femoral midshaft by pQCT (LOD = 5.4). A previously reported QTL on chromosome 7 was found to interact with a novel locus on chromosome 20 to affect whole lumbar BMD by pQCT (LOD = 6.2). These results provide new information regarding the mode of action of previously identified rat QTLs, as well as identifying novel loci that act in combination with known QTLs or with other novel loci to contribute to the risk factors for osteoporotic fracture.

A multiplexed quantitative proteomics approach for investigating protein expression in the developing central nervous system.

PubMed

Orme, Rowan P; Gates, Monte A; Fricker-Gates, Rosemary A

2010-08-15

Cell transplantation using stem cell-derived neurons is commonly viewed as a candidate therapy for neurodegenerative diseases. However, methods for differentiating stem cells into homogenous populations of neurons suitable for transplant remain elusive. This suggests that there are as yet unknown signalling factors working in vivo to specify neuronal cell fate during development. These factors could be manipulated to better differentiate stem cells into neural populations useful for therapeutic transplantation. Here a quantitative proteomics approach is described for investigating cell signalling in the developing central nervous system (CNS), using the embryonic ventral mesencephalon as a model. Briefly, total protein was extracted from embryonic ventral midbrain tissue before, during and after the birth of dopaminergic neurons, and digested using trypsin. Two-dimensional liquid chromatography, coupled with tandem mass spectrometry, was then used to identify proteins from the tryptic peptides. Isobaric tagging for relative and absolute quantification (iTRAQ) reagents were used to label the tryptic peptides and facilitate relative quantitative analysis. The success of the experiment was confirmed by the identification of proteins known to be expressed in the developing ventral midbrain, as well as by Western blotting, and immunolabelling of embryonic tissue sections. This method of protein discovery improves upon previous attempts to identify novel signalling factors through microarray analysis. Importantly, the methods described here could be applied to virtually any aspect of development. (c) 2010 Elsevier B.V. All rights reserved.

Perceived barriers and facilitators to mental health help-seeking in young people: a systematic review

PubMed Central

2010-01-01

Background Adolescents and young adults frequently experience mental disorders, yet tend not to seek help. This systematic review aims to summarise reported barriers and facilitators of help-seeking in young people using both qualitative research from surveys, focus groups, and interviews and quantitative data from published surveys. It extends previous reviews through its systematic research methodology and by the inclusion of published studies describing what young people themselves perceive are the barriers and facilitators to help-seeking for common mental health problems. Methods Twenty two published studies of perceived barriers or facilitators in adolescents or young adults were identified through searches of PubMed, PsycInfo, and the Cochrane database. A thematic analysis was undertaken on the results reported in the qualitative literature and quantitative literature. Results Fifteen qualitative and seven quantitative studies were identified. Young people perceived stigma and embarrassment, problems recognising symptoms (poor mental health literacy), and a preference for self-reliance as the most important barriers to help-seeking. Facilitators were comparatively under-researched. However, there was evidence that young people perceived positive past experiences, and social support and encouragement from others as aids to the help-seeking process. Conclusions Strategies for improving help-seeking by adolescents and young adults should focus on improving mental health literacy, reducing stigma, and taking into account the desire of young people for self-reliance. PMID:21192795

Perceived barriers and facilitators to mental health help-seeking in young people: a systematic review.

PubMed

Gulliver, Amelia; Griffiths, Kathleen M; Christensen, Helen

2010-12-30

Adolescents and young adults frequently experience mental disorders, yet tend not to seek help. This systematic review aims to summarise reported barriers and facilitators of help-seeking in young people using both qualitative research from surveys, focus groups, and interviews and quantitative data from published surveys. It extends previous reviews through its systematic research methodology and by the inclusion of published studies describing what young people themselves perceive are the barriers and facilitators to help-seeking for common mental health problems. Twenty two published studies of perceived barriers or facilitators in adolescents or young adults were identified through searches of PubMed, PsycInfo, and the Cochrane database. A thematic analysis was undertaken on the results reported in the qualitative literature and quantitative literature. Fifteen qualitative and seven quantitative studies were identified. Young people perceived stigma and embarrassment, problems recognising symptoms (poor mental health literacy), and a preference for self-reliance as the most important barriers to help-seeking. Facilitators were comparatively under-researched. However, there was evidence that young people perceived positive past experiences, and social support and encouragement from others as aids to the help-seeking process. Strategies for improving help-seeking by adolescents and young adults should focus on improving mental health literacy, reducing stigma, and taking into account the desire of young people for self-reliance.

Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus.

PubMed

Shobahah, Jauharotus; Xue, Shengjie; Hu, Dongbing; Zhao, Cui; Wei, Ming; Quan, Yanping; Yu, Wei

2017-06-19

Bombyx mori has become an important model organism for many fundamental studies. Bombyx mori nucleopolyhedrovirus (BmNPV) is a significant pathogen to Bombyx mori, yet also an efficient vector for recombinant protein production. A previous study indicated that acetylation plays many vital roles in several cellular processes of Bombyx mori while global phosphorylation pattern upon BmNPV infection remains elusive. Employing tandem mass tag (TMT) labeling and phosphorylation affinity enrichment followed by high-resolution LC-MS/MS analysis and intensive bioinformatics analysis, the quantitative phosphoproteome in Bombyx mori cells infected by BmNPV at 24 hpi with an MOI of 10 was extensively examined. Totally, 6480 phosphorylation sites in 2112 protein groups were identified, among which 4764 sites in 1717 proteins were quantified. Among the quantified proteins, 81 up-regulated and 25 down-regulated sites were identified with significant criteria (the quantitative ratio above 1.3 was considered as up-regulation and below 0.77 was considered as down-regulation) and with significant p-value (p < 0.05). Some proteins of BmNPV were also hyperphosphorylated during infection, such as P6.9, 39 K, LEF-6, Ac58-like protein, Ac82-like protein and BRO-D. The phosphorylated proteins were primary involved in several specific functions, out of which, we focused on the binding activity, protein synthesis, viral replication and apoptosis through kinase activity.

Standardized observation of neighbourhood disorder: does it work in Canada?

PubMed Central

2010-01-01

Background There is a growing body of evidence that where you live is important to your health. Despite numerous previous studies investigating the relationship between neighbourhood deprivation (and structure) and residents' health, the precise nature of this relationship remains unclear. Relatively few investigations have relied on direct observation of neighbourhoods, while those that have were developed primarily in US settings. Evaluation of the transferability of such tools to other contexts is an important first step before applying such instruments to the investigation of health and well-being. This study evaluated the performance of a systematic social observational (SSO) tool (adapted from previous studies of American and British neighbourhoods) in a Canadian urban context. Methods This was a mixed-methods study. Quantitative SSO ratings and qualitative descriptions of 176 block faces were obtained in six Toronto neighbourhoods (4 low-income, and 2 middle/high-income) by trained raters. Exploratory factor analysis was conducted with the quantitative SSO ratings. Content analysis consisted of independent coding of qualitative data by three members of the research team to yield common themes and categories. Results Factor analysis identified three factors (physical decay/disorder, social accessibility, recreational opportunities), but only 'physical decay/disorder' reflected previous findings in the literature. Qualitative results (based on raters' fieldwork experiences) revealed the tool's shortcomings in capturing important features of the neighbourhoods under study, and informed interpretation of the quantitative findings. Conclusions This study tested the performance of an SSO tool in a Canadian context, which is an important initial step before applying it to the study of health and disease. The tool demonstrated important shortcomings when applied to six diverse Toronto neighbourhoods. The study's analyses challenge previously held assumptions (e.g. social 'disorder') regarding neighbourhood social and built environments. For example, neighbourhood 'order' has traditionally been assumed to be synonymous with a certain degree of homogeneity, however the neighbourhoods under study were characterized by high degrees of heterogeneity and low levels of disorder. Heterogeneity was seen as an appealing feature of a block face. Employing qualitative techniques with SSO represents a unique contribution, enhancing both our understanding of the quantitative ratings obtained and of neighbourhood characteristics that are not currently captured by such instruments. PMID:20146821

Proteomic Analysis of Pathogenic Fungi Reveals Highly Expressed Conserved Cell Wall Proteins

PubMed Central

Champer, Jackson; Ito, James I.; Clemons, Karl V.; Stevens, David A.; Kalkum, Markus

2016-01-01

We are presenting a quantitative proteomics tally of the most commonly expressed conserved fungal proteins of the cytosol, the cell wall, and the secretome. It was our goal to identify fungi-typical proteins that do not share significant homology with human proteins. Such fungal proteins are of interest to the development of vaccines or drug targets. Protein samples were derived from 13 fungal species, cultured in rich or in minimal media; these included clinical isolates of Aspergillus, Candida, Mucor, Cryptococcus, and Coccidioides species. Proteomes were analyzed by quantitative MSE (Mass Spectrometry—Elevated Collision Energy). Several thousand proteins were identified and quantified in total across all fractions and culture conditions. The 42 most abundant proteins identified in fungal cell walls or supernatants shared no to very little homology with human proteins. In contrast, all but five of the 50 most abundant cytosolic proteins had human homologs with sequence identity averaging 59%. Proteomic comparisons of the secreted or surface localized fungal proteins highlighted conserved homologs of the Aspergillus fumigatus proteins 1,3-β-glucanosyltransferases (Bgt1, Gel1-4), Crf1, Ecm33, EglC, and others. The fact that Crf1 and Gel1 were previously shown to be promising vaccine candidates, underlines the value of the proteomics data presented here. PMID:26878023

Comparison of Pancreas Juice Proteins from Cancer Versus Pancreatitis Using Quantitative Proteomic Analysis

PubMed Central

Chen, Ru; Pan, Sheng; Cooke, Kelly; Moyes, Kara White; Bronner, Mary P.; Goodlett, David R.; Aebersold, Ruedi; Brentnall, Teresa A.

2008-01-01

Objectives Pancreatitis is an inflammatory condition of the pancreas. However, it often shares many molecular features with pancreatic cancer. Biomarkers present in pancreatic cancer frequently occur in the setting of pancreatitis. The efforts to develop diagnostic biomarkers for pancreatic cancer have thus been complicated by the false-positive involvement of pancreatitis. Methods In an attempt to develop protein biomarkers for pancreatic cancer, we previously use quantitative proteomics to identify and quantify the proteins from pancreatic cancer juice. Pancreatic juice is a rich source of proteins that are shed by the pancreatic ductal cells. In this study, we used a similar approach to identify and quantify proteins from pancreatitis juice. Results In total, 72 proteins were identified and quantified in the comparison of pancreatic juice from pancreatitis patients versus pooled normal control juice. Nineteen of the juice proteins were overexpressed, and 8 were underexpressed in pancreatitis juice by at least 2-fold compared with normal pancreatic juice. Of these 27 differentially expressed proteins in pancreatitis, 9 proteins were also differentially expressed in the pancreatic juice from pancreatic cancer patient. Conclusions Identification of these differentially expressed proteins from pancreatitis juice provides useful information for future study of specific pancreatitis-associated proteins and to eliminate potential false-positive biomarkers for pancreatic cancer. PMID:17198186

Comparison of pancreas juice proteins from cancer versus pancreatitis using quantitative proteomic analysis.

PubMed

Chen, Ru; Pan, Sheng; Cooke, Kelly; Moyes, Kara White; Bronner, Mary P; Goodlett, David R; Aebersold, Ruedi; Brentnall, Teresa A

2007-01-01

Pancreatitis is an inflammatory condition of the pancreas. However, it often shares many molecular features with pancreatic cancer. Biomarkers present in pancreatic cancer frequently occur in the setting of pancreatitis. The efforts to develop diagnostic biomarkers for pancreatic cancer have thus been complicated by the false-positive involvement of pancreatitis. In an attempt to develop protein biomarkers for pancreatic cancer, we previously use quantitative proteomics to identify and quantify the proteins from pancreatic cancer juice. Pancreatic juice is a rich source of proteins that are shed by the pancreatic ductal cells. In this study, we used a similar approach to identify and quantify proteins from pancreatitis juice. In total, 72 proteins were identified and quantified in the comparison of pancreatic juice from pancreatitis patients versus pooled normal control juice. Nineteen of the juice proteins were overexpressed, and 8 were underexpressed in pancreatitis juice by at least 2-fold compared with normal pancreatic juice. Of these 27 differentially expressed proteins in pancreatitis, 9 proteins were also differentially expressed in the pancreatic juice from pancreatic cancer patient. Identification of these differentially expressed proteins from pancreatitis juice provides useful information for future study of specific pancreatitis-associated proteins and to eliminate potential false-positive biomarkers for pancreatic cancer.

Quantitative trait loci underlying resistance to sudden death syndrome (SDS) in MD96-5722 by 'Spencer' recombinant inbred line population of soybean.

PubMed

Anderson, J; Akond, M; Kassem, M A; Meksem, K; Kantartzi, S K

2015-04-01

The best way to protect yield loss of soybean [Glycine max (L.) Merr.] due to sudden death syndrome (SDS), caused by Fusarium virguliforme (Aoki, O'Donnel, Homma & Lattanzi), is the development and use of resistant lines. Mapping quantitative trait loci (QTL) linked to SDS help developing resistant soybean germplasm through molecular marker-assisted selection strategy. QTL for SDS presented herein are from a high-density SNP-based genetic linkage map of MD 96-5722 (a.k.a 'Monocacy') by 'Spencer' recombinant inbred line using SoySNP6K Illumina Infinium BeadChip genotyping array. Ninety-four F 5:7 lines were evaluated for 2 years (2010 and 2011) at two locations (Carbondale and Valmeyer) in southern Illinois, USA to identify QTL controlling SDS resistance using disease index (DX). Composite interval mapping identified 19 SDS controlling QTL which were mapped on 11 separate linkage group (LG) or chromosomes (Chr) out of 20 LG or Chr of soybean genome. Many of these significant QTL identified in one environment/year were confirmed in another year or environment, which suggests a common genetic effects and modes of the pathogen. These new QTL are useful sources for SDS resistance studies in soybean breeding, complementing previously reported loci.

Identification of common coexpression modules based on quantitative network comparison.

PubMed

Jo, Yousang; Kim, Sanghyeon; Lee, Doheon

2018-06-13

Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method. We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs. We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/ inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.

Quantitative profiling of drug-associated proteomic alterations by combined 2-nitrobenzenesulfenyl chloride (NBS) isotope labeling and 2DE/MS identification.

PubMed

Ou, Keli; Kesuma, Djohan; Ganesan, Kumaresan; Yu, Kun; Soon, Sou Yen; Lee, Suet Ying; Goh, Xin Pei; Hooi, Michelle; Chen, Wei; Jikuya, Hiroyuki; Ichikawa, Tetsuo; Kuyama, Hiroki; Matsuo, Ei-ichi; Nishimura, Osamu; Tan, Patrick

2006-09-01

The identification of drug-responsive biomarkers in complex protein mixtures is an important goal of quantitative proteomics. Here, we describe a novel approach for identifying such drug-induced protein alterations, which combines 2-nitrobenzenesulfenyl chloride (NBS) tryptophan labeling with two-dimensional gel electrophoresis (2DE)/mass spectrometry (MS). Lysates from drug-treated and control samples are labeled with light or heavy NBS moiety and separated on a common 2DE gel, and protein alterations are identified by MS through the differential intensity of paired NBS peptide peaks. Using NBS/2DE/MS, we profiled the proteomic alterations induced by tamoxifen (TAM) in the estrogen receptor (ER) positive MCF-7 breast cancer cell line. Of 88 protein spots that significantly changed upon TAM treatment, 44 spots representing 23 distinct protein species were successfully identified with NBS-paired peptides. Of these 23 TAM-altered proteins, 16 (70%) have not been previously associated with TAM or ER activity. We found the NBS labeling procedure to be both technically and biologically reproducible, and the NBS/2DE/MS alterations exhibited good concordance with conventional 2DE differential protein quantitation, with discrepancies largely due to the comigration of distinct proteins in the regular 2DE gels. To validate the NBS/2DE/MS results, we used immunoblotting to confirm GRP78, CK19, and PA2G4 as bona fide TAM-regulated proteins. Furthermore, we demonstrate that PA2G4 expression can serve as a novel prognostic factor for disease-free survival in two independent breast cancer patient cohorts. To our knowledge, this is the first report describing the proteomic changes in breast cancer cells induced by TAM, the most commonly used selective estrogen receptor modulator (SERM). Our results indicate that NBS/2DE/MS may represent a more reliable approach for cellular protein quantitation than conventional 2DE approaches.

Evaluation of a quantitative H2S MPN test for fecal microbes analysis of water using biochemical and molecular identification.

PubMed

McMahan, Lanakila; Grunden, Amy M; Devine, Anthony A; Sobsey, Mark D

2012-04-15

The sensitivity and specificity of the H(2)S test to detect fecal bacteria in water has been variable and uncertain in previous studies, partly due to its presence-absence results. Furthermore, in groundwater samples false-positive results have been reported, with H(2)S-positive samples containing no fecal coliforms or Escherichia coli. False-negative results also have been reported in other studies, with H(2)S-negative samples found to contain E. coli. Using biochemical and molecular methods and a novel quantitative test format, this research identified the types and numbers of microbial community members present in natural water samples, including fecal indicators and pathogens as well as other bacteria. Representative water sources tested in this study included cistern rainwater, a protected lake, and wells in agricultural and forest settings. Samples from quantitative H(2)S tests of water were further cultured for fecal bacteria by spread plating onto the selective media for detection and isolation of Aeromonas spp., E. coli, Clostridium spp., H(2)S-producers, and species of Salmonella and Shigella. Isolates were then tested for H(2)S production, and identified to the genus and species level using biochemical methods. Terminal Restriction Fragment Length Polymorphisms (TRFLP) was the molecular method employed to quantitatively characterize microbial community diversity. Overall, it was shown that water samples testing positive for H(2)S bacteria also had bacteria of likely fecal origin and waters containing fecal pathogens also were positive for H(2)S bacteria. Of the microorganisms isolated from natural water, greater than 70 percent were identified using TRFLP analysis to reveal a relatively stable group of organisms whose community composition differed with water source and over time. These results further document the validity of the H(2)S test for detecting and quantifying fecal contamination of water. Copyright © 2011 Elsevier Ltd. All rights reserved.

Label-Free Relative Quantitation of Isobaric and Isomeric Human Histone H2A and H2B Variants by Fourier Transform Ion Cyclotron Resonance Top-Down MS/MS.

PubMed

Dang, Xibei; Singh, Amar; Spetman, Brian D; Nolan, Krystal D; Isaacs, Jennifer S; Dennis, Jonathan H; Dalton, Stephen; Marshall, Alan G; Young, Nicolas L

2016-09-02

Histone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free approach. We extend the analysis to identify and relatively quantitate 16 proteoforms from 12 sequence variants of histone H2A and 10 proteoforms of histone H2B from three other cell lines: human embryonic stem cells (WA09), U937, and a prostate cancer cell line LaZ. The top-down MS/MS approach provides a path forward for more extensive elucidation of the biological role of many previously unstudied histone variants and post-translational modifications.

Cell Electrical Impedance as a Novel Approach for Studies on Senescence Not Based on Biomarkers

PubMed Central

Cha, Jung-Joon; Park, Yangkyu; Yun, Joho; Kim, Hyeon Woo; Park, Chang-Ju; Kang, Giseok; Jung, Minhyun; Pak, Boryeong; Jin, Suk-Won

2016-01-01

Senescence of cardiac myocytes is frequently associated with heart diseases. To analyze senescence in cardiac myocytes, a number of biomarkers have been isolated. However, due to the complex nature of senescence, multiple markers are required for a single assay to accurately depict complex physiological changes associated with senescence. In single cells, changes in both cytoplasm and cell membrane during senescence can affect the changes in electrical impedance. Based on this phenomenon, we developed MEDoS, a novel microelectrochemical impedance spectroscopy for diagnosis of senescence, which allows us to precisely measure quantitative changes in electrical properties of aging cells. Using cardiac myocytes isolated from 3-, 6-, and 18-month-old isogenic zebrafish, we examined the efficacy of MEDoS and showed that MEDoS can identify discernible changes in electrical impedance. Taken together, our data demonstrated that electrical impedance in cells at different ages is distinct with quantitative values; these results were comparable with previously reported ones. Therefore, we propose that MEDoS be used as a new biomarker-independent methodology to obtain quantitative data on the biological senescence status of individual cells. PMID:27812531

Quantitative measurement of intact alpha-synuclein proteoforms from post-mortem control and Parkinson's disease brain tissue by intact protein mass spectrometry.

PubMed

Kellie, John F; Higgs, Richard E; Ryder, John W; Major, Anthony; Beach, Thomas G; Adler, Charles H; Merchant, Kalpana; Knierman, Michael D

2014-07-23

A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03).

Use of a deuterated internal standard with pyrolysis-GC/MS dimeric marker analysis to quantify tire tread particles in the environment.

PubMed

Unice, Kenneth M; Kreider, Marisa L; Panko, Julie M

2012-11-08

Pyrolysis(pyr)-GC/MS analysis of characteristic thermal decomposition fragments has been previously used for qualitative fingerprinting of organic sources in environmental samples. A quantitative pyr-GC/MS method based on characteristic tire polymer pyrolysis products was developed for tread particle quantification in environmental matrices including soil, sediment, and air. The feasibility of quantitative pyr-GC/MS analysis of tread was confirmed in a method evaluation study using artificial soil spiked with known amounts of cryogenically generated tread. Tread concentration determined by blinded analyses was highly correlated (r2 ≥ 0.88) with the known tread spike concentration. Two critical refinements to the initial pyrolysis protocol were identified including use of an internal standard and quantification by the dimeric markers vinylcyclohexene and dipentene, which have good specificity for rubber polymer with no other appreciable environmental sources. A novel use of deuterated internal standards of similar polymeric structure was developed to correct the variable analyte recovery caused by sample size, matrix effects, and ion source variability. The resultant quantitative pyr-GC/MS protocol is reliable and transferable between laboratories.

Peptides in low molecular weight fraction of serum associated with hepatocellular carcinoma.

PubMed

An, Yanming; Bekesova, Slavka; Edwards, Nathan; Goldman, Radoslav

2010-01-01

The incidence of hepatocellular carcinoma (HCC) in the United States is increasing and the increase is projected to continue for several decades. The overall survival of HCC patients is poor and treatments are not effective in part because most of the diagnoses come at a late stage. The development of new markers for detection of HCC would significantly improve patient prognosis. This paper describes identification of candidate markers previously reported in our serologic study of an Egyptian population by quantitative comparison of matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectra. To identify these marker candidates, we performed LC-MS/MS sequencing that identified nine native peptides associated with HCC, including two reported previously. Four truncations of N terminus of complement C3f and a fibrinopeptide increased in control sera; two complement C4alpha peptides, a zyxin peptide, and a coagulation factor XIII peptide increased in cancer patient sera. We have also identified increased biliverdin diglucuronide in the sera of cancer patients. These peptides could potentially serve as markers of HCC following additional validation studies; however, association of similar peptides with other diseases and cancers dictates a very cautious approach.

Fluorescent recovery after photobleaching (FRAP) analysis of nuclear export rates identifies intrinsic features of nucleocytoplasmic transport.

PubMed

Cardarelli, Francesco; Tosti, Luca; Serresi, Michela; Beltram, Fabio; Bizzarri, Ranieri

2012-02-17

A quantitative description of carrier-mediated nuclear export in live cells is presented. To this end, we fused a prototypical leucine-rich nuclear export signal (NES) to GFP as a cargo model and expressed the fluorescent chimera in live CHO-K1 cells. By modeling FRAP data, we calculate the NES affinity for the export machinery and the maximum rate of nuclear export achievable at saturation of endogenous carriers. The measured active-export time through the Nuclear Pore Complex (NPC) is 18 ms, remarkably similar to the previously determined active-import rate. Also, our results reveal that active export/import and active export/passive diffusion fluxes are uncoupled, thus complementing previous reports on active import/passive diffusion uncoupling. These findings suggest differential gating at the NPC level.

Proteomic analysis of single mammalian cells enabled by microfluidic nanodroplet sample preparation and ultrasensitive nanoLC-MS.

PubMed

Zhu, Ying; Clair, Geremy; Chrisler, William; Shen, Yufeng; Zhao, Rui; Shukla, Anil; Moore, Ronald; Misra, Ravi; Pryhuber, Gloria; Smith, Richard; Ansong, Charles; Kelly, Ryan T

2018-05-24

We report on the quantitative proteomic analysis of single mammalian cells. Fluorescence-activated cell sorting was employed to deposit cells into a newly developed nanodroplet sample processing chip, after which samples were analysed by ultrasensitive nanoLC-MS. An average of ~670 protein groups were confidently identified from single HeLa cells, which is a far greater level of proteome coverage for single cells than has been previously reported. We demonstrate that the single cell proteomics platform can be used to differentiate cell types from enzyme-dissociated human lung primary cells and identify specific protein markers for epithelial and mesenchymal cells. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of quantitative trait loci for yield and yield components in an advanced backcross population derived from the Oryza sativa variety IR64 and the wild relative O. rufipogon.

PubMed

Septiningsih, E M; Prasetiyono, J; Lubis, E; Tai, T H; Tjubaryat, T; Moeljopawiro, S; McCouch, S R

2003-11-01

A BC(2)F(2) population developed from an interspecific cross between Oryza sativa (cv IR64) and O. rufipogon (IRGC 105491) was used in an advanced backcross QTL analysis to identify and introduce agronomically useful genes from this wild relative into the cultivated gene pool. The objectives of this study were: (1) to identify putative yield and yield component QTLs that can be useful to improve the elite cultivar IR64; (2) to compare the QTLs within this study with previously reported QTLs in rice as the basis for identifying QTLs that are stable across different environments and genetic backgrounds; and (3) to compare the identified QTLs with previously reported QTLs from maize to examine the degree of QTL conservation across the grass family. Two hundred eighty-five families were evaluated in two field environments in Indonesia, with two replications each, for 12 agronomic traits. A total of 165 markers consisting of 131 SSRs and 34 RFLPs were used to construct the genetic linkage map. By employing interval mapping and composite interval mapping, 42 QTLs were identified. Despite its inferior performance, 33% of the QTL alleles originating from O. rufipogon had a beneficial effect for yield and yield components in the IR64 background. Twenty-two QTLs (53.4%) were located in similar regions as previously reported rice QTLs, suggesting the existence of stable QTLs across genetic backgrounds and environments. Twenty QTLs (47.6%) were exclusively detected in this study, uncovering potentially novel alleles from the wild, some of which might improve the performance of the tropical indica variety IR64. Additionally, several QTLs for plant height, grain weight, and flowering time detected in this study corresponded to homeologous regions in maize containing previously detected maize QTLs for these traits.

Quantitative Global Heat Transfer in a Mach-6 Quiet Tunnel

NASA Technical Reports Server (NTRS)

Sullivan, John P.; Schneider, Steven P.; Liu, Tianshu; Rubal, Justin; Ward, Chris; Dussling, Joseph; Rice, Cody; Foley, Ryan; Cai, Zeimin; Wang, Bo;

[A quantitative approach to sports training-adapted social determinants concerning sport].

PubMed

Alvis-Gómez, Martina K; Neira-Tolosa, Nury A

2013-01-01

Identifying and quantitatively analysing social determinants affecting disabled teenagers' inclusion/exclusion in high-performance sports. This was a descriptive cross-sectional study involving 19 12- to 19-year-old athletes suffering physical and sensory disability and 17 staff from the District Institute of Recreation and Sport. Likert-type rating scales were used, based on four analysis categories, i.e. social structure, socio-economic, educational and living condition determinants. Social inequity pervades the national paralympic sports' system. This is because 74 % of individuals only become recognised as sportspeople when they have obtained meritorious results in set competition without appropriate conditions having been previously provided by such paralympic sports institution to enable them to overcome structural and intermediate barriers. The social structure imposed on district-based paralympic sport stigmatises individuals regarding their individual abilities, affects their empowerment and freedom due to the discrimination experienced by disabled teenagers regarding their competitive achievements.

Assessing the Performance of a Machine Learning Algorithm in Identifying Bubbles in Dust Emission

NASA Astrophysics Data System (ADS)

Xu, Duo; Offner, Stella S. R.

2017-12-01

Stellar feedback created by radiation and winds from massive stars plays a significant role in both physical and chemical evolution of molecular clouds. This energy and momentum leaves an identifiable signature (“bubbles”) that affects the dynamics and structure of the cloud. Most bubble searches are performed “by eye,” which is usually time-consuming, subjective, and difficult to calibrate. Automatic classifications based on machine learning make it possible to perform systematic, quantifiable, and repeatable searches for bubbles. We employ a previously developed machine learning algorithm, Brut, and quantitatively evaluate its performance in identifying bubbles using synthetic dust observations. We adopt magnetohydrodynamics simulations, which model stellar winds launching within turbulent molecular clouds, as an input to generate synthetic images. We use a publicly available three-dimensional dust continuum Monte Carlo radiative transfer code, HYPERION, to generate synthetic images of bubbles in three Spitzer bands (4.5, 8, and 24 μm). We designate half of our synthetic bubbles as a training set, which we use to train Brut along with citizen-science data from the Milky Way Project (MWP). We then assess Brut’s accuracy using the remaining synthetic observations. We find that Brut’s performance after retraining increases significantly, and it is able to identify yellow bubbles, which are likely associated with B-type stars. Brut continues to perform well on previously identified high-score bubbles, and over 10% of the MWP bubbles are reclassified as high-confidence bubbles, which were previously marginal or ambiguous detections in the MWP data. We also investigate the influence of the size of the training set, dust model, evolutionary stage, and background noise on bubble identification.

Quantitative Characterization of the Filiform Mechanosensory Hair Array on the Cricket Cercus

PubMed Central

Miller, John P.; Krueger, Susan; Heys, Jeffrey J.; Gedeon, Tomas

2011-01-01

Background Crickets and other orthopteran insects sense air currents with a pair of abdominal appendages resembling antennae, called cerci. Each cercus in the common house cricket Acheta domesticus is approximately 1 cm long, and is covered with 500 to 750 filiform mechanosensory hairs. The distribution of the hairs on the cerci, as well as the global patterns of their movement vectors, have been characterized semi-quantitatively in studies over the last 40 years, and have been shown to be very stereotypical across different animals in this species. Although the cercal sensory system has been the focus of many studies in the areas of neuroethology, development, biomechanics, sensory function and neural coding, there has not yet been a quantitative study of the functional morphology of the receptor array of this important model system. Methodology/Principal Findings We present a quantitative characterization of the structural characteristics and functional morphology of the cercal filiform hair array. We demonstrate that the excitatory direction along each hair's movement plane can be identified by features of its socket that are visible at the light-microscopic level, and that the length of the hair associated with each socket can also be estimated accurately from a structural parameter of the socket. We characterize the length and directionality of all hairs on the basal half of a sample of three cerci, and present statistical analyses of the distributions. Conclusions/Significance The inter-animal variation of several global organizational features is low, consistent with constraints imposed by functional effectiveness and/or developmental processes. Contrary to previous reports, however, we show that the filiform hairs are not re-identifiable in the strict sense. PMID:22132155

A comparative proteomics method for multiple samples based on a 18O-reference strategy and a quantitation and identification-decoupled strategy.

PubMed

Wang, Hongbin; Zhang, Yongqian; Gui, Shuqi; Zhang, Yong; Lu, Fuping; Deng, Yulin

2017-08-15

Comparisons across large numbers of samples are frequently necessary in quantitative proteomics. Many quantitative methods used in proteomics are based on stable isotope labeling, but most of these are only useful for comparing two samples. For up to eight samples, the iTRAQ labeling technique can be used. For greater numbers of samples, the label-free method has been used, but this method was criticized for low reproducibility and accuracy. An ingenious strategy has been introduced, comparing each sample against a 18 O-labeled reference sample that was created by pooling equal amounts of all samples. However, it is necessary to use proportion-known protein mixtures to investigate and evaluate this new strategy. Another problem for comparative proteomics of multiple samples is the poor coincidence and reproducibility in protein identification results across samples. In present study, a method combining 18 O-reference strategy and a quantitation and identification-decoupled strategy was investigated with proportion-known protein mixtures. The results obviously demonstrated that the 18 O-reference strategy had greater accuracy and reliability than other previously used comparison methods based on transferring comparison or label-free strategies. By the decoupling strategy, the quantification data acquired by LC-MS and the identification data acquired by LC-MS/MS are matched and correlated to identify differential expressed proteins, according to retention time and accurate mass. This strategy made protein identification possible for all samples using a single pooled sample, and therefore gave a good reproducibility in protein identification across multiple samples, and allowed for optimizing peptide identification separately so as to identify more proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Comprehensive Analysis of Proteomic Differences between Escherichia coli K-12 and B Strains Using Multiplexed Isobaric Tandem Mass Tag (TMT) Labeling.

PubMed

Han, Mee-Jung

2017-11-28

The Escherichia coli K-12 and B strains are among the most frequently used bacterial hosts for scientific research and biotechnological applications. However, omics analyses have revealed that E. coli K-12 and B exhibit notably different genotypic and phenotypic attributes, even though they were derived from the same ancestor. In a previous study, we identified a limited number of proteins from the two strains using two-dimensional gel electrophoresis and tandem mass spectrometry (MS/MS). In this study, an in-depth analysis of the physiological behavior of the E. coli K-12 and B strains at the proteomic level was performed using six-plex isobaric tandem mass tag-based quantitative MS. Additionally, the best lysis buffer for increasing the efficiency of protein extraction was selected from three tested buffers prior to the quantitative proteomic analysis. This study identifies the largest number of proteins in the two E. coli strains reported to date and is the first to show the dynamics of these proteins. Notable differences in proteins associated with key cellular properties, including some metabolic pathways, the biosynthesis and degradation of amino acids, membrane integrity, cellular tolerance, and motility, were found between the two representative strains. Compared with previous studies, these proteomic results provide a more holistic view of the overall state of E. coli cells based on a single proteomic study and reveal significant insights into why the two strains show distinct phenotypes. Additionally, the resulting data provide in-depth information that will help fine-tune processes in the future.

Identification of head and neck squamous cell carcinoma biomarker candidates through proteomic analysis of cancer cell secretome.

PubMed

Marimuthu, Arivusudar; Chavan, Sandip; Sathe, Gajanan; Sahasrabuddhe, Nandini A; Srikanth, Srinivas M; Renuse, Santosh; Ahmad, Sartaj; Radhakrishnan, Aneesha; Barbhuiya, Mustafa A; Kumar, Rekha V; Harsha, H C; Sidransky, David; Califano, Joseph; Pandey, Akhilesh; Chatterjee, Aditi

2013-11-01

Protein biomarker discovery for early detection of head and neck squamous cell carcinoma (HNSCC) is a crucial unmet need to improve patient outcomes. Mass spectrometry-based proteomics has emerged as a promising tool for identification of biomarkers in different cancer types. Proteins secreted from cancer cells can serve as potential biomarkers for early diagnosis. In the current study, we have used isobaric tag for relative and absolute quantitation (iTRAQ) labeling methodology coupled with high resolution mass spectrometry to identify and quantitate secreted proteins from a panel of head and neck carcinoma cell lines. In all, we identified 2,472 proteins, of which 225 proteins were secreted at higher or lower abundance in HNSCC-derived cell lines. Of these, 148 were present in higher abundance and 77 were present in lower abundance in the cancer-cell derived secretome. We detected a higher abundance of some previously known markers for HNSCC including insulin like growth factor binding protein 3, IGFBP3 (11-fold) and opioid growth factor receptor, OGFR (10-fold) demonstrating the validity of our approach. We also identified several novel secreted proteins in HNSCC including olfactomedin-4, OLFM4 (12-fold) and hepatocyte growth factor activator, HGFA (5-fold). IHC-based validation was conducted in HNSCC using tissue microarrays which revealed overexpression of IGFBP3 and OLFM4 in 70% and 75% of the tested cases, respectively. Our study illustrates quantitative proteomics of secretome as a robust approach for identification of potential HNSCC biomarkers. This article is part of a Special Issue entitled: An Updated Secretome. Copyright © 2013 Elsevier B.V. All rights reserved.

A hot topic: the genetics of adaptation to geothermal vents in Mimulus guttatus.

PubMed

Ferris, Kathleen G

2016-11-01

Identifying the individual loci and mutations that underlie adaptation to extreme environments has long been a goal of evolutionary biology. However, finding the genes that underlie adaptive traits is difficult for several reasons. First, because many traits and genes evolve simultaneously as populations diverge, it is difficult to disentangle adaptation from neutral demographic processes. Second, finding the individual loci involved in any trait is challenging given the respective limitations of quantitative and population genetic methods. In this issue of Molecular Ecology, Hendrick et al. (2016) overcome these difficulties and determine the genetic basis of microgeographic adaptation between geothermal vent and nonthermal populations of Mimulus guttatus in Yellowstone National Park. The authors accomplish this by combining population and quantitative genetic techniques, a powerful, but labour-intensive, strategy for identifying individual causative adaptive loci that few studies have used (Stinchcombe & Hoekstra ). In a previous common garden experiment (Lekberg et al. 2012), thermal M. guttatus populations were found to differ from their closely related nonthermal neighbours in various adaptive phenotypes including trichome density. Hendrick et al. (2016) combine quantitative trait loci (QTL) mapping, population genomic scans for selection and admixture mapping to identify a single genetic locus underlying differences in trichome density between thermal and nonthermal M. guttatus. The candidate gene, R2R3 MYB, is homologous to genes involved in trichome development across flowering plants. The major trichome QTL, Tr14, is also involved in trichome density differences in an independent M. guttatus population comparison (Holeski et al. 2010) making this an example of parallel genetic evolution. © 2016 John Wiley & Sons Ltd.

Integrated genomic approaches to identification of candidate genes underlying metabolic and cardiovascular phenotypes in the spontaneously hypertensive rat.

PubMed

Morrissey, Catherine; Grieve, Ian C; Heinig, Matthias; Atanur, Santosh; Petretto, Enrico; Pravenec, Michal; Hubner, Norbert; Aitman, Timothy J

2011-11-07

The spontaneously hypertensive rat (SHR) is a widely used rodent model of hypertension and metabolic syndrome. Previously we identified thousands of cis-regulated expression quantitative trait loci (eQTLs) across multiple tissues using a panel of rat recombinant inbred (RI) strains derived from Brown Norway and SHR progenitors. These cis-eQTLs represent potential susceptibility loci underlying physiological and pathophysiological traits manifested in SHR. We have prioritized 60 cis-eQTLs and confirmed differential expression between the parental strains by quantitative PCR in 43 (72%) of the eQTL transcripts. Quantitative trait transcript (QTT) analysis in the RI strains showed highly significant correlation between cis-eQTL transcript abundance and clinically relevant traits such as systolic blood pressure and blood glucose, with the physical location of a subset of the cis-eQTLs colocalizing with "physiological" QTLs (pQTLs) for these same traits. These colocalizing correlated cis-eQTLs (c3-eQTLs) are highly attractive as primary susceptibility loci for the colocalizing pQTLs. Furthermore, sequence analysis of the c3-eQTL genes identified single nucleotide polymorphisms (SNPs) that are predicted to affect transcription factor binding affinity, splicing and protein function. These SNPs, which potentially alter transcript abundance and stability, represent strong candidate factors underlying not just eQTL expression phenotypes, but also the correlated metabolic and physiological traits. In conclusion, by integration of genomic sequence, eQTL and QTT datasets we have identified several genes that are strong positional candidates for pathophysiological traits observed in the SHR strain. These findings provide a basis for the functional testing and ultimate elucidation of the molecular basis of these metabolic and cardiovascular phenotypes.

Patterns of change: the dynamics of medicinal plant trade in far-western Nepal.

PubMed

Pyakurel, Dipesh; Sharma, Indira Bhattarai; Smith-Hall, Carsten

2018-06-06

Combined quantitative and qualitative environmental product trade studies, undertaken in the same location over time, are instrumental in identifying plant species with commercial demand and explaining what drives temporal changes. Yet such dynamic studies are rare, including for Himalayan medicinal plants that have been large-scale traded for millennia. To (i) investigate changes in medicinal plant trade in the past 17 years, and (ii) identify the main factors driving changes, using a study of Darchula District in far-western Nepal. Medicinal plant production network data were collected from March to August 2016, for the fiscal year 2014-15, for Darchula District in far-western Nepal through 167 quantitative (58 harvesters, 38 sub-local traders, 25 local traders, 25 central wholesalers, and 21 regional wholesalers), 61 qualitative (15 sub-local traders, 19 local traders, 15 central wholesalers, and 12 regional wholesalers) interviews, and four focus group discussions. Results were compared to previously unpublished similar data for Darchula District for the year 1997-98, using quantitative and qualitative interviews with 10 local traders, 20 central wholesalers, and 53 regional wholesalers. Data analysis was guided by an analytical framework derived from Global Production Network theory. Quantitative data were used to estimate changes in 12 indicators while the qualitative information allowed identification of the factors driving observed changes in the indicators. The volume of medicinal plants traded from Darchula District in the fiscal year 2014-15 was 401 t with a harvester value of USD 5.5 million, representing a 2.3 fold increase in volume and 17.2 fold increase in value compared to 1997-98. Trade in the two observation years comprised 30 air-dried plant products (from 28 identified species as well as lichens and a mineral substance); 12 products were traded in both periods, while seven disappeared, and 11 new products entered the trade. The number of traders increased from 10 to 63, mainly due to the emergence of a single high value product yarsagumba (Ophiocordyceps sinensis), a fungus-caterpillar complex which alone contributed 85% of total trade value. Over the observed time period, harvesters and traders increased their margins at the cost of central wholesalers, indicating that market changes favoured lower tier actors, eroding the previously identified passive central wholesaler oligopsony in Nepal. Important drivers of market changes are: (i) rising incomes in China and India, expressed through demand for new products and increasing per unit prices for a range of products, (ii) expanding infrastructure (roads and telecommunications) towards and into harvesting sites, reducing transport costs and increasing market efficiency, and (iii) government interventions, causing disappearance of some species from trade. These market changes also led to increased cultivation at lower altitudes, and a sharp increase in the number of processor industries in Nepal. Trade in medicinal plant products in far-western Nepal in the past two decades has increased substantially, doubling in volume and increasing 17 fold in value. There is a backbone of constantly traded species but also species that disappear from trade and new species that enter. Changes favour harvesters and traders at the benefit of central wholesalers whose previous passive oligopsony is disappearing. The three main drivers of change are rising incomes in China and India, expanding infrastructure, and government interventions in Nepal. Commercial medicinal plant resources are a substantial asset that appears to offer opportunities for economic development in far-western Nepal. The trade, however, may pose sustainability threats that are best understood by combining species-level biophysical, trade, and consumer studies. Copyright © 2018. Published by Elsevier B.V.

Mapping quantitative trait loci for yield, yield components and morphological traits in an advanced backcross population between Oryza rufipogon and the Oryza sativa cultivar Jefferson.

PubMed

Thomson, M J; Tai, T H; McClung, A M; Lai, X-H; Hinga, M E; Lobos, K B; Xu, Y; Martinez, C P; McCouch, S R

2003-08-01

An advanced backcross population between an accession of Oryza rufipogon (IRGC 105491) and the U.S. cultivar Jefferson (Oryza sativa ssp. japonica) was developed to identify quantitative trait loci (QTLs) for yield, yield components and morphological traits. The genetic linkage map generated for this population consisted of 153 SSR and RFLP markers with an average interval size of 10.3 cM. Thirteen traits were examined, nine of which were measured in multiple environments. Seventy-six QTLs above an experiment-wise significance threshold of P<0.01 (corresponding to an interval mapping LOD>3.6 or a composite interval mapping LOD>3.9) were identified. For the traits measured in multiple environments, 47% of the QTLs were detected in at least two environments. The O. rufipogon allele was favorable for 53% of the yield and yield component QTLs, including loci for yield, grains per panicle, panicle length, and grain weight. Morphological traits related to the domestication process and/or weedy characteristics, including plant height, shattering, tiller type and awns, were found clustered on chromosomes 1 and 4. Comparisons to previous studies involving wild x cultivated crosses revealed O. rufipogon alleles with stable effects in multiple genetic backgrounds and environments, several of which have not been detected in studies between Oryza sativa cultivars, indicating potentially novel alleles from O. rufipogon. Some O. rufipogon-derived QTLs, however, were in similar regions as previously reported QTLs from Oryza sativa cultivars, providing evidence for conservation of these QTLs across the Oryza genus. In addition, several QTLs for grain weight, plant height, and flowering time were localized to putative homeologous regions in maize where QTLs for these traits have been previously reported, supporting the hypothesis of functional conservation of QTLs across the grasses.

Quantitative proteomics of bronchoalveolar lavage fluid in lung adenocarcinoma.

PubMed

Almatroodi, Saleh A; McDonald, Christine F; Collins, Allison L; Darby, Ian A; Pouniotis, Dodie S

2015-01-01

The most commonly reported primary lung cancer subtype is adenocarcinoma, which is associated with a poor prognosis and short survival. Proteomic studies on human body fluids such as bronchoalveolar lavage fluid (BALF) have become essential methods for biomarker discovery, examination of tumor pathways and investigation of potential treatments. This study used quantitative proteomics to investigate the up-regulation of novel proteins in BALF from patients with primary lung adenocarcinoma in order to identify potential biomarkers. BALF samples from individuals with and without primary lung adenocarcinoma were analyzed using liquid chromatography-mass spectrometry. One thousand and one hundred proteins were identified, 33 of which were found to be consistently overexpressed in all lung adenocarcinoma samples compared to non-cancer controls. A number of overexpressed proteins have been previously shown to be related to lung cancer progression including S100-A8, annexin A1, annexin A2, thymidine phosphorylase and transglutaminase 2. The overexpression of a number of specific proteins in BALF from patients with primary lung adenocarcinoma may be used as a potential biomarker for lung adenocarcinoma. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Seniors' online communities: a quantitative content analysis.

PubMed

Nimrod, Galit

2010-06-01

To examine the contents and characteristics of seniors' online communities and to explore their potential benefits to older adults. Quantitative content analysis of a full year's data from 14 leading online communities using a novel computerized system. The overall database included 686,283 messages. There was a constant increase in the daily activity level during the research period. Content analysis identified 13 main subjects discussed in the communities, including (in descending order) "Fun on line," "Retirement," "Family," "Health," "Work and Study," "Recreation" "Finance," "Religion and Spirituality," "Technology," "Aging," "Civic and Social," "Shopping," and "Travels." The overall tone was somewhat more positive than negative. The findings suggest that the utilities of Information and Communications Technologies for older adults that were identified in previous research are valid for seniors' online communities as well. However, the findings suggest several other possible benefits, which may be available only to online communities. The communities may provide social support, contribute to self-preservation, and serve as an opportunity for self-discovery and growth. Because they offer both leisure activity and an expanded social network, it is suggested that active participation in the communities may contribute to the well-being of older adults. Directions for future research and applied implications are further discussed.

Statistical Evaluation of Causal Factors Associated with Astronaut Shoulder Injury in Space Suits.

PubMed

Anderson, Allison P; Newman, Dava J; Welsch, Roy E

2015-07-01

Shoulder injuries due to working inside the space suit are some of the most serious and debilitating injuries astronauts encounter. Space suit injuries occur primarily in the Neutral Buoyancy Laboratory (NBL) underwater training facility due to accumulated musculoskeletal stress. We quantitatively explored the underlying causal mechanisms of injury. Logistic regression was used to identify relevant space suit components, training environment variables, and anthropometric dimensions related to an increased propensity for space-suited injury. Two groups of subjects were analyzed: those whose reported shoulder incident is attributable to the NBL or working in the space suit, and those whose shoulder incidence began in active duty, meaning working in the suit could be a contributing factor. For both groups, percent of training performed in the space suit planar hard upper torso (HUT) was the most important predictor variable for injury. Frequency of training and recovery between training were also significant metrics. The most relevant anthropometric dimensions were bideltoid breadth, expanded chest depth, and shoulder circumference. Finally, record of previous injury was found to be a relevant predictor for subsequent injury. The first statistical model correctly identifies 39% of injured subjects, while the second model correctly identifies 68% of injured subjects. A review of the literature suggests this is the first work to quantitatively evaluate the hypothesized causal mechanisms of all space-suited shoulder injuries. Although limited in predictive capability, each of the identified variables can be monitored and modified operationally to reduce future impacts on an astronaut's health.

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment.

PubMed

Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d'Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

2016-01-01

The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS ≤ 2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment

PubMed Central

Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d’Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

2016-01-01

Introduction The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. Methods 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Results Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Conclusions Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size. PMID:26824672

Uncovering Global SUMOylation Signaling Networks in a Site-Specific Manner

PubMed Central

Hendriks, Ivo A.; D’Souza, Rochelle C.J.; Yang, Bing; Verlaan-de Vries, Matty; Mann, Matthias; Vertegaal, Alfred C.O.

2014-01-01

SUMOylation is a reversible post-translational modification essential for genome stability. Using high-resolution mass spectrometry, we have studied global SUMOylation in human cells and in a site-specific manner, identifying a total of over 4,300 SUMOylation sites in over 1,600 proteins. Moreover, for the first time in excess of 1,000 SUMOylation sites were identified under standard growth conditions. SUMOylation dynamics were quantitatively studied in response to SUMO protease inhibition, proteasome inhibition and heat shock. A considerable amount of SUMOylated lysines have previously been reported to be ubiquitylated, acetylated or methylated, indicating crosstalk between SUMO and other post-translational modifications. We identified 70 phosphorylation and 4 acetylation events in close proximity to SUMOylation sites, and provide evidence for acetylation-dependent SUMOylation of endogenous histone H3. SUMOylation regulates target proteins involved in all nuclear processes including transcription, DNA repair, chromatin remodeling, pre-mRNA splicing and ribosome assembly. PMID:25218447

Actinobaculum schaalii, a Common Uropathogen in Elderly Patients, Denmark

PubMed Central

Jensen, Anders; Hansen, Thomas M.; Søby, Karen M.; Prag, Jørgen

2010-01-01

Actinobaculum schaalii can cause urinary tract infections and septicemia but is difficult to identify by cultivation. To obtain a fast diagnosis and identify A. schaalii, we developed a TaqMan real-time quantitative PCR. Routine urine samples were obtained from 177 hospitalized patients and 75 outpatients in Viborg County, Denmark, in 2008–2009. The PCR detected A. schaalii in 22% of samples from patients >60 years of age. This assay showed that A. schaalii is more common than implied by routine cultivation. In 90% of PCR-positive urine samples, other common uropathogens were identified. This finding suggests that A. schaalii is a common, undetected, bacterial pathogen. Our results suggest that A. schaalii may be a more common pathogen than previously thought, especially in patients with unexplained chronic urinary tract infections, who are often treated with trimethoprim or ciprofloxacin, to which A. schaalii is resistant. PMID:20031046

Analyses of volatile organic compounds from human skin

PubMed Central

Gallagher, M.; Wysocki, C.J.; Leyden, J.J.; Spielman, A.I.; Sun, X.; Preti, G.

2008-01-01

Summary Background Human skin emits a variety of volatile metabolites, many of them odorous. Much previous work has focused upon chemical structure and biogenesis of metabolites produced in the axillae (underarms), which are a primary source of human body odour. Nonaxillary skin also harbours volatile metabolites, possibly with different biological origins than axillary odorants. Objectives To take inventory of the volatile organic compounds (VOCs) from the upper back and forearm skin, and assess their relative quantitative variation across 25 healthy subjects. Methods Two complementary sampling techniques were used to obtain comprehensive VOC profiles, viz., solid-phase micro extraction and solvent extraction. Analyses were performed using both gas chromatography/mass spectrometry and gas chromatography with flame photometric detection. Results Nearly 100 compounds were identified, some of which varied with age. The VOC profiles of the upper back and forearm within a subject were, for the most part, similar, although there were notable differences. Conclusions The natural variation in nonaxillary skin odorants described in this study provides a baseline of compounds we have identified from both endogenous and exogenous sources. Although complex, the profiles of volatile constituents suggest that the two body locations share a considerable number of compounds, but both quantitative and qualitative differences are present. In addition, quantitative changes due to ageing are also present. These data may provide future investigators of skin VOCs with a baseline against which any abnormalities can be viewed in searching for biomarkers of skin diseases. PMID:18637798

Buildings vs. ballistics: Quantifying the vulnerability of buildings to volcanic ballistic impacts using field studies and pneumatic cannon experiments

NASA Astrophysics Data System (ADS)

Williams, G. T.; Kennedy, B. M.; Wilson, T. M.; Fitzgerald, R. H.; Tsunematsu, K.; Teissier, A.

2017-09-01

Recent casualties in volcanic eruptions due to trauma from blocks and bombs necessitate more rigorous, ballistic specific risk assessment. Quantitative assessments are limited by a lack of experimental and field data on the vulnerability of buildings to ballistic hazards. An improved, quantitative understanding of building vulnerability to ballistic impacts is required for informing appropriate life safety actions and other risk reduction strategies. We assessed ballistic impacts to buildings from eruptions at Usu Volcano and Mt. Ontake in Japan and compiled available impact data from eruptions elsewhere to identify common damage patterns from ballistic impacts to buildings. We additionally completed a series of cannon experiments which simulate ballistic block impacts to building claddings to investigate their performance over a range of ballistic projectile velocities, masses and energies. Our experiments provide new insights by quantifying (1) the hazard associated with post-impact shrapnel from building and rock fragments; (2) the effect of impact obliquity on damage; and (3) the additional impact resistance buildings possess when claddings are struck in areas directly supported by framing components. This was not well identified in previous work which may have underestimated building vulnerability to ballistic hazards. To improve assessment of building vulnerability to ballistics, we use our experimental and field data to develop quantitative vulnerability models known as fragility functions. Our fragility functions and field studies show that although unreinforced buildings are highly vulnerable to large ballistics (> 20 cm diameter), they can still provide shelter, preventing death during eruptions.

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

PubMed

Yang, Wei; Kim, Yongsoo; Kim, Taek-Kyun; Keay, Susan K; Kim, Kwang Pyo; Steen, Hanno; Freeman, Michael R; Hwang, Daehee; Kim, Jayoung

2012-12-01

What's known on the subject? and What does the study add? Interstitial cystitis (IC) is a prevalent and debilitating pelvic disorder generally accompanied by chronic pain combined with chronic urinating problems. Over one million Americans are affected, especially middle-aged women. However, its aetiology or mechanism remains unclear. No efficient drug has been provided to patients. Several urinary biomarker candidates have been identified for IC; among the most promising is antiproliferative factor (APF), whose biological activity is detectable in urine specimens from >94% of patients with both ulcerative and non-ulcerative IC. The present study identified several important mediators of the effect of APF on bladder cell physiology, suggesting several candidate drug targets against IC. In an attempt to identify potential proteins and genes regulated by APF in vivo, and to possibly expand the APF-regulated network identified by stable isotope labelling by amino acids in cell culture (SILAC), we performed an integration analysis of our own SILAC data and the microarray data of Gamper et al. (2009) BMC Genomics 10: 199. Notably, two of the proteins (i.e. MAPKSP1 and GSPT1) that are down-regulated by APF are involved in the activation of mTORC1, suggesting that the mammalian target of rapamycin (mTOR) pathway is potentially a critical pathway regulated by APF in vivo. Several components of the mTOR pathway are currently being studied as potential therapeutic targets in other diseases. Our analysis suggests that this pathway might also be relevant in the design of diagnostic tools and medications targeting IC. • To enhance our understanding of the interstitial cystitis urine biomarker antiproliferative factor (APF), as well as interstitial cystitis biology more generally at the systems level, we reanalyzed recently published large-scale quantitative proteomics and in vivo transcriptomics data sets using an integration analysis tool that we have developed. • To identify more differentially expressed genes with a lower false discovery rate from a previously published microarray data set, an integrative hypothesis-testing statistical approach was applied. • For validation experiments, expression and phosphorylation levels of select proteins were evaluated by western blotting. • Integration analysis of this transcriptomics data set with our own quantitative proteomics data set identified 10 genes that are potentially regulated by APF in vivo from 4140 differentially expressed genes identified with a false discovery rate of 1%. • Of these, five (i.e. JUP, MAPKSP1, GSPT1, PTGS2/COX-2 and XPOT) were found to be prominent after network modelling of the common genes identified in the proteomics and microarray studies. • This molecular signature reflects the biological processes of cell adhesion, cell proliferation and inflammation, which is consistent with the known physiological effects of APF. • Lastly, we found the mammalian target of rapamycin pathway was down-regulated in response to APF. • This unbiased integration analysis of in vitro quantitative proteomics data with in vivo quantitative transcriptomics data led to the identification of potential downstream mediators of the APF signal transduction pathway. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

Influence of surfactant upon air entrainment hysteresis in curtain coating

NASA Astrophysics Data System (ADS)

Marston, J. O.; Hawkins, V.; Decent, S. P.; Simmons, M. J. H.

2009-03-01

The onset of air entrainment for curtain coating onto a pre-wetted substrate was studied experimentally in similar parameter regimes to commercial coating ( Re = ρ Q/μ = O(1), We = ρ Q u c /σ = O(10), Ca = μ U/σ = O(1)). Impingement speed and viscosity were previously shown to be critical parameters in correlating air entrainment data with three qualitatively different regimes of hydrodynamic assist identified (Marston et al. in Exp Fluids 42(3):483-488, 2007a). The interaction of the impinging curtain with the pre-existing film also led to a significant hysteretic effect throughout the flow rate-substrate speed parameter space. For the first time, results considering the influence of surfactants are presented in attempt to elucidate the relative importance of surface tension in this inertia-dominated system. The results show quantitative and qualitative differences to previous results with much more complex hysteretic behaviour which has only been reported previously for rough surfaces.

Essentiality, toxicity, and uncertainty in the risk assessment of manganese.

PubMed

Boyes, William K

2010-01-01

Risk assessments of manganese by inhalation or oral routes of exposure typically acknowledge the duality of manganese as an essential element at low doses and a toxic metal at high doses. Previously, however, risk assessors were unable to describe manganese pharmacokinetics quantitatively across dose levels and routes of exposure, to account for mass balance, and to incorporate this information into a quantitative risk assessment. In addition, the prior risk assessment of inhaled manganese conducted by the U.S. Environmental Protection Agency (EPA) identified a number of specific factors that contributed to uncertainty in the risk assessment. In response to a petition regarding the use of a fuel additive containing manganese, methylcyclopentadienyl manganese tricarbonyl (MMT), the U.S. EPA developed a test rule under the U.S. Clean Air Act that required, among other things, the generation of pharmacokinetic information. This information was intended not only to aid in the design of health outcome studies, but also to help address uncertainties in the risk assessment of manganese. To date, the work conducted in response to the test rule has yielded substantial pharmacokinetic data. This information will enable the generation of physiologically based pharmacokinetic (PBPK) models capable of making quantitative predictions of tissue manganese concentrations following inhalation and oral exposure, across dose levels, and accounting for factors such as duration of exposure, different species of manganese, and changes of age, gender, and reproductive status. The work accomplished in response to the test rule, in combination with other scientific evidence, will enable future manganese risk assessments to consider tissue dosimetry more comprehensively than was previously possible.

Determining Image Processing Features Describing the Appearance of Challenging Mitotic Figures and Miscounted Nonmitotic Objects

PubMed Central

Gandomkar, Ziba; Brennan, Patrick C.; Mello-Thoms, Claudia

2017-01-01

Context: Previous studies showed that the agreement among pathologists in recognition of mitoses in breast slides is fairly modest. Aims: Determining the significantly different quantitative features among easily identifiable mitoses, challenging mitoses, and miscounted nonmitoses within breast slides and identifying which color spaces capture the difference among groups better than others. Materials and Methods: The dataset contained 453 mitoses and 265 miscounted objects in breast slides. The mitoses were grouped into three categories based on the confidence degree of three pathologists who annotated them. The mitoses annotated as “probably a mitosis” by the majority of pathologists were considered as the challenging category. The miscounted objects were recognized as a mitosis or probably a mitosis by only one of the pathologists. The mitoses were segmented using k-means clustering, followed by morphological operations. Morphological, intensity-based, and textural features were extracted from the segmented area and also the image patch of 63 × 63 pixels in different channels of eight color spaces. Holistic features describing the mitoses' surrounding cells of each image were also extracted. Statistical Analysis Used: The Kruskal–Wallis H-test followed by the Tukey-Kramer test was used to identify significantly different features. Results: The results indicated that challenging mitoses were smaller and rounder compared to other mitoses. Among different features, the Gabor textural features differed more than others between challenging mitoses and the easily identifiable ones. Sizes of the non-mitoses were similar to easily identifiable mitoses, but nonmitoses were rounder. The intensity-based features from chromatin channels were the most discriminative features between the easily identifiable mitoses and the miscounted objects. Conclusions: Quantitative features can be used to describe the characteristics of challenging mitoses and miscounted nonmitotic objects. PMID:28966834

A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network

PubMed Central

Unnikrishnan, Ashwin; Guan, Yi F.; Huang, Yizhou; Beck, Dominik; Thoms, Julie A. I.; Peirs, Sofie; Knezevic, Kathy; Ma, Shiyong; de Walle, Inge V.; de Jong, Ineke; Ali, Zara; Zhong, Ling; Raftery, Mark J.; Taghon, Tom; Larsson, Jonas; MacKenzie, Karen L.; Van Vlierberghe, Pieter; Wong, Jason W. H.; Pimanda, John E.

2016-01-01

Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells. Using this approach, we identified a number of known binders of the +85 enhancer in leukaemic cells along with previously unknown binders, including ETV6 and IKZF1. We confirmed that ETV6 and IKZF1 were also bound at the +85 enhancer in both leukaemic cells and in healthy human CD34+ haematopoietic stem and progenitor cells. Knockdown experiments confirmed that ETV6 and IKZF1 are transcriptional regulators not just of ERG, but also of a number of genes regulated by a densely interconnected network of seven transcription factors. At last, we show that ETV6 and IKZF1 expression levels are positively correlated with expression of a number of heptad genes in AML and high expression of all nine genes confers poorer overall prognosis. PMID:27604872

Assessment of reference gene stability in Rice stripe virus and Rice black streaked dwarf virus infection rice by quantitative Real-time PCR.

PubMed

Fang, Peng; Lu, Rongfei; Sun, Feng; Lan, Ying; Shen, Wenbiao; Du, Linlin; Zhou, Yijun; Zhou, Tong

2015-10-24

Stably expressed reference gene(s) normalization is important for the understanding of gene expression patterns by quantitative Real-time PCR (RT-qPCR), particularly for Rice stripe virus (RSV) and Rice black streaked dwarf virus (RBSDV) that caused seriously damage on rice plants in China and Southeast Asia. The expression of fourteen common used reference genes of Oryza sativa L. were evaluated by RT-qPCR in RSV and RBSDV infected rice plants. Suitable normalization reference gene(s) were identified by geNorm and NormFinder algorithms. UBQ 10 + GAPDH and UBC + Actin1 were identified as suitable reference genes for RT-qPCR normalization under RSV and RBSDV infection, respectively. When using multiple reference genes, the expression patterns of OsPRIb and OsWRKY, two virus resistance genes, were approximately similar with that reported previously. Comparatively, by using single reference gene (TIP41-Like), a weaker inducible response was observed. We proposed that the combination of two reference genes could obtain more accurate and reliable normalization of RT-qPCR results in RSV- and RBSDV-infected plants. This work therefore sheds light on establishing a standardized RT-qPCR procedure in RSV- and RBSDV-infected rice plants, and might serve as an important point for discovering complex regulatory networks and identifying genes relevant to biological processes or implicated in virus.

Identification of a novel polymorphism in X-linked sterol-4-alpha-carboxylate 3-dehydrogenase (Nsdhl) associated with reduced high-density lipoprotein cholesterol levels in I/LnJ mice.

PubMed

Bautz, David J; Broman, Karl W; Threadgill, David W

2013-10-03

Loci controlling plasma lipid concentrations were identified by performing a quantitative trait locus analysis on genotypes from 233 mice from a F2 cross between KK/HlJ and I/LnJ, two strains known to differ in their high-density lipoprotein (HDL) cholesterol levels. When fed a standard diet, HDL cholesterol concentration was affected by two significant loci, the Apoa2 locus on Chromosome (Chr) 1 and a novel locus on Chr X, along with one suggestive locus on Chr 6. Non-HDL concentration also was affected by loci on Chr 1 and X along with a suggestive locus on Chr 3. Additional loci that may be sex-specific were identified for HDL cholesterol on Chr 2, 3, and 4 and for non-HDL cholesterol on Chr 5, 7, and 14. Further investigation into the potential causative gene on Chr X for reduced HDL cholesterol levels revealed a novel, I/LnJ-specific nonsynonymous polymorphism in Nsdhl, which codes for sterol-4-alpha-carboxylate 3-dehydrogenase in the cholesterol synthesis pathway. Although many lipid quantitative trait locus have been reported previously, these data suggest there are additional genes left to be identified that control lipid levels and that can provide new pharmaceutical targets.

Fluorescent Recovery after Photobleaching (FRAP) Analysis of Nuclear Export Rates Identifies Intrinsic Features of Nucleocytoplasmic Transport*

PubMed Central

Cardarelli, Francesco; Tosti, Luca; Serresi, Michela; Beltram, Fabio; Bizzarri, Ranieri

2012-01-01

A quantitative description of carrier-mediated nuclear export in live cells is presented. To this end, we fused a prototypical leucine-rich nuclear export signal (NES) to GFP as a cargo model and expressed the fluorescent chimera in live CHO-K1 cells. By modeling FRAP data, we calculate the NES affinity for the export machinery and the maximum rate of nuclear export achievable at saturation of endogenous carriers. The measured active-export time through the Nuclear Pore Complex (NPC) is 18 ms, remarkably similar to the previously determined active-import rate. Also, our results reveal that active export/import and active export/passive diffusion fluxes are uncoupled, thus complementing previous reports on active import/passive diffusion uncoupling. These findings suggest differential gating at the NPC level. PMID:22190681

Using Pictures to Assess Pain Location in Children.

PubMed

Mesko, Phyllis J; Eliades, Aris Beoglos

2018-06-01

This study uses the Pain Area Locator (PAL) tool, a picture communication aid with body and medical equipment icons, to identify pain location in postoperative pediatric patients and assesses discrepancies between nurses' pain location assessment and pain location identified using the PAL tool. This descriptive study used a quantitative, comparative design, with a convenience sample of pediatric postoperative patients undergoing same-day surgeries at a free-standing, acute care, Magnet designated pediatric hospital. The child's pain location was assessed by asking the child to point to one of the 12 pictures on the PAL tool of where they hurt. All 41 (100%) of the postoperative children in the study demonstrated ability to use the PAL tool. The child identified a pain location in 34 assessments (83%) when the nurse documented no pain location. This investigation expands on previous evidence supporting that children can use the PAL tool to identify the pain location postoperatively. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

A new three-locus model for rootstock-induced dwarfing in apple revealed by genetic mapping of root bark percentage

PubMed Central

Harrison, Nicola; Harrison, Richard J.; Barber-Perez, Nuria; Cascant-Lopez, Emma; Cobo-Medina, Magdalena; Lipska, Marzena; Conde-Ruíz, Rebeca; Brain, Philip; Gregory, Peter J.; Fernández-Fernández, Felicidad

2016-01-01

Rootstock-induced dwarfing of apple scions revolutionized global apple production during the twentieth century, leading to the development of modern intensive orchards. A high root bark percentage (the percentage of the whole root area constituted by root cortex) has previously been associated with rootstock-induced dwarfing in apple. In this study, the root bark percentage was measured in a full-sib family of ungrafted apple rootstocks and found to be under the control of three loci. Two quantitative trait loci (QTLs) for root bark percentage were found to co-localize to the same genomic regions on chromosome 5 and chromosome 11 previously identified as controlling dwarfing, Dw1 and Dw2, respectively. A third QTL was identified on chromosome 13 in a region that has not been previously associated with dwarfing. The development of closely linked sequence-tagged site markers improved the resolution of allelic classes, thereby allowing the detection of dominance and epistatic interactions between loci, with high root bark percentage only occurring in specific allelic combinations. In addition, we report a significant negative correlation between root bark percentage and stem diameter (an indicator of tree vigour), measured on a clonally propagated grafted subset of the mapping population. The demonstrated link between root bark percentage and rootstock-induced dwarfing of the scion leads us to propose a three-locus model that is able to explain levels of dwarfing from the dwarf ‘M.27’ to the semi-invigorating rootstock ‘M.116’. Moreover, we suggest that the QTL on chromosome 13 (Rb3) might be analogous to a third dwarfing QTL, Dw3, which has not previously been identified. PMID:26826217

Identification of TOEFAZ1-interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis.

PubMed

Hilton, Nicholas A; Sladewski, Thomas E; Perry, Jenna A; Pataki, Zemplen; Sinclair-Davis, Amy N; Muniz, Richard S; Tran, Holly L; Wurster, Jenna I; Seo, Jiwon; de Graffenried, Christopher L

2018-05-21

The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly-polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely-configured process in kinetoplastids. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

Replication of long-bone length QTL in the F9-F10 LG,SM advanced intercross.

PubMed

Norgard, Elizabeth A; Jarvis, Joseph P; Roseman, Charles C; Maxwell, Taylor J; Kenney-Hunt, Jane P; Samocha, Kaitlin E; Pletscher, L Susan; Wang, Bing; Fawcett, Gloria L; Leatherwood, Christopher J; Wolf, Jason B; Cheverud, James M

2009-04-01

Quantitative trait locus (QTL) mapping techniques are frequently used to identify genomic regions associated with variation in phenotypes of interest. However, the F(2) intercross and congenic strain populations usually employed have limited genetic resolution resulting in relatively large confidence intervals that greatly inhibit functional confirmation of statistical results. Here we use the increased resolution of the combined F(9) and F(10) generations (n = 1455) of the LG,SM advanced intercross to fine-map previously identified QTL associated with the lengths of the humerus, ulna, femur, and tibia. We detected 81 QTL affecting long-bone lengths. Of these, 49 were previously identified in the combined F(2)-F(3) population of this intercross, while 32 represent novel contributors to trait variance. Pleiotropy analysis suggests that most QTL affect three to four long bones or serially homologous limb segments. We also identified 72 epistatic interactions involving 38 QTL and 88 novel regions. This analysis shows that using later generations of an advanced intercross greatly facilitates fine-mapping of confidence intervals, resolving three F(2)-F(3) QTL into multiple linked loci and narrowing confidence intervals of other loci, as well as allowing identification of additional QTL. Further characterization of the biological bases of these QTL will help provide a better understanding of the genetics of small variations in long-bone length.

A new approach to hazardous materials transportation risk analysis: decision modeling to identify critical variables.

PubMed

Clark, Renee M; Besterfield-Sacre, Mary E

2009-03-01

We take a novel approach to analyzing hazardous materials transportation risk in this research. Previous studies analyzed this risk from an operations research (OR) or quantitative risk assessment (QRA) perspective by minimizing or calculating risk along a transport route. Further, even though the majority of incidents occur when containers are unloaded, the research has not focused on transportation-related activities, including container loading and unloading. In this work, we developed a decision model of a hazardous materials release during unloading using actual data and an exploratory data modeling approach. Previous studies have had a theoretical perspective in terms of identifying and advancing the key variables related to this risk, and there has not been a focus on probability and statistics-based approaches for doing this. Our decision model empirically identifies the critical variables using an exploratory methodology for a large, highly categorical database involving latent class analysis (LCA), loglinear modeling, and Bayesian networking. Our model identified the most influential variables and countermeasures for two consequences of a hazmat incident, dollar loss and release quantity, and is one of the first models to do this. The most influential variables were found to be related to the failure of the container. In addition to analyzing hazmat risk, our methodology can be used to develop data-driven models for strategic decision making in other domains involving risk.

75 FR 54117 - Building Energy Standards Program: Preliminary Determination Regarding Energy Efficiency...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

... Response to Comments on Previous Analysis C. Summary of the Comparative Analysis 1. Quantitative Analysis 2... preliminary quantitative analysis are specific building designs, in most cases with specific spaces defined... preliminary determination. C. Summary of the Comparative Analysis DOE carried out both a broad quantitative...

Quantitative trait loci (QTLs) for water use and crop production traits co-locate with major QTL for tolerance to water deficit in a fine-mapping population of pearl millet (Pennisetum glaucum L. R.Br.).

PubMed

Tharanya, Murugesan; Kholova, Jana; Sivasakthi, Kaliamoorthy; Seghal, Deepmala; Hash, Charles Tom; Raj, Basker; Srivastava, Rakesh Kumar; Baddam, Rekha; Thirunalasundari, Thiyagarajan; Yadav, Rattan; Vadez, Vincent

2018-04-21

Four genetic regions associated with water use traits, measured at different levels of plant organization, and with agronomic traits were identified within a previously reported region for terminal water deficit adaptation on linkage group 2. Close linkages between these traits showed the value of phenotyping both for agronomic and secondary traits to better understand plant productive processes. Water saving traits are critical for water stress adaptation of pearl millet, whereas maximizing water use is key to the absence of stress. This research aimed at demonstrating the close relationship between traits measured at different levels of plant organization, some putatively involved in water stress adaptation, and those responsible for agronomic performance. A fine-mapping population of pearl millet, segregating for a previously identified quantitative trait locus (QTL) for adaptation to terminal drought stress on LG02, was phenotyped for traits at different levels of plant organization in different experimental environments (pot culture, high-throughput phenotyping platform, lysimeters, and field). The linkages among traits across the experimental systems were analysed using principal component analysis and QTL co-localization approach. Four regions within the LG02-QTL were found and revealed substantial co-mapping of water use and agronomic traits. These regions, identified across experimental systems, provided genetic evidence of the tight linkages between traits phenotyped at a lower level of plant organization and agronomic traits assessed in the field, therefore deepening our understanding of complex traits and then benefiting both geneticists and breeders. In short: (1) under no/mild stress conditions, increasing biomass and tiller production increased water use and eventually yield; (2) under severe stress conditions, water savings at vegetative stage, from lower plant vigour and fewer tillers in that population, led to more water available during grain filling, expression of stay-green phenotypes, and higher yield.

Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies.

PubMed

Hedman, Åsa K; Mendelson, Michael M; Marioni, Riccardo E; Gustafsson, Stefan; Joehanes, Roby; Irvin, Marguerite R; Zhi, Degui; Sandling, Johanna K; Yao, Chen; Liu, Chunyu; Liang, Liming; Huan, Tianxiao; McRae, Allan F; Demissie, Serkalem; Shah, Sonia; Starr, John M; Cupples, L Adrienne; Deloukas, Panos; Spector, Timothy D; Sundström, Johan; Krauss, Ronald M; Arnett, Donna K; Deary, Ian J; Lind, Lars; Levy, Daniel; Ingelsson, Erik

2017-01-01

Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage ( P <1.08E-07) and replicated 33 (at Bonferroni-corrected P <0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglycerides and high-density lipoprotein cholesterol (HDL-C; cg27243685; P =8.1E-26 and 9.3E-19) was associated with cis -expression of a reverse cholesterol transporter ( ABCG1; P =7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P =0.0007). We found significant cis -methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels ( P TC =0.004, P HDL-C =0.008 and P triglycerides =0.00003) and coronary heart disease ( P =0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis -methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events. © 2017 The Authors.

Quantitative phosphoproteomics using acetone-based peptide labeling: Method evaluation and application to a cardiac ischemia/reperfusion model

PubMed Central

Wijeratne, Aruna B.; Manning, Janet R.; Schultz, Jo El J.; Greis, Kenneth D.

2013-01-01

Mass spectrometry (MS) techniques to globally profile protein phosphorylation in cellular systems that are relevant to physiological or pathological changes have been of significant interest in biological research. In this report, an MS-based strategy utilizing an inexpensive acetone-based peptide labeling technique known as reductive alkylation by acetone (RABA) for quantitative phosphoproteomics was explored to evaluate its capacity. Since the chemistry for RABA-labeling for phosphorylation profiling had not been previously reported, it was first validated using a standard phosphoprotein and identical phosphoproteomes from cardiac tissue extracts. A workflow was then utilized to compare cardiac tissue phosphoproteomes from mouse hearts not expressing FGF2 vs. hearts expressing low molecular weight fibroblast growth factor-2 (LMW FGF2) to relate low molecular weight fibroblast growth factor-2 (LMW FGF2) mediated cardioprotective phenomena induced by ischemia/reperfusion (I/R) injury of hearts, with downstream phosphorylation changes in LMW FGF2 signaling cascades. Statistically significant phosphorylation changes were identified at 14 different sites on 10 distinct proteins including some with mechanisms already established for LMW FGF2-mediated cardioprotective signaling (e.g. connexin-43), some with new details linking LMW FGF2 to the cardioprotective mechanisms (e.g. cardiac myosin binding protein C or cMyBPC), and also several new downstream effectors not previously recognized for cardio-protective signaling by LMW FGF2. Additionally, one of the phosphopeptides, cMyBPC/pSer-282, identified was further verified with site-specific quantification using an SRM (selected reaction monitoring)-based approach that also relies on isotope labeling of a synthetic phosphopeptide with deuterated acetone as an internal standard. Overall, this study confirms that the inexpensive acetone-based peptide labeling can be used in both exploratory and targeted quantification phosphoproteomic studies to identify and verify biologically-relevant phosphorylation changes in whole tissues. PMID:24016359

Expression quantitative trait loci (eQTL) mapping in Puerto Rican children.

PubMed

Chen, Wei; Brehm, John M; Lin, Jerome; Wang, Ting; Forno, Erick; Acosta-Pérez, Edna; Boutaoui, Nadia; Canino, Glorisa; Celedón, Juan C

2015-01-01

Expression quantitative trait loci (eQTL) have been identified using tissue or cell samples from diverse human populations, thus enhancing our understanding of regulation of gene expression. However, few studies have attempted to identify eQTL in racially admixed populations such as Hispanics. We performed a systematic eQTL study to identify regulatory variants of gene expression in whole blood from 121 Puerto Rican children with (n = 63) and without (n = 58) asthma. Genome-wide genotyping was conducted using the Illumina Omni2.5M Bead Chip, and gene expression was assessed using the Illumina HT-12 microarray. After completing quality control, we performed a pair-wise genome analysis of ~15 K transcripts and ~1.3 M SNPs for both local and distal effects. This analysis was conducted under a regression framework adjusting for age, gender and principal components derived from both genotypic and mRNA data. We used a false discovery rate (FDR) approach to identify significant eQTL signals, which were next compared to top eQTL signals from existing eQTL databases. We then performed a pathway analysis for our top genes. We identified 36,720 local pairs in 3,391 unique genes and 1,851 distal pairs in 446 unique genes at FDR <0.05, corresponding to unadjusted P values lower than 1.5x10-4 and 4.5x10-9, respectively. A significant proportion of genes identified in our study overlapped with those identified in previous studies. We also found an enrichment of disease-related genes in our eQTL list. We present results from the first eQTL study in Puerto Rican children, who are members of a unique Hispanic cohort disproportionately affected with asthma, prematurity, obesity and other common diseases. Our study confirmed eQTL signals identified in other ethnic groups, while also detecting additional eQTLs unique to our study population. The identified eQTLs will help prioritize findings from future genome-wide association studies in Puerto Ricans.

Genetic variation affecting host-parasite interactions: major-effect quantitative trait loci affect the transmission of sigma virus in Drosophila melanogaster.

PubMed

Bangham, Jenny; Knott, Sara A; Kim, Kang-Wook; Young, Robert S; Jiggins, Francis M

2008-09-01

In natural populations, genetic variation affects resistance to disease. Whether that genetic variation comprises lots of small-effect polymorphisms or a small number of large-effect polymorphisms has implications for adaptation, selection and how genetic variation is maintained in populations. Furthermore, how much genetic variation there is, and the genes that underlie this variation, affects models of co-evolution between parasites and their hosts. We are studying the genetic variation that affects the resistance of Drosophila melanogaster to its natural pathogen--the vertically transmitted sigma virus. We have carried out three separate quantitative trait locus mapping analyses to map gene variants on the second chromosome that cause variation in the rate at which males transmit the infection to their offspring. All three crosses identified a locus in a similar chromosomal location that causes a large drop in the rate at which the virus is transmitted. We also found evidence for an additional smaller-effect quantitative trait locus elsewhere on the chromosome. Our data, together with previous experiments on the sigma virus and parasitoid wasps, indicate that the resistance of D. melanogaster to co-evolved pathogens is controlled by a limited number of major-effect polymorphisms.

Quantifying cryptic Symbiodinium diversity within Orbicella faveolata and Orbicella franksi at the Flower Garden Banks, Gulf of Mexico

PubMed Central

Green, Elizabeth A.; Davies, Sarah W.; Matz, Mikhail V.

2014-01-01

The genetic composition of the resident Symbiodinium endosymbionts can strongly modulate the physiological performance of reef-building corals. Here, we used quantitative metabarcoding to investigate Symbiodinium genetic diversity in two species of mountainous star corals, Orbicella franksi and Orbicella faveolata, from two reefs separated by 19 km of deep water. We aimed to determine if the frequency of different symbiont genotypes varied with respect to coral host species or geographic location. Our results demonstrate that across the two reefs both coral species contained seven haplotypes of Symbiodinium, all identifiable as clade B and most closely related to type B1. Five of these haplotypes have not been previously described and may be endemic to the Flower Garden Banks. No significant differences in symbiont composition were detected between the two coral species. However, significant quantitative differences were detected between the east and west banks for three background haplotypes comprising 0.1%–10% of the total. The quantitative metabarcoding approach described here can help to sensitively characterize cryptic genetic diversity of Symbiodinium and potentially contribute to the understanding of physiological variations among coral populations. PMID:24883247

Use of a Deuterated Internal Standard with Pyrolysis-GC/MS Dimeric Marker Analysis to Quantify Tire Tread Particles in the Environment

PubMed Central

Unice, Kenneth M.; Kreider, Marisa L.; Panko, Julie M.

2012-01-01

Pyrolysis(pyr)-GC/MS analysis of characteristic thermal decomposition fragments has been previously used for qualitative fingerprinting of organic sources in environmental samples. A quantitative pyr-GC/MS method based on characteristic tire polymer pyrolysis products was developed for tread particle quantification in environmental matrices including soil, sediment, and air. The feasibility of quantitative pyr-GC/MS analysis of tread was confirmed in a method evaluation study using artificial soil spiked with known amounts of cryogenically generated tread. Tread concentration determined by blinded analyses was highly correlated (r2 ≥ 0.88) with the known tread spike concentration. Two critical refinements to the initial pyrolysis protocol were identified including use of an internal standard and quantification by the dimeric markers vinylcyclohexene and dipentene, which have good specificity for rubber polymer with no other appreciable environmental sources. A novel use of deuterated internal standards of similar polymeric structure was developed to correct the variable analyte recovery caused by sample size, matrix effects, and ion source variability. The resultant quantitative pyr-GC/MS protocol is reliable and transferable between laboratories. PMID:23202830

Quantifying cryptic Symbiodinium diversity within Orbicella faveolata and Orbicella franksi at the Flower Garden Banks, Gulf of Mexico.

PubMed

Green, Elizabeth A; Davies, Sarah W; Matz, Mikhail V; Medina, Mónica

2014-01-01

The genetic composition of the resident Symbiodinium endosymbionts can strongly modulate the physiological performance of reef-building corals. Here, we used quantitative metabarcoding to investigate Symbiodinium genetic diversity in two species of mountainous star corals, Orbicella franksi and Orbicella faveolata, from two reefs separated by 19 km of deep water. We aimed to determine if the frequency of different symbiont genotypes varied with respect to coral host species or geographic location. Our results demonstrate that across the two reefs both coral species contained seven haplotypes of Symbiodinium, all identifiable as clade B and most closely related to type B1. Five of these haplotypes have not been previously described and may be endemic to the Flower Garden Banks. No significant differences in symbiont composition were detected between the two coral species. However, significant quantitative differences were detected between the east and west banks for three background haplotypes comprising 0.1%-10% of the total. The quantitative metabarcoding approach described here can help to sensitively characterize cryptic genetic diversity of Symbiodinium and potentially contribute to the understanding of physiological variations among coral populations.

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs

PubMed Central

Jima, Dereje D.; Zhang, Jenny; Jacobs, Cassandra; Richards, Kristy L.; Dunphy, Cherie H.; Choi, William W. L.; Yan Au, Wing; Srivastava, Gopesh; Czader, Magdalena B.; Rizzieri, David A.; Lagoo, Anand S.; Lugar, Patricia L.; Mann, Karen P.; Flowers, Christopher R.; Bernal-Mizrachi, Leon; Naresh, Kikkeri N.; Evens, Andrew M.; Gordon, Leo I.; Luftig, Micah; Friedman, Daphne R.; Weinberg, J. Brice; Thompson, Michael A.; Gill, Javed I.; Liu, Qingquan; How, Tam; Grubor, Vladimir; Gao, Yuan; Patel, Amee; Wu, Han; Zhu, Jun; Blobe, Gerard C.; Lipsky, Peter E.; Chadburn, Amy

2010-01-01

A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions. PMID:20733160

ATG18 and FAB1 are involved in dehydration stress tolerance in Saccharomyces cerevisiae.

PubMed

López-Martínez, Gema; Margalef-Català, Mar; Salinas, Francisco; Liti, Gianni; Cordero-Otero, Ricardo

2015-01-01

Recently, different dehydration-based technologies have been evaluated for the purpose of cell and tissue preservation. Although some early results have been promising, they have not satisfied the requirements for large-scale applications. The long experience of using quantitative trait loci (QTLs) with the yeast Saccharomyces cerevisiae has proven to be a good model organism for studying the link between complex phenotypes and DNA variations. Here, we use QTL analysis as a tool for identifying the specific yeast traits involved in dehydration stress tolerance. Three hybrids obtained from stable haploids and sequenced in the Saccharomyces Genome Resequencing Project showed intermediate dehydration tolerance in most cases. The dehydration resistance trait of 96 segregants from each hybrid was quantified. A smooth, continuous distribution of the anhydrobiosis tolerance trait was found, suggesting that this trait is determined by multiple QTLs. Therefore, we carried out a QTL analysis to identify the determinants of this dehydration tolerance trait at the genomic level. Among the genes identified after reciprocal hemizygosity assays, RSM22, ATG18 and DBR1 had not been referenced in previous studies. We report new phenotypes for these genes using a previously validated test. Finally, our data illustrates the power of this approach in the investigation of the complex cell dehydration phenotype.

ATG18 and FAB1 Are Involved in Dehydration Stress Tolerance in Saccharomyces cerevisiae

PubMed Central

López-Martínez, Gema; Margalef-Català, Mar; Salinas, Francisco; Liti, Gianni; Cordero-Otero, Ricardo

2015-01-01

Recently, different dehydration-based technologies have been evaluated for the purpose of cell and tissue preservation. Although some early results have been promising, they have not satisfied the requirements for large-scale applications. The long experience of using quantitative trait loci (QTLs) with the yeast Saccharomyces cerevisiae has proven to be a good model organism for studying the link between complex phenotypes and DNA variations. Here, we use QTL analysis as a tool for identifying the specific yeast traits involved in dehydration stress tolerance. Three hybrids obtained from stable haploids and sequenced in the Saccharomyces Genome Resequencing Project showed intermediate dehydration tolerance in most cases. The dehydration resistance trait of 96 segregants from each hybrid was quantified. A smooth, continuous distribution of the anhydrobiosis tolerance trait was found, suggesting that this trait is determined by multiple QTLs. Therefore, we carried out a QTL analysis to identify the determinants of this dehydration tolerance trait at the genomic level. Among the genes identified after reciprocal hemizygosity assays, RSM22, ATG18 and DBR1 had not been referenced in previous studies. We report new phenotypes for these genes using a previously validated test. Finally, our data illustrates the power of this approach in the investigation of the complex cell dehydration phenotype. PMID:25803831

Quantitative background parenchymal uptake on molecular breast imaging and breast cancer risk: a case-control study.

PubMed

Hruska, Carrie B; Geske, Jennifer R; Swanson, Tiffinee N; Mammel, Alyssa N; Lake, David S; Manduca, Armando; Conners, Amy Lynn; Whaley, Dana H; Scott, Christopher G; Carter, Rickey E; Rhodes, Deborah J; O'Connor, Michael K; Vachon, Celine M

2018-06-05

Background parenchymal uptake (BPU), which refers to the level of Tc-99m sestamibi uptake within normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor, independent of mammographic density. Prior analyses have used subjective categories to describe BPU. We evaluate a new quantitative method for assessing BPU by testing its reproducibility, comparing quantitative results with previously established subjective BPU categories, and determining the association of quantitative BPU with breast cancer risk. Two nonradiologist operators independently performed region-of-interest analysis on MBI images viewed in conjunction with corresponding digital mammograms. Quantitative BPU was defined as a unitless ratio of the average pixel intensity (counts/pixel) within the fibroglandular tissue versus the average pixel intensity in fat. Operator agreement and the correlation of quantitative BPU measures with subjective BPU categories assessed by expert radiologists were determined. Percent density on mammograms was estimated using Cumulus. The association of quantitative BPU with breast cancer (per one unit BPU) was examined within an established case-control study of 62 incident breast cancer cases and 177 matched controls. Quantitative BPU ranged from 0.4 to 3.2 across all subjects and was on average higher in cases compared to controls (1.4 versus 1.2, p < 0.007 for both operators). Quantitative BPU was strongly correlated with subjective BPU categories (Spearman's r = 0.59 to 0.69, p < 0.0001, for each paired combination of two operators and two radiologists). Interoperator and intraoperator agreement in the quantitative BPU measure, assessed by intraclass correlation, was 0.92 and 0.98, respectively. Quantitative BPU measures showed either no correlation or weak negative correlation with mammographic percent density. In a model adjusted for body mass index and percent density, higher quantitative BPU was associated with increased risk of breast cancer for both operators (OR = 4.0, 95% confidence interval (CI) 1.6-10.1, and 2.4, 95% CI 1.2-4.7). Quantitative measurement of BPU, defined as the ratio of average counts in fibroglandular tissue relative to that in fat, can be reliably performed by nonradiologist operators with a simple region-of-interest analysis tool. Similar to results obtained with subjective BPU categories, quantitative BPU is a functional imaging biomarker of breast cancer risk, independent of mammographic density and hormonal factors.

Identification of genotoxic compounds using isogenic DNA repair deficient DT40 cell lines on a quantitative high throughput screening platform

PubMed Central

Nishihara, Kana; Huang, Ruili; Zhao, Jinghua; Shahane, Sampada A.; Witt, Kristine L.; Smith-Roe, Stephanie L.; Tice, Raymond R.; Takeda, Shunichi; Xia, Menghang

2016-01-01

DNA repair pathways play a critical role in maintaining cellular homeostasis by repairing DNA damage induced by endogenous processes and xenobiotics, including environmental chemicals. Induction of DNA damage may lead to genomic instability, disruption of cellular homeostasis and potentially tumours. Isogenic chicken DT40 B-lymphocyte cell lines deficient in DNA repair pathways can be used to identify genotoxic compounds and aid in characterising the nature of the induced DNA damage. As part of the US Tox21 program, we previously optimised several different DT40 isogenic clones on a high-throughput screening platform and confirmed the utility of this approach for detecting genotoxicants by measuring differential cytotoxicity in wild-type and DNA repair-deficient clones following chemical exposure. In the study reported here, we screened the Tox21 10K compound library against two isogenic DNA repair-deficient DT40 cell lines (KU70 −/−/RAD54 −/− and REV3 −/−) and the wild-type cell line using a cell viability assay that measures intracellular adenosine triphosphate levels. KU70 and RAD54 are genes associated with DNA double-strand break repair processes, and REV3 is associated with translesion DNA synthesis pathways. Active compounds identified in the primary screening included many well-known genotoxicants (e.g. adriamycin, melphalan) and several compounds previously untested for genotoxicity. A subset of compounds was further evaluated by assessing their ability to induce micronuclei and phosphorylated H2AX. Using this comprehensive approach, three compounds with previously undefined genotoxicity—2-oxiranemethanamine, AD-67 and tetraphenylolethane glycidyl ether—were identified as genotoxic. These results demonstrate the utility of this approach for identifying and prioritising compounds that may damage DNA. PMID:26243743

Shedding quantitative fluorescence light on novel regulatory mechanisms in skeletal biomedicine and biodentistry.

PubMed

Lee, Ji-Won; Iimura, Tadahiro

2017-02-01

Digitalized fluorescence images contain numerical information such as color (wavelength), fluorescence intensity and spatial position. However, quantitative analyses of acquired data and their validation remained to be established. Our research group has applied quantitative fluorescence imaging on tissue sections and uncovered novel findings in skeletal biomedicine and biodentistry. This review paper includes a brief background of quantitative fluorescence imaging and discusses practical applications by introducing our previous research. Finally, the future perspectives of quantitative fluorescence imaging are discussed.

Delayed Psychological Morbidity Associated with Snakebite Envenoming

PubMed Central

Williams, Shehan S.; Wijesinghe, Chamara A.; Jayamanne, Shaluka F.; Buckley, Nicholas A.; Dawson, Andrew H.; Lalloo, David G.; de Silva, H. Janaka

2011-01-01

Introduction The psychological impact of snakebite on its victims, especially possible late effects, has not been systematically studied. Objectives To assess delayed somatic symptoms, depressive disorder, post-traumatic stress disorder (PTSD), and impairment in functioning, among snakebite victims. Methods The study had qualitative and quantitative arms. In the quantitative arm, 88 persons who had systemic envenoming following snakebite from the North Central Province of Sri Lanka were randomly identified from an established research database and interviewed 12 to 48 months (mean 30) after the incident. Persons with no history of snakebite, matched for age, sex, geograpical location and occupation, acted as controls. A modified version of the Beck Depression Inventory, Post-Traumatic Stress Symptom Scale, Hopkins Somatic Symptoms Checklist, Sheehan Disability Inventory and a structured questionnaire were administered. In the qualitative arm, focus group discussions among snakebite victims explored common somatic symptoms attributed to envenoming. Results Previous snakebite victims (cases) had more symptoms than controls as measured by the modified Beck Depression Scale (mean 19.1 Vs 14.4; p<0.001) and Hopkins Symptoms Checklist (38.9 vs. 28.2; p<0.001). 48 (54%) cases met criteria for depressive disorder compared to 13 (15%) controls. 19 (21.6%) cases also met criteria for PTSD. 24 (27%) claimed that the snakebite caused a negative change in their employment; nine (10.2%) had stopped working and 15 (17%) claimed residual physical disability. The themes identified in the qualitative arm included blindness, tooth decay, body aches, headaches, tiredness and weakness. Conclusions Snakebite causes significant ongoing psychological morbidity, a complication not previously documented. The economic and social impacts of this problem need further investigation. PMID:21829741

Similar Genetic Architecture with Shared and Unique Quantitative Trait Loci for Bacterial Cold Water Disease Resistance in Two Rainbow Trout Breeding Populations

PubMed Central

Vallejo, Roger L.; Liu, Sixin; Gao, Guangtu; Fragomeni, Breno O.; Hernandez, Alvaro G.; Leeds, Timothy D.; Parsons, James E.; Martin, Kyle E.; Evenhuis, Jason P.; Welch, Timothy J.; Wiens, Gregory D.; Palti, Yniv

2017-01-01

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect quantitative trait loci (QTL) for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a 57 K SNP array and a reference genome assembly have enabled us to conduct genome-wide association studies (GWAS) that overcome several experimental limitations from our previous work. In the current study, we conducted GWAS for BCWD resistance in two rainbow trout breeding populations using two genotyping platforms, the 57 K Affymetrix SNP array and restriction-associated DNA (RAD) sequencing. Overall, we identified 14 moderate-large effect QTL that explained up to 60.8% of the genetic variance in one of the two populations and 27.7% in the other. Four of these QTL were found in both populations explaining a substantial proportion of the variance, although major differences were also detected between the two populations. Our results confirm that BCWD resistance is controlled by the oligogenic inheritance of few moderate-large effect loci and a large-unknown number of loci each having a small effect on BCWD resistance. We detected differences in QTL number and genome location between two GWAS models (weighted single-step GBLUP and Bayes B), which highlights the utility of using different models to uncover QTL. The RAD-SNPs detected a greater number of QTL than the 57 K SNP array in one population, suggesting that the RAD-SNPs may uncover polymorphisms that are more unique and informative for the specific population in which they were discovered. PMID:29109734

Similar Genetic Architecture with Shared and Unique Quantitative Trait Loci for Bacterial Cold Water Disease Resistance in Two Rainbow Trout Breeding Populations.

PubMed

Vallejo, Roger L; Liu, Sixin; Gao, Guangtu; Fragomeni, Breno O; Hernandez, Alvaro G; Leeds, Timothy D; Parsons, James E; Martin, Kyle E; Evenhuis, Jason P; Welch, Timothy J; Wiens, Gregory D; Palti, Yniv

2017-01-01

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonid aquaculture. In previous studies, we identified moderate-large effect quantitative trait loci (QTL) for BCWD resistance in rainbow trout ( Oncorhynchus mykiss ). However, the recent availability of a 57 K SNP array and a reference genome assembly have enabled us to conduct genome-wide association studies (GWAS) that overcome several experimental limitations from our previous work. In the current study, we conducted GWAS for BCWD resistance in two rainbow trout breeding populations using two genotyping platforms, the 57 K Affymetrix SNP array and restriction-associated DNA (RAD) sequencing. Overall, we identified 14 moderate-large effect QTL that explained up to 60.8% of the genetic variance in one of the two populations and 27.7% in the other. Four of these QTL were found in both populations explaining a substantial proportion of the variance, although major differences were also detected between the two populations. Our results confirm that BCWD resistance is controlled by the oligogenic inheritance of few moderate-large effect loci and a large-unknown number of loci each having a small effect on BCWD resistance. We detected differences in QTL number and genome location between two GWAS models (weighted single-step GBLUP and Bayes B), which highlights the utility of using different models to uncover QTL. The RAD-SNPs detected a greater number of QTL than the 57 K SNP array in one population, suggesting that the RAD-SNPs may uncover polymorphisms that are more unique and informative for the specific population in which they were discovered.

Natural Variation at sympathy for the ligule Controls Penetrance of the Semidominant Liguleless narrow-R Mutation in Zea mays

PubMed Central

Buescher, Elizabeth M.; Moon, Jihyun; Runkel, Anne; Hake, Sarah; Dilkes, Brian P.

2014-01-01

Leaf architecture determines plant structural integrity, light harvesting, and economic considerations such as plant density. Ligules, junctions at the leaf sheath and blade in grasses, protect stalks from environmental stresses and, in conjunction with auricles, controls leaf angle. Previous studies in mutants have recessive liguleless mutants (lg1 and lg2) and dominant mutations in knotted1-like homeobox genes (Lg3-O, Lg4, and Kn1) involved in ligule development. Recently, a new semidominant liguleless mutant, Liguleless narrow (Lgn-R), has been characterized in maize that affects ligule and auricle development and results in a narrow leaf phenotype. We show that quantitative genetic variation affects penetrance of Lgn-R. To examine the genetic architecture underlying Lgn-R expressivity, crosses between Lgn-R/+ mutants in a B73 background and intermated B73 x Mo17 recombinant inbred lines were evaluated in multiple years and locations. A single main-effect quantitative trait locus (QTL) on chromosome 1 (sympathy for the ligule; sol) was discovered with a Mo17-contributed allele that suppressed Lgn-R mutant phenotypes. This QTL has a genetic-interaction with a locus on chromosome 7 (lucifer; lcf) for which the B73-contributed allele increases the ability of the solMo17 allele to suppress Lgn-R. Neither of the genetic intervals likely to contain sol or lcf overlap with any current liguleless genes nor with previously identified genome-wide association QTL connected to leaf architecture. Analysis of phenotypes across environments further identified a genotype by enviroment interaction determining the strength of the sol x lcf interaction. PMID:25344411

A Quantitative Study Identifying Political Strategies Used by Principals of Dual Language Programs

ERIC Educational Resources Information Center

Girard, Guadalupe

2017-01-01

Purpose. The purpose of this quantitative study was to identify the external and internal political strategies used by principals that allow them to successfully navigate the political environment surrounding dual language programs. Methodology. This quantitative study used descriptive research to collect, analyze, and report data that identified…

Quantitative force measurements in liquid using frequency modulation atomic force microscopy

NASA Astrophysics Data System (ADS)

Uchihashi, Takayuki; Higgins, Michael J.; Yasuda, Satoshi; Jarvis, Suzanne P.; Akita, Seiji; Nakayama, Yoshikazu; Sader, John E.

2004-10-01

The measurement of short-range forces with the atomic force microscope (AFM) typically requires implementation of dynamic techniques to maintain sensitivity and stability. While frequency modulation atomic force microscopy (FM-AFM) is used widely for high-resolution imaging and quantitative force measurements in vacuum, quantitative force measurements using FM-AFM in liquids have proven elusive. Here we demonstrate that the formalism derived for operation in vacuum can also be used in liquids, provided certain modifications are implemented. To facilitate comparison with previous measurements taken using surface forces apparatus, we choose a model system (octamethylcyclotetrasiloxane) that is known to exhibit short-ranged structural ordering when confined between two surfaces. Force measurements obtained are found to be in excellent agreement with previously reported results. This study therefore establishes FM-AFM as a powerful tool for the quantitative measurement of forces in liquid.

Sibling recurrence and the genetic epidemiology of autism

PubMed Central

Constantino, John N.; Zhang, Yi; Frazier, Thomas; Abbacchi, Anna M.; Law, Paul

2010-01-01

Objective Although the symptoms of autism exhibit quantitative distributions in nature, estimates of recurrence risk in families have never previously considered or incorporated quantitative characterization of the autistic phenotype among siblings. Method We report the results of quantitative characterization of 2,920 children from 1,235 families participating in a national volunteer register who met the criteria of having at least one child clinically-affected by an autism spectrum disorder (ASD) and at least one full biological sibling. Results The occurrence of a traditionally-defined ASD in an additional child occurred in 10.9% of the families. An additional 20% of non-ASD-affected siblings had a history of language delay, half of whom had exhibited autistic qualities of speech. Quantitative characterization using the Social Responsiveness Scale (SRS) supported previously-reported aggregation of a wide range of subclinical (quantitative) autistic traits among otherwise unaffected children in multiple-incidence families, and a relative absence of quantitative autistic traits among siblings in single-incidence autism families. Girls whose standardized severity ratings fell above a first percentile severity threshold (relative to the general population distribution) were significantly less likely to have elicited community diagnoses than their male counterparts. Conclusions These data suggest that, depending on how it is defined, sibling recurrence in ASD may exceed previously-published estimates, and varies as a function of family type. The results support differences in mechanisms of genetic transmission between simplex and multiplex autism, and advance current understanding of the genetic epidemiology of autism. PMID:20889652

A Systematic Review and Quantitative Meta-Analysis of Oxytocin's Effects on Feeding.

PubMed

Leslie, Monica; Silva, Paulo; Paloyelis, Yannis; Blevins, James; Treasure, Janet

2018-02-26

Oxytocin's anorexigenic effects have been widely documented and accepted; however, no paper has yet used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to compile previous findings in a single systematic review and quantitative meta-analysis. The current paper aimed to identify published and unpublished studies examining the effects of oxytocin on energy intake in animals and humans, and the factors that moderate this effect. Web of Science, Pub Med, and Ovid were searched for published and unpublished studies reporting the effects of oxytocin on energy intake in wild-type animals and in humans, when administered in the absence of other active drugs or surgery. 2049 articles were identified through the original systematic literature search, from which 54 articles were identified as relevant for inclusion in this review. An additional 3 relevant articles were identified in a later update of the literature search. Overall, a single-dose of oxytocin was found to reduce feeding in animals. Despite several individual studies which found that this effect persists to the end of the third week of chronic administration in rodent models, overall, this anorexigenic effect did not hold in the meta-analyses testing the effects of chronic administration. There was no overall effect of oxytocin on energy intake in humans, although a trend was identified for oxytocin to reduce consumption of solid foods. Oxytocin reduces energy intake when administered as a single dose. Oxytocin can inhibit feeding over two- to three-week periods in rodent models. These effects typically do not persist beyond the third week of treatment. The anorexigenic effect of oxytocin is moderated by pregnant status, dose, method of administration, and diet composition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Expanding the domains of attitudes towards evidence-based practice: the evidence based practice attitude scale-50.

PubMed

Aarons, Gregory A; Cafri, Guy; Lugo, Lindsay; Sawitzky, Angelina

2012-09-01

Mental health and social service provider attitudes toward evidence-based practice have been measured through the development and validation of the Evidence-Based Practice Attitude Scale (EBPAS; Aarons, Ment Health Serv Res 6(2):61-74, 2004). Scores on the EBPAS scales are related to provider demographic characteristics, organizational characteristics, and leadership. However, the EBPAS assesses only four domains of attitudes toward EBP. The current study expands and further identifies additional domains of attitudes towards evidence-based practice. A qualitative and quantitative mixed-methods approach was used to: (1) generate items from multiples sources (researcher, mental health program manager, clinician/therapist), (2) identify potential content domains, and (3) examine the preliminary domains and factor structure through exploratory factor analysis. Participants for item generation included the investigative team, a group of mental health program managers (n = 6), and a group of clinicians/therapists (n = 8). For quantitative analyses a sample of 422 mental health service providers from 65 outpatient programs in San Diego County completed a survey that included the new items. Eight new EBPAS factors comprised of 35 items were identified. Factor loadings were moderate to large and internal consistency reliabilities were fair to excellent. We found that the convergence of these factors with the four previously identified evidence-based practice attitude factors (15 items) was small to moderate suggesting that the newly identified factors represent distinct dimensions of mental health and social service provider attitudes toward adopting EBP. Combining the original 15 items with the 35 new items comprises the EBPAS 50-item version (EBPAS-50) that adds to our understanding of provider attitudes toward adopting EBPs. Directions for future research are discussed.

A mixed-methods study of interprofessional learning of resuscitation skills.

PubMed

Bradley, Paul; Cooper, Simon; Duncan, Fiona

2009-09-01

This study aimed to identify the effects of interprofessional resuscitation skills teaching on medical and nursing students' attitudes, leadership, team-working and performance skills. Year 2 medical and nursing students learned resuscitation skills in uniprofessional or interprofessional settings, prior to undergoing observational ratings of video-recorded leadership, teamwork and skills performance and subsequent focus group interviews. The Readiness for Interprofessional Learning Scale (RIPLS) was administered pre- and post-intervention and again 3-4 months later. There was no significant difference between interprofessional and uniprofessional teams for leadership, team dynamics or resuscitation tasks performance. Gender, previous interprofessional learning experience, professional background and previous leadership experience had no significant effect. Interview analysis showed broad support for interprofessional education (IPE) matched to clinical reality with perceived benefits for teamwork, communication and improved understanding of roles and perspectives. Concerns included inappropriate role adoption, hierarchy issues, professional identity and the timing of IPE episodes. The RIPLS subscales for professional identity and team-working increased significantly post-intervention for interprofessional groups but returned to pre-test levels by 3-4 months. However, interviews showed interprofessional groups retained a 'residual positivity' towards IPE, more so than uniprofessional groups. An intervention based on common, relevant, shared learning outcomes set in a realistic educational context can work with students who have differing levels of previous IPE and skills training experience. Qualitatively, positive attitudes outlast quantitative changes measured using the RIPLS. Further quantitative and qualitative work is required to examine other domains of learning, the timing of interventions and impact on attitudes towards IPE.

Continuing discrepancy between patient perception of asthma control and real-world symptoms: a quantitative online survey of 1,083 adults with asthma from the UK.

PubMed

Fletcher, Monica; Hiles, David

2013-12-01

Previous studies have identified a discrepancy between patient perception of asthma control and real-world symptoms; despite several hypotheses, the reasons remain unclear. To explore patients' experiences of asthma symptoms and disease management and their educational needs in the UK; to assess recent progress in asthma control and management. A quantitative questionnaire-based online survey of UK patients aged >18 years with self-reported asthma. Of the 1,083 individuals (55% female, 49% aged >55 years) who completed the survey, 79% described their asthma control as 'good' or 'very good'. Despite this, in the previous 2 years, 65% had experienced 'frequent' day-time symptoms, 37% had 'frequent' night-time symptoms, and 25% had used oral steroids for asthma; 41% of those prescribed a reliever inhaler used it >1 a day. Overall, 76% had a 'good' or 'very good' relationship with their healthcare professional (HCP); 32% had not attended regular asthma reviews and only 12% were using a personal asthma action plan. Moreover, 70% of respondents felt that they had the 'main responsibility' for managing their asthma; 29% believed this responsibility to be shared with their HCP. This survey indicates a continuing discrepancy between patient perception of asthma control and real-world symptoms, with little change from previous studies. Many patients accept symptoms as the norm. The diversity among respondents' attitudes demonstrates a need to help patients change some of their beliefs and understanding about asthma, and to improve asthma management with better education about the understanding of control for patients and HCPs.

QTLomics in Soybean: A Way Forward for Translational Genomics and Breeding

PubMed Central

Kumawat, Giriraj; Gupta, Sanjay; Ratnaparkhe, Milind B.; Maranna, Shivakumar; Satpute, Gyanesh K.

2016-01-01

Food legumes play an important role in attaining both food and nutritional security along with sustainable agricultural production for the well-being of humans globally. The various traits of economic importance in legume crops are complex and quantitative in nature, which are governed by quantitative trait loci (QTLs). Mapping of quantitative traits is a tedious and costly process, however, a large number of QTLs has been mapped in soybean for various traits albeit their utilization in breeding programmes is poorly reported. For their effective use in breeding programme it is imperative to narrow down the confidence interval of QTLs, to identify the underlying genes, and most importantly allelic characterization of these genes for identifying superior variants. In the field of functional genomics, especially in the identification and characterization of gene responsible for quantitative traits, soybean is far ahead from other legume crops. The availability of genic information about quantitative traits is more significant because it is easy and effective to identify homologs than identifying shared syntenic regions in other crop species. In soybean, genes underlying QTLs have been identified and functionally characterized for phosphorous efficiency, flowering and maturity, pod dehiscence, hard-seededness, α-Tocopherol content, soybean cyst nematode, sudden death syndrome, and salt tolerance. Candidate genes have also been identified for many other quantitative traits for which functional validation is required. Using the sequence information of identified genes from soybean, comparative genomic analysis of homologs in other legume crops could discover novel structural variants and useful alleles for functional marker development. The functional markers may be very useful for molecular breeding in soybean and harnessing benefit of translational research from soybean to other leguminous crops. Thus, soybean crop can act as a model crop for translational genomics and breeding of quantitative traits in legume crops. In this review, we summarize current status of identification and characterization of genes underlying QTLs for various quantitative traits in soybean and their significance in translational genomics and breeding of other legume crops. PMID:28066449

Quantitative Trait Loci for BMD in an SM/J by NZB/BlNJ Intercross Population and Identification of Trps1 as a Probable Candidate Gene

PubMed Central

Ishimori, Naoki; Stylianou, Ioannis M; Korstanje, Ron; Marion, Michael A; Li, Renhua; Donahue, Leah Rae; Rosen, Clifford J; Beamer, Wesley G; Paigen, Beverly; Churchill, Gary A

2008-01-01

Identification of genes that regulate BMD will enhance our understanding of osteoporosis and could provide novel molecular targets for treatment or prevention. We generated a mouse intercross population and carried out a quantitative trait locus (QTL) analysis of 143 female and 124 male F2 progeny from progenitor strains SM/J and NZB/BlNJ using whole body and vertebral areal BMD (aBMD) as measured by DXA. We found that both whole body and vertebral aBMD was affected by two loci on chromosome 9: one with a significant epistatic interaction on distal chromosome 8 and the other with a sex-specific effect. Two additional significant QTLs were identified on chromosome 12, and several suggestive ones were identified on chromosomes 5, 8, 15, and 19. The chromosome 9, 12, and 15 loci have been previously identified in other crosses. SNP-based haplotype analysis of the progenitor strains identified blocks within the QTL region that distinguish the low allele strains from the high allele strains, significantly narrowing the QTL region and reducing the possible candidate genes to 98 for chromosome 9, 31 for chromosome 12, and only 2 for chromosome 15. Trps1 is the most probable candidate gene for the chromosome 15 QTL. The sex-specific effects may help to elucidate the BMD differences between males and females. This study shows the power of statistical modeling to resolve linked QTLs and the use of haplotype analysis in narrowing the list of candidates. PMID:18442308

Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits.

PubMed

Yadav, Anupama; Dhole, Kaustubh; Sinha, Himanshu

2016-12-01

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets.

Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits

PubMed Central

Yadav, Anupama; Dhole, Kaustubh

2016-01-01

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets. PMID:28172852

Two independent proteomic approaches provide a comprehensive analysis of the synovial fluid proteome response to Autologous Chondrocyte Implantation.

PubMed

Hulme, Charlotte H; Wilson, Emma L; Fuller, Heidi R; Roberts, Sally; Richardson, James B; Gallacher, Pete; Peffers, Mandy J; Shirran, Sally L; Botting, Catherine H; Wright, Karina T

2018-05-02

Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling. Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.

Distribution and Abundance of Hopanoid Producers in Low-Oxygen Environments of the Eastern Pacific Ocean.

PubMed

Kharbush, Jenan J; Kejriwal, Kanchi; Aluwihare, Lihini I

2016-02-01

Hopanoids are bacterial membrane lipid biomarker molecules that feature prominently in the molecular fossil record. In the modern marine water column, recent reports implicate bacteria inhabiting low-oxygen environments as important sources of hopanoids to marine sediments. However, the preliminary biogeography reported by recent studies and the environmental conditions governing such distributions can only be confirmed when the numerical abundance of these organisms is known with more certainty. In this study, we employ two different approaches to examine the quantitative significance of phylogenetically distinct hopanoid producers in low-oxygen environments. First, we develop a novel quantitative PCR (qPCR) assay for the squalene hopene cyclase (sqhC) gene, targeting a subset of hopanoid producers previously identified to be important in the eastern North Pacific Ocean. The results represent the first quantitative gene abundance data of any kind for hopanoid producers in the marine water column and show that these putative alphaproteobacterial hopanoid producers are rare, comprising at most 0.2 % of the total bacterial community in our samples. Second, a complementary analysis of existing low-oxygen metagenomic datasets further examined the generality of the qPCR observation. We find that the dominant sqhC sequences in these metagenomic datasets are associated with phyla such as Nitrospinae rather than Proteobacteria, consistent with the qPCR finding that alphaproteobacterial hopanoid producers are not very abundant in low-oxygen environments. In fact, positive correlations between sqhC gene abundance and environmental parameters in these samples identify nitrite availability as a potentially important factor in the ecology of hopanoid producers that dominate low-oxygen environments.

Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 2. Label-free relative quantitative proteomics.

PubMed

Mudaliar, Manikhandan; Tassi, Riccardo; Thomas, Funmilola C; McNeilly, Tom N; Weidt, Stefan K; McLaughlin, Mark; Wilson, David; Burchmore, Richard; Herzyk, Pawel; Eckersall, P David; Zadoks, Ruth N

2016-08-16

Mastitis, inflammation of the mammary gland, is the most common and costly disease of dairy cattle in the western world. It is primarily caused by bacteria, with Streptococcus uberis as one of the most prevalent causative agents. To characterize the proteome during Streptococcus uberis mastitis, an experimentally induced model of intramammary infection was used. Milk whey samples obtained from 6 cows at 6 time points were processed using label-free relative quantitative proteomics. This proteomic analysis complements clinical, bacteriological and immunological studies as well as peptidomic and metabolomic analysis of the same challenge model. A total of 2552 non-redundant bovine peptides were identified, and from these, 570 bovine proteins were quantified. Hierarchical cluster analysis and principal component analysis showed clear clustering of results by stage of infection, with similarities between pre-infection and resolution stages (0 and 312 h post challenge), early infection stages (36 and 42 h post challenge) and late infection stages (57 and 81 h post challenge). Ingenuity pathway analysis identified upregulation of acute phase protein pathways over the course of infection, with dominance of different acute phase proteins at different time points based on differential expression analysis. Antimicrobial peptides, notably cathelicidins and peptidoglycan recognition protein, were upregulated at all time points post challenge and peaked at 57 h, which coincided with 10 000-fold decrease in average bacterial counts. The integration of clinical, bacteriological, immunological and quantitative proteomics and other-omic data provides a more detailed systems level view of the host response to mastitis than has been achieved previously.

Qualitative and quantitative analysis of an alkaloid fraction from Piper longum L. using ultra-high performance liquid chromatography-diode array detector-electrospray ionization mass spectrometry.

PubMed

Li, Kuiyong; Fan, Yunpeng; Wang, Hui; Fu, Qing; Jin, Yu; Liang, Xinmiao

2015-05-10

In a previous research, an alkaloid fraction and 18 alkaloid compounds were prepared from Piper longum L. by series of purification process. In this paper, a qualitative and quantitative analysis method using ultra-high performance liquid chromatography-diode array detector-mass spectrometry (UHPLC-DAD-MS) was developed to evaluate the alkaloid fraction. Qualitative analysis of the alkaloid fraction was firstly completed by UHPLC-DAD method and 18 amide alkaloid compounds were identified. A further qualitative analysis of the alkaloid fraction was accomplished by UHPLC-MS/MS method. Another 25 amide alkaloids were identified according to their characteristic ions and neutral losses. At last, a quantitative method for the alkaloid fraction was established using four marker compounds including piperine, pipernonatine, guineensine and N-isobutyl-2E,4E-octadecadienamide. After the validation of this method, the contents of above four marker compounds in the alkaloid fraction were 57.5mg/g, 65.6mg/g, 17.7mg/g and 23.9mg/g, respectively. Moreover, the relative response factors of other three compounds to piperine were calculated. A comparative study between external standard quantification and relative response factor quantification proved no remarkable difference. UHPLC-DAD-MS method was demonstrated to be a powerful tool for the characterization of the alkaloid fraction from P. longum L. and the result proved that the quality of alkaloid fraction was efficiently improved after appropriate purification. Copyright © 2015. Published by Elsevier B.V.

Spatial association between dissection density and environmental factors over the entire conterminous United States

NASA Astrophysics Data System (ADS)

Luo, Wei; Jasiewicz, Jaroslaw; Stepinski, Tomasz; Wang, Jinfeng; Xu, Chengdong; Cang, Xuezhi

2016-01-01

Previous studies of land dissection density (D) often find contradictory results regarding factors controlling its spatial variation. We hypothesize that the dominant controlling factors (and the interactions between them) vary from region to region due to differences in each region's local characteristics and geologic history. We test this hypothesis by applying a geographical detector method to eight physiographic divisions of the conterminous United States and identify the dominant factor(s) in each. The geographical detector method computes the power of determinant (q) that quantitatively measures the affinity between the factor considered and D. Results show that the factor (or factor combination) with the largest q value is different for physiographic regions with different characteristics and geologic histories. For example, lithology dominates in mountainous regions, curvature dominates in plains, and glaciation dominates in previously glaciated areas. The geographical detector method offers an objective framework for revealing factors controlling Earth surface processes.

Sequence of eruptive events in the Vesuvio area recorded in shallow-water Ionian Sea sediments

NASA Astrophysics Data System (ADS)

Taricco, C.; Alessio, S.; Vivaldo, G.

2008-01-01

The dating of the cores we drilled from the Gallipoli terrace in the Gulf of Taranto (Ionian Sea), previously obtained by tephroanalysis, is checked by applying a method to objectively recognize volcanic events. This automatic statistical procedure allows identifying pulse-like features in a series and evaluating quantitatively the confidence level at which the significant peaks are detected. We applied it to the 2000-years-long pyroxenes series of the GT89-3 core, on which the dating is based. The method confirms the dating previously performed by detecting at a high confidence level the peaks originally used and indicates a few possible undocumented eruptions. Moreover, a spectral analysis, focussed on the long-term variability of the pyroxenes series and performed by several advanced methods, reveals that the volcanic pulses are superimposed to a millennial trend and a 400 years oscillation.

Mineralogy from Cores in Prospect Gulch, San Juan County, Colorado

USGS Publications Warehouse

Bove, Dana J.; Johnson, Raymond H.; Yager, Douglas B.

2007-01-01

In the late nineteenth century, San Juan County, Colorado, was the center of a metal mining boom in the San Juan Mountains. Although most mining activity ceased by the 1990s, the effects of historical mining continue to contribute metals to ground water and surface water. Previous research by the U.S. Geological Survey identified ground-water discharge as a significant pathway for the loading of metals to surface water from both acid-mine drainage and acid-rock drainage. In an effort to understand the ground-water flow system in the upper Animas River watershed, Prospect Gulch was selected for further study because of the amount of previous data provided in and around that particular watershed. In support of this ground-water research effort, data was collected from drill core, which included: (1) detailed descriptions of the subsurface geology and hydrothermal alteration patterns, (2) depth of sulfide oxidation, and (3) quantitative mineralogy.

Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes

PubMed Central

Baker, Richard; Camosso-Stefinovic, Janette; Gillies, Clare; Shaw, Elizabeth J; Cheater, Francine; Flottorp, Signe; Robertson, Noelle

2014-01-01

Background In the previous version of this review, the effectiveness of interventions tailored to barriers to change was found to be uncertain. Objectives To assess the effectiveness of interventions tailored to address identified barriers to change on professional practice or patient outcomes. Search methods For this update, in addition to the EPOC Register and pending files, we searched the following databases without language restrictions, from inception until August 2007: MEDLINE, EMBASE, CINAHL, BNI and HMIC. We searched the National Research Register to November 2007. We undertook further searches to October 2009 to identify potentially eligible published or ongoing trials. Selection criteria Randomised controlled trials (RCTs) of interventions tailored to address prospectively identified barriers to change that reported objectively measured professional practice or healthcare outcomes in which at least one group received an intervention designed to address prospectively identified barriers to change. Data collection and analysis Two reviewers independently assessed quality and extracted data. We undertook quantitative and qualitative analyses. The quantitative analyses had two elements. We carried out a meta-regression to compare interventions tailored to address identified barriers to change with either no interventions or an intervention(s) not tailored to the barriers.We carried out heterogeneity analyses to investigate sources of differences in the effectiveness of interventions. These included the effects of: risk of bias, concealment of allocation, rigour of barrier analysis, use of theory, complexity of interventions, and the reported presence of administrative constraints. Main results We included 26 studies comparing an intervention tailored to address identified barriers to change to no intervention or an intervention(s) not tailored to the barriers. The effect sizes of these studies varied both across and within studies. Twelve studies provided enough data to be included in the quantitative analysis. A meta-regression model was fitted adjusting for baseline odds by fitting it as a covariate, to obtain the pooled odds ratio of 1.54 (95% CI, 1.16 to 2.01) from Bayesian analysis and 1.52 (95% CI, 1.27 to 1.82, P < 0.001) from classical analysis. The heterogeneity analyses found that no study attributes investigated were significantly associated with effectiveness of the interventions. Authors’ conclusions Interventions tailored to prospectively identified barriers are more likely to improve professional practice than no intervention or dissemination of guidelines. However, the methods used to identify barriers and tailor interventions to address them need further development. Research is required to determine the effectiveness of tailored interventions in comparison with other interventions. PMID:20238340

Identification of positional candidates for bovine placental genes responsible for early embryonic death during cloning-attempted pregnancy.

PubMed

Yamada, Takahisa; Muramatsu, Youji; Taniguchi, Yukio; Sasaki, Yoshiyuki

Our previous study detected 291 and 77 genes showing early embryonic death-associated elevation and reduction of expression, respectively, in the fetal placenta of the cow carrying somatic nuclear transfer-derived cloned embryo. In this study, we mapped the 10 genes showing the elevation and the 10 genes doing the reduction most significantly, using somatic cell hybrid and bovine draft genome sequence. We then compared the mapped positions for these genes with the genomic locations of bovine quantitative trait loci for still-birth and/or abortion. Among the mapped genes, peptidylglycine alpha-amidating monooxygenase (PAM), spectrin, beta, nonerythrocytic 1 (SPTBNI), and an unknown novel gene containing AU277832 expressed sequence tag were intriguing, in that the mapped positions were consistent with the genomic locations of bovine still-birth and/or abortion quantitative trait loci, and thus identified as positional candidates for bovine placental genes responsible for the early embryonic death during the pregnancy attempted by somatic nuclear transfer-derived cloning.

Over-seasons analysis of quantitative trait loci affecting phenolic content and antioxidant capacity in raspberry.

PubMed

Dobson, Patricia; Graham, Julie; Stewart, D; Brennan, Rex; Hackett, Christine A; McDougall, Gordon J

2012-05-30

This study examined the total phenol content (TPC) and total anthocyanin content (TAC) in ripe fruit of progeny of a mapping population generated from a cross between the European red raspberry cv. Glen Moy ( Rubus ideaus var. idaeus) and the North American red raspberry cv. Latham ( Rubus ideaus var. strigosus) over five seasons in two different growing environments. Measurements of antioxidant capacity (FRAP and TEAC) were also carried out. TPC was highly correlated with TEAC and FRAP across the entire data set. The subset of anthocyanin content was genotype-dependent but also correlated with TPC, although the proportion of anthocyanin compounds varied between progeny. Quantitative trait locus (QTL) analysis was carried out, and key markers were tested for consistency of effects over sites and years. Four regions, on linkage groups 2, 3, 5, and 6, were identified. These agree with QTLs from a previous study over a single season and indicate that QTL effects were robust over seasons.

Italian news coverage of radiation in the early decades of the twentieth century: A qualitative and quantitative analysis.

PubMed

Candela, Andrea; Pasquarè Mariotto, Federico

2016-02-01

This work uses a qualitative approach coupled with a quantitative software-based methodology to examine the Italian news media coverage of radiation in the early decades of the twentieth century. We analyze 80 news stories from two of the most influential Italian newspapers from that time: La Stampa (a daily newspaper) and La Domenica del Corriere (an Italian Sunday supplement). While much of previous research on media coverage of scientific topics was generally focused on present-day news, our work revolves around the ground-breaking discovery of X-rays and radioactivity at the dawn of the last century. Our analysis aims to identify journalistic frames in the news coverage of radiation that journalists might have used to emphasize the benefits (or the risks) of the new discoveries. We also hypothesize how this kind of news coverage might have influenced public perception of technological, commercial, and public health applications of the new scientific advancements. © The Author(s) 2014.

Quantitative theory of hydrophobic effect as a driving force of protein structure

PubMed Central

Perunov, Nikolay; England, Jeremy L

2014-01-01

Various studies suggest that the hydrophobic effect plays a major role in driving the folding of proteins. In the past, however, it has been challenging to translate this understanding into a predictive, quantitative theory of how the full pattern of sequence hydrophobicity in a protein shapes functionally important features of its tertiary structure. Here, we extend and apply such a phenomenological theory of the sequence-structure relationship in globular protein domains, which had previously been applied to the study of allosteric motion. In an effort to optimize parameters for the model, we first analyze the patterns of backbone burial found in single-domain crystal structures, and discover that classic hydrophobicity scales derived from bulk physicochemical properties of amino acids are already nearly optimal for prediction of burial using the model. Subsequently, we apply the model to studying structural fluctuations in proteins and establish a means of identifying ligand-binding and protein–protein interaction sites using this approach. PMID:24408023

Mental health and sexual identity in a sample of male sex workers in the Czech Republic.

PubMed

Bar-Johnson, Michael; Weiss, Petr

2014-09-20

Previous qualitative research has examined male sex workers in the Czech Republic, but this mapping study is the first to investigate male sex work in a quantitative research design and focus on the mental health of these sex workers. This study also examines male sex workers' mental health problems in relation to their sexual identity or orientation. A sample of Czech male sex workers (N=40) were examined on a range of sexual and psychological variables using a quantitative survey administered face-to-face. The study employed locally validated versions of Beck's Depression Inventory and Zung's Self-Report Anxiety Scale. The results indicate that for homosexuals, working as a male sex worker is not related to any serious mental health problems. However, those identifying as heterosexual and bisexual more frequently reported symptoms of depression and bisexuals showed significantly more anxiety. These findings suggest sexual identity is an important issue to consider when addressing the mental health needs of this population.

Mapping eQTLs in the Norfolk Island Genetic Isolate Identifies Candidate Genes for CVD Risk Traits

PubMed Central

Benton, Miles C.; Lea, Rod A.; Macartney-Coxson, Donia; Carless, Melanie A.; Göring, Harald H.; Bellis, Claire; Hanna, Michelle; Eccles, David; Chambers, Geoffrey K.; Curran, Joanne E.; Harper, Jacquie L.; Blangero, John; Griffiths, Lyn R.

2013-01-01

Cardiovascular disease (CVD) affects millions of people worldwide and is influenced by numerous factors, including lifestyle and genetics. Expression quantitative trait loci (eQTLs) influence gene expression and are good candidates for CVD risk. Founder-effect pedigrees can provide additional power to map genes associated with disease risk. Therefore, we identified eQTLs in the genetic isolate of Norfolk Island (NI) and tested for associations between these and CVD risk factors. We measured genome-wide transcript levels of blood lymphocytes in 330 individuals and used pedigree-based heritability analysis to identify heritable transcripts. eQTLs were identified by genome-wide association testing of these transcripts. Testing for association between CVD risk factors (i.e., blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712 heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to 0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p < 1.84 × 10−7) An eQTL-centric analysis of CVD risk traits revealed multiple associations, including 12 previously associated with CVD-related traits. Trait versus eQTL regression modeling identified four CVD risk candidates (NAAA, PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In addition, we implicated several genes previously associated with CVD risk traits, including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in the NI pedigree and used this to implicate several genes in CVD risk. Future studies are required for further assessing the functional importance of these eQTLs and whether the findings here also relate to outbred populations. PMID:24314549

Advancing the speed, sensitivity and accuracy of biomolecular detection using multi-length-scale engineering

PubMed Central

Kelley, Shana O.; Mirkin, Chad A.; Walt, David R.; Ismagilov, Rustem F.; Toner, Mehmet; Sargent, Edward H.

2015-01-01

Rapid progress in identifying disease biomarkers has increased the importance of creating high-performance detection technologies. Over the last decade, the design of many detection platforms has focused on either the nano or micro length scale. Here, we review recent strategies that combine nano- and microscale materials and devices to produce large improvements in detection sensitivity, speed and accuracy, allowing previously undetectable biomarkers to be identified in clinical samples. Microsensors that incorporate nanoscale features can now rapidly detect disease-related nucleic acids expressed in patient samples. New microdevices that separate large clinical samples into nanocompartments allow precise quantitation of analytes, and microfluidic systems that utilize nanoscale binding events can detect rare cancer cells in the bloodstream more accurately than before. These advances will lead to faster and more reliable clinical diagnostic devices. PMID:25466541

Advancing the speed, sensitivity and accuracy of biomolecular detection using multi-length-scale engineering

NASA Astrophysics Data System (ADS)

Kelley, Shana O.; Mirkin, Chad A.; Walt, David R.; Ismagilov, Rustem F.; Toner, Mehmet; Sargent, Edward H.

2014-12-01

Rapid progress in identifying disease biomarkers has increased the importance of creating high-performance detection technologies. Over the last decade, the design of many detection platforms has focused on either the nano or micro length scale. Here, we review recent strategies that combine nano- and microscale materials and devices to produce large improvements in detection sensitivity, speed and accuracy, allowing previously undetectable biomarkers to be identified in clinical samples. Microsensors that incorporate nanoscale features can now rapidly detect disease-related nucleic acids expressed in patient samples. New microdevices that separate large clinical samples into nanocompartments allow precise quantitation of analytes, and microfluidic systems that utilize nanoscale binding events can detect rare cancer cells in the bloodstream more accurately than before. These advances will lead to faster and more reliable clinical diagnostic devices.

HPLC-MS and GC-MS analyses combined with orthogonal partial least squares to identify cytotoxic constituents from turmeric (Curcuma longa L.).

PubMed

Jiang, Jianlan; Zhang, Huan; Li, Zidan; Zhang, Xiaohang; Su, Xin; Li, Yan; Qiao, Bin; Yuan, Yingjin

2013-08-01

We investigated the fingerprints of 48 batches of turmeric total extracts (TTE) by HPLC-MS-MS and GC-MS analyses and 43 characteristic peaks (22 constituents from HPLC-MS-MS; 21 from GC-MS) were analyzed qualitatively and quantitatively. An MTT {3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide} assay was implemented to measure the cytotoxicity of the TTE against HeLa cells. Then we utilized orthogonal partial least squares analysis, which correlated the chemical composition of the TTE to its cytotoxic activity, to identify potential cytotoxic constituents from turmeric. The result showed that 19 constituents contributed significantly to the cytotoxicity. The obtained result was verified by canonical correlation analysis. Comparison with previous reports also indicated some interaction between the curcuminoids and sesquiterpenoids in turmeric.

A Qualitative Study of Provider Perceptions of Influences on Uptake of Pediatric Hospital Guidelines in Lao PDR.

PubMed

Gray, Amy Z; Soukaloun, Douangdao; Soumphonphakdy, Bandith

2017-08-01

Strategies to improve the quality of hospital care are needed if ongoing gains in child health and survival are to be made. We previously reported on improvements in the quality of case management in hospitals following a guideline-based intervention in Lao PDR, with variation in the degree of change achieved between clinical conditions. This study aims to understand the factors that influenced the uptake of the guideline-based intervention, and its impact on care. This qualitative study was embedded in a mixed-methods evaluation of guideline implementation in nine hospitals in Lao PDR. Focus groups and individual interviews were conducted with 70 health staff from central, provincial, and district hospitals. The interview guide was based on the Theoretical Domains Framework. Inductive content analysis was performed on interview transcripts to identify themes, supported by field notes from the intervention. Findings were triangulated against previously reported quantitative outcomes using driver diagrams. Key influences on guidelines uptake related to the guideline and intervention (filling a void, physical accessibility, comprehensibility, training in guideline use), health staff (behavior regulation, trust in guidelines, and beliefs about consequences), and the environment (social influences particularly consensus and incorporation into clinical norms). The major barrier was family preference for treatments in conflict with guideline recommendations. This study identifies contextual factors that explain, as well as validate previously identified improvements in care following guideline implementation in Lao PDR. It provides novel understanding of why the same intervention may have a differential impact on different clinical conditions.

Large Crater Clustering tool

NASA Astrophysics Data System (ADS)

Laura, Jason; Skinner, James A.; Hunter, Marc A.

2017-08-01

In this paper we present the Large Crater Clustering (LCC) tool set, an ArcGIS plugin that supports the quantitative approximation of a primary impact location from user-identified locations of possible secondary impact craters or the long-axes of clustered secondary craters. The identification of primary impact craters directly supports planetary geologic mapping and topical science studies where the chronostratigraphic age of some geologic units may be known, but more distant features have questionable geologic ages. Previous works (e.g., McEwen et al., 2005; Dundas and McEwen, 2007) have shown that the source of secondary impact craters can be estimated from secondary impact craters. This work adapts those methods into a statistically robust tool set. We describe the four individual tools within the LCC tool set to support: (1) processing individually digitized point observations (craters), (2) estimating the directional distribution of a clustered set of craters, back projecting the potential flight paths (crater clusters or linearly approximated catenae or lineaments), (3) intersecting projected paths, and (4) intersecting back-projected trajectories to approximate the local of potential source primary craters. We present two case studies using secondary impact features mapped in two regions of Mars. We demonstrate that the tool is able to quantitatively identify primary impacts and supports the improved qualitative interpretation of potential secondary crater flight trajectories.

Enhanced method to reconstruct mode shapes of continuous scanning measurements using the Hilbert Huang transform and the modal analysis method

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

Lee, Jongsuh; Hussain, Syed Hassaan; Wang, Semyung, E-mail: smwang@gist.ac.kr

2014-09-15

Generally, it is time consuming to experimentally identify the operating deflection shape or mode shape of a structure. To overcome this problem, the Hilbert Huang transform (HHT) technique has been recently proposed. This technique is used to extract the mode shape from measurements that continuously measure the vibration of a region of interest within a structure using a non-contact laser sensor. In previous research regarding the HHT, two technical processes were needed to obtain the mode shape for each mode. The purpose of this study is to improve and complement our previous research, and for this purpose, a modal analysismore » approach is adapted without using the two technical processes to obtain an accurate un-damped impulse response of each mode for continuous scanning measurements. In addition, frequency response functions for each type of beam are derived, making it possible to make continuously scanned measurements along a straight profile. In this paper, the technical limitations and drawbacks of the damping compensation technique used in previous research are identified. In addition, the separation of resonant frequency (the Doppler effect) that occurs in continuous scanning measurements and the separation of damping phenomenon are also observed. The proposed method is quantitatively verified by comparing it with the results obtained from a conventional approach to estimate the mode shape with an impulse response.« less

A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers

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

Manish M Patel, Alan P Janssen, Richard Tardif, Mark Herring, Umesh Parashar

2007-10-18

In 2006, a new rotavirus vaccine (RotaTeq) was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield) was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage. Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program.

Thermal magnetic field noise: electron optics and decoherence.

PubMed

Uhlemann, Stephan; Müller, Heiko; Zach, Joachim; Haider, Max

2015-04-01

Thermal magnetic field noise from magnetic and non-magnetic conductive parts close to the electron beam recently has been identified as a reason for decoherence in high-resolution transmission electron microscopy (TEM). Here, we report about new experimental results from measurements for a layered structure of magnetic and non-magnetic materials. For a simplified version of this setup and other situations we derive semi-analytical models in order to predict the strength, bandwidth and spatial correlation of the noise fields. The results of the simulations are finally compared to previous and new experimental data in a quantitative manner. Copyright © 2014 Elsevier B.V. All rights reserved.

From the voices of women: facilitating survivor access to IPV services.

PubMed

Simmons, Catherine A; Farrar, Melissa; Frazer, Kitty; Thompson, Mary Jane

2011-10-01

This mixed-method study investigated perceptions women domestic violence survivors/victims have about why women do not seek help from formal support structures and actions domestic helping agencies can take to facilitate survivor access to services. Congruent with previous research, quantitative analysis identified 17 reasons women do not seek help from formal support structures. Expanding current knowledge, concept mapping revealed six ways family violence programs can better reach women in abusive relationships, including (1) remove barriers to services, (2) improve comfort with services, (3) "talk about it," (4) improve community awareness, (5) victim-targeted marketing, and (6) "I honestly don't know."

QUANTITATIVE PROCEDURES FOR NEUROTOXICOLOGY RISK ASSESSMENT

EPA Science Inventory

In this project, previously published information on biologically based dose-response model for brain development was used to quantitatively evaluate critical neurodevelopmental processes, and to assess potential chemical impacts on early brain development. This model has been ex...

High-throughput screening to identify selective inhibitors of microbial sulfate reduction (and beyond)

NASA Astrophysics Data System (ADS)

Carlson, H. K.; Coates, J. D.; Deutschbauer, A. M.

2015-12-01

The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive and corrosive. Current strategies to selectively inhibit sulfidogenesis are based on non-specific biocide treatments, bio-competitive exclusion by alternative electron acceptors or sulfate-analogs which are competitive inhibitors or futile/alternative substrates of the sulfate reduction pathway. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to target SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Once inhibitor selectivity is defined, high-throughput characterization of microbial community structure across compound gradients and identification of fitness determinants using isolate bar-coded transposon mutant libraries can give insights into the genetic mechanisms whereby compounds structure microbial communities. The high-throughput (HT) approach we present can be readily applied to target SRM in diverse environments and more broadly, could be used to identify and quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant for engineering environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space.

Determination of burn patient outcome by large-scale quantitative discovery proteomics

PubMed Central

Finnerty, Celeste C.; Jeschke, Marc G.; Qian, Wei-Jun; Kaushal, Amit; Xiao, Wenzhong; Liu, Tao; Gritsenko, Marina A.; Moore, Ronald J.; Camp, David G.; Moldawer, Lyle L.; Elson, Constance; Schoenfeld, David; Gamelli, Richard; Gibran, Nicole; Klein, Matthew; Arnoldo, Brett; Remick, Daniel; Smith, Richard D.; Davis, Ronald; Tompkins, Ronald G.; Herndon, David N.

2013-01-01

Objective Emerging proteomics techniques can be used to establish proteomic outcome signatures and to identify candidate biomarkers for survival following traumatic injury. We applied high-resolution liquid chromatography-mass spectrometry (LC-MS) and multiplex cytokine analysis to profile the plasma proteome of survivors and non-survivors of massive burn injury to determine the proteomic survival signature following a major burn injury. Design Proteomic discovery study. Setting Five burn hospitals across the U.S. Patients Thirty-two burn patients (16 non-survivors and 16 survivors), 19–89 years of age, were admitted within 96 h of injury to the participating hospitals with burns covering >20% of the total body surface area and required at least one surgical intervention. Interventions None. Measurements and Main Results We found differences in circulating levels of 43 proteins involved in the acute phase response, hepatic signaling, the complement cascade, inflammation, and insulin resistance. Thirty-two of the proteins identified were not previously known to play a role in the response to burn. IL-4, IL-8, GM-CSF, MCP-1, and β2-microglobulin correlated well with survival and may serve as clinical biomarkers. Conclusions These results demonstrate the utility of these techniques for establishing proteomic survival signatures and for use as a discovery tool to identify candidate biomarkers for survival. This is the first clinical application of a high-throughput, large-scale LC-MS-based quantitative plasma proteomic approach for biomarker discovery for the prediction of patient outcome following burn, trauma or critical illness. PMID:23507713

A mixed methods approach to exploring the relationship between Norway rat (Rattus norvegicus) abundance and features of the urban environment in an inner-city neighborhood of Vancouver, Canada.

PubMed

Himsworth, Chelsea G; Parsons, Kirbee L; Feng, Alice Y T; Kerr, Thomas; Jardine, Claire M; Patrick, David M

2014-01-01

Urban rats (Rattus spp.) are among the most ubiquitous pest species in the world. Previous research has shown that rat abundance is largely determined by features of the environment; however, the specific urban environmental factors that influence rat population density within cities have yet to be clearly identified. Additionally, there are no well described tools or methodologies for conducting an in-depth evaluation of the relationship between urban rat abundance and the environment. In this study, we developed a systematic environmental observation tool using methods borrowed from the field of systematic social observation. This tool, which employed a combination of quantitative and qualitative methodologies, was then used to identify environmental factors associated with the relative abundance of Norway rats (Rattus norvegicus) in an inner-city neighborhood of Vancouver, Canada. Using a multivariate zero-inflated negative binomial model, we found that a variety of factors, including specific land use, building condition, and amount of refuse, were related to rat presence and abundance. Qualitative data largely supported and further clarified observed statistical relationships, but also identified conflicting and unique situations not easily captured through quantitative methods. Overall, the tool helped us to better understand the relationship between features of the urban environment and relative rat abundance within our study area and may useful for studying environmental determinants of zoonotic disease prevalence/distribution among urban rat populations in the future.

A Mixed Methods Approach to Exploring the Relationship between Norway Rat (Rattus norvegicus) Abundance and Features of the Urban Environment in an Inner-City Neighborhood of Vancouver, Canada

PubMed Central

Himsworth, Chelsea G.; Parsons, Kirbee L.; Feng, Alice Y. T.; Kerr, Thomas; Jardine, Claire M.; Patrick, David M.

2014-01-01

Urban rats (Rattus spp.) are among the most ubiquitous pest species in the world. Previous research has shown that rat abundance is largely determined by features of the environment; however, the specific urban environmental factors that influence rat population density within cities have yet to be clearly identified. Additionally, there are no well described tools or methodologies for conducting an in-depth evaluation of the relationship between urban rat abundance and the environment. In this study, we developed a systematic environmental observation tool using methods borrowed from the field of systematic social observation. This tool, which employed a combination of quantitative and qualitative methodologies, was then used to identify environmental factors associated with the relative abundance of Norway rats (Rattus norvegicus) in an inner-city neighborhood of Vancouver, Canada. Using a multivariate zero-inflated negative binomial model, we found that a variety of factors, including specific land use, building condition, and amount of refuse, were related to rat presence and abundance. Qualitative data largely supported and further clarified observed statistical relationships, but also identified conflicting and unique situations not easily captured through quantitative methods. Overall, the tool helped us to better understand the relationship between features of the urban environment and relative rat abundance within our study area and may useful for studying environmental determinants of zoonotic disease prevalence/distribution among urban rat populations in the future. PMID:24830847

Linking Yeast Gcn5p Catalytic Function and Gene Regulation Using a Quantitative, Graded Dominant Mutant Approach

PubMed Central

Lanza, Amanda M.; Blazeck, John J.; Crook, Nathan C.; Alper, Hal S.

2012-01-01

Establishing causative links between protein functional domains and global gene regulation is critical for advancements in genetics, biotechnology, disease treatment, and systems biology. This task is challenging for multifunctional proteins when relying on traditional approaches such as gene deletions since they remove all domains simultaneously. Here, we describe a novel approach to extract quantitative, causative links by modulating the expression of a dominant mutant allele to create a function-specific competitive inhibition. Using the yeast histone acetyltransferase Gcn5p as a case study, we demonstrate the utility of this approach and (1) find evidence that Gcn5p is more involved in cell-wide gene repression, instead of the accepted gene activation associated with HATs, (2) identify previously unknown gene targets and interactions for Gcn5p-based acetylation, (3) quantify the strength of some Gcn5p-DNA associations, (4) demonstrate that this approach can be used to correctly identify canonical chromatin modifications, (5) establish the role of acetyltransferase activity on synthetic lethal interactions, and (6) identify new functional classes of genes regulated by Gcn5p acetyltransferase activity—all six of these major conclusions were unattainable by using standard gene knockout studies alone. We recommend that a graded dominant mutant approach be utilized in conjunction with a traditional knockout to study multifunctional proteins and generate higher-resolution data that more accurately probes protein domain function and influence. PMID:22558379

High-resolution identification and abundance profiling of cassava (Manihot esculenta Crantz) microRNAs.

PubMed

Khatabi, Behnam; Arikit, Siwaret; Xia, Rui; Winter, Stephan; Oumar, Doungous; Mongomake, Kone; Meyers, Blake C; Fondong, Vincent N

2016-01-28

Small RNAs (sRNAs) are endogenous sRNAs that play regulatory roles in plant growth, development, and biotic and abiotic stress responses. In plants, one subset of sRNAs, microRNAs (miRNAs) exhibit tissue-differential expression and regulate gene expression mainly through direct cleavage of mRNA or indirectly via production of secondary phased siRNAs (phasiRNAs) that silence cognate target transcripts in trans. Here, we have identified cassava (Manihot esculenta Crantz) miRNAs using high resolution sequencing of sRNA libraries from leaf, stem, callus, male and female flower tissues. To analyze the data, we built a cassava genome database and, via sequence analysis and secondary structure prediction, 38 miRNAs not previously reported in cassava were identified. These new cassava miRNAs included two miRNAs not previously been reported in any plant species. The miRNAs exhibited tissue-differential accumulation as confirmed by quantitative RT-PCR and Northern blot analysis, largely reflecting levels observed in sequencing data. Some of the miRNAs identified were predicted to trigger production of secondary phased siRNAs (phasiRNAs) from 80 PHAS loci. Cassava is a woody perennial shrub, grown principally for its starch-rich storage roots, which are rich in calories. In this study, new miRNAs were identified and their expression was validated using qRT-PCR of RNA from five different tissues. The data obtained expand the list of annotated miRNAs and provide additional new resources for cassava improvement research.

Criterion for Identifying Vortices in High-Pressure Flows

NASA Technical Reports Server (NTRS)

Bellan, Josette; Okong'o, Nora

2007-01-01

A study of four previously published computational criteria for identifying vortices in high-pressure flows has led to the selection of one of them as the best. This development can be expected to contribute to understanding of high-pressure flows, which occur in diverse settings, including diesel, gas turbine, and rocket engines and the atmospheres of Jupiter and other large gaseous planets. Information on the atmospheres of gaseous planets consists mainly of visual and thermal images of the flows over the planets. Also, validation of recently proposed computational models of high-pressure flows entails comparison with measurements, which are mainly of visual nature. Heretofore, the interpretation of images of high-pressure flows to identify vortices has been based on experience with low-pressure flows. However, high-pressure flows have features distinct from those of low-pressure flows, particularly in regions of high pressure gradient magnitude caused by dynamic turbulent effects and by thermodynamic mixing of chemical species. Therefore, interpretations based on low-pressure behavior may lead to misidentification of vortices and other flow structures in high-pressure flows. The study reported here was performed in recognition of the need for one or more quantitative criteria for identifying coherent flow structures - especially vortices - from previously generated flow-field data, to complement or supersede the determination of flow structures by visual inspection of instantaneous fields or flow animations. The focus in the study was on correlating visible images of flow features with various quantities computed from flow-field data.

New insights into the diets of harbor seals in the Salish Sea revealed by quantitative fatty acid signature analysis

USGS Publications Warehouse

Bromaghin, Jeffrey F.; Lance, Monique M.; Elliott, Elizabeth W.; Jeffries, Steven J.; Acevedo-Gutiérrez, Alejandro; Kennish, John M.

2013-01-01

Harbor seals (Phoca vitulina) are an abundant predator along the west coast of North America, and there is considerable interest in their diet composition, especially in regard to predation on valued fish stocks. Available information on harbor seal diets, primarily derived from scat analysis, suggests that adult salmon (Oncorhynchus spp.), Pacific Herring (Clupea pallasii), and gadids predominate. Because diet assessments based on scat analysis may be biased, we investigated diet composition through quantitative analysis of fatty acid signatures. Blubber samples from 49 harbor seals captured in western North America from haul-outs within the area of the San Juan Islands and southern Strait of Georgia in the Salish Sea were analyzed for fatty acid composition, along with 269 fish and squid specimens representing 27 potential prey classes. Diet estimates varied spatially, demographically, and among individual harbor seals. Findings confirmed the prevalence of previously identified prey species in harbor seal diets, but other species also contributed significantly. In particular, Black (Sebastes melanops) and Yellowtail (S. flavidus) Rockfish were estimated to compose up to 50% of some individual seal diets. Specialization and high predation rates on Black and Yellowtail Rockfish by a subset of harbor seals may play a role in the population dynamics of these regional rockfish stocks that is greater than previously realized.

Quantitative Proteomics Uncovers Novel Factors Involved in Developmental Differentiation of Trypanosoma brucei

PubMed Central

Dejung, Mario; Subota, Ines; Bucerius, Ferdinand; Dindar, Gülcin; Freiwald, Anja; Engstler, Markus; Boshart, Michael; Butter, Falk; Janzen, Christian J.

2016-01-01

Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes. PMID:26910529

Student Perceptions of an Online Medical Dosimetry Program

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

Lenards, Nishele, E-mail: lenards.nish@uwlax.ed

2011-07-01

The University of Wisconsin-La Crosse offers the first online medical dosimetry program in the nation. There is no data to research a program of this type. This research consisted of the evaluation of other distance education programs including health profession programs in addition to face-to-face medical dosimetry programs. There was a need to collect and analyze student perceptions of online learning in medical dosimetry. This research provided a guide for future implementation by other programs as well as validated the University of Wisconsin-La Crosse program. Methodology used consisted of an electronic survey sent to all previous and currently enrolled studentsmore » in the University of Wisconsin-La Crosse medical dosimetry program. The survey was both quantitative and qualitative in demonstrating attitudinal perceptions of students in the program. Quantitative data was collected and analyzed using a 5-point Likert scale. Qualitative data was gathered based on the open-ended responses and the identifying themes from the responses. The results demonstrated an overall satisfaction with this program, the instructor, and the online courses. Students felt a sense of belonging to the courses and the program. Considering that a majority of the students had never taken an online course previously, the students felt there were no technology issues. Future research should include an evaluation of board exam statistics for students enrolled in the online and face-to-face medical dosimetry programs.« less

Priorities and strategies for improving disabled women's access to maternity services when they are affected by domestic abuse: a multi-method study using concept maps.

PubMed

Bradbury-Jones, Caroline; Breckenridge, Jenna P; Devaney, John; Duncan, Fiona; Kroll, Thilo; Lazenbatt, Anne; Taylor, Julie

2015-12-28

Domestic abuse is a significant public health issue. It occurs more frequently among disabled women than those without a disability and evidence suggests that a great deal of domestic abuse begins or worsens during pregnancy. All women and their infants are entitled to equal access to high quality maternity care. However, research has shown that disabled women who experience domestic abuse face numerous barriers to accessing care. The aim of the study was to identify the priority areas for improving access to maternity services for this group of women; develop strategies for improved access and utilisation; and explore the feasibility of implementing the identified strategies. This multi-method study was the third and final part of a larger study conducted in the UK between 2012 and 2014. The study used a modified concept mapping approach and was theoretically underpinned by Andersen's model of healthcare use. Seven focus group interviews were conducted with a range of maternity care professionals (n = 45), incorporating quantitative and qualitative components. Participants ranked perceived barriers to women's access and utilisation of maternity services in order of priority using a 5-point Likert scale. Quantitative data exploration used descriptive and non-parametric analyses. In the qualitative component of each focus group, participants discussed the barriers and identified potential improvement strategies (and feasibility of implementing these). Qualitative data were analysed inductively using a framework analysis approach. The three most highly ranked barriers to women's access and utilisation of maternity services identified in the quantitative component were: 1) staff being unaware and not asking about domestic abuse and disability; 2) the impact of domestic abuse on women; 3) women's fear of disclosure. The top two priority strategies were: providing information about domestic abuse to all women and promoting non-judgemental staff attitude. These were also considered very feasible. The qualitative analysis identified a range of psychosocial and environmental barriers experienced by this group of women in accessing maternity care. Congruent with the quantitative results, the main themes were lack of awareness and fear of disclosure. Key strategies were identified as demystifying disclosure and creating physical spaces to facilitate disclosure. The study supports findings of previous research regarding the barriers that women face in accessing and utilising maternity services, particularly regarding the issue of disclosure. But the study provides new evidence on the perceived importance and feasibility of strategies to address such barriers. This is an important step in ensuring practice-based acceptability and ease with which improvement strategies might be implemented in maternity care settings.

Application of Microextraction Techniques Including SPME and MESI to the Thermal Degradation of Polymers: A Review.

PubMed

Kaykhaii, Massoud; Linford, Matthew R

2017-03-04

Here, we discuss the newly developed micro and solventless sample preparation techniques SPME (Solid Phase Microextraction) and MESI (Membrane Extraction with a Sorbent Interface) as applied to the qualitative and quantitative analysis of thermal oxidative degradation products of polymers and their stabilizers. The coupling of these systems to analytical instruments is also described. Our comprehensive literature search revealed that there is no previously published review article on this topic. It is shown that these extraction techniques are valuable sample preparation tools for identifying complex series of degradation products in polymers. In general, the number of products identified by traditional headspace (HS-GC-MS) is much lower than with SPME-GC-MS. MESI is particularly well suited for the detection of non-polar compounds, therefore number of products identified by this technique is not also to the same degree of SPME. Its main advantage, however, is its ability of (semi-) continuous monitoring, but it is more expensive and not yet commercialized.

Evidence of a louse-borne outbreak involving typhus in Douai, 1710-1712 during the war of Spanish succession.

PubMed

Nguyen-Hieu, Tung; Aboudharam, Gérard; Signoli, Michel; Rigeade, Catherine; Drancourt, Michel; Raoult, Didier

2010-10-27

The new field of paleomicrobiology allows past outbreaks to be identified by testing dental pulp of human remains with PCR. We identified a mass grave in Douai, France dating from the early XVIII(th) century. This city was besieged during the European war of Spanish succession. We tested dental pulp from 1192 teeth (including 40 from Douai) by quantitative PCR (qPCR) for R. prowazekii and B. quintana. We also used ultra-sensitive suicide PCR to detect R. prowazekii and genotyped positive samples. In the Douai remains, we identified one case of B. quintana infection (by qPCR) and R. prowazekii (by suicide PCR) in 6/21 individuals (29%). The R. prowazekii was genotype B, a genotype previously found in a Spanish isolate obtained in the first part of the XX(th) century. Louse-borne outbreaks were raging during the XVIII(th) century; our results support the hypothesis that typhus was imported into Europe by Spanish soldiers from America.

Evidence of a Louse-Borne Outbreak Involving Typhus in Douai, 1710-1712 during the War of Spanish Succession

PubMed Central

Nguyen-Hieu, Tung; Aboudharam, Gérard; Signoli, Michel; Rigeade, Catherine; Drancourt, Michel; Raoult, Didier

2010-01-01

Background The new field of paleomicrobiology allows past outbreaks to be identified by testing dental pulp of human remains with PCR. Methods We identified a mass grave in Douai, France dating from the early XVIIIth century. This city was besieged during the European war of Spanish succession. We tested dental pulp from 1192 teeth (including 40 from Douai) by quantitative PCR (qPCR) for R. prowazekii and B. quintana. We also used ultra-sensitive suicide PCR to detect R. prowazekii and genotyped positive samples. Results and Discussion In the Douai remains, we identified one case of B. quintana infection (by qPCR) and R. prowazekii (by suicide PCR) in 6/21 individuals (29%). The R. prowazekii was genotype B, a genotype previously found in a Spanish isolate obtained in the first part of the XXth century. Conclusion Louse-borne outbreaks were raging during the XVIIIth century; our results support the hypothesis that typhus was imported into Europe by Spanish soldiers from America. PMID:21060879

Schistosoma mansoni: resistant specific infection-induced gene expression in Biomphalaria glabrata identified by fluorescent-based differential display.

PubMed

Lockyer, Anne E; Noble, Leslie R; Rollinson, David; Jones, Catherine S

2004-01-01

The freshwater tropical snail Biomphalaria glabrata is an intermediate host for Schistosoma mansoni, the causative agent of human intestinal schistosomiasis, and strains differ in their susceptibility to parasite infection. Changes in gene expression in response to parasite infection have been simultaneously examined in a susceptible strain (NHM1742) and a resistant strain (NHM1981) using a newly developed fluorescent-based differential display method. Such RNA profiling techniques allow the examination of changes in gene expression in response to parasite infection, without requiring previous sequence knowledge, or selecting candidate genes that may be involved in the complex neuroendocrine or defence systems of the snail. Thus, novel genes may be identified. Ten transcripts were initially identified, present only in the profiles derived from snails of the resistant strain when exposed to infection. The differential expression of five of these genes, including HSP70 and several novel transcripts with one containing at least two globin-like domains, has been confirmed by semi-quantitative RT-PCR.

Challenges and Opportunities for Quantitative Clinical Pharmacology in Cancer Immunotherapy: Something Old, Something New, Something Borrowed, and Something Blue.

PubMed

Stroh, M; Carlile, D J; Li, C-C; Wagg, J; Ribba, B; Ramanujan, S; Jin, J; Xu, J; Charoin, J-E; Xhu, Z-X; Morcos, P N; Davis, J D; Phipps, A

2015-09-01

Cancer immunotherapy (CIT) initiates or enhances the host immune response against cancer. Following decades of development, patients with previously few therapeutic options may now benefit from CIT. Although the quantitative clinical pharmacology (qCP) of previous classes of anticancer drugs has matured during this time, application to CIT may not be straightforward since CIT acts via the immune system. Here we discuss where qCP approaches might best borrow or start anew for CIT.

Steps to achieve quantitative measurements of microRNA using two step droplet digital PCR.

PubMed

Stein, Erica V; Duewer, David L; Farkas, Natalia; Romsos, Erica L; Wang, Lili; Cole, Kenneth D

2017-01-01

Droplet digital PCR (ddPCR) is being advocated as a reference method to measure rare genomic targets. It has consistently been proven to be more sensitive and direct at discerning copy numbers of DNA than other quantitative methods. However, one of the largest obstacles to measuring microRNA (miRNA) using ddPCR is that reverse transcription efficiency depends upon the target, meaning small RNA nucleotide composition directly effects primer specificity in a manner that prevents traditional quantitation optimization strategies. Additionally, the use of reagents that are optimized for miRNA measurements using quantitative real-time PCR (qRT-PCR) appear to either cause false positive or false negative detection of certain targets when used with traditional ddPCR quantification methods. False readings are often related to using inadequate enzymes, primers and probes. Given that two-step miRNA quantification using ddPCR relies solely on reverse transcription and uses proprietary reagents previously optimized only for qRT-PCR, these barriers are substantial. Therefore, here we outline essential controls, optimization techniques, and an efficacy model to improve the quality of ddPCR miRNA measurements. We have applied two-step principles used for miRNA qRT-PCR measurements and leveraged the use of synthetic miRNA targets to evaluate ddPCR following cDNA synthesis with four different commercial kits. We have identified inefficiencies and limitations as well as proposed ways to circumvent identified obstacles. Lastly, we show that we can apply these criteria to a model system to confidently quantify miRNA copy number. Our measurement technique is a novel way to quantify specific miRNA copy number in a single sample, without using standard curves for individual experiments. Our methodology can be used for validation and control measurements, as well as a diagnostic technique that allows scientists, technicians, clinicians, and regulators to base miRNA measures on a single unit of measurement rather than a ratio of values.

Steps to achieve quantitative measurements of microRNA using two step droplet digital PCR

PubMed Central

Duewer, David L.; Farkas, Natalia; Romsos, Erica L.; Wang, Lili; Cole, Kenneth D.

2017-01-01

Droplet digital PCR (ddPCR) is being advocated as a reference method to measure rare genomic targets. It has consistently been proven to be more sensitive and direct at discerning copy numbers of DNA than other quantitative methods. However, one of the largest obstacles to measuring microRNA (miRNA) using ddPCR is that reverse transcription efficiency depends upon the target, meaning small RNA nucleotide composition directly effects primer specificity in a manner that prevents traditional quantitation optimization strategies. Additionally, the use of reagents that are optimized for miRNA measurements using quantitative real-time PCR (qRT-PCR) appear to either cause false positive or false negative detection of certain targets when used with traditional ddPCR quantification methods. False readings are often related to using inadequate enzymes, primers and probes. Given that two-step miRNA quantification using ddPCR relies solely on reverse transcription and uses proprietary reagents previously optimized only for qRT-PCR, these barriers are substantial. Therefore, here we outline essential controls, optimization techniques, and an efficacy model to improve the quality of ddPCR miRNA measurements. We have applied two-step principles used for miRNA qRT-PCR measurements and leveraged the use of synthetic miRNA targets to evaluate ddPCR following cDNA synthesis with four different commercial kits. We have identified inefficiencies and limitations as well as proposed ways to circumvent identified obstacles. Lastly, we show that we can apply these criteria to a model system to confidently quantify miRNA copy number. Our measurement technique is a novel way to quantify specific miRNA copy number in a single sample, without using standard curves for individual experiments. Our methodology can be used for validation and control measurements, as well as a diagnostic technique that allows scientists, technicians, clinicians, and regulators to base miRNA measures on a single unit of measurement rather than a ratio of values. PMID:29145448

Quantitative Assay of Pyrazofurin a New Antiviral, Antitumor Antibiotic1

PubMed Central

Westhead, J. E.; Price, H. D.

1974-01-01

Pyrazofurin, a carbon-linked nucleoside, has been previously reported to possess antiviral and antitumor activity. The antagonistic effect of pyrazofurin against Neurospora crassa has been utilized to develop a quantitative assay for the compound. PMID:4275616

Different binding motifs of the celiac disease-associated HLA molecules DQ2.5, DQ2.2, and DQ7.5 revealed by relative quantitative proteomics of endogenous peptide repertoires.

PubMed

Bergseng, Elin; Dørum, Siri; Arntzen, Magnus Ø; Nielsen, Morten; Nygård, Ståle; Buus, Søren; de Souza, Gustavo A; Sollid, Ludvig M

2015-02-01

Celiac disease is caused by intolerance to cereal gluten proteins, and HLA-DQ molecules are involved in the disease pathogenesis by presentation of gluten peptides to CD4(+) T cells. The α- or β-chain sharing HLA molecules DQ2.5, DQ2.2, and DQ7.5 display different risks for the disease. It was recently demonstrated that T cells of DQ2.5 and DQ2.2 patients recognize distinct sets of gluten epitopes, suggesting that these two DQ2 variants select different peptides for display. To explore whether this is the case, we performed a comprehensive comparison of the endogenous self-peptides bound to HLA-DQ molecules of B-lymphoblastoid cell lines. Peptides were eluted from affinity-purified HLA molecules of nine cell lines and subjected to quadrupole orbitrap mass spectrometry and MaxQuant software analysis. Altogether, 12,712 endogenous peptides were identified at very different relative abundances. Hierarchical clustering of normalized quantitative data demonstrated significant differences in repertoires of peptides between the three DQ variant molecules. The neural network-based method, NNAlign, was used to identify peptide-binding motifs. The binding motifs of DQ2.5 and DQ7.5 concurred with previously established binding motifs. The binding motif of DQ2.2 was strikingly different from that of DQ2.5 with position P3 being a major anchor having a preference for threonine and serine. This is notable as three recently identified epitopes of gluten recognized by T cells of DQ2.2 celiac patients harbor serine at position P3. This study demonstrates that relative quantitative comparison of endogenous peptides sampled from our protein metabolism by HLA molecules provides clues to understand HLA association with disease.

Understanding the relationships between the physical environment and physical activity in older adults: a systematic review of qualitative studies.

PubMed

Moran, Mika; Van Cauwenberg, Jelle; Hercky-Linnewiel, Rachel; Cerin, Ester; Deforche, Benedicte; Plaut, Pnina

2014-07-17

While physical activity (PA) provides many physical, social, and mental health benefits for older adults, they are the least physically active age group. Ecological models highlight the importance of the physical environment in promoting PA. However, results of previous quantitative research revealed inconsistencies in environmental correlates of older adults' PA that may be explained by methodological issues. Qualitative studies can inform and complement quantitative research on environment-PA relationships by providing insight into how and why the environment influences participants' PA behaviors. The current study aimed to provide a systematic review of qualitative studies exploring the potential impact of the physical environment on older adults' PA behaviors. A systematic search was conducted in databases of various disciplines, including: health, architecture and urban planning, transportation, and interdisciplinary databases. From 3,047 articles identified in the physical activity, initial search, 31 articles published from 1996 to 2012 met all inclusion criteria. An inductive content analysis was performed on the extracted findings to identify emerging environmental elements related to older adults' PA. The identified environmental elements were then grouped by study methodologies [indoor interviews (individual or focus groups) vs spatial methods (photo-voice, observations, walk-along interviews)]. This review provides detailed information about environmental factors that potentially influence older adults' PA behaviors. These factors were categorized into five themes: pedestrian infrastructure, safety, access to amenities, aesthetics, and environmental conditions. Environmental factors especially relevant to older adults (i.e., access to facilities, green open spaces and rest areas) tended to emerge more frequently in studies that combined interviews with spatial qualitative methods. Findings showed that qualitative research can provide in-depth information on environmental elements that influence older adults' PA. Future qualitative studies on the physical environment and older adults' PA would benefit from combining interviews with more spatially-oriented methods. Multidisciplinary mixed-methods studies are recommended to establish quantitative relationships complemented with in-depth qualitative information.

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

PubMed

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

2016-11-01

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

Genome-Wide Association Studies of the Human Gut Microbiota.

PubMed

Davenport, Emily R; Cusanovich, Darren A; Michelini, Katelyn; Barreiro, Luis B; Ober, Carole; Gilad, Yoav

2015-01-01

The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

Development of quantitative risk acceptance criteria

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

Griesmeyer, J. M.; Okrent, D.

Some of the major considerations for effective management of risk are discussed, with particular emphasis on risks due to nuclear power plant operations. Although there are impacts associated with the rest of the fuel cycle, they are not addressed here. Several previously published proposals for quantitative risk criteria are reviewed. They range from a simple acceptance criterion on individual risk of death to a quantitative risk management framework. The final section discussed some of the problems in the establishment of a framework for the quantitative management of risk.

Quantified acoustic-optical speech signal incongruity identifies cortical sites of audiovisual speech processing

PubMed Central

Bernstein, Lynne E.; Lu, Zhong-Lin; Jiang, Jintao

2008-01-01

A fundamental question about human perception is how the speech perceiving brain combines auditory and visual phonetic stimulus information. We assumed that perceivers learn the normal relationship between acoustic and optical signals. We hypothesized that when the normal relationship is perturbed by mismatching the acoustic and optical signals, cortical areas responsible for audiovisual stimulus integration respond as a function of the magnitude of the mismatch. To test this hypothesis, in a previous study, we developed quantitative measures of acoustic-optical speech stimulus incongruity that correlate with perceptual measures. In the current study, we presented low incongruity (LI, matched), medium incongruity (MI, moderately mismatched), and high incongruity (HI, highly mismatched) audiovisual nonsense syllable stimuli during fMRI scanning. Perceptual responses differed as a function of the incongruity level, and BOLD measures were found to vary regionally and quantitatively with perceptual and quantitative incongruity levels. Each increase in level of incongruity resulted in an increase in overall levels of cortical activity and in additional activations. However, the only cortical region that demonstrated differential sensitivity to the three stimulus incongruity levels (HI > MI > LI) was a subarea of the left supramarginal gyrus (SMG). The left SMG might support a fine-grained analysis of the relationship between audiovisual phonetic input in comparison with stored knowledge, as hypothesized here. The methods here show that quantitative manipulation of stimulus incongruity is a new and powerful tool for disclosing the system that processes audiovisual speech stimuli. PMID:18495091

Disposable MoS2-Arrayed MALDI MS Chip for High-Throughput and Rapid Quantification of Sulfonamides in Multiple Real Samples.

PubMed

Zhao, Yaju; Tang, Minmin; Liao, Qiaobo; Li, Zhoumin; Li, Hui; Xi, Kai; Tan, Li; Zhang, Mei; Xu, Danke; Chen, Hong-Yuan

2018-04-27

In this work, we demonstrate, for the first time, the development of a disposable MoS 2 -arrayed matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) chip combined with an immunoaffinity enrichment method for high-throughput, rapid, and simultaneous quantitation of multiple sulfonamides (SAs). The disposable MALDI MS chip was designed and fabricated by MoS 2 array formation on a commercial indium tin oxide (ITO) glass slide. A series of SAs were analyzed, and clear deprotonated signals were obtained in negative-ion mode. Compared with MoS 2 -arrayed commercial steel plate, the prepared MALDI MS chip exhibited comparable LDI efficiency, providing a good alternative and disposable substrate for MALDI MS analysis. Furthermore, internal standard (IS) was previously deposited onto the MoS 2 array to simplify the experimental process for MALDI MS quantitation. 96 sample spots could be analyzed within 10 min in one single chip to perform quantitative analysis, recovery studies, and real foodstuff detection. Upon targeted extraction and enrichment by antibody conjugated magnetic beads, five SAs were quantitatively determined by the IS-first method with the linear range of 0.5-10 ng/mL ( R 2 > 0.990). Good recoveries and repeatability were obtained for spiked pork, egg, and milk samples. SAs in several real foodstuffs were successfully identified and quantified. The developed method may provide a promising tool for the routine analysis of antibiotic residues in real samples.

Effects of music therapy and music-based interventions in the treatment of substance use disorders: A systematic review

PubMed Central

Hohmann, Louisa; Bradt, Joke; Stegemann, Thomas; Koelsch, Stefan

2017-01-01

Music therapy (MT) and music-based interventions (MBIs) are increasingly used for the treatment of substance use disorders (SUD). Previous reviews on the efficacy of MT emphasized the dearth of research evidence for this topic, although various positive effects were identified. Therefore, we conducted a systematic search on published articles examining effects of music, MT and MBIs and found 34 quantitative and six qualitative studies. There was a clear increase in the number of randomized controlled trials (RCTs) during the past few years. We had planned for a meta-analysis, but due to the diversity of the quantitative studies, effect sizes were not computed. Beneficial effects of MT/ MBI on emotional and motivational outcomes, participation, locus of control, and perceived helpfulness were reported, but results were inconsistent across studies. Furthermore, many RCTs focused on effects of single sessions. No published longitudinal trials could be found. The analysis of the qualitative studies revealed four themes: emotional expression, group interaction, development of skills, and improvement of quality of life. Considering these issues for quantitative research, there is a need to examine social and health variables in future studies. In conclusion, due to the heterogeneity of the studies, the efficacy of MT/ MBI in SUD treatment still remains unclear. PMID:29141012

Label-free protein profiling of formalin-fixed paraffin-embedded (FFPE) heart tissue reveals immediate mitochondrial impairment after ionising radiation.

PubMed

Azimzadeh, Omid; Scherthan, Harry; Yentrapalli, Ramesh; Barjaktarovic, Zarko; Ueffing, Marius; Conrad, Marcus; Neff, Frauke; Calzada-Wack, Julia; Aubele, Michaela; Buske, Christian; Atkinson, Michael J; Hauck, Stefanie M; Tapio, Soile

2012-04-18

Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue is advancing the field of clinical proteomics. However, quantitative proteome analysis of FFPE tissue is hampered by the lack of an efficient labelling method. The usage of conventional protein labelling on FFPE tissue has turned out to be inefficient. Classical labelling targets lysine residues that are blocked by the formalin treatment. The aim of this study was to establish a quantitative proteomics analysis of FFPE tissue by combining the label-free approach with optimised protein extraction and separation conditions. As a model system we used FFPE heart tissue of control and exposed C57BL/6 mice after total body irradiation using a gamma ray dose of 3 gray. We identified 32 deregulated proteins (p≤0.05) in irradiated hearts 24h after the exposure. The proteomics data were further evaluated and validated by bioinformatics and immunoblotting investigation. In good agreement with our previous results using fresh-frozen tissue, the analysis indicated radiation-induced alterations in three main biological pathways: respiratory chain, lipid metabolism and pyruvate metabolism. The label-free approach enables the quantitative measurement of radiation-induced alterations in FFPE tissue and facilitates retrospective biomarker identification using clinical archives. Copyright © 2012 Elsevier B.V. All rights reserved.

Underwater image enhancement based on the dark channel prior and attenuation compensation

NASA Astrophysics Data System (ADS)

Guo, Qingwen; Xue, Lulu; Tang, Ruichun; Guo, Lingrui

2017-10-01

Aimed at the two problems of underwater imaging, fog effect and color cast, an Improved Segmentation Dark Channel Prior (ISDCP) defogging method is proposed to solve the fog effects caused by physical properties of water. Due to mass refraction of light in the process of underwater imaging, fog effects would lead to image blurring. And color cast is closely related to different degree of attenuation while light with different wavelengths is traveling in water. The proposed method here integrates the ISDCP and quantitative histogram stretching techniques into the image enhancement procedure. Firstly, the threshold value is set during the refinement process of the transmission maps to identify the original mismatching, and to conduct the differentiated defogging process further. Secondly, a method of judging the propagating distance of light is adopted to get the attenuation degree of energy during the propagation underwater. Finally, the image histogram is stretched quantitatively in Red-Green-Blue channel respectively according to the degree of attenuation in each color channel. The proposed method ISDCP can reduce the computational complexity and improve the efficiency in terms of defogging effect to meet the real-time requirements. Qualitative and quantitative comparison for several different underwater scenes reveals that the proposed method can significantly improve the visibility compared with previous methods.

Applying pollen DNA metabarcoding to the study of plant–pollinator interactions1

PubMed Central

Bell, Karen L.; Fowler, Julie; Burgess, Kevin S.; Dobbs, Emily K.; Gruenewald, David; Lawley, Brice; Morozumi, Connor; Brosi, Berry J.

2017-01-01

Premise of the study: To study pollination networks in a changing environment, we need accurate, high-throughput methods. Previous studies have shown that more highly resolved networks can be constructed by studying pollen loads taken from bees, relative to field observations. DNA metabarcoding potentially allows for faster and finer-scale taxonomic resolution of pollen compared to traditional approaches (e.g., light microscopy), but has not been applied to pollination networks. Methods: We sampled pollen from 38 bee species collected in Florida from sites differing in forest management. We isolated DNA from pollen mixtures and sequenced rbcL and ITS2 gene regions from all mixtures in a single run on the Illumina MiSeq platform. We identified species from sequence data using comprehensive rbcL and ITS2 databases. Results: We successfully built a proof-of-concept quantitative pollination network using pollen metabarcoding. Discussion: Our work underscores that pollen metabarcoding is not quantitative but that quantitative networks can be constructed based on the number of interacting individuals. Due to the frequency of contamination and false positive reads, isolation and PCR negative controls should be used in every reaction. DNA metabarcoding has advantages in efficiency and resolution over microscopic identification of pollen, and we expect that it will have broad utility for future studies of plant–pollinator interactions. PMID:28690929

The Brain Network for Deductive Reasoning: A Quantitative Meta-analysis of 28 Neuroimaging Studies

PubMed Central

Prado, Jérôme; Chadha, Angad; Booth, James R.

2011-01-01

Over the course of the past decade, contradictory claims have been made regarding the neural bases of deductive reasoning. Researchers have been puzzled by apparent inconsistencies in the literature. Some have even questioned the effectiveness of the methodology used to study the neural bases of deductive reasoning. However, the idea that neuroimaging findings are inconsistent is not based on any quantitative evidence. Here, we report the results of a quantitative meta-analysis of 28 neuroimaging studies of deductive reasoning published between 1997 and 2010, combining 382 participants. Consistent areas of activations across studies were identified using the multilevel kernel density analysis method. We found that results from neuroimaging studies are more consistent than what has been previously assumed. Overall, studies consistently report activations in specific regions of a left fronto-parietal system, as well as in the left Basal Ganglia. This brain system can be decomposed into three subsystems that are specific to particular types of deductive arguments: relational, categorical, and propositional. These dissociations explain inconstancies in the literature. However, they are incompatible with the notion that deductive reasoning is supported by a single cognitive system relying either on visuospatial or rule-based mechanisms. Our findings provide critical insight into the cognitive organization of deductive reasoning and need to be accounted for by cognitive theories. PMID:21568632

UHPLC-MS/MS method for the quantitation of penicillin G and metabolites in citrus fruit using internal standards.

PubMed

Canzani, Daniele; Hsieh, Kevin; Standland, Matthew; Hammack, Walter; Aldeek, Fadi

2017-02-15

Penicillin G has been applied to citrus trees as a potential treatment in the fight against Huanglongbing (HLB). Here, we have developed and validated a method to identify and quantitate penicillin G and two of its metabolites, penillic acid and penilloic acid, in citrus fruit using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). This method improves upon a previous method by incorporating isotopically labeled internal standards, namely, penillic acid-D 5 , and penilloic acid-D 5 . These standards greatly enhanced the accuracy and precision of our measurements by compensating for recovery losses, degradation, and matrix effects. When 2g of citrus fruit sample is extracted, the limits of detection (LOD) were determined to be 0.1ng/g for penicillin G and penilloic acid, and 0.25ng/g for penillic acid. At fortification levels of 0.1, 0.25, 1, and 10ng/g, absolute recoveries for penillic and penilloic acids were generally between 50-70%. Recoveries corrected with the isotopically labeled standards were approximately 90-110%. This method will be useful for the identification and quantitation of drug residues and their degradation products using isotopically labeled standards and UHPLC-MS/MS. Published by Elsevier B.V.

Genetic variants associated with the root system architecture of oilseed rape (Brassica napus L.) under contrasting phosphate supply.

PubMed

Wang, Xiaohua; Chen, Yanling; Thomas, Catherine L; Ding, Guangda; Xu, Ping; Shi, Dexu; Grandke, Fabian; Jin, Kemo; Cai, Hongmei; Xu, Fangsen; Yi, Bin; Broadley, Martin R; Shi, Lei

2017-08-01

Breeding crops with ideal root system architecture for efficient absorption of phosphorus is an important strategy to reduce the use of phosphate fertilizers. To investigate genetic variants leading to changes in root system architecture, 405 oilseed rape cultivars were genotyped with a 60K Brassica Infinium SNP array in low and high P environments. A total of 285 single-nucleotide polymorphisms were associated with root system architecture traits at varying phosphorus levels. Nine single-nucleotide polymorphisms corroborate a previous linkage analysis of root system architecture quantitative trait loci in the BnaTNDH population. One peak single-nucleotide polymorphism region on A3 was associated with all root system architecture traits and co-localized with a quantitative trait locus for primary root length at low phosphorus. Two more single-nucleotide polymorphism peaks on A5 for root dry weight at low phosphorus were detected in both growth systems and co-localized with a quantitative trait locus for the same trait. The candidate genes identified on A3 form a haplotype 'BnA3Hap', that will be important for understanding the phosphorus/root system interaction and for the incorporation into Brassica napus breeding programs. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

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

Zhang, Qibin; Monroe, Matthew E.; Schepmoes, Athena A.

Non-enzymatic glycation of proteins is implicated in diabetes mellitus and its related complications. In this report, we extend our previous development and refinement of proteomics-based methods for the analysis of non-enzymatically glycated proteins to comprehensively identify glycated proteins in normal and diabetic human plasma and erythrocytes. Using immunodepletion, enrichment, and fractionation strategies, we identified 7749 unique glycated peptides, corresponding to 3742 unique glycated proteins. Semi-quantitative comparisons revealed a number of proteins with glycation levels significantly increased in diabetes relative to control samples and that erythrocyte proteins are more extensively glycated than plasma proteins. A glycation motif analysis revealed amino acidsmore » that are favored more than others in the protein primary structures in the vicinity of the glycation sites in both sample types. The glycated peptides and corresponding proteins reported here provide a foundation for the potential identification of novel markers for diabetes, glycemia, or diabetic complications.« less

Barriers to self-care in women of reproductive age with HIV/AIDS in Iran: a qualitative study.

PubMed

Oskouie, Fatemeh; Kashefi, Farzaneh; Rafii, Forough; Gouya, Mohammad Mehdi

2017-01-01

Although increasing attention is paid to HIV/AIDS, patients with HIV still experience several barriers to self-care. These barriers have been previously identified in small quantitative studies on women with HIV, but qualitative studies are required to clarify barriers to self-care. We conducted our study using the grounded theory methodological approach. A total of 28 women with HIV and their family members, were interviewed. The data were analyzed with the Corbin and Strauss method (1998). The key barriers to self-care in women with HIV/AIDS included social stigma, addiction, psychological problems, medication side-effects and financial problems. Women with HIV/AIDS face several barriers to self-care. Therefore, when designing self-care models for these women, social and financial barriers should be identified. Mental health treatment should also be incorporated into such models and patients' access to health care services should be facilitated.

Metabolome-genome-wide association study dissects genetic architecture for generating natural variation in rice secondary metabolism

PubMed Central

Matsuda, Fumio; Nakabayashi, Ryo; Yang, Zhigang; Okazaki, Yozo; Yonemaru, Jun-ichi; Ebana, Kaworu; Yano, Masahiro; Saito, Kazuki

2015-01-01

Plants produce structurally diverse secondary (specialized) metabolites to increase their fitness for survival under adverse environments. Several bioactive compounds for new drugs have been identified through screening of plant extracts. In this study, genome-wide association studies (GWAS) were conducted to investigate the genetic architecture behind the natural variation of rice secondary metabolites. GWAS using the metabolome data of 175 rice accessions successfully identified 323 associations among 143 single nucleotide polymorphisms (SNPs) and 89 metabolites. The data analysis highlighted that levels of many metabolites are tightly associated with a small number of strong quantitative trait loci (QTLs). The tight association may be a mechanism generating strains with distinct metabolic composition through the crossing of two different strains. The results indicate that one plant species produces more diverse phytochemicals than previously expected, and plants still contain many useful compounds for human applications. PMID:25267402

Large-scale Phenotyping of Noise-Induced Hearing Loss in 100 Strains of Mice

PubMed Central

Myint, Anthony; White, Cory H.; Ohmen, Jeffrey D.; Li, Xin; Wang, Juemei; Lavinsky, Joel; Salehi, Pezhman; Crow, Amanda L.; Ohyama, Takahiro; Friedman, Rick A.

2015-01-01

A cornerstone technique in the study of hearing is the Auditory Brainstem Response (ABR), an electrophysiologic technique that can be used as a quantitative measure of hearing function. Previous studies have published databases of baseline ABR thresholds for mouse strains, providing a valuable resource for the study of baseline hearing function and genetic mapping of hearing traits in mice. In this study, we further expand upon the existing literature by characterizing the baseline ABR characteristics of 100 inbred mouse strains, 47 of which are newly characterized for hearing function. We identify several distinct patterns of baseline hearing deficits and provide potential avenues for further investigation. Additionally, we characterize the sensitivity of the same 100 strains to noise exposure using permanent thresholds shifts, identifying several distinct patterns of noise-sensitivity. The resulting data provides a new resource for studying hearing loss and noise-sensitivity in mice. PMID:26706709

A public platform for the verification of the phenotypic effect of candidate genes for resistance to aflatoxin accumulation and Aspergillus flavus infection in maize.

PubMed

Warburton, Marilyn L; Williams, William Paul; Hawkins, Leigh; Bridges, Susan; Gresham, Cathy; Harper, Jonathan; Ozkan, Seval; Mylroie, J Erik; Shan, Xueyan

2011-07-01

A public candidate gene testing pipeline for resistance to aflatoxin accumulation or Aspergillus flavus infection in maize is presented here. The pipeline consists of steps for identifying, testing, and verifying the association of selected maize gene sequences with resistance under field conditions. Resources include a database of genetic and protein sequences associated with the reduction in aflatoxin contamination from previous studies; eight diverse inbred maize lines for polymorphism identification within any maize gene sequence; four Quantitative Trait Loci (QTL) mapping populations and one association mapping panel, all phenotyped for aflatoxin accumulation resistance and associated phenotypes; and capacity for Insertion/Deletion (InDel) and SNP genotyping in the population(s) for mapping. To date, ten genes have been identified as possible candidate genes and put through the candidate gene testing pipeline, and results are presented here to demonstrate the utility of the pipeline.

Fine mapping of a quantitative resistance gene for gray leaf spot of maize (Zea mays L.) derived from teosinte (Z. mays ssp. parviglumis).

PubMed

Zhang, Xinye; Yang, Qin; Rucker, Elizabeth; Thomason, Wade; Balint-Kurti, Peter

2017-06-01

In this study we mapped the QTL Qgls8 for gray leaf spot (GLS) resistance in maize to a ~130 kb region on chromosome 8 including five predicted genes. In previous work, using near isogenic line (NIL) populations in which segments of the teosinte (Zea mays ssp. parviglumis) genome had been introgressed into the background of the maize line B73, we had identified a QTL on chromosome 8, here called Qgls8, for gray leaf spot (GLS) resistance. We identified alternate teosinte alleles at this QTL, one conferring increased GLS resistance and one increased susceptibility relative to the B73 allele. Using segregating populations derived from NIL parents carrying these contrasting alleles, we were able to delimit the QTL region to a ~130 kb (based on the B73 genome) which encompassed five predicted genes.

Creativity and Bipolar Disorder: Igniting a Dialogue.

PubMed

Johnson, Sheri L; Moezpoor, Michelle; Murray, Greg; Hole, Rachelle; Barnes, Steven J; Michalak, Erin E

2016-01-01

Bipolar disorder (BD) has been related to heightened creativity, yet core questions remain unaddressed about this association. We used qualitative methods to investigate how highly creative individuals with BD understand the role of symptoms and treatment in their creativity, and possible mechanisms underpinning this link. Twenty-two individuals self-identified as highly creative and living with BD took part in focus groups and completed quantitative measures of symptoms, quality of life (QoL), and creativity. Using thematic analysis, five themes emerged: the pros and cons of mania for creativity, benefits of altered thinking, the relationship between creativity and medication, creativity as central to one's identity, and creativity's importance in stigma reduction and treatment. Despite reliance on a small sample who self-identified as having BD, findings shed light on previously mixed results regarding the influence of mania and treatment and suggest new directions for the study of mechanisms driving the creative advantage in BD. © The Author(s) 2015.

Integrative strategies to identify candidate genes in rodent models of human alcoholism.

PubMed

Treadwell, Julie A

2006-01-01

The search for genes underlying alcohol-related behaviours in rodent models of human alcoholism has been ongoing for many years with only limited success. Recently, new strategies that integrate several of the traditional approaches have provided new insights into the molecular mechanisms underlying ethanol's actions in the brain. We have used alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) genetic strains of mice in an integrative strategy combining high-throughput gene expression screening, genetic segregation analysis, and mapping to previously published quantitative trait loci to uncover candidate genes for the ethanol-preference phenotype. In our study, 2 genes, retinaldehyde binding protein 1 (Rlbp1) and syntaxin 12 (Stx12), were found to be strong candidates for ethanol preference. Such experimental approaches have the power and the potential to greatly speed up the laborious process of identifying candidate genes for the animal models of human alcoholism.

Quantitative and qualitative approaches to identifying migration chronology in a continental migrant

USGS Publications Warehouse

Beatty, William S.; Kesler, Dylan C.; Webb, Elisabeth B.; Raedeke, Andrew H.; Naylor, Luke W.; Humburg, Dale D.

2013-01-01

The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted conservation plans can be developed to support planning for habitat management and evaluation of long-term climate effects.

Genome investigation suggests MdSHN3, an APETALA2-domain transcription factor gene, to be a positive regulator of apple fruit cuticle formation and an inhibitor of russet development

PubMed Central

Lashbrooke, Justin; Aharoni, Asaph; Costa, Fabrizio

2015-01-01

The outer epidermal layer of apple fruit is covered by a protective cuticle. Composed of a polymerized cutin matrix embedded with waxes, the cuticle is a natural waterproof barrier and protects against several abiotic and biotic stresses. In terms of apple production, the cuticle is essential to maintain long post-harvest storage, while severe failure of the cuticle can result in the formation of a disorder known as russet. Apple russet results from micro-cracking of the cuticle and the formation of a corky suberized layer. This is typically an undesirable consumer trait, and negatively impacts the post-harvest storage of apples. In order to identify genetic factors controlling cuticle biosynthesis (and thus preventing russet) in apple, a quantitative trait locus (QTL) mapping survey was performed on a full-sib population. Two genomic regions located on chromosomes 2 and 15 that could be associated with russeting were identified. Apples with compromised cuticles were identified through a novel and high-throughput tensile analysis of the skin, while histological analysis confirmed cuticle failure in a subset of the progeny. Additional genomic investigation of the determined QTL regions identified a set of underlying genes involved in cuticle biosynthesis. Candidate gene expression profiling by quantitative real-time PCR on a subset of the progeny highlighted the specific expression pattern of a SHN1/WIN1 transcription factor gene (termed MdSHN3) on chromosome 15. Orthologues of SHN1/WIN1 have been previously shown to regulate cuticle formation in Arabidopsis, tomato, and barley. The MdSHN3 transcription factor gene displayed extremely low expression in lines with improper cuticle formation, suggesting it to be a fundamental regulator of cuticle biosynthesis in apple fruit. PMID:26220084

Quantitative and qualitative approaches to identifying migration chronology in a continental migrant.

PubMed

Beatty, William S; Kesler, Dylan C; Webb, Elisabeth B; Raedeke, Andrew H; Naylor, Luke W; Humburg, Dale D

2013-01-01

The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted conservation plans can be developed to support planning for habitat management and evaluation of long-term climate effects.

THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression.

PubMed

Cheng, Fu Bo; Ozelius, Laurie J; Wan, Xin Hua; Feng, Jia Chun; Ma, Ling Yan; Yang, Ying Mai; Wang, Lin

2012-02-01

Mutations in the THAP1 gene were recently identified as the cause of DYT6 primary dystonia. More than 40 mutations in this gene have been described in different populations. However, no previous report has identified sequence variations that affect the transcript process of the THAP1 gene. In addition, the mutation frequency in Chinese early-onset primary dystonia has not been well characterized. One hundred and two unrelated patients with non-DYT1 early-onset primary dystonia (age at onset <26 years), family members of participants with mutations, and 200 neurologically normal controls were screened for THAP1 gene mutations. The effects of the identified mutations on RNA expression were analyzed using semi-quantitative real-time PCR. Seven sequence variants (c.63_66del TTTC, c.161G>T, c.224A>T, c.267G>A, c.339T>C, c.449A>C, and c.539T>C) were identified in this group of patients (6.9%). In this cohort, 15 subjects (seven unrelated patients and eight family members) were detected to have THAP1 sequence variants. Among these 15 subjects, 11 were manifested (penetrance of DYT6 was 73.3%) and seven presented with craniocervical involvement (63.6%). However, one patient manifested paroxysmal headshake, and one presented with essential hand tremor. Semi-quantitative real-time PCR indicated that a novel silent mutation (c.267G>A) decreased the expression of THAP1 in human lymphocytes. Our findings indicated that THAP1 sequence variants are not common in non-DYT1 early-onset primary dystonia in China and that the clinical manifestation may vary. One silent mutation (c.267G>A) was shown to affect THAP1 expression.

Genome Wide Association Study for Drought, Aflatoxin Resistance, and Important Agronomic Traits of Maize Hybrids in the Sub-Tropics

PubMed Central

Farfan, Ivan D. Barrero; De La Fuente, Gerald N.; Murray, Seth C.; Isakeit, Thomas; Huang, Pei-Cheng; Warburton, Marilyn; Williams, Paul; Windham, Gary L.; Kolomiets, Mike

2015-01-01

The primary maize (Zea mays L.) production areas are in temperate regions throughout the world and this is where most maize breeding is focused. Important but lower yielding maize growing regions such as the sub-tropics experience unique challenges, the greatest of which are drought stress and aflatoxin contamination. Here we used a diversity panel consisting of 346 maize inbred lines originating in temperate, sub-tropical and tropical areas testcrossed to stiff-stalk line Tx714 to investigate these traits. Testcross hybrids were evaluated under irrigated and non-irrigated trials for yield, plant height, ear height, days to anthesis, days to silking and other agronomic traits. Irrigated trials were also inoculated with Aspergillus flavus and evaluated for aflatoxin content. Diverse maize testcrosses out-yielded commercial checks in most trials, which indicated the potential for genetic diversity to improve sub-tropical breeding programs. To identify genomic regions associated with yield, aflatoxin resistance and other important agronomic traits, a genome wide association analysis was performed. Using 60,000 SNPs, this study found 10 quantitative trait variants for grain yield, plant and ear height, and flowering time after stringent multiple test corrections, and after fitting different models. Three of these variants explained 5–10% of the variation in grain yield under both water conditions. Multiple identified SNPs co-localized with previously reported QTL, which narrows the possible location of causal polymorphisms. Novel significant SNPs were also identified. This study demonstrated the potential to use genome wide association studies to identify major variants of quantitative and complex traits such as yield under drought that are still segregating between elite inbred lines. PMID:25714370

Association mapping of seed quality traits using the Canadian flax (Linum usitatissimum L.) core collection.

PubMed

Soto-Cerda, Braulio J; Duguid, Scott; Booker, Helen; Rowland, Gordon; Diederichsen, Axel; Cloutier, Sylvie

2014-04-01

The identification of stable QTL for seed quality traits by association mapping of a diverse panel of linseed accessions establishes the foundation for assisted breeding and future fine mapping in linseed. Linseed oil is valued for its food and non-food applications. Modifying its oil content and fatty acid (FA) profiles to meet market needs in a timely manner requires clear understanding of their quantitative trait loci (QTL) architectures, which have received little attention to date. Association mapping is an efficient approach to identify QTL in germplasm collections. In this study, we explored the quantitative nature of seed quality traits including oil content (OIL), palmitic acid, stearic acid, oleic acid, linoleic acid (LIO) linolenic acid (LIN) and iodine value in a flax core collection of 390 accessions assayed with 460 microsatellite markers. The core collection was grown in a modified augmented design at two locations over 3 years and phenotypic data for all seven traits were obtained from all six environments. Significant phenotypic diversity and moderate to high heritability for each trait (0.73-0.99) were observed. Most of the candidate QTL were stable as revealed by multivariate analyses. Nine candidate QTL were identified, varying from one for OIL to three for LIO and LIN. Candidate QTL for LIO and LIN co-localized with QTL previously identified in bi-parental populations and some mapped nearby genes known to be involved in the FA biosynthesis pathway. Fifty-eight percent of the QTL alleles were absent (private) in the Canadian cultivars suggesting that the core collection possesses QTL alleles potentially useful to improve seed quality traits. The candidate QTL identified herein will establish the foundation for future marker-assisted breeding in linseed.

Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients

PubMed Central

Armas-López, Leonel; Piña-Sánchez, Patricia; Arrieta, Oscar; de Alba, Enrique Guzman; Ortiz-Quintero, Blanca; Santillán-Doherty, Patricio; Christiani, David C.; Zúñiga, Joaquín; Ávila-Moreno, Federico

2017-01-01

Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis. Chromatin immunoprecipitation (ChIP) assays derived from non-small cell lung carcinomas (NSCLC) hybridized on gene promoter tiling arrays and bioinformatics analyses were performed, and quantitative, functional and clinical validation were also carried out. We statistically identified a common profile consisting of 78 gene promoter targets, including Hedgehog-GLI1 gene promoter sequences (FDR≤0.1 and FDR≤0.2). The GLI-1 gene promoter region from −2,192 to −109 was occupied by MEOX2, accompanied by transcriptionally active RNA Pol II and was epigenetically linked to the active histones H3K27Ac and H3K4me3; these associations were quantitatively validated. Moreover, siRNA genetic silencing assays identified a MEOX2-GLI1 axis involved in cellular cytotoxic resistance to cisplatinum in a dose-dependent manner, as well as cellular migration and proliferation. Finally, Kaplan-Maier survival analyses identified significant MEOX2-dependent GLI-1 protein expression associated with clinical progression and poorer overall survival using an independent cohort of NSCLC patients undergoing platinum-based oncological therapy with both epidermal growth factor receptor (EGFR)-non-mutated and EGFR-mutated status. In conclusion, this is the first study to investigate epigenome-wide MEOX2-transcription factor occupation identifying a novel overexpressed MEOX2-GLI1 axis and its clinical association with platinum-based cancer drug resistance and EGFR-tyrosine kinase inhibitor (TKI)-based therapy responses in NSCLC patients. PMID:28978016

Slowed articulation rate is a sensitive diagnostic marker for identifying non-fluent primary progressive aphasia

PubMed Central

Cordella, Claire; Dickerson, Bradford C.; Quimby, Megan; Yunusova, Yana; Green, Jordan R.

2016-01-01

Background Primary progressive aphasia (PPA) is a neurodegenerative aphasic syndrome with three distinct clinical variants: non-fluent (nfvPPA), logopenic (lvPPA), and semantic (svPPA). Speech (non-) fluency is a key diagnostic marker used to aid identification of the clinical variants, and researchers have been actively developing diagnostic tools to assess speech fluency. Current approaches reveal coarse differences in fluency between subgroups, but often fail to clearly differentiate nfvPPA from the variably fluent lvPPA. More robust subtype differentiation may be possible with finer-grained measures of fluency. Aims We sought to identify the quantitative measures of speech rate—including articulation rate and pausing measures—that best differentiated PPA subtypes, specifically the non-fluent group (nfvPPA) from the more fluent groups (lvPPA, svPPA). The diagnostic accuracy of the quantitative speech rate variables was compared to that of a speech fluency impairment rating made by clinicians. Methods and Procedures Automatic estimates of pause and speech segment durations and rate measures were derived from connected speech samples of participants with PPA (N=38; 11 nfvPPA, 14 lvPPA, 13 svPPA) and healthy age-matched controls (N=8). Clinician ratings of fluency impairment were made using a previously validated clinician rating scale developed specifically for use in PPA. Receiver operating characteristic (ROC) analyses enabled a quantification of diagnostic accuracy. Outcomes and Results Among the quantitative measures, articulation rate was the most effective for differentiating between nfvPPA and the more fluent lvPPA and svPPA groups. The diagnostic accuracy of both speech and articulation rate measures was markedly better than that of the clinician rating scale, and articulation rate was the best classifier overall. Area under the curve (AUC) values for articulation rate were good to excellent for identifying nfvPPA from both svPPA (AUC=.96) and lvPPA (AUC=.86). Cross-validation of accuracy results for articulation rate showed good generalizability outside the training dataset. Conclusions Results provide empirical support for (1) the efficacy of quantitative assessments of speech fluency and (2) a distinct non-fluent PPA subtype characterized, at least in part, by an underlying disturbance in speech motor control. The trend toward improved classifier performance for quantitative rate measures demonstrates the potential for a more accurate and reliable approach to subtyping in the fluency domain, and suggests that articulation rate may be a useful input variable as part of a multi-dimensional clinical subtyping approach. PMID:28757671

Identifying new persistent and bioaccumulative organics among chemicals in commerce II: pharmaceuticals.

PubMed

Howard, Philip H; Muir, Derek C G

2011-08-15

The goal of this study was to identify commercial pharmaceuticals that might be persistent and bioaccumulative (P&B) and that were not being considered in current wastewater and aquatic environmental measurement programs. We developed a database of 3193 pharmaceuticals from two U.S. Food and Drug Administration (FDA) databases and some lists of top ranked or selling drugs. Of the 3193 pharmaceuticals, 275 pharmaceuticals have been found in the environment and 399 pharmaceuticals were, based upon production volumes, designated as high production volume (HPV) pharmaceuticals. All pharmaceuticals that had reported chemical structures were evaluated for potential bioaccumulation (B) or persistence (P) using quantitative structure property relationships (QSPR) or scientific judgment. Of the 275 drugs detected in the environment, 92 were rated as potentially bioaccumulative, 121 were rated as potentially persistent, and 99 were HPV pharmaceuticals. After removing the 275 pharmaceuticals previously detected in the environment, 58 HPV compounds were identified that were both P&B and 48 were identified as P only. Of the non-HPV compounds, 364 pharmaceuticals were identified that were P&B. This study has yielded some interesting and probable P&B pharmaceuticals that should be considered for further study.

Molecular characterization of G6PD deficiency in Cyprus.

PubMed

Drousiotou, Anthi; Touma, Elias H; Andreou, Nicoletta; Loiselet, Jacques; Angastiniotis, Michalis; Verrelli, Brian C; Tishkoff, Sarah A

2004-01-01

In the present study, we determined the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Cyprus using two different procedures in two separate adult population groups: a semiquantitative fluorescence test on blood spotted on filter paper and a quantitative spectrophotometric test on liquid blood. The frequency of G6PD deficiency among healthy adult males was found to be 5.1% using the semiquantitative procedure and 6.4% using the quantitative procedure. Neither method was able to detect all the expected female heterozygotes (5.3% and 47.1% of the expected number, respectively). A total of 21 male hemizygotes, 1 female homozygote and 9 female heterozygotes that tested positive for G6PD deficiency were studied at the molecular level. All 32 chromosomes were genotyped and five different mutations were identified. The Mediterranean mutation in exon 6 (563C-->T) (Ser188Phe) was found to be the most common variant in the Cypriot population, accounting for 52.6% of the deficient alleles. In the remaining chromosomes, four different mutations were identified: three known mutations, Kaiping 1388G-->A (Arg463His), Chatham 1003G-->A (Ala335Thr) and Acrokorinthos 463C-->G (His155Asp), and one previously undescribed mutation in exon 3, 148C-->T (Pro50Ser), which we called G6PD Kambos. We conclude that the frequency of G6PD deficiency in Cypriot males is 6.4%, and that this deficiency is the result of several different mutations. Although all the individuals carrying the Mediterranean variant can be detected using a semiquantitative screening method, a quantitative enzyme measurement is required to detect the G6PD variants with less severe enzyme deficiencies, while the most appropriate method for heterozygote detection is DNA analysis.

Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 2. Label-free relative quantitative proteomics† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6mb00290k Click here for additional data file.

PubMed Central

Mudaliar, Manikhandan; Tassi, Riccardo; Thomas, Funmilola C.; McNeilly, Tom N.; Weidt, Stefan K.; McLaughlin, Mark; Wilson, David; Burchmore, Richard; Herzyk, Pawel; Eckersall, P. David

2016-01-01

Mastitis, inflammation of the mammary gland, is the most common and costly disease of dairy cattle in the western world. It is primarily caused by bacteria, with Streptococcus uberis as one of the most prevalent causative agents. To characterize the proteome during Streptococcus uberis mastitis, an experimentally induced model of intramammary infection was used. Milk whey samples obtained from 6 cows at 6 time points were processed using label-free relative quantitative proteomics. This proteomic analysis complements clinical, bacteriological and immunological studies as well as peptidomic and metabolomic analysis of the same challenge model. A total of 2552 non-redundant bovine peptides were identified, and from these, 570 bovine proteins were quantified. Hierarchical cluster analysis and principal component analysis showed clear clustering of results by stage of infection, with similarities between pre-infection and resolution stages (0 and 312 h post challenge), early infection stages (36 and 42 h post challenge) and late infection stages (57 and 81 h post challenge). Ingenuity pathway analysis identified upregulation of acute phase protein pathways over the course of infection, with dominance of different acute phase proteins at different time points based on differential expression analysis. Antimicrobial peptides, notably cathelicidins and peptidoglycan recognition protein, were upregulated at all time points post challenge and peaked at 57 h, which coincided with 10 000-fold decrease in average bacterial counts. The integration of clinical, bacteriological, immunological and quantitative proteomics and other-omic data provides a more detailed systems level view of the host response to mastitis than has been achieved previously. PMID:27412694

Natural bacterial communities serve as quantitative geochemical biosensors.

PubMed

Smith, Mark B; Rocha, Andrea M; Smillie, Chris S; Olesen, Scott W; Paradis, Charles; Wu, Liyou; Campbell, James H; Fortney, Julian L; Mehlhorn, Tonia L; Lowe, Kenneth A; Earles, Jennifer E; Phillips, Jana; Techtmann, Steve M; Joyner, Dominique C; Elias, Dwayne A; Bailey, Kathryn L; Hurt, Richard A; Preheim, Sarah P; Sanders, Matthew C; Yang, Joy; Mueller, Marcella A; Brooks, Scott; Watson, David B; Zhang, Ping; He, Zhili; Dubinsky, Eric A; Adams, Paul D; Arkin, Adam P; Fields, Matthew W; Zhou, Jizhong; Alm, Eric J; Hazen, Terry C

2015-05-12

Biological sensors can be engineered to measure a wide range of environmental conditions. Here we show that statistical analysis of DNA from natural microbial communities can be used to accurately identify environmental contaminants, including uranium and nitrate at a nuclear waste site. In addition to contamination, sequence data from the 16S rRNA gene alone can quantitatively predict a rich catalogue of 26 geochemical features collected from 93 wells with highly differing geochemistry characteristics. We extend this approach to identify sites contaminated with hydrocarbons from the Deepwater Horizon oil spill, finding that altered bacterial communities encode a memory of prior contamination, even after the contaminants themselves have been fully degraded. We show that the bacterial strains that are most useful for detecting oil and uranium are known to interact with these substrates, indicating that this statistical approach uncovers ecologically meaningful interactions consistent with previous experimental observations. Future efforts should focus on evaluating the geographical generalizability of these associations. Taken as a whole, these results indicate that ubiquitous, natural bacterial communities can be used as in situ environmental sensors that respond to and capture perturbations caused by human impacts. These in situ biosensors rely on environmental selection rather than directed engineering, and so this approach could be rapidly deployed and scaled as sequencing technology continues to become faster, simpler, and less expensive. Here we show that DNA from natural bacterial communities can be used as a quantitative biosensor to accurately distinguish unpolluted sites from those contaminated with uranium, nitrate, or oil. These results indicate that bacterial communities can be used as environmental sensors that respond to and capture perturbations caused by human impacts. Copyright © 2015 Smith et al.

Quantitative statistical analysis of cis-regulatory sequences in ABA/VP1- and CBF/DREB1-regulated genes of Arabidopsis.

PubMed

Suzuki, Masaharu; Ketterling, Matthew G; McCarty, Donald R

2005-09-01

We have developed a simple quantitative computational approach for objective analysis of cis-regulatory sequences in promoters of coregulated genes. The program, designated MotifFinder, identifies oligo sequences that are overrepresented in promoters of coregulated genes. We used this approach to analyze promoter sequences of Viviparous1 (VP1)/abscisic acid (ABA)-regulated genes and cold-regulated genes, respectively, of Arabidopsis (Arabidopsis thaliana). We detected significantly enriched sequences in up-regulated genes but not in down-regulated genes. This result suggests that gene activation but not repression is mediated by specific and common sequence elements in promoters. The enriched motifs include several known cis-regulatory sequences as well as previously unidentified motifs. With respect to known cis-elements, we dissected the flanking nucleotides of the core sequences of Sph element, ABA response elements (ABREs), and the C repeat/dehydration-responsive element. This analysis identified the motif variants that may correlate with qualitative and quantitative differences in gene expression. While both VP1 and cold responses are mediated in part by ABA signaling via ABREs, these responses correlate with unique ABRE variants distinguished by nucleotides flanking the ACGT core. ABRE and Sph motifs are tightly associated uniquely in the coregulated set of genes showing a strict dependence on VP1 and ABA signaling. Finally, analysis of distribution of the enriched sequences revealed a striking concentration of enriched motifs in a proximal 200-base region of VP1/ABA and cold-regulated promoters. Overall, each class of coregulated genes possesses a discrete set of the enriched motifs with unique distributions in their promoters that may account for the specificity of gene regulation.

Natural bacterial communities serve as quantitative geochemical biosensors

DOE PAGES

Smith, Mark B.; Rocha, Andrea M.; Smillie, Chris S.; ...

2015-05-12

Biological sensors can be engineered to measure a wide range of environmental conditions. Here we show that statistical analysis of DNA from natural microbial communities can be used to accurately identify environmental contaminants, including uranium and nitrate at a nuclear waste site. In addition to contamination, sequence data from the 16S rRNA gene alone can quantitatively predict a rich catalogue of 26 geochemical features collected from 93 wells with highly differing geochemistry characteristics. We extend this approach to identify sites contaminated with hydrocarbons from the Deepwater Horizon oil spill, finding that altered bacterial communities encode a memory of prior contamination,more » even after the contaminants themselves have been fully degraded. We show that the bacterial strains that are most useful for detecting oil and uranium are known to interact with these substrates, indicating that this statistical approach uncovers ecologically meaningful interactions consistent with previous experimental observations. Future efforts should focus on evaluating the geographical generalizability of these associations. Taken as a whole, these results indicate that ubiquitous, natural bacterial communities can be used as in situ environmental sensors that respond to and capture perturbations caused by human impacts. These in situ biosensors rely on environmental selection rather than directed engineering, and so this approach could be rapidly deployed and scaled as sequencing technology continues to become faster, simpler, and less expensive. Here we show that DNA from natural bacterial communities can be used as a quantitative biosensor to accurately distinguish unpolluted sites from those contaminated with uranium, nitrate, or oil. These results indicate that bacterial communities can be used as environmental sensors that respond to and capture perturbations caused by human impacts.« less

Development and prospective evaluation of an automated software system for quality control of quantitative 99mTc-MAG3 renal studies.

PubMed

Folks, Russell D; Garcia, Ernest V; Taylor, Andrew T

2007-03-01

Quantitative nuclear renography has numerous potential sources of error. We previously reported the initial development of a computer software module for comprehensively addressing the issue of quality control (QC) in the analysis of radionuclide renal images. The objective of this study was to prospectively test the QC software. The QC software works in conjunction with standard quantitative renal image analysis using a renal quantification program. The software saves a text file that summarizes QC findings as possible errors in user-entered values, calculated values that may be unreliable because of the patient's clinical condition, and problems relating to acquisition or processing. To test the QC software, a technologist not involved in software development processed 83 consecutive nontransplant clinical studies. The QC findings of the software were then tabulated. QC events were defined as technical (study descriptors that were out of range or were entered and then changed, unusually sized or positioned regions of interest, or missing frames in the dynamic image set) or clinical (calculated functional values judged to be erroneous or unreliable). Technical QC events were identified in 36 (43%) of 83 studies. Clinical QC events were identified in 37 (45%) of 83 studies. Specific QC events included starting the camera after the bolus had reached the kidney, dose infiltration, oversubtraction of background activity, and missing frames in the dynamic image set. QC software has been developed to automatically verify user input, monitor calculation of renal functional parameters, summarize QC findings, and flag potentially unreliable values for the nuclear medicine physician. Incorporation of automated QC features into commercial or local renal software can reduce errors and improve technologist performance and should improve the efficiency and accuracy of image interpretation.

Evaluation of chemotherapy response in ovarian cancer treatment using quantitative CT image biomarkers: a preliminary study

NASA Astrophysics Data System (ADS)

Qiu, Yuchen; Tan, Maxine; McMeekin, Scott; Thai, Theresa; Moore, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

2015-03-01

The purpose of this study is to identify and apply quantitative image biomarkers for early prediction of the tumor response to the chemotherapy among the ovarian cancer patients participated in the clinical trials of testing new drugs. In the experiment, we retrospectively selected 30 cases from the patients who participated in Phase I clinical trials of new drug or drug agents for ovarian cancer treatment. Each case is composed of two sets of CT images acquired pre- and post-treatment (4-6 weeks after starting treatment). A computer-aided detection (CAD) scheme was developed to extract and analyze the quantitative image features of the metastatic tumors previously tracked by the radiologists using the standard Response Evaluation Criteria in Solid Tumors (RECIST) guideline. The CAD scheme first segmented 3-D tumor volumes from the background using a hybrid tumor segmentation scheme. Then, for each segmented tumor, CAD computed three quantitative image features including the change of tumor volume, tumor CT number (density) and density variance. The feature changes were calculated between the matched tumors tracked on the CT images acquired pre- and post-treatments. Finally, CAD predicted patient's 6-month progression-free survival (PFS) using a decision-tree based classifier. The performance of the CAD scheme was compared with the RECIST category. The result shows that the CAD scheme achieved a prediction accuracy of 76.7% (23/30 cases) with a Kappa coefficient of 0.493, which is significantly higher than the performance of RECIST prediction with a prediction accuracy and Kappa coefficient of 60% (17/30) and 0.062, respectively. This study demonstrated the feasibility of analyzing quantitative image features to improve the early predicting accuracy of the tumor response to the new testing drugs or therapeutic methods for the ovarian cancer patients.

KRN4 Controls Quantitative Variation in Maize Kernel Row Number

PubMed Central

Liu, Lei; Du, Yanfang; Shen, Xiaomeng; Li, Manfei; Sun, Wei; Huang, Juan; Liu, Zhijie; Tao, Yongsheng; Zheng, Yonglian; Yan, Jianbing; Zhang, Zuxin

2015-01-01

Kernel row number (KRN) is an important component of yield during the domestication and improvement of maize and controlled by quantitative trait loci (QTL). Here, we fine-mapped a major KRN QTL, KRN4, which can enhance grain productivity by increasing KRN per ear. We found that a ~3-Kb intergenic region about 60 Kb downstream from the SBP-box gene Unbranched3 (UB3) was responsible for quantitative variation in KRN by regulating the level of UB3 expression. Within the 3-Kb region, the 1.2-Kb Presence-Absence variant was found to be strongly associated with quantitative variation in KRN in diverse maize inbred lines, and our results suggest that this 1.2-Kb transposon-containing insertion is likely responsible for increased KRN. A previously identified A/G SNP (S35, also known as Ser220Asn) in UB3 was also found to be significantly associated with KRN in our association-mapping panel. Although no visible genetic effect of S35 alone could be detected in our linkage mapping population, it was found to genetically interact with the 1.2-Kb PAV to modulate KRN. The KRN4 was under strong selection during maize domestication and the favorable allele for the 1.2-Kb PAV and S35 has been significantly enriched in modern maize improvement process. The favorable haplotype (Hap1) of 1.2-Kb-PAV-S35 was selected during temperate maize improvement, but is still rare in tropical and subtropical maize germplasm. The dissection of the KRN4 locus improves our understanding of the genetic basis of quantitative variation in complex traits in maize. PMID:26575831

Quantitative measurement of a candidate serum biomarker peptide derived from α2-HS-glycoprotein, and a preliminary trial of multidimensional peptide analysis in females with pregnancy-induced hypertension.

PubMed

Hamamura, Kensuke; Yanagida, Mitsuaki; Ishikawa, Hitoshi; Banzai, Michio; Yoshitake, Hiroshi; Nonaka, Daisuke; Tanaka, Kenji; Sakuraba, Mayumi; Miyakuni, Yasuka; Takamori, Kenji; Nojima, Michio; Yoshida, Koyo; Fujiwara, Hiroshi; Takeda, Satoru; Araki, Yoshihiko

2018-03-01

Purpose We previously attempted to develop quantitative enzyme-linked immunosorbent assay (ELISA) systems for the PDA039/044/071 peptides, potential serum disease biomarkers (DBMs) of pregnancy-induced hypertension (PIH), primarily identified by a peptidomic approach (BLOTCHIP®-mass spectrometry (MS)). However, our methodology did not extend to PDA071 (cysteinyl α2-HS-glycoprotein 341-367 ), due to difficulty to produce a specific antibody against the peptide. The aim of the present study was to establish an alternative PDA071 quantitation system using liquid chromatography-multiple reaction monitoring (LC-MRM)/MS, to explore the potential utility of PDA071 as a DBM for PIH. Methods We tested heat/acid denaturation methods in efforts to purify serum PDA071 and developed an LC-MRM/MS method allowing for specific quantitation thereof. We measured serum PDA071 concentrations, and these results were validated including by three-dimensional (3D) plotting against PDA039 (kininogen-1 439-456 )/044 (kininogen-1 438-456 ) concentrations, followed by discriminant analysis. Results PDA071 was successfully extracted from serum using a heat denaturation method. Optimum conditions for quantitation via LC-MRM/MS were developed; the assayed serum PDA071 correlated well with the BLOTCHIP® assay values. Although the PDA071 alone did not significantly differ between patients and controls, 3D plotting of PDA039/044/071 peptide concentrations and construction of a Jackknife classification matrix were satisfactory in terms of PIH diagnostic precision. Conclusions Combination analysis using both PDA071 and PDA039/044 concentrations allowed PIH diagnostic accuracy to be attained, and our method will be valuable in future pathophysiological studies of hypertensive disorders of pregnancy.

Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed Tomography Image Analysis.

PubMed

Attiyeh, Marc A; Chakraborty, Jayasree; Doussot, Alexandre; Langdon-Embry, Liana; Mainarich, Shiana; Gönen, Mithat; Balachandran, Vinod P; D'Angelica, Michael I; DeMatteo, Ronald P; Jarnagin, William R; Kingham, T Peter; Allen, Peter J; Simpson, Amber L; Do, Richard K

2018-04-01

Pancreatic cancer is a highly lethal cancer with no established a priori markers of survival. Existing nomograms rely mainly on post-resection data and are of limited utility in directing surgical management. This study investigated the use of quantitative computed tomography (CT) features to preoperatively assess survival for pancreatic ductal adenocarcinoma (PDAC) patients. A prospectively maintained database identified consecutive chemotherapy-naive patients with CT angiography and resected PDAC between 2009 and 2012. Variation in CT enhancement patterns was extracted from the tumor region using texture analysis, a quantitative image analysis tool previously described in the literature. Two continuous survival models were constructed, with 70% of the data (training set) using Cox regression, first based only on preoperative serum cancer antigen (CA) 19-9 levels and image features (model A), and then on CA19-9, image features, and the Brennan score (composite pathology score; model B). The remaining 30% of the data (test set) were reserved for independent validation. A total of 161 patients were included in the analysis. Training and test sets contained 113 and 48 patients, respectively. Quantitative image features combined with CA19-9 achieved a c-index of 0.69 [integrated Brier score (IBS) 0.224] on the test data, while combining CA19-9, imaging, and the Brennan score achieved a c-index of 0.74 (IBS 0.200) on the test data. We present two continuous survival prediction models for resected PDAC patients. Quantitative analysis of CT texture features is associated with overall survival. Further work includes applying the model to an external dataset to increase the sample size for training and to determine its applicability.

Development of propidium iodide as a fluorescence probe for the on-line screening of non-specific DNA-intercalators in Fufang Banbianlian Injection.

PubMed

Niu, Yanyan; Li, Sensen; Lin, Zongtao; Liu, Meixian; Wang, Daidong; Wang, Hong; Chen, Shizhong

2016-09-09

Fufang Banbianlian Injection (FBI) has been widely used as an anti-inflammatory and anti-tumor prescription. To understand the relationships between its bioactive ingredients and pharmacological efficacies, our previous study has been successfully identified some DNA-binding compounds in FBI using an established on-line screening system, in which 4',6-diamidino-2-phenylindole (DAPI) was developed as a probe. However, DAPI can be only used to screen ATT-specific DNA minor groove binders, leaving the potential active intercalators unknown in FBI. As a continuation of our studies on FBI, here we present a sensitive analytical method for rapid identification and evaluation of DNA-intercalators using propidium iodide (PI) as a fluorescent probe. We have firstly established the technique of high-performance liquid chromatography-diode-array detector-multistage mass spectrometry-deoxyribonucleic acid-propidium iodide-fluorescence detector (HPLC-DAD-MS(n)-DNA-PI-FLD) system. As a result, 38 of 58 previously identified compounds in FBI were DNA-intercalation active. Interestingly, all previously reported DNA-binders also showed intercalative activities, suggesting they are dual-mode DNA-binders. Quantitative study showed that flavonoid glycosides and chlorogenic acids were the main active compounds in FBI, and displayed similar DNA-binding ability using either DAPI or PI. In addition, 13 active compounds were used to establish the structure-activity relationships. In this study, PI was developed into an on-line method for identifying DNA-intercalators for the first time, and thus it will be a useful high-throughput screening technique for other related samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Calculator Use on the "GRE"® Revised General Test Quantitative Reasoning Measure. ETS GRE® Board Research Report. ETS GRE®-14-02. ETS Research Report. RR-14-25

ERIC Educational Resources Information Center

Attali, Yigal

2014-01-01

Previous research on calculator use in standardized assessments of quantitative ability focused on the effect of calculator availability on item difficulty and on whether test developers can predict these effects. With the introduction of an on-screen calculator on the Quantitative Reasoning measure of the "GRE"® revised General Test, it…

Nonparticipatory Stiffness in the Male Perioral Complex

ERIC Educational Resources Information Center

Chu, Shin-Ying; Barlow, Steven M.; Lee, Jaehoon

2009-01-01

Purpose: The objective of this study was to extend previous published findings in the authors' laboratory using a new automated technology to quantitatively characterize nonparticipatory perioral stiffness in healthy male adults. Method: Quantitative measures of perioral stiffness were sampled during a nonparticipatory task using a…

LANDSCAPE STRUCTURE AND ESTUARINE CONDITION IN THE MID-ATLANTIC REGION OF THE UNITED STATES: I. DEVELOPING QUANTITATIVE RELATIONSHIPS

EPA Science Inventory

In a previously published study, quantitative relationships were developed between landscape metrics and sediment contamination for 25 small estuarine systems within Chesapeake Bay. Nonparametric statistical analysis (rank transformation) was used to develop an empirical relation...

Assessing organisational readiness for change: use of diagnostic analysis prior to the implementation of a multidisciplinary assessment for acute stroke care

PubMed Central

Hamilton, Sharon; McLaren, Susan; Mulhall, Anne

2007-01-01

Background Achieving evidence-based practice in health care is integral to the drive for quality improvement in the National Health Service in the UK. Encapsulated within this policy agenda are challenges inherent in leading and managing organisational change. Not least of these is the need to change the behaviours of individuals and groups in order to embed new practices. Such changes are set within a context of organisational culture that can present a number of barriers and facilitators to change. Diagnostic analysis has been recommended as a precursor to the implementation of change to enable such barriers and facilitators to be identified and a targeted implementation strategy developed. Although diagnostic analysis is recommended, there is a paucity of advice on appropriate methods to use. This paper addresses the paucity and builds on previous work by recommending a mixed method approach to diagnostic analysis comprising both quantitative and qualitative data. Methods Twenty staff members with strategic accountability for stroke care were purposively sampled to take part in semi-structured interviews. Six recently discharged patients were also interviewed. Focus groups were conducted with one group of registered ward-based nurses (n = 5) and three specialist registrars (n = 3) purposively selected for their interest in stroke care. All professional staff on the study wards were sent the Team Climate Inventory questionnaire (n = 206). This elicited a response rate of 72% (n = 148). Results A number of facilitators for change were identified, including stakeholder support, organisational commitment to education, strong team climate in some teams, exemplars of past successful organisational change, and positive working environments. A number of barriers were also identified, including: unidisciplinary assessment/recording practices, varying in structure and evidence-base; weak team climate in some teams; negative exemplars of organisational change; and uncertainty created by impending organisational merger. Conclusion This study built on previous research by proposing a mixed method approach for diagnostic analysis. The combination of qualitative and quantitative data were able to capture multiple perspectives on barriers and facilitators to change. These data informed the tailoring of the implementation strategy to the specific needs of the Trust. PMID:17629929

Assessing organisational readiness for change: use of diagnostic analysis prior to the implementation of a multidisciplinary assessment for acute stroke care.

PubMed

Hamilton, Sharon; McLaren, Susan; Mulhall, Anne

2007-07-14

Achieving evidence-based practice in health care is integral to the drive for quality improvement in the National Health Service in the UK. Encapsulated within this policy agenda are challenges inherent in leading and managing organisational change. Not least of these is the need to change the behaviours of individuals and groups in order to embed new practices. Such changes are set within a context of organisational culture that can present a number of barriers and facilitators to change. Diagnostic analysis has been recommended as a precursor to the implementation of change to enable such barriers and facilitators to be identified and a targeted implementation strategy developed. Although diagnostic analysis is recommended, there is a paucity of advice on appropriate methods to use. This paper addresses the paucity and builds on previous work by recommending a mixed method approach to diagnostic analysis comprising both quantitative and qualitative data. Twenty staff members with strategic accountability for stroke care were purposively sampled to take part in semi-structured interviews. Six recently discharged patients were also interviewed. Focus groups were conducted with one group of registered ward-based nurses (n = 5) and three specialist registrars (n = 3) purposively selected for their interest in stroke care. All professional staff on the study wards were sent the Team Climate Inventory questionnaire (n = 206). This elicited a response rate of 72% (n = 148). A number of facilitators for change were identified, including stakeholder support, organisational commitment to education, strong team climate in some teams, exemplars of past successful organisational change, and positive working environments. A number of barriers were also identified, including: unidisciplinary assessment/recording practices, varying in structure and evidence-base; weak team climate in some teams; negative exemplars of organisational change; and uncertainty created by impending organisational merger. This study built on previous research by proposing a mixed method approach for diagnostic analysis. The combination of qualitative and quantitative data were able to capture multiple perspectives on barriers and facilitators to change. These data informed the tailoring of the implementation strategy to the specific needs of the Trust.

Air pollution or global warming: Attribution of extreme precipitation changes in eastern China—Comments on "Trends of extreme precipitation in Eastern China and their possible causes"

NASA Astrophysics Data System (ADS)

Wang, Yuan

2015-10-01

The recent study "Trends of Extreme Precipitation in Eastern China and Their Possible Causes" attributed the observed decrease/increase of light/heavy precipitation in eastern China to global warming rather than the regional aerosol effects. However, there exist compelling evidence from previous long-term observations and numerical modeling studies, suggesting that anthropogenic pollution is closely linked to the recent changes in precipitation intensity because of considerably modulated cloud physical properties by aerosols in eastern China. Clearly, a quantitative assessment of the aerosol and greenhouse effects on the regional scale is required to identify the primary cause for the extreme precipitation changes.

Measuring Constraint-Set Utility for Partitional Clustering Algorithms

NASA Technical Reports Server (NTRS)

Davidson, Ian; Wagstaff, Kiri L.; Basu, Sugato

2006-01-01

Clustering with constraints is an active area of machine learning and data mining research. Previous empirical work has convincingly shown that adding constraints to clustering improves the performance of a variety of algorithms. However, in most of these experiments, results are averaged over different randomly chosen constraint sets from a given set of labels, thereby masking interesting properties of individual sets. We demonstrate that constraint sets vary significantly in how useful they are for constrained clustering; some constraint sets can actually decrease algorithm performance. We create two quantitative measures, informativeness and coherence, that can be used to identify useful constraint sets. We show that these measures can also help explain differences in performance for four particular constrained clustering algorithms.

Modern Scientific Visualization is more than Just Pretty Pictures

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

Bethel, E Wes; Rubel, Oliver; Wu, Kesheng

2008-12-05

While the primary product of scientific visualization is images and movies, its primary objective is really scientific insight. Too often, the focus of visualization research is on the product, not the mission. This paper presents two case studies, both that appear in previous publications, that focus on using visualization technology to produce insight. The first applies"Query-Driven Visualization" concepts to laser wakefield simulation data to help identify and analyze the process of beam formation. The second uses topological analysis to provide a quantitative basis for (i) understanding the mixing process in hydrodynamic simulations, and (ii) performing comparative analysis of data frommore » two different types of simulations that model hydrodynamic instability.« less

Identification of agricultural crops by computer processing of ERTS MSS data

NASA Technical Reports Server (NTRS)

Bauer, M. E.; Cipra, J. E.

1973-01-01

Quantitative evaluation of computer-processed ERTS MSS data classifications has shown that major crop species (corn and soybeans) can be accurately identified. The classifications of satellite data over a 2000 square mile area not only covered more than 100 times the area previously covered using aircraft, but also yielded improved results through the use of temporal and spatial data in addition to the spectral information. Furthermore, training sets could be extended over far larger areas than was ever possible with aircraft scanner data. And, preliminary comparisons of acreage estimates from ERTS data and ground-based systems agreed well. The results demonstrate the potential utility of this technology for obtaining crop production information.

Ephaptic conduction in a cardiac strand model with 3D electrodiffusion

PubMed Central

Mori, Yoichiro; Fishman, Glenn I.; Peskin, Charles S.

2008-01-01

We study cardiac action potential propagation under severe reduction in gap junction conductance. We use a mathematical model of cellular electrical activity that takes into account both three-dimensional geometry and ionic concentration effects. Certain anatomical and biophysical parameters are varied to see their impact on cardiac action potential conduction velocity. This study uncovers quantitative features of ephaptic propagation that differ from previous studies based on one-dimensional models. We also identify a mode of cardiac action potential propagation in which the ephaptic and gap-junction-mediated mechanisms alternate. Our study demonstrates the usefulness of this modeling approach for electrophysiological systems especially when detailed membrane geometry plays an important role. PMID:18434544

UV testing of solar cells: Effects of antireflective coating, prior irradiation, and UV source

NASA Technical Reports Server (NTRS)

Meulenberg, A.

1993-01-01

Short-circuit current degradation of electron irradiated double-layer antireflective-coated cells after 3000 hours ultraviolet (UV) exposure exceeds 3 percent; extrapolation of the data to 10(exp 5) hours (11.4 yrs.) gives a degradation that exceeds 10 percent. Significant qualitative and quantitative differences in degradation were observed in cells with double- and single-layer antireflective coatings. The effects of UV-source age were observed and corrections were made to the data. An additional degradation mechanism was identified that occurs only in previously electron-irradiated solar cells since identical unirradiated cells degrade to only 6 +/- 3 percent when extrapolated 10(exp 5) hours of UV illumination.

BATSE Gamma-Ray Burst Line Search. IV. Line Candidates from the Visual Search

NASA Astrophysics Data System (ADS)

Band, D. L.; Ryder, S.; Ford, L. A.; Matteson, J. L.; Palmer, D. M.; Teegarden, B. J.; Briggs, M. S.; Paciesas, W. S.; Pendleton, G. N.; Preece, R. D.

1996-02-01

We evaluate the significance of the line candidates identified by a visual search of burst spectra from BATSE's Spectroscopy Detectors. None of the candidates satisfy our detection criteria: an F-test probability less than 10-4 for a feature in one detector and consistency among the detectors that viewed the burst. Most of the candidates are not very significant and are likely to be fluctuations. Because of the expectation of finding absorption lines, the search was biased toward absorption features. We do not have a quantitative measure of the completeness of the search, which would enable a comparison with previous missions. Therefore, a more objective computerized search has begun.

Testing new approaches to carbonate system simulation at the reef scale: the ReefSam model first results, application to a question in reef morphology and future challenges.

NASA Astrophysics Data System (ADS)

Barrett, Samuel; Webster, Jody

2016-04-01

Numerical simulation of the stratigraphy and sedimentology of carbonate systems (carbonate forward stratigraphic modelling - CFSM) provides significant insight into the understanding of both the physical nature of these systems and the processes which control their development. It also provides the opportunity to quantitatively test conceptual models concerning stratigraphy, sedimentology or geomorphology, and allows us to extend our knowledge either spatially (e.g. between bore holes) or temporally (forwards or backwards in time). The later is especially important in determining the likely future development of carbonate systems, particularly regarding the effects of climate change. This application, by its nature, requires successful simulation of carbonate systems on short time scales and at high spatial resolutions. Previous modelling attempts have typically focused on the scales of kilometers and kilo-years or greater (the scale of entire carbonate platforms), rather than at the scale of centuries or decades, and tens to hundreds of meters (the scale of individual reefs). Previous work has identified limitations in common approaches to simulating important reef processes. We present a new CFSM, Reef Sedimentary Accretion Model (ReefSAM), which is designed to test new approaches to simulating reef-scale processes, with the aim of being able to better simulate the past and future development of coral reefs. Four major features have been tested: 1. A simulation of wave based hydrodynamic energy with multiple simultaneous directions and intensities including wave refraction, interaction, and lateral sheltering. 2. Sediment transport simulated as sediment being moved from cell to cell in an iterative fashion until complete deposition. 3. A coral growth model including consideration of local wave energy and composition of the basement substrate (as well as depth). 4. A highly quantitative model testing approach where dozens of output parameters describing the reef morphology and development are compared with observational data. Despite being a test-bed and work in progress, ReefSAM was able to simulate the Holocene development of One Tree Reef in the Southern Great Barrier Reef (Australia) and was able to improve upon previous modelling attempts in terms of both quantitative measures and qualitative outputs, such as the presence of previously un-simulated reef features. Given the success of the model in simulating the Holocene development of OTR, we used it to quantitatively explore the effect of basement substrate depth and morphology on reef maturity/lagoonal filling (as discussed by Purdy and Gischer 2005). Initial results show a number of non-linear relationships between basement substrate depth, lagoonal filling and volume of sand produced on the reef rims and deposited in the lagoon. Lastly, further testing of the model has revealed new challenges which are likely to manifest in any attempt at reef-scale simulation. Subtly different sets of energy direction and magnitude input parameters (different in each time step but with identical probability distributions across the entire model run) resulted in a wide range of quantitative model outputs. Time step length is a likely contributing factor and the results of further testing to address this challenge will be presented.

Epistasis between QTLs for bone density variation in Copenhagen × dark agouti F2 rats

PubMed Central

Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J.; Foroud, Tatiana; Turner, Charles H.

2010-01-01

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation. PMID:19153792

Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2 rats.

PubMed

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2009-03-01

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation.

Internal controls for quantitative polymerase chain reaction of swine mammary glands during pregnancy and lactation.

PubMed

Tramontana, S; Bionaz, M; Sharma, A; Graugnard, D E; Cutler, E A; Ajmone-Marsan, P; Hurley, W L; Loor, J J

2008-08-01

High-throughput microarray analysis is an efficient means of obtaining a genome-wide view of transcript profiles across physiological states. However, quantitative PCR (qPCR) remains the chosen method for high-precision mRNA abundance analysis. Essential for reliability of qPCR data is normalization using appropriate internal control genes (ICG), which is now, more than ever before, a fundamental step for accurate gene expression profiling. We mined mammary tissue microarray data on >13,000 genes at -34, -14, 0, 7, 14, 21, and 28 d relative to parturition in 27 crossbred primiparous gilts to identify suitable ICG. Initial analysis revealed TBK1, PCSK2, PTBP1, API5, VAPB, QTRT1, TRIM41, TMEM24, PPP2R5B, and AP1S1 as the most stable genes (sample/reference = 1 +/- 0.2). We also included 9 genes previously identified as ICG in bovine mammary tissue. Gene network analysis of the 19 genes identified AP1S1, API5, MTG1, VAPB, TRIM41, MRPL39, and RPS15A as having no known co-regulation. In addition, UXT and ACTB were added to this list, and mRNA abundance of these 9 genes was measured by qPCR. Expression of all 9 of these genes was decreased markedly during lactation. In a previous study with bovine mammary tissue, mRNA of stably expressed genes decreased during lactation due to a dilution effect brought about by large increases in expression of highly abundant genes. To verify this effect, highly abundant mammary genes such as CSN1S2, SCD, FABP3, and LTF were evaluated by qPCR. The tested ICG had a negative correlation with these genes, demonstrating a dilution effect in the porcine mammary tissue. Gene stability analysis identified API5, VABP, and MRPL39 as the most stable ICG in porcine mammary tissue and indicated that the use of those 3 genes was most appropriate for calculating a normalization factor. Overall, results underscore the importance of proper validation of internal controls for qPCR and highlight the limitations of using absence of time effects as the criteria for selection of appropriate ICG. Further, we showed that use of the same ICG from one organism might not be suitable for qPCR normalization in other species.

Identification of Actin-Binding Proteins from Maize Pollen

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

Staiger, C.J.

Specific Aims--The goal of this project was to gain an understanding of how actin filament organization and dynamics are controlled in flowering plants. Specifically, we proposed to identify unique proteins with novel functions by investigating biochemical strategies for the isolation and characterization of actin-binding proteins (ABPs). In particular, our hunt was designed to identify capping proteins and nucleation factors. The specific aims included: (1) to use F-actin affinity chromatography (FAAC) as a general strategy to isolate pollen ABPs (2) to produce polyclonal antisera and perform subcellular localization in pollen tubes (3) to isolate cDNA clones for the most promising ABPsmore » (4) to further purify and characterize ABP interactions with actin in vitro. Summary of Progress By employing affinity chromatography on F-actin or DNase I columns, we have identified at least two novel ABPs from pollen, PrABP80 (gelsolin-like) and ZmABP30, We have also cloned and expressed recombinant protein, as well as generated polyclonal antisera, for 6 interesting ABPs from Arabidopsis (fimbrin AtFIM1, capping protein a/b (AtCP), adenylyl cyclase-associated protein (AtCAP), AtCapG & AtVLN1). We performed quantitative analyses of the biochemical properties for two of these previously uncharacterized ABPs (fimbrin and capping protein). Our studies provide the first evidence for fimbrin activity in plants, demonstrate the existence of barbed-end capping factors and a gelsolin-like severing activity, and provide the quantitative data necessary to establish and test models of F-actin organization and dynamics in plant cells.« less

Identification of candidate periodontal pathogens and beneficial species by quantitative 16S clonal analysis.

PubMed

Kumar, Purnima S; Griffen, Ann L; Moeschberger, Melvin L; Leys, Eugene J

2005-08-01

Most studies of the bacterial etiology of periodontitis have used either culture-based or targeted DNA approaches, and so it is likely that pathogens remain undiscovered. The purpose of this study was to use culture-independent, quantitative analysis of biofilms associated with chronic periodontitis and periodontal health to identify pathogens and beneficial species. Samples from subjects with periodontitis and controls were analyzed using ribosomal 16S cloning and sequencing. Several genera, many of them uncultivated, were associated with periodontitis, the most numerous of which were gram positive, including Peptostreptococcus and Filifactor. The genera Megasphaera and Desulfobulbus were elevated in periodontitis, and the levels of several species or phylotypes of Campylobacter, Selenomonas, Deferribacteres, Dialister, Catonella, Tannerella, Streptococcus, Atopobium, Eubacterium, and Treponema were elevated in disease. Streptococcus and Veillonella spp. were found in high numbers in all samples and accounted for a significantly greater fraction of the microbial community in healthy subjects than in those with periodontitis. The microbial profile of periodontal health also included the less-abundant genera Campylobacter, Abiotrophia, Gemella, Capnocytophaga, and Neisseria. These newly identified candidates outnumbered Porphyromonas gingivalis and other species previously implicated as periodontopathogens, and it is not clear if newly identified and more numerous species may play a more important role in pathogenesis. Finally, more differences were found in the bacterial profile between subjects with periodontitis and healthy subjects than between deep and shallow sites within the same subject. This suggests that chronic periodontitis is the result of a global perturbation of the oral bacterial ecology rather than a disease-site specific microbial shift.

iTRAQ-Based Quantitative Proteomic Comparison of Early- and Late-Passage Human Dermal Papilla Cell Secretome in Relation to Inducing Hair Follicle Regeneration.

PubMed

Zhang, Huan; Zhu, Ning-Xia; Huang, Keng; Cai, Bo-Zhi; Zeng, Yang; Xu, Yan-Ming; Liu, Yang; Yuan, Yan-Ping; Lin, Chang-Min

2016-01-01

Alopecia is an exceedingly prevalent problem that lacks effective therapy. Recently, research has focused on early-passage dermal papilla cells (DPCs), which have hair inducing activity both in vivo and in vitro. Our previous study indicated that factors secreted from early-passage DPCs contribute to hair follicle (HF) regeneration. To identify which factors are responsible for HF regeneration and why late-passage DPCs lose this potential, we collected 48-h-culture medium (CM) from both of passage 3 and 9 DPCs, and subcutaneously injected the DPC-CM into NU/NU mice. Passage 3 DPC-CM induced HF regeneration, based on the emergence of a white hair coat, but passage 9 DPC-CM did not. In order to identify the key factors responsible for hair induction, CM from passage 3 and 9 DPCs was analyzed by iTRAQ-based quantitative proteomic technology. We identified 1360 proteins, of which 213 proteins were differentially expressed between CM from early-passage vs. late-passage DPCs, including SDF1, MMP3, biglycan and LTBP1. Further analysis indicated that the differentially-expressed proteins regulated the Wnt, TGF-β and BMP signaling pathways, which directly and indirectly participate in HF morphogenesis and regeneration. Subsequently, we selected 19 proteins for further verification by multiple reaction monitoring (MRM) between the two types of CM. These results indicate DPC-secreted proteins play important roles in HF regeneration, with SDF1, MMP3, biglycan, and LTBP1 being potential key inductive factors secreted by dermal papilla cells in the regeneration of hair follicles.

The Vermicelli Handling Test: A Simple Quantitative Measure of Dexterous Forepaw Function in Rats

PubMed Central

Allred, Rachel P.; Adkins, DeAnna L.; Woodlee, Martin T.; Husbands, Lincoln C.; Maldonado, Mónica A.; Kane, Jacqueline R.; Schallert, Timothy; Jones, Theresa A.

2008-01-01

Loss of function in the hands occurs with many brain disorders, but there are few measures of skillful forepaw use in rats available to model these impairments that are both sensitive and simple to administer. Whishaw and Coles (1996) previously described the dexterous manner in which rats manipulate food items with their paws, including thin pieces of pasta. We set out to develop a measure of this food handling behavior that would be quantitative, easy to administer, sensitive to the effects of damage to sensory and motor systems of the CNS and useful for identifying the side of lateralized impairments. When rats handle 7 cm lengths of vermicelli, they manipulate the pasta by repeatedly adjusting the forepaw hold on the pasta piece. As operationally defined, these adjustments can be easily identified and counted by an experimenter without specialized equipment. After unilateral sensorimotor cortex (SMC) lesions, transient middle cerebral artery occlusion (MCAO) and striatal dopamine depleting (6-hydroxydopamine, 6-OHDA) lesions in adult rats, there were enduring reductions in adjustments made with the contralateral forepaw. Additional pasta handling characteristics distinguished between the lesion types. MCAO and 6-OHDA lesions increased the frequency of several identified atypical handling patterns. Severe dopamine depletion increased eating time and adjustments made with the ipsilateral forepaw. However, contralateral forepaw adjustment number most sensitively detected enduring impairments across lesion types. Because of its ease of administration and sensitivity to lateralized impairments in skilled forepaw use, this measure may be useful in rat models of upper extremity impairment. PMID:18325597

Are quantitative sensitivity analysis methods always reliable?

NASA Astrophysics Data System (ADS)

Huang, X.

2016-12-01

Physical parameterizations developed to represent subgrid-scale physical processes include various uncertain parameters, leading to large uncertainties in today's Earth System Models (ESMs). Sensitivity Analysis (SA) is an efficient approach to quantitatively determine how the uncertainty of the evaluation metric can be apportioned to each parameter. Also, SA can identify the most influential parameters, as a result to reduce the high dimensional parametric space. In previous studies, some SA-based approaches, such as Sobol' and Fourier amplitude sensitivity testing (FAST), divide the parameters into sensitive and insensitive groups respectively. The first one is reserved but the other is eliminated for certain scientific study. However, these approaches ignore the disappearance of the interactive effects between the reserved parameters and the eliminated ones, which are also part of the total sensitive indices. Therefore, the wrong sensitive parameters might be identified by these traditional SA approaches and tools. In this study, we propose a dynamic global sensitivity analysis method (DGSAM), which iteratively removes the least important parameter until there are only two parameters left. We use the CLM-CASA, a global terrestrial model, as an example to verify our findings with different sample sizes ranging from 7000 to 280000. The result shows DGSAM has abilities to identify more influential parameters, which is confirmed by parameter calibration experiments using four popular optimization methods. For example, optimization using Top3 parameters filtered by DGSAM could achieve substantial improvement against Sobol' by 10%. Furthermore, the current computational cost for calibration has been reduced to 1/6 of the original one. In future, it is necessary to explore alternative SA methods emphasizing parameter interactions.

A short insertion mutation disrupts genesis of miR-16 and causes increased body weight in domesticated chicken.

PubMed

Jia, Xinzheng; Lin, Huiran; Nie, Qinghua; Zhang, Xiquan; Lamont, Susan J

2016-11-03

Body weight is one of the most important quantitative traits with high heritability in chicken. We previously mapped a quantitative trait locus (QTL) for body weight by genome-wide association study (GWAS) in an F2 chicken resource population. To identify the causal mutations linked to this QTL, expression profiles were determined on livers of high-weight and low-weight chicken lines by microarray. Combining the expression pattern with SNP effects by GWAS, miR-16 was identified as the most likely potential candidate with a 3.8-fold decrease in high-weight lines. Re-sequencing revealed that a 54-bp insertion mutation in the upstream region of miR-15a-16 displayed high allele frequencies in high-weight commercial broiler line. This mutation resulted in lower miR-16 expression by introducing three novel splicing sites instead of the missing 5' terminal splicing of mature miR-16. Elevating miR-16 significantly inhibited DF-1 chicken embryo cell proliferation, consistent with a role in suppression of cellular growth. The 54-bp insertion was significantly associated with increased body weight, bone size and muscle mass. Also, the insertion mutation tended towards fixation in commercial broilers (Fst > 0.4). Our findings revealed a novel causative mutation for body weight regulation that aids our basic understanding of growth regulation in birds.

A short insertion mutation disrupts genesis of miR-16 and causes increased body weight in domesticated chicken

PubMed Central

Jia, Xinzheng; Lin, Huiran; Nie, Qinghua; Zhang, Xiquan; Lamont, Susan J.

2016-01-01

Body weight is one of the most important quantitative traits with high heritability in chicken. We previously mapped a quantitative trait locus (QTL) for body weight by genome-wide association study (GWAS) in an F2 chicken resource population. To identify the causal mutations linked to this QTL, expression profiles were determined on livers of high-weight and low-weight chicken lines by microarray. Combining the expression pattern with SNP effects by GWAS, miR-16 was identified as the most likely potential candidate with a 3.8-fold decrease in high-weight lines. Re-sequencing revealed that a 54-bp insertion mutation in the upstream region of miR-15a-16 displayed high allele frequencies in high-weight commercial broiler line. This mutation resulted in lower miR-16 expression by introducing three novel splicing sites instead of the missing 5′ terminal splicing of mature miR-16. Elevating miR-16 significantly inhibited DF-1 chicken embryo cell proliferation, consistent with a role in suppression of cellular growth. The 54-bp insertion was significantly associated with increased body weight, bone size and muscle mass. Also, the insertion mutation tended towards fixation in commercial broilers (Fst > 0.4). Our findings revealed a novel causative mutation for body weight regulation that aids our basic understanding of growth regulation in birds. PMID:27808177

Natural Bacterial Communities Serve as Quantitative Geochemical Biosensors

PubMed Central

Smith, Mark B.; Rocha, Andrea M.; Smillie, Chris S.; Olesen, Scott W.; Paradis, Charles; Wu, Liyou; Campbell, James H.; Fortney, Julian L.; Mehlhorn, Tonia L.; Lowe, Kenneth A.; Earles, Jennifer E.; Phillips, Jana; Joyner, Dominique C.; Elias, Dwayne A.; Bailey, Kathryn L.; Hurt, Richard A.; Preheim, Sarah P.; Sanders, Matthew C.; Yang, Joy; Mueller, Marcella A.; Brooks, Scott; Watson, David B.; Zhang, Ping; He, Zhili; Dubinsky, Eric A.; Adams, Paul D.; Arkin, Adam P.; Fields, Matthew W.; Zhou, Jizhong; Alm, Eric J.

2015-01-01

ABSTRACT Biological sensors can be engineered to measure a wide range of environmental conditions. Here we show that statistical analysis of DNA from natural microbial communities can be used to accurately identify environmental contaminants, including uranium and nitrate at a nuclear waste site. In addition to contamination, sequence data from the 16S rRNA gene alone can quantitatively predict a rich catalogue of 26 geochemical features collected from 93 wells with highly differing geochemistry characteristics. We extend this approach to identify sites contaminated with hydrocarbons from the Deepwater Horizon oil spill, finding that altered bacterial communities encode a memory of prior contamination, even after the contaminants themselves have been fully degraded. We show that the bacterial strains that are most useful for detecting oil and uranium are known to interact with these substrates, indicating that this statistical approach uncovers ecologically meaningful interactions consistent with previous experimental observations. Future efforts should focus on evaluating the geographical generalizability of these associations. Taken as a whole, these results indicate that ubiquitous, natural bacterial communities can be used as in situ environmental sensors that respond to and capture perturbations caused by human impacts. These in situ biosensors rely on environmental selection rather than directed engineering, and so this approach could be rapidly deployed and scaled as sequencing technology continues to become faster, simpler, and less expensive. PMID:25968645

Assessing the impact of representational and contextual problem features on student use of right-hand rules

NASA Astrophysics Data System (ADS)

Kustusch, Mary Bridget

2016-06-01

Students in introductory physics struggle with vector algebra and these challenges are often associated with contextual and representational features of the problems. Performance on problems about cross product direction is particularly poor and some research suggests that this may be primarily due to misapplied right-hand rules. However, few studies have had the resolution to explore student use of right-hand rules in detail. This study reviews literature in several disciplines, including spatial cognition, to identify ten contextual and representational problem features that are most likely to influence performance on problems requiring a right-hand rule. Two quantitative measures of performance (correctness and response time) and two qualitative measures (methods used and type of errors made) were used to explore the impact of these problem features on student performance. Quantitative results are consistent with expectations from the literature, but reveal that some features (such as the type of reasoning required and the physical awkwardness of using a right-hand rule) have a greater impact than others (such as whether the vectors are placed together or separate). Additional insight is gained by the qualitative analysis, including identifying sources of difficulty not previously discussed in the literature and revealing that the use of supplemental methods, such as physically rotating the paper, can mitigate errors associated with certain features.

Access to HIV/AIDS care: a systematic review of socio-cultural determinants in low and high income countries.

PubMed

Gari, Sara; Doig-Acuña, Camilo; Smail, Tino; Malungo, Jacob R S; Martin-Hilber, Adriane; Merten, Sonja

2013-05-28

The role of socio-cultural factors in influencing access to HIV/AIDS treatment, care and support is increasingly recognized by researchers, international donors and policy makers. Although many of them have been identified through qualitative studies, the evidence gathered by quantitative studies has not been systematically analysed. To fill this knowledge gap, we did a systematic review of quantitative studies comparing surveys done in high and low income countries to assess the extent to which socio-cultural determinants of access, identified through qualitative studies, have been addressed in epidemiological survey studies. Ten electronic databases were searched (Cinahl, EMBASE, ISI Web of Science, IBSS, JSTOR, MedLine, Psyinfo, Psyindex and Cochrane). Two independent reviewers selected eligible publications based on the inclusion/exclusion criteria. Meta-analysis was used to synthesize data comparing studies between low and high income countries. Thirty-four studies were included in the final review, 21 (62%) done in high income countries and 13 (38%) in low income countries. In low income settings, epidemiological research on access to HIV/AIDS services focused on socio-economic and health system factors while in high income countries the focus was on medical and psychosocial factors. These differences depict the perceived different barriers in the two regions. Common factors between the two regions were also found to affect HIV testing, including stigma, high risk sexual behaviours such as multiple sexual partners and not using condoms, and alcohol abuse. On the other hand, having experienced previous illness or other health conditions and good family communication was associated with adherence to ART uptake. Due to insufficient consistent data, a meta-analysis was only possible on adherence to treatment. This review offers evidence of the current challenges for interdisciplinary work in epidemiology and public health. Quantitative studies did not systematically address in their surveys important factors identified in qualitative studies as playing a critical role on the access to HIV/AIDS services. The evidences suggest that the problem lies in the exclusion of the qualitative information during the questionnaire design. With the changing face of the epidemic, we need a new and improved research strategy that integrates the results of qualitative studies into quantitative surveys.

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

PubMed Central

Weiser, Keith C.; Liu, Bin; Hansen, Gwenn M.; Skapura, Darlene; Hentges, Kathryn E.; Yarlagadda, Sujatha; Morse III, Herbert C.

2007-01-01

AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFκB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision. PMID:17926094

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

PubMed

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

2007-10-01

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

Genetic determinants of leucocyte telomere length in children: a neglected and challenging field.

PubMed

Stathopoulou, Maria G; Petrelis, Alexandros M; Buxton, Jessica L; Froguel, Philippe; Blakemore, Alexandra I F; Visvikis-Siest, Sophie

2015-03-01

Telomere length is associated with a large range of human diseases. Genome-wide association studies (GWAS) have identified genetic variants that are associated with leucocyte telomere length (LTL). However, these studies are limited to adult populations. Nevertheless, childhood is a crucial period for the determination of LTL, and the assessment of age-specific genetic determinants, although neglected, could be of great importance. Our aim was to provide insights and preliminary results on genetic determinants of LTL in children. Healthy children (n = 322, age range = 6.75-17 years) with available GWAS data (Illumina Human CNV370-Duo array) were included. The LTL was measured using multiplex quantitative real-time polymerase chain reaction. Linear regression models adjusted for age, gender, parental age at child's birth, and body mass index were used to test the associations of LTL with polymorphisms identified in adult GWAS and to perform a discovery-only GWAS. The previously GWAS-identified variants in adults were not associated with LTL in our paediatric sample. This lack of association was not due to possible interactions with age or gene × gene interactions. Furthermore, a discovery-only GWAS approach demonstrated six novel variants that reached the level of suggestive association (P ≤ 5 × 10(-5)) and explain a high percentage of children's LTL. The study of genetic determinants of LTL in children may identify novel variants not previously identified in adults. Studies in large-scale children populations are needed for the confirmation of these results, possibly through a childhood consortium that could better handle the methodological challenges of LTL genetic epidemiology field. © 2015 John Wiley & Sons Ltd.

Genetic architecture of kernel composition in global sorghum germplasm.

PubMed

Rhodes, Davina H; Hoffmann, Leo; Rooney, William L; Herald, Thomas J; Bean, Scott; Boyles, Richard; Brenton, Zachary W; Kresovich, Stephen

2017-01-05

Sorghum [Sorghum bicolor (L.) Moench] is an important cereal crop for dryland areas in the United States and for small-holder farmers in Africa. Natural variation of sorghum grain composition (protein, fat, and starch) between accessions can be used for crop improvement, but the genetic controls are still unresolved. The goals of this study were to quantify natural variation of sorghum grain composition and to identify single-nucleotide polymorphisms (SNPs) associated with variation in grain composition concentrations. In this study, we quantified protein, fat, and starch in a global sorghum diversity panel using near-infrared spectroscopy (NIRS). Protein content ranged from 8.1 to 18.8%, fat content ranged from 1.0 to 4.3%, and starch content ranged from 61.7 to 71.1%. Durra and bicolor-durra sorghum from Ethiopia and India had the highest protein and fat and the lowest starch content, while kafir sorghum from USA, India, and South Africa had the lowest protein and the highest starch content. Genome-wide association studies (GWAS) identified quantitative trait loci (QTL) for sorghum protein, fat, and starch. Previously published RNAseq data was used to identify candidate genes within a GWAS QTL region. A putative alpha-amylase 3 gene, which has previously been shown to be associated with grain composition traits, was identified as a strong candidate for protein and fat variation. We identified promising sources of genetic material for manipulation of grain composition traits, and several loci and candidate genes that may control sorghum grain composition. This survey of grain composition in sorghum germplasm and identification of protein, fat, and starch QTL contributes to our understanding of the genetic basis of natural variation in sorghum grain nutritional traits.

Exercise Capacity and Response to Training Quantitative Trait Loci in a NZW X 129S1 Intercross and Combined Cross Analysis of Inbred Mouse Strains

PubMed Central

Massett, Michael P.; Avila, Joshua J.; Kim, Seung Kyum

2015-01-01

Genetic factors determining exercise capacity and the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with exercise training in mice. Based on marked differences in training responses in inbred NZW (-0.65 ± 1.73 min) and 129S1 (6.18 ± 3.81 min) mice, a reciprocal intercross breeding scheme was used to generate 285 F2 mice. All F2 mice completed an exercise performance test before and after a 4-week treadmill running program, resulting in an increase in exercise capacity of 1.54 ± 3.69 min (range = -10 to +12 min). Genome-wide linkage scans were performed for pre-training, post-training, and change in run time. For pre-training exercise time, suggestive QTL were identified on Chromosomes 5 (57.4 cM, 2.5 LOD) and 6 (47.8 cM, 2.9 LOD). A significant QTL for post-training exercise capacity was identified on Chromosome 5 (43.4 cM, 4.1 LOD) and a suggestive QTL on Chromosomes 1 (55.7 cM, 2.3 LOD) and 8 (66.1 cM, 2.2 LOD). A suggestive QTL for the change in run time was identified on Chromosome 6 (37.8 cM, 2.7 LOD). To identify shared QTL, this data set was combined with data from a previous F2 cross between B6 and FVB strains. In the combined cross analysis, significant novel QTL for pre-training exercise time and change in exercise time were identified on Chromosome 12 (54.0 cM, 3.6 LOD) and Chromosome 6 (28.0 cM, 3.7 LOD), respectively. Collectively, these data suggest that combined cross analysis can be used to identify novel QTL and narrow the confidence interval of QTL for exercise capacity and responses to training. Furthermore, these data support the use of larger and more diverse mapping populations to identify the genetic basis for exercise capacity and responses to training. PMID:26710100

Data from quantitative label free proteomics analysis of rat spleen.

PubMed

Dudekula, Khadar; Le Bihan, Thierry

2016-09-01

The dataset presented in this work has been obtained using a label-free quantitative proteomic analysis of rat spleen. A robust method for extraction of proteins from rat spleen tissue and LC-MS-MS analysis was developed using a urea and SDS-based buffer. Different fractionation methods were compared. A total of 3484 different proteins were identified from the pool of all experiments run in this study (a total of 2460 proteins with at least two peptides). A total of 1822 proteins were identified from nine non-fractionated pulse gels, 2288 proteins and 2864 proteins were identified by SDS-PAGE fractionation into three and five fractions respectively. The proteomics data are deposited in ProteomeXchange Consortium via PRIDE PXD003520, Progenesis and Maxquant output are presented in the supported information. The generated list of proteins under different regimes of fractionation allow assessing the nature of the identified proteins; variability in the quantitative analysis associated with the different sampling strategy and allow defining a proper number of replicates for future quantitative analysis.

Mammogram screening in Chile: Using mixed methods to implement health policy planning at the primary care level

PubMed Central

Puschel, Klaus; Thompson, Beti

2011-01-01

Summary Breast cancer has the highest incidence of all cancers among women in Chile. In 2005, a national health program progressively introduced free mammography screening for women aged 50 and older; however, three years later the rates of compliance with mammographic screening was only 12% in Santiago, the capital city of Chile. This implementation article combines the findings of two previous studies that applied qualitative and quantitative methods to improve mammography screening in an area of Santiago. Socio-cultural and accessibility factors were identified as barriers and facilitators during the qualitative phase of the study and then applied to the design of a quantitative randomized clinical trial. After six months of intervention, 6% of women in the standard care group, 51.8% in the low intensity intervention group, and 70.1% in the high intensity intervention group had undergone a screening mammogram. This review discusses how the utilization of mixed methods research can contribute to the improvement of the implementation of health policies in local communities. PMID:21334897

Rapid Screening for Deleted Form of β-thalassemia by Real-Time Quantitative PCR.

PubMed

Ke, Liang-Yin; Chang, Jan-Gowth; Chang, Chao-Sung; Hsieh, Li-Ling; Liu, Ta-Chih

2017-01-01

Thalassemia is the most common single gene disease in human beings. The prevalence rate of β-thalassemia in Taiwan is approximately 1-3%. Previously methods to reveal and diagnose severe deleted form of α- or β-thalassemia were insufficient and inappropriate for prenatal diagnosis. A real-time quantitative PCR method was set up for rapid screening of the deleted form of β-thalassemia. Our results show that ΔΔCt between deleted form of β-thalassemia and normal individuals were 1.0674 ± 0.0713. On the contrary, mutation form β-thalassemia showed no difference with normal healthy control. The HBB/CCR5 ratio for deleted form of β-thalassemia patients was 0.48, whether normal individuals and mutation form of β-thalassemia was 1.0. This RQ-PCR technique is an alternative rapid screening assay for deleted form of β-thalassemia. In addition, it could also identify undefined type. Our technique by using RQ-PCR to quantify gene copies is a reliable and time-saving method that can screen deleted form of β-thalassemia. © 2016 Wiley Periodicals, Inc.

The Central Symmetry Analysis of Wrinkle Ridges in Lunar Mare Serenitatis

NASA Astrophysics Data System (ADS)

Yao, Meijuan; Chen, Jianping

2018-03-01

Wrinkle ridges are one of the most common structures usually found in lunar mare basalts, and their formations are closely related to the lunar mare. In this paper, wrinkle ridges in Mare Serenitatis were identified and mapped via high-resolution data acquired from SELENE, and a quantitative method was introduced to analyze the degree of central symmetry of the wrinkle ridges distributed in a concentric or radial pattern. Meanwhile, two methods were used to measure the lengths and orientations of wrinkle ridges before calculating their central symmetry value. Based on the mapped wrinkle ridges, we calculated the central symmetry value of the wrinkle ridges for the whole Mare Serenitatis as well as for the four circular ridge systems proposed by a previous study via this method. We also analyzed the factors that would cause discrepancies when calculating the central symmetry value. The results indicate that the method can be used to quantitatively analyze the degree of central symmetry of the linear features that were concentrically or radially oriented and can reflect the stress field characteristics.

Quantitative Differential Expression Analysis Reveals Mir-7 As Major Islet MicroRNA

PubMed Central

Bravo-Egana, Valia; Rosero, Samuel; Molano, R. Damaris; Pileggi, Antonello; Ricordi, Camillo; Domínguez-Bendala, Juan; Pastori, Ricardo L.

2008-01-01

MicroRNAs (miRNAs) are non-coding gene products that regulate gene expression through specific binding to target mRNAs. Cell-specific patterns of miRNAs are associated with the acquisition and maintenance of a given phenotype, such as endocrine pancreas (islets). We hypothesized that a subset of miRNAs could be differentially expressed in the islets. Using miRNA microarray technology and quantitative RT-PCR we identified a subset of miRNAs that are the most differentially expressed islet miRNAs (ratio islet/acinar >150-fold), mir-7 being the most abundant. A similarly high ratio for mir-7 was observed in human islets. The ratio islet/acinar for mir-375, a previously described islet miRNA, was <10, and is 2.5X more abundant in the islets than mir-7. Therefore, we conclude that mir-7 is the most abundant endocrine miRNA in islets while mir-375 is the most abundant intra-islet miRNA. Our results may offer new insights into regulatory pathways of islet gene expression. PMID:18086561

Insights into the Key Compounds of Durian (Durio zibethinus L. 'Monthong') Pulp Odor by Odorant Quantitation and Aroma Simulation Experiments.

PubMed

Li, Jia-Xiao; Schieberle, Peter; Steinhaus, Martin

2017-01-25

Sixteen compounds, previously identified as potent odorants by application of an aroma extract dilution analysis and the gas chromatography-olfactometry analysis of static headspace samples, were quantitated in the pulp of durians, variety Monthong, and odor activity values (OAVs) were calculated by dividing the concentrations obtained by the odor thresholds of the compounds in water. In combination with data recently reported for hydrogen sulfide and short-chain alkanethiols, OAVs > 1 were obtained for 19 compounds, among which ethyl (2S)-2-methylbutanoate (fruity; OAV 1700000), ethanethiol (rotten onion; OAV 480000), and 1-(ethylsulfanyl)ethane-1-thiol (roasted onion; OAV 250000) were the most potent, followed by methanethiol (rotten, cabbage; OAV 45000), ethane-1,1-dithiol (sulfury, durian; OAV 23000), and ethyl 2-methylpropanoate (fruity; OAV 22000). Aroma simulation and omission experiments revealed that the overall odor of durian pulp could be mimicked by only two compounds, namely, ethyl (2S)-2-methylbutanoate and 1-(ethylsulfanyl)ethane-1-thiol, when combined in their natural concentrations.

Quantitation of normal CFTR mRNA in CF patients with splice-site mutations

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

Zhou, Z.; Olsen, J.C.; Silverman, L.M.

Previously we identified two mutations in introns of the CFTR gene associated with partially active splice sites and unusual clinical phenotypes. One mutation in intron 19 (3849+10 kb C to T) is common in CF patients with normal sweat chloride values; an 84 bp sequence from intron 19, which contains a stop codon, is inserted between exon 19 and exon 20 in most nasal CFTR transcripts. The other mutation in intron 14B (2789+5 G to A) is associated with elevated sweat chloride levels, but mild pulmonary disease; exon 14B (38 bp) is spliced out of most nasal CFTR transcipts. Themore » remaining CFTR cDNA sequences, other than the 84 bp insertion of exon 14B deletion, are identical to the published sequence. To correlate genotype and phenotype, we used quantitative RT-PCR to determine the levels of normally-spliced CFTR mRNA in nasal epithelia from these patients. CFTR cDNA was amplified (25 cycles) by using primers specific for normally-spliced species, {gamma}-actin cDNA was amplified as a standard.« less

Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.

PubMed

Rusin, Scott F; Schlosser, Kate A; Adamo, Mark E; Kettenbach, Arminja N

2015-10-13

Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry-based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2-dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. Copyright © 2015, American Association for the Advancement of Science.

Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells

PubMed Central

Rusin, Scott F.; Schlosser, Kate A.; Adamo, Mark E.; Kettenbach, Arminja N.

2017-01-01

Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry–based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c–dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2–dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. PMID:26462736

A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder.

PubMed

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-01-01

The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. Afocused linkage and family-based association study was carried out using this memory-related endophenotype. In the largest 77-strong Afrikaner pedigree significant evidence for linkage was detected on chromosome 22q11, a region previously implicated in BPD. The quantitative transmission disequilibrium tests-based association analysis suggested that functional variants of the DRD4 and MAO-A genes modulate memory-related cognition. We speculate that polymorphisms at these loci may predispose to a subtype of BPD characterized by memory-related deficits.

Investigation of the cortical activation by touching fabric actively using fingers.

PubMed

Wang, Q; Yu, W; He, N; Chen, K

2015-11-01

Human subjects can tactually estimate the perception of touching fabric. Although many psychophysical and neurophysiological experiments have elucidated the peripheral neural mechanisms that underlie fabric hand estimation, the associated cortical mechanisms are not well understood. To identify the brain regions responsible for the tactile stimulation of fabric against human skin, we used the technology of functional magnetic resonance imaging (fMRI), to observe brain activation when the subjects touched silk fabric actively using fingers. Consistent with previous research about brain cognition on sensory stimulation, large activation in the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII) and moto cortex, and little activation in the posterior insula cortex and Broca's Area were observed when the subjects touched silk fabric. The technology of fMRI is a promising tool to observe and characterize the brain cognition on the tactile stimulation of fabric quantitatively. The intensity and extent of activation in the brain regions, especially the primary somatosensory cortex (SI) and the secondary somatosensory cortex (SII), can represent the perception of stimulation of fabric quantitatively. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dynamic Redox Regulation of IL-4 Signaling.

PubMed

Dwivedi, Gaurav; Gran, Margaret A; Bagchi, Pritha; Kemp, Melissa L

2015-11-01

Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation.

Dynamic Redox Regulation of IL-4 Signaling

PubMed Central

Dwivedi, Gaurav; Gran, Margaret A.; Bagchi, Pritha; Kemp, Melissa L.

2015-01-01

Quantifying the magnitude and dynamics of protein oxidation during cell signaling is technically challenging. Computational modeling provides tractable, quantitative methods to test hypotheses of redox mechanisms that may be simultaneously operative during signal transduction. The interleukin-4 (IL-4) pathway, which has previously been reported to induce reactive oxygen species and oxidation of PTP1B, may be controlled by several other putative mechanisms of redox regulation; widespread proteomic thiol oxidation observed via 2D redox differential gel electrophoresis upon IL-4 treatment suggests more than one redox-sensitive protein implicated in this pathway. Through computational modeling and a model selection strategy that relied on characteristic STAT6 phosphorylation dynamics of IL-4 signaling, we identified reversible protein tyrosine phosphatase (PTP) oxidation as the primary redox regulatory mechanism in the pathway. A systems-level model of IL-4 signaling was developed that integrates synchronous pan-PTP oxidation with ROS-independent mechanisms. The model quantitatively predicts the dynamics of IL-4 signaling over a broad range of new redox conditions, offers novel hypotheses about regulation of JAK/STAT signaling, and provides a framework for interrogating putative mechanisms involving receptor-initiated oxidation. PMID:26562652

Quantitative phase-digital holographic microscopy: a new imaging modality to identify original cellular biomarkers of diseases

NASA Astrophysics Data System (ADS)

Marquet, P.; Rothenfusser, K.; Rappaz, B.; Depeursinge, C.; Jourdain, P.; Magistretti, P. J.

2016-03-01

Quantitative phase microscopy (QPM) has recently emerged as a powerful label-free technique in the field of living cell imaging allowing to non-invasively measure with a nanometric axial sensitivity cell structure and dynamics. Since the phase retardation of a light wave when transmitted through the observed cells, namely the quantitative phase signal (QPS), is sensitive to both cellular thickness and intracellular refractive index related to the cellular content, its accurate analysis allows to derive various cell parameters and monitor specific cell processes, which are very likely to identify new cell biomarkers. Specifically, quantitative phase-digital holographic microscopy (QP-DHM), thanks to its numerical flexibility facilitating parallelization and automation processes, represents an appealing imaging modality to both identify original cellular biomarkers of diseases as well to explore the underlying pathophysiological processes.

A natural variant of NAL1, selected in high-yield rice breeding programs, pleiotropically increases photosynthesis rate.

PubMed

Takai, Toshiyuki; Adachi, Shunsuke; Taguchi-Shiobara, Fumio; Sanoh-Arai, Yumiko; Iwasawa, Norio; Yoshinaga, Satoshi; Hirose, Sakiko; Taniguchi, Yojiro; Yamanouchi, Utako; Wu, Jianzhong; Matsumoto, Takashi; Sugimoto, Kazuhiko; Kondo, Katsuhiko; Ikka, Takashi; Ando, Tsuyu; Kono, Izumi; Ito, Sachie; Shomura, Ayahiko; Ookawa, Taiichiro; Hirasawa, Tadashi; Yano, Masahiro; Kondo, Motohiko; Yamamoto, Toshio

2013-01-01

Improvement of leaf photosynthesis is an important strategy for greater crop productivity. Here we show that the quantitative trait locus GPS (GREEN FOR PHOTOSYNTHESIS) in rice (Oryza sativa L.) controls photosynthesis rate by regulating carboxylation efficiency. Map-based cloning revealed that GPS is identical to NAL1 (NARROW LEAF1), a gene previously reported to control lateral leaf growth. The high-photosynthesis allele of GPS was found to be a partial loss-of-function allele of NAL1. This allele increased mesophyll cell number between vascular bundles, which led to thickened leaves, and it pleiotropically enhanced photosynthesis rate without the detrimental side effects observed in previously identified nal1 mutants, such as dwarf plant stature. Furthermore, pedigree analysis suggested that rice breeders have repeatedly selected the high-photosynthesis allele in high-yield breeding programs. The identification and utilization of NAL1 (GPS) can enhance future high-yield breeding and provides a new strategy for increasing rice productivity.

A natural variant of NAL1, selected in high-yield rice breeding programs, pleiotropically increases photosynthesis rate

PubMed Central

Takai, Toshiyuki; Adachi, Shunsuke; Taguchi-Shiobara, Fumio; Sanoh-Arai, Yumiko; Iwasawa, Norio; Yoshinaga, Satoshi; Hirose, Sakiko; Taniguchi, Yojiro; Yamanouchi, Utako; Wu, Jianzhong; Matsumoto, Takashi; Sugimoto, Kazuhiko; Kondo, Katsuhiko; Ikka, Takashi; Ando, Tsuyu; Kono, Izumi; Ito, Sachie; Shomura, Ayahiko; Ookawa, Taiichiro; Hirasawa, Tadashi; Yano, Masahiro; Kondo, Motohiko; Yamamoto, Toshio

2013-01-01

Improvement of leaf photosynthesis is an important strategy for greater crop productivity. Here we show that the quantitative trait locus GPS (GREEN FOR PHOTOSYNTHESIS) in rice (Oryza sativa L.) controls photosynthesis rate by regulating carboxylation efficiency. Map-based cloning revealed that GPS is identical to NAL1 (NARROW LEAF1), a gene previously reported to control lateral leaf growth. The high-photosynthesis allele of GPS was found to be a partial loss-of-function allele of NAL1. This allele increased mesophyll cell number between vascular bundles, which led to thickened leaves, and it pleiotropically enhanced photosynthesis rate without the detrimental side effects observed in previously identified nal1 mutants, such as dwarf plant stature. Furthermore, pedigree analysis suggested that rice breeders have repeatedly selected the high-photosynthesis allele in high-yield breeding programs. The identification and utilization of NAL1 (GPS) can enhance future high-yield breeding and provides a new strategy for increasing rice productivity. PMID:23985993

Measurement of replication structures at the nanometer scale using super-resolution light microscopy

PubMed Central

Baddeley, D.; Chagin, V. O.; Schermelleh, L.; Martin, S.; Pombo, A.; Carlton, P. M.; Gahl, A.; Domaing, P.; Birk, U.; Leonhardt, H.; Cremer, C.; Cardoso, M. C.

2010-01-01

DNA replication, similar to other cellular processes, occurs within dynamic macromolecular structures. Any comprehensive understanding ultimately requires quantitative data to establish and test models of genome duplication. We used two different super-resolution light microscopy techniques to directly measure and compare the size and numbers of replication foci in mammalian cells. This analysis showed that replication foci vary in size from 210 nm down to 40 nm. Remarkably, spatially modulated illumination (SMI) and 3D-structured illumination microscopy (3D-SIM) both showed an average size of 125 nm that was conserved throughout S-phase and independent of the labeling method, suggesting a basic unit of genome duplication. Interestingly, the improved optical 3D resolution identified 3- to 5-fold more distinct replication foci than previously reported. These results show that optical nanoscopy techniques enable accurate measurements of cellular structures at a level previously achieved only by electron microscopy and highlight the possibility of high-throughput, multispectral 3D analyses. PMID:19864256

Characterization of large price variations in financial markets

NASA Astrophysics Data System (ADS)

Johansen, Anders

2003-06-01

Statistics of drawdowns (loss from the last local maximum to the next local minimum) plays an important role in risk assessment of investment strategies. As they incorporate higher (> two) order correlations, they offer a better measure of real market risks than the variance or other cumulants of daily (or some other fixed time scale) of returns. Previous results have shown that the vast majority of drawdowns occurring on the major financial markets have a distribution which is well represented by a stretched exponential, while the largest drawdowns are occurring with a significantly larger rate than predicted by the bulk of the distribution and should thus be characterized as outliers (Eur. Phys. J. B 1 (1998) 141; J. Risk 2001). In the present analysis, the definition of drawdowns is generalized to coarse-grained drawdowns or so-called ε-drawdowns and a link between such ε- outliers and preceding log-periodic power law bubbles previously identified (Quantitative Finance 1 (2001) 452) is established.

Identification and quantification of glucosinolate and flavonol compounds in rocket salad (Eruca sativa, Eruca vesicaria and Diplotaxis tenuifolia) by LC–MS: Highlighting the potential for improving nutritional value of rocket crops

PubMed Central

Bell, Luke; Oruna-Concha, Maria Jose; Wagstaff, Carol

2015-01-01

Liquid chromatography mass spectrometry (LC–MS) was used to obtain glucosinolate and flavonol content for 35 rocket accessions and commercial varieties. 13 glucosinolates and 11 flavonol compounds were identified. Semi-quantitative methods were used to estimate concentrations of both groups of compounds. Minor glucosinolate composition was found to be different between accessions; concentrations varied significantly. Flavonols showed differentiation between genera, with Diplotaxis accumulating quercetin glucosides and Eruca accumulating kaempferol glucosides. Several compounds were detected in each genus that have only previously been reported in the other. We highlight how knowledge of phytochemical content and concentration can be used to breed new, nutritionally superior varieties. We also demonstrate the effects of controlled environment conditions on the accumulations of glucosinolates and flavonols and explore the reasons for differences with previous studies. We stress the importance of consistent experimental design between research groups to effectively compare and contrast results. PMID:25442630

Investigation of Association Between Hip Osteoarthritis Susceptibility Loci and Radiographic Proximal Femur Shape

PubMed Central

Thiagarajah, Shankar; Wilkinson, J. Mark; Panoutsopoulou, Kalliope; Day‐Williams, Aaron G.; Cootes, Timothy F.; Wallis, Gillian A.; Loughlin, John; Arden, Nigel; Birrell, Fraser; Carr, Andrew; Chapman, Kay; Deloukas, Panos; Doherty, Michael; McCaskie, Andrew; Ollier, William E. R.; Rai, Ashok; Ralston, Stuart H.; Spector, Timothy D.; Valdes, Ana M.; Wallis, Gillian A.; Mark Wilkinson, J.; Zeggini, Eleftheria

2015-01-01

Objective To test whether previously reported hip morphology or osteoarthritis (OA) susceptibility loci are associated with proximal femur shape as represented by statistical shape model (SSM) modes and as univariate or multivariate quantitative traits. Methods We used pelvic radiographs and genotype data from 929 subjects with unilateral hip OA who had been recruited previously for the Arthritis Research UK Osteoarthritis Genetics Consortium genome‐wide association study. We built 3 SSMs capturing the shape variation of the OA‐unaffected proximal femur in the entire mixed‐sex cohort and for male/female‐stratified cohorts. We selected 41 candidate single‐nucleotide polymorphisms (SNPs) previously reported as being associated with hip morphology (for replication analysis) or OA (for discovery analysis) and for which genotype data were available. We performed 2 types of analysis for genotype–phenotype associations between these SNPs and the modes of the SSMs: 1) a univariate analysis using individual SSM modes and 2) a multivariate analysis using combinations of SSM modes. Results The univariate analysis identified association between rs4836732 (within the ASTN2 gene) and mode 5 of the female SSM (P = 0.0016) and between rs6976 (within the GLT8D1 gene) and mode 7 of the mixed‐sex SSM (P = 0.0003). The multivariate analysis identified association between rs5009270 (near the IFRD1 gene) and a combination of modes 3, 4, and 9 of the mixed‐sex SSM (P = 0.0004). Evidence of associations remained significant following adjustment for multiple testing. All 3 SNPs had previously been associated with hip OA. Conclusion These de novo findings suggest that rs4836732, rs6976, and rs5009270 may contribute to hip OA susceptibility by altering proximal femur shape. PMID:25939412

Identification of 4-(3-Pyridyl)-4-oxobutyl-2'-deoxycytidine Adducts Formed in the Reaction of DNA with 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone: A Chemically Activated Form of Tobacco-Specific Carcinogens.

PubMed

Michel, Anna K; Zarth, Adam T; Upadhyaya, Pramod; Hecht, Stephen S

2017-03-31

Metabolic activation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1 ) and N '-nitrosonornicotine (NNN, 2 ) results in the formation of 4-(3-pyridyl)-4-oxobutyl (POB)-DNA adducts, several of which have been previously identified both in vitro and in tissues of laboratory animals treated with NNK or NNN. However, 2'-deoxycytidine adducts formed in this process have been incompletely examined in previous studies. Therefore, in this study we prepared characterized standards for the identification of previously unknown 2'-deoxycytidine and 2'-deoxyuridine adducts that could be produced in these reactions. The formation of these products in reactions of 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc, 3 ), a model 4-(3-pyridyl)-4-oxobutylating agent, with DNA was investigated. The major 2'-deoxycytidine adduct, identified as its stable cytosine analogue O 2 -[4-(3-pyridyl)-4-oxobut-1-yl]-cytosine ( 12 ), was O 2 -[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxycytidine ( 13 ), whereas lesser amounts of 3-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxycytidine ( 14 ) and N 4 -[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxycytidine ( 15 ) were also observed. The potential conversion of relatively unstable 2'-deoxycytidine adducts to stable 2'-deoxyuridine adducts by treatment of the adducted DNA with bisulfite was also investigated, but the harsh conditions associated with this approach prevented quantitation. The results of this study provide new validated standards for the study of 4-(3-pyridyl)-4-oxobutylation of DNA, a critical reaction in the carcinogenesis by 1 and 2 , and demonstrate the presence of previously unidentified 2'-deoxycytidine adducts in this DNA.

Potential Use of {sup 18}F-fluorodeoxyglucose Positron Emission Tomography–Based Quantitative Imaging Features for Guiding Dose Escalation in Stage III Non-Small Cell Lung Cancer

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

Fried, David V., E-mail: dvfried@mdanderson.org; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas; Mawlawi, Osama

2016-02-01

Purpose: To determine whether previously identified quantitative image features (QIFs) based on {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) (co-occurrence matrix energy and solidity) are able to isolate subgroups of patients who would receive a benefit or detriment from dose escalation in terms of overall survival (OS) or progression-free survival (PFS). Methods and Materials: Subgroups of a previously analyzed 225 patient cohort were generated with the use of 5-percentile increment cutoff values of disease solidity and primary tumor co-occurrence matrix energy. The subgroups were analyzed with a log-rank test to determine whether there was a difference in OS and PFS betweenmore » patients treated with 60 to 70 Gy and those receiving 74 Gy. Results: In the entire patient cohort, there was no statistical difference in terms of OS or PFS between patients receiving 74 Gy and those receiving 60 to 70 Gy. It was qualitatively observed that as disease solidity and primary co-occurrence matrix energy increased, patients receiving 74 Gy had an improved OS and PFS compared with those receiving 60 to 70 Gy. The opposite trend (detriment of receiving 74 Gy) was also observed regarding low values of disease solidity and primary co-occurrence matrix energy. Conclusions: FDG-PET–based QIFs were found to be capable of isolating subgroups of patients who received a benefit or detriment from dose escalation.« less

Predictors of effective leadership in industry - should engineering education focus on traditional intelligence, personality, or emotional intelligence?

NASA Astrophysics Data System (ADS)

Lappalainen, Pia

2015-03-01

Despite the changing global and industrial conditions requiring new approaches to leadership, management training as part of higher engineering education still remains understudied. The subsequent gap in engineering education calls for research on today's leader requirements and pedagogy supporting the inclusion of management competence in higher engineering education. Previous organisation and management studies have, on a general level, established the importance of managerial qualities for industrial performance, but the nature and make-up of these qualifications has not been adequately analysed. To fill the related research gap, the present work embarked on a quantitative empirical effort to identify predictors of successful leadership in engineering. In particular, this study investigated relationships between perceived leader performance and three dimensions of managerial capability: (1) mathematical-logical intelligence, (2) personality, and (3) socio-emotional intelligence. This work complemented previous research by resorting to both self-reports and other-reports: the results acquired from the managerial sample were compared to subordinate perceptions as measured through an emotive intelligence other-report and a general managerial competence multi-source appraisal. The sample comprised 80 superiors and 354 subordinates operating in seven organisations in engineering industries. The results from the quantitative measurements signalled the strongest correlation for socio-emotional intelligence and certain personality dimensions with successful leadership. Mathematical-logical intelligence demonstrated no correlation with subordinate perceptions of good leadership. These findings lay the foundation for the incorporation of socio-emotive skills into higher engineering education.

A Comprehensive Reanalysis of the Distal Iliotibial Band: Quantitative Anatomy, Radiographic Markers, and Biomechanical Properties.

PubMed

Godin, Jonathan A; Chahla, Jorge; Moatshe, Gilbert; Kruckeberg, Bradley M; Muckenhirn, Kyle J; Vap, Alexander R; Geeslin, Andrew G; LaPrade, Robert F

2017-09-01

The qualitative anatomy of the distal iliotibial band (ITB) has previously been described. However, a comprehensive characterization of the quantitative anatomic, radiographic, and biomechanical properties of the Kaplan fibers of the deep distal ITB has not yet been established. It is paramount to delineate these characteristics to fully understand the distal ITB's contribution to rotational knee stability. Purpose/Hypothesis: There were 2 distinct purposes for this study: (1) to perform a quantitative anatomic and radiographic evaluation of the distal ITB's attachment sites and their relationships to pertinent osseous and soft tissue landmarks, and (2) to quantify the biomechanical properties of the deep (Kaplan) fibers of the distal ITB. It was hypothesized that the distal ITB has definable parameters concerning its anatomic attachments and consistent relationships to surgically pertinent landmarks with correlating plain radiographic findings. In addition, it was hypothesized that the biomechanical properties of the Kaplan fibers would support their role as important restraints against internal rotation. Descriptive laboratory study. Ten nonpaired, fresh-frozen human cadaveric knees (mean age, 61.1 years; range, 54-65 years) were dissected for anatomic and radiographic purposes. A coordinate measuring device quantified the attachment areas of the distal ITB to the distal femur, patella, and proximal tibia and their relationships to pertinent bony landmarks. A radiographic analysis was performed by inserting pins into the attachment sites of relevant anatomic structures to assess their location relative to pertinent bony landmarks with fluoroscopic guidance. A further biomechanical assessment of 10 cadaveric knees quantified the load to failure and stiffness of the Kaplan fibers' insertion on the distal femur after a preconditioning protocol. Two separate deep (Kaplan) fiber bundles were identified with attachments to 2 newly identified femoral bony prominences (ridges). The proximal and distal bundles inserted on the distal femur 53.6 mm (95% CI, 50.7-56.6 mm) and 31.4 mm (95% CI, 27.3-35.5 mm) proximal to the lateral epicondyle, respectively. The centers of the bundle insertions were 22.5 mm (95% CI, 19.1-25.9 mm) apart. The total insertion area of the distal ITB on the proximal tibia was 429.1 mm 2 (95% CI, 349.2-509.1 mm 2 ). A distinct capsulo-osseous layer of the distal ITB was also identified that was intimately related to the lateral knee capsule. Its origin was in close proximity to the lateral gastrocnemius tubercle, and it inserted on the proximal tibia at the lateral tibial tubercle between the fibular head and the Gerdy tubercle. Radiographic analysis supported the quantitative anatomic findings. The mean maximum load during pull-to-failure testing was 71.3 N (95% CI, 41.2-101.4 N) and 170.2 N (95% CI, 123.6-216.8 N) for the proximal and distal Kaplan bundles, respectively. The most important finding of this study was that 2 distinct deep bundles (Kaplan fibers) of the distal ITB were identified. Each bundle of the deep layer of the ITB was associated with a newly identified distinct bony ridge. Radiographic analysis confirmed the measurements previously recorded and established reproducible landmarks for the newly described structures. Biomechanical testing revealed that the Kaplan fibers had a strong attachment to the distal femur, thereby supporting a role in rotational knee stability. The identification of 2 distinct deep fiber (Kaplan) attachments clarifies the function of the ITB more definitively. The results also support the role of the ITB in rotatory knee stability because of the fibers' vectors and their identified maximum loads. These findings provide the anatomic and biomechanical foundation needed for the development of reconstruction or repair techniques to anatomically address these deficiencies in knee ligament injuries.

Quantitative trait loci associated with anthracnose resistance in sorghum

USDA-ARS?s Scientific Manuscript database

With an aim to develop a durable resistance to the fungal disease anthracnose, two unique genetic sources of resistance were selected to create genetic mapping populations to identify regions of the sorghum genome that encode anthracnose resistance. A series of quantitative trait loci were identifi...

The Effectiveness of Psychotherapeutic Interventions for Bereaved Persons: A Comprehensive Quantitative Review

ERIC Educational Resources Information Center

Currier, Joseph M.; Neimeyer, Robert A.; Berman, Jeffrey S.

2008-01-01

Previous quantitative reviews of research on psychotherapeutic interventions for bereaved persons have yielded divergent findings and have not included many of the available controlled outcome studies. This meta-analysis summarizes results from 61 controlled studies to offer a more comprehensive integration of this literature. This review examined…

78 FR 76658 - Report on the Selection of Eligible Countries for Fiscal Year 2014

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-18

... particular indicators. Where appropriate, the Board took into account additional quantitative and qualitative... previous years, a number of countries that performed well on the quantitative elements of the selection... caused by historical data revisions or methodological changes from the indicator institutions. In neither...

Quantitative Analysis of Nail Polish Remover Using Nuclear Magnetic Resonance Spectroscopy Revisited

ERIC Educational Resources Information Center

Hoffmann, Markus M.; Caccamis, Joshua T.; Heitz, Mark P.; Schlecht, Kenneth D.

2008-01-01

Substantial modifications are presented for a previously described experiment using nuclear magnetic resonance (NMR) spectroscopy to quantitatively determine analytes in commercial nail polish remover. The revised experiment is intended for a second- or third-year laboratory course in analytical chemistry and can be conducted for larger laboratory…

Racial Battle Fatigue for Latina/o Students: A Quantitative Perspective

ERIC Educational Resources Information Center

Franklin, Jeremy D.; Smith, William A.; Hung, Man

2014-01-01

Previous literature demonstrates that as a result of racial microaggressions and hostile campus racial climates, Latina/o students often state they experience psychological, physiological, and behavioral stress responses during and after racialized incidents on campuses. The purpose of this study is to quantitatively test the racial battle fatigue…

Recent Progress in the Remote Detection of Vapours and Gaseous Pollutants.

ERIC Educational Resources Information Center

Moffat, A. J.; And Others

Work has been continuing on the correlation spectrometry techniques described at previous remote sensing symposiums. Advances in the techniques are described which enable accurate quantitative measurements of diffused atmospheric gases to be made using controlled light sources, accurate quantitative measurements of gas clouds relative to…

Computer-aided design of liposomal drugs: In silico prediction and experimental validation of drug candidates for liposomal remote loading.

PubMed

Cern, Ahuva; Barenholz, Yechezkel; Tropsha, Alexander; Goldblum, Amiram

2014-01-10

Previously we have developed and statistically validated Quantitative Structure Property Relationship (QSPR) models that correlate drugs' structural, physical and chemical properties as well as experimental conditions with the relative efficiency of remote loading of drugs into liposomes (Cern et al., J. Control. Release 160 (2012) 147-157). Herein, these models have been used to virtually screen a large drug database to identify novel candidate molecules for liposomal drug delivery. Computational hits were considered for experimental validation based on their predicted remote loading efficiency as well as additional considerations such as availability, recommended dose and relevance to the disease. Three compounds were selected for experimental testing which were confirmed to be correctly classified by our previously reported QSPR models developed with Iterative Stochastic Elimination (ISE) and k-Nearest Neighbors (kNN) approaches. In addition, 10 new molecules with known liposome remote loading efficiency that were not used by us in QSPR model development were identified in the published literature and employed as an additional model validation set. The external accuracy of the models was found to be as high as 82% or 92%, depending on the model. This study presents the first successful application of QSPR models for the computer-model-driven design of liposomal drugs. © 2013.

Computer-aided design of liposomal drugs: in silico prediction and experimental validation of drug candidates for liposomal remote loading

PubMed Central

Cern, Ahuva; Barenholz, Yechezkel; Tropsha, Alexander; Goldblum, Amiram

2014-01-01

Previously we have developed and statistically validated Quantitative Structure Property Relationship (QSPR) models that correlate drugs’ structural, physical and chemical properties as well as experimental conditions with the relative efficiency of remote loading of drugs into liposomes (Cern et al, Journal of Controlled Release, 160(2012) 14–157). Herein, these models have been used to virtually screen a large drug database to identify novel candidate molecules for liposomal drug delivery. Computational hits were considered for experimental validation based on their predicted remote loading efficiency as well as additional considerations such as availability, recommended dose and relevance to the disease. Three compounds were selected for experimental testing which were confirmed to be correctly classified by our previously reported QSPR models developed with Iterative Stochastic Elimination (ISE) and k-nearest neighbors (kNN) approaches. In addition, 10 new molecules with known liposome remote loading efficiency that were not used in QSPR model development were identified in the published literature and employed as an additional model validation set. The external accuracy of the models was found to be as high as 82% or 92%, depending on the model. This study presents the first successful application of QSPR models for the computer-model-driven design of liposomal drugs. PMID:24184343

Drilling Predation on Serpulid Polychaetes (Ditrupa arietina) from the Pliocene of the Cope Basin, Murcia Region, Southeastern Spain

PubMed Central

Martinell, Jordi; Kowalewski, Michał; Domènech, Rosa

2012-01-01

We report quantitative analyses of drilling predation on the free-living, tube-dwelling serpulid polychaete Ditrupa arietina from the Cope Cabo marine succession (Pliocene, Spain). Tubes of D. arietina are abundant in the sampled units: 9 bulk samples from 5 horizons yielded ∼5925 specimens of D. arietina. Except for fragmentation, tubes were well preserved. Complete specimens ranged from 3.1 to 13.4 mm in length and displayed allometric growth patterns, with larger specimens being relatively slimmer. Drilled Ditrupa tubes were observed in all samples. Drillholes, identified as Oichnus paraboloides, were characterized by circular to elliptical outline (drillhole eccentricity increased with its diameter), parabolic vertical profile, outer diameter larger than inner diameter, penetration of one tube wall only, narrow range of drill-hole sizes, and non-random (anterior) distribution of drillholes. A total of 233 drilled specimens were identified, with drilling frequencies varying across horizons from 2.7% to 21% (3.9% for pooled data). Many tube fragments were broken across a drillhole suggesting that the reported frequencies are conservative and that biologically-facilitated (drill-hole induced) fragmentation hampers fossil preservation of complete serpulid tubes. No failed or repaired holes were observed. Multiple complete drillholes were present (3.9%). Drilled specimens were significantly smaller than undrilled specimens and tube length and drill-hole diameter were weakly correlated. The results suggest that drillholes were produced by a size-selective, site-stereotypic predatory organism of unknown affinity. The qualitative and quantitative patterns reported here are mostly consistent with previous reports on recent and fossil Ditrupa and reveal parallels with drilling patterns documented for scaphopod mollusks, a group that is ecologically and morphologically similar to Ditrupa. Consistent with previous studies, the results suggest that free-dwelling serpulid polychaetes are preyed upon by drilling predators and may provide a viable source of data on biotic interactions in the fossil record. PMID:22496828

Protease and lipase activities of fungal and bacterial strains derived from an artisanal raw ewe's milk cheese.

PubMed

Ozturkoglu-Budak, Sebnem; Wiebenga, Ad; Bron, Peter A; de Vries, Ronald P

2016-11-21

We previously identified the microbiota present during cheese ripening and observed high protease and lipase activity in Divle Cave cheese. To determine the contribution of individual isolates to enzyme activities, we investigated a range of species representing this microbiota for their proteolytic and lipolytic ability. In total, 17 fungal, 5 yeast and 18 bacterial strains, previously isolated from Divle Cave cheese, were assessed. Qualitative protease and lipase activities were performed on skim-milk agar and spirit-blue lipase agar, respectively, and resulted in a selection of strains for quantitative assays. For the quantitative assays, the strains were grown on minimal medium containing irradiated Divle Cave cheese, obtained from the first day of ripening. Out of 16 selected filamentous fungi, Penicillium brevicompactum, Penicillium cavernicola and Penicillium olsonii showed the highest protease activity, while Mucor racemosus was the best lipase producer. Yarrowia lipolytica was the best performing yeast with respect to protease and lipase activity. From the 18 bacterial strains, 14 and 11 strains, respectively showed protease and lipase activity in agar plates. Micrococcus luteus, Bacillus stratosphericus, Brevibacterium antiquum, Psychrobacter glacincola and Pseudomonas proteolytica displayed the highest protease and lipase activity. The proteases of yeast and filamentous fungi were identified as mainly aspartic protease by specific inhibition with Pepstatin A, whereas inhibition by PMSF (phenylmethylsulfonyl fluoride) indicated that most bacterial enzymes belong to serine type protease. Our results demonstrate that aspartic proteases, which usually have high milk clotting activity, are predominantly derived from fungal strains, and therefore fungal enzymes appear to be more suitable for use in the cheese industry. Microbial enzymes studied in this research might be alternatives for rennin (chymosin) from animal source because of their low cost and stable availability. Future studies will aim to purify these enzymes to test their suitability for use in similar artisanal cheeses or in large scale commercial cheeses. Copyright © 2016 Elsevier B.V. All rights reserved.

Understanding the full breadth of cancer-related patient costs in Ontario: a qualitative exploration.

PubMed

Longo, Christopher J; Fitch, Margaret; Grignon, Michel; McAndrew, Alison

2016-11-01

This research informs existing work by examining the full scope of out-of-pocket costs and lost income, patients' private insurance behaviors, and their overall management of finances during their cancer treatment. The intent was to gain a deeper understanding of patient circumstances and the related costs. Participant qualitative interviews were conducted in person during outpatient clinic visits or by telephone and were recorded between June 2011 and July 2012. Interviews were transcribed verbatim and subjected to a descriptive qualitative analysis. The research team collaborated early in the process (after three subjects were enrolled) to develop a preliminary coding framework. The coding framework was modified to incorporate additional emerging content until saturation of data was evident. Transcripts were coded using the qualitative software NVivo version 9.0. Fifteen patients agreed to participate in the study and 14 completed the interview (seven breast, three colorectal, two lung, and two prostate). Consistent with existing published work, participants expressed concerns regarding expenses related to medications, complementary/alternative medicines, devices, parking and travel. These concerns were exacerbated if patients did not have insurance or lost insurance coverage due to loss of work. Although many acknowledged in hindsight that additional insurance would have helped, they also recognized that at the time of their diagnoses, it was not a viable option. Previously unidentified categorical costs identified in this study included modifications to housing arrangements or renovations, special clothing, fitness costs and the impact of an altered diet. We confirmed the results of earlier Canadian quantitative work. Additionally, cost categories not previously explored were identified, which will facilitate the development of an improved and more comprehensive quantitative questionnaire for future research. Many patients indicated that supplemental health insurance would have made their cancer journey less stressful, highlighting existing gaps in the government funded health care system.

Infant social attention: an endophenotype of ASD-related traits?

PubMed

Jones, Emily J H; Venema, Kaitlin; Earl, Rachel K; Lowy, Rachel; Webb, Sara J

2017-03-01

As a neurodevelopmental disorder, symptoms of ASD likely emerge from a complex interaction between preexisting genetic vulnerabilities and the child's environment. One way to understand causal paths to ASD is to identify dimensional ASD-related traits that vary in the general population and that predispose individuals with other risk factors toward ASD. Moving beyond behavioral traits to explore underlying neurocognitive processes may further constrain the underlying genetics. Endophenotypes are quantitative, heritable, trait-related differences that are generally assessed with laboratory-based methods, can be identified in the general population, and may be more closely tied to particular causal chains that have a more restricted set of genetic roots. The most fruitful endophenotypes may be those observed in infancy, prior to the emergence of behavioral symptoms that they are hypothesized to cause. Social motivation is an ASD-related trait that is highly heritable. In this study, we investigate whether infant endophenotypes of social attention relate to familial risk for lower social motivation in the general population. We examined whether infant social attention (measured using habituation, EEG power, and event-related potential tasks previously used in infants/toddlers with ASD) varies quantitatively with parental social motivation in 117 six-month-old and 106 twelve-month-old typically developing infants assessed cross-sectionally. To assess heritable aspects of social motivation, primary caregiver biological parents completed two self-report measures of social avoidance and discomfort that have shown high heritability in previous work. Parents with higher social discomfort and avoidance had infants who showed shorter looks to faces but not objects; reduced theta power during naturalistic social attention; and smaller P400 responses to faces versus objects. Early reductions in social attention are continuously related to lower parental social motivation. Alterations in social attention may be infant endophenotypes of social motivation traits related to ASD. © 2016 Association for Child and Adolescent Mental Health.

Unveiling the Biodiversity of Deep-Sea Nematodes through Metabarcoding: Are We Ready to Bypass the Classical Taxonomy?

PubMed Central

2015-01-01

Nematodes inhabiting benthic deep-sea ecosystems account for >90% of the total metazoan abundances and they have been hypothesised to be hyper-diverse, but their biodiversity is still largely unknown. Metabarcoding could facilitate the census of biodiversity, especially for those tiny metazoans for which morphological identification is difficult. We compared, for the first time, different DNA extraction procedures based on the use of two commercial kits and a previously published laboratory protocol and tested their suitability for sequencing analyses of 18S rDNA of marine nematodes. We also investigated the reliability of Roche 454 sequencing analyses for assessing the biodiversity of deep-sea nematode assemblages previously morphologically identified. Finally, intra-genomic variation in 18S rRNA gene repeats was investigated by Illumina MiSeq in different deep-sea nematode morphospecies to assess the influence of polymorphisms on nematode biodiversity estimates. Our results indicate that the two commercial kits should be preferred for the molecular analysis of biodiversity of deep-sea nematodes since they consistently provide amplifiable DNA suitable for sequencing. We report that the morphological identification of deep-sea nematodes matches the results obtained by metabarcoding analysis only at the order-family level and that a large portion of Operational Clustered Taxonomic Units (OCTUs) was not assigned. We also show that independently from the cut-off criteria and bioinformatic pipelines used, the number of OCTUs largely exceeds the number of individuals and that 18S rRNA gene of different morpho-species of nematodes displayed intra-genomic polymorphisms. Our results indicate that metabarcoding is an important tool to explore the diversity of deep-sea nematodes, but still fails in identifying most of the species due to limited number of sequences deposited in the public databases, and in providing quantitative data on the species encountered. These aspects should be carefully taken into account before using metabarcoding in quantitative ecological research and monitoring programmes of marine biodiversity. PMID:26701112

Unveiling the Biodiversity of Deep-Sea Nematodes through Metabarcoding: Are We Ready to Bypass the Classical Taxonomy?

PubMed

Dell'Anno, Antonio; Carugati, Laura; Corinaldesi, Cinzia; Riccioni, Giulia; Danovaro, Roberto

2015-01-01

Nematodes inhabiting benthic deep-sea ecosystems account for >90% of the total metazoan abundances and they have been hypothesised to be hyper-diverse, but their biodiversity is still largely unknown. Metabarcoding could facilitate the census of biodiversity, especially for those tiny metazoans for which morphological identification is difficult. We compared, for the first time, different DNA extraction procedures based on the use of two commercial kits and a previously published laboratory protocol and tested their suitability for sequencing analyses of 18S rDNA of marine nematodes. We also investigated the reliability of Roche 454 sequencing analyses for assessing the biodiversity of deep-sea nematode assemblages previously morphologically identified. Finally, intra-genomic variation in 18S rRNA gene repeats was investigated by Illumina MiSeq in different deep-sea nematode morphospecies to assess the influence of polymorphisms on nematode biodiversity estimates. Our results indicate that the two commercial kits should be preferred for the molecular analysis of biodiversity of deep-sea nematodes since they consistently provide amplifiable DNA suitable for sequencing. We report that the morphological identification of deep-sea nematodes matches the results obtained by metabarcoding analysis only at the order-family level and that a large portion of Operational Clustered Taxonomic Units (OCTUs) was not assigned. We also show that independently from the cut-off criteria and bioinformatic pipelines used, the number of OCTUs largely exceeds the number of individuals and that 18S rRNA gene of different morpho-species of nematodes displayed intra-genomic polymorphisms. Our results indicate that metabarcoding is an important tool to explore the diversity of deep-sea nematodes, but still fails in identifying most of the species due to limited number of sequences deposited in the public databases, and in providing quantitative data on the species encountered. These aspects should be carefully taken into account before using metabarcoding in quantitative ecological research and monitoring programmes of marine biodiversity.

Infant social attention: an endophenotype of ASD-related traits?

PubMed Central

Jones, Emily J.H.; Venema, Kaitlin; Earl, Rachel K.; Lowy, Rachel; Webb, Sara J.

2018-01-01

Background As a neurodevelopmental disorder, symptoms of ASD likely emerge from a complex interaction between preexisting genetic vulnerabilities and the child’s environment. One way to understand causal paths to ASD is to identify dimensional ASD-related traits that vary in the general population and that predispose individuals with other risk factors toward ASD. Moving beyond behavioral traits to explore underlying neurocognitive processes may further constrain the underlying genetics. Endophenotypes are quantitative, heritable, trait-related differences that are generally assessed with laboratory-based methods, can be identified in the general population, and may be more closely tied to particular causal chains that have a more restricted set of genetic roots. The most fruitful endophenotypes may be those observed in infancy, prior to the emergence of behavioral symptoms that they are hypothesized to cause. Social motivation is an ASD-related trait that is highly heritable. In this study, we investigate whether infant endophenotypes of social attention relate to familial risk for lower social motivation in the general population. Methods We examined whether infant social attention (measured using habituation, EEG power, and event-related potential tasks previously used in infants/toddlers with ASD) varies quantitatively with parental social motivation in 117 six-month-old and 106 twelve-month-old typically developing infants assessed cross-sectionally. To assess heritable aspects of social motivation, primary caregiver biological parents completed two self-report measures of social avoidance and discomfort that have shown high heritability in previous work. Results Parents with higher social discomfort and avoidance had infants who showed shorter looks to faces but not objects; reduced theta power during naturalistic social attention; and smaller P400 responses to faces versus objects. Conclusions Early reductions in social attention are continuously related to lower parental social motivation. Alterations in social attention may be infant endophenotypes of social motivation traits related to ASD. PMID:27861851

Identification and validation of quantitative trait loci for seed yield, oil and protein contents in two recombinant inbred line populations of soybean.

PubMed

Wang, Xianzhi; Jiang, Guo-Liang; Green, Marci; Scott, Roy A; Song, Qijian; Hyten, David L; Cregan, Perry B

2014-10-01

Soybean seeds contain high levels of oil and protein, and are the important sources of vegetable oil and plant protein for human consumption and livestock feed. Increased seed yield, oil and protein contents are the main objectives of soybean breeding. The objectives of this study were to identify and validate quantitative trait loci (QTLs) associated with seed yield, oil and protein contents in two recombinant inbred line populations, and to evaluate the consistency of QTLs across different environments, studies and genetic backgrounds. Both the mapping population (SD02-4-59 × A02-381100) and validation population (SD02-911 × SD00-1501) were phenotyped for the three traits in multiple environments. Genetic analysis indicated that oil and protein contents showed high heritabilities while yield exhibited a lower heritability in both populations. Based on a linkage map constructed previously with the mapping population and using composite interval mapping and/or interval mapping analysis, 12 QTLs for seed yield, 16 QTLs for oil content and 11 QTLs for protein content were consistently detected in multiple environments and/or the average data over all environments. Of the QTLs detected in the mapping population, five QTLs for seed yield, eight QTLs for oil content and five QTLs for protein content were confirmed in the validation population by single marker analysis in at least one environment and the average data and by ANOVA over all environments. Eight of these validated QTLs were newly identified. Compared with the other studies, seven QTLs for seed yield, eight QTLs for oil content and nine QTLs for protein content further verified the previously reported QTLs. These QTLs will be useful for breeding higher yield and better quality cultivars, and help effectively and efficiently improve yield potential and nutritional quality in soybean.

Genome-wide Linkage Analysis for Identifying Quantitative Trait Loci Involved in the Regulation of Lipoprotein a (Lpa) Levels

PubMed Central

López, Sonia; Buil, Alfonso; Ordoñez, Jordi; Souto, Juan Carlos; Almasy, Laura; Lathrop, Mark; Blangero, John; Blanco-Vaca, Francisco; Fontcuberta, Jordi; Soria, José Manuel

2009-01-01

Lipoprotein Lp(a) levels are highly heritable and are associated with cardiovascular risk. We performed a genome-wide linkage analysis to delineate the genomic regions that influence the concentration of Lp(a) in families from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project. Lp(a) levels were measured in 387 individuals belonging to 21 extended Spanish families. A total of 485 DNA microsatellite markers were genotyped to provide a 7.1 cM genetic map. A variance component linkage method was used to evaluate linkage and to detect quantitative trait loci (QTLs). The main QTL that showed strong evidence of linkage with Lp(a) levels was located at the structural gene for apo(a) on Chromosome 6 (LOD score=13.8). Interestingly, another QTL influencing Lp(a) concentration was located on Chromosome 2 with a LOD score of 2.01. This region contains several candidate genes. One of them is the tissue factor pathway inhibitor (TFPI), which has antithrombotic action and also has the ability to bind lipoproteins. However, quantitative trait association analyses performed with 12 SNPs in TFPI gene revealed no association with Lp(a) levels. Our study confirms previous results on the genetic basis of Lp(a) levels. In addition, we report a new QTL on Chromosome 2 involved in the quantitative variation of Lp(a). These data should serve as the basis for further detection of candidate genes and to elucidate the relationship between the concentration of Lp(a) and cardiovascular risk. PMID:18560444

A Stratified Transcriptomics Analysis of Polygenic Fat and Lean Mouse Adipose Tissues Identifies Novel Candidate Obesity Genes

PubMed Central

Morton, Nicholas M.; Nelson, Yvonne B.; Michailidou, Zoi; Di Rollo, Emma M.; Ramage, Lynne; Hadoke, Patrick W. F.; Seckl, Jonathan R.; Bunger, Lutz; Horvat, Simon; Kenyon, Christopher J.; Dunbar, Donald R.

2011-01-01

Background Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain. Results To enrich for adipose tissue obesity genes a ‘snap-shot’ pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. Conclusions A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity. PMID:21915269

A large QTL for fear and anxiety mapped using an F2 cross can be dissected into multiple smaller QTLs.

PubMed

Parker, C C; Sokoloff, G; Leung, E; Kirkpatrick, S L; Palmer, A A

2013-10-01

Using chromosome substitution strains (CSS), we previously identified a large quantitative trait locus (QTL) for conditioned fear (CF) on mouse chromosome 10. Here, we used an F2 cross between CSS-10 and C57BL/6J (B6) to localize that QTL to distal chromosome 10. That QTL accounted for all the difference between CSS-10 and B6. We then produced congenic strains to fine-map that interval. We identified two congenic strains that captured some or all the QTL. The larger congenic strain (Line 1: 122.387121-129.068 Mb; build 37) appeared to account for all the difference between CSS-10 and B6. The smaller congenic strain (Line 2: 127.277-129.068 Mb) was intermediate between CSS-10 and B6. We used haplotype mapping followed by quantitative polymerase chain reaction to identify one gene that was differentially expressed in both lines relative to B6 (Rnf41) and one that was differentially expressed between only Line 1 and B6 (Shmt2). These cis-eQTLs may cause the behavioral QTLs; however, further studies are required to validate these candidate genes. More generally, our observation that a large QTL mapped using CSS and F2 crosses can be dissected into multiple smaller QTLs shows a weaknesses of two-stage approaches that seek to use coarse mapping to identify large regions followed by fine-mapping. Indeed, additional dissection of these congenic strains might result in further subdivision of these QTL regions. Despite these limitations, we have successfully fine-mapped two QTLs to small regions and identified putative candidate genes, showing that the congenic approach can be effective for fine-mapping QTLs. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Quantitative High-Throughput Screen Identifies Inhibitors of the Schistosoma mansoni Redox Cascade

PubMed Central

Simeonov, Anton; Jadhav, Ajit; Sayed, Ahmed A.; Wang, Yuhong; Nelson, Michael E.; Thomas, Craig J.; Inglese, James; Williams, David L.; Austin, Christopher P.

2008-01-01

Schistosomiasis is a tropical disease associated with high morbidity and mortality, currently affecting over 200 million people worldwide. Praziquantel is the only drug used to treat the disease, and with its increased use the probability of developing drug resistance has grown significantly. The Schistosoma parasites can survive for up to decades in the human host due in part to a unique set of antioxidant enzymes that continuously degrade the reactive oxygen species produced by the host's innate immune response. Two principal components of this defense system have been recently identified in S. mansoni as thioredoxin/glutathione reductase (TGR) and peroxiredoxin (Prx) and as such these enzymes present attractive new targets for anti-schistosomiasis drug development. Inhibition of TGR/Prx activity was screened in a dual-enzyme format with reducing equivalents being transferred from NADPH to glutathione via a TGR-catalyzed reaction and then to hydrogen peroxide via a Prx-catalyzed step. A fully automated quantitative high-throughput (qHTS) experiment was performed against a collection of 71,028 compounds tested as 7- to 15-point concentration series at 5 µL reaction volume in 1536-well plate format. In order to generate a robust data set and to minimize the effect of compound autofluorescence, apparent reaction rates derived from a kinetic read were utilized instead of end-point measurements. Actives identified from the screen, along with previously untested analogues, were subjected to confirmatory experiments using the screening assay and subsequently against the individual targets in secondary assays. Several novel active series were identified which inhibited TGR at a range of potencies, with IC50s ranging from micromolar to the assay response limit (∼25 nM). This is, to our knowledge, the first report of a large-scale HTS to identify lead compounds for a helminthic disease, and provides a paradigm that can be used to jump-start development of novel therapeutics for other neglected tropical diseases. PMID:18235848

A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

PubMed

Morton, Nicholas M; Nelson, Yvonne B; Michailidou, Zoi; Di Rollo, Emma M; Ramage, Lynne; Hadoke, Patrick W F; Seckl, Jonathan R; Bunger, Lutz; Horvat, Simon; Kenyon, Christopher J; Dunbar, Donald R

2011-01-01

Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain. To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.

Quantitative Characterisation and Analysis of Siliciclastic Fluvial Depositional Systems Using 3D Digital Outcrop Models

NASA Astrophysics Data System (ADS)

Burnham, Brian Scott

Outcrop analogue studies of fluvial sedimentary systems are often undertaken to identify spatial and temporal characteristics (e.g. stacking patterns, lateral continuity, lithofacies proportions). However, the lateral extent typically exceeds that of the exposure, and/or the true width and thickness are not apparent. Accurate characterisation of fluvial sand bodies is integral for accurate identification and subsequent modelling of aquifer and hydrocarbon reservoir architecture. The studies presented in this thesis utilise techniques that integrate lidar, highresolution photography and differential geospatial measurements, to create accurate three-dimensional (3D) digital outcrop models (DOMs) of continuous 3D and laterally extensive 2D outcrop exposures. The sedimentary architecture of outcrops in the medial portion of a large Distributive Fluvial System (DFS) (Huesca fluvial fan) in the Ebro Basin, north-east Spain, and in the fluvio-deltaic succession of the Breathitt Group in the eastern Appalachian Basin, USA, are evaluated using traditional sedimentological and digital outcrop analytical techniques. The major sand bodies in the study areas are quantitatively analysed to accurately characterise spatial and temporal changes in sand body architecture, from two different outcrop exposure types and scales. Several stochastic reservoir simulations were created to approximate fluvial sand body lithological component and connectivity within the medial portion of the Huesca DFS. Results demonstrate a workflow and current methodology adaptation of digital outcrop techniques required for each study to approximate true geobody widths, thickness and characterise architectural patterns (internal and external) of major fluvial sand bodies interpreted as products of DFSs in the Huesca fluvial fan, and both palaeovalleys and progradational DFSs in the Pikeville and Hyden Formations in the Breathitt Group. The results suggest key geostatistical metrics, which are translatable across any fluvial system that can be used to analyse 3D digital outcrop data, and identify spatial attributes of sand bodies to identify their genetic origin and lithological component within fluvial reservoir systems, and the rock record. 3D quantitative analysis of major sand bodies have allowed more accurate width vs. thickness relationships within the La Serreta area, showing a vertical increase in width and channel-fill facies, and demonstrates a 22% increase of in-channel facies from previous interpretations. Additionally, identification of deposits that are products of a nodal avulsion event have been characterised and are interpreted to be the cause for the increase in width and channel-fill facies. Furthermore, analysis of the Pikeville and Hyden Fms contain sand bodies of stacked distributaries and palaeovalleys, as previously interpreted, and demonstrates that a 3D spatial approach to determine basin-wide architectural trends is integral to identifying the genetic origin, and preservation potential of sand bodies of both palaeovalleys and distributive fluvial systems. The resultant geostatistics assimilated in the thesis demonstrates the efficacy of integrated lidar studies of outcrop analogues, and provide empirical relationships which can be applied to subsurface analogues for reservoir model development and the distribution of both DFS and palaeovalley depositional systems in the rock record.

Dioscin Inhibits HSC-T6 Cell Migration via Adjusting SDC-4 Expression: Insights from iTRAQ-Based Quantitative Proteomics.

PubMed

Yin, Lianhong; Qi, Yan; Xu, Youwei; Xu, Lina; Han, Xu; Tao, Xufeng; Song, Shasha; Peng, Jinyong

2017-01-01

Hepatic stellate cells (HSCs) migration, an important bioprocess, contributes to the development of liver fibrosis. Our previous studies have found the potent activity of dioscin against liver fibrosis by inhibiting HSCs proliferation, triggering the senescence and inducing apoptosis of activated HSCs, but the molecular mechanisms associated with cell migration were not clarified. In this work, iTRAQ (isobaric tags for relative and absolution quantitation)-based quantitative proteomics study was carried out, and a total of 1566 differentially expressed proteins with fold change ≥2.0 and p < 0.05 were identified in HSC-T6 cells treated by dioscin (5.0 μg/mL). Based on Gene Ontology classification, String and KEGG pathway assays, the effects of dioscin to inhibit cell migration via regulating SDC-4 were carried out. The results of wound-healing, cell migration and western blotting assays indicated that dioscin significantly inhibit HSC-T6 cell migration through SDC-4-dependent signal pathway by affecting the expression levels of Fn, PKCα, Src, FAK, and ERK1/2. Specific SDC-4 knockdown by shRNA also blocked HSC-T6 cell migration, and dioscin slightly enhanced the inhibiting effect. Taken together, the present work showed that SDC-4 played a crucial role on HSC-T6 cell adhesion and migration of dioscin against liver fibrosis, which may be one potent therapeutic target for fibrotic diseases.

Quantitative and temporal proteome analysis of butyrate-treated colorectal cancer cells.

PubMed

Tan, Hwee Tong; Tan, Sandra; Lin, Qingsong; Lim, Teck Kwang; Hew, Choy Leong; Chung, Maxey C M

2008-06-01

Colorectal cancer is one of the most common cancers in developed countries, and its incidence is negatively associated with high dietary fiber intake. Butyrate, a short-chain fatty acid fermentation by-product of fiber induces cell maturation with the promotion of growth arrest, differentiation, and/or apoptosis of cancer cells. The stimulation of cell maturation by butyrate in colonic cancer cells follows a temporal progression from the early phase of growth arrest to the activation of apoptotic cascades. Previously we performed two-dimensional DIGE to identify differentially expressed proteins induced by 24-h butyrate treatment of HCT-116 colorectal cancer cells. Herein we used quantitative proteomics approaches using iTRAQ (isobaric tags for relative and absolute quantitation), a stable isotope labeling methodology that enables multiplexing of four samples, for a temporal study of HCT-116 cells treated with butyrate. In addition, cleavable ICAT, which selectively tags cysteine-containing proteins, was also used, and the results complemented those obtained from the iTRAQ strategy. Selected protein targets were validated by real time PCR and Western blotting. A model is proposed to illustrate our findings from this temporal analysis of the butyrate-responsive proteome that uncovered several integrated cellular processes and pathways involved in growth arrest, apoptosis, and metastasis. These signature clusters of butyrate-regulated pathways are potential targets for novel chemopreventive and therapeutic drugs for treatment of colorectal cancer.

Quantitative profiling of CpG island methylation in human stool for colorectal cancer detection.

PubMed

Elliott, Giles O; Johnson, Ian T; Scarll, Jane; Dainty, Jack; Williams, Elizabeth A; Garg, D; Coupe, Amanda; Bradburn, David M; Mathers, John C; Belshaw, Nigel J

2013-01-01

The aims of this study were to investigate the use of quantitative CGI methylation data from stool DNA to classify colon cancer patients and to relate stool CGI methylation levels to those found in corresponding tissue samples. We applied a quantitative methylation-specific PCR assay to determine CGI methylation levels of six genes, previously shown to be aberrantly methylated during colorectal carcinogenesis. Assays were performed on DNA from biopsies of "normal" mucosa and stool samples from 57 patients classified as disease-free, adenoma, or cancer by endoscopy, and in tumour tissue from cancer patients. Additionally, CGI methylation was analysed in stool DNA from an asymptomatic population of individuals covering a broad age range (mean = 47 ± 24 years) CGI methylation levels in stool DNA were significantly higher than in DNA from macroscopically normal mucosa, and a significant correlation between stool and mucosa was observed for ESR1 only. Multivariate statistical analyses using the methylation levels of each CGI in stool DNA as a continuous variable revealed a highly significant (p = 0.003) classification of cancer vs. non-cancer (adenoma + disease-free) patients (sensitivity = 65 %, specificity = 81 %). CGI methylation profiling of stool DNA successfully identified patients with cancer despite the methylation status of CGIs in stool DNA not generally reflecting those in DNA from the colonic mucosa.

Restriction fragment length polymorphism mapping of quantitative trait loci for malaria parasite susceptibility in the mosquito Aedes aegypti

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

Severson, D.W.; Thathy, V.; Mori, A.

Susceptibility of the mosquito Aedes aegypti to the malarial parasite Plasmodium gallinaceum was investigated as a quantitative trait using restriction fragment length polymorphisms (RFLP). Two F{sub 2} populations of mosquitoes were independently prepared from pairwise matings between a highly susceptible and a refractory strain of A. aegypti. RFLP were tested for association with oocyst development on the mosquito midgut. Two putative quantitative trait loci (QTL) were identified that significantly affect susceptibility. One QTL, pgs [2,LF98], is located on chromosome 2 and accounted for 65 and 49% of the observed phenotypic variance in the two populations, respectively. A second QTL, pgs[3,MalI],more » is located on chromosome 3 and accounted for 14 and 10% of the observed phenotypic variance in the two populations, respectively. Both QTL exhibit a partial dominance effect on susceptibility, wherein the dominance effect is derived from the refractory parent. No indication of epistasis between these QTL was detected. Evidence suggests that either a tightly linked cluster of independent genes or a single locus affecting susceptibility to various mosquito-borne parasites and pathogens has evolved near the LF98 locus; in addition to P. gallinaceum susceptibility, this general genome region has previously been implicated in susceptibility to the filaria nematode Brugia malayi and the yellow fever virus. 35 refs., 2 figs., 3 tabs.« less

Is Early Experience Destiny? Review of Research on Long-Term Outcomes following International Adoption with Special Reference to the British Chinese Adoption Study.

PubMed

Grant, Margaret; Rushton, Alan; Simmonds, John

2016-01-01

The pathway from adverse early experience to adulthood for internationally adopted children is complex in identifying key influences, impacts, and outcomes. This review arose from the authors' involvement in the British Chinese Adoption Study, a recent outcomes study that explored the links between early orphanage care, adoptive experiences, and midadulthood. It differs from previous reviews in focusing on a greater length of time since adoption. Both quantitative and qualitative studies were included to allow for examination of a fuller range of adult-related outcomes rather than mental health scores alone. The sampling, methods, and results of reviewed articles are summarised and a critical commentary is provided. Despite methodological differences and identified strengths and weaknesses, conclusions are drawn on the basis of the evidence available. Special attention is paid to the interpretation of negative outcomes. Findings identify areas that should be explored further in order to gain a fuller understanding of midlife outcomes of people who experienced a poor start in life followed by international adoption. Such studies help in refining lifespan developmental theories.

Mitochondrial carrier family inventory of Trypanosoma brucei brucei: Identification, expression and subcellular localisation.

PubMed

Colasante, Claudia; Peña Diaz, P; Clayton, Christine; Voncken, Frank

2009-10-01

The mitochondrial carrier family (MCF) is a group of structurally conserved proteins that mediate the transport of a wide range of metabolic intermediates across the mitochondrial inner membrane. In this paper, an overview of the mitochondrial carrier proteins (MCPs) of the early-branching kinetoplastid parasite Trypanosoma brucei brucei is presented. Sequence analysis and phylogenetic reconstruction gave insight into the evolution and conservation of the 24 identified TbMCPs; for most of these, putative transport functions could be predicted. Comparison of the kinetoplastid MCP inventory to those previously reported for other eukaryotes revealed remarkable deviations: T. b. brucei lacks genes encoding some prototypical MCF members, such as the citrate carrier and uncoupling proteins. The in vivo expression of the identified TbMCPs in the two replicating life-cycle forms of T. b. brucei, the bloodstream-form and procyclic-form, was quantitatively assessed at the mRNA level by Northern blot analysis. Immunolocalisation studies confirmed that majority of the 24 identified TbMCPs is found in the mitochondrion of procyclic-form T. b. brucei.

Genetic mapping of the rice resistance-breaking gene of the brown planthopper Nilaparvata lugens

PubMed Central

Kobayashi, Tetsuya; Yamamoto, Kimiko; Suetsugu, Yoshitaka; Kuwazaki, Seigo; Hattori, Makoto; Jairin, Jirapong; Sanada-Morimura, Sachiyo; Matsumura, Masaya

2014-01-01

Host plant resistance has been widely used for controlling the major rice pest brown planthopper (BPH, Nilaparvata lugens). However, adaptation of the wild BPH population to resistance limits the effective use of resistant rice varieties. Quantitative trait locus (QTL) analysis was conducted to identify resistance-breaking genes against the anti-feeding mechanism mediated by the rice resistance gene Bph1. QTL analysis in iso-female BPH lines with single-nucleotide polymorphism (SNP) markers detected a single region on the 10th linkage group responsible for the virulence. The QTL explained from 57 to 84% of the total phenotypic variation. Bulked segregant analysis with next-generation sequencing in F2 progenies identified five SNPs genetically linked to the virulence. These analyses showed that virulence to Bph1 was controlled by a single recessive gene. In contrast to previous studies, the gene-for-gene relationship between the major resistance gene Bph1 and virulence gene of BPH was confirmed. Identified markers are available for map-based cloning of the major gene controlling BPH virulence to rice resistance. PMID:24870048

Predicting patient aggression against nurses in all hospital areas.

PubMed

Chapman, Rose; Perry, Laura; Styles, Irene; Combs, Shane

Workplace violence directed at nurses is an alarming phenomenon across the world. To intervene and manage these episodes as quickly as possible, nurses need to identify those factors that can alert them to the possibility that a violent event may occur. However, frameworks to help nurses predict episodes of workplace violence are limited. This article presents the findings of a study of nurses experience of workplace violence and identifies those factors and behaviours that nurses reported as indicating that an episode of workplace violence is likely to occur. A case study approach was used involving quantitative and qualitative data. One hundred and thirteen questionnaires were completed and 20 interviews were conducted in 2006. Nurses identified nine behaviours and factors that assist them to predict workplace violence. The first five factors comprising staring, tone of voice, anxiety, mumbling and pacing (STAMP) matched those identified in a previous study. However, the last four factors, comprising emotions, disease process, assertive/non-assertive behaviour and resources (EDAR) expand upon that study. Therefore, the acronym STAMPEDAR was used to classify the nine components. Being alert to these behaviours and factors may help nurses predict that an episode of workplace violence is likely to occur.

Comparing GWAS Results of Complex Traits Using Full Genetic Model and Additive Models for Revealing Genetic Architecture

PubMed Central

Monir, Md. Mamun; Zhu, Jun

2017-01-01

Most of the genome-wide association studies (GWASs) for human complex diseases have ignored dominance, epistasis and ethnic interactions. We conducted comparative GWASs for total cholesterol using full model and additive models, which illustrate the impacts of the ignoring genetic variants on analysis results and demonstrate how genetic effects of multiple loci could differ across different ethnic groups. There were 15 quantitative trait loci with 13 individual loci and 3 pairs of epistasis loci identified by full model, whereas only 14 loci (9 common loci and 5 different loci) identified by multi-loci additive model. Again, 4 full model detected loci were not detected using multi-loci additive model. PLINK-analysis identified two loci and GCTA-analysis detected only one locus with genome-wide significance. Full model identified three previously reported genes as well as several new genes. Bioinformatics analysis showed some new genes are related with cholesterol related chemicals and/or diseases. Analyses of cholesterol data and simulation studies revealed that the full model performs were better than the additive-model performs in terms of detecting power and unbiased estimations of genetic variants of complex traits. PMID:28079101

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci

PubMed Central

Ju, Jin Hyun; Crystal, Ronald G.

2017-01-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In light of these results, we discuss the broad impact eQTL that have been previously reported from the analysis of human data and suggest that considerable caution should be exercised when making biological inferences based on these reported eQTL. PMID:28505156

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci.

PubMed

Ju, Jin Hyun; Shenoy, Sushila A; Crystal, Ronald G; Mezey, Jason G

2017-05-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In light of these results, we discuss the broad impact eQTL that have been previously reported from the analysis of human data and suggest that considerable caution should be exercised when making biological inferences based on these reported eQTL.

The Work Compatibility Improvement Framework: an integrated perspective of the human-at-work system.

PubMed

Genaidy, Ash; Salem, Sam; Karwowski, Waldemar; Paez, Omar; Tuncel, Setenay

2007-01-15

The industrial revolution demonstrated the limitations of a pure mechanistic approach towards work design. Human work is now seen as a complex entity that involves different scientific branches and blurs the line between mental and physical activities. Job design has been a traditional concern of applied psychology, which has provided insight into the interaction between the individual and the work environment. The goal of this paper is to introduce the human-at-work system as a holistic approach to organizational design. It postulates that the well-being of workers and work outcomes are issues that need to be addressed jointly, moving beyond traditional concepts of job satisfaction and work stress. The work compatibility model (WCM) is introduced as an engineering approach that seeks to integrate previous constructs of job and organizational design. The WCM seeks a balance between energy expenditure and replenishment. The implementation of the WCM in industrial settings is described within the context of the Work Compatibility Improvement Framework. A sample review of six models (motivation-hygiene theory; job characteristics theory; person-environment fit; demand-control model; and balance theory) provides the foundation for the interaction between the individual and the work environment. A review of three workload assessment methods (position analysis questionnaire, job task analysis and NASA task load index) gives an example of the foundation for the taxonomy of work environment domains. Previous models have sought to identify a balance state for the human-at-work system. They differentiated between the objective and subjective effects of the environment and the worker. An imbalance between the person and the environment has been proven to increase health risks. The WCM works with a taxonomy of 12 work domains classified in terms of the direct (acting) or indirect (experienced) effect on the worker. In terms of measurement, two quantitative methods are proposed to measure the state of the system. The first method introduced by Abdallah et al. (2004) identifies operating zones. The second method introduced by Salem et al. (2006) identifies the distribution of the work elements on the x/y coordinate plane. While previous efforts have identified some relevant elements of the systems, they failed to provide a holistic, quantitative approach combining organizational and human factors into a common framework. It is postulated that improving the well-being of workers will simultaneously improve organizational outcomes. The WCM moves beyond previous models by providing a hierarchical structure of work domains and a combination of methods to diagnose any organizational setting. The WCM is an attempt to achieve organizational excellence in human resource management, moving beyond job design to an integrated improvement strategy. A joint approach to organizational and job design will not only result in decreased prevalence of health risks, but in enhanced organizational effectiveness as well. The implementation of the WCM, that is, the Work Compatibility Improvement Framework, provides the basis for integrating different elements of the work environment into a single reliable construct. An improvement framework is essential to ensure that the measures of the WCM result in a system that is adaptive and self-regulated.

Comparative evaluation of two quantitative test methods for determining the efficacy of liquid sporicides and sterilants on a hard surface: a precollaborative study.

PubMed

Tomasino, Stephen F; Hamilton, Martin A

2007-01-01

Two quantitative carrier-based test methods for determining the efficacy of liquid sporicides and sterilants on a hard surface, the Standard Quantitative Carrier Test Method-ASTM E 2111-00 and an adaptation of a quantitative micro-method as reported by Sagripanti and Bonifacino, were compared in this study. The methods were selected based on their desirable characteristics (e.g., well-developed protocol, previous use with spores, fully quantitative, and use of readily available equipment) for testing liquid sporicides and sterilants on a hard surface. In this paper, the Sagripanti-Bonifacino procedure is referred to as the Three Step Method (TSM). AOAC Official Method 966.04 was included in this study as a reference method. Three laboratories participated in the evaluation. Three chemical treatments were tested: (1) 3000 ppm sodium hypochlorite with pH adjusted to 7.0, (2) a hydrogen peroxide/peroxyacetic acid product, and (3) 3000 ppm sodium hypochlorite with pH unadjusted (pH of approximately 10.0). A fourth treatment, 6000 ppm sodium hypochlorite solution with pH adjusted to 7.0, was included only for Method 966.04 as a positive control (high level of efficacy). The contact time was 10 min for all chemical treatments except the 6000 ppm sodium hypochlorite treatment which was tested at 30 min. Each chemical treatment was tested 3 times using each of the methods. Only 2 of the laboratories performed the AOAC method. Method performance was assessed by the within-laboratory variance, between-laboratory variance, and total variance associated with the log reduction (LR) estimates generated by each quantitative method. The quantitative methods performed similarly, and the LR values generated by each method were not statistically different for the 3 treatments evaluated. Based on feedback from the participating laboratories, compared to the TSM, ASTM E 2111-00 was more resource demanding and required more set-up time. The logistical and resource concerns identified for ASTM E 2111-00 were largely associated with the filtration process and counting bacterial colonies on filters. Thus, the TSM was determined to be the most suitable method.

Comparison of quantitative PCR assays for Escherichia coli targeting ribosomal RNA and single copy genes

EPA Science Inventory

Aims: Compare specificity and sensitivity of quantitative PCR (qPCR) assays targeting single and multi-copy gene regions of Escherichia coli. Methods and Results: A previously reported assay targeting the uidA gene (uidA405) was used as the basis for comparing the taxono...

78 FR 64202 - Quantitative Messaging Research

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... COMMODITY FUTURES TRADING COMMISSION Quantitative Messaging Research AGENCY: Commodity Futures... survey will follow qualitative message testing research (for which CFTC received fast- track OMB approval... comments. Please submit your comments using only one method and identify that it is for the ``Quantitative...

Construction of a high-density genetic map by specific locus amplified fragment sequencing (SLAF-seq) and its application to Quantitative Trait Loci (QTL) analysis for boll weight in upland cotton (Gossypium hirsutum.).

PubMed

Zhang, Zhen; Shang, Haihong; Shi, Yuzhen; Huang, Long; Li, Junwen; Ge, Qun; Gong, Juwu; Liu, Aiying; Chen, Tingting; Wang, Dan; Wang, Yanling; Palanga, Koffi Kibalou; Muhammad, Jamshed; Li, Weijie; Lu, Quanwei; Deng, Xiaoying; Tan, Yunna; Song, Weiwu; Cai, Juan; Li, Pengtao; Rashid, Harun or; Gong, Wankui; Yuan, Youlu

2016-04-11

Upland Cotton (Gossypium hirsutum) is one of the most important worldwide crops it provides natural high-quality fiber for the industrial production and everyday use. Next-generation sequencing is a powerful method to identify single nucleotide polymorphism markers on a large scale for the construction of a high-density genetic map for quantitative trait loci mapping. In this research, a recombinant inbred lines population developed from two upland cotton cultivars 0-153 and sGK9708 was used to construct a high-density genetic map through the specific locus amplified fragment sequencing method. The high-density genetic map harbored 5521 single nucleotide polymorphism markers which covered a total distance of 3259.37 cM with an average marker interval of 0.78 cM without gaps larger than 10 cM. In total 18 quantitative trait loci of boll weight were identified as stable quantitative trait loci and were detected in at least three out of 11 environments and explained 4.15-16.70 % of the observed phenotypic variation. In total, 344 candidate genes were identified within the confidence intervals of these stable quantitative trait loci based on the cotton genome sequence. These genes were categorized based on their function through gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and eukaryotic orthologous groups analysis. This research reported the first high-density genetic map for Upland Cotton (Gossypium hirsutum) with a recombinant inbred line population using single nucleotide polymorphism markers developed by specific locus amplified fragment sequencing. We also identified quantitative trait loci of boll weight across 11 environments and identified candidate genes within the quantitative trait loci confidence intervals. The results of this research would provide useful information for the next-step work including fine mapping, gene functional analysis, pyramiding breeding of functional genes as well as marker-assisted selection.

Evaluation of the clinical sensitivity for the quantification of human immunodeficiency virus type 1 RNA in plasma: Comparison of the new COBAS TaqMan HIV-1 with three current HIV-RNA assays--LCx HIV RNA quantitative, VERSANT HIV-1 RNA 3.0 (bDNA) and COBAS AMPLICOR HIV-1 Monitor v1.5.

PubMed

Katsoulidou, Antigoni; Petrodaskalaki, Maria; Sypsa, Vana; Papachristou, Eleni; Anastassopoulou, Cleo G; Gargalianos, Panagiotis; Karafoulidou, Anastasia; Lazanas, Marios; Kordossis, Theodoros; Andoniadou, Anastasia; Hatzakis, Angelos

2006-02-01

The COBAS TaqMan HIV-1 test (Roche Diagnostics) was compared with the LCx HIV RNA quantitative assay (Abbott Laboratories), the Versant HIV-1 RNA 3.0 (bDNA) assay (Bayer) and the COBAS Amplicor HIV-1 Monitor v1.5 test (Roche Diagnostics), using plasma samples of various viral load levels from HIV-1-infected individuals. In the comparison of TaqMan with LCx, TaqMan identified as positive 77.5% of the 240 samples versus 72.1% identified by LCx assay, while their overall agreement was 94.6% and the quantitative results of samples that were positive by both methods were strongly correlated (r=0.91). Similarly, in the comparison of TaqMan with bDNA 3.0, both methods identified 76.3% of the 177 samples as positive, while their overall agreement was 95.5% and the quantitative results of samples that were positive by both methods were strongly correlated (r=0.95). Finally, in the comparison of TaqMan with Monitor v1.5, TaqMan identified 79.5% of the 156 samples as positive versus 80.1% identified by Monitor v1.5, while their overall agreement was 95.5% and the quantitative results of samples that were positive by both methods were strongly correlated (r=0.96). In conclusion, the new COBAS TaqMan HIV-1 test showed excellent agreement with other widely used commercially available tests for the quantitation of HIV-1 viral load.

The development and application of a quantitative peptide microarray platform to SH2 domain specificity space

NASA Astrophysics Data System (ADS)

Engelmann, Brett Warren

The Src homology 2 (SH2) domains evolved alongside protein tyrosine kinases (PTKs) and phosphatases (PTPs) in metazoans to recognize the phosphotyrosine (pY) post-translational modification. The human genome encodes 121 SH2 domains within 111 SH2 domain containing proteins that represent the primary mechanism for cellular signal transduction immediately downstream of PTKs. Despite pY recognition contributing to roughly half of the binding energy, SH2 domains possess substantial binding specificity, or affinity discrimination between phosphopeptide ligands. This specificity is largely imparted by amino acids (AAs) adjacent to the pY, typically from positions +1 to +4 C-terminal to the pY. Much experimental effort has been undertaken to construct preferred binding motifs for many SH2 domains. However, due to limitations in previous experimental methodologies these motifs do not account for the interplay between AAs. It was therefore not known how AAs within the context of individual peptides function to impart SH2 domain specificity. In this work we identified the critical role context plays in defining SH2 domain specificity for physiological ligands. We also constructed a high quality interactome using 50 SH2 domains and 192 physiological ligands. We next developed a quantitative high-throughput (Q-HTP) peptide microarray platform to assess the affinities four SH2 domains have for 124 physiological ligands. We demonstrated the superior characteristics of our platform relative to preceding approaches and validated our results using established biophysical techniques, literature corroboration, and predictive algorithms. The quantitative information provided by the arrays was leveraged to investigate SH2 domain binding distributions and identify points of binding overlap. Our microarray derived affinity estimates were integrated to produce quantitative interaction motifs capable of predicting interactions. Furthermore, our microarrays proved capable of resolving subtle contextual differences within motifs that modulate interaction affinities. We conclude that contextually informed specificity profiling of protein interaction domains using the methodologies developed in this study can inform efforts to understand the interconnectivity of signaling networks in normal and aberrant states. Three supplementary tables containing detailed lists of peptides, interactions, and sources of corroborative information are provided.

A comprehensively quantitative method of evaluating the impact of drought on crop yield using daily multi-scale SPEI and crop growth process model.

PubMed

Wang, Qianfeng; Wu, Jianjun; Li, Xiaohan; Zhou, Hongkui; Yang, Jianhua; Geng, Guangpo; An, Xueli; Liu, Leizhen; Tang, Zhenghong

2017-04-01

The quantitative evaluation of the impact of drought on crop yield is one of the most important aspects in agricultural water resource management. To assess the impact of drought on wheat yield, the Environmental Policy Integrated Climate (EPIC) crop growth model and daily Standardized Precipitation Evapotranspiration Index (SPEI), which is based on daily meteorological data, are adopted in the Huang Huai Hai Plain. The winter wheat crop yields are estimated at 28 stations, after calibrating the cultivar coefficients based on the experimental site data, and SPEI data was taken 11 times across the growth season from 1981 to 2010. The relationship between estimated yield and multi-scale SPEI were analyzed. The optimum time scale SPEI to monitor drought during the crop growth period was determined. The reference yield was determined by averaging the yields from numerous non-drought years. From this data, we propose a comprehensive quantitative method which can be used to predict the impact of drought on wheat yields by combining the daily multi-scale SPEI and crop growth process model. This method was tested in the Huang Huai Hai Plain. The results suggested that estimation of calibrated EPIC was a good predictor of crop yield in the Huang Huai Hai Plain, with lower RMSE (15.4 %) between estimated yield and observed yield at six agrometeorological stations. The soil moisture at planting time was affected by the precipitation and evapotranspiration during the previous 90 days (about 3 months) in the Huang Huai Hai Plain. SPEI G90 was adopted as the optimum time scale SPEI to identify the drought and non-drought years, and identified a drought year in 2000. The water deficit in the year 2000 was significant, and the rate of crop yield reduction did not completely correspond with the volume of water deficit. Our proposed comprehensive method which quantitatively evaluates the impact of drought on crop yield is reliable. The results of this study further our understanding why the adoption of counter measures against drought is important and direct farmers to choose drought-resistant crops.

Faculty Grading of Quantitative Problems: A Mismatch between Values and Practice

ERIC Educational Resources Information Center

Petcovic, Heather L.; Fynewever, Herb; Henderson, Charles; Mutambuki, Jacinta M.; Barney, Jeffrey A.

2013-01-01

Grading practices can send a powerful message to students about course expectations. A study by Henderson et al. ("American Journal of Physics" 72:164-169, 2004) in physics education has identified a misalignment between what college instructors say they value and their actual scoring of quantitative student solutions. This work identified three…

Identification of downy mildew resistance gene candidates by positional cloning in maize (Zea mays subsp. mays; Poaceae)1

PubMed Central

Kim, Jae Yoon; Moon, Jun-Cheol; Kim, Hyo Chul; Shin, Seungho; Song, Kitae; Kim, Kyung-Hee; Lee, Byung-Moo

2017-01-01

Premise of the study: Positional cloning in combination with phenotyping is a general approach to identify disease-resistance gene candidates in plants; however, it requires several time-consuming steps including population or fine mapping. Therefore, in the present study, we suggest a new combined strategy to improve the identification of disease-resistance gene candidates. Methods and Results: Downy mildew (DM)–resistant maize was selected from five cultivars using a spreader row technique. Positional cloning and bioinformatics tools were used to identify the DM-resistance quantitative trait locus marker (bnlg1702) and 47 protein-coding gene annotations. Eventually, five DM-resistance gene candidates, including bZIP34, Bak1, and Ppr, were identified by quantitative reverse-transcription PCR (RT-PCR) without fine mapping of the bnlg1702 locus. Conclusions: The combined protocol with the spreader row technique, quantitative trait locus positional cloning, and quantitative RT-PCR was effective for identifying DM-resistance candidate genes. This cloning approach may be applied to other whole-genome-sequenced crops or resistance to other diseases. PMID:28224059

Salmon silk genes contribute to the elucidation of the flavone pathway in maize (Zea mays L.).

PubMed

McMullen, M D; Kross, H; Snook, M E; Cortés-Cruz, M; Houchins, K E; Musket, T A; Coe, E H

2004-01-01

We utilized maize (Zea mays L.) lines expressing the salmon silk (sm) phenotype, quantitative trait locus analysis, and analytical chemistry of flavone compounds to establish the order of undefined steps in the synthesis of the flavone maysin in maize silks. In addition to the previously described sm1 gene, we identified a second sm locus, which we designate sm2, located on the long arm of maize chromosome 2. Our data indicate that the sm1 gene encodes or controls a glucose modification enzyme and sm2 encodes or controls a rhamnosyl transferase. The order of intermediates in the late steps of maysin synthesis was established as luteolin --> isoorientin --> rhamnosylisoorientin --> maysin. Copyright 2004 The American Genetic Association

An experimental and theoretical core-level study of tautomerism in guanine.

PubMed

Plekan, Oksana; Feyer, Vitaliy; Richter, Robert; Coreno, Marcello; Vall-Llosera, Gemma; Prince, Kevin C; Trofimov, Alexander B; Zaytseva, Irina L; Moskovskaya, Tatyana E; Gromov, Evgeniy V; Schirmer, Jochen

2009-08-20

The core level photoemission and near edge X-ray photoabsorption spectra of guanine in the gas phase have been measured and the results interpreted with the aid of high level ab initio calculations. Tautomers are clearly identified spectroscopically, and their relative free energies and Boltzmann populations at the temperature of the experiment (600 K) have been calculated and compared with the experimental results and with previous calculations. We obtain good agreement between experiment and the Boltzmann weighted theoretical photoemission spectra, which allows a quantitative determination of the ratio of oxo to hydroxy tautomer populations. For the photoabsorption spectra, good agreement is found for the C 1s and O 1s spectra but only fair agreement for the N 1s edge.

Electrical Components for Marine Renewable Energy Arrays: A Techno-Economic Review

DOE PAGES

Collin, Adam J.; Nambiar, Anup J.; Bould, David; ...

2017-11-27

This paper presents a review of the main electrical components that are expected to be present in marine renewable energy arrays. The review is put in context by appraising the current needs of the industry and identifying the key components required in both device and array-scale developments. For each component, electrical, mechanical and cost considerations are discussed; with quantitative data collected during the review made freely available for use by the community via an open access online repository. Here, this data collection updates previous research and addresses gaps specific to emerging offshore technologies, such as marine and floating wind, andmore » provides a comprehensive resource for the techno-economic assessment of offshore energy arrays.« less

Enhancing Induction Coil Reliability

NASA Astrophysics Data System (ADS)

Kreter, K.; Goldstein, R.; Yakey, C.; Nemkov, V.

2014-12-01

In induction hardening, thermal fatigue is one of the main copper failure modes of induction heat treating coils. There have been papers published that describe this failure mode and others that describe some good design practices. The variables previously identified as the sources of thermal fatigue include radiation from the part surface, frequency, current, concentrator losses, water pressure and coil wall thickness. However, there is very little quantitative data on the factors that influence thermal fatigue in induction coils is available in the public domain. By using finite element analysis software this study analyzes the effect of common design variables of inductor cooling, and quantifies the relative importance of these variables. A comprehensive case study for a single shot induction coil with Fluxtrol A concentrator applied is used for the analysis.

Electrical Components for Marine Renewable Energy Arrays: A Techno-Economic Review

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

Collin, Adam J.; Nambiar, Anup J.; Bould, David

This paper presents a review of the main electrical components that are expected to be present in marine renewable energy arrays. The review is put in context by appraising the current needs of the industry and identifying the key components required in both device and array-scale developments. For each component, electrical, mechanical and cost considerations are discussed; with quantitative data collected during the review made freely available for use by the community via an open access online repository. Here, this data collection updates previous research and addresses gaps specific to emerging offshore technologies, such as marine and floating wind, andmore » provides a comprehensive resource for the techno-economic assessment of offshore energy arrays.« less

Effects of wastewater sludge and its detergents on the stability of rotavirus

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

Ward, R.L.; Ashley, C.S.

1980-06-01

Wastewater sludge reduced the heat required to inactivate rotavirus SA-11, and ionic detergents were identified as the sludge components responsible for this effect. A similar result was found previously with reovirus. The quantitative effects of individual ionic detergents on rotavirus and reovirus were very different, and rotavirus was found to be extremely sensitive to several of these detergents. However, neither virus was destabilized by nonionic detergents. On the contrary, rotavirus was stabilized by a nonionic detergent against the potent destabilizing effects of the ionic detergent sodium dodecyl sulfate. The destabilizing effects of both cationic and anionic detergents on rotavirus weremore » greatly altered by changes in the pH of the medium.« less

V/V(max) test applied to SMM gamma-ray bursts

NASA Technical Reports Server (NTRS)

Matz, S. M.; Higdon, J. C.; Share, G. H.; Messina, D. C.; Iadicicco, A.

1992-01-01

We have applied the V/V(max) test to candidate gamma-ray bursts detected by the Gamma-Ray Spectrometer (GRS) aboard the SMM satellite to examine quantitatively the uniformity of the burst source population. For a sample of 132 candidate bursts identified in the GRS data by an automated search using a single uniform trigger criterion we find average V/V(max) = 0.40 +/- 0.025. This value is significantly different from 0.5, the average for a uniform distribution in space of the parent population of burst sources; however, the shape of the observed distribution of V/V(max) is unusual and our result conflicts with previous measurements. For these reasons we can currently draw no firm conclusion about the distribution of burst sources.

A large-scale RNA interference screen identifies genes that regulate autophagy at different stages.

PubMed

Guo, Sujuan; Pridham, Kevin J; Virbasius, Ching-Man; He, Bin; Zhang, Liqing; Varmark, Hanne; Green, Michael R; Sheng, Zhi

2018-02-12

Dysregulated autophagy is central to the pathogenesis and therapeutic development of cancer. However, how autophagy is regulated in cancer is not well understood and genes that modulate cancer autophagy are not fully defined. To gain more insights into autophagy regulation in cancer, we performed a large-scale RNA interference screen in K562 human chronic myeloid leukemia cells using monodansylcadaverine staining, an autophagy-detecting approach equivalent to immunoblotting of the autophagy marker LC3B or fluorescence microscopy of GFP-LC3B. By coupling monodansylcadaverine staining with fluorescence-activated cell sorting, we successfully isolated autophagic K562 cells where we identified 336 short hairpin RNAs. After candidate validation using Cyto-ID fluorescence spectrophotometry, LC3B immunoblotting, and quantitative RT-PCR, 82 genes were identified as autophagy-regulating genes. 20 genes have been reported previously and the remaining 62 candidates are novel autophagy mediators. Bioinformatic analyses revealed that most candidate genes were involved in molecular pathways regulating autophagy, rather than directly participating in the autophagy process. Further autophagy flux assays revealed that 57 autophagy-regulating genes suppressed autophagy initiation, whereas 21 candidates promoted autophagy maturation. Our RNA interference screen identifies identified genes that regulate autophagy at different stages, which helps decode autophagy regulation in cancer and offers novel avenues to develop autophagy-related therapies for cancer.

Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain.

PubMed

Welch, Carrie L; Bretschger, Sara; Wen, Ping-Zi; Mehrabian, Margarete; Latib, Nashat; Fruchart-Najib, Jamila; Fruchart, Jean Charles; Myrick, Christy; Lusis, Aldons J

2004-03-12

Atherosclerosis is a complex disease resulting from the interaction of multiple genes, including those causing dyslipidemia. Relatively few of the causative genes have been identified. Previously, we identified Apoa2 as a major determinant of high-density lipoprotein cholesterol (HDL-C) levels in the mouse model. To identify additional HDL-C level quantitative trait loci (QTLs), while controlling for the effect of the Apoa2 locus, we performed linkage analysis in 179 standard diet-fed F(2) mice derived from strains BALB/cJ and B6.C-H25(c) (a congenic strain carrying the BALB/c Apoa2 allele). Three significant QTLs and one suggestive locus were identified. A female-specific locus mapping to chromosome 6 (Chr 6) also exhibited effects on plasma non-HDL-C, apolipoprotein AII (apoAII), apoB, and apoE levels. A Chr 6 QTL was independently isolated in a related congenic strain (C57BL/6J vs. B6.NODc6: P = 0.003 and P = 0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans.

Genome-wide association analysis of seedling root development in maize (Zea mays L.).

PubMed

Pace, Jordon; Gardner, Candice; Romay, Cinta; Ganapathysubramanian, Baskar; Lübberstedt, Thomas

2015-02-05

Plants rely on the root system for anchorage to the ground and the acquisition and absorption of nutrients critical to sustaining productivity. A genome wide association analysis enables one to analyze allelic diversity of complex traits and identify superior alleles. 384 inbred lines from the Ames panel were genotyped with 681,257 single nucleotide polymorphism markers using Genotyping-by-Sequencing technology and 22 seedling root architecture traits were phenotyped. Utilizing both a general linear model and mixed linear model, a GWAS study was conducted identifying 268 marker trait associations (p ≤ 5.3×10(-7)). Analysis of significant SNP markers for multiple traits showed that several were located within gene models with some SNP markers localized within regions of previously identified root quantitative trait loci. Gene model GRMZM2G153722 located on chromosome 4 contained nine significant markers. This predicted gene is expressed in roots and shoots. This study identifies putatively associated SNP markers associated with root traits at the seedling stage. Some SNPs were located within or near (<1 kb) gene models. These gene models identify possible candidate genes involved in root development at the seedling stage. These and respective linked or functional markers could be targets for breeders for marker assisted selection of seedling root traits.

A Novel Porcine Circovirus Distantly Related to Known Circoviruses Is Associated with Porcine Dermatitis and Nephropathy Syndrome and Reproductive Failure.

PubMed

Palinski, Rachel; Piñeyro, Pablo; Shang, Pengcheng; Yuan, Fangfeng; Guo, Rui; Fang, Ying; Byers, Emily; Hause, Ben M

2017-01-01

Porcine circovirus-associated disease (PCVAD) is clinically manifested by postweaning multisystemic wasting syndrome (PMWS), respiratory and enteric disease, reproductive failure, and porcine dermatitis and nephropathy syndrome (PDNS). Porcine circovirus 2 (PCV2) is an essential component of PCVAD, although an etiologic role in PDNS is not well established. Here, a novel circovirus, designated porcine circovirus 3 (PCV3), was identified in sows that died acutely with PDNS-like clinical signs. The capsid and replicase proteins of PCV3 are only 37% and 55% identical to PCV2 and bat circoviruses, respectively. Aborted fetuses from sows with PDNS contained high levels of PCV3 (7.57 × 10 7 genome copies/ml), and no other viruses were detected by PCR and metagenomic sequencing. Immunohistochemistry (IHC) analysis of sow tissue samples identified PCV3 antigen in skin, kidney, lung, and lymph node samples localized in typical PDNS lesions, including necrotizing vasculitis, glomerulonephritis, granulomatous lymphadenitis, and bronchointerstitial pneumonia. Further study of archived PDNS tissue samples that were negative for PCV2 by IHC analysis identified 45 of 48 that were PCV3 positive by quantitative PCR (qPCR), with 60% of a subset also testing positive for PCV3 by IHC analysis. Analysis by qPCR of 271 porcine respiratory disease diagnostic submission samples identified 34 PCV3-positive cases (12.5%), and enzyme-linked immunosorbent assay detection of anti-PCV3 capsid antibodies in serum samples found that 46 (55%) of 83 samples tested were positive. These results suggest that PCV3 commonly circulates within U.S. swine and may play an etiologic role in reproductive failure and PDNS. Because of the high economic impact of PCV2, this novel circovirus warrants further studies to elucidate its significance and role in PCVAD. While porcine circovirus 2 (PCV2) was first identified in sporadic cases of postweaning multisystemic wasting syndrome in Canada in the early 1990s, an epidemic of severe systemic disease due to PCV2 spread worldwide in the ensuing decade. Despite being effectively controlled by commercial vaccines, PCV2 remains one of the most economically significant viruses of swine. Here, a novel porcine circovirus (PCV3) that is distantly related to known circoviruses was identified in sows with porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure. PCV2, which has previously been associated with these clinical presentations, was not identified. High levels of PCV3 nucleic acid were observed in aborted fetuses by quantitative PCR, and PCV3 antigen was localized in histologic lesions typical of PDNS in sows by immunohistochemistry (IHC) analysis. PCV3 was also identified in archival PDNS diagnostic samples that previously tested negative for PCV2 by IHC analysis. The emergence of PCV3 warrants further investigation. Copyright © 2016 American Society for Microbiology.

Quantitative determination of mineral composition by powder x-ray diffraction

DOEpatents

Pawloski, G.A.

1984-08-10

An external standard intensity ratio method is used for quantitatively determining mineralogic compositions of samples by x-ray diffraction. The method uses ratios of x-ray intensity peaks from a single run. Constants are previously determined for each mineral which is to be quantitatively measured. Ratios of the highest intensity peak of each mineral to be quantified in the sample and the highest intensity peak of a reference mineral contained in the sample are used to calculate sample composition.

Quantitative determination of mineral composition by powder X-ray diffraction

DOEpatents

Pawloski, Gayle A.

1986-01-01

An external standard intensity ratio method is used for quantitatively determining mineralogic compositions of samples by x-ray diffraction. The method uses ratios of x-ray intensity peaks from a single run. Constants are previously determined for each mineral which is to be quantitatively measured. Ratios of the highest intensity peak of each mineral to be quantified in the sample and the highest intensity peak of a reference mineral contained in the sample are used to calculate sample composition.

Quinone-based stable isotope probing for assessment of 13C substrate-utilizing bacteria

NASA Astrophysics Data System (ADS)

Kunihiro, Tadao; Katayama, Arata; Demachi, Toyoko; Veuger, Bart; Boschker, Henricus T. S.; van Oevelen, Dick

2015-04-01

In this study, we attempted to establish quinone-stable-isotope probing (SIP) technique to link substrate-utilizing bacterial group to chemotaxonomic group in bacterial community. To identify metabolically active bacterial group in various environments, SIP techniques combined with biomarkers have been widely utilized as an attractive method for environmental study. Quantitative approaches of the SIP technique have unique advantage to assess substrate-incorporation into bacteria. As a most major quantitative approach, SIP technique based on phospholipid-derived fatty acids (PLFA) have been applied to simultaneously assess substrate-incorporation rate into bacteria and microbial community structure. This approach is powerful to estimate the incorporation rate because of the high sensitivity due to the detection by a gas chromatograph-combustion interface-isotope ratio mass spectrometer (GC-c-IRMS). However, its phylogenetic resolution is limited by specificity of a compound-specific marker. We focused on respiratory quinone as a biomarker. Our previous study found a good correlation between concentrations of bacteria-specific PLFAs and quinones over several orders of magnitude in various marine sediments, and the quinone method has a higher resolution (bacterial phylum level) for resolving differences in bacterial community composition more than that of bacterial PLFA. Therefore, respiratory quinones are potentially good biomarkers for quantitative approaches of the SIP technique. The LC-APCI-MS method as molecular-mass based detection method for quinone was developed and provides useful structural information for identifying quinone molecular species in environmental samples. LC-MS/MS on hybrid triple quadrupole/linear ion trap, which enables to simultaneously identify and quantify compounds in a single analysis, can detect high molecular compounds with their isotope ions. Use of LC-MS/MS allows us to develop quinone-SIP based on molecular mass differences due to 13C abundance in the quinone. In this study, we verified carbon stable isotope of quinone compared with bulk carbon stable isotope of bacterial culture. Results indicated a good correlation between carbon stable isotope of quinone compared with bulk carbon stable isotope. However, our measurement conditions for detection of quinone isotope-ions incurred underestimation of 13C abundance in the quinone. The quinone-SIP technique needs further optimization for measurement conditions of LC-MS/MS.

Comparative analysis of the surface exposed proteome of two canine osteosarcoma cell lines and normal canine osteoblasts.

PubMed

Milovancev, Milan; Hilgart-Martiszus, Ian; McNamara, Michael J; Goodall, Cheri P; Seguin, Bernard; Bracha, Shay; Wickramasekara, Samanthi I

2013-06-13

Osteosarcoma (OSA) is the most common primary bone tumor of dogs and carries a poor prognosis despite aggressive treatment. An improved understanding of the biology of OSA is critically needed to allow for development of novel diagnostic, prognostic, and therapeutic tools. The surface-exposed proteome (SEP) of a cancerous cell includes a multifarious array of proteins critical to cellular processes such as proliferation, migration, adhesion, and inter-cellular communication. The specific aim of this study was to define a SEP profile of two validated canine OSA cell lines and a normal canine osteoblast cell line utilizing a biotinylation/streptavidin system to selectively label, purify, and identify surface-exposed proteins by mass spectrometry (MS) analysis. Additionally, we sought to validate a subset of our MS-based observations via quantitative real-time PCR, Western blot and semi-quantitative immunocytochemistry. Our hypothesis was that MS would detect differences in the SEP composition between the OSA and the normal osteoblast cells. Shotgun MS identified 133 putative surface proteins when output from all samples were combined, with good consistency between biological replicates. Eleven of the MS-detected proteins underwent analysis of gene expression by PCR, all of which were actively transcribed, but varied in expression level. Western blot of whole cell lysates from all three cell lines was effective for Thrombospondin-1, CYR61 and CD44, and indicated that all three proteins were present in each cell line. Semi-quantitative immunofluorescence indicated that CD44 was expressed at much higher levels on the surface of the OSA than the normal osteoblast cell lines. The results of the present study identified numerous differences, and similarities, in the SEP of canine OSA cell lines and normal canine osteoblasts. The PCR, Western blot, and immunocytochemistry results, for the subset of proteins evaluated, were generally supportive of the mass spectrometry data. These methods may be applied to other cell lines, or other biological materials, to highlight unique and previously unrecognized differences between samples. While this study yielded data that may prove useful for OSA researchers and clinicians, further refinements of the described techniques are expected to yield greater accuracy and produce a more thorough SEP analysis.

Quantitative analysis of drugs in hair by UHPLC high resolution mass spectrometry.

PubMed

Kronstrand, Robert; Forsman, Malin; Roman, Markus

2018-02-01

Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are few recommendations regarding the parameters and their criteria to identify a compound. In this study we present a method for the identification and quantification of a range of drugs and discuss the parameters used to identify a compound with high resolution mass spectrometry. Drugs were extracted from hair by incubation in a buffer:solvent mixture at 37°C during 18h. Analysis was performed on a chromatographic system comprised of an Agilent 6550 QTOF coupled to a 1290 Infinity UHPLC system. High resolution accurate mass data were acquired in the All Ions mode and exported into Mass Hunter Quantitative software for quantitation and identification using qualifier fragment ions. Validation included selectivity, matrix effects, calibration range, within day and between day precision and accuracy. The analytes were 7-amino-flunitrazepam, 7-amino-clonazepam, 7-amino-nitrazepam, acetylmorphine, alimemazine, alprazolam, amphetamine, benzoylecgonine, buprenorphine, diazepam, ethylmorphine, fentanyl, hydroxyzine, ketobemidone, codeine, cocaine, MDMA, methadone, methamphetamine, morphine, oxycodone, promethazine, propiomazine, propoxyphene, tramadol, zaleplone, zolpidem, and zopiclone. As proof of concept, hair from 29 authentic post mortem cases were analysed. The calibration range was established between 0.05ng/mg to 5.0ng/mg for all analytes except fentanyl (0.02-2.0), buprenorphine (0.04-2.0), and ketobemidone (0.05-4.0) as well as for alimemazine, amphetamine, cocaine, methadone, and promethazine (0.10-5.0). For all analytes, the accuracy of the fortified pooled hair matrix was 84-108% at the low level and 89-106% at the high level. The within series precisions were between 1.4 and 6.7% and the between series precisions were between 1.4 and 10.1%. From the 29 autopsy cases, 121 positive findings were encountered from 23 of the analytes in concentrations similar to those previously published. We conclude that the developed method proved precise and accurate and that it had sufficient performance for the purpose of detecting regular use of drugs or treatment with prescription drugs. To identify a compound we recommend the use of ion ratios as a complement to instrument software "matching scores". Copyright © 2018 Elsevier B.V. All rights reserved.

Relationship between student selection criteria and learner success for medical dosimetry students

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

Baker, Jamie, E-mail: jabaker@mdanderson.org; Tucker, Debra; Raynes, Edilberto

Medical dosimetry education occupies a specialized branch of allied health higher education. Noted international shortages of health care workers, reduced university funding, limitations on faculty staffing, trends in learner attrition, and increased enrollment of nontraditional students force medical dosimetry educational leadership to reevaluate current admission practices. Program officials wish to select medical dosimetry students with the best chances of successful graduation. The purpose of the quantitative ex post facto correlation study was to investigate the relationship between applicant characteristics (cumulative undergraduate grade point average (GPA), science grade point average (SGPA), prior experience as a radiation therapist, and previous academic degrees)more » and the successful completion of a medical dosimetry program, as measured by graduation. A key finding from the quantitative study was the statistically significant positive correlation between a student's previous degree and his or her successful graduation from the medical dosimetry program. Future research investigations could include a larger research sample, representative of more medical dosimetry student populations, and additional studies concerning the relationship of previous work as a radiation therapist and the effect on success as a medical dosimetry student. Based on the quantitative correlation analysis, medical dosimetry leadership on admissions committees could revise student selection rubrics to place less emphasis on an applicant's undergraduate cumulative GPA and increase the weight assigned to previous degrees.« less

Relationship between student selection criteria and learner success for medical dosimetry students.

PubMed

Baker, Jamie; Tucker, Debra; Raynes, Edilberto; Aitken, Florence; Allen, Pamela

2016-01-01

Medical dosimetry education occupies a specialized branch of allied health higher education. Noted international shortages of health care workers, reduced university funding, limitations on faculty staffing, trends in learner attrition, and increased enrollment of nontraditional students force medical dosimetry educational leadership to reevaluate current admission practices. Program officials wish to select medical dosimetry students with the best chances of successful graduation. The purpose of the quantitative ex post facto correlation study was to investigate the relationship between applicant characteristics (cumulative undergraduate grade point average (GPA), science grade point average (SGPA), prior experience as a radiation therapist, and previous academic degrees) and the successful completion of a medical dosimetry program, as measured by graduation. A key finding from the quantitative study was the statistically significant positive correlation between a student׳s previous degree and his or her successful graduation from the medical dosimetry program. Future research investigations could include a larger research sample, representative of more medical dosimetry student populations, and additional studies concerning the relationship of previous work as a radiation therapist and the effect on success as a medical dosimetry student. Based on the quantitative correlation analysis, medical dosimetry leadership on admissions committees could revise student selection rubrics to place less emphasis on an applicant׳s undergraduate cumulative GPA and increase the weight assigned to previous degrees. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

The abundance of cis-acting loci leading to differential allele expression in F1 mice and their relationship to loci harboring genes affecting complex traits.

PubMed

Yeo, Seungeun; Hodgkinson, Colin A; Zhou, Zhifeng; Jung, Jeesun; Leung, Ming; Yuan, Qiaoping; Goldman, David

2016-08-11

Genome-wide surveys have detected cis-acting quantitative trait loci altering levels of RNA transcripts (RNA-eQTLs) by associating SNV alleles to transcript levels. However, the sensitivity and specificity of detection of cis- expression quantitative trait loci (eQTLs) by genetic approaches, reliant as it is on measurements of transcript levels in recombinant inbred strains or offspring from arranged crosses, is unknown, as is their relationship to QTL's for complex phenotypes. We used transcriptome-wide differential allele expression (DAE) to detect cis-eQTLs in forebrain and kidney from reciprocal crosses between three mouse inbred strains, 129S1/SvlmJ, DBA/2J, and CAST/EiJ and C57BL/6 J. Two of these crosses were previously characterized for cis-eQTLs and QTLs for various complex phenotypes by genetic analysis of recombinant inbred (RI) strains. 5.4 %, 1.9 % and 1.5 % of genes assayed in forebrain of B6/129SF1, B6/DBAF1, and B6/CASTF1 mice, respectively, showed differential allelic expression, indicative of cis-acting alleles at these genes. Moreover, the majority of DAE QTLs were observed to be tissue-specific with only a small fraction showing cis-effects in both tissues. Comparing DAE QTLs in F1 mice to cis-eQTLs previously mapped in RI strains we observed that many of the cis-eQTLs were not confirmed by DAE. Additionally several novel DAE-QTLs not identified as cis-eQTLs were identified suggesting that there are differences in sensitivity and specificity for QTL detection between the two methodologies. Strain specific DAE QTLs in B6/DBAF1 mice were located in excess at candidate genes for alcohol use disorders, seizures, and angiogenesis previously implicated by genetic linkage in C57BL/6J × DBA/2JF2 mice or BXD RI strains. Via a survey for differential allele expression in F1 mice, a substantial proportion of genes were found to have alleles altering expression in cis-acting fashion. Comparing forebrain and kidney, many or most of these alleles were tissue-specific in action. The identification of strain specific DAE QTLs, can assist in assessment of candidate genes located within the large intervals associated with trait QTLs.

Combining gene expression and genetic analyses to identify candidate genes involved in cold responses in pea.

PubMed

Legrand, Sylvain; Marque, Gilles; Blassiau, Christelle; Bluteau, Aurélie; Canoy, Anne-Sophie; Fontaine, Véronique; Jaminon, Odile; Bahrman, Nasser; Mautord, Julie; Morin, Julie; Petit, Aurélie; Baranger, Alain; Rivière, Nathalie; Wilmer, Jeroen; Delbreil, Bruno; Lejeune-Hénaut, Isabelle

2013-09-01

Cold stress affects plant growth and development. In order to better understand the responses to cold (chilling or freezing tolerance), we used two contrasted pea lines. Following a chilling period, the Champagne line becomes tolerant to frost whereas the Terese line remains sensitive. Four suppression subtractive hybridisation libraries were obtained using mRNAs isolated from pea genotypes Champagne and Terese. Using quantitative polymerase chain reaction (qPCR) performed on 159 genes, 43 and 54 genes were identified as differentially expressed at the initial time point and during the time course study, respectively. Molecular markers were developed from the differentially expressed genes and were genotyped on a population of 164 RILs derived from a cross between Champagne and Terese. We identified 5 candidate genes colocalizing with 3 different frost damage quantitative trait loci (QTL) intervals and a protein quantity locus (PQL) rich region previously reported. This investigation revealed the role of constitutive differences between both genotypes in the cold responses, in particular with genes related to glycine degradation pathway that could confer to Champagne a better frost tolerance. We showed that freezing tolerance involves a decrease of expression of genes related to photosynthesis and the expression of a gene involved in the production of cysteine and methionine that could act as cryoprotectant molecules. Although it remains to be confirmed, this study could also reveal the involvement of the jasmonate pathway in the cold responses, since we observed that two genes related to this pathway were mapped in a frost damage QTL interval and in a PQL rich region interval, respectively. Copyright © 2013 Elsevier GmbH. All rights reserved.

Proteomics, bioinformatics and targeted gene expression analysis reveals up-regulation of cochlin and identifies other potential biomarkers in the mouse model for deafness in usher syndrome type 1F

PubMed Central

Chance, Mark R.; Chang, Jinsook; Liu, Shuqing; Gokulrangan, Giridharan; Chen, Daniel H.-C.; Lindsay, Aaron; Geng, Ruishuang; Zheng, Qing Y.; Alagramam, Kumar

2010-01-01

Proteins and protein networks associated with cochlear pathogenesis in the Ames waltzer (av) mouse, a model for deafness in Usher syndrome 1F (USH1F), were identified. Cochlear protein from wild-type and av mice at postnatal day 30, a time point in which cochlear pathology is well established, was analyzed by quantitative 2D gel electrophoresis followed by mass spectrometry (MS). The analytic gel resolved 2270 spots; 69 spots showed significant changes in intensity in the av cochlea compared with the control. The cochlin protein was identified in 20 peptide spots, most of which were up-regulated, while a few were down-regulated. Analysis of MS sequence data showed that, in the av cochlea, a set of full-length isoforms of cochlin was up-regulated, while isoforms missing the N-terminal FCH/LCCL domain were down-regulated. Protein interaction network analysis of all differentially expressed proteins was performed with Metacore software. That analysis revealed a number of statistically significant candidate protein networks predicted to be altered in the affected cochlea. Quantitative PCR (qPCR) analysis of select candidates from the proteomic and bioinformatic investigations showed up-regulation of Coch mRNA and those of p53, Brn3a and Nrf2, transcription factors linked to stress response and survival. Increased mRNA of Brn3a and Nrf2 has previously been associated with increased expression of cochlin in human glaucomatous trabecular meshwork. Our report strongly suggests that increased level of cochlin is an important etiologic factor leading to the degeneration of cochlear neuroepithelia in the USH1F model. PMID:20097680

Genome-wide survey and characterization of the WRKY gene family in Populus trichocarpa.

PubMed

He, Hongsheng; Dong, Qing; Shao, Yuanhua; Jiang, Haiyang; Zhu, Suwen; Cheng, Beijiu; Xiang, Yan

2012-07-01

WRKY transcription factors participate in diverse physiological and developmental processes in plants. They have highly conserved WRKYGQK amino acid sequences in their N-termini, followed by the novel zinc-finger-like motifs, Cys₂His₂ or Cys₂HisCys. To date, numerous WRKY genes have been identified and characterized in a number of herbaceous species. Survey and characterization of WRKY genes in a ligneous species would facilitate a better understanding of the evolutionary processes and functions of this gene family. In this study, 104 poplar WRKY genes (PtWRKY) were identified in the latest poplar genome sequence. According to their structural features, the predicted members were divided into the previously defined groups I-III, as described in rice. In addition, chromosomal localization of the genes demonstrated that there might be WRKY gene hot spots in 2.3 Mb regions on chromosome 14. Furthermore, approximately 83% (86 out of 104) WRKY genes participated in gene duplication events, including 69% (29 out of 42) gene pairs which exhibited segmental duplication. Using semi-quantitative RT-PCR, the expression patterns of subgroup III genes were investigated under different stresses [cold, drought, salinity and salicylic acid (SA)]. The data revealed that these genes presented different expression levels in response to various stress conditions. Expression analysis exhibited PtWRKY76 gene induced markedly in 0.1 mM SA or 25% PEG-6000 treatment. The results presented here provide a fundamental clue for cloning specific function genes in further studies and applications. This study identified 104 poplar WRKY genes and demonstrated WRKY gene hot spots on chromosome 14. Furthermore, semi-quantitative RT-PCR showed variable stress responses in subgroup III.

Resequencing of IRS2 reveals rare variants for obesity but not fasting glucose homeostasis in Hispanic children.

PubMed

Butte, Nancy F; Voruganti, V Saroja; Cole, Shelley A; Haack, Karin; Comuzzie, Anthony G; Muzny, Donna M; Wheeler, David A; Chang, Kyle; Hawes, Alicia; Gibbs, Richard A

2011-09-22

Our objective was to resequence insulin receptor substrate 2 (IRS2) to identify variants associated with obesity- and diabetes-related traits in Hispanic children. Exonic and intronic segments, 5' and 3' flanking regions of IRS2 (∼14.5 kb), were bidirectionally sequenced for single nucleotide polymorphism (SNP) discovery in 934 Hispanic children using 3730XL DNA Sequencers. Additionally, 15 SNPs derived from Illumina HumanOmni1-Quad BeadChips were analyzed. Measured genotype analysis tested associations between SNPs and obesity and diabetes-related traits. Bayesian quantitative trait nucleotide analysis was used to statistically infer the most likely functional polymorphisms. A total of 140 SNPs were identified with minor allele frequencies (MAF) ranging from 0.001 to 0.47. Forty-two of the 70 coding SNPs result in nonsynonymous amino acid substitutions relative to the consensus sequence; 28 SNPs were detected in the promoter, 12 in introns, 28 in the 3'-UTR, and 2 in the 5'-UTR. Two insertion/deletions (indels) were detected. Ten independent rare SNPs (MAF = 0.001-0.009) were associated with obesity-related traits (P = 0.01-0.00002). SNP 10510452_139 in the promoter region was shown to have a high posterior probability (P = 0.77-0.86) of influencing BMI, fat mass, and waist circumference in Hispanic children. SNP 10510452_139 contributed between 2 and 4% of the population variance in body weight and composition. None of the SNPs or indels were associated with diabetes-related traits or accounted for a previously identified quantitative trait locus on chromosome 13 for fasting serum glucose. Rare but not common IRS2 variants may play a role in the regulation of body weight but not an essential role in fasting glucose homeostasis in Hispanic children.

Characteristics of Opioid-Users Whose Death Was Related to Opioid-Toxicity: A Population-Based Study in Ontario, Canada

PubMed Central

Madadi, Parvaz; Hildebrandt, Doris; Lauwers, Albert E.; Koren, Gideon

2013-01-01

Background The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity. Methods This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed. Results Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359). Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch), 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer. Significance/Conclusion These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users. PMID:23577131

Prioritizing Risks and Uncertainties from Intentional Release of Selected Category A Pathogens

PubMed Central

Hong, Tao; Gurian, Patrick L.; Huang, Yin; Haas, Charles N.

2012-01-01

This paper synthesizes available information on five Category A pathogens (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Variola major and Lassa) to develop quantitative guidelines for how environmental pathogen concentrations may be related to human health risk in an indoor environment. An integrated model of environmental transport and human health exposure to biological pathogens is constructed which 1) includes the effects of environmental attenuation, 2) considers fomite contact exposure as well as inhalational exposure, and 3) includes an uncertainty analysis to identify key input uncertainties, which may inform future research directions. The findings provide a framework for developing the many different environmental standards that are needed for making risk-informed response decisions, such as when prophylactic antibiotics should be distributed, and whether or not a contaminated area should be cleaned up. The approach is based on the assumption of uniform mixing in environmental compartments and is thus applicable to areas sufficiently removed in time and space from the initial release that mixing has produced relatively uniform concentrations. Results indicate that when pathogens are released into the air, risk from inhalation is the main component of the overall risk, while risk from ingestion (dermal contact for B. anthracis) is the main component of the overall risk when pathogens are present on surfaces. Concentrations sampled from untracked floor, walls and the filter of heating ventilation and air conditioning (HVAC) system are proposed as indicators of previous exposure risk, while samples taken from touched surfaces are proposed as indicators of future risk if the building is reoccupied. A Monte Carlo uncertainty analysis is conducted and input-output correlations used to identify important parameter uncertainties. An approach is proposed for integrating these quantitative assessments of parameter uncertainty with broader, qualitative considerations to identify future research priorities. PMID:22412915

Magnetic resonance imaging-based measures predictive of short-term surgical outcome in patients with Chiari malformation Type I: a pilot study.

PubMed

Alperin, Noam; Loftus, James Ryan; Bagci, Ahmet M; Lee, Sang H; Oliu, Carlos J; Shah, Ashish H; Green, Barth A

2017-01-01

OBJECTIVE This study identifies quantitative imaging-based measures in patients with Chiari malformation Type I (CM-I) that are associated with positive outcomes after suboccipital decompression with duraplasty. METHODS Fifteen patients in whom CM-I was newly diagnosed underwent MRI preoperatively and 3 months postoperatively. More than 20 previously described morphological and physiological parameters were derived to assess quantitatively the impact of surgery. Postsurgical clinical outcomes were assessed in 2 ways, based on resolution of the patient's chief complaint and using a modified Chicago Chiari Outcome Scale (CCOS). Statistical analyses were performed to identify measures that were different between the unfavorable- and favorable-outcome cohorts. Multivariate analysis was used to identify the strongest predictors of outcome. RESULTS The strongest physiological parameter predictive of outcome was the preoperative maximal cord displacement in the upper cervical region during the cardiac cycle, which was significantly larger in the favorable-outcome subcohorts for both outcome types (p < 0.05). Several hydrodynamic measures revealed significantly larger preoperative-to-postoperative changes in the favorable-outcome subcohort. Predictor sets for the chief-complaint classification included the cord displacement, percent venous drainage through the jugular veins, and normalized cerebral blood flow with 93.3% accuracy. Maximal cord displacement combined with intracranial volume change predicted outcome based on the modified CCOS classification with similar accuracy. CONCLUSIONS Tested physiological measures were stronger predictors of outcome than the morphological measures in patients with CM-I. Maximal cord displacement and intracranial volume change during the cardiac cycle together with a measure that reflects the cerebral venous drainage pathway emerged as likely predictors of decompression outcome in patients with CM-I.

Characteristics of opioid-users whose death was related to opioid-toxicity: a population-based study in Ontario, Canada.

PubMed

Madadi, Parvaz; Hildebrandt, Doris; Lauwers, Albert E; Koren, Gideon

2013-01-01

The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity. This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed. Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359). Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch), 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer. These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users.

Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia.

PubMed

Alikhani, Mehdi; Mirzaei, Mehdi; Sabbaghian, Marjan; Parsamatin, Pouria; Karamzadeh, Razieh; Adib, Samane; Sodeifi, Niloofar; Gilani, Mohammad Ali Sadighi; Zabet-Moghaddam, Masoud; Parker, Lindsay; Wu, Yunqi; Gupta, Vivek; Haynes, Paul A; Gourabi, Hamid; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

2017-06-06

Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS). The abundance of 520 proteins was significantly changed across three groups of samples. We were able to identify several functional biological pathways enriched in azoospermia samples and confirm selected differentially abundant proteins, using multiple histological methods. The results revealed that cell cycle and proteolysis, and RNA splicing were the most significant biological processes impaired by the substantial suppression of proteins related to the aforementioned categories in SCOS tissues. In the MA patient testes, generation of precursor metabolites and energy as well as oxidation-reduction were the most significantly altered processes. Novel candidate proteins identified in this study include key transcription factors, many of which have not previously been shown to be associated with azoospermia. Our findings can provide substantial insights into the molecular regulation of spermatogenesis and human reproduction. The obtained data showed a drastic suppression of proteins involved in spliceosome, cell cycle and proteasome proteins, as well as energy and metabolic production in Sertoli cell only syndrome testis tissue, and to a lesser extent in maturation arrest samples. Moreover, we identified new transcription factors that are highly down-regulated in SCOS and MA patients, thus helping to understand the molecular complexity of spermatogenesis in male infertility. Our findings provide novel candidate protein targets associated with SCOS or MA azoospermia. Copyright © 2017 Elsevier B.V. All rights reserved.

Genes responding to water deficit in apple (Malus × domestica Borkh.) roots.

PubMed

Bassett, Carole Leavel; Baldo, Angela M; Moore, Jacob T; Jenkins, Ryan M; Soffe, Doug S; Wisniewski, Michael E; Norelli, John L; Farrell, Robert E

2014-07-08

Individual plants adapt to their immediate environment using a combination of biochemical, morphological and life cycle strategies. Because woody plants are long-lived perennials, they cannot rely on annual life cycle strategies alone to survive abiotic stresses. In this study we used suppression subtractive hybridization to identify genes both up- and down-regulated in roots during water deficit treatment and recovery. In addition we followed the expression of select genes in the roots, leaves, bark and xylem of 'Royal Gala' apple subjected to a simulated drought and subsequent recovery. In agreement with studies from both herbaceous and woody plants, a number of common drought-responsive genes were identified, as well as a few not previously reported. Three genes were selected for more in depth analysis: a high affinity nitrate transporter (MdNRT2.4), a mitochondrial outer membrane translocase (MdTOM7.1), and a gene encoding an NPR1 homolog (MpNPR1-2). Quantitative expression of these genes in apple roots, bark and leaves was consistent with their roles in nutrition and defense. Additional genes from apple roots responding to drought were identified using suppression subtraction hybridization compared to a previous EST analysis from the same organ. Genes up- and down-regulated during drought recovery in roots were also identified. Elevated levels of a high affinity nitrate transporter were found in roots suggesting that nitrogen uptake shifted from low affinity transport due to the predicted reduction in nitrate concentration in drought-treated roots. Suppression of a NPR1 gene in leaves of drought-treated apple trees may explain in part the increased disease susceptibility of trees subjected to dehydrative conditions.

Mouse genome-wide association study identifies polymorphisms on chromosomes 4, 11, and 15 for age-related cardiac fibrosis.

PubMed

Li, Qiaoli; Berndt, Annerose; Sundberg, Beth A; Silva, Kathleen A; Kennedy, Victoria E; Cario, Clinton L; Richardson, Matthew A; Chase, Thomas H; Schofield, Paul N; Uitto, Jouni; Sundberg, John P

2016-06-01

Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. In previous mouse breeding studies between these DCC susceptible and the DCC-resistant strain C57BL/6J, 4 genetic loci harboring genes involved in DCC inheritance were identified and subsequently termed Dyscalc loci 1 through 4. Here, we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains. Eight strains showed cardiac fibrosis with highest frequency and severity in the moribund mice. Using genotype and phenotype information of the 28 investigated strains, we performed genome-wide association studies (GWAS) and identified the most significant associations on chromosome (Chr) 15 at 72 million base pairs (Mb) (P < 10(-13)) and Chr 4 at 122 Mb (P < 10(-11)) and 134 Mb (P < 10(-7)). At the Chr 15 locus, Col22a1 and Kcnk9 were identified. Both have been reported to be morphologically and functionally important in the heart muscle. The strongest Chr 4 associations were located approximately 6 Mb away from the Dyscalc 2 quantitative trait locus peak within the boundaries of the Extl1 gene and in close proximity to the Trim63 and Cap1 genes. In addition, a single-nucleotide polymorphism association was found on chromosome 11. This study provides evidence for more than the previously reported 4 genetic loci determining cardiac fibrosis and DCC. The study also highlights the power of GWAS in the mouse for dissecting complex genetic traits.

Mouse genome-wide association study identifies polymorphisms on chromosomes 4, 11 and 15 for age-related cardiac fibrosis

PubMed Central

Li, Qiaoli; Berndt, Annerose; Sundberg, Beth A.; Silva, Kathleen A.; Kennedy, Victoria E.; Cario, Clinton L; Richardson, Matthew A.; Chase, Thomas H.; Schofield, Paul N.; Uitto, Jouni; Sundberg, John P.

2017-01-01

Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. In previous mouse breeding studies between these DCC susceptible and the DCC resistant strain C57BL/6J, 4 genetic loci harboring genes involved in DCC inheritance were identified and subsequently termed Dyscal loci 1 through 4. Here we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains. Eight strains showed cardiac fibrosis with highest frequency and severity in the moribund mice. Using genotype and phenotype information of the 28 investigated strains we performed genome-wide association studies (GWAS) and identified the most significant associations on chromosome (Chr) 15 at 72 million base pairs (Mb) (P < 10−13) and Chr 4 at 122 Mb (P < 10−11) and 134 Mb (P < 10−7). At the Chr 15 locus Col22a1 and Kcnk9 were identified. Both have been reported to be morphologically and functionally important in the heart muscle. The strongest Chr 4 associations were located approximate 6 Mb away from the Dyscal 2 quantitative trait locus peak within the boundaries of the Extl1 gene and in close proximity to the Trim63 and Cap1 genes. In addition, a single nucleotide polymorphism association was found on chromosome 11. This study provides evidence for more than the previously reported 4 genetic loci determining cardiac fibrosis and DCC. The study also highlights the power of GWAS in the mouse for dissecting complex genetic traits. PMID:27126641

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study

PubMed Central

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-01-01

Background High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Results Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Conclusion Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions. PMID:14975161

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study.

PubMed

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-12-31

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions.

A Genome-Wide Association Study of Resistance to Stripe Rust (Puccinia striiformis f. sp. tritici) in a Worldwide Collection of Hexaploid Spring Wheat (Triticum aestivum L.)

PubMed Central

Maccaferri, Marco; Zhang, Junli; Bulli, Peter; Abate, Zewdie; Chao, Shiaoman; Cantu, Dario; Bossolini, Eligio; Chen, Xianming; Pumphrey, Michael; Dubcovsky, Jorge

2015-01-01

New races of Puccinia striiformis f. sp. tritici (Pst), the causal pathogen of wheat stripe rust, show high virulence to previously deployed resistance genes and are responsible for large yield losses worldwide. To identify new sources of resistance we performed a genome-wide association study (GWAS) using a worldwide collection of 1000 spring wheat accessions. Adult plants were evaluated under field conditions in six environments in the western United States, and seedlings were tested with four Pst races. A single-nucleotide polymorphism (SNP) Infinium 9K-assay provided 4585 SNPs suitable for GWAS. High correlations among environments and high heritabilities were observed for stripe rust infection type and severity. Greater levels of Pst resistance were observed in a subpopulation from Southern Asia than in other groups. GWAS identified 97 loci that were significant for at least three environments, including 10 with an experiment-wise adjusted Bonferroni probability < 0.10. These 10 quantitative trait loci (QTL) explained 15% of the phenotypic variation in infection type, a percentage that increased to 45% when all QTL were considered. Three of these 10 QTL were mapped far from previously identified Pst resistance genes and QTL, and likely represent new resistance loci. The other seven QTL mapped close to known resistance genes and allelism tests will be required to test their relationships. In summary, this study provides an integrated view of stripe rust resistance resources in spring wheat and identifies new resistance loci that will be useful to diversify the current set of resistance genes deployed to control this devastating disease. PMID:25609748

A genome-wide association study of resistance to stripe rust (Puccinia striiformis f. sp. tritici) in a worldwide collection of hexaploid spring wheat (Triticum aestivum L.).

PubMed

Maccaferri, Marco; Zhang, Junli; Bulli, Peter; Abate, Zewdie; Chao, Shiaoman; Cantu, Dario; Bossolini, Eligio; Chen, Xianming; Pumphrey, Michael; Dubcovsky, Jorge

2015-01-20

New races of Puccinia striiformis f. sp. tritici (Pst), the causal pathogen of wheat stripe rust, show high virulence to previously deployed resistance genes and are responsible for large yield losses worldwide. To identify new sources of resistance we performed a genome-wide association study (GWAS) using a worldwide collection of 1000 spring wheat accessions. Adult plants were evaluated under field conditions in six environments in the western United States, and seedlings were tested with four Pst races. A single-nucleotide polymorphism (SNP) Infinium 9K-assay provided 4585 SNPs suitable for GWAS. High correlations among environments and high heritabilities were observed for stripe rust infection type and severity. Greater levels of Pst resistance were observed in a subpopulation from Southern Asia than in other groups. GWAS identified 97 loci that were significant for at least three environments, including 10 with an experiment-wise adjusted Bonferroni probability < 0.10. These 10 quantitative trait loci (QTL) explained 15% of the phenotypic variation in infection type, a percentage that increased to 45% when all QTL were considered. Three of these 10 QTL were mapped far from previously identified Pst resistance genes and QTL, and likely represent new resistance loci. The other seven QTL mapped close to known resistance genes and allelism tests will be required to test their relationships. In summary, this study provides an integrated view of stripe rust resistance resources in spring wheat and identifies new resistance loci that will be useful to diversify the current set of resistance genes deployed to control this devastating disease. Copyright © 2015 Maccaferri et al.

Comparative study of contrast-enhanced ultrasound qualitative and quantitative analysis for identifying benign and malignant breast tumor lumps.

PubMed

Liu, Jian; Gao, Yun-Hua; Li, Ding-Dong; Gao, Yan-Chun; Hou, Ling-Mi; Xie, Ting

2014-01-01

To compare the value of contrast-enhanced ultrasound (CEUS) qualitative and quantitative analysis in the identification of breast tumor lumps. Qualitative and quantitative indicators of CEUS for 73 cases of breast tumor lumps were retrospectively analyzed by univariate and multivariate approaches. Logistic regression was applied and ROC curves were drawn for evaluation and comparison. The CEUS qualitative indicator-generated regression equation contained three indicators, namely enhanced homogeneity, diameter line expansion and peak intensity grading, which demonstrated prediction accuracy for benign and malignant breast tumor lumps of 91.8%; the quantitative indicator-generated regression equation only contained one indicator, namely the relative peak intensity, and its prediction accuracy was 61.5%. The corresponding areas under the ROC curve for qualitative and quantitative analyses were 91.3% and 75.7%, respectively, which exhibited a statistically significant difference by the Z test (P<0.05). The ability of CEUS qualitative analysis to identify breast tumor lumps is better than with quantitative analysis.

Allelic loss studies do not provide evidence for the "endometriosis-as-tumor" theory.

PubMed

Prowse, Amanda H; Fakis, Giannoulis; Manek, Sanjiv; Churchman, Michael; Edwards, Sarah; Rowan, Andrew; Koninckx, Philippe; Kennedy, Stephen; Tomlinson, Ian P M

2005-04-01

To identify consistent genetic changes in endometriosis samples to determine whether endometriosis lesions are true neoplasms. We analyzed ovarian endometriosis lesions for loss of heterozygosity (LOH) at 12 loci of potential importance (D9S1870, D9S265, D9S270, D9S161, D11S29, D1S199, D8S261, APOA2, PTCH, TP53, D10S541, and D10S1765), including some at which genetic changes were previously reported in endometriosis. Molecular biology laboratory in a university hospital department. Seventeen women with ovarian endometriosis. Laser capture microdissection to separate the endometriotic epithelium, the adjacent endometriotic stroma, and surrounding normal ovarian stromal tissue, followed by DNA extraction and polymerase chain reaction amplification of polymorphic microsatellite markers. Fluorescence-based quantitation for the LOH analysis. We identified LOH in only one lesion at one locus (D8S261). Our data do not support the hypothesis that ovarian endometriosis is a true neoplasm.

Symbiodinium Clade Affects Coral Skeletal Isotopic Ratio

NASA Astrophysics Data System (ADS)

Carilli, J.; Charles, C. D.; Garren, M.; McField, M.; Norris, R. D.

2011-12-01

The influence of different physiologies of Symbiodinium dinoflagellate symbiont clades on the skeletal chemistry of associated coral hosts has not previously been investigated. This is an important issue because coral skeletons are routinely used for tropical paleoclimatic reconstructions. We analyzed coral skeletal samples collected simultaneously from neighboring colonies off Belize and found that those harboring different clades of Symbiodinium displayed significantly different skeletal oxygen isotopic compositions. We also found evidence for mean shifts in skeletal oxygen isotopic composition after coral bleaching (the loss and potential exchange of symbionts) in two of four longer coral cores from the Mesoamerican Reef, though all experienced similar climatic conditions. Thus, we suggest that symbiont clade identity leaves a signature in the coral skeletal archive and that this influence must be considered for quantitative environmental reconstruction. In addition, we suggest that the skeletal isotopic signature may be used to identify changes in the dominant symbiont clade that have occurred in the past, to identify how common and widespread this phenomenon is--a potential adaptation to climate change.

Predictive Model for the Design of Zwitterionic Polymer Brushes: A Statistical Design of Experiments Approach.

PubMed

Kumar, Ramya; Lahann, Joerg

2016-07-06

The performance of polymer interfaces in biology is governed by a wide spectrum of interfacial properties. With the ultimate goal of identifying design parameters for stem cell culture coatings, we developed a statistical model that describes the dependence of brush properties on surface-initiated polymerization (SIP) parameters. Employing a design of experiments (DOE) approach, we identified operating boundaries within which four gel architecture regimes can be realized, including a new regime of associated brushes in thin films. Our statistical model can accurately predict the brush thickness and the degree of intermolecular association of poly[{2-(methacryloyloxy) ethyl} dimethyl-(3-sulfopropyl) ammonium hydroxide] (PMEDSAH), a previously reported synthetic substrate for feeder-free and xeno-free culture of human embryonic stem cells. DOE-based multifunctional predictions offer a powerful quantitative framework for designing polymer interfaces. For example, model predictions can be used to decrease the critical thickness at which the wettability transition occurs by simply increasing the catalyst quantity from 1 to 3 mol %.

In vivo insertion pool sequencing identifies virulence factors in a complex fungal–host interaction

PubMed Central

Uhse, Simon; Pflug, Florian G.; Stirnberg, Alexandra; Ehrlinger, Klaus; von Haeseler, Arndt

2018-01-01

Large-scale insertional mutagenesis screens can be powerful genome-wide tools if they are streamlined with efficient downstream analysis, which is a serious bottleneck in complex biological systems. A major impediment to the success of next-generation sequencing (NGS)-based screens for virulence factors is that the genetic material of pathogens is often underrepresented within the eukaryotic host, making detection extremely challenging. We therefore established insertion Pool-Sequencing (iPool-Seq) on maize infected with the biotrophic fungus U. maydis. iPool-Seq features tagmentation, unique molecular barcodes, and affinity purification of pathogen insertion mutant DNA from in vivo-infected tissues. In a proof of concept using iPool-Seq, we identified 28 virulence factors, including 23 that were previously uncharacterized, from an initial pool of 195 candidate effector mutants. Because of its sensitivity and quantitative nature, iPool-Seq can be applied to any insertional mutagenesis library and is especially suitable for genetically complex setups like pooled infections of eukaryotic hosts. PMID:29684023

Dynamical transitions associated with turbulence in a helicon plasma

NASA Astrophysics Data System (ADS)

Light, Adam D.; Tian, Li; Chakraborty Thakur, Saikat; Tynan, George R.

2017-10-01

Diagnostic capabilities are often cited as a limiting factor in our understanding of transport in fusion devices. Increasingly advanced multichannel diagnostics are being applied to classify transport regimes and to search for ``trigger'' features that signal an oncoming dynamical event, such as an ELM or an L-H transition. In this work, we explore a technique that yields information about global properties of plasma dynamics from a single time series of a relevant plasma quantity. Electrostatic probe data from the Controlled Shear Decorrelation eXperiment (CSDX) is analyzed using recurrence quantification analysis (RQA) in the context of previous work on the transition to weak drift-wave turbulence. The recurrence characteristics of a phase space trajectory provide a quantitative means to classify dynamics and identify transitions in a complex system. We present and quantify dynamical variations in the plasma variables as a function of the background magnetic field strength. A dynamical transition corresponding to the emergence of broadband fluctuations is identified using RQA measures.

Comprehensive Identification of Glycated Peptides and Their Glycation Motifs in Plasma and Erythrocytes of Control and Diabetic Subjects

PubMed Central

Zhang, Qibin; Monroe, Matthew E.; Schepmoes, Athena A.; Clauss, Therese R. W.; Gritsenko, Marina A.; Meng, Da; Petyuk, Vladislav A.; Smith, Richard D.; Metz, Thomas O.

2011-01-01

Non-enzymatic glycation of proteins sets the stage for formation of advanced glycation end-products and development of chronic complications of diabetes. In this report, we extended our previous methods on proteomics analysis of glycated proteins to comprehensively identify glycated proteins in control and diabetic human plasma and erythrocytes. Using immunodepletion, enrichment, and fractionation strategies, we identified 7749 unique glycated peptides, corresponding to 3742 unique glycated proteins. Semi-quantitative comparisons showed that glycation levels of a number of proteins were significantly increased in diabetes and that erythrocyte proteins were more extensively glycated than plasma proteins. A glycation motif analysis revealed that some amino acids were favored more than others in the protein primary structures in the vicinity of the glycation sites in both sample types. The glycated peptides and corresponding proteins reported here provide a foundation for potential identification of novel markers for diabetes, hyperglycemia, and diabetic complications in future studies. PMID:21612289

Propagating Qualitative Values Through Quantitative Equations

NASA Technical Reports Server (NTRS)

Kulkarni, Deepak

1992-01-01

In most practical problems where traditional numeric simulation is not adequate, one need to reason about a system with both qualitative and quantitative equations. In this paper, we address the problem of propagating qualitative values represented as interval values through quantitative equations. Previous research has produced exponential-time algorithms for approximate solution of the problem. These may not meet the stringent requirements of many real time applications. This paper advances the state of art by producing a linear-time algorithm that can propagate a qualitative value through a class of complex quantitative equations exactly and through arbitrary algebraic expressions approximately. The algorithm was found applicable to Space Shuttle Reaction Control System model.

Teaching Fundamental Skills in Microsoft Excel to First-Year Students in Quantitative Analysis

ERIC Educational Resources Information Center

Rubin, Samuel J.; Abrams, Binyomin

2015-01-01

Despite their technological savvy, most students entering university lack the necessary computer skills to succeed in a quantitative analysis course, in which they are often expected to input, analyze, and plot results of experiments without any previous formal education in Microsoft Excel or similar programs. This lack of formal education results…

Secondary Schools Principals and Their Job Satisfaction: A Test of Process Theories

ERIC Educational Resources Information Center

Maforah, Tsholofelo Paulinah

2015-01-01

The study aims to test the validity of process theories on the job satisfaction of previously disadvantaged Secondary School principals in the North West province. A mixed-method approach consisting of both quantitative and qualitative methods was used for the study. A questionnaire was administered during the quantitative phase with a sample that…

OZONE-SCAVENGING REAGENTS SUITABLE FOR USE IN THE QUANTITATIVE DETERMINATION OF ALDEHYDES AS THE O-(2,3,4,5,6-PENTAFLUOROBENZYL)OXIMES BY GC-ECD

EPA Science Inventory

Previously, we reported interference due to several ozone-scavenging reagents (OSRs) in the quantitation of aldehydes using 0-(2,3,4,5,6-pentafluorobenzyl)oxylamine (PFBOA) in the analysis of ozonated waters. Scavenging ozone is essential if ozonation byproduct concentrations ar...

Normalizing gene expression by quantitative PCR during somatic embryogenesis in two representative conifer species: Pinus pinaster and Picea abies.

PubMed

de Vega-Bartol, José J; Santos, Raquen Raissa; Simões, Marta; Miguel, Célia M

2013-05-01

Suitable internal control genes to normalize qPCR data from different stages of embryo development and germination were identified in two representative conifer species. Clonal propagation by somatic embryogenesis has a great application potentiality in conifers. Quantitative PCR (qPCR) is widely used for gene expression analysis during somatic embryogenesis and embryo germination. No single reference gene is universal, so a systematic characterization of endogenous genes for concrete conditions is fundamental for accuracy. We identified suitable internal control genes to normalize qPCR data obtained at different steps of somatic embryogenesis (embryonal mass proliferation, embryo maturation and germination) in two representative conifer species, Pinus pinaster and Picea abies. Candidate genes included endogenous genes commonly used in conifers, genes previously tested in model plants, and genes with a lower variation of the expression along embryo development according to genome-wide transcript profiling studies. Three different algorithms were used to evaluate expression stability. The geometric average of the expression values of elongation factor-1α, α-tubulin and histone 3 in P. pinaster, and elongation factor-1α, α-tubulin, adenosine kinase and CAC in P. abies were adequate for expression studies throughout somatic embryogenesis. However, improved accuracy was achieved when using other gene combinations in experiments with samples at a single developmental stage. The importance of studies selecting reference genes to use in different tissues or developmental stages within one or close species, and the instability of commonly used reference genes, is highlighted.

Fidgetin-Like1 Is a Strong Candidate for a Dynamic Impairment of Male Meiosis Leading to Reduced Testis Weight in Mice

PubMed Central

L'Hôte, David; Vatin, Magalie; Auer, Jana; Castille, Johan; Passet, Bruno; Montagutelli, Xavier

2011-01-01

Background In a previous work, using an interspecific recombinant congenic mouse model, we reported a genomic region of 23 Mb on mouse chromosome 11 implicated in testis weight decrease and moderate teratozoospermia (∼20–30%), a Quantitative Trait Locus (QTL) called Ltw1. The objective of the present study is to identify the gene underlying this phenotype. Results In the present study, we refined the QTL position to a 5 Mb fragment encompassing only 11 genes. We showed that the low testis weight phenotype was due to kinetic alterations occurring during the first wave of the spermatogenesis where we could point out to an abnormal lengthening of spermatocyte prophase. We identify Fidgetin-like 1 (Fignl1) as the gene underlying the phenotype, since if fulfilled both the physiological and molecular characteristics required. Indeed, amongst the 11 positional candidates it is the only gene that is expressed during meiosis at the spermatocyte stage, and that presents with non-synonymous coding variations differentiating the two mouse strains at the origin of the cross. Conclusions This work prompted us to propose Fignl1 as a novel actor in mammal's male meiosis dynamics which has fundamental interest. Besides, this gene is a new potential candidate for human infertilities caused by teratozoospermia and blockades of spermatogenesis. In addition this study demonstrates that interspecific models may be useful for understanding complex quantitative traits. PMID:22110678

Construction of a High-Density Genetic Map from RNA-Seq Data for an Arabidopsis Bay-0 × Shahdara RIL Population

PubMed Central

Serin, Elise A. R.; Snoek, L. B.; Nijveen, Harm; Willems, Leo A. J.; Jiménez-Gómez, Jose M.; Hilhorst, Henk W. M.; Ligterink, Wilco

2017-01-01

High-density genetic maps are essential for high resolution mapping of quantitative traits. Here, we present a new genetic map for an Arabidopsis Bayreuth × Shahdara recombinant inbred line (RIL) population, built on RNA-seq data. RNA-seq analysis on 160 RILs of this population identified 30,049 single-nucleotide polymorphisms (SNPs) covering the whole genome. Based on a 100-kbp window SNP binning method, 1059 bin-markers were identified, physically anchored on the genome. The total length of the RNA-seq genetic map spans 471.70 centimorgans (cM) with an average marker distance of 0.45 cM and a maximum marker distance of 4.81 cM. This high resolution genotyping revealed new recombination breakpoints in the population. To highlight the advantages of such high-density map, we compared it to two publicly available genetic maps for the same population, comprising 69 PCR-based markers and 497 gene expression markers derived from microarray data, respectively. In this study, we show that SNP markers can effectively be derived from RNA-seq data. The new RNA-seq map closes many existing gaps in marker coverage, saturating the previously available genetic maps. Quantitative trait locus (QTL) analysis for published phenotypes using the available genetic maps showed increased QTL mapping resolution and reduced QTL confidence interval using the RNA-seq map. The new high-density map is a valuable resource that facilitates the identification of candidate genes and map-based cloning approaches. PMID:29259624

Transplantation analysis of developmental mechanisms in Hydra.

PubMed

Shimizu, Hiroshi

2012-01-01

Since the pioneering work of Ethel Browne (1909) who demonstrated for the first time the concept of organizer activity, i.e. the potency of an apical Hydra tissue to induce a secondary axis when transplanted onto a host, Hydra flourished as a fruitful model system for developmental studies. Over the next 60 years this efficient transplantation approach identified graded biological activities along the body column of Hydra named Head Acti-vation and Head Inhibition. These properties inspired theoretical modelers including Lewis Wolpert, Alfred Gierer and Hans Meinhardt to propose models for morphogenesis, respectively the positional information (1969) and reaction-diffusion (1972) models. In 1973, Tsutomu Sugiyama and Toshitaka Fujisawa initiated in Mishima a unique project to analyze the properties of Hydra strains with distinct morphological and developmental characters. To this end, they collected in several areas of Japan multiple Hydra strains that they subsequently characterized and crossed. They also established a lateral transplantation strategy that was much more powerful than the previous ones, as it combined quantitative measurements with cellular analyses thanks to the chimera procedures developed by Campbell and colleagues. In-deed this approach provided a paradigm to quantify in any morphological phenotype the Head Activation and Head Inhibition levels along the body column. In this article, I review the various strains identified by Sugiyama and colleagues, the principles and the main results deduced from the quantitative lateral transplantation strategy. In addition, I briefly discuss the relevance of this approach in the era of molecular biology.

Balance Confidence and Falls in Non-Demented Essential Tremor Patients: The Role of Cognition

PubMed Central

Rao, Ashwini K.; Gilman, Arthur; Louis, Elan D.

2014-01-01

Objective To examine 1) the effect of cognitive ability on balance confidence and falls, 2) the relationship of balance confidence and falls with quantitative measures of gait, and 3) measures that predict falls, in people with Essential Tremor (ET). Design Cross-sectional study. Setting: General community. Participants One-hundred-eighty participants (132 people with ET and 48 controls). People with ET were divided into two groups based on the median score on the modified Mini Mental State Exam: ET-LCS vs. ET-HCS. Interventions Not applicable. Main Outcome Measures Activities of Balance Confidence-6 (ABC) scale and falls in the previous year. Results ET-LCS had lower ABC-6 scores and a greater number of falls than ET-HCS (p<0.05 for all measures) or controls (p<0.01 for all measures). Quantitative gait measures were significantly correlated with ABC-6 score and falls. Gait speed (p<0.007) and ABC-6 score (p<0.02) were significant predictors of falls. Receiver Operating Characteristic curve analysis revealed that gait speed < 0.9 m/s and ABC-6 score < 51% were associated with moderate sensitivity and specificity in identifying fallers. Conclusions People with ET with low cognitive scores have impaired gait, and report lower balance confidence, and higher number of falls than their counterparts with higher cognitive scores, and controls. We have identified assessments that are easily administered (gait speed and ABC-6 scale), and are associated with falls in ET. PMID:24769121

Applying Qualitative Hazard Analysis to Support Quantitative Safety Analysis for Proposed Reduced Wake Separation Conops

NASA Technical Reports Server (NTRS)

Shortle, John F.; Allocco, Michael

2005-01-01

This paper describes a scenario-driven hazard analysis process to identify, eliminate, and control safety-related risks. Within this process, we develop selective criteria to determine the applicability of applying engineering modeling to hypothesized hazard scenarios. This provides a basis for evaluating and prioritizing the scenarios as candidates for further quantitative analysis. We have applied this methodology to proposed concepts of operations for reduced wake separation for closely spaced parallel runways. For arrivals, the process identified 43 core hazard scenarios. Of these, we classified 12 as appropriate for further quantitative modeling, 24 that should be mitigated through controls, recommendations, and / or procedures (that is, scenarios not appropriate for quantitative modeling), and 7 that have the lowest priority for further analysis.

76 FR 22045 - Fluopicolide; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-20

... increased quantitative susceptibility of rat or rabbit fetuses to in utero or postnatal exposure to... is identified as docket ID number EPA-HQ-OPP-2006-0481. A quantitative reassessment of the BAM risk... fluopicolide and separately, its metabolite, BAM in food as follows: i. Acute exposure. Quantitative acute...

Signatures of Evolutionary Adaptation in Quantitative Trait Loci Influencing Trace Element Homeostasis in Liver

PubMed Central

Sabidó, Eduard; Bosch, Elena

2016-01-01

Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health and disease, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 single nucleotide polymorphism (SNPs) in the same sample set. We detected significant associations for 8 protein quantitative trait loci (pQTL), 10 expression quantitative trait loci (eQTLs), and 15 micronutrient quantitative trait loci (nutriQTL). Six of these exceeded the false discovery rate cutoff and were related to essential trace elements: 1) one pQTL for GPX2 (rs10133290); 2) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and 3) three nutriQTLs: The pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1, GPX3, SLC30A9, and SLC39A8. Overall, this detailed study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients. PMID:26582562

Development of a pressurized liquid extraction-solid-phase extraction followed by liquid chromatography-electrospray ionization tandem mass spectrometry method for the quantitative determination of benzoxazolinones and their degradation products in agricultural soil.

PubMed

Villagrasa, M; Guillamón, M; Navarro, A; Eljarrat, E; Barceló, D

2008-02-01

A new analytical method for the quantitative determination of benzoxazolinones and their degradation products in agricultural soils based on the use of pressurized liquid extraction (PLE) followed by solid-phase extraction (SPE) and then instrumental determination using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) is described. Using this method, the characterization, separation and quantitative detection of a mixture of two benzoxazolinones, benzoxazolin-2-one (BOA) and 6-methoxybenzoxazolin-2-one (MBOA) and their degradation products, 2-aminophenol (APH), N-(2-hydroxyphenyl)malonamic acid (HMPMA), 2-amino-3-H-phenoxazin-3-one (APO), 9-methoxy-2-amino-3-H-phenoxazin-3-one (AMPO), 2-acetylamino-3-H-phenoxazin-3-one (AAPO) and 2-acetylamino-9-methoxy-2-amino-3-H-phenoxazin-3-one (AAMPO) was achieved. The complete LC-ESI-MS-MS precursor-product ion fragmentation pathways for the degradation products of benzoxazolinones are described for the first time. Quantitative analysis was done in the multiple reaction mode using two specific combinations of precursor-product ion transitions for each compound. The optimized method was quality assessed by the measure of parameter as recovery, linearity, sensitivity, repeatability and reproducibility. Recoveries of the analytes ranged from 53 to 123%. The developed method offered improvements to the sensitivity as compared with our previously LC-MS method, with detection limits down to 2.4-21 ng/g of dry weight. This achievement allows us to identify and quantify for the first time degradation products of benzoxazolinones in real agricultural soil samples. Analytes were found in the range of 20.6-149 ng/g dry weight.

Quantitative analysis of arterial flow properties for detection of non-calcified plaques in ECG-gated coronary CT angiography

NASA Astrophysics Data System (ADS)

Wei, Jun; Zhou, Chuan; Chan, Heang-Ping; Chughtai, Aamer; Agarwal, Prachi; Kuriakose, Jean; Hadjiiski, Lubomir; Patel, Smita; Kazerooni, Ella

2015-03-01

We are developing a computer-aided detection system to assist radiologists in detection of non-calcified plaques (NCPs) in coronary CT angiograms (cCTA). In this study, we performed quantitative analysis of arterial flow properties in each vessel branch and extracted flow information to differentiate the presence and absence of stenosis in a vessel segment. Under rest conditions, blood flow in a single vessel branch was assumed to follow Poiseuille's law. For a uniform pressure distribution, two quantitative flow features, the normalized arterial compliance per unit length (Cu) and the normalized volumetric flow (Q) along the vessel centerline, were calculated based on the parabolic Poiseuille solution. The flow features were evaluated for a two-class classification task to differentiate NCP candidates obtained by prescreening as true NCPs and false positives (FPs) in cCTA. For evaluation, a data set of 83 cCTA scans was retrospectively collected from 83 patient files with IRB approval. A total of 118 NCPs were identified by experienced cardiothoracic radiologists. The correlation between the two flow features was 0.32. The discriminatory ability of the flow features evaluated as the area under the ROC curve (AUC) was 0.65 for Cu and 0.63 for Q in comparison with AUCs of 0.56-0.69 from our previous luminal features. With stepwise LDA feature selection, volumetric flow (Q) was selected in addition to three other luminal features. With FROC analysis, the test results indicated a reduction of the FP rates to 3.14, 1.98, and 1.32 FPs/scan at sensitivities of 90%, 80%, and 70%, respectively. The study indicated that quantitative blood flow analysis has the potential to provide useful features for the detection of NCPs in cCTA.

Visual Aggregate Analysis of Eligibility Features of Clinical Trials

PubMed Central

He, Zhe; Carini, Simona; Sim, Ida; Weng, Chunhua

2015-01-01

Objective To develop a method for profiling the collective populations targeted for recruitment by multiple clinical studies addressing the same medical condition using one eligibility feature each time. Methods Using a previously published database COMPACT as the backend, we designed a scalable method for visual aggregate analysis of clinical trial eligibility features. This method consists of four modules for eligibility feature frequency analysis, query builder, distribution analysis, and visualization, respectively. This method is capable of analyzing (1) frequently used qualitative and quantitative features for recruiting subjects for a selected medical condition, (2) distribution of study enrollment on consecutive value points or value intervals of each quantitative feature, and (3) distribution of studies on the boundary values, permissible value ranges, and value range widths of each feature. All analysis results were visualized using Google Charts API. Five recruited potential users assessed the usefulness of this method for identifying common patterns in any selected eligibility feature for clinical trial participant selection. Results We implemented this method as a Web-based analytical system called VITTA (Visual Analysis Tool of Clinical Study Target Populations). We illustrated the functionality of VITTA using two sample queries involving quantitative features BMI and HbA1c for conditions “hypertension” and “Type 2 diabetes”, respectively. The recruited potential users rated the user-perceived usefulness of VITTA with an average score of 86.4/100. Conclusions We contributed a novel aggregate analysis method to enable the interrogation of common patterns in quantitative eligibility criteria and the collective target populations of multiple related clinical studies. A larger-scale study is warranted to formally assess the usefulness of VITTA among clinical investigators and sponsors in various therapeutic areas. PMID:25615940

Visual aggregate analysis of eligibility features of clinical trials.

PubMed

He, Zhe; Carini, Simona; Sim, Ida; Weng, Chunhua

2015-04-01

To develop a method for profiling the collective populations targeted for recruitment by multiple clinical studies addressing the same medical condition using one eligibility feature each time. Using a previously published database COMPACT as the backend, we designed a scalable method for visual aggregate analysis of clinical trial eligibility features. This method consists of four modules for eligibility feature frequency analysis, query builder, distribution analysis, and visualization, respectively. This method is capable of analyzing (1) frequently used qualitative and quantitative features for recruiting subjects for a selected medical condition, (2) distribution of study enrollment on consecutive value points or value intervals of each quantitative feature, and (3) distribution of studies on the boundary values, permissible value ranges, and value range widths of each feature. All analysis results were visualized using Google Charts API. Five recruited potential users assessed the usefulness of this method for identifying common patterns in any selected eligibility feature for clinical trial participant selection. We implemented this method as a Web-based analytical system called VITTA (Visual Analysis Tool of Clinical Study Target Populations). We illustrated the functionality of VITTA using two sample queries involving quantitative features BMI and HbA1c for conditions "hypertension" and "Type 2 diabetes", respectively. The recruited potential users rated the user-perceived usefulness of VITTA with an average score of 86.4/100. We contributed a novel aggregate analysis method to enable the interrogation of common patterns in quantitative eligibility criteria and the collective target populations of multiple related clinical studies. A larger-scale study is warranted to formally assess the usefulness of VITTA among clinical investigators and sponsors in various therapeutic areas. Copyright © 2015 Elsevier Inc. All rights reserved.

Critical appraisal of emergency medicine education research: the best publications of 2012.

PubMed

Lin, Michelle; Fisher, Jonathan; Coates, Wendy C; Farrell, Susan E; Shayne, Philip; Maggio, Lauren; Kuhn, Gloria

2014-03-01

The objective was to critically appraise and highlight medical education research published in 2012 that was methodologically superior and whose outcomes were pertinent to teaching and education in emergency medicine (EM). A search of the English language literature in 2012 querying Education Resources Information Center (ERIC), PsychInfo, PubMed, and Scopus identified EM studies using hypothesis-testing or observational investigations of educational interventions. Two reviewers independently screened all of the publications and removed articles using established exclusion criteria. This year, publications limited to a single-site survey design that measured satisfaction or self-assessment on unvalidated instruments were not formally reviewed. Six reviewers then independently ranked all remaining publications using one of two scoring systems depending on whether the study methodology was primarily qualitative or quantitative. Each scoring system had nine criteria, including four related to methodology, that were chosen a priori, to standardize evaluation by reviewers. The quantitative study scoring system was used previously to appraise medical education published annually in 2008 through 2011, while a separate, new qualitative study scoring system was derived and implemented consisting of parallel metrics. Forty-eight medical education research papers met the a priori criteria for inclusion, and 33 (30 quantitative and three qualitative studies) were reviewed. Seven quantitative and two qualitative studies met the criteria for inclusion as exemplary and are summarized in this article. This critical appraisal series aims to promote superior education research by reviewing and highlighting nine of the 48 major education research studies with relevance to EM published in 2012. Current trends and common methodologic pitfalls in the 2012 papers are noted. © 2014 by the Society for Academic Emergency Medicine.

A Quantitative and Novel Approach to the Prioritization of Zoonotic Diseases in North America: A Public Perspective

PubMed Central

Ng, Victoria; Sargeant, Jan M.

2012-01-01

Background Zoonoses account for over half of all communicable diseases causing illness in humans. As there are limited resources available for the control and prevention of zoonotic diseases, a framework for their prioritization is necessary to ensure resources are directed into those of highest importance. Although zoonotic outbreaks are a significant burden of disease in North America, the systematic prioritization of zoonoses in this region has not been previously evaluated. Methodology/Principal Findings This study describes the novel use of a well-established quantitative method, conjoint analysis (CA), to identify the relative importance of 21 key characteristics of zoonotic diseases that can be used for their prioritization in Canada and the US. Relative importance weights from the CA were used to develop a point-scoring system to derive a recommended list of zoonoses for prioritization in Canada and the US. Over 1,500 participants from the general public were recruited to complete the online survey (761 from Canada and 778 from the US). Hierarchical Bayes models were fitted to the survey data to derive CA-weighted scores. Scores were applied to 62 zoonotic diseases of public health importance in Canada and the US to rank diseases in order of priority. Conclusions/Significance This was the first study to describe a systematic and quantitative approach to the prioritization of zoonoses in North America involving public participants. We found individuals with no prior knowledge or experience in prioritizing zoonoses were capable of producing meaningful results using CA as a novel quantitative approach to prioritization. More similarities than differences were observed between countries suggesting general agreement in disease prioritization between Canadians and Americans. We demonstrate CA as a potential tool for the prioritization of zoonoses; other prioritization exercises may also consider this approach. PMID:23133639

SCOPA and META-SCOPA: software for the analysis and aggregation of genome-wide association studies of multiple correlated phenotypes.

PubMed

Mägi, Reedik; Suleimanov, Yury V; Clarke, Geraldine M; Kaakinen, Marika; Fischer, Krista; Prokopenko, Inga; Morris, Andrew P

2017-01-11

Genome-wide association studies (GWAS) of single nucleotide polymorphisms (SNPs) have been successful in identifying loci contributing genetic effects to a wide range of complex human diseases and quantitative traits. The traditional approach to GWAS analysis is to consider each phenotype separately, despite the fact that many diseases and quantitative traits are correlated with each other, and often measured in the same sample of individuals. Multivariate analyses of correlated phenotypes have been demonstrated, by simulation, to increase power to detect association with SNPs, and thus may enable improved detection of novel loci contributing to diseases and quantitative traits. We have developed the SCOPA software to enable GWAS analysis of multiple correlated phenotypes. The software implements "reverse regression" methodology, which treats the genotype of an individual at a SNP as the outcome and the phenotypes as predictors in a general linear model. SCOPA can be applied to quantitative traits and categorical phenotypes, and can accommodate imputed genotypes under a dosage model. The accompanying META-SCOPA software enables meta-analysis of association summary statistics from SCOPA across GWAS. Application of SCOPA to two GWAS of high-and low-density lipoprotein cholesterol, triglycerides and body mass index, and subsequent meta-analysis with META-SCOPA, highlighted stronger association signals than univariate phenotype analysis at established lipid and obesity loci. The META-SCOPA meta-analysis also revealed a novel signal of association at genome-wide significance for triglycerides mapping to GPC5 (lead SNP rs71427535, p = 1.1x10 -8 ), which has not been reported in previous large-scale GWAS of lipid traits. The SCOPA and META-SCOPA software enable discovery and dissection of multiple phenotype association signals through implementation of a powerful reverse regression approach.

Retrieving cloud, dust and ozone abundances in the Martian atmosphere using SPICAM/UV nadir spectra

NASA Astrophysics Data System (ADS)

Willame, Y.; Vandaele, A. C.; Depiesse, C.; Lefèvre, F.; Letocart, V.; Gillotay, D.; Montmessin, F.

2017-08-01

We present the retrieval algorithm developed to analyse nadir spectra from SPICAM/UV aboard Mars-Express. The purpose is to retrieve simultaneously several parameters of the Martian atmosphere and surface: the dust optical depth, the ozone total column, the cloud opacity and the surface albedo. The retrieval code couples the use of an existing complete radiative transfer code, an inversion method and a cloud detection algorithm. We describe the working principle of our algorithm and the parametrisation used to model the required absorption, scattering and reflection processes of the solar UV radiation that occur in the Martian atmosphere and at its surface. The retrieval method has been applied on 4 Martian years of SPICAM/UV data to obtain climatologies of the different quantities under investigation. An overview of the climatology is given for each species showing their seasonal and spatial distributions. The results show a good qualitative agreement with previous observations. Quantitative comparisons of the retrieved dust optical depths indicate generally larger values than previous studies. Possible shortcomings in the dust modelling (altitude profile) have been identified and may be part of the reason for this difference. The ozone results are found to be influenced by the presence of clouds. Preliminary quantitative comparisons show that our retrieved ozone columns are consistent with other results when no ice clouds are present, and are larger for the cases with clouds at high latitude. Sensitivity tests have also been performed showing that the use of other a priori assumptions such as the altitude distribution or some scattering properties can have an important impact on the retrieval.

Amino acid distribution in meteorites: diagenesis, extraction methods, and standard metrics in the search for extraterrestrial biosignatures.

PubMed

McDonald, Gene D; Storrie-Lombardi, Michael C

2006-02-01

The relative abundance of the protein amino acids has been previously investigated as a potential marker for biogenicity in meteoritic samples. However, these investigations were executed without a quantitative metric to evaluate distribution variations, and they did not account for the possibility of interdisciplinary systematic error arising from inter-laboratory differences in extraction and detection techniques. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and stochastic probabilistic artificial neural networks (ANNs) were used to compare the distributions for nine protein amino acids previously reported for the Murchison carbonaceous chondrite, Mars meteorites (ALH84001, Nakhla, and EETA79001), prebiotic synthesis experiments, and terrestrial biota and sediments. These techniques allowed us (1) to identify a shift in terrestrial amino acid distributions secondary to diagenesis; (2) to detect differences in terrestrial distributions that may be systematic differences between extraction and analysis techniques in biological and geological laboratories; and (3) to determine that distributions in meteoritic samples appear more similar to prebiotic chemistry samples than they do to the terrestrial unaltered or diagenetic samples. Both diagenesis and putative interdisciplinary differences in analysis complicate interpretation of meteoritic amino acid distributions. We propose that the analysis of future samples from such diverse sources as meteoritic influx, sample return missions, and in situ exploration of Mars would be less ambiguous with adoption of standardized assay techniques, systematic inclusion of assay standards, and the use of a quantitative, probabilistic metric. We present here one such metric determined by sequential feature extraction and normalization (PCA), information-driven automated exploration of classification possibilities (HCA), and prediction of classification accuracy (ANNs).

Perspectives of People Living with HIV on Access to Health Care: Protocol for a Scoping Review.

PubMed

Asghari, Shabnam; Maybank, Allison; Hurley, Oliver; Modir, Hilary; Farrell, Alison; Marshall, Zack; Kendall, Claire; Johnston, Sharon; Hogel, Matthew; Rourke, Sean B; Liddy, Clare

2016-05-18

Strategies to improve access to health care for people living with human immunodeficiency virus (PLHIV) have demonstrated limited success. Whereas previous approaches have been informed by the views of health providers and decision-makers, it is believed that incorporating patient perspectives into the design and evaluations of health care programs will lead to improved access to health care services. We aim to map the literature on the perspectives of PLHIV concerning access to health care services, to identify gaps in evidence, and to produce an evidence-informed research action plan to guide the Living with HIV program of research. This scoping review includes peer-reviewed and grey literature from 1946 to May 2014 using double data extraction. Variations of the search terms "HIV", "patient satisfaction", and "health services accessibility" are used to identify relevant literature. The search strategy is being developed in consultation with content experts, review methodologists, and a librarian, and validated using gold standard studies identified by those stakeholders. The inclusion criteria are (1) the study includes the perspectives of PLHIV, (2) study design includes qualitative, quantitative, or mixed methods, and (3) outcome measures are limited to patient satisfaction, their implied needs, beliefs, and desires in relation to access to health care. The papers are extracted by two independent reviewers, including quality assessment. Data is then collated, summarized, and thematically analyzed. A total of 12,857 references were retrieved, of which 326 documents were identified as eligible in pre-screening, and 64 articles met the inclusion criteria (56% qualitative studies, 38% quantitative studies and 6% mixed-method studies). Only four studies were conducted in Canada. Data synthesis is in progress and full results are expected in June, 2016. This scoping review will record and characterize the extensive body of literature on perspectives of PLHIV regarding access to health care. A literature repository will be developed to assist stakeholders, decision-makers, and PLHIV in developing and implementing patient-oriented health care programs.

Identification, Replication, and Functional Fine-Mapping of Expression Quantitative Trait Loci in Primary Human Liver Tissue

PubMed Central

Stanaway, Ian B.; Gamazon, Eric R.; Smith, Joshua D.; Mirkov, Snezana; Ramirez, Jacqueline; Liu, Wanqing; Lin, Yvonne S.; Moloney, Cliona; Aldred, Shelly Force; Trinklein, Nathan D.; Schuetz, Erin; Nickerson, Deborah A.; Thummel, Ken E.; Rieder, Mark J.; Rettie, Allan E.; Ratain, Mark J.; Cox, Nancy J.; Brown, Christopher D.

2011-01-01

The discovery of expression quantitative trait loci (“eQTLs”) can help to unravel genetic contributions to complex traits. We identified genetic determinants of human liver gene expression variation using two independent collections of primary tissue profiled with Agilent (n = 206) and Illumina (n = 60) expression arrays and Illumina SNP genotyping (550K), and we also incorporated data from a published study (n = 266). We found that ∼30% of SNP-expression correlations in one study failed to replicate in either of the others, even at thresholds yielding high reproducibility in simulations, and we quantified numerous factors affecting reproducibility. Our data suggest that drug exposure, clinical descriptors, and unknown factors associated with tissue ascertainment and analysis have substantial effects on gene expression and that controlling for hidden confounding variables significantly increases replication rate. Furthermore, we found that reproducible eQTL SNPs were heavily enriched near gene starts and ends, and subsequently resequenced the promoters and 3′UTRs for 14 genes and tested the identified haplotypes using luciferase assays. For three genes, significant haplotype-specific in vitro functional differences correlated directly with expression levels, suggesting that many bona fide eQTLs result from functional variants that can be mechanistically isolated in a high-throughput fashion. Finally, given our study design, we were able to discover and validate hundreds of liver eQTLs. Many of these relate directly to complex traits for which liver-specific analyses are likely to be relevant, and we identified dozens of potential connections with disease-associated loci. These included previously characterized eQTL contributors to diabetes, drug response, and lipid levels, and they suggest novel candidates such as a role for NOD2 expression in leprosy risk and C2orf43 in prostate cancer. In general, the work presented here will be valuable for future efforts to precisely identify and functionally characterize genetic contributions to a variety of complex traits. PMID:21637794

Quantitative trait locus mapping in mice identifies phospholipase Pla2g12a as novel atherosclerosis modifier.

PubMed

Nicolaou, Alexandros; Northoff, Bernd H; Sass, Kristina; Ernst, Jana; Kohlmaier, Alexander; Krohn, Knut; Wolfrum, Christian; Teupser, Daniel; Holdt, Lesca M

2017-10-01

In a previous work, a female-specific atherosclerosis risk locus on chromosome (Chr) 3 was identified in an intercross of atherosclerosis-resistant FVB and atherosclerosis-susceptible C57BL/6 (B6) mice on the LDL-receptor deficient (Ldlr -/- ) background. It was the aim of the current study to identify causative genes at this locus. We established a congenic mouse model, where FVB.Chr3 B6/B6 mice carried an 80 Mb interval of distal Chr3 on an otherwise FVB.Ldlr -/- background, to validate the Chr3 locus. Candidate genes were identified using genome-wide expression analyses. Differentially expressed genes were validated using quantitative PCRs in F0 and F2 mice and their functions were investigated in pathophysiologically relevant cells. Fine-mapping of the Chr3 locus revealed two overlapping, yet independent subloci for female atherosclerosis susceptibility: when transmitted by grandfathers to granddaughters, the B6 risk allele increased atherosclerosis and downregulated the expression of the secreted phospholipase Pla2g12a (2.6 and 2.2 fold, respectively); when inherited by grandmothers, the B6 risk allele induced vascular cell adhesion molecule 1 (Vcam1). Down-regulation of Pla2g12a and up-regulation of Vcam1 were validated in female FVB.Chr3 B6/B6 congenic mice, which developed 2.5 greater atherosclerotic lesions compared to littermate controls (p=0.039). Pla2g12a was highly expressed in aortic endothelial cells in vivo, and knocking-down Pla2g12a expression by RNAi in cultured vascular endothelial cells or macrophages increased their adhesion to ECs in vitro. Our data establish Pla2g12a as an atheroprotective candidate gene in mice, where high expression levels in ECs and macrophages may limit the recruitment and accumulation of these cells in nascent atherosclerotic lesions. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat.

PubMed

Coan, Philip M; Hummel, Oliver; Garcia Diaz, Ana; Barrier, Marjorie; Alfazema, Neza; Norsworthy, Penny J; Pravenec, Michal; Petretto, Enrico; Hübner, Norbert; Aitman, Timothy J

2017-03-01

We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl , RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1 , Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively. Comparative genome analysis showed a marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole-body phenotypes associated with the SHR chromosome 12 and 16 insulin-resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the underlying genes and cellular mechanisms. © 2017. Published by The Company of Biologists Ltd.

Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

PubMed Central

Hummel, Oliver; Garcia Diaz, Ana; Barrier, Marjorie; Alfazema, Neza; Norsworthy, Penny J.; Pravenec, Michal; Petretto, Enrico; Hübner, Norbert

2017-01-01

ABSTRACT We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl, RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1, Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively. Comparative genome analysis showed a marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole-body phenotypes associated with the SHR chromosome 12 and 16 insulin-resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the underlying genes and cellular mechanisms. PMID:28130354

Genome investigation suggests MdSHN3, an APETALA2-domain transcription factor gene, to be a positive regulator of apple fruit cuticle formation and an inhibitor of russet development.

PubMed

Lashbrooke, Justin; Aharoni, Asaph; Costa, Fabrizio

2015-11-01

The outer epidermal layer of apple fruit is covered by a protective cuticle. Composed of a polymerized cutin matrix embedded with waxes, the cuticle is a natural waterproof barrier and protects against several abiotic and biotic stresses. In terms of apple production, the cuticle is essential to maintain long post-harvest storage, while severe failure of the cuticle can result in the formation of a disorder known as russet. Apple russet results from micro-cracking of the cuticle and the formation of a corky suberized layer. This is typically an undesirable consumer trait, and negatively impacts the post-harvest storage of apples. In order to identify genetic factors controlling cuticle biosynthesis (and thus preventing russet) in apple, a quantitative trait locus (QTL) mapping survey was performed on a full-sib population. Two genomic regions located on chromosomes 2 and 15 that could be associated with russeting were identified. Apples with compromised cuticles were identified through a novel and high-throughput tensile analysis of the skin, while histological analysis confirmed cuticle failure in a subset of the progeny. Additional genomic investigation of the determined QTL regions identified a set of underlying genes involved in cuticle biosynthesis. Candidate gene expression profiling by quantitative real-time PCR on a subset of the progeny highlighted the specific expression pattern of a SHN1/WIN1 transcription factor gene (termed MdSHN3) on chromosome 15. Orthologues of SHN1/WIN1 have been previously shown to regulate cuticle formation in Arabidopsis, tomato, and barley. The MdSHN3 transcription factor gene displayed extremely low expression in lines with improper cuticle formation, suggesting it to be a fundamental regulator of cuticle biosynthesis in apple fruit. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17). part 1: development and content validity.

PubMed

Morris, S; Li, Y; Smith, J A M; Dube', S; Burbridge, C; Symonds, T

2017-05-16

Fibromyalgia (FM), a disorder characterized by chronic widespread pain and tenderness, affects greater than five million individuals in the United States alone. Patients experience multiple symptoms in addition to pain, and among them, fatigue is one of the most bothersome and disabling. There is a growing body of literature suggesting that fatigue is a multidimensional concept. Currently, to our knowledge, no multidimensional Patient Reported Outcome (PRO) measure of FM-related fatigue meets Food and Drug Administration (FDA) requirements to support a product label claim. Therefore, the objective of this research was to evaluate qualitative and quantitative data previously gathered to inform the development of a comprehensive, multidimensional, PRO measure to assess FM-related fatigue in FM clinical trials. Existing qualitative and quantitative data from three previously conducted studies in patients with FM were reviewed to inform the initial development of a multidimensional PRO measure of FM-related fatigue: 1) a concept elicitation study involving in-depth, open-ended interviews with patients with FM in the United States (US) (N = 20), Germany (N = 10), and France (N = 10); 2) a cognitive debriefing and pilot study of a preliminary pool of 23 items (N = 20 US patients with FM); and 3) a methodology study that explored initial psychometrics of the item pool (N = 145 US patients with FM). Five domains were identified that intend to capture the broad experience of FM-related fatigue reported in the qualitative research: the Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue, Motivation, and Impact on Function. Seventeen of the original pool of 23 items were selected to best capture these five dimensions. These 17 items formed the basis of a newly developed multidimensional PRO measure to assess FM-related fatigue in clinical trials: the Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 (MDF-Fibro-17). Qualitative analysis, and preliminary quantitative item level data, confirmed that FM-related fatigue is multidimensional and provided strong support for the content validity of the MDF-Fibro-17. The next stage was to quantitatively evaluate the measure to confirm the factor structure, psychometric properties, sensitivity to change, and meaningful change. This has been conducted and is being reported separately.

Mapping Late Leaf Spot Resistance in Peanut (Arachis hypogaea) Using QTL-seq Reveals Markers for Marker-Assisted Selection.

PubMed

Clevenger, Josh; Chu, Ye; Chavarro, Carolina; Botton, Stephanie; Culbreath, Albert; Isleib, Thomas G; Holbrook, C C; Ozias-Akins, Peggy

2018-01-01

Late leaf spot (LLS; Cercosporidium personatum ) is a major fungal disease of cultivated peanut ( Arachis hypogaea ). A recombinant inbred line population segregating for quantitative field resistance was used to identify quantitative trait loci (QTL) using QTL-seq. High rates of false positive SNP calls using established methods in this allotetraploid crop obscured significant QTLs. To resolve this problem, robust parental SNPs were first identified using polyploid-specific SNP identification pipelines, leading to discovery of significant QTLs for LLS resistance. These QTLs were confirmed over 4 years of field data. Selection with markers linked to these QTLs resulted in a significant increase in resistance, showing that these markers can be immediately applied in breeding programs. This study demonstrates that QTL-seq can be used to rapidly identify QTLs controlling highly quantitative traits in polyploid crops with complex genomes. Markers identified can then be deployed in breeding programs, increasing the efficiency of selection using molecular tools. Key Message: Field resistance to late leaf spot is a quantitative trait controlled by many QTLs. Using polyploid-specific methods, QTL-seq is faster and more cost effective than QTL mapping.

Mapping Late Leaf Spot Resistance in Peanut (Arachis hypogaea) Using QTL-seq Reveals Markers for Marker-Assisted Selection

PubMed Central

Clevenger, Josh; Chu, Ye; Chavarro, Carolina; Botton, Stephanie; Culbreath, Albert; Isleib, Thomas G.; Holbrook, C. C.; Ozias-Akins, Peggy

2018-01-01

Late leaf spot (LLS; Cercosporidium personatum) is a major fungal disease of cultivated peanut (Arachis hypogaea). A recombinant inbred line population segregating for quantitative field resistance was used to identify quantitative trait loci (QTL) using QTL-seq. High rates of false positive SNP calls using established methods in this allotetraploid crop obscured significant QTLs. To resolve this problem, robust parental SNPs were first identified using polyploid-specific SNP identification pipelines, leading to discovery of significant QTLs for LLS resistance. These QTLs were confirmed over 4 years of field data. Selection with markers linked to these QTLs resulted in a significant increase in resistance, showing that these markers can be immediately applied in breeding programs. This study demonstrates that QTL-seq can be used to rapidly identify QTLs controlling highly quantitative traits in polyploid crops with complex genomes. Markers identified can then be deployed in breeding programs, increasing the efficiency of selection using molecular tools. Key Message: Field resistance to late leaf spot is a quantitative trait controlled by many QTLs. Using polyploid-specific methods, QTL-seq is faster and more cost effective than QTL mapping. PMID:29459876

Using PSEA-Quant for Protein Set Enrichment Analysis of Quantitative Mass Spectrometry-Based Proteomics

PubMed Central

Lavallée-Adam, Mathieu

2017-01-01

PSEA-Quant analyzes quantitative mass spectrometry-based proteomics datasets to identify enrichments of annotations contained in repositories such as the Gene Ontology and Molecular Signature databases. It allows users to identify the annotations that are significantly enriched for reproducibly quantified high abundance proteins. PSEA-Quant is available on the web and as a command-line tool. It is compatible with all label-free and isotopic labeling-based quantitative proteomics methods. This protocol describes how to use PSEA-Quant and interpret its output. The importance of each parameter as well as troubleshooting approaches are also discussed. PMID:27010334

Analysis of X chromosome genomic DNA sequence copy number variation associated with premature ovarian failure (POF)

PubMed Central

Quilter, C.R.; Karcanias, A.C.; Bagga, M.R.; Duncan, S.; Murray, A.; Conway, G.S.; Sargent, C.A.; Affara, N.A.

2013-01-01

BACKGROUND Premature ovarian failure (POF) is a heterogeneous disease defined as amenorrhoea for >6 months before age 40, with an FSH serum level >40 mIU/ml (menopausal levels). While there is a strong genetic association with POF, familial studies have also indicated that idiopathic POF may also be genetically linked. Conventional cytogenetic analyses have identified regions of the X chromosome that are strongly associated with ovarian function, as well as several POF candidate genes. Cryptic chromosome abnormalities that have been missed might be detected by array comparative genomic hybridization. METHODS In this study, samples from 42 idiopathic POF patients were subjected to a complete end-to-end X/Y chromosome tiling path array to achieve a detailed copy number variation (CNV) analysis of X chromosome involvement in POF. The arrays also contained a 1 Mb autosomal tiling path as a reference control. Quantitative PCR for selected genes contained within the CNVs was used to confirm the majority of the changes detected. The expression pattern of some of these genes in human tissue RNA was examined by reverse transcription (RT)–PCR. RESULTS A number of CNVs were identified on both Xp and Xq, with several being shared among the POF cases. Some CNVs fall within known polymorphic CNV regions, and others span previously identified POF candidate regions and genes. CONCLUSIONS The new data reported in this study reveal further discrete X chromosome intervals not previously associated with the disease and therefore implicate new clusters of candidate genes. Further studies will be required to elucidate their involvement in POF. PMID:20570974

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

PubMed

Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

2016-12-01

Usher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients

PubMed Central

Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

2016-01-01

Usher syndrome (USH), the most prevalent cause of hereditary deafness–blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1–3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods. PMID:27460420

Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation

PubMed Central

Liang, Jian; Song, Wenjun; Tromp, Gail; Kolattukudy, Pappachan E.; Fu, Mingui

2008-01-01

Previously, we have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. To gain an overall insight into the entire CCCH zinc finger gene family and to evaluate their potential role in macrophage activation, here we performed a genome-wide survey of CCCH zinc finger genes in mouse and human. Totally 58 CCCH zinc finger genes in mouse and 55 in human were identified and most of them have not been reported previously. Phylogenetic analysis revealed that the mouse CCCH family was divided into 6 groups. Meanwhile, we employed quantitative real-time PCR to profile their tissue expression patterns in adult mice. Clustering analysis showed that most of CCCH genes were broadly expressed in all of tissues examined with various levels. Interestingly, several CCCH genes Mbnl3, Zfp36l2, Zfp36, Zc3h12a, Zc3h12d, Zc3h7a and Leng9 were enriched in macrophage-related organs such as thymus, spleen, lung, intestine and adipose. Consistently, a comprehensive assessment of changes in expression of the 58 members of the mouse CCCH family during macrophage activation also revealed that these CCCH zinc finger genes were associated with the activation of bone marrow-derived macrophages by lipopolysaccharide. Taken together, this study not only identified a functional module of CCCH zinc finger genes in the regulation of macrophage activation but also provided the framework for future studies to dissect the function of this emerging gene family. PMID:18682727

An Extended Proteome Map of the Lysosomal Membrane Reveals Novel Potential Transporters*

PubMed Central

Chapel, Agnès; Kieffer-Jaquinod, Sylvie; Sagné, Corinne; Verdon, Quentin; Ivaldi, Corinne; Mellal, Mourad; Thirion, Jaqueline; Jadot, Michel; Bruley, Christophe; Garin, Jérôme; Gasnier, Bruno; Journet, Agnès

2013-01-01

Lysosomes are membrane-bound endocytic organelles that play a major role in degrading cell macromolecules and recycling their building blocks. A comprehensive knowledge of the lysosome function requires an extensive description of its content, an issue partially addressed by previous proteomic analyses. However, the proteins underlying many lysosomal membrane functions, including numerous membrane transporters, remain unidentified. We performed a comparative, semi-quantitative proteomic analysis of rat liver lysosome-enriched and lysosome-nonenriched membranes and used spectral counts to evaluate the relative abundance of proteins. Among a total of 2,385 identified proteins, 734 proteins were significantly enriched in the lysosomal fraction, including 207 proteins already known or predicted as endo-lysosomal and 94 proteins without any known or predicted subcellular localization. The remaining 433 proteins had been previously assigned to other subcellular compartments but may in fact reside on lysosomes either predominantly or as a secondary location. Many membrane-associated complexes implicated in diverse processes such as degradation, membrane trafficking, lysosome biogenesis, lysosome acidification, signaling, and nutrient sensing were enriched in the lysosomal fraction. They were identified to an unprecedented extent as most, if not all, of their subunits were found and retained by our screen. Numerous transporters were also identified, including 46 novel potentially lysosomal proteins. We expressed 12 candidates in HeLa cells and observed that most of them colocalized with the lysosomal marker LAMP1, thus confirming their lysosomal residency. This list of candidate lysosomal proteins substantially increases our knowledge of the lysosomal membrane and provides a basis for further characterization of lysosomal functions. PMID:23436907

Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease

PubMed Central

Peters, James E.; Lyons, Paul A.; Lee, James C.; Richard, Arianne C.; Fortune, Mary D.; Newcombe, Paul J.; Richardson, Sylvia; Smith, Kenneth G. C.

2016-01-01

Genome-wide association studies (GWAS) have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs) is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91), anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46) and healthy controls (n = 43), revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases. PMID:27015630

Genetic architecture of adiposity and organ weight using combined generation QTL analysis.

PubMed

Fawcett, Gloria L; Roseman, Charles C; Jarvis, Joseph P; Wang, Bing; Wolf, Jason B; Cheverud, James M

2008-08-01

We present here a detailed study of the genetic contributions to adult body size and adiposity in the LG,SM advanced intercross line (AIL), an obesity model. This study represents a first step in fine-mapping obesity quantitative trait loci (QTLs) in an AIL. QTLs for adiposity in this model were previously isolated to chromosomes 1, 6, 7, 8, 9, 12, 13, and 18. This study focuses on heritable contributions and the genetic architecture of fatpad and organ weights. We analyzed both the F(2) and F(3) generations of the LG,SM AIL population single-nucleotide polymorphism (SNP) genotyped with a marker density of approximately 4 cM. We replicate 88% of the previously identified obesity QTLs and identify 13 new obesity QTLs. Nearly half of the single-trait QTLs were sex-specific. Several broad QTL regions were resolved into multiple, narrower peaks. The 113 single-trait QTLs for organs and body weight clustered into 27 pleiotropic loci. A large number of epistatic interactions are described which begin to elucidate potential interacting molecular networks. We present a relatively rapid means to obtain fine-mapping details from AILs using dense marker maps and consecutive generations. Analysis of the complex genetic architecture underlying fatpad and organ weights in this model may eventually help to elucidate not only heritable contributions to obesity but also common gene sets for obesity and its comorbidities.

Life history and spatial traits predict extinction risk due to climate change

NASA Astrophysics Data System (ADS)

Pearson, Richard G.; Stanton, Jessica C.; Shoemaker, Kevin T.; Aiello-Lammens, Matthew E.; Ersts, Peter J.; Horning, Ned; Fordham, Damien A.; Raxworthy, Christopher J.; Ryu, Hae Yeong; McNees, Jason; Akçakaya, H. Reşit

2014-03-01

There is an urgent need to develop effective vulnerability assessments for evaluating the conservation status of species in a changing climate. Several new assessment approaches have been proposed for evaluating the vulnerability of species to climate change based on the expectation that established assessments such as the IUCN Red List need revising or superseding in light of the threat that climate change brings. However, although previous studies have identified ecological and life history attributes that characterize declining species or those listed as threatened, no study so far has undertaken a quantitative analysis of the attributes that cause species to be at high risk of extinction specifically due to climate change. We developed a simulation approach based on generic life history types to show here that extinction risk due to climate change can be predicted using a mixture of spatial and demographic variables that can be measured in the present day without the need for complex forecasting models. Most of the variables we found to be important for predicting extinction risk, including occupied area and population size, are already used in species conservation assessments, indicating that present systems may be better able to identify species vulnerable to climate change than previously thought. Therefore, although climate change brings many new conservation challenges, we find that it may not be fundamentally different from other threats in terms of assessing extinction risks.

Genome-Wide Association Mapping of Crown Rust Resistance in Oat Elite Germplasm.

PubMed

Klos, Kathy Esvelt; Yimer, Belayneh A; Babiker, Ebrahiem M; Beattie, Aaron D; Bonman, J Michael; Carson, Martin L; Chong, James; Harrison, Stephen A; Ibrahim, Amir M H; Kolb, Frederic L; McCartney, Curt A; McMullen, Michael; Fetch, Jennifer Mitchell; Mohammadi, Mohsen; Murphy, J Paul; Tinker, Nicholas A

2017-07-01

Oat crown rust, caused by f. sp. , is a major constraint to oat ( L.) production in many parts of the world. In this first comprehensive multienvironment genome-wide association map of oat crown rust, we used 2972 single-nucleotide polymorphisms (SNPs) genotyped on 631 oat lines for association mapping of quantitative trait loci (QTL). Seedling reaction to crown rust in these lines was assessed as infection type (IT) with each of 10 crown rust isolates. Adult plant reaction was assessed in the field in a total of 10 location-years as percentage severity (SV) and as infection reaction (IR) in a 0-to-1 scale. Overall, 29 SNPs on 12 linkage groups were predictive of crown rust reaction in at least one experiment at a genome-wide level of statistical significance. The QTL identified here include those in regions previously shown to be linked with seedling resistance genes , , , , , and and also with adult-plant resistance and adaptation-related QTL. In addition, QTL on linkage groups Mrg03, Mrg08, and Mrg23 were identified in regions not previously associated with crown rust resistance. Evaluation of marker genotypes in a set of crown rust differential lines supported as the identity of . The SNPs with rare alleles associated with lower disease scores may be suitable for use in marker-assisted selection of oat lines for crown rust resistance. Copyright © 2017 Crop Science Society of America.

Population Variation Reveals Independent Selection toward Small Body Size in Chinese Debao Pony

PubMed Central

Kader, Adiljan; Li, Yan; Dong, Kunzhe; Irwin, David M.; Zhao, Qianjun; He, Xiaohong; Liu, Jianfeng; Pu, Yabin; Gorkhali, Neena Amatya; Liu, Xuexue; Jiang, Lin; Li, Xiangchen; Guan, Weijun; Zhang, Yaping; Wu, Dong-Dong; Ma, Yuehui

2016-01-01

Body size, one of the most important quantitative traits under evolutionary scrutiny, varies considerably among species and among populations within species. Revealing the genetic basis underlying this variation is very important, particularly in humans where there is a close relationship with diseases and in domestic animals as the selective patterns are associated with improvements in production traits. The Debao pony is a horse breed with small body size that is unique to China; however, it is unknown whether the size-related candidate genes identified in Western breeds also account for the small body size of the Debao pony. Here, we compared individual horses from the Debao population with other two Chinese horse populations using single nucleotide polymorphisms (SNPs) identified with the Equine SNP 65 Bead Chip. The previously reported size-related candidate gene HMGA2 showed a significant signature for selection, consistent with its role observed in human populations. More interestingly, we found a candidate gene TBX3, which had not been observed in previous studies on horse body size that displayed the highest differentiation and most significant association, and thus likely is the dominating factor for the small stature of the Debao pony. Further comparison between the Debao pony and other breeds of horses from around the world demonstrated that TBX3 was selected independently in the Debao pony, suggesting that there were multiple origins of small stature in the horse. PMID:26637467

Measurement of /sup 125/I-low density lipoprotein uptake in selected tissues of the squirrel monkey by quantitative autoradiography

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

Tompkins, R.G.; Schnitzer, J.J.; Yarmush, M.L.

1988-09-01

A recently developed technique of absolute quantitative light microscopic autoradiography of /sup 125/I-labeled proteins in biologic specimens was used to measure /sup 125/I-low density lipoprotein (/sup 125/I-LDL) concentration levels in various tissues of the squirrel monkey after 30 minutes of in vivo LDL circulation. Liver and adrenal cortex exhibited high /sup 125/I-LDL concentrations, presumably because of binding to specific cell surface receptors and/or internalization in vascular beds with high permeability to LDL. High tissue concentrations of LDL were associated with the zona fasciculata and reticularis of the adrenal cortex and the interstitial cells of Leydig in the testis; significantly lowermore » levels of /sup 125/I-LDL were observed in the adrenal medulla, the zona glomerulosa, and germinal centers of the testis. Contrary to previous reports, low /sup 125/I-LDL concentrations were observed throughout the gastrointestinal tract and in lymph nodes. In addition, multiple arterial intramural focal areas of high /sup 125/I-LDL concentrations were identified in arteries supplying the adrenal gland, lymph node, small bowel, and liver.« less

Quali-quantitative analysis of the phenolic fraction of the flowers of Corylus avellana, source of the Italian PGI product "Nocciola di Giffoni": Isolation of antioxidant diarylheptanoids.

PubMed

Masullo, Milena; Mari, Angela; Cerulli, Antonietta; Bottone, Alfredo; Kontek, Bogdan; Olas, Beata; Pizza, Cosimo; Piacente, Sonia

2016-10-01

There is only limited information available on the chemical composition of the non-edible parts of Corylus avellana, source of the Italian PGI product "Nocciola di Giffoni" (hazelnut). An initial LC-MS profile of the methanolic extract of the male flowers of C. avellana, cultivar 'Tonda di Giffoni' led to the isolation of 12 compounds, of which the structures were elucidated by NMR spectroscopy. These were identified as three previously undescribed diarylheptanoids, named giffonins Q-S, along with nine known compounds. Furthermore, the quantitative determination of the main compounds occurring in the methanolic extract of C. avellana flowers was carried out by an analytical approach based on LC-ESI(QqQ)MS, using the Multiple Reaction Monitoring (MRM) experiment. In order to explore the antioxidant ability of C. avellana flowers, the methanolic extract and the isolated compounds were evaluated for their inhibitory effects on human plasma lipid peroxidation induced by H2O2 and H2O2/Fe(2+), by measuring the concentration of TBARS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Participant recruitment to FiCTION, a primary dental care trial - survey of facilitators and barriers.

PubMed

Keightley, A; Clarkson, J; Maguire, A; Speed, C; Innes, N

2014-11-01

To identify reasons behind a lower than expected participant recruitment rate within the FiCTION trial, a multi-centre paediatric primary dental care randomised controlled trial (RCT). An online survey, based on a previously published tool, consisting of both quantitative and qualitative responses, completed by staff in dental practices recruiting to FiCTION. Ratings from quantitative responses were aggregated to give overall scores for factors related to participant recruitment. Qualitative responses were independently grouped into themes. Thirty-nine anonymous responses were received. Main facilitators related to the support received from the central research team and importance of the research question. The main barriers related to low child eligibility rates and the integration of trial processes within routine workloads. These findings have directed strategies for enhancing participant recruitment at existing practices and informed recruitment of further practices. The results help provide a profile of the features required of practices to successfully screen and recruit participants. Future trials in this setting should consider the level of interest in the research question within practices, and ensure trial processes are as streamlined as possible. Research teams should actively support practices with participant recruitment and maintain enthusiasm among the entire practice team.

Yeast Metabolites of Glycated Amino Acids in Beer.

PubMed

Hellwig, Michael; Beer, Falco; Witte, Sophia; Henle, Thomas

2018-06-01

Glycation reactions (Maillard reactions) during the malting and brewing processes are important for the development of the characteristic color and flavor of beer. Recently, free and protein-bound Maillard reaction products (MRPs) such as pyrraline, formyline, and maltosine were found in beer. Furthermore, these amino acid derivatives are metabolized by Saccharomyces cerevisiae via the Ehrlich pathway. In this study, a method was developed for quantitation of individual Ehrlich intermediates derived from pyrraline, formyline, and maltosine. Following synthesis of the corresponding reference material, the MRP-derived new Ehrlich alcohols pyrralinol (up to 207 μg/L), formylinol (up to 50 μg/L), and maltosinol (up to 6.9 μg/L) were quantitated for the first time in commercial beer samples by reverse phase high performance liquid chromatography tandem mass spectrometry in the multiple reaction monitoring mode. This is equivalent to ca. 20-40% of the concentrations of the parent glycated amino acids. The metabolites were almost absent from alcohol-free beers and malt-based beverages. Two previously unknown valine-derived pyrrole derivatives were characterized and qualitatively identified in beer. The metabolites investigated represent new process-induced alkaloids that may influence brewing yeast performance due to structural similarities to quorum sensing and metal-binding molecules.

Modeling susceptibility difference artifacts produced by metallic implants in magnetic resonance imaging with point-based thin-plate spline image registration.

PubMed

Pauchard, Y; Smith, M; Mintchev, M

2004-01-01

Magnetic resonance imaging (MRI) suffers from geometric distortions arising from various sources. One such source are the non-linearities associated with the presence of metallic implants, which can profoundly distort the obtained images. These non-linearities result in pixel shifts and intensity changes in the vicinity of the implant, often precluding any meaningful assessment of the entire image. This paper presents a method for correcting these distortions based on non-rigid image registration techniques. Two images from a modelled three-dimensional (3D) grid phantom were subjected to point-based thin-plate spline registration. The reference image (without distortions) was obtained from a grid model including a spherical implant, and the corresponding test image containing the distortions was obtained using previously reported technique for spatial modelling of magnetic susceptibility artifacts. After identifying the nonrecoverable area in the distorted image, the calculated spline model was able to quantitatively account for the distortions, thus facilitating their compensation. Upon the completion of the compensation procedure, the non-recoverable area was removed from the reference image and the latter was compared to the compensated image. Quantitative assessment of the goodness of the proposed compensation technique is presented.

Monofluorophosphate is a selective inhibitor of respiratory sulfate-reducing microorganisms.

PubMed

Carlson, Hans K; Stoeva, Magdalena K; Justice, Nicholas B; Sczesnak, Andrew; Mullan, Mark R; Mosqueda, Lorraine A; Kuehl, Jennifer V; Deutschbauer, Adam M; Arkin, Adam P; Coates, John D

2015-03-17

Despite the environmental and economic cost of microbial sulfidogenesis in industrial operations, few compounds are known as selective inhibitors of respiratory sulfate reducing microorganisms (SRM), and no study has systematically and quantitatively evaluated the selectivity and potency of SRM inhibitors. Using general, high-throughput assays to quantitatively evaluate inhibitor potency and selectivity in a model sulfate-reducing microbial ecosystem as well as inhibitor specificity for the sulfate reduction pathway in a model SRM, we screened a panel of inorganic oxyanions. We identified several SRM selective inhibitors including selenate, selenite, tellurate, tellurite, nitrate, nitrite, perchlorate, chlorate, monofluorophosphate, vanadate, molydate, and tungstate. Monofluorophosphate (MFP) was not known previously as a selective SRM inhibitor, but has promising characteristics including low toxicity to eukaryotic organisms, high stability at circumneutral pH, utility as an abiotic corrosion inhibitor, and low cost. MFP remains a potent inhibitor of SRM growing by fermentation, and MFP is tolerated by nitrate and perchlorate reducing microorganisms. For SRM inhibition, MFP is synergistic with nitrite and chlorite, and could enhance the efficacy of nitrate or perchlorate treatments. Finally, MFP inhibition is multifaceted. Both inhibition of the central sulfate reduction pathway and release of cytoplasmic fluoride ion are implicated in the mechanism of MFP toxicity.

Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle

PubMed Central

Takasuga, Akiko; Sato, Kunio; Nakamura, Ryouichi; Saito, Yosuke; Sasaki, Shinji; Tsuji, Takehito; Suzuki, Akio; Kobayashi, Hiroshi; Matsuhashi, Tamako; Setoguchi, Koji; Okabe, Hiroshi; Ootsubo, Toshitake; Tabuchi, Ichiro; Fujita, Tatsuo; Watanabe, Naoto; Hirano, Takashi; Nishimura, Shota; Watanabe, Toshio; Hayakawa, Makio; Sugimoto, Yoshikazu; Kojima, Takatoshi

2015-01-01

Recessive skeletal dysplasia, characterized by joint- and/or hip bone-enlargement, was mapped within the critical region for a major quantitative trait locus (QTL) influencing carcass weight; previously named CW-3 in Japanese Black cattle. The risk allele was on the same chromosome as the Q allele that increases carcass weight. Phenotypic characterization revealed that the risk allele causes disproportional tall stature and bone size that increases carcass weight in heterozygous individuals but causes disproportionately narrow chest width in homozygotes. A non-synonymous variant of FGD3 was identified as a positional candidate quantitative trait nucleotide (QTN) and the corresponding mutant protein showed reduced activity as a guanine nucleotide exchange factor for Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function. This would be consistent with the columnar disorganization of proliferating chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the first report showing association of FGD3 with skeletal dysplasia. PMID:26306008

Connecting the Kinetics and Energy Landscape of tRNA Translocation on the Ribosome

PubMed Central

Whitford, Paul C.; Blanchard, Scott C.; Cate, Jamie H. D.; Sanbonmatsu, Karissa Y.

2013-01-01

Functional rearrangements in biomolecular assemblies result from diffusion across an underlying energy landscape. While bulk kinetic measurements rely on discrete state-like approximations to the energy landscape, single-molecule methods can project the free energy onto specific coordinates. With measures of the diffusion, one may establish a quantitative bridge between state-like kinetic measurements and the continuous energy landscape. We used an all-atom molecular dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds) to provide this bridge for specific conformational events associated with the process of tRNA translocation. Starting from a pre-translocation configuration, we identified sets of residues that collectively undergo rotary rearrangements implicated in ribosome function. Estimates of the diffusion coefficients along these collective coordinates for translocation were then used to interconvert between experimental rates and measures of the energy landscape. This analysis, in conjunction with previously reported experimental rates of translocation, provides an upper-bound estimate of the free-energy barriers associated with translocation. While this analysis was performed for a particular kinetic scheme of translocation, the quantitative framework is general and may be applied to energetic and kinetic descriptions that include any number of intermediates and transition states. PMID:23555233

Connecting the kinetics and energy landscape of tRNA translocation on the ribosome.

PubMed

Whitford, Paul C; Blanchard, Scott C; Cate, Jamie H D; Sanbonmatsu, Karissa Y

2013-01-01

Functional rearrangements in biomolecular assemblies result from diffusion across an underlying energy landscape. While bulk kinetic measurements rely on discrete state-like approximations to the energy landscape, single-molecule methods can project the free energy onto specific coordinates. With measures of the diffusion, one may establish a quantitative bridge between state-like kinetic measurements and the continuous energy landscape. We used an all-atom molecular dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds) to provide this bridge for specific conformational events associated with the process of tRNA translocation. Starting from a pre-translocation configuration, we identified sets of residues that collectively undergo rotary rearrangements implicated in ribosome function. Estimates of the diffusion coefficients along these collective coordinates for translocation were then used to interconvert between experimental rates and measures of the energy landscape. This analysis, in conjunction with previously reported experimental rates of translocation, provides an upper-bound estimate of the free-energy barriers associated with translocation. While this analysis was performed for a particular kinetic scheme of translocation, the quantitative framework is general and may be applied to energetic and kinetic descriptions that include any number of intermediates and transition states.

Antibiotic Resistome: Improving Detection and Quantification Accuracy for Comparative Metagenomics.

PubMed

Elbehery, Ali H A; Aziz, Ramy K; Siam, Rania

2016-04-01

The unprecedented rise of life-threatening antibiotic resistance (AR), combined with the unparalleled advances in DNA sequencing of genomes and metagenomes, has pushed the need for in silico detection of the resistance potential of clinical and environmental metagenomic samples through the quantification of AR genes (i.e., genes conferring antibiotic resistance). Therefore, determining an optimal methodology to quantitatively and accurately assess AR genes in a given environment is pivotal. Here, we optimized and improved existing AR detection methodologies from metagenomic datasets to properly consider AR-generating mutations in antibiotic target genes. Through comparative metagenomic analysis of previously published AR gene abundance in three publicly available metagenomes, we illustrate how mutation-generated resistance genes are either falsely assigned or neglected, which alters the detection and quantitation of the antibiotic resistome. In addition, we inspected factors influencing the outcome of AR gene quantification using metagenome simulation experiments, and identified that genome size, AR gene length, total number of metagenomics reads and selected sequencing platforms had pronounced effects on the level of detected AR. In conclusion, our proposed improvements in the current methodologies for accurate AR detection and resistome assessment show reliable results when tested on real and simulated metagenomic datasets.

A Statistics-based Platform for Quantitative N-terminome Analysis and Identification of Protease Cleavage Products*

PubMed Central

auf dem Keller, Ulrich; Prudova, Anna; Gioia, Magda; Butler, Georgina S.; Overall, Christopher M.

2010-01-01

Terminal amine isotopic labeling of substrates (TAILS), our recently introduced platform for quantitative N-terminome analysis, enables wide dynamic range identification of original mature protein N-termini and protease cleavage products. Modifying TAILS by use of isobaric tag for relative and absolute quantification (iTRAQ)-like labels for quantification together with a robust statistical classifier derived from experimental protease cleavage data, we report reliable and statistically valid identification of proteolytic events in complex biological systems in MS2 mode. The statistical classifier is supported by a novel parameter evaluating ion intensity-dependent quantification confidences of single peptide quantifications, the quantification confidence factor (QCF). Furthermore, the isoform assignment score (IAS) is introduced, a new scoring system for the evaluation of single peptide-to-protein assignments based on high confidence protein identifications in the same sample prior to negative selection enrichment of N-terminal peptides. By these approaches, we identified and validated, in addition to known substrates, low abundance novel bioactive MMP-2 targets including the plasminogen receptor S100A10 (p11) and the proinflammatory cytokine proEMAP/p43 that were previously undescribed. PMID:20305283

An Analysis of NASA Technology Transfer. Degree awarded by Pennsylvania State Univ.

NASA Technical Reports Server (NTRS)

Bush, Lance B.

1996-01-01

A review of previous technology transfer metrics, recommendations, and measurements is presented within the paper. A quantitative and qualitative analysis of NASA's technology transfer efforts is performed. As a relative indicator, NASA's intellectual property performance is benchmarked against a database of over 100 universities. Successful technology transfer (commercial sales, production savings, etc.) cases were tracked backwards through their history to identify the key critical elements that lead to success. Results of this research indicate that although NASA's performance is not measured well by quantitative values (intellectual property stream data), it has a net positive impact on the private sector economy. Policy recommendations are made regarding technology transfer within the context of the documented technology transfer policies since the framing of the Constitution. In the second thrust of this study, researchers at NASA Langley Research Center were surveyed to determine their awareness of, attitude toward, and perception about technology transfer. Results indicate that although researchers believe technology transfer to be a mission of the Agency, they should not be held accountable or responsible for its performance. In addition, the researchers are not well educated about the mechanisms to perform, or policies regarding, technology transfer.

Comparison of two trajectory based models for locating particle sources for two rural New York sites

NASA Astrophysics Data System (ADS)

Zhou, Liming; Hopke, Philip K.; Liu, Wei

Two back trajectory-based statistical models, simplified quantitative transport bias analysis and residence-time weighted concentrations (RTWC) have been compared for their capabilities of identifying likely locations of source emissions contributing to observed particle concentrations at Potsdam and Stockton, New York. Quantitative transport bias analysis (QTBA) attempts to take into account the distribution of concentrations around the directions of the back trajectories. In full QTBA approach, deposition processes (wet and dry) are also considered. Simplified QTBA omits the consideration of deposition. It is best used with multiple site data. Similarly the RTWC approach uses concentrations measured at different sites along with the back trajectories to distribute the concentration contributions across the spatial domain of the trajectories. In this study, these models are used in combination with the source contribution values obtained by the previous positive matrix factorization analysis of particle composition data from Potsdam and Stockton. The six common sources for the two sites, sulfate, soil, zinc smelter, nitrate, wood smoke and copper smelter were analyzed. The results of the two methods are consistent and locate large and clearly defined sources well. RTWC approach can find more minor sources but may also give unrealistic estimations of the source locations.

Smarter elder care? A cost-effectiveness analysis of implementing technology in elder care.

PubMed

Aanesen, Margrethe; Lotherington, Ann Therese; Olsen, Frank

2011-09-01

Whereas in most sectors, technology has taken over trivial and labour consuming tasks, this transformation has been delayed in the healthcare sector. Although appropriate technology is available, there is general resistance to substituting 'warm' hands with 'cold' technology. In the future, this may change as the number of elderly people increases relative to the people in the work force. In combination with an increasing demand for healthcare services, there are calls for efforts to increase productivity in the sector. Based on experience data from previous studies on information and communication technology efforts in the healthcare sector, we quantitatively assess the use of smart house technology and video visits in home care. Having identified healthcare providers, hospitals and relatives as the main affected groups, we show that smart house technology is cost-effective, even if only relatives gain from it. Video visits, which have higher implementation costs, demand effects on both relatives and health care providers in order to be a cost-effective tool in home care. As the analysis is purely quantitative, these results need to be complemented with qualitative effects and with more thorough discussions of the ethical, medical and legal aspects of the use of technology in home care.

Tuition Reductions: A Quantitative Analysis of the Prevalence, Circumstances and Outcomes of an Emerging Pricing Strategy in Higher Education

ERIC Educational Resources Information Center

Kottich, Sarah

2017-01-01

This study analyzed tuition reductions in the private not-for-profit sector of higher education, utilizing a quantitative descriptive and correlational approach with secondary data analysis. It resulted in a listing of 45 institutions with verified tuition reductions from 2007 to 2017, more than previously thought. It found that the…

Comparison study of two procedures for the determination of emamectin benzoate in medicated fish feed.

PubMed

Farer, Leslie J; Hayes, John M

2005-01-01

A new method has been developed for the determination of emamectin benzoate in fish feed. The method uses a wet extraction, cleanup by solid-phase extraction, and quantitation and separation by liquid chromatography (LC). In this paper, we compare the performance of this method with that of a previously reported LC assay for the determination of emamectin benzoate in fish feed. Although similar to the previous method, the new procedure uses a different sample pretreatment, wet extraction, and quantitation method. The performance of the new method was compared with that of the previously reported method by analyses of 22 medicated feed samples from various commercial sources. A comparison of the results presented here reveals slightly lower assay values obtained with the new method. Although a paired sample t-test indicates the difference in results is significant, this difference is within the method precision of either procedure.

[Scientific publication output of Spanish emergency physicians from 2005 to 2014: a comparative study].

PubMed

Fernández-Guerrero, Inés María; Martín-Sánchez, Francisco Javier; Burillo-Putze, Guillermo; Miró, Òscar

2017-10-01

To analyze the research output of Spanish emergency physicians between 2005 and 2014 and to compare it to their output in the previous 10-year period (1995-2004) as well as to that of emergency physicians in other countries and Spanish physicians in other specialties. Original articles indexed in the Science Citation Index Expanded of the Web of Science were included. Documents from Spanish emergency physicians were identified by combining the word Spain and any other search term identifying an emergency service or unit in Spain. To identify articles from 7 other Spanish specialties (hematology, endocrinology, cardiology, pneumology, digestive medicine, pediatrics, surgery and orthopedic medicine or traumatology) and emergency physicians in 8 other countries (United States, United Kingdom, Ireland, Italy, France, Germany, Netherlands, Belgium) we used similar strategies. Information about production between 1995 and 2004 was extracted from a prior publication. Spanish emergency physicians signed 1254 articles (mean [SD], 125 [44] articles/y) between 2005 and 2014. That level of productivity was greater than in the 1995-2004 period (mean, 26 [14] articles/y), although the annual growth rate fell from 12.5% in the previous 10-year period to 5.2% in the most recent one. Emergency medicine was among the least productive Spanish specialties we studied, but our discipline's annual growth rate of 5.2% was the highest. Spanish emergency medicine occupies an intermediate position (ranking fifth) among the 9 countries studied, although the population-adjusted rank was higher (fourth). When output was adjusted for gross domestic product, Spain climbed higher in rank, to second position. The annual growth rate was the fourth highest among countries, after Germany (9.9%), the Netherlands (7.3%), and Italy (6.0%). The research output of Spanish emergency physicians continues to be quantitatively lower than that of other Spanish specialties and of emergency physicians in other countries. The annual rate of growth in publications, although good, fell below the growth rate of the previous period.

Genetic analysis of glucosinolate variability in broccoli florets using genome-anchored single nucleotide polymorphisms.

PubMed

Brown, Allan F; Yousef, Gad G; Reid, Robert W; Chebrolu, Kranthi K; Thomas, Aswathy; Krueger, Christopher; Jeffery, Elizabeth; Jackson, Eric; Juvik, John A

2015-07-01

The identification of genetic factors influencing the accumulation of individual glucosinolates in broccoli florets provides novel insight into the regulation of glucosinolate levels in Brassica vegetables and will accelerate the development of vegetables with glucosinolate profiles tailored to promote human health. Quantitative trait loci analysis of glucosinolate (GSL) variability was conducted with a B. oleracea (broccoli) mapping population, saturated with single nucleotide polymorphism markers from a high-density array designed for rapeseed (Brassica napus). In 4 years of analysis, 14 QTLs were associated with the accumulation of aliphatic, indolic, or aromatic GSLs in floret tissue. The accumulation of 3-carbon aliphatic GSLs (2-propenyl and 3-methylsulfinylpropyl) was primarily associated with a single QTL on C05, but common regulation of 4-carbon aliphatic GSLs was not observed. A single locus on C09, associated with up to 40 % of the phenotypic variability of 2-hydroxy-3-butenyl GSL over multiple years, was not associated with the variability of precursor compounds. Similarly, QTLs on C02, C04, and C09 were associated with 4-methylsulfinylbutyl GSL concentration over multiple years but were not significantly associated with downstream compounds. Genome-specific SNP markers were used to identify candidate genes that co-localized to marker intervals and previously sequenced Brassica oleracea BAC clones containing known GSL genes (GSL-ALK, GSL-PRO, and GSL-ELONG) were aligned to the genomic sequence, providing support that at least three of our 14 QTLs likely correspond to previously identified GSL loci. The results demonstrate that previously identified loci do not fully explain GSL variation in broccoli. The identification of additional genetic factors influencing the accumulation of GSL in broccoli florets provides novel insight into the regulation of GSL levels in Brassicaceae and will accelerate development of vegetables with modified or enhanced GSL profiles.

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

PubMed

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

2008-04-09

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics.

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

PubMed Central

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

2008-01-01

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics. PMID:18398478

Investigation of Pokemon-regulated proteins in hepatocellular carcinoma using mass spectrometry-based multiplex quantitative proteomics.

PubMed

Bi, Xin; Jin, Yibao; Gao, Xiang; Liu, Feng; Gao, Dan; Jiang, Yuyang; Liu, Hongxia

2013-01-01

Pokemon is a transcription regulator involved in embryonic development, cellular differentiation and oncogenesis. It is aberrantly overexpressed in multiple human cancers including Hepatocellular carcinoma (HCC) and is considered as a promising biomarker for HCC. In this work, the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics strategy was used to investigate the proteomic profile associated with Pokemon in human HCC cell line QGY7703 and human hepatocyte line HL7702. Samples were labeled with four-plex iTRAQ reagents followed by two-dimensional liquid chromatography coupled with tandem mass spectrometry analysis. A total of 24 differentially expressed proteins were selected as significant. Nine proteins were potentially up-regulated by Pokemon while 15 proteins were potentially down-regulated and many proteins were previously identified as potential biomarkers for HCC. Gene ontology (GO) term enrichment revealed that the listed proteins were mainly involved in DNA metabolism and biosynthesis process. The changes of glucose-6-phosphate 1-dehydrogenase (G6PD, up-regulated) and ribonucleoside-diphosphate reductase large sub-unit (RIM1, down-regulated) were validated by Western blotting analysis and denoted as Pokemon's function of oncogenesis. We also found that Pokemon potentially repressed the expression of highly clustered proteins (MCM3, MCM5, MCM6, MCM7) which played key roles in promoting DNA replication. Altogether, our results may help better understand the role of Pokemon in HCC and promote the clinical applications.

Quantitative Sensory Testing and Current Perception Threshold Testing in Patients With Chronic Pain Following Lower Extremity Fracture.

PubMed

Griffioen, Mari A; Greenspan, Joel D; Johantgen, Meg; Von Rueden, Kathryn; O'Toole, Robert V; Dorsey, Susan G; Renn, Cynthia L

2018-01-01

Chronic pain is a significant problem for patients with lower extremity injuries. While pain hypersensitivity has been identified in many chronic pain conditions, it is not known whether patients with chronic pain following lower extremity fracture report pain hypersensitivity in the injured leg. To quantify and compare peripheral somatosensory function and sensory nerve activation thresholds in persons with chronic pain following lower extremity fractures with a cohort of persons with no history of lower extremity fractures. This was a cross-sectional study where quantitative sensory testing and current perception threshold testing were conducted on the injured and noninjured legs of cases and both legs of controls. A total of 14 cases and 28 controls participated in the study. Mean time since injury at the time of testing for cases was 22.3 (standard deviation = 12.1) months. The warmth detection threshold ( p = .024) and nerve activation thresholds at 2,000 Hz ( p < .001) and 250 Hz ( p = .002), respectively, were significantly higher in cases compared to controls. This study suggests that patients with chronic pain following lower extremity fractures may experience hypoesthesia in the injured leg, which contrasts with the finding of hyperesthesia previously observed in other chronic pain conditions but is in accord with patients with nerve injuries and surgeries. This is the first study to examine peripheral sensory nerve function at the site of injury in patients with chronic pain following lower extremity fractures using quantitative sensory testing and current perception threshold testing.

Correlation of Rock Spectra with Quantitative Morphologic Indices: Evidence for a Single Rock Type at the Mars Pathfinder Landing Site

NASA Technical Reports Server (NTRS)

Yingst, R. A.; Biedermann, K. L.; Pierre, N. M.; Haldemann, A. F. C.; Johnson, J. R.

2005-01-01

The Mars Pathfinder (MPF) landing site was predicted to contain a broad sampling of rock types varying in mineralogical, physical, mechanical and geochemical characteristics. Although rocks have been divided into several spectral categories based on Imager for Mars Pathfinder (IMP) visible/near-infrared data, efforts in isolating and classifying spectral units among MPF rocks and soils have met with varying degrees of success, as many factors influencing spectral signatures cannot be quantified to a sufficient level to be removed. It has not been fully determined which spectral categories stem from intrinsic mineralogical differences between rocks or rock surfaces, and which result from factors such as physical or chemical weathering. This has made isolation of unique rock mineralogies difficult. Morphology, like composition, is a characteristic tied to the intrinsic properties and geologic and weathering history of rocks. Rock morphologies can be assessed quantitatively and compared with spectral data, to identify and classify rock types at the MPF landing site. They can also isolate actual rock spectra from spectral types that are surficial in origin, as compositions associated with mantling dust or chemical coatings would presumably not influence rock morphology during weathering events. We previously reported on an initial classification of rocks using the quantitative morphologic indices of size, roundness, sphericity and elongation. Here, we compare this database of rock characteristics with associated rock surface spectra to improve our ability to discriminate between spectra associated with rock types and those from other sources.

Critical appraisal of emergency medicine education research: the best publications of 2013.

PubMed

Farrell, Susan E; Kuhn, Gloria J; Coates, Wendy C; Shayne, Phillip H; Fisher, Jonathan; Maggio, Lauren A; Lin, Michelle

2014-11-01

The objective was to critically appraise and highlight methodologically superior medical education research articles published in 2013 whose outcomes are pertinent to teaching and education in emergency medicine (EM). A search of the English-language literature in 2013 querying Education Resources Information Center (ERIC), PsychINFO, PubMed, and Scopus identified 251 EM-related studies using hypothesis-testing or observational investigations of educational interventions. Two reviewers independently screened all of the publications and removed articles using established exclusion criteria. Six reviewers then independently scored the remaining 43 publications using either a qualitative a or quantitative scoring system, based on the research methodology of each article. Each scoring system consisted of nine criteria. Selected criteria were based on accepted educational review literature and chosen a priori. Both scoring systems used parallel scoring metrics and have been used previously within this annual review. Forty-three medical education research papers (37 quantitative and six qualitative studies) met the a priori criteria for inclusion and were reviewed. Six quantitative and one qualitative study were scored and ranked most highly by the reviewers as exemplary and are summarized in this article. This annual critical appraisal article aims to promote superior research in EM-related education, by reviewing and highlighting seven of 43 major education research studies, meeting a priori criteria, and published in 2013. Common methodologic pitfalls in the 2013 papers are noted, and current trends in medical education research in EM are discussed. © 2014 by the Society for Academic Emergency Medicine.

Quantitative assessment of the mechanical properties of prostate tissue with optical coherence elastography

NASA Astrophysics Data System (ADS)

Ling, Yuting; Li, Chunhui; Zhou, Kanheng; Guan, Guangying; Lang, Stephen; McGloin, David; Nabi, Ghulam; Huang, Zhihong

2018-02-01

Prostate cancer (PCa) is a heterogeneous disease with multifocal origin. In current clinical care, the Gleason scoring system is the well-established diagnosis by microscopic evaluation of the tissue from trans-rectal ultrasound (TRUS) guided biopsies. Nevertheless, the sensitivity and specificity in detecting PCa can range from 40 to 50% for conventional TRUS B-mode imaging. Tissue elasticity is associated with the disease progression and elastography technique has recently shown promise in aiding PCa diagnosis. However, many cancer foci in the prostate gland has very small size less than 1 mm and those detected by medical elastography were larger than 2 mm. Hereby, we introduce optical coherence elastography (OCE) to quantify the prostate stiffness with high resolution in the magnitude of 10 µm. Following our feasibility study of 10 patients reported previously, we recruited 60 more patients undergoing 12-core TRUS guided biopsies for suspected PCa with a total of 720 biopsies. The stiffness of cancer tissue was approximately 57.63% higher than that of benign ones. Using histology as reference standard and cut-off threshold of 600kPa, the data analysis showed sensitivity and specificity of 89.6% and 99.8% respectively. The method also demonstrated potential in characterising different grades of PCa based on the change of tissue morphology and quantitative mechanical properties. In conclusion, quantitative OCE can be a reliable technique to identify PCa lesion and differentiate indolent from aggressive cancer.

Patterns of functional vision loss in glaucoma determined with archetypal analysis

PubMed Central

Elze, Tobias; Pasquale, Louis R.; Shen, Lucy Q.; Chen, Teresa C.; Wiggs, Janey L.; Bex, Peter J.

2015-01-01

Glaucoma is an optic neuropathy accompanied by vision loss which can be mapped by visual field (VF) testing revealing characteristic patterns related to the retinal nerve fibre layer anatomy. While detailed knowledge about these patterns is important to understand the anatomic and genetic aspects of glaucoma, current classification schemes are typically predominantly derived qualitatively. Here, we classify glaucomatous vision loss quantitatively by statistically learning prototypical patterns on the convex hull of the data space. In contrast to component-based approaches, this method emphasizes distinct aspects of the data and provides patterns that are easier to interpret for clinicians. Based on 13 231 reliable Humphrey VFs from a large clinical glaucoma practice, we identify an optimal solution with 17 glaucomatous vision loss prototypes which fit well with previously described qualitative patterns from a large clinical study. We illustrate relations of our patterns to retinal structure by a previously developed mathematical model. In contrast to the qualitative clinical approaches, our results can serve as a framework to quantify the various subtypes of glaucomatous visual field loss. PMID:25505132

Efficacy ranking of triterpenoids as inducers of a cytoprotective enzyme and as inhibitors of a cellular inflammatory response via their electron affinity and their electrophilicity index

PubMed Central

Bensasson, René V.; Zoete, Vincent; Berthier, Gaston; Talalay, Paul; Dinkova-Kostova, Albena T.

2010-01-01

Electron affinity (EA) and electrophilicity index (ω) of 16 synthetic triterpenoids (TP), previously identified as inducers of cytoprotective enzymes and as inhibitors of cellular inflammatory responses, have been calculated by the molecular orbital method. Linear correlations were obtained by plotting the values of EA, as well as those of ω versus (i) the potencies of induction of NAD(P)H quinone reductase (NQO1, EC 1.6.99.2), a cytoprotective enzyme, expressed via the concentration of TP required to double the specific activity of NQO1 (CD value) and (ii) the values of their anti-inflammatory activity expressed via the IC-50 of TP for suppression of upregulation of inducible nitric oxide synthase (iNOS, EC 1.14.13.39), both previously experimentally determined. The observed correlations demonstrate quantitatively for a series of triterpenoids that their electrophilicity is a major factor determining their potency as inducers of the cytoprotective phase 2 response and as inhibitors of inflammatory processes. PMID:20433811