Use of globally unique identifiers (GUIDs) to link herbarium specimen records to physical specimens.

PubMed

Nelson, Gil; Sweeney, Patrick; Gilbert, Edward

2018-02-01

With the advent of the U.S. National Science Foundation's Advancing Digitization of Biodiversity Collections program and related worldwide digitization initiatives, the rate of herbarium specimen digitization in the United States has expanded exponentially. As the number of electronic herbarium records proliferates, the importance of linking these records to the physical specimens they represent as well as to related records from other sources will intensify. Although a rich and diverse literature has developed over the past decade that addresses the use of specimen identifiers for facilitating linking across the internet, few implementable guidelines or recommended practices for herbaria have been advanced. Here we review this literature with the express purpose of distilling a specific set of recommendations especially tailored to herbarium specimen digitization, curation, and management. We argue that associating globally unique identifiers (GUIDs) with physical herbarium specimens and including these identifiers in all electronic records about those specimens is essential to effective digital data curation. We also address practical applications for ensuring these associations.

Potential of commercial microwave link network derived rainfall for river runoff simulations

NASA Astrophysics Data System (ADS)

Smiatek, Gerhard; Keis, Felix; Chwala, Christian; Fersch, Benjamin; Kunstmann, Harald

2017-03-01

Commercial microwave link networks allow for the quantification of path integrated precipitation because the attenuation by hydrometeors correlates with rainfall between transmitter and receiver stations. The networks, operated and maintained by cellphone companies, thereby provide completely new and country wide precipitation measurements. As the density of traditional precipitation station networks worldwide is significantly decreasing, microwave link derived precipitation estimates receive increasing attention not only by hydrologists but also by meteorological and hydrological services. We investigate the potential of microwave derived precipitation estimates for streamflow prediction and water balance analyses, exemplarily shown for an orographically complex region in the German Alps (River Ammer). We investigate the additional value of link derived rainfall estimations combined with station observations compared to station and weather radar derived values. Our river runoff simulation system employs a distributed hydrological model at 100 × 100 m grid resolution. We analyze the potential of microwave link derived precipitation estimates for two episodes of 30 days with typically moderate river flow and an episode of extreme flooding. The simulation results indicate the potential of this novel precipitation monitoring method: a significant improvement in hydrograph reproduction has been achieved in the extreme flooding period that was characterized by a large number of local strong precipitation events. The present rainfall monitoring gauges alone were not able to correctly capture these events.

Nightmares in the general population: identifying potential causal factors.

PubMed

Rek, Stephanie; Sheaves, Bryony; Freeman, Daniel

2017-09-01

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

Persistent Identifiers: a Prerequisite to Establish the Framework for Scholarly Link Exchange—Scholix

NASA Astrophysics Data System (ADS)

Stocker, M.; Mokrane, M.; Burton, A.; Koers, H.

2016-12-01

The Scholix framework—Scholarly Link Exchange—is a set of aspirational principles and practical guidelines developed under the umbrella of a joint Working Group of the Research Data Alliance (RDA) and the World Data System (WDS). It supports a global open information ecosystem unveiling the links between scholarly literature and underpinning research data. The core objectives of the framework are to (1) increase visibility and discoverability of data and articles, (2) place data in context to enable re-use, and (3) support credit attribution mechanisms. Thus, facilitating reproducibility and the transparent evaluation of science. Scholix provides an evolving lightweight set of Guidelines to increase interoperability rather than a normative standard. It consists initially of a conceptual and information models, information standards and encoding guidelines, and options for encoding and exchange protocols. An essential prerequisite to enable the proposed framework is the use of global, unique and persistent identifiers for research objects (such as data and literature). Scholix provides incentives and encourages best practice in the use of such identifiers and standardised referencing. The Data and Literature Interlinking Service (DLI: dliservice.research-infrastructures.eu) is the first exemplar of an aggregation and query service supported by the Scholix framework which will allow the emergence of third party services such as domain-specific aggregations, integrations with other global services, discovery tools, impact assessments, etc. Scholix is already implemented by existing hubs or global aggregators of data-literature link information such as DataCite, CrossRef, OpenAIRE, and EMBL-EBI building on the capacities of existing Persistent Identifier Systems (PIDs) such as Digital Object Identifiers (DOI) and Accession Numbers. These hubs in turn work with their natural communities of data centres or literature publishers to collect the information through

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

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

Wendt, Jeremy Daniel.

2013-07-01

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

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

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

Hammack, R.W.

2008-01-01

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

Advanced development and calibration of the network robustness index to identify critical road network links.

DOT National Transportation Integrated Search

2010-05-31

In this research project, transportation flexibility and reliability concepts are extended and applied : to a new method for identifying the most critical links in a road network. Current transportation : management practices typically utilize locali...

Bulked segregant analysis identifies molecular markers linked to Melampsora medusae resistance in Populus deltoides

Treesearch

G. M. Tabor; Thomas L. Kubisiak; N. B. Klopfenstein; R. B. Hall; Henry S. McNabb

2000-01-01

In the north central United States, leaf rust caused by Melampsora medusae is a major disease problem on Populus deltoides. In this study we identified molecular markers linked to a M. medusae resistance locus (Lrd1) that was segregating 1:1 within an intraspecific P. deltoides...

The NIF LinkOut broker: a web resource to facilitate federated data integration using NCBI identifiers.

PubMed

Marenco, Luis; Ascoli, Giorgio A; Martone, Maryann E; Shepherd, Gordon M; Miller, Perry L

2008-09-01

This paper describes the NIF LinkOut Broker (NLB) that has been built as part of the Neuroscience Information Framework (NIF) project. The NLB is designed to coordinate the assembly of links to neuroscience information items (e.g., experimental data, knowledge bases, and software tools) that are (1) accessible via the Web, and (2) related to entries in the National Center for Biotechnology Information's (NCBI's) Entrez system. The NLB collects these links from each resource and passes them to the NCBI which incorporates them into its Entrez LinkOut service. In this way, an Entrez user looking at a specific Entrez entry can LinkOut directly to related neuroscience information. The information stored in the NLB can also be utilized in other ways. A second approach, which is operational on a pilot basis, is for the NLB Web server to create dynamically its own Web page of LinkOut links for each NCBI identifier in the NLB database. This approach can allow other resources (in addition to the NCBI Entrez) to LinkOut to related neuroscience information. The paper describes the current NLB system and discusses certain design issues that arose during its implementation.

The NIF LinkOut Broker: A Web Resource to Facilitate Federated Data Integration using NCBI Identifiers

PubMed Central

Ascoli, Giorgio A.; Martone, Maryann E.; Shepherd, Gordon M.; Miller, Perry L.

2009-01-01

This paper describes the NIF LinkOut Broker (NLB) that has been built as part of the Neuroscience Information Framework (NIF) project. The NLB is designed to coordinate the assembly of links to neuroscience information items (e.g., experimental data, knowledge bases, and software tools) that are (1) accessible via the Web, and (2) related to entries in the National Center for Biotechnology Information’s (NCBI’s) Entrez system. The NLB collects these links from each resource and passes them to the NCBI which incorporates them into its Entrez LinkOut service. In this way, an Entrez user looking at a specific Entrez entry can LinkOut directly to related neuroscience information. The information stored in the NLB can also be utilized in other ways. A second approach, which is operational on a pilot basis, is for the NLB Web server to create dynamically its own Web page of LinkOut links for each NCBI identifier in the NLB database. This approach can allow other resources (in addition to the NCBI Entrez) to LinkOut to related neuroscience information. The paper describes the current NLB system and discusses certain design issues that arose during its implementation. PMID:18975149

TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.

PubMed

Xu, Yan; Chen, Yan; Li, Daliang; Liu, Qing; Xuan, Zhenyu; Li, Wen-Hong

2017-02-01

MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

Unreported links between trial registrations and published articles were identified using document similarity measures in a cross-sectional analysis of ClinicalTrials.gov.

PubMed

Dunn, Adam G; Coiera, Enrico; Bourgeois, Florence T

2018-03-01

Trial registries can be used to measure reporting biases and support systematic reviews, but 45% of registrations do not provide a link to the article reporting on the trial. We evaluated the use of document similarity methods to identify unreported links between ClinicalTrials.gov and PubMed. We extracted terms and concepts from a data set of 72,469 ClinicalTrials.gov registrations and 276,307 PubMed articles and tested methods for ranking articles across 16,005 reported links and 90 manually identified unreported links. Performance was measured by the median rank of matching articles and the proportion of unreported links that could be found by screening ranked candidate articles in order. The best-performing concept-based representation produced a median rank of 3 (interquartile range [IQR] 1-21) for reported links and 3 (IQR 1-19) for the manually identified unreported links, and term-based representations produced a median rank of 2 (1-20) for reported links and 2 (IQR 1-12) in unreported links. The matching article was ranked first for 40% of registrations, and screening 50 candidate articles per registration identified 86% of the unreported links. Leveraging the growth in the corpus of reported links between ClinicalTrials.gov and PubMed, we found that document similarity methods can assist in the identification of unreported links between trial registrations and corresponding articles. Copyright © 2017 Elsevier Inc. All rights reserved.

Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease.

PubMed

Ashbrook, David G; Williams, Robert W; Lu, Lu; Stein, Jason L; Hibar, Derrek P; Nichols, Thomas E; Medland, Sarah E; Thompson, Paul M; Hager, Reinmar

2014-10-03

Variation in hippocampal volume has been linked to significant differences in memory, behavior, and cognition among individuals. To identify genetic variants underlying such differences and associated disease phenotypes, multinational consortia such as ENIGMA have used large magnetic resonance imaging (MRI) data sets in human GWAS studies. In addition, mapping studies in mouse model systems have identified genetic variants for brain structure variation with great power. A key challenge is to understand how genetically based differences in brain structure lead to the propensity to develop specific neurological disorders. We combine the largest human GWAS of brain structure with the largest mammalian model system, the BXD recombinant inbred mouse population, to identify novel genetic targets influencing brain structure variation that are linked to increased risk for neurological disorders. We first use a novel cross-species, comparative analysis using mouse and human genetic data to identify a candidate gene, MGST3, associated with adult hippocampus size in both systems. We then establish the coregulation and function of this gene in a comprehensive systems-analysis. We find that MGST3 is associated with hippocampus size and is linked to a group of neurodegenerative disorders, such as Alzheimer's.

In situ trans ligands of CD22 identified by glycan-protein photocross-linking-enabled proteomics.

PubMed

Ramya, T N C; Weerapana, Eranthie; Liao, Lujian; Zeng, Ying; Tateno, Hiroaki; Liao, Liang; Yates, John R; Cravatt, Benjamin F; Paulson, James C

2010-06-01

CD22, a regulator of B-cell signaling, is a siglec that recognizes the sequence NeuAcalpha2-6Gal on glycoprotein glycans as ligands. CD22 interactions with glycoproteins on the same cell (in cis) and apposing cells (in trans) modulate its activity in B-cell receptor signaling. Although CD22 predominantly recognizes neighboring CD22 molecules as cis ligands on B-cells, little is known about the trans ligands on apposing cells. We conducted a proteomics scale study to identify candidate trans ligands of CD22 on B-cells by UV photocross-linking CD22-Fc chimera bound to B-cell glycoproteins engineered to carry sialic acids with a 9-aryl azide moiety. Using mass spectrometry-based quantitative proteomics to analyze the cross-linked products, 27 glycoproteins were identified as candidate trans ligands. Next, CD22 expressed on the surface of one cell was photocross-linked to glycoproteins on apposing B-cells followed by immunochemical analysis of the products with antibodies to the candidate ligands. Of the many candidate ligands, only the B-cell receptor IgM was found to be a major in situ trans ligand of CD22 that is selectively redistributed to the site of cell contact upon interaction with CD22 on the apposing cell.

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

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

Das, I.

2016-06-15

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

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

PubMed

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

2015-04-01

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

Flight tests show potential benefits of data link as primary communication medium

NASA Technical Reports Server (NTRS)

Scanlon, Charles H.; Knox, Charles E.

1991-01-01

Message exchange for air traffic control (ATC) purposes via data link offers the potential benefits of increasing the airspace system safety and efficiency. This is accomplished by reducing communication errors and relieving the overloaded ATC radio frequencies, which hamper efficient message exchanges during peak traffic periods in many busy terminal areas. However, the many uses and advantages of data link create additional questions concerning the interface among the human-users and the cockpit and ground systems. A flight test was conducted in the NASA Langley B-737 airplane to contrast flight operations using current voice communications with the use of data link for transmitting both strategic and tactical ATC clearances during a typical commercial airline flight from takeoff to landing. Commercial airplane pilots were used as test subjects.

Identifying potential academic leaders

PubMed Central

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

2016-01-01

Objective To identify variables associated with willingness to undertake leadership roles among academic family medicine faculty. Design Web-based survey. Bivariate and multivariable analyses (logistic regression) were used to identify variables associated with willingness to undertake leadership roles. Setting Department of Family and Community Medicine at the University of Toronto in Ontario. Participants A total of 687 faculty members. Main outcome measures Variables related to respondents’ willingness to take on various academic leadership roles. Results Of all 1029 faculty members invited to participate in the survey, 687 (66.8%) members responded. Of the respondents, 596 (86.8%) indicated their level of willingness to take on various academic leadership roles. Multivariable analysis revealed that the predictors associated with willingness to take on leadership roles were as follows: pursuit of professional development opportunities (odds ratio [OR] 3.79, 95% CI 2.29 to 6.27); currently holding at least 1 leadership role (OR 5.37, 95% CI 3.38 to 8.53); a history of leadership training (OR 1.86, 95% CI 1.25 to 2.78); the perception that mentorship is important for one’s current role (OR 2.25, 95% CI 1.40 to 3.60); and younger age (OR 0.97, 95% CI 0.95 to 0.99). Conclusion Willingness to undertake new or additional leadership roles was associated with 2 variables related to leadership experiences, 2 variables related to perceptions of mentorship and professional development, and 1 demographic variable (younger age). Interventions that support opportunities in these areas might expand the pool and strengthen the academic leadership potential of faculty members. PMID:27331226

Identifying social factors amongst older individuals in linked electronic health records: An assessment in a population based study

PubMed Central

van Hoek, Albert J.; Walker, Jemma L.; Mathur, Rohini; Smeeth, Liam; Thomas, Sara L.

2017-01-01

Identification and quantification of health inequities amongst specific social groups is a pre-requisite for designing targeted healthcare interventions. This study investigated the recording of social factors in linked electronic health records (EHR) of individuals aged ≥65 years, to assess the potential of these data to identify the social determinants of disease burden and uptake of healthcare interventions. Methodology was developed for ascertaining social factors recorded on or before a pre-specified index date (01/01/2013) using primary care data from Clinical Practice Research Datalink (CPRD) linked to hospitalisation and deprivation data in a cross-sectional study. Social factors included: religion, ethnicity, immigration status, small area-level deprivation, place of residence (including communal establishments such as care homes), marital status and living arrangements (e.g. living alone, cohabitation). Each social factor was examined for: completeness of recording including improvements in completeness by using other linked EHR, timeliness of recording for factors that might change over time and their representativeness (compared with English 2011 Census data when available). Data for 591,037 individuals from 389 practices from England were analysed. The completeness of recording varied from 1.6% for immigration status to ~80% for ethnicity. Linkages provided the deprivation data (available for 82% individuals) and improved completeness of ethnicity recording from 55% to 79% (when hospitalisation data were added). Data for ethnicity, deprivation, living arrangements and care home residence were comparable to the Census data. For time-varying variables such as residence and living alone, ~60% and ~35% respectively of those with available data, had this information recorded within the last 5 years of the index date. This work provides methods to identify social factors in EHR relevant to older individuals and shows that factors such as ethnicity

Cross-disciplinary links in environmental systems science: Current state and claimed needs identified in a meta-review of process models.

PubMed

Ayllón, Daniel; Grimm, Volker; Attinger, Sabine; Hauhs, Michael; Simmer, Clemens; Vereecken, Harry; Lischeid, Gunnar

2018-05-01

Terrestrial environmental systems are characterised by numerous feedback links between their different compartments. However, scientific research is organized into disciplines that focus on processes within the respective compartments rather than on interdisciplinary links. Major feedback mechanisms between compartments might therefore have been systematically overlooked so far. Without identifying these gaps, initiatives on future comprehensive environmental monitoring schemes and experimental platforms might fail. We performed a comprehensive overview of feedbacks between compartments currently represented in environmental sciences and explores to what degree missing links have already been acknowledged in the literature. We focused on process models as they can be regarded as repositories of scientific knowledge that compile findings of numerous single studies. In total, 118 simulation models from 23 model types were analysed. Missing processes linking different environmental compartments were identified based on a meta-review of 346 published reviews, model intercomparison studies, and model descriptions. Eight disciplines of environmental sciences were considered and 396 linking processes were identified and ascribed to the physical, chemical or biological domain. There were significant differences between model types and scientific disciplines regarding implemented interdisciplinary links. The most wide-spread interdisciplinary links were between physical processes in meteorology, hydrology and soil science that drive or set the boundary conditions for other processes (e.g., ecological processes). In contrast, most chemical and biological processes were restricted to links within the same compartment. Integration of multiple environmental compartments and interdisciplinary knowledge was scarce in most model types. There was a strong bias of suggested future research foci and model extensions towards reinforcing existing interdisciplinary knowledge rather than

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

PubMed

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

2017-01-01

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

Incorporating the Last Four Digits of Social Security Numbers Substantially Improves Linking Patient Data from De-identified Hospital Claims Databases.

PubMed

Naessens, James M; Visscher, Sue L; Peterson, Stephanie M; Swanson, Kristi M; Johnson, Matthew G; Rahman, Parvez A; Schindler, Joe; Sonneborn, Mark; Fry, Donald E; Pine, Michael

2015-08-01

Assess algorithms for linking patients across de-identified databases without compromising confidentiality. Hospital discharges from 11 Mayo Clinic hospitals during January 2008-September 2012 (assessment and validation data). Minnesota death certificates and hospital discharges from 2009 to 2012 for entire state (application data). Cross-sectional assessment of sensitivity and positive predictive value (PPV) for four linking algorithms tested by identifying readmissions and posthospital mortality on the assessment data with application to statewide data. De-identified claims included patient gender, birthdate, and zip code. Assessment records were matched with institutional sources containing unique identifiers and the last four digits of Social Security number (SSNL4). Gender, birthdate, and five-digit zip code identified readmissions with a sensitivity of 98.0 percent and a PPV of 97.7 percent and identified postdischarge mortality with 84.4 percent sensitivity and 98.9 percent PPV. Inclusion of SSNL4 produced nearly perfect identification of readmissions and deaths. When applied statewide, regions bordering states with unavailable hospital discharge data had lower rates. Addition of SSNL4 to administrative data, accompanied by appropriate data use and data release policies, can enable trusted repositories to link data with nearly perfect accuracy without compromising patient confidentiality. States maintaining centralized de-identified databases should add SSNL4 to data specifications. © Health Research and Educational Trust.

Incorporating the Last Four Digits of Social Security Numbers Substantially Improves Linking Patient Data from De-identified Hospital Claims Databases

PubMed Central

Naessens, James M; Visscher, Sue L; Peterson, Stephanie M; Swanson, Kristi M; Johnson, Matthew G; Rahman, Parvez A; Schindler, Joe; Sonneborn, Mark; Fry, Donald E; Pine, Michael

2015-01-01

Objective Assess algorithms for linking patients across de-identified databases without compromising confidentiality. Data Sources/Study Setting Hospital discharges from 11 Mayo Clinic hospitals during January 2008–September 2012 (assessment and validation data). Minnesota death certificates and hospital discharges from 2009 to 2012 for entire state (application data). Study Design Cross-sectional assessment of sensitivity and positive predictive value (PPV) for four linking algorithms tested by identifying readmissions and posthospital mortality on the assessment data with application to statewide data. Data Collection/Extraction Methods De-identified claims included patient gender, birthdate, and zip code. Assessment records were matched with institutional sources containing unique identifiers and the last four digits of Social Security number (SSNL4). Principal Findings Gender, birthdate, and five-digit zip code identified readmissions with a sensitivity of 98.0 percent and a PPV of 97.7 percent and identified postdischarge mortality with 84.4 percent sensitivity and 98.9 percent PPV. Inclusion of SSNL4 produced nearly perfect identification of readmissions and deaths. When applied statewide, regions bordering states with unavailable hospital discharge data had lower rates. Conclusion Addition of SSNL4 to administrative data, accompanied by appropriate data use and data release policies, can enable trusted repositories to link data with nearly perfect accuracy without compromising patient confidentiality. States maintaining centralized de-identified databases should add SSNL4 to data specifications. PMID:26073819

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

EPA Science Inventory

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

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

NASA Astrophysics Data System (ADS)

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

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

Identifying Potential Kidney Donors Using Social Networking Websites

PubMed Central

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

2013-01-01

Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion, and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2–69); 88% were U.S. residents. Other posted information included the individual’s photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. PMID:23600791

Evaluating Testing Strategies for Identifying Youths With HIV Infection and Linking Youths to Biomedical and Other Prevention Services

PubMed Central

Boyer, Cherrie B.; Chiaramonte, Danielle; Lindeman, Peter; Chutuape, Kate; Cooper-Walker, Bendu; Kapogiannis, Bill G.; Wilson, Craig M.; Fortenberry, J. Dennis

2017-01-01

Importance Most human immunodeficiency virus (HIV)–infected youths are unaware of their serostatus (approximately 60%) and therefore not linked to HIV medical or prevention services. The need to identify promising and scalable approaches to promote uptake of HIV testing among youths at risk is critical. Objective To evaluate a multisite HIV testing program designed to encourage localized HIV testing programs focused on self-identified sexual minority males and to link youths to appropriate prevention services after receipt of their test results. Design, Setting, and Participants Testing strategies were evaluated using an observational design during a 9-month period (June 1, 2015, through February 28, 2016). Testing strategies were implemented by 12 adolescent medicine HIV primary care programs and included targeted testing, universal testing, or a combination. Data were collected from local youth at high risk of HIV infection and, specifically, sexual minority males of color. Main Outcomes and Measures Proportion of sexual minority males and sexual minority males of color tested, proportion of previously undiagnosed HIV-positive youths identified, and rates of linkage to prevention services. Results A total of 3301 youths underwent HIV testing. Overall, 35 (3.6%) of those who underwent universal testing in primary care clinical settings, such as emergency departments and community health centers, were sexual minority males (35 [3.6%] were males of color) compared with 236 (46.7%) (201 [39.8%] were males of color) who were tested through targeted testing and 693 (37.8%) (503 [27.4%] were males of color) through combination efforts. Identification of new HIV-positive cases varied by strategy: 1 (0.1%) via universal testing, 39 (2.1%) through combination testing, and 16 (3.2%) through targeted testing. However, when targeted tests were separated from universal testing results for sites using a combined strategy, the rate of newly identified HIV-positive cases

Mutagenic Potential of Nitroguanidine in the Drosophila melanogaster Sex-Linked Recessive Lethal Test

DTIC Science & Technology

1988-07-01

Security Classification) Mtutagenic potential of nitroguan idine in the Drosophila melano- gaster sex-linked recessive lethal test 12. PERSONAL AUTHOR(S...Frederick, MD 21701-5012 Commander Commandant US Army Environmental Hygine Academy of Health Sciences. US Army Agency ATTN: AHS-CDM ATTN: Librarian, HSDH

Release of genetically engineered insects: a framework to identify potential ecological effects

PubMed Central

David, Aaron S; Kaser, Joe M; Morey, Amy C; Roth, Alexander M; Andow, David A

2013-01-01

Genetically engineered (GE) insects have the potential to radically change pest management worldwide. With recent approvals of GE insect releases, there is a need for a synthesized framework to evaluate their potential ecological and evolutionary effects. The effects may occur in two phases: a transitory phase when the focal population changes in density, and a steady state phase when it reaches a new, constant density. We review potential effects of a rapid change in insect density related to population outbreaks, biological control, invasive species, and other GE organisms to identify a comprehensive list of potential ecological and evolutionary effects of GE insect releases. We apply this framework to the Anopheles gambiae mosquito – a malaria vector being engineered to suppress the wild mosquito population – to identify effects that may occur during the transitory and steady state phases after release. Our methodology reveals many potential effects in each phase, perhaps most notably those dealing with immunity in the transitory phase, and with pathogen and vector evolution in the steady state phase. Importantly, this framework identifies knowledge gaps in mosquito ecology. Identifying effects in the transitory and steady state phases allows more rigorous identification of the potential ecological effects of GE insect release. PMID:24198955

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

PubMed Central

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

2017-01-01

Severe acute malnutrition is the world-leading cause of children under-five's death. Recent metagenomics studies have established a link between gut microbiota and severe acute malnutrition, describing an immaturity with a striking depletion in oxygen-sensitive prokaryotes. Amoxicillin and therapeutic diet cure most of the children with severe acute malnutrition but an irreversible disruption of the gut microbiota is suspected in the refractory and most severe cases. In these cases, therapeutic diet may be unable to reverse the microbiota alteration leading to persistent impaired development or death. In addition, as enteric sepsis is a major cause of death in this context, identification of missing gut microbes to be tested as probiotics (live bacteria that confer a benefit to the host) to restore rapidly the healthy gut microbiota and prevent the gut pathogenic invasion is of foremost importance. In this study, stool samples of malnourished patients with kwashiorkor and healthy children were collected from Niger and Senegal and analyzed by culturomics and metagenomics. We found a globally decreased diversity, a decrease in the hitherto unknown diversity (new species isolation), a depletion in oxygen-sensitive prokaryotes including Methanobrevibacter smithii and an enrichment in potentially pathogenic Proteobacteria, Fusobacteria and Streptococcus gallolyticus. A complex of 12 species identified only in healthy children using culturomics and metagenomics were identified as probiotics candidates, providing a possible, defined, reproducible, safe, and convenient alternative to fecal transplantation to restore a healthy gut microbiota in malnourished children. Microbiotherapy based on selected strains has the potential to improve the current treatment of severe acute malnutrition and prevent relapse and death by reestablishing a healthy gut microbiota. PMID:28588566

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

PubMed

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

2009-12-01

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

Genome Wide Association Mapping in Arabidopsis thaliana Identifies Novel Genes Involved in Linking Allyl Glucosinolate to Altered Biomass and Defense.

PubMed

Francisco, Marta; Joseph, Bindu; Caligagan, Hart; Li, Baohua; Corwin, Jason A; Lin, Catherine; Kerwin, Rachel E; Burow, Meike; Kliebenstein, Daniel J

2016-01-01

A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS) have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL), may provide direct feedback regulation, linking defense metabolism outputs to the growth, and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s) that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 μM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis.

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

ERIC Educational Resources Information Center

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

2008-01-01

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

Linking admiration and adoration to self-expansion: different ways to enhance one's potential.

PubMed

Schindler, Ines; Paech, Juliane; Löwenbrück, Fabian

2015-01-01

How is admiration different from adoration? We provided one answer to this question by examining the pathways through which admiration and adoration linked to self-expansion in a questionnaire and an experimental (autobiographical recall of emotion episodes) study. Both emotions were associated with increased potential efficacy to accomplish goals (i.e., self-expansion), but different action tendencies accounted for these links. While our emotion inductions did not successfully distinguish between admiration and adoration, we could statistically disentangle their effects through mediator models. In both studies, self-reported admiration linked to self-expansion through the tendency to emulate admired others. Adoration related to self-expansion through the tendency to affiliate with adored others. These findings were obtained after controlling for other emotions in response to the target person (awe, love, hope, benign envy) and mutuality of the relationship. Our findings also suggest that considering specific emotions (rather than undifferentiated positive affect) helps uncover different pathways to self-expansion.

Possible Links between Intestinal Permeablity and Food Processing: A Potential Therapeutic Niche for Glutamine

PubMed Central

Rapin, Jean Robert; Wiernsperger, Nicolas

2010-01-01

Increased intestinal permeability is a likely cause of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Intestinal permeability is found in many severe clinical situations and in common disorders such as irritable bowel syndrome. In these conditions, substances that are normally unable to cross the epithelial barrier gain access to the systemic circulation. To illustrate the potential harmfulness of leaky gut, we present an argument based on examples linked to protein or lipid glycation induced by modern food processing. Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening. This brief review aims to increase physician awareness of this common, albeit largely unrecognized, pathology, which may be easily prevented or improved by means of simple nutritional changes. PMID:20613941

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

NASA Astrophysics Data System (ADS)

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

2011-10-01

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

Identifying potential kidney donors using social networking web sites.

PubMed

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

2013-01-01

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

Single-Exome sequencing identified a novel RP2 mutation in a child with X-linked retinitis pigmentosa.

PubMed

Lim, Hassol; Park, Young-Mi; Lee, Jong-Keuk; Taek Lim, Hyun

2016-10-01

To present an efficient and successful application of a single-exome sequencing study in a family clinically diagnosed with X-linked retinitis pigmentosa. Exome sequencing study based on clinical examination data. An 8-year-old proband and his family. The proband and his family members underwent comprehensive ophthalmologic examinations. Exome sequencing was undertaken in the proband using Agilent SureSelect Human All Exon Kit and Illumina HiSeq 2000 platform. Bioinformatic analysis used Illumina pipeline with Burrows-Wheeler Aligner-Genome Analysis Toolkit (BWA-GATK), followed by ANNOVAR to perform variant functional annotation. All variants passing filter criteria were validated by Sanger sequencing to confirm familial segregation. Analysis of exome sequence data identified a novel frameshift mutation in RP2 gene resulting in a premature stop codon (c.665delC, p.Pro222fsTer237). Sanger sequencing revealed this mutation co-segregated with the disease phenotype in the child's family. We identified a novel causative mutation in RP2 from a single proband's exome sequence data analysis. This study highlights the effectiveness of the whole-exome sequencing in the genetic diagnosis of X-linked retinitis pigmentosa, over the conventional sequencing methods. Even using a single exome, exome sequencing technology would be able to pinpoint pathogenic variant(s) for X-linked retinitis pigmentosa, when properly applied with aid of adequate variant filtering strategy. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Classifying quantum entanglement through topological links

NASA Astrophysics Data System (ADS)

Quinta, Gonçalo M.; André, Rui

2018-04-01

We propose an alternative classification scheme for quantum entanglement based on topological links. This is done by identifying a nonrigid ring to a particle, attributing the act of cutting and removing a ring to the operation of tracing out the particle, and associating linked rings to entangled particles. This analogy naturally leads us to a classification of multipartite quantum entanglement based on all possible distinct links for a given number of rings. To determine all different possibilities, we develop a formalism that associates any link to a polynomial, with each polynomial thereby defining a distinct equivalence class. To demonstrate the use of this classification scheme, we choose qubit quantum states as our example of physical system. A possible procedure to obtain qubit states from the polynomials is also introduced, providing an example state for each link class. We apply the formalism for the quantum systems of three and four qubits and demonstrate the potential of these tools in a context of qubit networks.

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma.

PubMed

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

2017-03-03

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

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

PubMed Central

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

2017-01-01

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

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

EPA Science Inventory

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

Phylogenetic and functional potential links pH and N2O emissions in pasture soils.

PubMed

Samad, Md Sainur; Biswas, Ambarish; Bakken, Lars R; Clough, Timothy J; de Klein, Cecile A M; Richards, Karl G; Lanigan, Gary J; Morales, Sergio E

2016-10-26

Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N 2 O and N 2 emissions. Soil pH regulates the reduction of N 2 O to N 2 , however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N 2 O emission ratio (N 2 O/(NO + N 2 O + N 2 )) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N 2 O emission ratio and community changes. Soil pH was negatively associated with N 2 O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir &nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N 2 O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N 2 O emission ratio through more efficient conversion of N 2 O to N 2 .

Phylogenetic and functional potential links pH and N2O emissions in pasture soils

NASA Astrophysics Data System (ADS)

Samad, M. D. Sainur; Biswas, Ambarish; Bakken, Lars R.; Clough, Timothy J.; de Klein, Cecile A. M.; Richards, Karl G.; Lanigan, Gary J.; Morales, Sergio E.

2016-10-01

Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N2O and N2 emissions. Soil pH regulates the reduction of N2O to N2, however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N2O emission ratio (N2O/(NO + N2O + N2)) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N2O emission ratio and community changes. Soil pH was negatively associated with N2O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir & nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N2O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N2O emission ratio through more efficient conversion of N2O to N2.

Phylogenetic and functional potential links pH and N2O emissions in pasture soils

PubMed Central

Samad, M. d. Sainur; Biswas, Ambarish; Bakken, Lars R.; Clough, Timothy J.; de Klein, Cecile A. M.; Richards, Karl G.; Lanigan, Gary J.; Morales, Sergio E.

2016-01-01

Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N2O and N2 emissions. Soil pH regulates the reduction of N2O to N2, however, it can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N2O emission ratio (N2O/(NO + N2O + N2)) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes: nirS, nirK, nosZI and nosZII) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N2O emission ratio and community changes. Soil pH was negatively associated with N2O emission ratio, while being positively associated with both community diversity and total denitrification gene (nir & nos) abundance. Abundance of nosZII was positively linked to pH, and negatively linked to N2O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N2O emission ratio through more efficient conversion of N2O to N2. PMID:27782174

Beyond Failure: Potentially Mitigating Failed Author Searches in the Online Library Catalog through the Use of Linked Data

ERIC Educational Resources Information Center

Moulaison, Heather Lea; Stanley, Susan Nicole

2013-01-01

Linked data stores house vetted content that can supplement the information available through online library catalogs, potentially mitigating failed author searches if information about the author exists in linked data formats. In this case study, a total of 689 failed author index queries from a large Midwestern academic library's online library…

Using a watershed-centric approach to identify potentially impacted beaches

EPA Science Inventory

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

Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms

PubMed Central

Hernández, Antonio F.; Menéndez, Pablo

2016-01-01

Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events. PMID:27043530

A guide to evaluating linkage quality for the analysis of linked data.

PubMed

Harron, Katie L; Doidge, James C; Knight, Hannah E; Gilbert, Ruth E; Goldstein, Harvey; Cromwell, David A; van der Meulen, Jan H

2017-10-01

Linked datasets are an important resource for epidemiological and clinical studies, but linkage error can lead to biased results. For data security reasons, linkage of personal identifiers is often performed by a third party, making it difficult for researchers to assess the quality of the linked dataset in the context of specific research questions. This is compounded by a lack of guidance on how to determine the potential impact of linkage error. We describe how linkage quality can be evaluated and provide widely applicable guidance for both data providers and researchers. Using an illustrative example of a linked dataset of maternal and baby hospital records, we demonstrate three approaches for evaluating linkage quality: applying the linkage algorithm to a subset of gold standard data to quantify linkage error; comparing characteristics of linked and unlinked data to identify potential sources of bias; and evaluating the sensitivity of results to changes in the linkage procedure. These approaches can inform our understanding of the potential impact of linkage error and provide an opportunity to select the most appropriate linkage procedure for a specific analysis. Evaluating linkage quality in this way will improve the quality and transparency of epidemiological and clinical research using linked data. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

The link between otitis media with effusion and allergy: a potential role for intranasal corticosteroids.

PubMed

Lack, Gideon; Caulfield, Helen; Penagos, Martin

2011-05-01

We reviewed the evidence linking otitis media with effusion (OME) and atopy, with the goal of clarifying the possible role of intranasal corticosteroids (INSs) in OME treatment. In August 2009, the MEDLINE database was searched for primary studies on OME epidemiology, pathophysiology, and treatment. Relevant clinical guidelines were obtained. Interpreting OME research is complicated by variable disease definitions, patient populations, methodologies, and outcomes assessments, along with the possibility of spontaneous resolution. However, evidence links OME with atopic conditions including allergic rhinitis; observed prevalence of allergic rhinitis in patients with chronic or recurrent OME ranges from 24% to 89%. Such findings have prompted evaluations of common allergy medications for OME treatment. While short-term use of INSs alone or combined with antibiotics has shown benefit in some studies, more prolonged treatment protocols and long-term clinical outcomes will require critical assessment. Evidence suggesting epidemiologic and pathophysiologic links between allergy and OME has prompted investigation into a potential role for INSs in OME management, with promising initial results. Benefits of considering medical treatment in patients with OME prior to surgery include both the potential reductions in allergic inflammation and the naturally occurring spontaneous resolution of OME in these patients. © 2011 John Wiley & Sons A/S.

Design and Development of a Linked Open Data-Based Health Information Representation and Visualization System: Potentials and Preliminary Evaluation

PubMed Central

Kauppinen, Tomi; Keßler, Carsten; Fritz, Fleur

2014-01-01

Background Healthcare organizations around the world are challenged by pressures to reduce cost, improve coordination and outcome, and provide more with less. This requires effective planning and evidence-based practice by generating important information from available data. Thus, flexible and user-friendly ways to represent, query, and visualize health data becomes increasingly important. International organizations such as the World Health Organization (WHO) regularly publish vital data on priority health topics that can be utilized for public health policy and health service development. However, the data in most portals is displayed in either Excel or PDF formats, which makes information discovery and reuse difficult. Linked Open Data (LOD)—a new Semantic Web set of best practice of standards to publish and link heterogeneous data—can be applied to the representation and management of public level health data to alleviate such challenges. However, the technologies behind building LOD systems and their effectiveness for health data are yet to be assessed. Objective The objective of this study is to evaluate whether Linked Data technologies are potential options for health information representation, visualization, and retrieval systems development and to identify the available tools and methodologies to build Linked Data-based health information systems. Methods We used the Resource Description Framework (RDF) for data representation, Fuseki triple store for data storage, and Sgvizler for information visualization. Additionally, we integrated SPARQL query interface for interacting with the data. We primarily use the WHO health observatory dataset to test the system. All the data were represented using RDF and interlinked with other related datasets on the Web of Data using Silk—a link discovery framework for Web of Data. A preliminary usability assessment was conducted following the System Usability Scale (SUS) method. Results We developed an LOD

Design and development of a linked open data-based health information representation and visualization system: potentials and preliminary evaluation.

PubMed

Tilahun, Binyam; Kauppinen, Tomi; Keßler, Carsten; Fritz, Fleur

2014-10-25

Healthcare organizations around the world are challenged by pressures to reduce cost, improve coordination and outcome, and provide more with less. This requires effective planning and evidence-based practice by generating important information from available data. Thus, flexible and user-friendly ways to represent, query, and visualize health data becomes increasingly important. International organizations such as the World Health Organization (WHO) regularly publish vital data on priority health topics that can be utilized for public health policy and health service development. However, the data in most portals is displayed in either Excel or PDF formats, which makes information discovery and reuse difficult. Linked Open Data (LOD)-a new Semantic Web set of best practice of standards to publish and link heterogeneous data-can be applied to the representation and management of public level health data to alleviate such challenges. However, the technologies behind building LOD systems and their effectiveness for health data are yet to be assessed. The objective of this study is to evaluate whether Linked Data technologies are potential options for health information representation, visualization, and retrieval systems development and to identify the available tools and methodologies to build Linked Data-based health information systems. We used the Resource Description Framework (RDF) for data representation, Fuseki triple store for data storage, and Sgvizler for information visualization. Additionally, we integrated SPARQL query interface for interacting with the data. We primarily use the WHO health observatory dataset to test the system. All the data were represented using RDF and interlinked with other related datasets on the Web of Data using Silk-a link discovery framework for Web of Data. A preliminary usability assessment was conducted following the System Usability Scale (SUS) method. We developed an LOD-based health information representation, querying

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

EPA Science Inventory

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

Parkin Somatic Mutations Link Melanoma and Parkinson's Disease.

PubMed

Levin, Lotan; Srour, Shani; Gartner, Jared; Kapitansky, Oxana; Qutob, Nouar; Dror, Shani; Golan, Tamar; Dayan, Roy; Brener, Ronen; Ziv, Tamar; Khaled, Mehdi; Schueler-Furman, Ora; Samuels, Yardena; Levy, Carmit

2016-06-20

Epidemiological studies suggest a direct link between melanoma and Parkinson's disease (PD); however, the underlying molecular basis is unknown. Since mutations in Parkin are the major driver of early-onset PD and Parkin was recently reported to play a role in cancer development, we hypothesized that Parkin links melanoma and PD. By analyzing whole exome/genome sequencing of Parkin from 246 melanoma patients, we identified five non-synonymous mutations, three synonymous mutations, and one splice region variant in Parkin in 3.6% of the samples. In vitro analysis showed that wild-type Parkin plays a tumor suppressive role in melanoma development resulting in cell-cycle arrest, reduction of metabolic activity, and apoptosis. Using a mass spectrometry-based analysis, we identified potential Parkin substrates in melanoma and generated a functional protein association network. The activity of mutated Parkin was assessed by protein structure modeling and examination of Parkin E3 ligase activity. The Parkin-E28K mutation impairs Parkin ubiquitination activity and abolishes its tumor suppressive effect. Taken together, our analysis of genomic sequence and in vitro data indicate that Parkin is a potential link between melanoma and Parkinson's disease. Our findings suggest new approaches for early diagnosis and treatment against both diseases. Copyright © 2016. Published by Elsevier Ltd.

Air pollution, inflammation and preterm birth: a potential mechanistic link.

PubMed

Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A; Sánchez, Brisa N; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G; O'Neill, Marie S

2014-02-01

Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. Copyright © 2013 Elsevier Ltd. All rights reserved.

AIR POLLUTION, INFLAMMATION AND PRETERM BIRTH: A POTENTIAL MECHANISTIC LINK

PubMed Central

Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A.; Sánchez, Brisa N.; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G.; O´Neill, Marie S.

2014-01-01

Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. PMID:24382337

Linking Data for Mothers and Babies in De-Identified Electronic Health Data.

PubMed

Harron, Katie; Gilbert, Ruth; Cromwell, David; van der Meulen, Jan

2016-01-01

Linkage of longitudinal administrative data for mothers and babies supports research and service evaluation in several populations around the world. We established a linked mother-baby cohort using pseudonymised, population-level data for England. Retrospective linkage study using electronic hospital records of mothers and babies admitted to NHS hospitals in England, captured in Hospital Episode Statistics between April 2001 and March 2013. Of 672,955 baby records in 2012/13, 280,470 (42%) linked deterministically to a maternal record using hospital, GP practice, maternal age, birthweight, gestation, birth order and sex. A further 380,164 (56%) records linked using probabilistic methods incorporating additional variables that could differ between mother/baby records (admission dates, ethnicity, 3/4-character postcode district) or that include missing values (delivery variables). The false-match rate was estimated at 0.15% using synthetic data. Data quality improved over time: for 2001/02, 91% of baby records were linked (holding the estimated false-match rate at 0.15%). The linked cohort was representative of national distributions of gender, gestation, birth weight and maternal age, and captured approximately 97% of births in England. Probabilistic linkage of maternal and baby healthcare characteristics offers an efficient way to enrich maternity data, improve data quality, and create longitudinal cohorts for research and service evaluation. This approach could be extended to linkage of other datasets that have non-disclosive characteristics in common.

Discovering Potential Pathogens among Fungi Identified as Nonsporulating Molds▿

PubMed Central

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

2007-01-01

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

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

PubMed

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

2010-01-01

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

The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross-linking agents and their chemotherapeutic potential.

PubMed

Su, Tsann-Long; Lee, Te-Chang; Kakadiya, Rajesh

2013-11-01

Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents in clinics. The advance in the development of these agents as potential antitumor agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order to develop highly effective anticancer agents, it is necessary to understand the chemophysical properties, structure-activity relationships, therapeutic potency, toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide more information for future drug design and strategies for combination chemotherapy. The rational drug design, chemical syntheses, antitumor activity, mechanism of action, and development of combined chemotherapy regimens, including a DNA repair inhibitor, are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Linking Data for Mothers and Babies in De-Identified Electronic Health Data

PubMed Central

Gilbert, Ruth; Cromwell, David; van der Meulen, Jan

2016-01-01

Objective Linkage of longitudinal administrative data for mothers and babies supports research and service evaluation in several populations around the world. We established a linked mother-baby cohort using pseudonymised, population-level data for England. Design and Setting Retrospective linkage study using electronic hospital records of mothers and babies admitted to NHS hospitals in England, captured in Hospital Episode Statistics between April 2001 and March 2013. Results Of 672,955 baby records in 2012/13, 280,470 (42%) linked deterministically to a maternal record using hospital, GP practice, maternal age, birthweight, gestation, birth order and sex. A further 380,164 (56%) records linked using probabilistic methods incorporating additional variables that could differ between mother/baby records (admission dates, ethnicity, 3/4-character postcode district) or that include missing values (delivery variables). The false-match rate was estimated at 0.15% using synthetic data. Data quality improved over time: for 2001/02, 91% of baby records were linked (holding the estimated false-match rate at 0.15%). The linked cohort was representative of national distributions of gender, gestation, birth weight and maternal age, and captured approximately 97% of births in England. Conclusion Probabilistic linkage of maternal and baby healthcare characteristics offers an efficient way to enrich maternity data, improve data quality, and create longitudinal cohorts for research and service evaluation. This approach could be extended to linkage of other datasets that have non-disclosive characteristics in common. PMID:27764135

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

PubMed

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

2018-03-01

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

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

PubMed

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

2016-04-01

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

The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life

PubMed Central

Molloy, John; Allen, Katrina; Collier, Fiona; Tang, Mimi L. K.; Ward, Alister C.; Vuillermin, Peter

2013-01-01

There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gut microbiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gut microbiota and food allergy. Although the exact link between gut microbiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gut microbiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gut microbiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gut microbiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gut microbiota, and the types of studies required to advance knowledge in the field. PMID:24351744

Hot spot analysis applied to identify ecosystem services potential in Lithuania

NASA Astrophysics Data System (ADS)

Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

2016-04-01

Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, p<0.001). The Z score of providing services (0.096±2.239) were significantly higher than the total (0.093±2.045), cultural (0.080±1.979) and regulating (0.076±1.961). These

Identifying novel drug indications through automated reasoning.

PubMed

Tari, Luis; Vo, Nguyen; Liang, Shanshan; Patel, Jagruti; Baral, Chitta; Cai, James

2012-01-01

With the large amount of pharmacological and biological knowledge available in literature, finding novel drug indications for existing drugs using in silico approaches has become increasingly feasible. Typical literature-based approaches generate new hypotheses in the form of protein-protein interactions networks by means of linking concepts based on their cooccurrences within abstracts. However, this kind of approaches tends to generate too many hypotheses, and identifying new drug indications from large networks can be a time-consuming process. In this work, we developed a method that acquires the necessary facts from literature and knowledge bases, and identifies new drug indications through automated reasoning. This is achieved by encoding the molecular effects caused by drug-target interactions and links to various diseases and drug mechanism as domain knowledge in AnsProlog, a declarative language that is useful for automated reasoning, including reasoning with incomplete information. Unlike other literature-based approaches, our approach is more fine-grained, especially in identifying indirect relationships for drug indications. To evaluate the capability of our approach in inferring novel drug indications, we applied our method to 943 drugs from DrugBank and asked if any of these drugs have potential anti-cancer activities based on information on their targets and molecular interaction types alone. A total of 507 drugs were found to have the potential to be used for cancer treatments. Among the potential anti-cancer drugs, 67 out of 81 drugs (a recall of 82.7%) are indeed known cancer drugs. In addition, 144 out of 289 drugs (a recall of 49.8%) are non-cancer drugs that are currently tested in clinical trials for cancer treatments. These results suggest that our method is able to infer drug indications (original or alternative) based on their molecular targets and interactions alone and has the potential to discover novel drug indications for existing drugs.

Modeling Protein Excited-state Structures from "Over-length" Chemical Cross-links.

PubMed

Ding, Yue-He; Gong, Zhou; Dong, Xu; Liu, Kan; Liu, Zhu; Liu, Chao; He, Si-Min; Dong, Meng-Qiu; Tang, Chun

2017-01-27

Chemical cross-linking coupled with mass spectroscopy (CXMS) provides proximity information for the cross-linked residues and is used increasingly for modeling protein structures. However, experimentally identified cross-links are sometimes incompatible with the known structure of a protein, as the distance calculated between the cross-linked residues far exceeds the maximum length of the cross-linker. The discrepancies may persist even after eliminating potentially false cross-links and excluding intermolecular ones. Thus the "over-length" cross-links may arise from alternative excited-state conformation of the protein. Here we present a method and associated software DynaXL for visualizing the ensemble structures of multidomain proteins based on intramolecular cross-links identified by mass spectrometry with high confidence. Representing the cross-linkers and cross-linking reactions explicitly, we show that the protein excited-state structure can be modeled with as few as two over-length cross-links. We demonstrate the generality of our method with three systems: calmodulin, enzyme I, and glutamine-binding protein, and we show that these proteins alternate between different conformations for interacting with other proteins and ligands. Taken together, the over-length chemical cross-links contain valuable information about protein dynamics, and our findings here illustrate the relationship between dynamic domain movement and protein function. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Identifying potential impact of lead contamination using a geographic information system

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

Bocco, G.; Sanchez, R.

1997-01-01

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

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

PubMed

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

2018-04-30

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

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

PubMed

Horikoshi, Momoko; Yaghootkar, Hanieh; Mook-Kanamori, Dennis O; Sovio, Ulla; Taal, H Rob; Hennig, Branwen J; Bradfield, Jonathan P; St Pourcain, Beate; Evans, David M; Charoen, Pimphen; Kaakinen, Marika; Cousminer, Diana L; Lehtimäki, Terho; Kreiner-Møller, Eskil; Warrington, Nicole M; Bustamante, Mariona; Feenstra, Bjarke; Berry, Diane J; Thiering, Elisabeth; Pfab, Thiemo; Barton, Sheila J; Shields, Beverley M; Kerkhof, Marjan; van Leeuwen, Elisabeth M; Fulford, Anthony J; Kutalik, Zoltán; Zhao, Jing Hua; den Hoed, Marcel; Mahajan, Anubha; Lindi, Virpi; Goh, Liang-Kee; Hottenga, Jouke-Jan; Wu, Ying; Raitakari, Olli T; Harder, Marie N; Meirhaeghe, Aline; Ntalla, Ioanna; Salem, Rany M; Jameson, Karen A; Zhou, Kaixin; Monies, Dorota M; Lagou, Vasiliki; Kirin, Mirna; Heikkinen, Jani; Adair, Linda S; Alkuraya, Fowzan S; Al-Odaib, Ali; Amouyel, Philippe; Andersson, Ehm Astrid; Bennett, Amanda J; Blakemore, Alexandra I F; Buxton, Jessica L; Dallongeville, Jean; Das, Shikta; de Geus, Eco J C; Estivill, Xavier; Flexeder, Claudia; Froguel, Philippe; Geller, Frank; Godfrey, Keith M; Gottrand, Frédéric; Groves, Christopher J; Hansen, Torben; Hirschhorn, Joel N; Hofman, Albert; Hollegaard, Mads V; Hougaard, David M; Hyppönen, Elina; Inskip, Hazel M; Isaacs, Aaron; Jørgensen, Torben; Kanaka-Gantenbein, Christina; Kemp, John P; Kiess, Wieland; Kilpeläinen, Tuomas O; Klopp, Norman; Knight, Bridget A; Kuzawa, Christopher W; McMahon, George; Newnham, John P; Niinikoski, Harri; Oostra, Ben A; Pedersen, Louise; Postma, Dirkje S; Ring, Susan M; Rivadeneira, Fernando; Robertson, Neil R; Sebert, Sylvain; Simell, Olli; Slowinski, Torsten; Tiesler, Carla M T; Tönjes, Anke; Vaag, Allan; Viikari, Jorma S; Vink, Jacqueline M; Vissing, Nadja Hawwa; Wareham, Nicholas J; Willemsen, Gonneke; Witte, Daniel R; Zhang, Haitao; Zhao, Jianhua; Wilson, James F; Stumvoll, Michael; Prentice, Andrew M; Meyer, Brian F; Pearson, Ewan R; Boreham, Colin A G; Cooper, Cyrus; Gillman, Matthew W; Dedoussis, George V; Moreno, Luis A; Pedersen, Oluf; Saarinen, Maiju; Mohlke, Karen L; Boomsma, Dorret I; Saw, Seang-Mei; Lakka, Timo A; Körner, Antje; Loos, Ruth J F; Ong, Ken K; Vollenweider, Peter; van Duijn, Cornelia M; Koppelman, Gerard H; Hattersley, Andrew T; Holloway, John W; Hocher, Berthold; Heinrich, Joachim; Power, Chris; Melbye, Mads; Guxens, Mònica; Pennell, Craig E; Bønnelykke, Klaus; Bisgaard, Hans; Eriksson, Johan G; Widén, Elisabeth; Hakonarson, Hakon; Uitterlinden, André G; Pouta, Anneli; Lawlor, Debbie A; Smith, George Davey; Frayling, Timothy M; McCarthy, Mark I; Grant, Struan F A; Jaddoe, Vincent W V; Jarvelin, Marjo-Riitta; Timpson, Nicholas J; Prokopenko, Inga; Freathy, Rachel M

2013-01-01

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

PubMed Central

Horikoshi, Momoko; Yaghootkar, Hanieh; Mook-Kanamori, Dennis O.; Sovio, Ulla; Taal, H. Rob; Hennig, Branwen J.; Bradfield, Jonathan P.; St. Pourcain, Beate; Evans, David M.; Charoen, Pimphen; Kaakinen, Marika; Cousminer, Diana L.; Lehtimäki, Terho; Kreiner-Møller, Eskil; Warrington, Nicole M.; Bustamante, Mariona; Feenstra, Bjarke; Berry, Diane J.; Thiering, Elisabeth; Pfab, Thiemo; Barton, Sheila J.; Shields, Beverley M.; Kerkhof, Marjan; van Leeuwen, Elisabeth M.; Fulford, Anthony J.; Kutalik, Zoltán; Zhao, Jing Hua; den Hoed, Marcel; Mahajan, Anubha; Lindi, Virpi; Goh, Liang-Kee; Hottenga, Jouke-Jan; Wu, Ying; Raitakari, Olli T.; Harder, Marie N.; Meirhaeghe, Aline; Ntalla, Ioanna; Salem, Rany M.; Jameson, Karen A.; Zhou, Kaixin; Monies, Dorota M.; Lagou, Vasiliki; Kirin, Mirna; Heikkinen, Jani; Adair, Linda S.; Alkuraya, Fowzan S.; Al-Odaib, Ali; Amouyel, Philippe; Andersson, Ehm Astrid; Bennett, Amanda J.; Blakemore, Alexandra I.F.; Buxton, Jessica L.; Dallongeville, Jean; Das, Shikta; de Geus, Eco J. C.; Estivill, Xavier; Flexeder, Claudia; Froguel, Philippe; Geller, Frank; Godfrey, Keith M.; Gottrand, Frédéric; Groves, Christopher J.; Hansen, Torben; Hirschhorn, Joel N.; Hofman, Albert; Hollegaard, Mads V.; Hougaard, David M.; Hyppönen, Elina; Inskip, Hazel M.; Isaacs, Aaron; Jørgensen, Torben; Kanaka-Gantenbein, Christina; Kemp, John P.; Kiess, Wieland; Kilpeläinen, Tuomas O.; Klopp, Norman; Knight, Bridget A.; Kuzawa, Christopher W.; McMahon, George; Newnham, John P.; Niinikoski, Harri; Oostra, Ben A.; Pedersen, Louise; Postma, Dirkje S.; Ring, Susan M.; Rivadeneira, Fernando; Robertson, Neil R.; Sebert, Sylvain; Simell, Olli; Slowinski, Torsten; Tiesler, Carla M.T.; Tönjes, Anke; Vaag, Allan; Viikari, Jorma S.; Vink, Jacqueline M.; Vissing, Nadja Hawwa; Wareham, Nicholas J.; Willemsen, Gonneke; Witte, Daniel R.; Zhang, Haitao; Zhao, Jianhua; Wilson, James F.; Stumvoll, Michael; Prentice, Andrew M.; Meyer, Brian F.; Pearson, Ewan R.; Boreham, Colin A.G.; Cooper, Cyrus; Gillman, Matthew W.; Dedoussis, George V.; Moreno, Luis A; Pedersen, Oluf; Saarinen, Maiju; Mohlke, Karen L.; Boomsma, Dorret I.; Saw, Seang-Mei; Lakka, Timo A.; Körner, Antje; Loos, Ruth J.F.; Ong, Ken K.; Vollenweider, Peter; van Duijn, Cornelia M.; Koppelman, Gerard H.; Hattersley, Andrew T.; Holloway, John W.; Hocher, Berthold; Heinrich, Joachim; Power, Chris; Melbye, Mads; Guxens, Mònica; Pennell, Craig E.; Bønnelykke, Klaus; Bisgaard, Hans; Eriksson, Johan G.; Widén, Elisabeth; Hakonarson, Hakon; Uitterlinden, André G.; Pouta, Anneli; Lawlor, Debbie A.; Smith, George Davey; Frayling, Timothy M.; McCarthy, Mark I.; Grant, Struan F.A.; Jaddoe, Vincent W.V.; Jarvelin, Marjo-Riitta; Timpson, Nicholas J.; Prokopenko, Inga; Freathy, Rachel M.

2012-01-01

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood1. Previous genome-wide association studies identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes, and a second variant, near CCNL1, with no obvious link to adult traits2. In an expanded genome-wide association meta-analysis and follow-up study (up to 69,308 individuals of European descent from 43 studies), we have now extended the number of genome-wide significant loci to seven, accounting for a similar proportion of variance to maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes; ADRB1 with adult blood pressure; and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism. PMID:23202124

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

PubMed

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

2013-12-01

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

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

PubMed Central

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

2014-01-01

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

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

EPA Science Inventory

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

Identifying Potential Norovirus Epidemics in China via Internet Surveillance

PubMed Central

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

2017-01-01

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

The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.

PubMed

Christensen, G B; Knight, S; Camp, N J

2009-11-01

We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.

Walking the interactome to identify human miRNA-disease associations through the functional link between miRNA targets and disease genes

PubMed Central

2013-01-01

Background MicroRNAs (miRNAs) are important post-transcriptional regulators that have been demonstrated to play an important role in human diseases. Elucidating the associations between miRNAs and diseases at the systematic level will deepen our understanding of the molecular mechanisms of diseases. However, miRNA-disease associations identified by previous computational methods are far from completeness and more effort is needed. Results We developed a computational framework to identify miRNA-disease associations by performing random walk analysis, and focused on the functional link between miRNA targets and disease genes in protein-protein interaction (PPI) networks. Furthermore, a bipartite miRNA-disease network was constructed, from which several miRNA-disease co-regulated modules were identified by hierarchical clustering analysis. Our approach achieved satisfactory performance in identifying known cancer-related miRNAs for nine human cancers with an area under the ROC curve (AUC) ranging from 71.3% to 91.3%. By systematically analyzing the global properties of the miRNA-disease network, we found that only a small number of miRNAs regulated genes involved in various diseases, genes associated with neurological diseases were preferentially regulated by miRNAs and some immunological diseases were associated with several specific miRNAs. We also observed that most diseases in the same co-regulated module tended to belong to the same disease category, indicating that these diseases might share similar miRNA regulatory mechanisms. Conclusions In this study, we present a computational framework to identify miRNA-disease associations, and further construct a bipartite miRNA-disease network for systematically analyzing the global properties of miRNA regulation of disease genes. Our findings provide a broad perspective on the relationships between miRNAs and diseases and could potentially aid future research efforts concerning miRNA involvement in disease pathogenesis

Connecting the Dots: Linking Environmental Justice Indicators to Daily Dose Model Estimates

EPA Science Inventory

Many different quantitative techniques have been developed to either assess Environmental Justice (EJ) issues or estimate exposure and dose for risk assessment. However, very few approaches have been applied to link EJ factors to exposure dose estimate and identify potential impa...

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

PubMed

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

2016-06-16

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

SASH1, a new potential link between smoking and atherosclerosis.

PubMed

Weidmann, Henri; Touat-Hamici, Zahia; Durand, Herve; Mueller, Christian; Chardonnet, Solenne; Pionneau, Cedric; Charlotte, Frédéric; Janssen, Klaus-Peter; Verdugo, Ricardo; Cambien, Francois; Blankenberg, Stefan; Tiret, Laurence; Zeller, Tanja; Ninio, Ewa

2015-10-01

We have previously reported that SASH1 expression is increased in circulating human monocytes from smokers and was positively correlated with the number of carotid atherosclerotic plaques. The aim of this study was to further validate the link between smoking, SASH1 and atherosclerosis within the vascular wall and to assess the impact of SASH1 expression on endothelial cell functions. Human carotids with atherosclerotic plaques were obtained from 58 patients (45 of them with known smoking status: smoker, non-smoker, ex-smokers), and were processed for gene expression analyses and immunostaining. To investigate its function, SASH1 was silenced in human aortic endothelial cells (HAECs) using two different siRNA and subcellular localization of SASH1 was determined by immunostaining and subcellular fractionation. Subsequently the transcriptomic analyses and functional experiments (wound healing, WST-1 proliferation or Matrigel assays) were performed to characterize SASH1 function. SASH1 was expressed in human vascular cells (HAECs, smooth muscle cells) and in monocytes/macrophages. Its tissue expression was significantly higher in the atherosclerotic carotids of smokers compared to non-smokers (p < 0.01). In HAECs, SASH1 was expressed mostly in the cytoplasm and SASH1 knockdown resulted in an increased cell migration, proliferation and angiogenesis. Transcriptomic and pathway analyses showed that SASH1 silencing results in a decreased CYP1A1 expression possibly through the inhibition of TP53 activity. We showed that SASH1 expression is increased in atherosclerotic carotids in smokers and its silencing affects endothelial angiogenic functions; therefore we provide a potential link between smoking and atherosclerosis through SASH1 expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Modified Cross-Linking, Ligation, and Sequencing of Hybrids (qCLASH) Identifies Kaposi's Sarcoma-Associated Herpesvirus MicroRNA Targets in Endothelial Cells.

PubMed

Gay, Lauren A; Sethuraman, Sunantha; Thomas, Merin; Turner, Peter C; Renne, Rolf

2018-04-15

Kaposi's sarcoma (KS) tumors are derived from endothelial cells and express Kaposi's sarcoma-associated herpesvirus (KSHV) microRNAs (miRNAs). Although miRNA targets have been identified in B cell lymphoma-derived cells and epithelial cells, little has been done to characterize the KSHV miRNA targetome in endothelial cells. A recent innovation in the identification of miRNA targetomes, cross-linking, ligation, and sequencing of hybrids (CLASH), unambiguously identifies miRNAs and their targets by ligating the two species while both species are still bound within the RNA-induced silencing complex (RISC). We developed a streamlined quick CLASH (qCLASH) protocol that requires a lower cell input than the original method and therefore has the potential to be used on patient biopsy samples. Additionally, we developed a fast-growing, KSHV-negative endothelial cell line derived from telomerase-immortalized vein endothelial long-term culture (TIVE-LTC) cells. qCLASH was performed on uninfected cells and cells infected with either wild-type KSHV or a mutant virus lacking miR-K12-11/11*. More than 1,400 cellular targets of KSHV miRNAs were identified. Many of the targets identified by qCLASH lacked a canonical seed sequence match. Additionally, most target regions in mRNAs originated from the coding DNA sequence (CDS) rather than the 3' untranslated region (UTR). This set of genes includes some that were previously identified in B cells and some new genes that warrant further study. Pathway analysis of endothelial cell targets showed enrichment in cell cycle control, apoptosis, and glycolysis pathways, among others. Characterization of these new targets and the functional consequences of their repression will be important in furthering our understanding of the role of KSHV miRNAs in oncogenesis. IMPORTANCE KS lesions consist of endothelial cells latently infected with KSHV. Cells that make up these lesions express KSHV miRNAs. Identification of the targets of KSHV miRNAs will

Flour mill stream blending affects sugar snap cookie and Japanese sponge cake quality and oxidative cross-linking potential of soft white wheat.

PubMed

Ramseyer, Daniel D; Bettge, Arthur D; Morris, Craig F

2011-01-01

The purpose of this research was to study the functional differences between straight grade (75% extraction rate) and patent (60% extraction rate) flour blends from 28 genetically pure soft white and club wheat grain lots, as evidenced by variation in sugar snap cookie and Japanese sponge cake quality. Functional differences were examined relative to arabinoxylan content, protein content, and oxidative cross-linking potential of flour slurries. Oxidative cross-linking measurements were obtained on flour slurries with a low shear Bostwick consistometer and considered endogenous oxidative cross-linking potential (water alone) or enhanced oxidative cross-linking potential (with added hydrogen peroxide-peroxidase). A 2-way ANOVA indicated that flour blend was the greater source of variation compared to grain lot for all response variables except water-extractable arabinoxylan content. Patent flours produced larger sugar snap cookies and Japanese sponge cakes, and contained significantly less total and water-unextractable arabinoxylans, protein, and ash than did straight grade flours. Patent flours produced more viscous slurries for endogenous and enhanced cross-linking measurements compared to the straight grade flours. The functional differences between patent and straight grade flours appear to be related to the particular mill streams that were utilized in the formulation of the 2 flour blends and compositional differences among those streams. Journal of Food Science © 2011 Institute of Food Technologists® No claim to original US government works.

Identifying High Academic Potential in Australian Aboriginal Children Using Dynamic Testing

ERIC Educational Resources Information Center

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

2015-01-01

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

On the link between martian total ozone and potential vorticity

NASA Astrophysics Data System (ADS)

Holmes, James A.; Lewis, Stephen R.; Patel, Manish R.

2017-01-01

We demonstrate for the first time that total ozone in the martian atmosphere is highly correlated with the dynamical tracer, potential vorticity, under certain conditions. The degree of correlation is investigated using a Mars global circulation model including a photochemical model. Potential vorticity is the quantity of choice to explore the dynamical nature of polar vortices because it contains information on winds and temperature in a single scalar variable. The correlation is found to display a distinct seasonal variation, with a strong positive correlation in both northern and southern winter at poleward latitudes in the northern and southern hemisphere respectively. The identified strong correlation implies variations in polar total ozone during winter are predominantly controlled by dynamical processes in these spatio-temporal regions. The weak correlation in northern and southern summer is due to the dominance of photochemical reactions resulting from extended exposure to sunlight. The total ozone/potential vorticity correlation is slightly weaker in southern winter due to topographical variations and the preference for ozone to accumulate in Hellas basin. In northern winter, total ozone can be used to track the polar vortex edge. The ozone/potential vorticity ratio is calculated for both northern and southern winter on Mars for the first time. Using the strong correlation in total ozone and potential vorticity in northern winter inside the polar vortex, it is shown that potential vorticity can be used as a proxy to deduce the distribution of total ozone where satellites cannot observe for the majority of northern winter. Where total ozone observations are available on the fringes of northern winter at poleward latitudes, the strong relationship of total ozone and potential vorticity implies that total ozone anomalies in the surf zone of the northern polar vortex can potentially be used to determine the origin of potential vorticity filaments.

Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

DTIC Science & Technology

2015-04-01

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

Genome Comparison of Human and Non-Human Malaria Parasites Reveals Species Subset-Specific Genes Potentially Linked to Human Disease

PubMed Central

Frech, Christian; Chen, Nansheng

2011-01-01

Genes underlying important phenotypic differences between Plasmodium species, the causative agents of malaria, are frequently found in only a subset of species and cluster at dynamically evolving subtelomeric regions of chromosomes. We hypothesized that chromosome-internal regions of Plasmodium genomes harbour additional species subset-specific genes that underlie differences in human pathogenicity, human-to-human transmissibility, and human virulence. We combined sequence similarity searches with synteny block analyses to identify species subset-specific genes in chromosome-internal regions of six published Plasmodium genomes, including Plasmodium falciparum, Plasmodium vivax, Plasmodium knowlesi, Plasmodium yoelii, Plasmodium berghei, and Plasmodium chabaudi. To improve comparative analysis, we first revised incorrectly annotated gene models using homology-based gene finders and examined putative subset-specific genes within syntenic contexts. Confirmed subset-specific genes were then analyzed for their role in biological pathways and examined for molecular functions using publicly available databases. We identified 16 genes that are well conserved in the three primate parasites but not found in rodent parasites, including three key enzymes of the thiamine (vitamin B1) biosynthesis pathway. Thirteen genes were found to be present in both human parasites but absent in the monkey parasite P. knowlesi, including genes specifically upregulated in sporozoites or gametocytes that could be linked to parasite transmission success between humans. Furthermore, we propose 15 chromosome-internal P. falciparum-specific genes as new candidate genes underlying increased human virulence and detected a currently uncharacterized cluster of P. vivax-specific genes on chromosome 6 likely involved in erythrocyte invasion. In conclusion, Plasmodium species harbour many chromosome-internal differences in the form of protein-coding genes, some of which are potentially linked to human

Genome-wide association study of serum coenzyme Q10 levels identifies susceptibility loci linked to neuronal diseases.

PubMed

Degenhardt, Frauke; Niklowitz, Petra; Szymczak, Silke; Jacobs, Gunnar; Lieb, Wolfgang; Menke, Thomas; Laudes, Matthias; Esko, Tõnu; Weidinger, Stephan; Franke, Andre; Döring, Frank; Onur, Simone

2016-07-01

Coenzyme Q 10 (CoQ 10 ) is a lipophilic redox molecule that is present in membranes of almost all cells in human tissues. CoQ 10 is, amongst other functions, essential for the respiratory transport chain and is a modulator of inflammatory processes and gene expression. Rare monogenetic CoQ 10 deficiencies show noticeable symptoms in tissues (e.g. kidney) and cell types (e.g. neurons) with a high energy demand. To identify common genetic variants influencing serum CoQ 10 levels, we performed a fixed effects meta-analysis in two independent cross-sectional Northern German cohorts comprising 1300 individuals in total. We identified two genome-wide significant susceptibility loci. The best associated single nucleotide polymorphism (SNP) was rs9952641 (P value = 1.31 × 10 - 8 , β = 0.063, CI 0.95 [0.041, 0.085]) within the COLEC12 gene on chromosome 18. The SNP rs933585 within the NRXN-1 gene on chromosome 2 also showed genome wide significance (P value = 3.64 × 10 - 8 , β = -0.034, CI 0.95 [-0.046, -0.022]). Both genes have been previously linked to neuronal diseases like Alzheimer's disease, autism and schizophrenia. Among our 'top-10' associated variants, four additional loci with known neuronal connections showed suggestive associations with CoQ 10 levels. In summary, this study demonstrates that serum CoQ 10 levels are associated with common genetic loci that are linked to neuronal diseases. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Epidemiological links between tuberculosis cases identified twice as efficiently by whole genome sequencing than conventional molecular typing: A population-based study.

PubMed

Jajou, Rana; de Neeling, Albert; van Hunen, Rianne; de Vries, Gerard; Schimmel, Henrieke; Mulder, Arnout; Anthony, Richard; van der Hoek, Wim; van Soolingen, Dick

2018-01-01

Patients with Mycobacterium tuberculosis isolates sharing identical DNA fingerprint patterns can be epidemiologically linked. However, municipal health services in the Netherlands are able to confirm an epidemiological link in only around 23% of the patients with isolates clustered by the conventional variable number of tandem repeat (VNTR) genotyping. This research aims to investigate whether whole genome sequencing (WGS) is a more reliable predictor of epidemiological links between tuberculosis patients than VNTR genotyping. VNTR genotyping and WGS were performed in parallel on all Mycobacterium tuberculosis complex isolates received at the Netherlands National Institute for Public Health and the Environment in 2016. Isolates were clustered by VNTR when they shared identical 24-loci VNTR patterns; isolates were assigned to a WGS cluster when the pair-wise genetic distance was ≤ 12 single nucleotide polymorphisms (SNPs). Cluster investigation was performed by municipal health services on all isolates clustered by VNTR in 2016. The proportion of epidemiological links identified among patients clustered by either method was calculated. In total, 535 isolates were genotyped, of which 25% (134/535) were clustered by VNTR and 14% (76/535) by WGS; the concordance between both typing methods was 86%. The proportion of epidemiological links among WGS clustered cases (57%) was twice as common than among VNTR clustered cases (31%). When WGS was applied, the number of clustered isolates was halved, while all epidemiologically linked cases remained clustered. WGS is therefore a more reliable tool to predict epidemiological links between tuberculosis cases than VNTR genotyping and will allow more efficient transmission tracing, as epidemiological investigations based on false clustering can be avoided.

On the link between martian total ozone and potential vorticity

NASA Astrophysics Data System (ADS)

Lewis, S.; Holmes, J.; Patel, M.

2016-12-01

We demonstrate for the first time that total ozone in the martian atmosphere is highly correlated with the dynamical tracer, potential vorticity, under certain conditions. The degree of correlation is investigated using a Mars global circulation model including a photochemical model. Potential vorticity is the quantity of choice to explore the dynamical nature of polar vortices because it contains information on winds and temperature in a single scalar variable.The correlation is found to display a distinct seasonal variation, with a strong positive correlation in both northern and southern winter at poleward latitudes in the northern and southern hemisphere respectively. The identified strong correlation implies variations in polar total ozone during winter are predominantly controlled by dynamical processes in these spatio-temporal regions. The weak correlation in northern and southern summer is due to the dominance of photochemical reactions resulting from extended exposure to sunlight. The total ozone/potential vorticity correlation is slightly weaker in southern winter due to topographical variations and the preference for ozone to accumulate in Hellas basin. In northern winter, total ozone can be used to track the polar vortex edge. The ozone/potential vorticity ratio is calculated for both northern and southern winter on Mars for the first time. Using the strong correlation in total ozone and potential vorticity in northern winter inside the polar vortex, it is shown that potential vorticity can be used as a proxy to deduce the distribution of total ozone where satellites cannot observe for the majority of northern winter. Where total ozone observations are available on the fringes of northern winter at poleward latitudes, the strong relationship of total ozone and potential vorticity implies that total ozone anomalies in the surf zone can be of use to investigate the origin of potential vorticity filaments.

Recycling potential for low voltage and high voltage high rupturing capacity fuse links.

PubMed

Psomopoulos, Constantinos S; Barkas, Dimitrios A; Kaminaris, Stavros D; Ioannidis, George C; Karagiannopoulos, Panagiotis

2017-12-01

Low voltage and high voltage high-rupturing-capacity fuse links are used in LV and HV installations respectively, protecting mainly the LV and HV electricity distribution and transportation networks. The Waste Electrical and Electronic Equipment Directive (2002/96/EC) for "Waste of electrical and electronic equipment" is the main related legislation and as it concerns electrical and electronic equipment, it includes electric fuses. Although, the fuse links consist of recyclable materials, only small scale actions have been implemented for their recycling around Europe. This work presents the possibilities for material recovery from this specialized industrial waste for which there are only limited volume data. Furthermore, in order to present the huge possibilities and environmental benefits, it presents the potential for recycling of HRC fuses used by the Public Power Corporation of Greece, which is the major consumer for the country, but one of the smallest ones in Europe and globally, emphasizing in this way in the issue. According to the obtained results, fuse recycling could contribute to the effort for minimize the impacts on the environment through materials recovery and reduction of the wastes' volume disposed of in landfills. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comprehensive comparison of network similarities for link prediction and spurious link elimination

NASA Astrophysics Data System (ADS)

Zhang, Peng; Qiu, Dan; Zeng, An; Xiao, Jinghua

2018-06-01

Identifying missing interactions in complex networks, known as link prediction, is realized by estimating the likelihood of the existence of a link between two nodes according to the observed links and nodes' attributes. Similar approaches have also been employed to identify and remove spurious links in networks which is crucial for improving the reliability of network data. In network science, the likelihood for two nodes having a connection strongly depends on their structural similarity. The key to address these two problems thus becomes how to objectively measure the similarity between nodes in networks. In the literature, numerous network similarity metrics have been proposed and their accuracy has been discussed independently in previous works. In this paper, we systematically compare the accuracy of 18 similarity metrics in both link prediction and spurious link elimination when the observed networks are very sparse or consist of inaccurate linking information. Interestingly, some methods have high prediction accuracy, they tend to perform low accuracy in identification spurious interaction. We further find that methods can be classified into several cluster according to their behaviors. This work is useful for guiding future use of these similarity metrics for different purposes.

Light-induced cross-linking and post-cross-linking modification of polyglycidol.

PubMed

Marquardt, F; Bruns, M; Keul, H; Yagci, Y; Möller, M

2018-02-08

The photoinduced radical generation process has received renewed interest due to its economic and ecological appeal. Herein the light-induced cross-linking of functional polyglycidol and its post-cross-linking modification are presented. Linear polyglycidol was first functionalized with a tertiary amine in a two-step reaction. Dimethylaminopropyl functional polyglycidol was cross-linked in a UV-light mediated reaction with camphorquinone as a type II photoinitiator. The cross-linked polyglycidol was further functionalized by quaternization with various organoiodine compounds. Aqueous dispersions of the cross-linked polymers were investigated by means of DLS and zeta potential measurements. Polymer films were evaluated by DSC and XPS.

Age differences in search of web pages: the effects of link size, link number, and clutter.

PubMed

Grahame, Michael; Laberge, Jason; Scialfa, Charles T

2004-01-01

Reaction time, eye movements, and errors were measured during visual search of Web pages to determine age-related differences in performance as a function of link size, link number, link location, and clutter. Participants (15 young adults, M = 23 years; 14 older adults, M = 57 years) searched Web pages for target links that varied from trial to trial. During one half of the trials, links were enlarged from 10-point to 12-point font. Target location was distributed among the left, center, and bottom portions of the screen. Clutter was manipulated according to the percentage of used space, including graphics and text, and the number of potentially distracting nontarget links was varied. Increased link size improved performance, whereas increased clutter and links hampered search, especially for older adults. Results also showed that links located in the left region of the page were found most easily. Actual or potential applications of this research include Web site design to increase usability, particularly for older adults.

An automated, fast and accurate registration method to link stranded seeds in permanent prostate implants

NASA Astrophysics Data System (ADS)

Westendorp, Hendrik; Nuver, Tonnis T.; Moerland, Marinus A.; Minken, André W.

2015-10-01

The geometry of a permanent prostate implant varies over time. Seeds can migrate and edema of the prostate affects the position of seeds. Seed movements directly influence dosimetry which relates to treatment quality. We present a method that tracks all individual seeds over time allowing quantification of seed movements. This linking procedure was tested on transrectal ultrasound (TRUS) and cone-beam CT (CBCT) datasets of 699 patients. These datasets were acquired intraoperatively during a dynamic implantation procedure, that combines both imaging modalities. The procedure was subdivided in four automatic linking steps. (I) The Hungarian Algorithm was applied to initially link seeds in CBCT and the corresponding TRUS datasets. (II) Strands were identified and optimized based on curvature and linefits: non optimal links were removed. (III) The positions of unlinked seeds were reviewed and were linked to incomplete strands if within curvature- and distance-thresholds. (IV) Finally, seeds close to strands were linked, also if the curvature-threshold was violated. After linking the seeds an affine transformation was applied. The procedure was repeated until the results were stable or the 6th iteration ended. All results were visually reviewed for mismatches and uncertainties. Eleven implants showed a mismatch and in 12 cases an uncertainty was identified. On average the linking procedure took 42 ms per case. This accurate and fast method has the potential to be used for other time spans, like Day 30, and other imaging modalities. It can potentially be used during a dynamic implantation procedure to faster and better evaluate the quality of the permanent prostate implant.

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

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

Nelson, W.R.

1997-10-01

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

Use of Persistent Identifiers to link Heterogeneous Data Systems in the Integrated Earth Data Applications (IEDA) Facility

NASA Astrophysics Data System (ADS)

Hsu, L.; Lehnert, K. A.; Carbotte, S. M.; Arko, R. A.; Ferrini, V.; O'hara, S. H.; Walker, J. D.

2012-12-01

for a GeoPass account ID, write a proposal to NSF and create a data plan using the IEDA Data Management Plan Tool. Having received the grant, the investigator then collects rock samples on a scientific cruise from dredges and registers the samples with IGSNs. The investigator then performs analytical geochemistry on the samples, and submits the full dataset to the Geochemical Resource Library for a dataset DOI. Finally, the investigator writes an article that is published in Science Direct. Knowing any of the following IDs: Investigator GeoPass ID, NSF Award Number, Cruise ID, Sample IGSNs, dataset DOI, or publication DOI, a user would be able to navigate to all samples, datasets, and publications in IEDA and external systems. Use of persistent identifiers to link heterogeneous data systems in IEDA thus increases access, discovery, and proper citation of hard-earned investigator datasets.

SPARQL-enabled identifier conversion with Identifiers.org

PubMed Central

Wimalaratne, Sarala M.; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

2015-01-01

Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: sarala@ebi.ac.uk PMID:25638809

SPARQL-enabled identifier conversion with Identifiers.org.

PubMed

Wimalaratne, Sarala M; Bolleman, Jerven; Juty, Nick; Katayama, Toshiaki; Dumontier, Michel; Redaschi, Nicole; Le Novère, Nicolas; Hermjakob, Henning; Laibe, Camille

2015-06-01

On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. © The Author 2015. Published by Oxford University Press.

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

PubMed

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

2008-12-01

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

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

EPA Science Inventory

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

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

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

NONE

2016-06-15

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

Identifying Links Between Sexual Violence and Youth Violence Perpetration: New Opportunities for Sexual Violence Prevention

PubMed Central

DeGue, Sarah; Massetti, Greta M.; Holt, Melissa K.; Tharp, Andra Teten; Valle, Linda Anne; Matjasko, Jennifer L.; Lippy, Caroline

2018-01-01

Objective One promising opportunity for advancing sexual violence (SV) research and identifying new avenues for prevention involves examining other forms of violence that may share risk factors with SV. Youth violence (YV) is ideal for consideration given evidence of overlap in SV and YV risk factors, a large set of established YV risk factors across the social ecology, and the number of evidence-based YV prevention strategies available. The current paper identifies shared and unique risk factors for SV and YV and highlights evidence-based YV prevention strategies that impact these shared risk factors. Conclusions Researchers and program developers should consider adapting and evaluating evidence-based YV prevention strategies to prevent SV. Modifying these programs to address SV’s unique risk factors may maximize their potential effectiveness. In addition, expanding SV research at the outer levels of the social ecology is critical to developing community-level prevention strategies. The YV literature suggests several potential risk factors at these levels in need of research for SV, including school connectedness, social disorganization, and availability of alcohol and drugs. Using the YV literature as a starting point for expanding SV research leverages prior investments in YV research, may help identify new SV prevention strategies at a limited cost, and moves the field more quickly toward implementation of cost-effective, multidomain violence prevention strategies in communities. PMID:29644117

Green synthesis and anticancer potential of chalcone linked-1,2,3-triazoles.

PubMed

Yadav, Pinki; Lal, Kashmiri; Kumar, Ashwani; Guru, Santosh Kumar; Jaglan, Sundeep; Bhushan, Shashi

2017-01-27

A series of chalcone linked-1,2,3-triazoles was synthesized via cellulose supported copper nanoparticle catalyzed click reaction in water. The structures of all the compounds were analyzed by IR, NMR and Mass spectral techniques. All the synthesized products were subjected to 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay against a panel of four human cancer cell lines (MCF-7, MIA-Pa-Ca-2, A549, HepG2) to check their anticancer potential. Compound 6h was found to be most active against all the tested cancer cell lines with IC 50 values in the range of 4-11 μM and showed better or comparable activity to the reference drug against all the tested cell lines. Cell cycle analysis revealed that compound 6h induces apoptosis and G2/S arrest in MIA-Pa-Ca-2 cells. Compound 6h triggers mitochondrial potential loss in pancreatic cancer MIA-Pa-Ca-2 cells. Further, Compound 6h also triggers caspase-3 and PARP-1 cleavage, which increases in dose dependent manner. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

ERIC Educational Resources Information Center

Suárez Flórez, Sergio Andrés; Basto Basto, Edwin Arley

2017-01-01

This study aims at identifying pre-service teachers' beliefs about teaching English as a foreign language and tracking their potential changes throughout the teaching practicum. Participants were two pre-service teachers in their fifth year of their Bachelor of Arts in Foreign Languages program in a public university in Colombia. Data were…

Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases

PubMed Central

Lundmark, Anna; Davanian, Haleh; Båge, Tove; Johannsen, Gunnar; Koro, Catalin; Lundeberg, Joakim; Yucel-Lindberg, Tülay

2015-01-01

The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID:26686060

Designing cross-linked xylanase aggregates for bioconversion of agroindustrial waste biomass towards potential production of nutraceuticals.

PubMed

Hero, J S; Romero, C M; Pisa, J H; Perotti, N I; Olivaro, C; Martinez, M A

2018-05-01

Immobilized biocatalysts design has the potential to efficiently produce valuable bioproducts from lignocellulosic biomass. Among them, the carrier-free immobilization through the cross-linked enzyme aggregates technology is a simple and low-cost alternative. A two steps statistical approach was utilized to evaluate the synthesis of a cross-linked enzyme aggregate from a xylanolytic preparation, which was produced by Cohnella sp. AR92 grown in a peptone-based culture medium. The resulting immobilized biocatalyst, Xyl-CLEA, was significate more stable (25 to 45%) towards temperatures up to 50°C with respect to the free enzyme, and retained over 50% of its initial activity after 5 consecutive cycles of reuse. By means of infrared spectroscopy and electron microscopy, the Xyl-CLEA showed architectural features described as signature of type I and type II of protein aggregates. These, were the result of the simultaneous aggregation of a multiplicity of proteins from the crude enzymatic extract. The enzymatic activity was assessed using alkali pretreated sugar cane bagasse as substrate. Whereas the free enzymatic preparation released xylose as the main product, the immobilized xylanase produced xylooligosaccharides, thus showing that the immobilization procedure modified the potential application of the extracellular xylanase from Conhella sp. AR92. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-11-25

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

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

PubMed Central

2013-01-01

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

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

PubMed Central

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

2014-01-01

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

Proteomic Analysis of Saliva Identifies Potential Biomarkers for Orthodontic Tooth Movement

PubMed Central

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

2012-01-01

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

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

PubMed

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

2011-08-01

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

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

PubMed

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

2013-10-01

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

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

Code of Federal Regulations, 2010 CFR

2010-07-01

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

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

USGS Publications Warehouse

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

2014-01-01

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

Linking Antimicrobial Potential of Natural Products Derived from Aquatic Organisms and Microbes Involved in Alzheimer's Disease - A Review.

PubMed

Stojkovic, Dejan; Kostic, Marina; Smiljkovic, Marija; Aleksic, Milena; Vasiljevic, Perica; Nikolic, Milos; Sokovic, Marina

2018-03-08

The following review is oriented towards microbes linked to Alzheimer's disease (AD) and antimicrobial effect of compounds and extracts derived from aquatic organisms against specific bacteria, fungi and viruses which were found previously in patients suffering from AD. Major group of microbes linked to AD include bacteria: Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Actinomyces naeslundii, spirochete group; fungi: Candida sp., Cryptococcus sp., Saccharomyces sp., Malassezia sp., Botrytis sp., and viruses: herpes simplex virus type 1 (HSV-1), Human cytomegalovirus (CMV), hepatitis C virus (HCV). In the light of that fact, this review is the first to link antimicrobial potential of aquatic organisms against these sorts of microbes. This literature review might serve as a starting platform to develop novel supportive therapy for patients suffering from AD and to possibly prevent escalation of the disease in patients already having high risk factors for AD occurrence. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enrichment of Cross-Linked Peptides Using Charge-Based Fractional Diagonal Chromatography (ChaFRADIC).

PubMed

Tinnefeld, Verena; Venne, A Saskia; Sickmann, Albert; Zahedi, René P

2017-02-03

Chemical cross-linking of proteins is an emerging field with huge potential for the structural investigation of proteins and protein complexes. Owing to the often relatively low yield of cross-linking products, their identification in complex samples benefits from enrichment procedures prior to mass spectrometry analysis. So far, this is mainly accomplished by using biotin moieties in specific cross-linkers or by applying strong cation exchange chromatography (SCX) for a relatively crude enrichment. We present a novel workflow to enrich cross-linked peptides by utilizing charge-based fractional diagonal chromatography (ChaFRADIC). On the basis of two-dimensional diagonal SCX separation, we could increase the number of identified cross-linked peptides for samples of different complexity: pure cross-linked BSA, cross-linked BSA spiked into a simple protein mixture, and cross-linked BSA spiked into a HeLa lysate. We also compared XL-ChaFRADIC with size exclusion chromatography-based enrichment of cross-linked peptides. The XL-ChaFRADIC approach is straightforward, reproducible, and independent of the cross-linking chemistry and cross-linker properties.

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

PubMed

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

2018-04-01

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

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

PubMed Central

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

2018-01-01

Pteropus poliocephalus (grey-headed flying foxes) are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%), Pasteurellaceae (19.9% ± 25.7%) and Moraxellaceae (9.4% ± 11.8%) dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals. PMID:29360880

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

Cancer.gov

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

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

PubMed Central

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

2015-01-01

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

Photouncaged Sequence-specific Interstrand DNA Cross-Linking with Photolabile 4-oxo-enal-modified Oligonucleotides

PubMed Central

Sun, Jingjing; Tang, Xinjing

2015-01-01

DNA cross-linking technology is an attractive tool for the detection, regulation, and manipulation of genes. In this study, a series of photolabile 4-oxo-enal-modified oligonucleotides functionalized with photosensitive ο-nitrobenzyl derivatives were rationally designed as a new kind of photocaged cross-linking agents. A comprehensive evaluation of cross-linking reactions for different nucleobases in complementary strands under different conditions suggested that the modified DNA oligonucleotides tended to form interstrand cross-linking to nucleobases with the potential of thymidine > guanosine » cytidine ~ adenosine. Different from previous literature reports that cytidine and adenosine were preferential cross-linked nucleobases with 4-oxo-enal moieties, our study represents the first example of DNA cross-linking for T and G selectivity using 4-oxo-enal moiety. The cross-linked adducts were identified and their cross-linking mechanism was also illustrated. This greatly expands the applications of 4-oxo-enal derivatives in the studies of DNA damage and RNA structure PMID:26020694

Photouncaged Sequence-specific Interstrand DNA Cross-Linking with Photolabile 4-oxo-enal-modified Oligonucleotides.

PubMed

Sun, Jingjing; Tang, Xinjing

2015-05-28

DNA cross-linking technology is an attractive tool for the detection, regulation, and manipulation of genes. In this study, a series of photolabile 4-oxo-enal-modified oligonucleotides functionalized with photosensitive ο-nitrobenzyl derivatives were rationally designed as a new kind of photocaged cross-linking agents. A comprehensive evaluation of cross-linking reactions for different nucleobases in complementary strands under different conditions suggested that the modified DNA oligonucleotides tended to form interstrand cross-linking to nucleobases with the potential of thymidine > guanosine » cytidine ~ adenosine. Different from previous literature reports that cytidine and adenosine were preferential cross-linked nucleobases with 4-oxo-enal moieties, our study represents the first example of DNA cross-linking for T and G selectivity using 4-oxo-enal moiety. The cross-linked adducts were identified and their cross-linking mechanism was also illustrated. This greatly expands the applications of 4-oxo-enal derivatives in the studies of DNA damage and RNA structure.

Functional analysis of the Helicobacter pullorum N-linked protein glycosylation system.

PubMed

Jervis, Adrian J; Wood, Alison G; Cain, Joel A; Butler, Jonathan A; Frost, Helen; Lord, Elizabeth; Langdon, Rebecca; Cordwell, Stuart J; Wren, Brendan W; Linton, Dennis

2018-04-01

N-linked protein glycosylation systems operate in species from all three domains of life. The model bacterial N-linked glycosylation system from Campylobacter jejuni is encoded by pgl genes present at a single chromosomal locus. This gene cluster includes the pglB oligosaccharyltransferase responsible for transfer of glycan from lipid carrier to protein. Although all genomes from species of the Campylobacter genus contain a pgl locus, among the related Helicobacter genus only three evolutionarily related species (H. pullorum, H. canadensis and H. winghamensis) potentially encode N-linked protein glycosylation systems. Helicobacter putative pgl genes are scattered in five chromosomal loci and include two putative oligosaccharyltransferase-encoding pglB genes per genome. We have previously demonstrated the in vitro N-linked glycosylation activity of H. pullorum resulting in transfer of a pentasaccharide to a peptide at asparagine within the sequon (D/E)XNXS/T. In this study, we identified the first H. pullorum N-linked glycoprotein, termed HgpA. Production of histidine-tagged HgpA in the background of insertional knockout mutants of H. pullorum pgl/wbp genes followed by analysis of HgpA glycan structures demonstrated the role of individual gene products in the PglB1-dependent N-linked protein glycosylation pathway. Glycopeptide purification by zwitterionic-hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry identified six glycosites from five H. pullorum proteins, which was consistent with proteins reactive with a polyclonal antiserum generated against glycosylated HgpA. This study demonstrates functioning of a H. pullorum N-linked general protein glycosylation system.

A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

PubMed Central

Jiang, Peng; Scarpa, Joseph R.; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D.; Hao, Ke; Summa, Keith C.; Yang, He S.; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H.; Turek, Fred W.; Kasarskis, Andrew

2016-01-01

SUMMARY Sleep dysfunction and stress susceptibility are co-morbid complex traits, which often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multi-level organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J×A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests the interplay between sleep, stress, and neuropathology emerge from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework to interrogate the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. PMID:25921536

Potential Links between Hepadnavirus and Bornavirus Sequences in the Host Genome and Cancer.

PubMed

Honda, Tomoyuki

2017-01-01

Various viruses leave their sequences in the host genomes during infection. Such events occur mainly in retrovirus infection but also sometimes in DNA and non-retroviral RNA virus infections. If viral sequences are integrated into the genomes of germ line cells, the sequences can become inherited as endogenous viral elements (EVEs). The integration events of viral sequences may have oncogenic potential. Because proviral integrations of some retroviruses and/or reactivation of endogenous retroviruses are closely linked to cancers, viral insertions related to non-retroviral viruses also possibly contribute to cancer development. This article focuses on genomic viral sequences derived from two non-retroviral viruses, whose endogenization is already reported, and discusses their possible contributions to cancer. Viral insertions of hepatitis B virus play roles in the development of hepatocellular carcinoma. Endogenous bornavirus-like elements, the only non-retroviral RNA virus-related EVEs found in the human genome, may also be involved in cancer formation. In addition, the possible contribution of the interactions between viruses and retrotransposons, which seem to be a major driving force for generating EVEs related to non-retroviral RNA viruses, to cancers will be discussed. Future studies regarding the possible links described here may open a new avenue for the development of novel therapeutics for tumor virus-related cancers and/or provide novel insights into EVE functions.

Focused glycomic analysis of the N-linked glycan biosynthetic pathway in ovarian cancer

PubMed Central

Abbott, Karen L.; Nairn, Alison V.; Hall, Erica M.; Horton, Marc B.; McDonald, John F.; Moremen, Kelley W.; Dinulescu, Daniela M.; Pierce, Michael

2014-01-01

Epithelial ovarian cancer is the deadliest female reproductive tract malignancy in Western countries. Less than 25% of cases are diagnosed when the cancer is confined, however, pointing to the critical need for early diagnostics for ovarian cancer. Identifying the changes that occur in the glycome of ovarian cancer cells may provide an avenue to develop a new generation of potential biomarkers for early detection of this disease. We performed a glycotranscriptomic analysis of endometrioid ovarian carcinoma using human tissue, as well as a newly developed mouse model that mimics this disease. Our results show that the N-linked glycans expressed in both non-diseased mouse and human ovarian tissues are similar; moreover, malignant changes in the expression of N-linked glycans in both mouse and human endometrioid ovarian carcinoma are qualitatively similar. Lectin reactivity was used as a means for rapid validation of glycan structural changes in the carcinomas that were predicted by the glycotranscriptome analysis. Among several changes in glycan expression noted, the increase of bisected N-linked glycans and the transcripts of the enzyme responsible for its biosynthesis, GnT-III, was the most significant. This study provides evidence that glycotranscriptome analysis can be an important tool in identifying potential cancer biomarkers. PMID:18690643

X-linked cataract and Nance-Horan syndrome are allelic disorders.

PubMed

Coccia, Margherita; Brooks, Simon P; Webb, Tom R; Christodoulou, Katja; Wozniak, Izabella O; Murday, Victoria; Balicki, Martha; Yee, Harris A; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J; Maher, Eamonn R; Moore, Anthony T; Russell-Eggitt, Isabelle M; Hardcastle, Alison J

2009-07-15

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication-triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved.

X-linked cataract and Nance-Horan syndrome are allelic disorders

PubMed Central

Coccia, Margherita; Brooks, Simon P.; Webb, Tom R.; Christodoulou, Katja; Wozniak, Izabella O.; Murday, Victoria; Balicki, Martha; Yee, Harris A.; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K.; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J.; Maher, Eamonn R.; Moore, Anthony T.; Russell-Eggitt, Isabelle M.; Hardcastle, Alison J.

2009-01-01

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication–triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved. PMID:19414485

User Interaction with the CNPC Link

NASA Technical Reports Server (NTRS)

Hobbs, Alan; Lyall, Elizabeth A.

2014-01-01

As part of NASAs UAS in the NAS project, human factor guidelines are being developed for the ground control station of unmanned aircraft systems. A critical task for the pilot of a UAS is the management and control of the terrestrial radio links used to provide control of the vehicle and relay communications with air traffic control. An analysis of the task of the UAS pilot has been conducted to identify areas where guidelines are required. This analysis has identified a set of information requirements that must be supported by the radio equipment used to provide Control and Non-payload Communication (CNPC). Key requirements include the need for an alert when the link is lost, information on the current quality and latency of the link, and information to enable the future quality of the link to be anticipated as the aircraft changes location. These identified requirements can assist in the development of minimum operational performance standards for CNPC equipment.

Identification of O-Linked Glycoproteins Binding to the Lectin Helix pomatia Agglutinin as Markers of Metastatic Colorectal Cancer.

PubMed

Peiris, Diluka; Ossondo, Marlène; Fry, Simon; Loizidou, Marilena; Smith-Ravin, Juliette; Dwek, Miriam V

2015-01-01

Protein glycosylation is an important post-translational modification shown to be altered in all tumour types studied to date. Mucin glycoproteins have been established as important carriers of O-linked glycans but other glycoproteins exhibiting altered glycosylation repertoires have yet to be identified but offer potential as biomarkers for metastatic cancer. In this study a glycoproteomic approach was used to identify glycoproteins exhibiting alterations in glycosylation in colorectal cancer and to evaluate the changes in O-linked glycosylation in the context of the p53 and KRAS (codon 12/13) mutation status. Affinity purification with the carbohydrate binding protein from Helix pomatia agglutinin (HPA) was coupled to 2-dimensional gel electrophoresis with mass spectrometry to enable the identification of low abundance O-linked glycoproteins from human colorectal cancer specimens. Aberrant O-linked glycosylation was observed to be an early event that occurred irrespective of the p53 and KRAS status and correlating with metastatic colorectal cancer. Affinity purification using the lectin HPA followed by proteomic analysis revealed annexin 4, annexin 5 and CLCA1 to be increased in the metastatic colorectal cancer specimens. The results were validated using a further independent set of specimens and this showed a significant association between the staining score for annexin 4 and HPA and the time to metastasis; independently (annexin A4: Chi square 11.45, P = 0.0007; HPA: Chi square 9.065, P = 0.0026) and in combination (annexin 4 and HPA combined: Chi square 13.47; P = 0.0002). Glycoproteins showing changes in O-linked glycosylation in metastatic colorectal cancer have been identified. The glycosylation changes were independent of p53 and KRAS status. These proteins offer potential for further exploration as biomarkers and potential targets for metastatic colorectal cancer.

Identification of O-Linked Glycoproteins Binding to the Lectin Helix pomatia Agglutinin as Markers of Metastatic Colorectal Cancer

PubMed Central

Peiris, Diluka; Ossondo, Marlène; Fry, Simon; Loizidou, Marilena; Smith-Ravin, Juliette; Dwek, Miriam V.

2015-01-01

Background Protein glycosylation is an important post-translational modification shown to be altered in all tumour types studied to date. Mucin glycoproteins have been established as important carriers of O-linked glycans but other glycoproteins exhibiting altered glycosylation repertoires have yet to be identified but offer potential as biomarkers for metastatic cancer. Methodology In this study a glycoproteomic approach was used to identify glycoproteins exhibiting alterations in glycosylation in colorectal cancer and to evaluate the changes in O-linked glycosylation in the context of the p53 and KRAS (codon 12/13) mutation status. Affinity purification with the carbohydrate binding protein from Helix pomatia agglutinin (HPA) was coupled to 2-dimensional gel electrophoresis with mass spectrometry to enable the identification of low abundance O-linked glycoproteins from human colorectal cancer specimens. Results Aberrant O-linked glycosylation was observed to be an early event that occurred irrespective of the p53 and KRAS status and correlating with metastatic colorectal cancer. Affinity purification using the lectin HPA followed by proteomic analysis revealed annexin 4, annexin 5 and CLCA1 to be increased in the metastatic colorectal cancer specimens. The results were validated using a further independent set of specimens and this showed a significant association between the staining score for annexin 4 and HPA and the time to metastasis; independently (annexin A4: Chi square 11.45, P = 0.0007; HPA: Chi square 9.065, P = 0.0026) and in combination (annexin 4 and HPA combined: Chi square 13.47; P = 0.0002). Conclusion Glycoproteins showing changes in O-linked glycosylation in metastatic colorectal cancer have been identified. The glycosylation changes were independent of p53 and KRAS status. These proteins offer potential for further exploration as biomarkers and potential targets for metastatic colorectal cancer. PMID:26495974

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

PubMed

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

2016-06-01

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

Identifying and exploiting genes that potentiate the evolution of antibiotic resistance.

PubMed

Gifford, Danna R; Furió, Victoria; Papkou, Andrei; Vogwill, Tom; Oliver, Antonio; MacLean, R Craig

2018-06-01

There is an urgent need to develop novel approaches for predicting and preventing the evolution of antibiotic resistance. Here, we show that the ability to evolve de novo resistance to a clinically important β-lactam antibiotic, ceftazidime, varies drastically across the genus Pseudomonas. This variation arises because strains possessing the ampR global transcriptional regulator evolve resistance at a high rate. This does not arise because of mutations in ampR. Instead, this regulator potentiates evolution by allowing mutations in conserved peptidoglycan biosynthesis genes to induce high levels of β-lactamase expression. Crucially, blocking this evolutionary pathway by co-administering ceftazidime with the β-lactamase inhibitor avibactam can be used to eliminate pathogenic P. aeruginosa populations before they can evolve resistance. In summary, our study shows that identifying potentiator genes that act as evolutionary catalysts can be used to both predict and prevent the evolution of antibiotic resistance.

Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity

PubMed Central

Bosi, Emanuele; Monk, Jonathan M.; Aziz, Ramy K.; Fondi, Marco; Nizet, Victor; Palsson, Bernhard Ø.

2016-01-01

Staphylococcus aureus is a preeminent bacterial pathogen capable of colonizing diverse ecological niches within its human host. We describe here the pangenome of S. aureus based on analysis of genome sequences from 64 strains of S. aureus spanning a range of ecological niches, host types, and antibiotic resistance profiles. Based on this set, S. aureus is expected to have an open pangenome composed of 7,411 genes and a core genome composed of 1,441 genes. Metabolism was highly conserved in this core genome; however, differences were identified in amino acid and nucleotide biosynthesis pathways between the strains. Genome-scale models (GEMs) of metabolism were constructed for the 64 strains of S. aureus. These GEMs enabled a systems approach to characterizing the core metabolic and panmetabolic capabilities of the S. aureus species. All models were predicted to be auxotrophic for the vitamins niacin (vitamin B3) and thiamin (vitamin B1), whereas strain-specific auxotrophies were predicted for riboflavin (vitamin B2), guanosine, leucine, methionine, and cysteine, among others. GEMs were used to systematically analyze growth capabilities in more than 300 different growth-supporting environments. The results identified metabolic capabilities linked to pathogenic traits and virulence acquisitions. Such traits can be used to differentiate strains responsible for mild vs. severe infections and preference for hosts (e.g., animals vs. humans). Genome-scale analysis of multiple strains of a species can thus be used to identify metabolic determinants of virulence and increase our understanding of why certain strains of this deadly pathogen have spread rapidly throughout the world. PMID:27286824

Identifying cross-cultural variations in psychostimulant use for attention deficit hyperactivity disorder using linked data.

PubMed

Ghosh, Manonita; Holman, C D'Arcy J; Preen, David B

2017-01-01

To validate the association between country-of-birth and disparities in the stimulant use for ADHD among individuals in Western Australia. Using linked data, a population-based retrospective cohort of individuals admitted to hospital before age 25 years was followed through to identify having stimulants for ADHD in 2003-2007. Multivariate logistic and linear regressions were used to characterise associations between stimulants and country-of-birth, geographical remoteness and socioeconomic status. Of 679,645 individuals, 14,122 (2.1%) had a record of having stimulants for ADHD. Of these, 205 (1.5%) were born in Africa, Asia, Middle-East or South America, while 13,664 (96.8%) were born in Australia/New Zealand, Europe or North America. Individuals with traditionally non-Anglophonic backgrounds were around one-half as likely to have stimulants as individuals with Anglophonic backgrounds (OR = 0.53, 95% CI 0.46-0.61, p < 0.001). Non-Anglophones were an average of 2.7 years older than Anglophones at onset of having stimulants. Individuals from remote and disadvantaged backgrounds had stimulants at younger ages than individuals living in metropolitan areas and with least disadvantage. The results highlight the importance of identifying factors underlying cultural differences in stimulant treatment for ADHD. Improving awareness of cultural variations may foster trust and rapport between patients and clinicians, and so better facilitate the appropriate and effective treatment of ADHD for each patient.

Newer Approaches to Identify Potential Untoward Effects in Functional Foods.

PubMed

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

2016-01-01

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

Barium-cross-linked alginate-gelatine microcapsule as a potential platform for stem cell production and modular tissue formation.

PubMed

Alizadeh Sardroud, Hamed; Nemati, Sorour; Baradar Khoshfetrat, Ali; Nabavinia, Mahbobeh; Beygi Khosrowshahi, Younes

2017-08-01

Influence of gelatine concentration and cross-linker ions of Ca 2+ and Ba 2+ was evaluated on characteristics of alginate hydrogels and proliferation behaviours of model adherent and suspendable stem cells of fibroblast and U937 embedded in alginate microcapsules. Increasing gelatine concentration to 2.5% increased extent of swelling to 15% and 25% for barium- and calcium-cross-linked hydrogels, respectively. Mechanical properties also decreased with increasing swelling of hydrogels. Both by increasing gelatine concentration and using barium ions increased considerably the proliferation of encapsulated model stem cells. Barium-cross-linked alginate-gelatine microcapsule tested for bone building block showed a 13.5 ± 1.5-fold expansion for osteoblast cells after 21 days with deposition of bone matrix. The haematopoietic stem cells cultured in the microcapsule after 7 days also showed up to 2-fold increase without adding any growth factor. The study demonstrates that barium-cross-linked alginate-gelatine microcapsule has potential for use as a simple and efficient 3D platform for stem cell production and modular tissue formation.

Two Linked Enteroinvasive Escherichia coli Outbreaks, Nottingham, UK, June 2014

PubMed Central

MacGregor, Vanessa; Robbins, Vivienne; Bayliss, Laura; Chattaway, Marie Anne; Dallman, Tim; Ready, Derren; Aird, Heather; Puleston, Richard; Hawker, Jeremy

2016-01-01

Enteroinvasive Escherichia coli (EIEC) outbreaks are uncommon in Europe. In June 2014, two EIEC outbreaks occurred in Nottingham, UK, within 2 days; outbreak A was linked to a takeaway restaurant and outbreak B to a wedding party. We conducted 2 analytical studies: a case–control study for outbreak A and a cohort study for outbreak B. We tested microbiological and environmental samples, including by using whole-genome sequencing. For both outbreaks combined, we identified 157 probable case-patients; 27 were laboratory-confirmed as EIEC O96:H19–positive. Combined epidemiologic, microbiological, and environmental findings implicated lettuce as the vehicle of infection in outbreak A, but the source of the organism remained unknown. Whole-genome sequencing identified the same organism in cases from both outbreaks, but no epidemiologic link was confirmed. These outbreaks highlight that EIEC has the capacity to cause large and severe gastrointestinal disease outbreaks and should be considered as a potential pathogen in foodborne outbreaks in Europe. PMID:27314432

Two Linked Enteroinvasive Escherichia coli Outbreaks, Nottingham, UK, June 2014.

PubMed

Newitt, Sophie; MacGregor, Vanessa; Robbins, Vivienne; Bayliss, Laura; Chattaway, Marie Anne; Dallman, Tim; Ready, Derren; Aird, Heather; Puleston, Richard; Hawker, Jeremy

2016-07-01

Enteroinvasive Escherichia coli (EIEC) outbreaks are uncommon in Europe. In June 2014, two EIEC outbreaks occurred in Nottingham, UK, within 2 days; outbreak A was linked to a takeaway restaurant and outbreak B to a wedding party. We conducted 2 analytical studies: a case-control study for outbreak A and a cohort study for outbreak B. We tested microbiological and environmental samples, including by using whole-genome sequencing. For both outbreaks combined, we identified 157 probable case-patients; 27 were laboratory-confirmed as EIEC O96:H19-positive. Combined epidemiologic, microbiological, and environmental findings implicated lettuce as the vehicle of infection in outbreak A, but the source of the organism remained unknown. Whole-genome sequencing identified the same organism in cases from both outbreaks, but no epidemiologic link was confirmed. These outbreaks highlight that EIEC has the capacity to cause large and severe gastrointestinal disease outbreaks and should be considered as a potential pathogen in foodborne outbreaks in Europe.

Project Engage: Snowball Sampling and Direct Recruitment to Identify and Link Hard-to-Reach HIV-Infected Persons Who Are Out of Care.

PubMed

Wohl, Amy Rock; Ludwig-Barron, Natasha; Dierst-Davies, Rhodri; Kulkarni, Sonali; Bendetson, Jesse; Jordan, Wilbert; Bolan, Robert; Smith, Terry; Cunningham, William; Pérez, Mario J

2017-06-01

Innovative strategies are needed to identify and link hard-to-find persons living with HIV (PLWH) who are out of care (OOC). Project Engage, a health department-based project in Los Angeles County, used a mixed-methods approach to locate and provide linkage for PLWH who have limited contact with HIV medical and nonmedical services. Incentivized social network recruitment (SNR) and direct recruitment (DR) was used to identify eligible OOC alters for a linkage intervention that included HIV clinic selection, appointment and transportation support, reminder calls/texts, and clinic navigation. Between 2012 and 2015, 112 alters were identified using SNR (n = 74) and DR (n = 38). Most alters were male (80%), African American (38%), and gay (60%). Sizable percentages were homeless (78%), had engaged in sex work (32%) in the previous 6 months, had injected drugs (47%), were incarcerated in the previous 12 months (50%), and had only received HIV care during the previous 5 years while incarcerated (24%). SNR alters were more likely than DR alters to be African American, uninsured, unemployed, homeless, sex workers, injection drug users, recently incarcerated, and have unmet service needs. Alters linked to care within 3 (69%), 4-6 (5%), and 7-12 months (8%), and 72% were retained at 6-12 months. The percent virally suppressed increased (27% vs. 41%) and the median viral load decreased (P = 0.003) between linkage and follow-up at 6-12 months. The alternative approaches presented were effective at locating marginalized HIV-positive persons who are OOC for linkage and retention. The SNR approach was most successful at identifying alters with serious social challenges and gaps in needed medical/ancillary services.

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

PubMed

Savage, Jeanne E; Jansen, Philip R; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien; de Leeuw, Christiaan A; Nagel, Mats; Awasthi, Swapnil; Barr, Peter B; Coleman, Jonathan R I; Grasby, Katrina L; Hammerschlag, Anke R; Kaminski, Jakob A; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A; Trampush, Joey W; Young, Hannah; Zabaneh, Delilah; Hägg, Sara; Hansell, Narelle K; Karlsson, Ida K; Linnarsson, Sten; Montgomery, Grant W; Muñoz-Manchado, Ana B; Quinlan, Erin B; Schumann, Gunter; Skene, Nathan G; Webb, Bradley T; White, Tonya; Arking, Dan E; Avramopoulos, Dimitrios; Bilder, Robert M; Bitsios, Panos; Burdick, Katherine E; Cannon, Tyrone D; Chiba-Falek, Ornit; Christoforou, Andrea; Cirulli, Elizabeth T; Congdon, Eliza; Corvin, Aiden; Davies, Gail; Deary, Ian J; DeRosse, Pamela; Dickinson, Dwight; Djurovic, Srdjan; Donohoe, Gary; Conley, Emily Drabant; Eriksson, Johan G; Espeseth, Thomas; Freimer, Nelson A; Giakoumaki, Stella; Giegling, Ina; Gill, Michael; Glahn, David C; Hariri, Ahmad R; Hatzimanolis, Alex; Keller, Matthew C; Knowles, Emma; Koltai, Deborah; Konte, Bettina; Lahti, Jari; Le Hellard, Stephanie; Lencz, Todd; Liewald, David C; London, Edythe; Lundervold, Astri J; Malhotra, Anil K; Melle, Ingrid; Morris, Derek; Need, Anna C; Ollier, William; Palotie, Aarno; Payton, Antony; Pendleton, Neil; Poldrack, Russell A; Räikkönen, Katri; Reinvang, Ivar; Roussos, Panos; Rujescu, Dan; Sabb, Fred W; Scult, Matthew A; Smeland, Olav B; Smyrnis, Nikolaos; Starr, John M; Steen, Vidar M; Stefanis, Nikos C; Straub, Richard E; Sundet, Kjetil; Tiemeier, Henning; Voineskos, Aristotle N; Weinberger, Daniel R; Widen, Elisabeth; Yu, Jin; Abecasis, Goncalo; Andreassen, Ole A; Breen, Gerome; Christiansen, Lene; Debrabant, Birgit; Dick, Danielle M; Heinz, Andreas; Hjerling-Leffler, Jens; Ikram, M Arfan; Kendler, Kenneth S; Martin, Nicholas G; Medland, Sarah E; Pedersen, Nancy L; Plomin, Robert; Polderman, Tinca J C; Ripke, Stephan; van der Sluis, Sophie; Sullivan, Patrick F; Vrieze, Scott I; Wright, Margaret J; Posthuma, Danielle

2018-06-25

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

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

Cases of human brucellosis in Sweden linked to Middle East and Africa.

PubMed

Garofolo, Giuliano; Fasanella, Antonio; Di Giannatale, Elisabetta; Platone, Ilenia; Sacchini, Lorena; Persiani, Tiziana; Boskani, Talar; Rizzardi, Kristina; Wahab, Tara

2016-05-17

Human brucellosis cases are still reported each year in Sweden despite eradication of the disease in animals. Epidemiological investigation has never been conducted to trace back the source of human infection in the country. The purpose of the study was to identify the source of infection for 16 human brucellosis cases that occurred in Sweden, during the period 2008-2012. The isolates were identified as Brucella melitensis and MLVA-16 genotyping revealed 14 different genotypes of East Mediterranean and Africa lineages. We also reported one case of laboratory-acquired brucellosis (LAB) that was shown to be epidemiological linked to one of the cases in the current study. Brucella melitensis was the only species diagnosed, confirming its highest zoonotic potential in the genus Brucella, and MLVA-16 results demonstrated that the cases of brucellosis in Sweden herein investigated, are imported and linked to travel in the Middle East and Africa. Due to its zoonotic concerns, any acute febrile illness linked to recent travel within those regions should be investigated for brucellosis and samples should be processed according to biosafety level 3 regulations.

Meaning in Life: One Link in the Chain from Religiousness to Well-Being

ERIC Educational Resources Information Center

Steger, Michael F.; Frazier, Patricia

2005-01-01

Meaning in life has been identified as a potential mediator of the link between religiousness and psychological health. The authors tested this hypothesis in 2 studies, using multiple methods and measures of religiousness and well-being. In the studies, meaning in life mediated the relation between religiousness and life satisfaction (Study 1A),…

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

PubMed Central

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

2004-01-01

Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix–turn-helix (HTH), helix–hairpin–helix (HhH) and helix–loop–helix (HLH). We find that the combination of these variables detect 78% of proteins with an HTH motif, which is a substantial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding proteins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif. PMID:15356290

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

PubMed

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

2015-02-01

Conservation agriculture (CA) is being promoted as an option for reducing soil degradation, conserving water, enhancing crop productivity, and maintaining yield stability. However, CA is a knowledge- and technology-intensive practice, and may not be feasible or may not perform better than conventional agriculture under all conditions and farming systems. Using high resolution (≈1 km(2)) biophysical and socioeconomic geospatial data, this study identified potential recommendation domains (RDs) for CA in Ethiopia, Kenya, and Malawi. The biophysical variables used were soil texture, surface slope, and rainfall while the socioeconomic variables were market access and human and livestock population densities. Based on feasibility and comparative performance of CA over conventional agriculture, the biophysical and socioeconomic factors were first used to classify cultivated areas into three biophysical and three socioeconomic potential domains, respectively. Combinations of biophysical and socioeconomic domains were then used to develop potential RDs for CA based on adoption potential within the cultivated areas. About 39, 12, and 5% of the cultivated areas showed high biophysical and socioeconomic potential while 50, 39, and 21% of the cultivated areas showed high biophysical and medium socioeconomic potential for CA in Malawi, Kenya, and Ethiopia, respectively. The results indicate considerable acreages of land with high CA adoption potential in the mixed crop-livestock systems of the studied countries. However, there are large differences among countries depending on biophysical and socio-economic conditions. The information generated in this study could be used for targeting CA and prioritizing CA-related agricultural research and investment priorities in the three countries.

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

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

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

PubMed

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

2016-05-31

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

Link Prediction in Evolving Networks Based on Popularity of Nodes.

PubMed

Wang, Tong; He, Xing-Sheng; Zhou, Ming-Yang; Fu, Zhong-Qian

2017-08-02

Link prediction aims to uncover the underlying relationship behind networks, which could be utilized to predict missing edges or identify the spurious edges. The key issue of link prediction is to estimate the likelihood of potential links in networks. Most classical static-structure based methods ignore the temporal aspects of networks, limited by the time-varying features, such approaches perform poorly in evolving networks. In this paper, we propose a hypothesis that the ability of each node to attract links depends not only on its structural importance, but also on its current popularity (activeness), since active nodes have much more probability to attract future links. Then a novel approach named popularity based structural perturbation method (PBSPM) and its fast algorithm are proposed to characterize the likelihood of an edge from both existing connectivity structure and current popularity of its two endpoints. Experiments on six evolving networks show that the proposed methods outperform state-of-the-art methods in accuracy and robustness. Besides, visual results and statistical analysis reveal that the proposed methods are inclined to predict future edges between active nodes, rather than edges between inactive nodes.

The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity.

PubMed

Reznikov, Leah R; Meyerholz, David K; Abou Alaiwa, Mahmoud H; Kuan, Shin-Ping; Liao, Yan-Shin J; Bormann, Nicholas L; Bair, Thomas B; Price, Margaret; Stoltz, David A; Welsh, Michael J

2018-04-05

Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity. As a comparison, we also utilized previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating airway hyperreactivity; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.

A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

PubMed

Jiang, Peng; Scarpa, Joseph R; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D; Hao, Ke; Summa, Keith C; Yang, He S; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

2015-05-05

Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Isolation of a sex-linked DNA sequence in cranes.

PubMed

Duan, W; Fuerst, P A

2001-01-01

A female-specific DNA fragment (CSL-W; crane sex-linked DNA on W chromosome) was cloned from female whooping cranes (Grus americana). From the nucleotide sequence of CSL-W, a set of polymerase chain reaction (PCR) primers was identified which amplify a 227-230 bp female-specific fragment from all existing crane species and some other noncrane species. A duplicated versions of the DNA segment, which is found to have a larger size (231-235 bp) than CSL-W in both sexes, was also identified, and was designated CSL-NW (crane sex-linked DNA on non-W chromosome). The nucleotide similarity between the sequences of CSL-W and CSL-NW from whooping cranes was 86.3%. The CSL primers do not amplify any sequence from mammalian DNA, limiting the potential for contamination from human sources. Using the CSL primers in combination with a quick DNA extraction method allows the noninvasive identification of crane gender in less than 10 h. A test of the methodology was carried out on fully developed body feathers from 18 captive cranes and resulted in 100% successful identification.

A Psychoevolutionary Approach to Identifying Preferred Nature Scenes With Potential to Provide Restoration From Stress.

PubMed

Thake, Carol L; Bambling, Matthew; Edirippulige, Sisira; Marx, Eric

2017-10-01

Research supports therapeutic use of nature scenes in healthcare settings, particularly to reduce stress. However, limited literature is available to provide a cohesive guide for selecting scenes that may provide optimal therapeutic effect. This study produced and tested a replicable process for selecting nature scenes with therapeutic potential. Psychoevolutionary theory informed the construction of the Importance for Survival Scale (IFSS), and its usefulness for identifying scenes that people generally prefer to view and that hold potential to reduce stress was tested. Relationships between Importance for Survival (IFS), preference, and restoration were tested. General community participants ( N = 20 males, 20 females; M age = 48 years) Q-sorted sets of landscape photographs (preranked by the researcher in terms of IFS using the IFSS) from most to least preferred, and then completed the Short-Version Revised Restoration Scale in response to viewing a selection of the scenes. Results showed significant positive relationships between IFS and each of scene preference (large effect), and restoration potential (medium effect), as well as between scene preference and restoration potential across the levels of IFS (medium effect), and for individual participants and scenes (large effect). IFS was supported as a framework for identifying nature scenes that people will generally prefer to view and that hold potential for restoration from emotional distress; however, greater therapeutic potential may be expected when people can choose which of the scenes they would prefer to view. Evidence for the effectiveness of the IFSS was produced.

Linking traumatic brain injury to chronic traumatic encephalopathy: identification of potential mechanisms leading to neurofibrillary tangle development.

PubMed

Lucke-Wold, Brandon Peter; Turner, Ryan Coddington; Logsdon, Aric Flint; Bailes, Julian Edwin; Huber, Jason Delwyn; Rosen, Charles Lee

2014-07-01

Significant attention has recently been drawn to the potential link between head trauma and the development of neurodegenerative disease, namely chronic traumatic encephalopathy (CTE). The acute neurotrauma associated with sports-related concussions in athletes and blast-induced traumatic brain injury in soldiers elevates the risk for future development of chronic neurodegenerative diseases such as CTE. CTE is a progressive disease distinguished by characteristic tau neurofibrillary tangles (NFTs) and, occasionally, transactive response DNA binding protein 43 (TDP43) oligomers, both of which have a predilection for perivascular and subcortical areas near reactive astrocytes and microglia. The disease is currently only diagnosed postmortem by neuropathological identification of NFTs. A recent workshop sponsored by National Institute of Neurological Disorders and Stroke emphasized the need for premortem diagnosis, to better understand disease pathophysiology and to develop targeted treatments. In order to accomplish this objective, it is necessary to discover the mechanistic link between acute neurotrauma and the development of chronic neurodegenerative and neuropsychiatric disorders such as CTE. In this review, we briefly summarize what is currently known about CTE development and pathophysiology, and subsequently discuss injury-induced pathways that warrant further investigation. Understanding the mechanistic link between acute brain injury and chronic neurodegeneration will facilitate the development of appropriate diagnostic and therapeutic options for CTE and other related disorders.

National Information Clearinghouse on Children Who Are Deaf-Blind (DB-LINK). National Resource Directory.

ERIC Educational Resources Information Center

National Information Clearinghouse on Children Who Are Deaf-Blind, Monmouth, OR.

This resource guide, consisting of pages downloaded from the DB-LINK Web site, is designed to assist parents, professionals, and others in identifying services that hold the potential for supporting and improving the lives of children and youth who experience combined vision and hearing loss. Information is provided on: (1) the American…

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

DOE PAGES

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

2015-03-30

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

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

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

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric

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

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

PubMed

Dey-Rao, Rama; Sinha, Animesh A

2017-01-28

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

Endolysosomal Cation Channels and Cancer-A Link with Great Potential.

PubMed

Grimm, Christian; Bartel, Karin; Vollmar, Angelika M; Biel, Martin

2018-01-05

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells.

Endolysosomal Cation Channels and Cancer—A Link with Great Potential

PubMed Central

Grimm, Christian; Bartel, Karin; Vollmar, Angelika M.; Biel, Martin

2018-01-01

The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism. The function of endolysosomes is critically dependent on both soluble and endolysosomal membrane proteins such as ion channels and transporters. Cation channels found in the ES include members of the TRP (transient receptor potential) channel superfamily, namely TRPML channels (mucolipins) as well as two-pore channels (TPCs). In recent studies, these channels have been found to play crucial roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or loss of these channel proteins can impact multiple endolysosomal trafficking pathways. A role for TPCs in cancer cell migration and metastasis, linked to distinct defects in endolysosomal trafficking such as integrin trafficking, has been recently established. In this review, we give an overview on the function of lysosomes in cancer with a particular focus on the roles which TPCs and TRPML channels play in the ES and how this can affect cancer cells. PMID:29303993

Linked Ocean Data

NASA Astrophysics Data System (ADS)

Leadbetter, Adam; Arko, Robert; Chandler, Cynthia; Shepherd, Adam

2014-05-01

"Linked Data" is a term used in Computer Science to encapsulate a methodology for publishing data and metadata in a structured format so that links may be created and exploited between objects. Berners-Lee (2006) outlines the following four design principles of a Linked Data system: Use Uniform Resource Identifiers (URIs) as names for things. Use HyperText Transfer Protocol (HTTP) URIs so that people can look up those names. When someone looks up a URI, provide useful information, using the standards (Resource Description Framework [RDF] and the RDF query language [SPARQL]). Include links to other URIs so that they can discover more things. In 2010, Berners-Lee revisited his original design plan for Linked Data to encourage data owners along a path to "good Linked Data". This revision involved the creation of a five star rating system for Linked Data outlined below. One star: Available on the web (in any format). Two stars: Available as machine-readable structured data (e.g. An Excel spreadsheet instead of an image scan of a table). Three stars: As two stars plus the use of a non-proprietary format (e.g. Comma Separated Values instead of Excel). Four stars: As three stars plus the use of open standards from the World Wide Web Commission (W3C) (i.e. RDF and SPARQL) to identify things, so that people can point to your data and metadata. Five stars: All the above plus link your data to other people's data to provide context Here we present work building on the SeaDataNet common vocabularies served by the NERC Vocabulary Server, connecting projects such as the Rolling Deck to Repository (R2R) and the Biological and Chemical Oceanography Data Management Office (BCO-DMO) and other vocabularies such as the Marine Metadata Interoperability Ontology Register and Repository and the NASA Global Change Master Directory to create a Linked Ocean Data cloud. Publishing the vocabularies and metadata in standard RDF XML and exposing SPARQL endpoints renders them five-star Linked

Identifying Potential Collapse Features Under Highways

DOT National Transportation Integrated Search

2003-01-01

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

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

PubMed

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

2018-04-15

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

Identifying areas of basin-floor recharge in the Trans-Pecos region and the link to vegetation

USGS Publications Warehouse

Walvoord, Michelle Ann; Phillips, Fred M.

2004-01-01

Comparative water potential and chloride profiles (∼10 m deep) collected from four vegetation communities in the Trans-Pecos region of the Chihuahuan Desert were assessed to evaluate the potential for using vegetation patterns as a means of efficiently improving large-scale estimates of basin-floor recharge in semiarid and arid regions. Analytical solutions and multiphase flow and transport modeling constrained flux histories and current fluxes across the water table at each site. Chloride bulge profiles containing ∼12–15 kyr of atmospheric deposition and long-term drying water potential profiles typified most desertscrub and grassland sites. In contrast, evidence of episodic sub-root zone percolation and chloride profiles containing <250 yr of atmospheric deposition characterized the woodland site. The results suggested that the desertscrub and grassland areas support small upward fluxes across the water table (nonrecharge), whereas the woodland site supports significant downward fluxes across the water table (recharge). A nonrecharge–recharge transition was identified to be collocated with a grassland–woodland ecotone. The establishment of vegetation–recharge relationships such as this will improve estimates of basin-scale recharge by identifying regions where no recharge is expected and regions where recharge is expected and point measurements should be concentrated. An approach integrating remotely sensed spatial distributions of vegetation and indicator relationships to recharge is both timely and warranted, although several caveats, as revealed in this study, should be noted. For example, the relative importance and distribution of vertical conduits that permit percolation to the water table merits future investigation.

Spatial overlap links seemingly unconnected genotype-matched TB cases in rural Uganda

PubMed Central

Kato-Maeda, Midori; Emperador, Devy M.; Wandera, Bonnie; Mugagga, Olive; Crandall, John; Janes, Michael; Marquez, Carina; Kamya, Moses R.; Charlebois, Edwin D.; Havlir, Diane V.

2018-01-01

Introduction Incomplete understanding of TB transmission dynamics in high HIV prevalence settings remains an obstacle for prevention. Understanding where transmission occurs could provide a platform for case finding and interrupting transmission. Methods From 2012–2015, we sought to recruit all adults starting TB treatment in a Ugandan community. Participants underwent household (HH) contact investigation, and provided names of social contacts, sites of work, healthcare and socializing, and two sputum samples. Mycobacterium tuberculosis culture-positive specimens underwent 24-loci MIRU-VNTR and spoligotyping. We sought to identify epidemiologic links between genotype-matched cases by analyzing social networks and mapping locations where cases reported spending ≥12 hours over the one-month pre-treatment. Sites of spatial overlap (≤100m) between genotype-matched cases were considered potential transmission sites. We analyzed social networks stratified by genotype clustering status, with cases linked by shared locations, and compared network density by location type between clustered vs. non-clustered cases. Results Of 173 adults with TB, 131 (76%) were enrolled, 108 provided sputum, and 84/131 (78%) were MTB culture-positive: 52% (66/131) tested HIV-positive. Of 118 adult HH contacts, 105 (89%) were screened and 3 (2.5%) diagnosed with active TB. Overall, 33 TB cases (39%) belonged to 15 distinct MTB genotype-matched clusters. Within each cluster, no cases shared a HH or reported shared non-HH contacts. In 6/15 (40%) clusters, potential epidemiologic links were identified by spatial overlap at specific locations: 5/6 involved health care settings. Genotype-clustered TB social networks had significantly greater network density based on shared clinics (p<0.001) and decreased density based on shared marketplaces (p<0.001), compared to non-clustered networks. Conclusions In this molecular epidemiologic study, links between MTB genotype-matched cases were only

Identifying potential collapse features under highways.

DOT National Transportation Integrated Search

2003-03-01

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

When He Said Linking, He Really Meant Linking

ERIC Educational Resources Information Center

Chudnov, Daniel

2009-01-01

There are many reasons to improve web links, starting with their design. The author tends to think about "design" on the web in terms of two things: (1) graphic/industrial design; and (2) human usability. A nice, clean URI (uniform resource identifier) that does not change, is readable to humans, is amenable to common web behaviors such as…

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

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

Japan Link Center (JaLC): link management and DOI assignment for Japanese electronic scholarly contents

NASA Astrophysics Data System (ADS)

Kato, Takafumi; Tsuchiya, Eri; Kubota, Soichi; Miyagawa, Yoshiyuki

JST, cooperated with several national institutes, is currently developing “Japan Link Center”, which manages Japanese electronic scholarly contents (journal articles, books, dissertations etc.) in an integrated fashion using Digital Object Identifier (DOI). Japan Link Center will manage metadata and whereabouts information of the contents in the digital environment and provide domestic and international linking information, cite/cited information to activate dissemination of S&T information, furthermore, to strengthen transmission of S&T information from Japan. Japan Link Center is expected to be appointed as the 9th DOI registration agency (RA) in the world by the International DOI Foundation (IDF) this spring.

Knowledge-Linking Perceptions of Late-Elementary Students

ERIC Educational Resources Information Center

Schuh, Kathy L.; Kuo, Yi-Lung; Knupp, Tawnya L.

2014-01-01

This study describes student perceptions of potential elaborative or generative learning strategies called student knowledge links. This construct was assessed using the Student Knowledge Linking Instrument-Perceptions (SKLIP), a new learning inventory to measure late-elementary student perceptions of the creation of student knowledge links. After…

Precipitation links (PrecipLinks) - a prototype directory for precipitation information

NASA Technical Reports Server (NTRS)

Velanthapillia, Balendran; Stocker, Erich Franz

2006-01-01

This poster describes a web directory of research oriented precipitation links. In this era of sophisticated search engines and web agents, it might seem counterproductive to establish such a directory of links. However, entering precipitation into a search engine like google will yield over one million hits. To further exacerbate this situation many of the returned links are dead, duplicates of other links, incomplete, or only marginally related to research precipitation or even the broader precipitation area. Sometimes connecting the linked URL causes the browser to lose context and not be able to get back to the original page. Even using more sophisticated search engines query parameters or agents while reducing the overall return doesn't eliminate all of the other issues listed. As part of the development of the measurement-based Precipitation Processing System (PPS) that will support Tropical Rainfall Measuring Mission (TRMM) version 7 reprocessing and the Global Precipitation Measurement (GPM) mission a precipitation links (PrecipLinks) facility is being developed. PrecipLinks is intended to share locations of other sites that contain information or data pertaining to precipitation research. Potential contributors can log-on to the PrecipLinks website and register their site for inclusion in the directory. The price for inclusion is the requirement to place a link back to PrecipLinks on the webpage that is registered. This ensures that users will be able to easily get back to PrecipLinks regardless of any context issues that browsers might have. Perhaps more importantly users while visiting one site that they know can be referred to a location that has many others sites with which they might not be familiar. PrecipLinks is designed to have a very flat structure. This poster summarizes these categories (information, data, services) and the reasons for their selection. Providers may register multiple pages to which they wish to direct users. However, each page

PCR-enzyme-linked immunosorbent assay and partial rRNA gene sequencing: a rational approach to identifying mycobacteria.

PubMed Central

Patel, S; Yates, M; Saunders, N A

1997-01-01

A PCR-enzyme-linked immunosorbent assay (ELISA) for amplification and rapid identification of mycobacterial DNA coding for 16S rRNA was developed. The PCR selectively targeted and amplified part of the 16S rRNA gene from all mycobacteria while simultaneously labelling one strand of the amplified product with a 5' fluorescein-labelled primer. The identity of the labelled strand was subsequently determined by hybridization to a panel of mycobacterial species-specific capture probes, which were immobilized via their 5' biotin ends to a streptavidin-coated microtiter plate. Specific hybridization of a 5' fluorescein-labelled strand to a species probe was detected colorimetrically with an anti-fluorescein enzyme conjugate. The assay was able to identify 10 Mycobacterium spp. A probe able to hybridize to all Mycobacterium species (All1) was also included. By a heminested PCR, the assay was sensitive enough to detect as little as 10 fg of DNA, which is equivalent to approximately three bacilli. The assay was able to detect and identify mycobacteria directly from sputa. The specificities of the capture probes were assessed by analysis of 60 mycobacterial strains corresponding to 18 species. Probes Avi1, Int1, Kan1, Xen1, Che1, For1, Mal1, Ter1, and Gor1 were specific. The probe Tbc1 cross-hybridized with the Mycobacterium terrae amplicon. Analysis of 35 strains tested blind resulted in 34 strains being correctly identified. This method could be used for rapid identification of early cultures and may be suitable for the detection and concurrent identification of mycobacteria within clinical specimens. PMID:9276419

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

Microtubule actin cross-linking factor 1, a novel potential target in cancer.

PubMed

Miao, Zhiping; Ali, Arshad; Hu, Lifang; Zhao, Fan; Yin, Chong; Chen, Chu; Yang, Tuanmin; Qian, Airong

2017-10-01

Cancer is a polygenic disease characterized by uncontrolled growth of normal body cells, deregulation of the cell cycle as well as resistance to apoptosis. The spectraplakin protein microtubule actin cross-linking factor 1 (MACF1) plays an essential function in various cellular processes, including cell proliferation, migration, signaling transduction and embryo development. MACF1 is also involved in processes such as metastatic invasion in which cytoskeleton organization is a critical element that contributes to tumor progression in various human cancers. Aberrant expression of MACF1 initiates the tumor cell proliferation, and migration and metastasis in numerous cancers, such as breast cancer, colon cancer, lung cancer and glioblastoma. In this review, we summarized the current knowledge of MACF1 and its critical role in different human cancers. This will be helpful for researchers to investigate the novel functional role of MACF1 in human cancers and as a potential target to enhance the efficacy of therapeutic treatment modalities. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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

NASA Technical Reports Server (NTRS)

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

1995-01-01

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

The Potential of School-Linked Centers To Promote Adolescent Health and Development. Working Paper.

ERIC Educational Resources Information Center

Millstein, Susan G.

The future of school-linked adolescent health centers cannot be determined without further evaluation. The recent development of school-linked health centers stems from concerns about the special health needs of adolescents. Currently there are 125 school-based and school-linked centers in operation. Characteristics include the following: (1) most…

LinkMind: link optimization in swarming mobile sensor networks.

PubMed

Ngo, Trung Dung

2011-01-01

A swarming mobile sensor network is comprised of a swarm of wirelessly connected mobile robots equipped with various sensors. Such a network can be applied in an uncertain environment for services such as cooperative navigation and exploration, object identification and information gathering. One of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm is demonstrated and evaluated in simulation.

LinkMind: Link Optimization in Swarming Mobile Sensor Networks

PubMed Central

Ngo, Trung Dung

2011-01-01

A swarming mobile sensor network is comprised of a swarm of wirelessly connected mobile robots equipped with various sensors. Such a network can be applied in an uncertain environment for services such as cooperative navigation and exploration, object identification and information gathering. One of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm is demonstrated and evaluated in simulation. PMID:22164070

Exploring DNA-binding Proteins with In Vivo Chemical Cross-linking and Mass Spectrometry

PubMed Central

Qiu, Haibo; Wang, Yinsheng

2009-01-01

DNA-binding proteins are very important constituents of proteomes of all species and play crucial roles in transcription, DNA replication, recombination, repair and other activities associated with DNA. Although a number of DNA-binding proteins have been identified, many proteins involved in gene regulation and DNA repair are likely still unknown because of their dynamic and/or weak interactions with DNA. In this report, we described an approach for the comprehensive identification of DNA-binding proteins with in vivo formaldehyde cross-linking and LC-MS/MS. DNA-binding proteins could be purified via the isolation of DNA-protein complexes and released from the complexes by reversing the cross-linking. By using this method, we were able to identify more than one hundred DNA-binding proteins, such as proteins involved in transcription, gene regulation, DNA replication and repair, and a large number of proteins which are potentially associated with DNA and DNA-binding proteins. This method should be generally applicable to the investigation of other nucleic acid-binding proteins, and hold great potential in the comprehensive study of gene regulation, DNA damage response and repair, as well as many other critical biological processes at proteomic level. PMID:19714816

Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

PubMed Central

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

2014-01-01

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

Generation of quinoneimine intermediates in the bioactivation of 3-(N-phenylamino)alanine (PAA) by human liver microsomes: a potential link between eosinophilia-myalgia syndrome and toxic oil syndrome.

PubMed

Martínez-Cabot, Anna; Messeguer, Angel

2007-10-01

Eosinophilia-myalgia syndrome (EMS) was an intoxication episode that occurred in the US in 1989 and affected 1,500 people. EMS was associated with the ingestion of manufactured L-tryptophan, and 3-(N-phenylamino)alanine (PAA) was identified as one of the contaminants present in the L-tryptophan batches responsible for intoxication. In previous studies (Martínez-Cabot et al., Chem Res. Toxicol., in press), we have shown that the incubation of 3-(N-phenylamino)propane-1,2-diol (PAP), a toxic biomarker of the oil batches that caused Toxic Oil Syndrome in Spain, with human liver microsomes generates a reactive quinoneimine intermediate. The structural similarity between PAA and PAP led Mayeno and co-workers (Mayeno et al. (1995) Chem. Res. Toxicol. 8, 911-916) to hypothesize that both xenobiotics could be linked to a common etiologic agent. We thus set about to study the bioactivation of PAA by human liver microsomes. Under these conditions, PAA is converted to its 4'-hydroxy derivative, an unstable intermediate that is rapidly transformed into the final metabolites 4-aminophenol and formylglycine, which were identified in the incubations by GC/MS using the H2(18)O-labeled medium. We also provide evidence that 4-aminophenol and formylglycine are formed from a quinoneimine intermediate via a pathway similar to that demonstrated for PAP bioactivation. This quinoneimine, in the absence of nucleophiles in the incubation medium, could isomerize to give the corresponding imine, which could undergo hydrolysis to yield the aforementioned final products. These findings establish that EMS and TOS are linked by a common toxic metabolite (4-aminophenol) and that they may be further linked by the concomitant release of potentially hazardous carbonyl species.

Metabolic endotoxaemia--a potential novel link between ovarian inflammation and impaired progesterone production.

PubMed

Tremellen, Kelton; Syedi, Naeema; Tan, Sze; Pearce, Karma

2015-04-01

Medical conditions such as obesity and inflammatory bowel disease are associated with impaired luteal function, menstrual disturbance and infertility. It is proposed that the disturbance in gut wall integrity ("leaky gut") seen in these conditions may result in the passage of bacterial endotoxin (LPS) from the colonic lumen into the circulation that may initiate inflammation in the ovary and subsequently impair hormone production. Quantify the association between systemic levels of LBP, a marker of endotoxin exposure, and levels of inflammation in the ovary (follicular fluid IL-6), plus steroid hormone production in 45 women undergoing IVF treatment. Endotoxaemia (LBP) were positively correlated with plasma CRP and inflammation within the ovary (follicular fluid IL-6). Furthermore, endotoxaemia was negatively correlated with progesterone production. The observed correlations, together with previously published animal studies linking endotoxin exposure to impaired luteal function, suggest that the translocation of bacterial endotoxin from the gut lumen into the circulation has the potential to interfere with progesterone production and result in luteal deficiency.

Intersatellite Link (ISL) application to commercial communications satellites. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

Young, S. Lee

1987-01-01

Based on a comprehensive evaluation of the fundamental Intersatellite Link (ISL) systems characteristics, potential applications of ISLs to domestic, regional, and global commercial satellite communications were identified, and their cost-effectiveness and other systems benefits quantified wherever possible. Implementation scenarios for the cost-effective communications satellite systems employing ISLs were developed for the first launch in 1993 to 1994 and widespread use of ISLs in the early 2000's. Critical technology requirements for both the microwave (60 GHz) and optical (0.85 micron) ISL implementations were identified, and their technology development programs, including schedule and cost estimates, were derived.

Collagen cross-linking: insights on the evolution of metazoan extracellular matrix.

PubMed

Rodriguez-Pascual, Fernando; Slatter, David Anthony

2016-11-23

Collagens constitute a large family of extracellular matrix (ECM) proteins that play a fundamental role in supporting the structure of various tissues in multicellular animals. The mechanical strength of fibrillar collagens is highly dependent on the formation of covalent cross-links between individual fibrils, a process initiated by the enzymatic action of members of the lysyl oxidase (LOX) family. Fibrillar collagens are present in a wide variety of animals, therefore often being associated with metazoan evolution, where the emergence of an ancestral collagen chain has been proposed to lead to the formation of different clades. While LOX-generated collagen cross-linking metabolites have been detected in different metazoan families, there is limited information about when and how collagen acquired this particular modification. By analyzing telopeptide and helical sequences, we identified highly conserved, potential cross-linking sites throughout the metazoan tree of life. Based on this analysis, we propose that they have importantly contributed to the formation and further expansion of fibrillar collagens.

Linking Supermarket Sales Data To Nutritional Information: An Informatics Feasibility Study

PubMed Central

Brinkerhoff, Kristina M.; Brewster, Philip J.; Clark, Edward B.; Jordan, Kristine C.; Cummins, Mollie R.; Hurdle, John F.

2011-01-01

Grocery sales are a data source of potential value to dietary assessment programs in public health informatics. However, the lack of a computable method for mapping between nutrient and food item information represents a major obstacle. We studied the feasibility of linking point-of-sale data to USDA-SR nutrient database information in a sustainable way. We analyzed 2,009,533 de-identified sales items purchased by 32,785 customers over a two-week period. We developed a method using the item category hierarchy in the supermarket’s database to link purchased items to records from the USDA-SR. We describe our methodology and its rationale and limitations. Approximately 70% of all items were mapped and linked to the SR; approximately 90% of all items could be mapped with an equivalent expenditure of additional effort. 100% of all items were mapped to USDA standard food groups. We conclude that mapping grocery sales data to nutritional information is feasible. PMID:22195115

Transcriptome analysis of cattle muscle identifies potential markers for skeletal muscle growth rate and major cell types.

PubMed

Guo, Bing; Greenwood, Paul L; Cafe, Linda M; Zhou, Guanghong; Zhang, Wangang; Dalrymple, Brian P

2015-03-13

This study aimed to identify markers for muscle growth rate and the different cellular contributors to cattle muscle and to link the muscle growth rate markers to specific cell types. The expression of two groups of genes in the longissimus muscle (LM) of 48 Brahman steers of similar age, significantly enriched for "cell cycle" and "ECM (extracellular matrix) organization" Gene Ontology (GO) terms was correlated with average daily gain/kg liveweight (ADG/kg) of the animals. However, expression of the same genes was only partly related to growth rate across a time course of postnatal LM development in two cattle genotypes, Piedmontese x Hereford (high muscling) and Wagyu x Hereford (high marbling). The deposition of intramuscular fat (IMF) altered the relationship between the expression of these genes and growth rate. K-means clustering across the development time course with a large set of genes (5,596) with similar expression profiles to the ECM genes was undertaken. The locations in the clusters of published markers of different cell types in muscle were identified and used to link clusters of genes to the cell type most likely to be expressing them. Overall correspondence between published cell type expression of markers and predicted major cell types of expression in cattle LM was high. However, some exceptions were identified: expression of SOX8 previously attributed to muscle satellite cells was correlated with angiogenesis. Analysis of the clusters and cell types suggested that the "cell cycle" and "ECM" signals were from the fibro/adipogenic lineage. Significant contributions to these signals from the muscle satellite cells, angiogenic cells and adipocytes themselves were not as strongly supported. Based on the clusters and cell type markers, sets of five genes predicted to be representative of fibro/adipogenic precursors (FAPs) and endothelial cells, and/or ECM remodelling and angiogenesis were identified. Gene sets and gene markers for the analysis of

Magnetic Properties of Strongly Correlated Hubbard Model and Quantum Spin-One Ferromagnets with Arbitrary Crystal-Field Potential: Linked Cluster Series Expansion Approach

NASA Astrophysics Data System (ADS)

Pan, Kok-Kwei

We have generalized the linked cluster expansion method to solve more many-body quantum systems, such as quantum spin systems with crystal-field potentials and the Hubbard model. The technique sums up all connected diagrams to a certain order of the perturbative Hamiltonian. The modified multiple-site Wick reduction theorem and the simple tau dependence of the standard basis operators have been used to facilitate the evaluation of the integration procedures in the perturbation expansion. Computational methods are developed to calculate all terms in the series expansion. As a first example, the perturbation series expansion of thermodynamic quantities of the single-band Hubbard model has been obtained using a linked cluster series expansion technique. We have made corrections to all previous results of several papers (up to fourth order). The behaviors of the three dimensional simple cubic and body-centered cubic systems have been discussed from the qualitative analysis of the perturbation series up to fourth order. We have also calculated the sixth-order perturbation series of this model. As a second example, we present the magnetic properties of spin-one Heisenberg model with arbitrary crystal-field potential using a linked cluster series expansion. The calculation of the thermodynamic properties using this method covers the whole range of temperature, in both magnetically ordered and disordered phases. The series for the susceptibility and magnetization have been obtained up to fourth order for this model. The method sums up all perturbation terms to certain order and estimates the result using a well -developed and highly successful extrapolation method (the standard ratio method). The dependence of critical temperature on the crystal-field potential and the magnetization as a function of temperature and crystal-field potential are shown. The critical behaviors at zero temperature are also shown. The range of the crystal-field potential for Ni(2+) compounds is

Cross-linking of type I collagen with microbial transglutaminase: identification of cross-linking sites.

PubMed

Stachel, Ines; Schwarzenbolz, Uwe; Henle, Thomas; Meyer, Michael

2010-03-08

Collagen is a popular biomaterial. To deal with its lack of thermal stability and its weak resistance to proteolytic degradation, collagen-based materials are stabilized via different cross-linking procedures. Regarding the potential toxicity of residual cross-linking agents, enzyme-mediated cross-linking would provide an alternative and nontoxic method for collagen stabilization. The results of this study show that type I collagen is a substrate for mTG. However, epsilon-(gamma-glutamyl)lysine cross-links are only incorporated at elevated temperatures when the protein is partially or completely denatured. A maximum number of 5.4 cross-links per collagen monomer were found for heat-denatured collagen. Labeling with the primary amine monodansylcadaverine revealed that at least half of the cross-links are located within the triple helical region of the collagen molecule. Because the triple helix is highly ordered in its native state, this finding might explain why the glutamine residues are inaccessible for mTG under nondenaturing conditions.

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

Code of Federal Regulations, 2013 CFR

2013-01-01

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

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

Intersatellite Link (ISL) application to commercial communications satellites. Volume 2: Technical final report

NASA Technical Reports Server (NTRS)

Young, S. Lee

1987-01-01

Intersatellite Link (ISL) applications can improve and expand communication satellite services in a number of ways. As the demand for orbital slots within prime regions of the geostationary arc increases, attention is being focused on ISLs as a method to utilize this resource more efficiently and circumvent saturation. Various GEO-to-GEO applications were determined that provide potential benefits over existing communication systems. A set of criteria was developed to assess the potential applications. Intersatellite link models, network system architectures, and payload configurations were developed. For each of the chosen ISL applications, ISL versus non-ISL satellite systems architectures were derived. Both microwave and optical ISL implementation approaches were evaluated for payload sizing and cost analysis. The technological availability for ISL implementations was assessed. Critical subsystems technology areas were identified, and an estamate of the schedule and cost to advance the technology to the requiered state of readiness was made.

Persistent Identifiers for Data Products: Adoption, Enhancement, and Use

NASA Astrophysics Data System (ADS)

Downs, R. R.; Schumacher, J.; Scialdone, J.; Hansen, M.

2016-12-01

Persistent identifiers offer value for science and for various science community stakeholders, such as data producers, data distributers, science article authors, scientific journal publishers, research sponsors, libraries, and affiliated institutions. However, to attain the benefits of persistent identifiers, they should be assigned to disseminated data products and included within the references reported in publications that describe the studies in which the data were used. Scientific data centers, archives, digital repositories, and other data publishers also need to determine the level of aggregation, or granularity, of data products to be assigned persistent identifiers as well as the elements to be included in the landing pages to which persistent identifiers will resolve. Similarly, policies and procedures should be clear on decisions about maintenance issues, including versioning of data products and how persistent identifiers to previous versions and new locations will be maintained. With some persistent identifiers, such as Digital Object Identifiers (DOIs), which provide capabilities to link to related identifiers of other works, decisions on the establishment of links also must be clear, including links between early versions of data products and subsequent versions, links between data products and associated documentation, and links between data products and other publications that describe the data. We describe decisions for enabling the adoption and assignment of DOIs as persistent identifiers for data products disseminated by the NASA Socioeconomic Data and Applications Center (SEDAC) along with considerations for policy decisions, testing, implementation, and enhancement. The prevalence of the adoption of DOIs for citing the use of Earth science data disseminated by SEDAC also is described to provide insight into how interdisciplinary data users have engaged in the use of DOIs within their publications along with the implications of such use.

Using SCOPE to identify potential regulatory motifs in coregulated genes.

PubMed

Martyanov, Viktor; Gross, Robert H

2011-05-31

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

Childhood Bestiality: A Potential Precursor to Adult Interpersonal Violence

ERIC Educational Resources Information Center

Hensley, Christopher; Tallichet, Suzanne E.; Dutkiewicz, Erik L.

2010-01-01

Although bestiality is an infrequent form of animal cruelty, the possibility of identifying a potential link between these acts and later interpersonal violence is an area of research that deserves further exploration. In a replication of the Hensley, Tallichet, and Singer study and based on survey data from male inmates at a medium- and…

Link-N: The missing link towards intervertebral disc repair is species-specific

PubMed Central

Bach, Frances C.; Laagland, Lisanne T.; Grant, Michael P.; Creemers, Laura B.; Ito, Keita; Meij, Björn P.; Mwale, Fackson

2017-01-01

Introduction Degeneration of the intervertebral disc (IVD) is a frequent cause for back pain in humans and dogs. Link-N stabilizes proteoglycan aggregates in cartilaginous tissues and exerts growth factor-like effects. The human variant of Link-N facilitates IVD regeneration in several species in vitro by inducing Smad1 signaling, but it is not clear whether this is species specific. Dogs with IVD disease could possibly benefit from Link-N treatment, but Link-N has not been tested on canine IVD cells. If Link-N appears to be effective in canines, this would facilitate translation of Link-N into the clinic using the dog as an in vivo large animal model for human IVD degeneration. Materials and methods This study’s objective was to determine the effect of the human and canine variant of Link-N and short (s) Link-N on canine chondrocyte-like cells (CLCs) and compare this to those on already studied species, i.e. human and bovine CLCs. Extracellular matrix (ECM) production was determined by measuring glycosaminoglycan (GAG) content and histological evaluation. Additionally, the micro-aggregates’ DNA content was measured. Phosphorylated (p) Smad1 and -2 levels were determined using ELISA. Results Human (s)Link-N induced GAG deposition in human and bovine CLCs, as expected. In contrast, canine (s)Link-N did not affect ECM production in human CLCs, while it mainly induced collagen type I and II deposition in bovine CLCs. In canine CLCs, both canine and human (s)Link-N induced negligible GAG deposition. Surprisingly, human and canine (s)Link-N did not induce Smad signaling in human and bovine CLCs. Human and canine (s)Link-N only mildly increased pSmad1 and Smad2 levels in canine CLCs. Conclusions Human and canine (s)Link-N exerted species-specific effects on CLCs from early degenerated IVDs. Both variants, however, lacked the potency as canine IVD regeneration agent. While these studies demonstrate the challenges of translational studies in large animal models, (s)Link

Link-N: The missing link towards intervertebral disc repair is species-specific.

PubMed

Bach, Frances C; Laagland, Lisanne T; Grant, Michael P; Creemers, Laura B; Ito, Keita; Meij, Björn P; Mwale, Fackson; Tryfonidou, Marianna A

2017-01-01

Degeneration of the intervertebral disc (IVD) is a frequent cause for back pain in humans and dogs. Link-N stabilizes proteoglycan aggregates in cartilaginous tissues and exerts growth factor-like effects. The human variant of Link-N facilitates IVD regeneration in several species in vitro by inducing Smad1 signaling, but it is not clear whether this is species specific. Dogs with IVD disease could possibly benefit from Link-N treatment, but Link-N has not been tested on canine IVD cells. If Link-N appears to be effective in canines, this would facilitate translation of Link-N into the clinic using the dog as an in vivo large animal model for human IVD degeneration. This study's objective was to determine the effect of the human and canine variant of Link-N and short (s) Link-N on canine chondrocyte-like cells (CLCs) and compare this to those on already studied species, i.e. human and bovine CLCs. Extracellular matrix (ECM) production was determined by measuring glycosaminoglycan (GAG) content and histological evaluation. Additionally, the micro-aggregates' DNA content was measured. Phosphorylated (p) Smad1 and -2 levels were determined using ELISA. Human (s)Link-N induced GAG deposition in human and bovine CLCs, as expected. In contrast, canine (s)Link-N did not affect ECM production in human CLCs, while it mainly induced collagen type I and II deposition in bovine CLCs. In canine CLCs, both canine and human (s)Link-N induced negligible GAG deposition. Surprisingly, human and canine (s)Link-N did not induce Smad signaling in human and bovine CLCs. Human and canine (s)Link-N only mildly increased pSmad1 and Smad2 levels in canine CLCs. Human and canine (s)Link-N exerted species-specific effects on CLCs from early degenerated IVDs. Both variants, however, lacked the potency as canine IVD regeneration agent. While these studies demonstrate the challenges of translational studies in large animal models, (s)Link-N still holds a regenerative potential for humans.

21 CFR 177.1211 - Cross-linked polyacrylate copolymers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... polyacrylate copolymers consist of: (1) The grafted copolymer of cross-linked sodium polyacrylate identified as... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Cross-linked polyacrylate copolymers. 177.1211... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1211 Cross-linked polyacrylate...

21 CFR 177.1211 - Cross-linked polyacrylate copolymers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... polyacrylate copolymers consist of: (1) The grafted copolymer of cross-linked sodium polyacrylate identified as... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Cross-linked polyacrylate copolymers. 177.1211... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1211 Cross-linked polyacrylate...

Polychlorinated biphenyls and links to cardiovascular disease.

PubMed

Perkins, Jordan T; Petriello, Michael C; Newsome, Bradley J; Hennig, Bernhard

2016-02-01

The pathology of cardiovascular disease is multi-faceted, with links to many modifiable and non-modifiable risk factors. Epidemiological evidence now implicates exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), with an increased risk of developing diabetes, hypertension, and obesity; all of which are clinically relevant to the onset and progression of cardiovascular disease. PCBs exert their cardiovascular toxicity either directly or indirectly via multiple mechanisms, which are highly dependent on the type and concentration of PCBs present. However, many PCBs may modulate cellular signaling pathways leading to common detrimental outcomes including induction of chronic oxidative stress, inflammation, and endocrine disruption. With the abundance of potential toxic pollutants increasing globally, it is critical to identify sensible means of decreasing associated disease risks. Emerging evidence now implicates a protective role of lifestyle modifications such as increased exercise and/or nutritional modulation via anti-inflammatory foods, which may help to decrease the vascular toxicity of PCBs. This review will outline the current state of knowledge linking coplanar and non-coplanar PCBs to cardiovascular disease and describe the possible molecular mechanism of this association.

An efficient link prediction index for complex military organization

NASA Astrophysics Data System (ADS)

Fan, Changjun; Liu, Zhong; Lu, Xin; Xiu, Baoxin; Chen, Qing

2017-03-01

Quality of information is crucial for decision-makers to judge the battlefield situations and design the best operation plans, however, real intelligence data are often incomplete and noisy, where missing links prediction methods and spurious links identification algorithms can be applied, if modeling the complex military organization as the complex network where nodes represent functional units and edges denote communication links. Traditional link prediction methods usually work well on homogeneous networks, but few for the heterogeneous ones. And the military network is a typical heterogeneous network, where there are different types of nodes and edges. In this paper, we proposed a combined link prediction index considering both the nodes' types effects and nodes' structural similarities, and demonstrated that it is remarkably superior to all the 25 existing similarity-based methods both in predicting missing links and identifying spurious links in a real military network data; we also investigated the algorithms' robustness under noisy environment, and found the mistaken information is more misleading than incomplete information in military areas, which is different from that in recommendation systems, and our method maintained the best performance under the condition of small noise. Since the real military network intelligence must be carefully checked at first due to its significance, and link prediction methods are just adopted to purify the network with the left latent noise, the method proposed here is applicable in real situations. In the end, as the FINC-E model, here used to describe the complex military organizations, is also suitable to many other social organizations, such as criminal networks, business organizations, etc., thus our method has its prospects in these areas for many tasks, like detecting the underground relationships between terrorists, predicting the potential business markets for decision-makers, and so on.

Constrained Active Learning for Anchor Link Prediction Across Multiple Heterogeneous Social Networks

PubMed Central

Zhu, Junxing; Zhang, Jiawei; Wu, Quanyuan; Jia, Yan; Zhou, Bin; Wei, Xiaokai; Yu, Philip S.

2017-01-01

Nowadays, people are usually involved in multiple heterogeneous social networks simultaneously. Discovering the anchor links between the accounts owned by the same users across different social networks is crucial for many important inter-network applications, e.g., cross-network link transfer and cross-network recommendation. Many different supervised models have been proposed to predict anchor links so far, but they are effective only when the labeled anchor links are abundant. However, in real scenarios, such a requirement can hardly be met and most anchor links are unlabeled, since manually labeling the inter-network anchor links is quite costly and tedious. To overcome such a problem and utilize the numerous unlabeled anchor links in model building, in this paper, we introduce the active learning based anchor link prediction problem. Different from the traditional active learning problems, due to the one-to-one constraint on anchor links, if an unlabeled anchor link a=(u,v) is identified as positive (i.e., existing), all the other unlabeled anchor links incident to account u or account v will be negative (i.e., non-existing) automatically. Viewed in such a perspective, asking for the labels of potential positive anchor links in the unlabeled set will be rewarding in the active anchor link prediction problem. Various novel anchor link information gain measures are defined in this paper, based on which several constraint active anchor link prediction methods are introduced. Extensive experiments have been done on real-world social network datasets to compare the performance of these methods with state-of-art anchor link prediction methods. The experimental results show that the proposed Mean-entropy-based Constrained Active Learning (MC) method can outperform other methods with significant advantages. PMID:28771201

Constrained Active Learning for Anchor Link Prediction Across Multiple Heterogeneous Social Networks.

PubMed

Zhu, Junxing; Zhang, Jiawei; Wu, Quanyuan; Jia, Yan; Zhou, Bin; Wei, Xiaokai; Yu, Philip S

2017-08-03

Nowadays, people are usually involved in multiple heterogeneous social networks simultaneously. Discovering the anchor links between the accounts owned by the same users across different social networks is crucial for many important inter-network applications, e.g., cross-network link transfer and cross-network recommendation. Many different supervised models have been proposed to predict anchor links so far, but they are effective only when the labeled anchor links are abundant. However, in real scenarios, such a requirement can hardly be met and most anchor links are unlabeled, since manually labeling the inter-network anchor links is quite costly and tedious. To overcome such a problem and utilize the numerous unlabeled anchor links in model building, in this paper, we introduce the active learning based anchor link prediction problem. Different from the traditional active learning problems, due to the one-to-one constraint on anchor links, if an unlabeled anchor link a = ( u , v ) is identified as positive (i.e., existing), all the other unlabeled anchor links incident to account u or account v will be negative (i.e., non-existing) automatically. Viewed in such a perspective, asking for the labels of potential positive anchor links in the unlabeled set will be rewarding in the active anchor link prediction problem. Various novel anchor link information gain measures are defined in this paper, based on which several constraint active anchor link prediction methods are introduced. Extensive experiments have been done on real-world social network datasets to compare the performance of these methods with state-of-art anchor link prediction methods. The experimental results show that the proposed Mean-entropy-based Constrained Active Learning (MC) method can outperform other methods with significant advantages.

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

PubMed Central

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

2018-01-01

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

Linking chloride mass balance infiltration rates with chlorofluorocarbon and SF6 groundwater dating in semi-arid settings: potential and limitations.

PubMed

Stadler, Susanne; Osenbruck, Karsten; Duijnisveld, Wilhelmus H M; Schwiede, Martin; Bottcher, Jurgen

2010-09-01

In the framework of the investigation of enrichment processes of nitrate in groundwater of the Kalahari of Botswana near Serowe, recharge processes were investigated. The thick unsaturated zone extending to up to 100 m of mostly unconsolidated sediments and very low recharge rates pose a serious challenge to study solute transport related to infiltration and recharge processes, as this extends past the conventional depths of soil scientific investigations and is difficult to describe using evidence from the groundwater due to the limitations imposed by available tracers. To determine the link between nitrate in the vadose zone and in the uppermost groundwater, sediment from the vadose zone was sampled up to a depth of 15-20 m (in one case also to 65 m) on several sites with natural vegetation in the research area. Among other parameters, sediment and water were analysed to determine chloride and nitrate concentration depth profiles. Using the chloride mass balance method, an estimation of groundwater infiltration rates produced values of 0.2-4 mm a(-1). The uncertainty of these values is, however, high. Because of the extreme thickness of the vadose zone, the travel time in the unsaturated zone might reach extreme values of up to 500 years and more. For investigations using groundwater, we applied the chlorofluorocarbons CFC-113, CFC-12, sulphur hexafluoride (SF(6)) and tritium to identify potential recharge, and found indications for some advective transport of the CFCs and SF(6), which we accounted for as constituting potential active localised recharge. In our contribution, we show the potential and limitations of the applied methods to determine groundwater recharge and coupled solute transport in semi-arid settings, and compare travel time ranges derived from soil science and groundwater investigations.

Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal hypoxia and impaired fetal growth

PubMed Central

Julian, Colleen G.; Yang, Ivana V.; Browne, Vaughn A.; Vargas, Enrique; Rodriguez, Carmelo; Pedersen, Brent S.; Moore, Lorna G.; Schwartz, David A.

2014-01-01

Chronic exposure to hypoxia raises the risk of pregnancy disorders characterized by maternal vascular dysfunction and diminished fetal growth. In an effort to identify novel pathways for these hypoxia-related effects, we assessed gene expression profiles of peripheral blood mononuclear cells (PBMCs) obtained from 43 female, high-altitude or sea-level residents in the nonpregnant state or during pregnancy (20 or 36 wk). Hypoxia-related fetal growth restriction becomes apparent between 25 and 29 wk of gestation and continues until delivery. Our sampling strategy was designed to capture changes occurring before (20 wk) and during (36 wk) the time frame of slowed fetal growth. PBMC gene expression profiles were generated using human gene expression microarrays and compared between altitudes. Biological pathways were identified using pathway analysis. Modest transcriptional differences were observed between altitudes in the nonpregnant state. Of the genes that were differentially expressed at high altitude vs. sea level during pregnancy (20 wk: 59 probes mapped to 41 genes; 36 wk: 985 probes mapped to 700 genes), several are of pathological relevance for fetal growth restriction. In particular, transcriptional changes were consistent with the negative regulation of peroxisome proliferator-activated receptor γ (PPARγ) at high altitude; such effects were accompanied by reduced birth weight (P <0.05) and head circumference (P <0.01) at high altitude vs. sea level. Our findings indicate that chronic exposure to hypoxia during pregnancy alters maternal gene expression patterns in general and, in particular, expression of key genes involved in metabolic homeostasis that have been proposed to play a role in the pathophysiology of fetal growth restriction.—Julian, C. G., Yang, I. V., Browne, V. A., Vargas, E., Rodriguez, C., Pedersen, B. S., Moore, L. G., Schwartz, D. A. Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal

Phospholipase C-ε links Epac2 activation to the potentiation of glucose-stimulated insulin secretion from mouse islets of Langerhans

PubMed Central

Dzhura, Igor; Chepurny, Oleg G; Leech, Colin A; Roe, Michael W; Dzhura, Elvira; Xu, Xin; Lu, Youming; Schwede, Frank; Genieser, Hans-G; Smrcka, Alan V

2011-01-01

Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is potentiated by cAMP-elevating agents, such as the incretin hormone glucagon-like peptide-1 (GLP-1) and cAMP exerts its insulin secretagogue action by activating both protein kinase A (PKA) and the cAMP-regulated guanine nucleotide exchange factor designated as Epac2. Although prior studies of mouse islets demonstrated that Epac2 acts via Rap1 GTPase to potentiate GSIS, it is not understood which downstream targets of Rap1 promote the exocytosis of insulin. Here, we measured insulin secretion stimulated by a cAMP analog that is a selective activator of Epac proteins in order to demonstrate that a Rap1-regulated phospholipase C-epsilon (PLC-ε) links Epac2 activation to the potentiation of GSIS. Our analysis demonstrates that the Epac activator 8-pCPT-2′-O-Me-cAMP-AM potentiates GSIS from the islets of wild-type (WT) mice, whereas it has a greatly reduced insulin secretagogue action in the islets of Epac2 (−/−) and PLC-ε (−/−) knockout (KO) mice. Importantly, the insulin secretagogue action of 8-pCPT-2′-O-Me-cAMP-AM in WT mouse islets cannot be explained by an unexpected action of this cAMP analog to activate PKA, as verified through the use of a FRET-based A-kinase activity reporter (AKAR3) that reports PKA activation. Since the KO of PLC-ε disrupts the ability of 8-pCPT-2′-O-Me-cAMP-AM to potentiate GSIS, while also disrupting its ability to stimulate an increase of β-cell [Ca2+]i, the available evidence indicates that it is a Rap1-regulated PLC-ε that links Epac2 activation to Ca2+-dependent exocytosis of insulin. PMID:21478675

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

PubMed Central

2010-01-01

Background Recruitment to clinical trials can be challenging. We identified anonymous potential participants to an existing pragmatic randomised controlled depression trial to assess the feasibility of using routinely collected data to identify potential trial participants. We discuss the strengths and limitations of this approach, assess its potential value, report challenges and ethical issues encountered. Methods Swansea University's Health Information Research Unit's Secure Anonymised Information Linkage (SAIL) database of routinely collected health records was interrogated, using Structured Query Language (SQL). Read codes were used to create an algorithm of inclusion/exclusion criteria with which to identify suitable anonymous participants. Two independent clinicians rated the eligibility of the potential participants' identified. Inter-rater reliability was assessed using the kappa statistic and inter-class correlation. Results The study population (N = 37263) comprised all adults registered at five general practices in Swansea UK. Using the algorithm 867 anonymous potential participants were identified. The sensitivity and specificity results > 0.9 suggested a high degree of accuracy from the algorithm. The inter-rater reliability results indicated strong agreement between the confirming raters. The Intra Class Correlation Coefficient (Cronbach's Alpha) > 0.9, suggested excellent agreement and Kappa coefficient > 0.8; almost perfect agreement. Conclusions This proof of concept study showed that routinely collected primary care data can be used to identify potential participants for a pragmatic randomised controlled trial of folate augmentation of antidepressant therapy for the treatment of depression. Further work will be needed to assess generalisability to other conditions and settings and the inclusion of this approach to support Electronic Enhanced Recruitment (EER). PMID:20398303

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

PubMed Central

Li, Ying; Wang, Jiaxing; Allingham, R. Rand; Hauser, Michael A.; Wiggs, Janey L.; Geisert, Eldon E.

2018-01-01

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

National variety trials identify clones with high potential

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

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

2016-07-01

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

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

PubMed

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

2008-08-01

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

Comparative secretome analysis of Colletotrichum falcatum identifies a cerato-platanin protein (EPL1) as a potential pathogen-associated molecular pattern (PAMP) inducing systemic resistance in sugarcane.

PubMed

Ashwin, N M R; Barnabas, Leonard; Ramesh Sundar, Amalraj; Malathi, Palaniyandi; Viswanathan, Rasappa; Masi, Antonio; Agrawal, Ganesh Kumar; Rakwal, Randeep

2017-10-03

Colletotrichum falcatum, an intriguing hemibiotrophic fungal pathogen causes red rot, a devastating disease of sugarcane. Repeated in vitro subculturing of C. falcatum under dark condition alters morphology and reduces virulence of the culture. Hitherto, no information is available on this phenomenon at molecular level. In this study, the in vitro secretome of C. falcatum cultured under light and dark conditions was analyzed using 2-DE coupled with MALDI TOF/TOF MS. Comparative analysis identified nine differentially abundant proteins. Among them, seven proteins were less abundant in the dark-cultured C. falcatum, wherein only two protein species of a cerato-platanin protein called EPL1 (eliciting plant response-like protein) were found to be highly abundant. Transcriptional expression of candidate high abundant proteins was profiled during host-pathogen interaction using qRT-PCR. Comprehensively, this comparative secretome analysis identified five putative effectors, two pathogenicity-related proteins and one pathogen-associated molecular pattern (PAMP) of C. falcatum. Functional characterization of three distinct domains of the PAMP (EPL1) showed that the major cerato-platanin domain (EPL1∆N1-92) is exclusively essential for inducing defense and hypersensitive response (HR) in sugarcane and tobacco, respectively. Further, priming with EPL1∆N1-92 protein induced systemic resistance and significantly suppressed the red rot severity in sugarcane. Being the first secretomic investigation of C. falcatum, this study has identified five potential effectors, two pathogenicity-related proteins and a PAMP. Although many reports have highlighted the influence of light on pathogenicity, this study has established a direct link between light and expression of effectors, for the first time. This study has presented the influence of a novel N-terminal domain of EPL1 in physical and biological properties and established the functional role of major cerato-platanin domain of

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

DTIC Science & Technology

1997-11-01

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

How Does Consecutive Interpreting Training Influence Working Memory: A Longitudinal Study of Potential Links Between the Two

PubMed Central

Dong, Yanping; Liu, Yuhua; Cai, Rendong

2018-01-01

With an intention to contribute to the issue of how language experience may influence working memory (WM), we focused on consecutive interpreting (CI), analyzed its potential links with WM functions and tested these links in a longitudinal experiment, trying to answer the specific question of how CI training may influence WM. Two comparable groups of Chinese learners of English received either CI or general second language (L2) training for one semester, and were tested before and after the training with the tasks of n-back (non-verbal updating), L2 listening span, and letter running span (verbal spans). CI performance was tested in the posttest. The results showed that (1) updating efficiency in both the pretest and posttest predicted CI performance, and CI training enhanced updating efficiency while general L2 training did not; (2) the relationship between verbal spans and CI performance was weaker (i.e., only pretest L2 listening span correlated with CI performance and predicted CI performance with marginal significance), and CI training did not make a unique contribution to these spans (i.e., no group differences). The results indicated an “interpreter advantage” in updating, which was probably due to that updating was more central in the CI task than WM spans. Theoretically, we believe that updating and CI are closely related because they share the same underlying mechanism, or more specifically updating and the recalling process in the CI task share the same attentional control process, a unique link between updating and the CI task. Methodological implications are discussed. PMID:29922199

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

PubMed

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

2016-03-03

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

Optimal Linking Design for Response Model Parameters

ERIC Educational Resources Information Center

Barrett, Michelle D.; van der Linden, Wim J.

2017-01-01

Linking functions adjust for differences between identifiability restrictions used in different instances of the estimation of item response model parameters. These adjustments are necessary when results from those instances are to be compared. As linking functions are derived from estimated item response model parameters, parameter estimation…

Linking vascular disorders and Alzheimer’s disease: Potential involvement of BACE1

PubMed Central

Cole, Sarah L.; Vassar, Robert

2012-01-01

The etiology of Alzheimer’s disease (AD) remains unknown. However, specific risk factors have been identified, and aging is the strongest AD risk factor. The majority of cardiovascular events occur in older people and a close relationship between vascular disorders and AD exists. Amyloid plaques, composed of the beta amyloid peptide (Aβ), are hallmark lesions in AD and evidence indicates that Aβ plays a central role in AD pathophysiology. The BACE1 enzyme is essential for Aβ generation, and BACE1 levels are elevated in AD brain. The cause(s) of this BACE1 elevation remains undetermined. Here we review the potential contribution of vascular disease to AD pathogenesis. We examine the putative vasoactive properties of Aβ and how the cellular changes associated with vascular disease may elevate BACE1 levels. Despite increasing evidence, the exact role(s) vascular disorders play in AD remains to be determined. However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation. PMID:18289733

Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes.

PubMed

Hernandez-Valladares, Maria; Rihet, Pascal; Iraqi, Fuad A

2014-01-01

There is growing evidence for human genetic factors controlling the outcome of malaria infection, while molecular basis of this genetic control is still poorly understood. Case-control and family-based studies have been carried out to identify genes underlying host susceptibility to malarial infection. Parasitemia and mild malaria have been genetically linked to human chromosomes 5q31-q33 and 6p21.3, and several immune genes located within those regions have been associated with malaria-related phenotypes. Association and linkage studies of resistance to malaria are not easy to carry out in human populations, because of the difficulty in surveying a significant number of families. Murine models have proven to be an excellent genetic tool for studying host response to malaria; their use allowed mapping 14 resistance loci, eight of them controlling parasitic levels and six controlling cerebral malaria. Once quantitative trait loci or genes have been identified, the human ortholog may then be identified. Comparative mapping studies showed that a couple of human and mouse might share similar genetically controlled mechanisms of resistance. In this way, char8, which controls parasitemia, was mapped on chromosome 11; char8 corresponds to human chromosome 5q31-q33 and contains immune genes, such as Il3, Il4, Il5, Il12b, Il13, Irf1, and Csf2. Nevertheless, part of the genetic factors controlling malaria traits might differ in both hosts because of specific host-pathogen interactions. Finally, novel genetic tools including animal models were recently developed and will offer new opportunities for identifying genetic factors underlying host phenotypic response to malaria, which will help in better therapeutic strategies including vaccine and drug development.

On the Reproducibility of Label-Free Quantitative Cross-Linking/Mass Spectrometry

NASA Astrophysics Data System (ADS)

Müller, Fränze; Fischer, Lutz; Chen, Zhuo Angel; Auchynnikava, Tania; Rappsilber, Juri

2018-02-01

Quantitative cross-linking/mass spectrometry (QCLMS) is an emerging approach to study conformational changes of proteins and multi-subunit complexes. Distinguishing protein conformations requires reproducibly identifying and quantifying cross-linked peptides. Here we analyzed the variation between multiple cross-linking reactions using bis[sulfosuccinimidyl] suberate (BS3)-cross-linked human serum albumin (HSA) and evaluated how reproducible cross-linked peptides can be identified and quantified by LC-MS analysis. To make QCLMS accessible to a broader research community, we developed a workflow that integrates the established software tools MaxQuant for spectra preprocessing, Xi for cross-linked peptide identification, and finally Skyline for quantification (MS1 filtering). Out of the 221 unique residue pairs identified in our sample, 124 were subsequently quantified across 10 analyses with coefficient of variation (CV) values of 14% (injection replica) and 32% (reaction replica). Thus our results demonstrate that the reproducibility of QCLMS is in line with the reproducibility of general quantitative proteomics and we establish a robust workflow for MS1-based quantitation of cross-linked peptides.

Using lice to identify cowbird hosts

USGS Publications Warehouse

Hahn, D.C.; Osenton, P.C.; Price, R.W.

1995-01-01

Avian lice may link fledgling Brown-headed Cowbirds to the host species that raised them. Lice, if host-specific and transferred to nestling cowbirds, could serve to identify the principal host species raising cowbirds in a local area. This approach of trapping cowbird fledglings in a feeding flock, then collecting and identifying the lice they carry is economical. The alternative requires a team of people to locate large numbers of parasitized host nests. We trapped 250 cowbird fledglings during June-August 1994 on Patuxent Research Center, and from them we collected 426 lice identified as representing 6 genera and 12 species. We. also collected and identified 347 lice from 30 known host species that were mist-netted on our Center. The lice found on cowbird fledglings in this population can be linked to Wood Thrush, Red-eyed Vireo, Common Yellowthroat, Rufous-sided Towhee, Red-winged Blackbird, Common Grackle, Song Sparrow, Field Sparrow, and Tree sparrow, based on this study and also on published reports.

Causal pathways linking Farm to School to childhood obesity prevention.

PubMed

Joshi, Anupama; Ratcliffe, Michelle M

2012-08-01

Farm to School programs are rapidly gaining attention as a potential strategy for preventing childhood obesity; however, the causal linkages between Farm to School activities and health outcomes are not well documented. To capitalize on the increased interest in and momentum for Farm to School, researchers and practitioners need to move from developing and implementing evidence informed programs and policies to ones that are evidence-based. The purpose of this article is to outline a framework for facilitating an evidence base for Farm to School programs and policies through a systematic and coordinated approach. Employing the concepts of causal pathways, the authors introduce a proposed framework for organizing and systematically testing out multiple hypotheses (or potential causal links) for how, why, and under what conditions Farm to School Inputs and Activities may result in what Outputs, Effects, and Impacts. Using the causal pathways framework may help develop and test competing hypotheses, identify multicausality, strength, and interactions of causes, and discern the difference between catalysts and causes. In this article, we introduce causal pathways, present menus of potential independent and dependent variables from which to create and test causal pathways linking Farm to School interventions and their role in preventing childhood obesity, discuss their applicability to Farm to School research and practice, and outline proposed next steps for developing a coordinated research framework for Farm to School programs.

Linked Data: what does it offer Earth Sciences?

NASA Astrophysics Data System (ADS)

Cox, Simon; Schade, Sven

2010-05-01

'Linked Data' is a current buzz-phrase promoting access to various forms of data on the internet. It starts from the two principles that have underpinned the architecture and scalability of the World Wide Web: 1. Universal Resource Identifiers - using the http protocol which is supported by the DNS system. 2. Hypertext - in which URIs of related resources are embedded within a document. Browsing is the key mode of interaction, with traversal of links between resources under control of the client. Linked Data also adds, or re-emphasizes: • Content negotiation - whereby the client uses http headers to tell the service what representation of a resource is acceptable, • Semantic Web principles - formal semantics for links, following the RDF data model and encoding, and • The 'mashup' effect - in which original and unexpected value may emerge from reuse of data, even if published in raw or unpolished form. Linked Data promotes typed links to all kinds of data, so is where the semantic web meets the 'deep web', i.e. resources which may be accessed using web protocols, but are in representations not indexed by search engines. Earth sciences are data rich, but with a strong legacy of specialized formats managed and processed by disconnected applications. However, most contemporary research problems require a cross-disciplinary approach, in which the heterogeneity resulting from that legacy is a significant challenge. In this context, Linked Data clearly has much to offer the earth sciences. But, there are some important questions to answer. What is a resource? Most earth science data is organized in arrays and databases. A subset useful for a particular study is usually identified by a parameterized query. The Linked Data paradigm emerged from the world of documents, and will often only resolve data-sets. It is impractical to create even nested navigation resources containing links to all potentially useful objects or subsets. From the viewpoint of human user

Attitude similarity and familiarity and their links to mental health: An examination of potential interpersonal mediators.

PubMed

Moore, Shannon M; Uchino, Bert N; Baucom, Brian R W; Behrends, Arwen A; Sanbonmatsu, David

2017-01-01

Similarity and familiarity with partner's attitudes are linked to positive relationship outcomes, while interpersonal variables have been linked to mental health. Using multilevel models (MLMs), we modeled the associations between these attitudinal variables and mental health outcomes in 74 married couples. We found that higher levels of attitude similarity in couples were linked to lower depression, while higher levels of attitude familiarity in couples were associated with greater satisfaction with life. Mediational analyses indicated marital satisfaction and interpersonal stress mediated the link between attitude similarity and depression. Marital satisfaction also mediated the link between familiarity and satisfaction with life. This study is the first linking attitude familiarity to mental health and provides evidence that familiarity and similarity have mental health effects partly due to their interpersonal consequences.

Chitosan supramolecularly cross linked with trimesic acid - Facile synthesis, characterization and evaluation of adsorption potential for chromium(VI).

PubMed

Bhatt, Ronak; Sreedhar, B; Padmaja, P

2017-11-01

A facile synthesis of Chitosan Supramolecularly cross-linked with Trimesic Acid (CTMA) is reported in this work. The adsorption potential of CTMA for removal of hexavalent chromium was evaluated and the influence of pH, temperature, contact time and adsorbent dose on the adsorption process was investigated. The experimental results showed that CTMA could efficiently adsorb Cr 6+ and partially reduce it to the less toxic Cr 3+ state. The maximum adsorption capacity of CTMA for Cr 6+ was found to be 129.53mg/g at pH 2.0. CTMA and chromium loaded CTMA were characterised by FT-IR, Raman, TGA-DSC, SEM-EDX, XRD, ESR and XPS spectroscopic techniques. Chitosan was observed to be cross- linked with TMA via ionic, hydrogen bonding and pi-pi supramolecular interactions while adsorption of chromium onto CTMA was by electrostatic forces and hydrogen bonding. From the observed results it was evident that CTMA was successfully applied for simultaneous removal of chromium, lead and iron from chrome plating effluent. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurocognition and symptoms identify links between facial recognition and emotion processing in schizophrenia: Meta-analytic findings

PubMed Central

Ventura, Joseph; Wood, Rachel C.; Jimenez, Amy M.; Hellemann, Gerhard S.

2014-01-01

Background In schizophrenia patients, one of the most commonly studied deficits of social cognition is emotion processing (EP), which has documented links to facial recognition (FR). But, how are deficits in facial recognition linked to emotion processing deficits? Can neurocognitive and symptom correlates of FR and EP help differentiate the unique contribution of FR to the domain of social cognition? Methods A meta-analysis of 102 studies (combined n = 4826) in schizophrenia patients was conducted to determine the magnitude and pattern of relationships between facial recognition, emotion processing, neurocognition, and type of symptom. Results Meta-analytic results indicated that facial recognition and emotion processing are strongly interrelated (r = .51). In addition, the relationship between FR and EP through voice prosody (r = .58) is as strong as the relationship between FR and EP based on facial stimuli (r = .53). Further, the relationship between emotion recognition, neurocognition, and symptoms is independent of the emotion processing modality – facial stimuli and voice prosody. Discussion The association between FR and EP that occurs through voice prosody suggests that FR is a fundamental cognitive process. The observed links between FR and EP might be due to bottom-up associations between neurocognition and EP, and not simply because most emotion recognition tasks use visual facial stimuli. In addition, links with symptoms, especially negative symptoms and disorganization, suggest possible symptom mechanisms that contribute to FR and EP deficits. PMID:24268469

Neurocognition and symptoms identify links between facial recognition and emotion processing in schizophrenia: meta-analytic findings.

PubMed

Ventura, Joseph; Wood, Rachel C; Jimenez, Amy M; Hellemann, Gerhard S

2013-12-01

In schizophrenia patients, one of the most commonly studied deficits of social cognition is emotion processing (EP), which has documented links to facial recognition (FR). But, how are deficits in facial recognition linked to emotion processing deficits? Can neurocognitive and symptom correlates of FR and EP help differentiate the unique contribution of FR to the domain of social cognition? A meta-analysis of 102 studies (combined n=4826) in schizophrenia patients was conducted to determine the magnitude and pattern of relationships between facial recognition, emotion processing, neurocognition, and type of symptom. Meta-analytic results indicated that facial recognition and emotion processing are strongly interrelated (r=.51). In addition, the relationship between FR and EP through voice prosody (r=.58) is as strong as the relationship between FR and EP based on facial stimuli (r=.53). Further, the relationship between emotion recognition, neurocognition, and symptoms is independent of the emotion processing modality - facial stimuli and voice prosody. The association between FR and EP that occurs through voice prosody suggests that FR is a fundamental cognitive process. The observed links between FR and EP might be due to bottom-up associations between neurocognition and EP, and not simply because most emotion recognition tasks use visual facial stimuli. In addition, links with symptoms, especially negative symptoms and disorganization, suggest possible symptom mechanisms that contribute to FR and EP deficits. © 2013 Elsevier B.V. All rights reserved.

Potential of calcium isotopes to identify fractionations in vegetation: experimental approach

NASA Astrophysics Data System (ADS)

Cobert, F.; Schmitt, A.; Bourgade, P.; Stille, P.; Chabaux, F. J.; Badot, P.; Jaegler, T.

2010-12-01

This study aims to better understand the role of vegetation on the Ca cycle at the level of the critical zone of the Earth, in order to specify the mechanisms controlling the Ca absorption by plants at the rock/plant interface. To do this, we performed experiments using hydroponic plant cultures in a way that we could control the cooccuring geochemical and biological processes and determine the impact of the nutritive solution on the Ca cycle within plants. A dicotyledon and calcicole plant with rapid growth, the French bean (Phaseolus vulgaris L.), has been chosen to have access to one complete growth cycle. Several experiments have been conducted with two Ca concentrations, 5 (L) and 60 (H) ppm and two pH values (4 and 6) in the nutritive solution, for which the Ca concentration was maintained constant, so its Ca content is considered to be infinite. We determined Ca concentrations and isotopic ratios in the nutritive solution and in different organs (main roots, secondary roots, old and young stems, old and young leaves and fruits) at two different growth stages (10 days and 6 weeks). Our results show, in accord with previously published field studies, that the bean organs are all enriched in the light 40Ca isotope compared to the nutritive solution (e.g. Wigand et al., 2005; Page et al., 2008; Cenki-Tok et al., 2009; Holmden and Bélanger, 2010). We identify two fractionation levels. The first occurs during the uptake of the nutrient elements by the lateral roots. This implies that the main mechanisms of light isotope enrichments in the plant are due to electrochemical gradient transport processes taking place at this interface. The second fractionation can be observed within the plant itself and is due to the nature of the considered organ itself. Indeed structural reservoirs (primary roots, stem, reproductive organs) incorporate more the light 40Ca isotope compared to the transfer reservoirs (lateral roots, xylem sap, leaves). This could be linked to ion

Pediatric sample inclusion in an opt-out biorepository linking DNA to de-identified medical records: Pediatric BioVU

PubMed Central

McGregor, Tracy L.; Van Driest, Sara L.; Brothers, Kyle B.; Bowton, Erica A.; Muglia, Louis J.; Roden, Dan M.

2013-01-01

The Vanderbilt DNA repository, BioVU, links DNA from leftover clinical blood samples to de-identified electronic medical records. After initiating adult sample collection, pediatric extension required consideration of ethical concerns specific to pediatrics and implementation of specialized DNA extraction methods. In the first year of pediatric sample collection, over 11,000 samples were included from individuals younger than 18 years. We compared the pediatric BioVU cohort to the overall Vanderbilt University Medical Center pediatric population and found similar demographic characteristics; however, the BioVU cohort has higher rates of select diseases, medication exposures, and laboratory testing, demonstrating enriched representation of severe or chronic disease. This unbalanced sample accumulation may accelerate research of some cohorts, but also may limit study of relatively benign conditions and the accrual of unaffected and unbiased control samples. BioVU represents a feasible model for pediatric DNA biobanking but involves both ethical and practical considerations specific to the pediatric population. PMID:23281421

Identifying technology innovations for marginalized smallholders-A conceptual approach.

PubMed

Malek, Mohammad Abdul; Gatzweiler, Franz W; Von Braun, Joachim

2017-05-01

This paper adds a contribution in the existing literature in terms of theoretical and conceptual background for the identification of idle potentials of marginal rural areas and people by means of technological and institutional innovations. The approach follows ex-ante assessment for identifying suitable technology and institutional innovations for marginalized smallholders in marginal areas-divided into three main parts (mapping, surveying and evaluating) and several steps. Finally, it contributes to the inclusion of marginalized smallholders by an improved way of understanding the interactions between technology needs, farming systems, ecological resources and poverty characteristics in the different segments of the poor, and to link these insights with productivity enhancing technologies.

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

PubMed Central

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

2016-01-01

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

Communications Technology Assessment for the Unmanned Aircraft System (UAS) Control and Non-Payload Communications (CNPC) Link

NASA Technical Reports Server (NTRS)

Bretmersky, Steven C.; Bishop, William D.; Dailey, Justin E.; Chevalier, Christine T.

2014-01-01

The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is performing communications systems research for the Unmanned Aircraft System (UAS) in the National Airspace System (NAS) Project. One of the goals of the communications element is to select and test a communications technology for the UAS Control and Non-Payload Communications (CNPC) link. The GRC UAS Modeling and Simulation (M/S) Sub Team will evaluate the performance of several potential technologies for the CNPC link through detailed software simulations. In parallel, an industry partner will implement a technology in hardware to be used for flight testing. The task necessitated a technical assessment of existing Radio Frequency (RF) communications technologies to identify the best candidate systems for use as the UAS CNPC link. The assessment provides a basis for selecting the technologies for the M/S effort and the hardware radio design. The process developed for the technical assessments for the Future Communications Study1 (FCS) was used as an initial starting point for this assessment. The FCS is a joint Federal Aviation Administration (FAA) and Eurocontrol study on technologies for use as a future aeronautical communications link. The FCS technology assessment process methodology can be applied to the UAS CNPC link; however the findings of the FCS are not directly applicable because of different requirements between a CNPC link and a general aeronautical data link. Additional technologies were added to the potential technologies list from the State of the Art Unmanned Aircraft System Communication Assessment developed by NASA GRC2. This document investigates the state of the art of communications as related to UAS. A portion of the document examines potential communications systems for a UAS communication architecture. Like the FCS, the state of the art assessment surveyed existing communications technologies. It did not, however, perform a detailed assessment of the

EarthCube GeoLink: Semantics and Linked Data for the Geosciences

NASA Astrophysics Data System (ADS)

Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Cheatham, M.; Fils, D.; Hitzler, P.; Janowicz, K.; Ji, P.; Jones, M. B.; Krisnadhi, A.; Lehnert, K. A.; Mickle, A.; Narock, T.; O'Brien, M.; Raymond, L. M.; Schildhauer, M.; Shepherd, A.; Wiebe, P. H.

2015-12-01

The NSF EarthCube initiative is building next-generation cyberinfrastructure to aid geoscientists in collecting, accessing, analyzing, sharing, and visualizing their data and knowledge. The EarthCube GeoLink Building Block project focuses on a specific set of software protocols and vocabularies, often characterized as the Semantic Web and "Linked Data", to publish data online in a way that is easily discoverable, accessible, and interoperable. GeoLink brings together specialists from the computer science, geoscience, and library science domains, and includes data from a network of NSF-funded repositories that support scientific studies in marine geology, marine ecosystems, biogeochemistry, and paleoclimatology. We are working collaboratively with closely-related Building Block projects including EarthCollab and CINERGI, and solicit feedback from RCN projects including Cyberinfrastructure for Paleogeosciences (C4P) and iSamples. GeoLink has developed a modular ontology that describes essential geoscience research concepts; published data from seven collections (to date) on the Web as geospatially-enabled Linked Data using this ontology; matched and mapped data between collections using shared identifiers for investigators, repositories, datasets, funding awards, platforms, research cruises, physical specimens, and gazetteer features; and aggregated the results in a shared knowledgebase that can be queried via a standard SPARQL endpoint. Client applications have been built around the knowledgebase, including a Web/map-based data browser using the Leaflet JavaScript library and a simple query service using the OpenSearch format. Future development will include extending and refining the GeoLink ontology, adding content from additional repositories, developing semi-automated algorithms to enhance metadata, and further work on client applications.

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

PubMed

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

2015-09-01

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

Attitude Similarity and Familiarity and Their Links to Mental Health: An Examination of Potential Interpersonal Mediators

PubMed Central

Uchino, Bert; Baucom, Brian; Behrends, Arwen; Sanbonmatsu, David

2017-01-01

Similarity and familiarity with partner's attitudes (Byrne, Clore, & Smeaton, 1986; Sanbonmatsu, Uchino, & Birmingham, 2011) are linked to positive relationship outcomes, while interpersonal variables have been linked to mental health (e.g., Lakey & Cronin, 2008). Using multilevel models (MLMs), we modeled the associations between these attitudinal variables and mental health outcomes in 74 married couples. We found that higher levels of attitude similarity in couples were linked to lower depression, while higher levels of attitude familiarity in couples were associated with greater satisfaction with life. Mediational analyses indicated marital satisfaction and interpersonal stress mediated the link between attitude similarity and depression. Marital satisfaction also mediated the link between familiarity and satisfaction with life. This study is the first linking attitude familiarity to mental health and provides evidence that familiarity and similarity have mental health effects partly due to their interpersonal consequences. PMID:27065059

Cell therapy for basement membrane-linked diseases.

PubMed

Nyström, Alexander; Bornert, Olivier; Kühl, Tobias

2017-01-01

For most disorders caused by mutations in genes encoding basement membrane (BM) proteins, there are at present only limited treatment options available. Genetic BM-linked disorders can be viewed as especially suited for treatment with cell-based therapy approaches because the proteins that need to be restored are located in the extracellular space. In consequence, complete and permanent engraftment of cells does not necessarily have to occur to achieve substantial causal therapeutic effects. For these disorders cells can be used as transient vehicles for protein replacement. In addition, it is becoming evident that BM-linked genetic disorders are modified by secondary diseases mechanisms. Cell-based therapies have also the ability to target such disease modifying mechanisms. Thus, cell therapies can simultaneously provide causal treatment and symptomatic relief, and accordingly hold great potential for treatment of BM-linked disorders. However, this potential has for most applications and diseases so far not been realized. Here, we will present the state of cell therapies for BM-linked diseases. We will discuss use of both pluripotent and differentiated cells, the limitation of the approaches, their challenges, and the way forward to potential wider implementation of cell therapies in the clinics. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-01-01

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

Treatment of Chronic Enterovirus Encephalitis With Fluoxetine in a Patient With X-Linked Agammaglobulinemia.

PubMed

Gofshteyn, Jacqueline; Cárdenas, Ana María; Bearden, David

2016-11-01

Enterovirus may result in a devastating chronic encephalitis in immunocompromised patients, particularly in patients with X-linked agammaglobulinemia. Prognosis for patients with chronic enterovirus encephalitis is poor, almost invariably resulting in mortality without specific treatment. There are currently no approved antiviral agents for enterovirus, but the antidepressant drug fluoxetine has been identified through library-based compound screening as a potential anti-enteroviral agent in vitro. However, use of fluoxetine has not previously been studied in humans with enteroviral disease. A five year old boy with X-linked agammaglobulinemia presented with progressive neurological deterioration and was found to have chronic enterovirus encephalitis by brain biopsy. He failed to respond to standard treatment with high dose intravenous immunoglobulin, but showed stabilization and improvement following treatment with fluoxetine. This is the first report to describe the use of fluoxetine as a potential therapy for chronic enterovirus infection. Further investigation of fluoxetine as a treatment option for chronic enterovirus encephalitis is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

PubMed Central

Ruiz de Garibay, Gorka; Herranz, Carmen; Llorente, Alicia; Boni, Jacopo; Serra-Musach, Jordi; Mateo, Francesca; Aguilar, Helena; Gómez-Baldó, Laia; Petit, Anna; Vidal, August; Climent, Fina; Hernández-Losa, Javier; Cordero, Álex; González-Suárez, Eva; Sánchez-Mut, José Vicente; Esteller, Manel; Llatjós, Roger; Varela, Mar; López, José Ignacio; García, Nadia; Extremera, Ana I.; Gumà, Anna; Ortega, Raúl; Plà, María Jesús; Fernández, Adela; Pernas, Sònia; Falo, Catalina; Morilla, Idoia; Campos, Miriam; Gil, Miguel; Román, Antonio; Molina-Molina, María; Ussetti, Piedad; Laporta, Rosalía; Valenzuela, Claudia; Ancochea, Julio; Xaubet, Antoni; Casanova, Álvaro; Pujana, Miguel Angel

2015-01-01

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM. PMID:26167915

Why should we publish Linked Data?

NASA Astrophysics Data System (ADS)

Blower, Jon; Riechert, Maik; Koubarakis, Manolis; Pace, Nino

2016-04-01

We use the Web every day to access information from all kinds of different sources. But the complexity and diversity of scientific data mean that discovering accessing and interpreting data remains a large challenge to researchers, decision-makers and other users. Different sources of useful information on data, algorithms, instruments and publications are scattered around the Web. How can we link all these things together to help users to better understand and exploit earth science data? How can we combine scientific data with other relevant data sources, when standards for describing and sharing data vary so widely between communities? "Linked Data" is a term that describes a set of standards and "best practices" for sharing data on the Web (http://www.w3.org/standards/semanticweb/data). These principles can be summarised as follows: 1. Create unique and persistent identifiers for the important "things" in a community (e.g. datasets, publications, algorithms, instruments). 2. Allow users to "look up" these identifiers on the web to find out more information about them. 3. Make this information machine-readable in a community-neutral format (such as RDF, Resource Description Framework). 4. Within this information, embed links to other things and concepts and say how these are related. 5. Optionally, provide web service interfaces to allow the user to perform sophisticated queries over this information (using a language such as SPARQL). The promise of Linked Data is that, through these techniques, data will be more discoverable, more comprehensible and more usable by different communities, not just the community that produced the data. As a result, many data providers (particularly public-sector institutions) are now publishing data in this way. However, this area is still in its infancy in terms of real-world applications. Data users need guidance and tools to help them use Linked Data. Data providers need reassurance that the investments they are making in

Positive selection moments identify potential functional residues in human olfactory receptors

NASA Technical Reports Server (NTRS)

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

1996-01-01

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

A new approach to chromosome-wide analysis of X-linked markers identifies new associations in Asian and European case-parent triads of orofacial clefts

PubMed Central

Gjerdevik, Miriam; Haaland, Øystein A.; Romanowska, Julia; Lie, Rolv T.

2017-01-01

Background GWAS discoveries on the X-chromosome are underrepresented in the literature primarily because the analytical tools that have been applied were originally designed for autosomal markers. Our objective here is to employ a new robust and flexible tool for chromosome-wide analysis of X-linked markers in complex traits. Orofacial clefts are good candidates for such analysis because of the consistently observed excess of females with cleft palate only (CPO) and excess of males with cleft lip with or without cleft palate (CL/P). Methods Genotypes for 14,486 X-chromosome SNPs in 1,291 Asian and 1,118 European isolated cleft triads were available from a previously published GWAS. The R-package HAPLIN enables genome-wide–level analyses as well as statistical power simulations for a range of biologic scenarios. We analyzed isolated CL/P and isolated CPO for each ethnicity in HAPLIN, using a sliding-window approach to haplotype analysis and two different statistical models, with and without X-inactivation in females. Results There was a larger number of associations in the Asian versus the European sample, and similar to previous reports that have analyzed the same GWAS dataset using different methods, we identified associations with EFNB1/PJA1 and DMD. In addition, new associations were detected with several other genes, among which KLHL4, TBX22, CPXCR1 and BCOR were noteworthy because of their roles in clefting syndromes. A few of the associations were only detected by one particular X-inactivation model, whereas a few others were only detected in one sex. Discussion/Conclusion We found new support for the involvement of X-linked variants in isolated clefts. The associations were specific for ethnicity, sex and model parameterization, highlighting the need for flexible tools that are capable of detecting and estimating such effects. Further efforts are needed to verify and elucidate the potential roles of EFNB1/PJA1, KLHL4, TBX22, CPXCR1 and BCOR in isolated

Hip Hop Dance Experience Linked to Sociocognitive Ability.

PubMed

Bonny, Justin W; Lindberg, Jenna C; Pacampara, Marc C

2017-01-01

Expertise within gaming (e.g., chess, video games) and kinesthetic (e.g., sports, classical dance) activities has been found to be linked with specific cognitive skills. Some of these skills, working memory, mental rotation, problem solving, are linked to higher performance in science, technology, math, and engineering (STEM) disciplines. In the present study, we examined whether experience in a different activity, hip hop dance, is also linked to cognitive abilities connected with STEM skills as well as social cognition ability. Dancers who varied in hip hop and other dance style experience were presented with a set of computerized tasks that assessed working memory capacity, mental rotation speed, problem solving efficiency, and theory of mind. We found that, when controlling for demographic factors and other dance style experience, those with greater hip hop dance experience were faster at mentally rotating images of hands at greater angle disparities and there was a trend for greater accuracy at identifying positive emotions displayed by cropped images of human faces. We suggest that hip hop dance, similar to other more technical activities such as video gameplay, tap some specific cognitive abilities that underlie STEM skills. Furthermore, we suggest that hip hop dance experience can be used to reach populations who may not otherwise be interested in other kinesthetic or gaming activities and potentially enhance select sociocognitive skills.

Hip Hop Dance Experience Linked to Sociocognitive Ability

PubMed Central

Bonny, Justin W.; Lindberg, Jenna C.; Pacampara, Marc C.

2017-01-01

Expertise within gaming (e.g., chess, video games) and kinesthetic (e.g., sports, classical dance) activities has been found to be linked with specific cognitive skills. Some of these skills, working memory, mental rotation, problem solving, are linked to higher performance in science, technology, math, and engineering (STEM) disciplines. In the present study, we examined whether experience in a different activity, hip hop dance, is also linked to cognitive abilities connected with STEM skills as well as social cognition ability. Dancers who varied in hip hop and other dance style experience were presented with a set of computerized tasks that assessed working memory capacity, mental rotation speed, problem solving efficiency, and theory of mind. We found that, when controlling for demographic factors and other dance style experience, those with greater hip hop dance experience were faster at mentally rotating images of hands at greater angle disparities and there was a trend for greater accuracy at identifying positive emotions displayed by cropped images of human faces. We suggest that hip hop dance, similar to other more technical activities such as video gameplay, tap some specific cognitive abilities that underlie STEM skills. Furthermore, we suggest that hip hop dance experience can be used to reach populations who may not otherwise be interested in other kinesthetic or gaming activities and potentially enhance select sociocognitive skills. PMID:28146562

tDCS potentiation provides no evidence for a link between right dorsal-lateral prefrontal cortical activity and empathic responding.

PubMed

Snowdon, Marion E; Cathcart, Stuart

2018-04-01

Previous studies suggest the dorsolateral prefrontal cortex (DLPFC) is involved in processing of empathic concern. This has not been experimentally tested to date. We tested the hypotheses that electrical potentiation in the right DLPFC would be associated with increased empathic concern and prosocial behavior. Participants were randomly allocated to one of three transcranial Direct Current Stimulation (tDCS) conditions: (a) relative right potentiation, (b) relative left potentiation, and (c) sham. Participants viewed images of African children in distressing circumstances, and completed measures of empathic concern pre- and post-tDCS manipulation. Contrary to our prediction, neither effects, nor interactions of heightened empathic concern were observed. These results conflict with previous studies using this bilateral tDCS montage. Explanations could be that stimulation used in this study had been simply too weak (1.5 mA). Alternatively, the area of the DLPFC involved in emotion regulation is closer to the cortex than the area involved in empathic concern, and more easily potentiated by tDCS. Therefore, the DLPFC potentiation in the present study may have linked empathic concern with adaptive emotion regulation strategies. Future research could examine this possibility using measures of emotion regulation and higher fidelity neurostimulation (e.g., repetitive Transcranial Magnetic Stimulation [rTMS]).

Identifying Chemical Groups for Biomonitoring

PubMed Central

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

2016-01-01

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

Forever young: Mechanisms of natural anoxia tolerance and potential links to longevity

PubMed Central

Krivoruchko, Anastasia

2010-01-01

While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater turtles belonging to the Trachemys and Chrysemys genera are the champion facultative anaerobes of the vertebrate world, often surviving without oxygen for many weeks at a time. The physiological and biochemical mechanisms that underlie anoxia tolerance in turtles include profound metabolic rate depression, post-translational modification of proteins, strong antioxidant defenses, activation of specific stress-responsive transcription factors, and enhanced expression of cyto-protective proteins. Turtles are also known for their incredible longevity and display characteristics of “negligible senescence.” We propose that the robust stress-tolerance mechanisms that permit long term anaerobiosis by turtles may also support the longevity of these animals. Many of the mechanisms involved in natural anoxia tolerance, such as hypometabolism or the induction of various protective proteins/pathways, have been shown to play important roles in mammalian oxygen-related diseases and improved understanding of how cells survive without oxygen could aid in the understanding and treatment of various pathological conditions that involve hypoxia or oxidative stress. In the present review we discuss the recent advances made in understanding the molecular nature of anoxia tolerance in turtles and the potential links between this tolerance and longevity. PMID:20716943

A lost link between a flightless parrot and a parasitic plant and the potential role of coprolites in conservation paleobiology.

PubMed

Wood, Jamie R; Wilmshurst, Janet M; Worthy, Trevor H; Holzapfel, Avi S; Cooper, Alan

2012-12-01

Late Quaternary extinctions and population fragmentations have severely disrupted animal-plant interactions globally. Detection of disrupted interactions often relies on anachronistic plant characteristics, such as spines in the absence of large herbivores or large fruit without dispersers. However, obvious anachronisms are relatively uncommon, and it can be difficult to prove a direct link between the anachronism and a particular faunal taxon. Analysis of coprolites (fossil feces) provides a novel way of exposing lost interactions between animals (depositors) and consumed organisms. We analyzed ancient DNA to show that a coprolite from the South Island of New Zealand was deposited by the rare and threatened kakapo (Strigops habroptilus), a large, nocturnal, flightless parrot. When we analyzed the pollen and spore content of the coprolite, we found pollen from the cryptic root-parasite Dactylanthus taylorii. The relatively high abundance (8.9% of total pollen and spores) of this zoophilous pollen type in the coprolite supports the hypothesis of a former direct feeding interaction between kakapo and D. taylorii. The ranges of both species have contracted substantially since human settlement, and their present distributions no longer overlap. Currently, the lesser short-tailed bat (Mystacina tuberculata) is the only known native pollinator of D. taylorii, but our finding raises the possibility that birds, and other small fauna, could have once fed on and pollinated the plant. If confirmed, through experimental work and observations, this finding may inform conservation of the plant. For example, it may be possible to translocate D. taylorii to predator-free offshore islands that lack bats but have thriving populations of endemic nectar-feeding birds. The study of coprolites of rare or extinct taxonomic groups provides a unique way forward to expand existing knowledge of lost plant and animal interactions and to identify pollination and dispersal syndromes. This

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

PubMed

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

2011-12-02

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

Identification of hybrid node and link communities in complex networks

PubMed Central

He, Dongxiao; Jin, Di; Chen, Zheng; Zhang, Weixiong

2015-01-01

Identifying communities in complex networks is an effective means for analyzing complex systems, with applications in diverse areas such as social science, engineering, biology and medicine. Finding communities of nodes and finding communities of links are two popular schemes for network analysis. These schemes, however, have inherent drawbacks and are inadequate to capture complex organizational structures in real networks. We introduce a new scheme and an effective approach for identifying complex mixture structures of node and link communities, called hybrid node-link communities. A central piece of our approach is a probabilistic model that accommodates node, link and hybrid node-link communities. Our extensive experiments on various real-world networks, including a large protein-protein interaction network and a large network of semantically associated words, illustrated that the scheme for hybrid communities is superior in revealing network characteristics. Moreover, the new approach outperformed the existing methods for finding node or link communities separately. PMID:25728010

Identification of hybrid node and link communities in complex networks.

PubMed

He, Dongxiao; Jin, Di; Chen, Zheng; Zhang, Weixiong

2015-03-02

Identifying communities in complex networks is an effective means for analyzing complex systems, with applications in diverse areas such as social science, engineering, biology and medicine. Finding communities of nodes and finding communities of links are two popular schemes for network analysis. These schemes, however, have inherent drawbacks and are inadequate to capture complex organizational structures in real networks. We introduce a new scheme and an effective approach for identifying complex mixture structures of node and link communities, called hybrid node-link communities. A central piece of our approach is a probabilistic model that accommodates node, link and hybrid node-link communities. Our extensive experiments on various real-world networks, including a large protein-protein interaction network and a large network of semantically associated words, illustrated that the scheme for hybrid communities is superior in revealing network characteristics. Moreover, the new approach outperformed the existing methods for finding node or link communities separately.

Identification of hybrid node and link communities in complex networks

NASA Astrophysics Data System (ADS)

He, Dongxiao; Jin, Di; Chen, Zheng; Zhang, Weixiong

2015-03-01

Identifying communities in complex networks is an effective means for analyzing complex systems, with applications in diverse areas such as social science, engineering, biology and medicine. Finding communities of nodes and finding communities of links are two popular schemes for network analysis. These schemes, however, have inherent drawbacks and are inadequate to capture complex organizational structures in real networks. We introduce a new scheme and an effective approach for identifying complex mixture structures of node and link communities, called hybrid node-link communities. A central piece of our approach is a probabilistic model that accommodates node, link and hybrid node-link communities. Our extensive experiments on various real-world networks, including a large protein-protein interaction network and a large network of semantically associated words, illustrated that the scheme for hybrid communities is superior in revealing network characteristics. Moreover, the new approach outperformed the existing methods for finding node or link communities separately.

Resting-state fMRI correlations: From link-wise unreliability to whole brain stability.

PubMed

Pannunzi, Mario; Hindriks, Rikkert; Bettinardi, Ruggero G; Wenger, Elisabeth; Lisofsky, Nina; Martensson, Johan; Butler, Oisin; Filevich, Elisa; Becker, Maxi; Lochstet, Martyna; Kühn, Simone; Deco, Gustavo

2017-08-15

The functional architecture of spontaneous BOLD fluctuations has been characterized in detail by numerous studies, demonstrating its potential relevance as a biomarker. However, the systematic investigation of its consistency is still in its infancy. Here, we analyze within- and between-subject variability and test-retest reliability of resting-state functional connectivity (FC) in a unique data set comprising multiple fMRI scans (42) from 5 subjects, and 50 single scans from 50 subjects. We adopt a statistical framework that enables us to identify different sources of variability in FC. We show that the low reliability of single links can be significantly improved by using multiple scans per subject. Moreover, in contrast to earlier studies, we show that spatial heterogeneity in FC reliability is not significant. Finally, we demonstrate that despite the low reliability of individual links, the information carried by the whole-brain FC matrix is robust and can be used as a functional fingerprint to identify individual subjects from the population. Copyright © 2017 Elsevier Inc. All rights reserved.

Link prediction in the network of global virtual water trade

NASA Astrophysics Data System (ADS)

Tuninetti, Marta; Tamea, Stefania; Laio, Francesco; Ridolfi, Luca

2016-04-01

Through the international food-trade, water resources are 'virtually' transferred from the country of production to the country of consumption. The international food-trade, thus, implies a network of virtual water flows from exporting to importing countries (i.e., nodes). Given the dynamical behavior of the network, where food-trade relations (i.e., links) are created and dismissed every year, link prediction becomes a challenge. In this study, we propose a novel methodology for link prediction in the virtual water network. The model aims at identifying the main factors (among 17 different variables) driving the creation of a food-trade relation between any two countries, along the period between 1986 and 2011. Furthermore, the model can be exploited to investigate the network configuration in the future, under different possible (climatic and demographic) scenarios. The model grounds the existence of a link between any two nodes on the link weight (i.e., the virtual water flow): a link exists when the nodes exchange a minimum (fixed) volume of virtual water. Starting from a set of potential links between any two nodes, we fit the associated virtual water flows (both the real and the null ones) by means of multivariate linear regressions. Then, links with estimated flows higher than a minimum value (i.e., threshold) are considered active-links, while the others are non-active ones. The discrimination between active and non-active links through the threshold introduces an error (called link-prediction error) because some real links are lost (i.e., missed links) and some non-existing links (i.e., spurious links) are inevitably introduced in the network. The major drivers are those significantly minimizing the link-prediction error. Once the structure of the unweighted virtual water network is known, we apply, again, linear regressions to assess the major factors driving the fluxes traded along (modelled) active-links. Results indicate that, on the one hand

Potential Theory for Directed Networks

PubMed Central

Zhang, Qian-Ming; Lü, Linyuan; Wang, Wen-Qiang; Zhou, Tao

2013-01-01

Uncovering factors underlying the network formation is a long-standing challenge for data mining and network analysis. In particular, the microscopic organizing principles of directed networks are less understood than those of undirected networks. This article proposes a hypothesis named potential theory, which assumes that every directed link corresponds to a decrease of a unit potential and subgraphs with definable potential values for all nodes are preferred. Combining the potential theory with the clustering and homophily mechanisms, it is deduced that the Bi-fan structure consisting of 4 nodes and 4 directed links is the most favored local structure in directed networks. Our hypothesis receives strongly positive supports from extensive experiments on 15 directed networks drawn from disparate fields, as indicated by the most accurate and robust performance of Bi-fan predictor within the link prediction framework. In summary, our main contribution is twofold: (i) We propose a new mechanism for the local organization of directed networks; (ii) We design the corresponding link prediction algorithm, which can not only testify our hypothesis, but also find out direct applications in missing link prediction and friendship recommendation. PMID:23408979

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

PubMed

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

2016-10-01

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

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

PubMed

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

2018-06-01

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

Combining Genotype, Phenotype, and Environment to Infer Potential Candidate Genes.

PubMed

Talbot, Benoit; Chen, Ting-Wen; Zimmerman, Shawna; Joost, Stéphane; Eckert, Andrew J; Crow, Taylor M; Semizer-Cuming, Devrim; Seshadri, Chitra; Manel, Stéphanie

2017-03-01

Population genomic analysis can be an important tool in understanding local adaptation. Identification of potential adaptive loci in such analyses is usually based on the survey of a large genomic dataset in combination with environmental variables. Phenotypic data are less commonly incorporated into such studies, although combining a genome scan analysis with a phenotypic trait analysis can greatly improve the insights obtained from each analysis individually. Here, we aimed to identify loci potentially involved in adaptation to climate in 283 Loblolly pine (Pinus taeda) samples from throughout the species' range in the southeastern United States. We analyzed associations between phenotypic, molecular, and environmental variables from datasets of 3082 single nucleotide polymorphism (SNP) loci and 3 categories of phenotypic traits (gene expression, metabolites, and whole-plant traits). We found only 6 SNP loci that displayed potential signals of local adaptation. Five of the 6 identified SNPs are linked to gene expression traits for lignin development, and 1 is linked with whole-plant traits. We subsequently compared the 6 candidate genes with environmental variables and found a high correlation in only 3 of them (R2 > 0.2). Our study highlights the need for a combination of genotypes, phenotypes, and environmental variables, and for an appropriate sampling scheme and study design, to improve confidence in the identification of potential candidate genes. © The American Genetic Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antibiotic efficacy is linked to bacterial cellular respiration

PubMed Central

Lobritz, Michael A.; Belenky, Peter; Porter, Caroline B. M.; Gutierrez, Arnaud; Yang, Jason H.; Schwarz, Eric G.; Dwyer, Daniel J.; Khalil, Ahmad S.; Collins, James J.

2015-01-01

Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes—the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy. PMID:26100898

Xilmass: A New Approach toward the Identification of Cross-Linked Peptides.

PubMed

Yılmaz, Şule; Drepper, Friedel; Hulstaert, Niels; Černič, Maša; Gevaert, Kris; Economou, Anastassios; Warscheid, Bettina; Martens, Lennart; Vandermarliere, Elien

2016-10-18

Chemical cross-linking coupled with mass spectrometry plays an important role in unravelling protein interactions, especially weak and transient ones. Moreover, cross-linking complements several structural determination approaches such as cryo-EM. Although several computational approaches are available for the annotation of spectra obtained from cross-linked peptides, there remains room for improvement. Here, we present Xilmass, a novel algorithm to identify cross-linked peptides that introduces two new concepts: (i) the cross-linked peptides are represented in the search database such that the cross-linking sites are explicitly encoded, and (ii) the scoring function derived from the Andromeda algorithm was adapted to score against a theoretical tandem mass spectrometry (MS/MS) spectrum that contains the peaks from all possible fragment ions of a cross-linked peptide pair. The performance of Xilmass was evaluated against the recently published Kojak and the popular pLink algorithms on a calmodulin-plectin complex data set, as well as three additional, published data sets. The results show that Xilmass typically had the highest number of identified distinct cross-linked sites and also the highest number of predicted cross-linked sites.

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment‐Based Drug Design Facilitated by Dynamic Combinatorial Chemistry

PubMed Central

Mondal, Milon; Radeva, Nedyalka; Fanlo‐Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard

2016-01-01

Abstract Fragment‐based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit‐identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X‐ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis‐acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240‐fold improvement in potency compared to the parent hits. Subsequent X‐ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit‐identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit‐to‐lead optimization. PMID:27400756

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

PubMed

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

2015-05-01

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

O-linked oligosaccharides on insulin receptor

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

Collier, E.; Gorden, P.

1991-02-01

The insulin receptor, an integral membrane glycoprotein, is synthesized as a single-chain precursor that is cleaved to produce two mature subunits, both of which contain N-linked oligosaccharide chains and covalently linked fatty acids. We report that the beta-subunit also contains O-linked oligosaccharides. The proreceptor, alpha-subunit, and beta-subunit were labeled with (3H)mannose and (3H)galactose in the presence or absence of an inhibitor of O-linked glycosylation. Tryptic peptides from each component were separated by reverse-phase high-performance liquid chromatography. N- and O-linked oligosaccharide chains were identified on these peptides by specific enzymatic digestions. The proreceptor and alpha-subunit contained only N-linked oligosaccharides, whereas themore » beta-subunit contained both N- and O-linked oligosaccharides. The O-linked oligosaccharide chains were attached to a single tryptic fraction of the beta-subunit, which also contained N-linked chains. This fraction was further localized to the NH2-terminal tryptic peptide of the beta-subunit by specific immunoprecipitation with an anti-peptide antibody with specificity for this region. Binding of insulin and autophosphorylation of the beta-subunit were not dependent on O-linked glycosylation, because cells grown in the presence of the inhibitor exhibited a normal dose response to insulin. Therefore, the insulin receptor contains O-linked oligosaccharides on the NH2-terminal tryptic peptide of the beta-subunit, and these O-linked oligosaccharides are not necessary to the binding or autophosphorylation function of the receptor.« less

Imaging Mitochondrial Redox Potential and Its Possible Link to Tumor Metastatic Potential

PubMed Central

Li, Lin Z.

2012-01-01

Cellular redox states can regulate cell metabolism, growth, differentiation, motility, apoptosis, signaling pathways, and gene expressions etc. Growing body of literature suggest importance of redox status for cancer progression. While most studies on redox state were done on cells and tissue lysates, it is important to understand the role of redox state in tissue in vivo/ex vivo and image its heterogeneity. Redox scanning is a clinically-translatable method for imaging tissue mitochondrial redox potential with a submillimeter resolution. Redox scanning data in mouse models of human cancers demonstrate a correlation between mitochondrial redox state and tumor metastatic potential. I will discuss the significance of this correlation and possible directions for future research. PMID:22895837

Study of Lateral Misalignment Tolerance of a Symmetric Free-Space Optical Link for Intra International Space Station Communication

NASA Technical Reports Server (NTRS)

Tedder, Sarah A.; Schoenholz, Bryan; Suddath, Shannon N.

2016-01-01

This paper describes the study of lateral misalignment tolerance of a symmetric high-rate free-space optical link (FSOL) for use between International Space Station (ISS) payload sites and the main cabin. The link will enable gigabit per second (Gbps) transmission of data, which is up to three orders of magnitude greater than the current capabilities. This application includes 10-20 meter links and requires minimum size, weight, and power (SWaP). The optical power must not present an eye hazard and must be easily integrated into the existing ISS infrastructure. On the ISS, rapid thermal changes and astronaut movement will cause flexure of the structure which will potentially misalign the free space transmit and receive optics 9 cm laterally and 0.2 degrees angularly. If this misalignment is not accounted for, a loss of the link or degradation of link performance will occur. Power measurements were collected to better understand the effect of various system design parameters on lateral misalignment. Parameters that were varied include: the type of small form pluggable (SFP) transceivers, type of fiber, and transmitted power level. A potential solution was identified that can reach the lateral misalignment tolerance (decenter span) required to create an FSOL on the ISS by using 105 m core fibers, a duplex SFP, two channels of light, and two fiber amplifiers.

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

EPA Science Inventory

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

Molecular characterization of a novel X-linked syndrome involving developmental delay and deafness.

PubMed

Hildebrand, Michael S; de Silva, Michelle G; Tan, Tiong Yang; Rose, Elizabeth; Nishimura, Carla; Tolmachova, Tanya; Hulett, Joanne M; White, Susan M; Silver, Jeremy; Bahlo, Melanie; Smith, Richard J H; Dahl, Hans-Henrik M

2007-11-01

X-linked syndromes associated with developmental delay and sensorineural hearing loss (SNHL) have been characterized at the molecular level, including Mohr-Tranebjaerg syndrome and Norrie disease. In this study we report on a novel X-linked recessive, congenital syndrome in a family with developmental delay and SNHL that maps to a locus associated with mental retardation (MR) for which no causative gene has been identified. The X-linked recessive inheritance and congenital nature of the syndrome was confirmed by detailed clinical investigation and the family history. Linkage mapping of the X-chromosome was conducted to ascertain the disease locus and candidate genes were screened by direct sequencing and STRP analysis. The recessive syndrome was mapped to Xp11.3-q21.32 and a deletion was identified in a regulatory region upstream of the POU3F4 gene in affected family members. Since mutations in POU3F4 cause deafness at the DFN3 locus, the deletion is the likely cause of the SNHL in this family. The choroideremia (CHM) gene was also screened and a novel missense change was identified. The alteration changes the serine residue at position 89 in the Rab escort 1 protein (REP-1) to a cysteine (S89C). Prenylation of Rab proteins was investigated in patients and the location of REP-1 expression in the brain determined. However, subsequent analysis revealed that this change in CHM was polymorphic having no effect on REP-1 function. Although the causative gene at the MR locus in this family has not been identified, there are a number of genes involved in syndromic and nonsyndromic forms of MR that are potential candidates. Copyright 2007 Wiley-Liss, Inc.

Physical Samples Linked Data in Action

NASA Astrophysics Data System (ADS)

Ji, P.; Arko, R. A.; Lehnert, K.; Bristol, S.

2017-12-01

Most data and metadata related to physical samples currently reside in isolated relational databases driven by diverse data models. How to approach the challenge for sharing, interchanging and integrating data from these difference relational databases motivated us to publish Linked Open Data for collections of physical samples, using Semantic Web technologies including the Resource Description Framework (RDF), RDF Query Language (SPARQL), and Web Ontology Language (OWL). In last few years, we have released four knowledge graphs concentrated on physical samples, including System for Earth Sample Registration (SESAR), USGS National Geochemical Database (NGDC), Ocean Biogeographic Information System (OBIS), and Earthchem Database. Currently the four knowledge graphs contain over 12 million facets (triples) about objects of interest to the geoscience domain. Choosing appropriate domain ontologies for representing context of data is the core of the whole work. Geolink ontology developed by Earthcube Geolink project was used as top level to represent common concepts like person, organization, cruise, etc. Physical sample ontology developed by Interdisciplinary Earth Data Alliance (IEDA) and Darwin Core vocabulary were used as second level to describe details about geological samples and biological diversity. We also focused on finding and building best tool chains to support the whole life cycle of publishing linked data we have, including information retrieval, linked data browsing and data visualization. Currently, Morph, Virtuoso Server, LodView, LodLive, and YASGUI were employed for converting, storing, representing, and querying data in a knowledge base (RDF triplestore). Persistent digital identifier is another main point we concentrated on. Open Researcher & Contributor IDs (ORCIDs), International Geo Sample Numbers (IGSNs), Global Research Identifier Database (GRID) and other persistent identifiers were used to link different resources from various graphs with

Discovery Proteomics Identifies a Molecular Link between the Coatomer Protein Complex I and Androgen Receptor-dependent Transcription*

PubMed Central

Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Lee, Jinhee; Wright, Michael E.

2016-01-01

Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the “AR-interactome.” Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR). A bioanalytical workflow involving streptavidin chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand-sensitive cytosolic proteins/protein complexes linked to AR activation in prostate tumor cells. Functional studies verified that ligand-sensitive proteins identified in the proteomic screen encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR-interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive coatomer protein complex I (COPI) retrograde trafficking complex in vitro. Extensive biochemical and molecular experiments showed that the COPI retrograde complex regulates ligand-mediated AR transcriptional activation, which correlated with the mobilization of the Golgi-localized ARA160 coactivator to the nuclear compartment of prostate tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR

Seismic link at plate boundary

NASA Astrophysics Data System (ADS)

Ramdani, Faical; Kettani, Omar; Tadili, Benaissa

2015-06-01

Seismic triggering at plate boundaries has a very complex nature that includes seismic events at varying distances. The spatial orientation of triggering cannot be reduced to sequences from the main shocks. Seismic waves propagate at all times in all directions, particularly in highly active zones. No direct evidence can be obtained regarding which earthquakes trigger the shocks. The first approach is to determine the potential linked zones where triggering may occur. The second step is to determine the causality between the events and their triggered shocks. The spatial orientation of the links between events is established from pre-ordered networks and the adapted dependence of the spatio-temporal occurrence of earthquakes. Based on a coefficient of synchronous seismic activity to grid couples, we derive a network link by each threshold. The links of high thresholds are tested using the coherence of time series to determine the causality and related orientation. The resulting link orientations at the plate boundary conditions indicate that causal triggering seems to be localized along a major fault, as a stress transfer between two major faults, and parallel to the geothermal area extension.

Public awareness of the link between alcohol and cancer in England in 2015: a population-based survey.

PubMed

Buykx, Penny; Li, Jessica; Gavens, Lucy; Hooper, Lucie; Lovatt, Melanie; Gomes de Matos, Elena; Meier, Petra; Holmes, John

2016-11-30

Public knowledge of the association between alcohol and cancer is reported to be low. We aimed to provide up-to-date evidence for England regarding awareness of the link between alcohol and different cancers and to determine whether awareness differs by demographic characteristics, alcohol use, and geographic region. A representative sample of 2100 adults completed an online survey in July 2015. Respondents were asked to identify which health outcomes, including specific cancers, may be caused by alcohol consumption. Logistic regressions explored whether demographic, alcohol use, and geographic characteristics predicted correctly identifying alcohol-related cancer risk. Unprompted, 12.9% of respondents identified cancer as a potential health outcome of alcohol consumption. This rose to 47% when prompted (compared to 95% for liver disease and 73% for heart disease). Knowledge of the link between alcohol and specific cancers varied between 18% (breast) and 80% (liver). Respondents identified the following cancers as alcohol-related where no such evidence exists: bladder (54%), brain (32%), ovarian (17%). Significant predictors of awareness of the link between alcohol and cancer were being female, more highly educated, and living in North-East England. There is generally low awareness of the relationship between alcohol consumption and cancer, particularly breast cancer. Greater awareness of the relationship between alcohol and breast cancer in North-East England, where a mass media campaign highlighted this relationship, suggests that population awareness can be influenced by social marketing.

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

PubMed

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

2010-09-01

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

Beyond human error taxonomies in assessment of risk in sociotechnical systems: a new paradigm with the EAST 'broken-links' approach.

PubMed

Stanton, Neville A; Harvey, Catherine

2017-02-01

Risk assessments in Sociotechnical Systems (STS) tend to be based on error taxonomies, yet the term 'human error' does not sit easily with STS theories and concepts. A new break-link approach was proposed as an alternative risk assessment paradigm to reveal the effect of information communication failures between agents and tasks on the entire STS. A case study of the training of a Royal Navy crew detecting a low flying Hawk (simulating a sea-skimming missile) is presented using EAST to model the Hawk-Frigate STS in terms of social, information and task networks. By breaking 19 social links and 12 task links, 137 potential risks were identified. Discoveries included revealing the effect of risk moving around the system; reducing the risks to the Hawk increased the risks to the Frigate. Future research should examine the effects of compounded information communication failures on STS performance. Practitioner Summary: The paper presents a step-by-step walk-through of EAST to show how it can be used for risk assessment in sociotechnical systems. The 'broken-links' method takes a systemic, rather than taxonomic, approach to identify information communication failures in social and task networks.

Organization of photosystem I polypeptides examined by chemical cross-linking

NASA Technical Reports Server (NTRS)

Armbrust, T. S.; Chitnis, P. R.; Guikema, J. A.; Spooner, B. S. (Principal Investigator)

1996-01-01

Photosystem I from the cyanobacterium Synechocystis sp. PCC 6803 was examined using the chemical cross-linkers glutaraldehyde and N-ethyl-1-3-[3-(dimethylamino)propyl]carbodiimide to investigate the organization of the polypeptide subunits. Thylakoid membranes and photosystem I, which was isolated by Triton X-100 fractionation, were treated with cross-linking reagents and were resolved using a Tricine/urea low-molecular-weight resolution gel system. Subunit-specific antibodies and western blotting analysis were used to identify the components of cross-linked species. These analyses identified glutaraldehyde-dependent cross-linking products composed of small amounts of PsaD and PsaC, PsaC and PsaE, and PsaE and PsaF. The novel cross-link between PsaE and PsaF was also observed following treatment with N-ethyl-1-3-[3-(dimethylamino)propyl]carbodiimide. These cross-linking results suggest a structural interaction between PsaE and PsaF and predict a transmembrane topology for PsaF.

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Identifying Key Networks Linked to Light-Independent Photoreceptor Degeneration in Visual Arrestin 1 Knockout Mice.

PubMed

Kim, Hwa Sun; Huang, Shun-Ping; Lee, Eun-Jin; Craft, Cheryl Mae

2018-01-01

When visual arrestin 1 (ARR1, S-antigen, 48 KDa protein) was genetically knocked out in mice (original Arr1 -/- , designated Arr1 -/-A ), rod photoreceptors degenerated in a light-dependent manner. Subsequently, a light-independent cone dystrophy was identified with minimal rod death in ARR1 knockout mice (Arr1 -/-A Arr4 +/+ , designated Arr1 -/-B ), which were F2 littermates from breeding the original Arr1 -/-A and cone arrestin knockout 4 (Arr4 -/- ) mice. To resolve the genetic and phenotypic differences between the two ARR1 knockouts, we performed Affymetrix™ exon array analysis to focus on the potential differential gene expression profile and to explore the molecular and cellular pathways leading to this observed susceptibility to cone dystrophy in Arr1 -/-B compared to Arr1 -/-A or control Arr1 +/+ Arr4 +/+ (wild type [WT]). Only in the Arr1 -/-B retina did we observe an up-regulation of retinal transcripts involved in the immune response, inflammatory response and JAK-STAT signaling molecules, OSMRβ and phosphorylation of STAT3. Of these responses, the complement system was significantly higher, and a variety of inflammatory responses by complement regulation and anti-inflammatory cytokine or factors were identified in Arr1 -/-B retinal transcripts. This discovery supports that Arr1 -/-B has a distinct genetic background from Arr1 -/-A that results in alterations in its retinal phenotype leading to susceptibility to cone degeneration induced by inappropriate inflammatory and immune responses.

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

PubMed Central

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

2016-01-01

Epstein-Barr virus, a B-lymphotropic herpesvirus, is the cause of infectious mononucleosis, has strong aetiologic links with several malignancies and has been implicated in certain autoimmune diseases. Efforts to develop a prophylactic vaccine to prevent or reduce EBV-associated disease have, to date, focused on the induction of neutralising antibody responses. However, such vaccines might be further improved by inducing T cell responses capable of recognising and killing recently-infected B cells. In that context, EBNA2, EBNA-LP and BHRF1 are the first viral antigens expressed during the initial stage of B cell growth transformation, yet have been poorly characterised as CD8+ T cell targets. Here we describe CD8+ T cell responses against each of these three “first wave” proteins, identifying target epitopes and HLA restricting alleles. While EBNA-LP and BHRF1 each contained one strong CD8 epitope, epitopes within EBNA2 induced immunodominant responses through several less common HLA class I alleles (e.g. B*3801 and B*5501), as well as subdominant responses through common class I alleles (e.g. B7 and C*0304). Importantly, such EBNA2-specific CD8+ T cells recognised B cells within the first day post-infection, prior to CD8+ T cells against well-characterised latent target antigens such as EBNA3B or LMP2, and effectively inhibited outgrowth of EBV-transformed B cell lines. We infer that “first wave” antigens of the growth-transforming infection, especially EBNA2, constitute potential CD8+ T cell immunogens for inclusion in prophylactic EBV vaccine design. PMID:27096949

Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

PubMed

Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

2018-01-01

Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Di-isodityrosine is the intermolecular cross-link of isodityrosine-rich extensin analogs cross-linked in vitro.

PubMed

Held, Michael A; Tan, Li; Kamyab, Abdolreza; Hare, Michael; Shpak, Elena; Kieliszewski, Marcia J

2004-12-31

Extensins are cell wall hydroxyproline-rich glycoproteins that form covalent networks putatively involving tyrosyl and lysyl residues in cross-links catalyzed by one or more extensin peroxidases. The precise cross-links remain to be chemically identified both as network components in muro and as enzymic products generated in vitro with native extensin monomers as substrates. However, some extensin monomers contain variations within their putative cross-linking motifs that complicate cross-link identification. Other simpler extensins are recalcitrant to isolation including the ubiquitous P3-type extensin whose major repetitive motif, Hyp)(4)-Ser-Hyp-Ser-(Hyp)(4)-Tyr-Tyr-Tyr-Lys, is of particular interest, not least because its Tyr-Tyr-Tyr intramolecular isodityrosine cross-link motifs are also putative candidates for further intermolecular cross-linking to form di-isodityrosine. Therefore, we designed a set of extensin analogs encoding tandem repeats of the P3 motif, including Tyr --> Phe and Lys --> Leu variations. Expression of these P3 analogs in Nicotiana tabacum cells yielded glycoproteins with virtually all Pro residues hydroxylated and subsequently arabinosylated and with likely galactosylated Ser residues. This was consistent with earlier analyses of P3 glycopeptides isolated from cell wall digests and the predictions of the Hyp contiguity hypothesis. The tyrosine-rich P3 analogs also contained isodityrosine, formed in vivo. Significantly, these isodityrosine-containing analogs were further cross-linked in vitro by an extensin peroxidase to form the tetra-tyrosine intermolecular cross-link amino acid di-isodityrosine. This is the first identification of an inter-molecular cross-link amino acid in an extensin module and corroborates earlier suggestions that di-isodityrosine represents one mechanism for cross-linking extensins in muro.

Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity.

PubMed

Chéreau, Ronan; Saraceno, G Ezequiel; Angibaud, Julie; Cattaert, Daniel; Nägerl, U Valentin

2017-02-07

Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.

Linking Schools and Workplaces: Lessons from Australia and Overseas.

ERIC Educational Resources Information Center

Sweet, Richard

Efforts to link schools and workplaces in Australia, Sweden, and elsewhere were examined to identify preconditions and effective strategies for linking school to work in Australia. An Australian program that combines applied, contextualized learning structured according to industry standards with students' general education was shown to produce…

Novel Magnetic Cross-Linked Cellulase Aggregates with a Potential Application in Lignocellulosic Biomass Bioconversion.

PubMed

Jia, Junqi; Zhang, Weiwei; Yang, Zengjie; Yang, Xianling; Wang, Na; Yu, Xiaoqi

2017-02-10

The utilization of renewable biomass resources to produce high-value chemicals by enzymatic processes is beneficial for alternative energy production, due to the accelerating depletion of fossil fuels. As immobilization techniques can improve enzyme stability and reusability, a novel magnetic cross-linked cellulase aggregate has been developed and applied for biomass bioconversion. The crosslinked aggregates could purify and immobilize enzymes in a single operation, and could then be combined with magnetic nanoparticles (MNPs), which provides easy separation of the materials. The immobilized cellulase showed a better activity at a wider temperature range and pH values than that of the free cellulase. After six cycles of consecutive reuse, the immobilized cellulase performed successful magnetic separation and retained 74% of its initial activity when carboxylmethyl cellulose (CMC) was used as the model substrate. Furthermore, the structure and morphology of the immobilized cellulase were studied by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Moreover, the immobilized cellulase was shown to hydrolyze bamboo biomass with a yield of 21%, and was re-used in biomass conversion up to four cycles with 38% activity retention, which indicated that the immobilized enzyme has good potential for biomass applications.

Using Link Disconnection Entropy Disorder to Detect Fast Moving Nodes in MANETs

PubMed Central

Palafox, Luis E.; Aguilar, Leocundo; Sanchez, Mauricio A.; Martinez, Luis G.

2016-01-01

Mobile ad-hoc networks (MANETs) are dynamic by nature; this dynamism comes from node mobility, traffic congestion, and other transmission conditions. Metrics to evaluate the effects of those conditions shine a light on node’s behavior in an ad-hoc network, helping to identify the node or nodes with better conditions of connection. In this paper, we propose a relative index to evaluate a single node reliability, based on the link disconnection entropy disorder using neighboring nodes as reference. Link disconnection entropy disorder is best used to identify fast moving nodes or nodes with unstable communications, this without the need of specialized sensors such as GPS. Several scenarios were studied to verify the index, measuring the effects of Speed and traffic density on the link disconnection entropy disorder. Packet delivery ratio is associated to the metric detecting a strong relationship, enabling the use of the link disconnection entropy disorder to evaluate the stability of a node to communicate with other nodes. To expand the utilization of the link entropy disorder, we identified nodes with higher speeds in network simulations just by using the link entropy disorder. PMID:27219671

Using Link Disconnection Entropy Disorder to Detect Fast Moving Nodes in MANETs.

PubMed

Alvarez, Carlos F; Palafox, Luis E; Aguilar, Leocundo; Sanchez, Mauricio A; Martinez, Luis G

2016-01-01

Mobile ad-hoc networks (MANETs) are dynamic by nature; this dynamism comes from node mobility, traffic congestion, and other transmission conditions. Metrics to evaluate the effects of those conditions shine a light on node's behavior in an ad-hoc network, helping to identify the node or nodes with better conditions of connection. In this paper, we propose a relative index to evaluate a single node reliability, based on the link disconnection entropy disorder using neighboring nodes as reference. Link disconnection entropy disorder is best used to identify fast moving nodes or nodes with unstable communications, this without the need of specialized sensors such as GPS. Several scenarios were studied to verify the index, measuring the effects of Speed and traffic density on the link disconnection entropy disorder. Packet delivery ratio is associated to the metric detecting a strong relationship, enabling the use of the link disconnection entropy disorder to evaluate the stability of a node to communicate with other nodes. To expand the utilization of the link entropy disorder, we identified nodes with higher speeds in network simulations just by using the link entropy disorder.

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

PubMed

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

2016-08-01

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

Cross-Link Guided Molecular Modeling with ROSETTA

PubMed Central

Leitner, Alexander; Rosenberger, George; Aebersold, Ruedi; Malmström, Lars

2013-01-01

Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these distance restraints can be best integrated into molecular modeling calculations. Here, we introduce three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking. We demonstrate that the cross-link validation and visualization software Xwalk facilitates successful cross-link data integration. Besides the protocols we introduce XLdb, a database of chemical cross-links from 14 different publications with 506 intra-protein and 62 inter-protein cross-links, where each cross-link can be mapped on an experimental structure from the Protein Data Bank. Finally, we demonstrate on a protein-protein docking reference data set the impact of virtual cross-links on protein docking calculations and show that an inter-protein cross-link can reduce on average the RMSD of a docking prediction by 5.0 Å. The methods and results presented here provide guidelines for the effective integration of chemical cross-link data in molecular modeling calculations and should advance the structural analysis of particularly large and transient protein complexes via hybrid structural biology methods. PMID:24069194

The Linked CENTURY Study: linking three decades of clinical and public health data to examine disparities in childhood obesity.

PubMed

Hawkins, Summer Sherburne; Gillman, Matthew W; Rifas-Shiman, Sheryl L; Kleinman, Ken P; Mariotti, Megan; Taveras, Elsie M

2016-03-09

Despite the need to identify the causes of disparities in childhood obesity, the existing epidemiologic studies of early life risk factors have several limitations. We report on the construction of the Linked CENTURY database, incorporating CENTURY (Collecting Electronic Nutrition Trajectory Data Using Records of Youth) Study data with birth certificates; and discuss the potential implications of combining clinical and public health data sources in examining the etiology of disparities in childhood obesity. We linked the existing CENTURY Study, a database of 269,959 singleton children from birth to age 18 years with measured heights and weights, with each child's Massachusetts birth certificate, which captures information on their mothers' pregnancy history and detailed socio-demographic information of both mothers and fathers. Overall, 74.2 % were matched, resulting in 200,343 children in the Linked CENTURY Study with 1,580,597 well child visits. Among this cohort, 94.0 % (188,334) of children have some father information available on the birth certificate and 60.9 % (121,917) of children have at least one other sibling in the dataset. Using maternal race/ethnicity from the birth certificate as an indicator of children's race/ethnicity, 75.7 % of children were white, 11.6 % black, 4.6 % Hispanic, and 5.7 % Asian. Based on socio-demographic information from the birth certificate, 20.0 % of mothers were non-US born, 5.9 % smoked during pregnancy, 76.3 % initiated breastfeeding, and 11.0 % of mothers had their delivery paid for by public health insurance. Using clinical data from the CENTURY Study, 22.7 % of children had a weight-for-length ≥ 95(th) percentile between 1 and 24 months and 12.0 % of children had a body mass index ≥ 95(th) percentile at ages 5 and 17 years. By linking routinely-collected data sources, it is possible to address research questions that could not be answered with either source alone. Linkage between a clinical

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

Code of Federal Regulations, 2014 CFR

2014-07-01

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

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

Code of Federal Regulations, 2012 CFR

2012-07-01

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

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

Code of Federal Regulations, 2013 CFR

2013-07-01

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

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

Code of Federal Regulations, 2011 CFR

2011-07-01

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

Identifying Potential Collapse Features Under Highways : Executive Summary

DOT National Transportation Integrated Search

2003-03-01

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

Employee adiposity and incivility: establishing a link and identifying demographic moderators and negative consequences.

PubMed

Sliter, Katherine A; Sliter, Michael T; Withrow, Scott A; Jex, Steve M

2012-10-01

The prevalence of increased adiposity among employees in the American workplace has resulted in significant economic costs to organizations. Unfortunately, relatively little research has examined the effects of excess adiposity on employees themselves. As a step toward remedying this, the current study examined a previously unknown link between adiposity and incivility, and how this might impact employee burnout and withdrawal. A student sample was used to initially establish a link between incivility and adiposity, and an applied sample of employees from across the United States was used to more fully test the relationships among incivility, adiposity, burnout, and withdrawal. Finally, the moderating effects of sex and race on these relationships were examined. Preliminary data from 341 student employees revealed that being overly adipose was related to greater reports of workplace incivility, with the effect strongest for those classified as obese. An interaction between sex and adiposity was also found, as well as a three-way interaction among sex, race, and adiposity. These relationships were replicated using a nationwide sample of 528 full-time employees. An interaction between race and adiposity was also found in this second sample. Finally, a model was tested in which incivility was shown to partially mediate the positive relationship between adiposity and the outcome of withdrawal, with both sex and race acting as moderators. Theoretical and practical implications of the findings and future directions are discussed.

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

PubMed

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

2006-10-01

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

Diatoms to human uses: linking nitrogen deposition, aquatic eutrophication, and ecosystem services

DOE PAGES

Rhodes, Charles; Bingham, Andrew; Heard, Andrea M.; ...

2017-07-24

Nitrogen (N) loading to aquatic ecosystems can lead to eutrophication, changing the ecosystem within a waterbody, including primary productivity, water clarity, and food web dynamics. Nutrient loading often first affects the primary productivity of aquatic systems through shifts in phytoplankton communities. However, ecologically important changes in phytoplankton are often not relatable to the general public—whose behavior would need to change to alter patterns of nutrient loading. Therefore, we use the STressor–Ecological Production function–final ecosystem Services Framework to develop 154 chains that link changes in biological indicators of aquatic eutrophication (a shift in phytoplankton community) to final ecosystem services that peoplemore » use or appreciate. We identify 13 ecological production functions (EPF) within three different ecosystems (alpine lakes, lakes, and estuaries) that connect changes in phytoplankton and algae to ecological endpoints that the general public and policy makers can appreciate. Using the Final Ecosystem Goods and Services Classification System, we identify 18 classes of human beneficiaries that potentially will be impacted by a change in one of these endpoints. We further assign strength-of-science scores to each link within the EPFs for the 154 chains according to how well each link is supported by current peer-reviewed literature. By identifying many pathways through which excess N loading in U.S. surface waters can affect ecosystems and ultimately the beneficiaries of ecosystem services, this work intends to draw attention to gaps in empirical ecological literature that constrain understanding of the magnitude of effects that excess N loading can have on human well-being. Here, results highlight the importance of intersections between the natural and social sciences when managers and policy makers evaluate impacts from ecological stressors. A balance between knowledgeable specialists proved key to applying this

Diatoms to human uses: linking nitrogen deposition, aquatic eutrophication, and ecosystem services

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

Rhodes, Charles; Bingham, Andrew; Heard, Andrea M.

Nitrogen (N) loading to aquatic ecosystems can lead to eutrophication, changing the ecosystem within a waterbody, including primary productivity, water clarity, and food web dynamics. Nutrient loading often first affects the primary productivity of aquatic systems through shifts in phytoplankton communities. However, ecologically important changes in phytoplankton are often not relatable to the general public—whose behavior would need to change to alter patterns of nutrient loading. Therefore, we use the STressor–Ecological Production function–final ecosystem Services Framework to develop 154 chains that link changes in biological indicators of aquatic eutrophication (a shift in phytoplankton community) to final ecosystem services that peoplemore » use or appreciate. We identify 13 ecological production functions (EPF) within three different ecosystems (alpine lakes, lakes, and estuaries) that connect changes in phytoplankton and algae to ecological endpoints that the general public and policy makers can appreciate. Using the Final Ecosystem Goods and Services Classification System, we identify 18 classes of human beneficiaries that potentially will be impacted by a change in one of these endpoints. We further assign strength-of-science scores to each link within the EPFs for the 154 chains according to how well each link is supported by current peer-reviewed literature. By identifying many pathways through which excess N loading in U.S. surface waters can affect ecosystems and ultimately the beneficiaries of ecosystem services, this work intends to draw attention to gaps in empirical ecological literature that constrain understanding of the magnitude of effects that excess N loading can have on human well-being. Here, results highlight the importance of intersections between the natural and social sciences when managers and policy makers evaluate impacts from ecological stressors. A balance between knowledgeable specialists proved key to applying this

Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements

PubMed Central

Mumbach, Maxwell R; Satpathy, Ansuman T; Boyle, Evan A; Dai, Chao; Gowen, Benjamin G; Cho, Seung Woo; Nguyen, Michelle L; Rubin, Adam J; Granja, Jeffrey M; Kazane, Katelynn R; Wei, Yuning; Nguyen, Trieu; Greenside, Peyton G; Corces, M Ryan; Tycko, Josh; Simeonov, Dimitre R; Suliman, Nabeela; Li, Rui; Xu, Jin; Flynn, Ryan A; Kundaje, Anshul; Khavari, Paul A; Marson, Alexander; Corn, Jacob E; Quertermous, Thomas; Greenleaf, William J; Chang, Howard Y

2018-01-01

The challenge of linking intergenic mutations to target genes has limited molecular understanding of human diseases. Here we show that H3K27ac HiChIP generates high-resolution contact maps of active enhancers and target genes in rare primary human T cell subtypes and coronary artery smooth muscle cells. Differentiation of naive T cells into T helper 17 cells or regulatory T cells creates subtype-specific enhancer–promoter interactions, specifically at regions of shared DNA accessibility. These data provide a principled means of assigning molecular functions to autoimmune and cardiovascular disease risk variants, linking hundreds of noncoding variants to putative gene targets. Target genes identified with HiChIP are further supported by CRISPR interference and activation at linked enhancers, by the presence of expression quantitative trait loci, and by allele-specific enhancer loops in patient-derived primary cells. The majority of disease-associated enhancers contact genes beyond the nearest gene in the linear genome, leading to a fourfold increase in the number of potential target genes for autoimmune and cardiovascular diseases. PMID:28945252

A general method for targeted quantitative cross-linking mass spectrometry

USDA-ARS?s Scientific Manuscript database

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, NM...

Evaluation of linking pavement related databases.

DOT National Transportation Integrated Search

2007-03-01

In general, the objectives of this study were to identify and solve various issues in linking pavement performance related database. The detailed objectives were: to evaluate the state-of-the-art in information technology for data integration and dat...

Crowd-sourced Ontology for Photoleukocoria: Identifying Common Internet Search Terms for a Potentially Important Pediatric Ophthalmic Sign.

PubMed

Staffieri, Sandra E; Kearns, Lisa S; Sanfilippo, Paul G; Craig, Jamie E; Mackey, David A; Hewitt, Alex W

2018-02-01

Leukocoria is the most common presenting sign for pediatric eye disease including retinoblastoma and cataract, with worse outcomes if diagnosis is delayed. We investigated whether individuals could identify leukocoria in photographs (photoleukocoria) and examined their subsequent Internet search behavior. Using a web-based questionnaire, in this cross-sectional study we invited adults aged over 18 years to view two photographs of a child with photoleukocoria, and then search the Internet to determine a possible diagnosis and action plan. The most commonly used search terms and websites accessed were recorded. The questionnaire was completed by 1639 individuals. Facebook advertisement was the most effective recruitment strategy. The mean age of all respondents was 38.95 ± 14.59 years (range, 18-83), 94% were female, and 59.3% had children. An abnormality in the images presented was identified by 1613 (98.4%) participants. The most commonly used search terms were: "white," "pupil," "photo," and "eye" reaching a variety of appropriate websites or links to print or social media articles. Different words or phrases were used to describe the same observation of photoleukocoria leading to a range of websites. Variations in the description of observed signs and search words influenced the sites reached, information obtained, and subsequent help-seeking intentions. Identifying the most commonly used search terms for photoleukocoria is an important step for search engine optimization. Being directed to the most appropriate websites informing of the significance of photoleukocoria and the appropriate actions to take could improve delays in diagnosis of important pediatric eye disease such as retinoblastoma or cataract.

Immunoblotting Quantification Approach for Identifying Potential Hypoallergenic Citrus Cultivars.

PubMed

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

2018-02-28

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

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry.

PubMed

Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K H

2016-08-01

Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

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

PubMed

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

2018-01-01

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

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

PubMed

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

2016-06-01

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

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

PubMed

Xiao, Yang; Xiao, Qiang

2018-03-29

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

Thioredoxin links redox to the regulation of fundamental processes of plant mitochondria

PubMed Central

Balmer, Yves; Vensel, William H.; Tanaka, Charlene K.; Hurkman, William J.; Gelhaye, Eric; Rouhier, Nicolas; Jacquot, Jean-Pierre; Manieri, Wanda; Schürmann, Peter; Droux, Michel; Buchanan, Bob B.

2004-01-01

Mitochondria contain thioredoxin (Trx), a regulatory disulfide protein, and an associated flavoenzyme, NADP/Trx reductase, which provide a link to NADPH in the organelle. Unlike animal and yeast counterparts, the function of Trx in plant mitochondria is largely unknown. Accordingly, we have applied recently devised proteomic approaches to identify soluble Trx-linked proteins in mitochondria isolated from photosynthetic (pea and spinach leaves) and heterotrophic (potato tubers) sources. Application of the mitochondrial extracts to mutant Trx affinity columns in conjunction with proteomics led to the identification of 50 potential Trx-linked proteins functional in 12 processes: photorespiration, citric acid cycle and associated reactions, lipid metabolism, electron transport, ATP synthesis/transformation, membrane transport, translation, protein assembly/folding, nitrogen metabolism, sulfur metabolism, hormone synthesis, and stress-related reactions. Almost all of these targets were also identified by a fluorescent gel electrophoresis procedure in which reduction by Trx can be observed directly. In some cases, the processes targeted by Trx depended on the source of the mitochondria. The results support the view that Trx acts as a sensor and enables mitochondria to adjust key reactions in accord with prevailing redox state. These and earlier findings further suggest that, by sensing redox in chloroplasts and mitochondria, Trx enables the two organelles of photosynthetic tissues to communicate by means of a network of transportable metabolites such as dihydroxyacetone phosphate, malate, and glycolate. In this way, light absorbed and processed by means of chlorophyll can be perceived and function in regulating fundamental mitochondrial processes akin to its mode of action in chloroplasts. PMID:14983062

Thioredoxin links redox to the regulation of fundamental processes of plant mitochondria.

PubMed

Balmer, Yves; Vensel, William H; Tanaka, Charlene K; Hurkman, William J; Gelhaye, Eric; Rouhier, Nicolas; Jacquot, Jean-Pierre; Manieri, Wanda; Schürmann, Peter; Droux, Michel; Buchanan, Bob B

2004-02-24

Mitochondria contain thioredoxin (Trx), a regulatory disulfide protein, and an associated flavoenzyme, NADP/Trx reductase, which provide a link to NADPH in the organelle. Unlike animal and yeast counterparts, the function of Trx in plant mitochondria is largely unknown. Accordingly, we have applied recently devised proteomic approaches to identify soluble Trx-linked proteins in mitochondria isolated from photosynthetic (pea and spinach leaves) and heterotrophic (potato tubers) sources. Application of the mitochondrial extracts to mutant Trx affinity columns in conjunction with proteomics led to the identification of 50 potential Trx-linked proteins functional in 12 processes: photorespiration, citric acid cycle and associated reactions, lipid metabolism, electron transport, ATP synthesis/transformation, membrane transport, translation, protein assembly/folding, nitrogen metabolism, sulfur metabolism, hormone synthesis, and stress-related reactions. Almost all of these targets were also identified by a fluorescent gel electrophoresis procedure in which reduction by Trx can be observed directly. In some cases, the processes targeted by Trx depended on the source of the mitochondria. The results support the view that Trx acts as a sensor and enables mitochondria to adjust key reactions in accord with prevailing redox state. These and earlier findings further suggest that, by sensing redox in chloroplasts and mitochondria, Trx enables the two organelles of photosynthetic tissues to communicate by means of a network of transportable metabolites such as dihydroxyacetone phosphate, malate, and glycolate. In this way, light absorbed and processed by means of chlorophyll can be perceived and function in regulating fundamental mitochondrial processes akin to its mode of action in chloroplasts.

Concentration- and time-dependent genotoxicity profiles of isoprene monoepoxides and diepoxide, and the cross-linking potential of isoprene diepoxide in cells.

PubMed

Li, Yan; Pelah, Avishay; An, Jing; Yu, Ying-Xin; Zhang, Xin-Yu

2014-01-01

Isoprene, a possible carcinogen, is a petrochemical and a natural product being primarily produced by plants. It is biotransformed to 2-ethenyl-2-methyloxirane (IP-1,2-O) and 2-(1-methylethenyl)oxirane (IP-3,4-O), both of which can be further metabolized to 2-methyl-2,2'-bioxirane (MBO). MBO is mutagenic, but IP-1,2-O and IP-3,4-O are not. While IP-1,2-O has been reported being genotoxic, the genotoxicity of IP-3,4-O and MBO, and the cross-linking potential of MBO have not been examined. In the present study, we used the comet assay to investigate the concentration- and time-dependent genotoxicity profiles of the three metabolites and the cross-linking potential of MBO in human hepatocyte L02 cells. For the incubation time of 1 h, all metabolites showed positive concentration-dependent profiles with a potency rank order of IP-3,4-O > MBO > IP-1,2-O. In human hepatocellular carcinoma (HepG2) and human leukemia (HL60) cells, IP-3,4-O was still more potent in inducing DNA breaks than MBO at high concentrations (>200 μM), although at low concentrations (≤200 μM) IP-3,4-O exhibited slightly lower or similar potency to MBO. Interestingly, their time-dependent genotoxicity profiles (0.5-4 h) in L02 cells were different from each other: IP-1,2-O and MBO (200 μM) exhibited negative and positive profiles, respectively, with IP-3,4-O lying in between, namely, IP-3,4-O-caused DNA breaks did not change over the exposure time. Further experiments demonstrated that hydrolysis of IP-1,2-O contributed to the negative profile and MBO induced cross-links at high concentrations and long incubation times. Collectively, the results suggested that IP-3,4-O might play a significant role in the toxicity of isoprene.

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

EPA Science Inventory

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

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

Mass spectra...

Intersatellite link application to commercial communications satellites

NASA Technical Reports Server (NTRS)

Lee, Young S.; Atia, Ali E.; Ponchak, Denise S.

1988-01-01

The fundamental characteristics of intersatellite link (ISL) systems, and their application to domestic, regional, and global satellite communications, are described. The quantitative advantages of using ISLs to improve orbit utilization, spectrum occupancy, transmission delay (compared to multi-hop links), coverage, and connectivity, and to reduce the number of earth station antennas, are also presented. Cost-effectiveness and other systems benefits of using ISLs are identified, and the technical and systems planning aspects of ISL systems implementation are addressed.

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

PubMed

Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

2017-06-01

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential Application of Digitally Linked Tuberculosis Diagnostics for Real-Time Surveillance of Drug-Resistant Tuberculosis Transmission: Validation and Analysis of Test Results.

PubMed

Ng, Kamela Charmaine; Meehan, Conor Joseph; Torrea, Gabriela; Goeminne, Léonie; Diels, Maren; Rigouts, Leen; de Jong, Bouke Catherine; André, Emmanuel

2018-02-27

Tuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results. However, these connected diagnostics and readily available test results are not used to their full capacity, as we have yet to capitalize on fully understanding the relationship between test results and specific rpoB mutations to elucidate its potential application to real-time surveillance. We aimed to validate and analyze RDT data in detail, and propose the potential use of connected diagnostics and associated test results for real-time evaluation of RR-TB transmission. We selected 107 RR-TB strains harboring 34 unique rpoB mutations, including 30 within the rifampicin resistance-determining region (RRDR), from the Belgian Coordinated Collections of Microorganisms, Antwerp, Belgium. We subjected these strains to Xpert MTB/RIF, GenoType MTBDRplus v2.0, and Genoscholar NTM + MDRTB II, the results of which were validated against the strains' available rpoB gene sequences. We determined the reproducibility of the results, analyzed and visualized the probe reactions, and proposed these for potential use in evaluating transmission. The RDT probe reactions detected most RRDR mutations tested, although we found a few critical discrepancies between observed results and manufacturers' claims. Based on published frequencies of probe reactions and RRDR mutations, we found specific probe reactions with high potential use in transmission studies: Xpert MTB/RIF probes A

Combined expressional analysis, bioinformatics and targeted proteomics identify new potential therapeutic targets in glioblastoma stem cells.

PubMed

Stangeland, Biljana; Mughal, Awais A; Grieg, Zanina; Sandberg, Cecilie Jonsgar; Joel, Mrinal; Nygård, Ståle; Meling, Torstein; Murrell, Wayne; Vik Mo, Einar O; Langmoen, Iver A

2015-09-22

Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures. The expression of these genes was confirmed in clinical samples (TCGA and REMBRANDT). The first nine genes were highly co-expressed in all GBM subtypes and were part of the same protein-protein interaction network. Furthermore, their combined up-regulation correlated negatively with patient survival in the mesenchymal GBM subtype. Using targeted proteomics and the COGNOSCENTE database we linked these genes to GBM signalling pathways.Nine genes: PBK, CENPA, KIF15, DEPDC1, CDC6, DLG7, KIF18A, EZH2 and HMMR should be further explored as targets for treatment of GBM.

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

PubMed

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

2018-01-01

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

Intragenic rearrangements in X-linked intellectual deficiency: results of a-CGH in a series of 54 patients and identification of TRPC5 and KLHL15 as potential XLID genes.

PubMed

Mignon-Ravix, Cécile; Cacciagli, Pierre; Choucair, Nancy; Popovici, Cornel; Missirian, Chantal; Milh, Mathieu; Mégarbané, André; Busa, Tiffany; Julia, Sophie; Girard, Nadine; Badens, Catherine; Sigaudy, Sabine; Philip, Nicole; Villard, Laurent

2014-08-01

High-resolution array comparative genomic hybridization (a-CGH) enables the detection of intragenic rearrangements, such as single exon deletion or duplication. This approach can lead to the identification of new disease genes. We report on the analysis of 54 male patients presenting with intellectual deficiency (ID) and a family history suggesting X-linked (XL) inheritance or maternal skewed X-chromosome inactivation (XCI), using a home-made X-chromosome-specific microarray covering the whole human X-chromosome at high resolution. The majority of patients had whole genome array-CGH prior to the selection and we did not include large rearrangements such as MECP2 and FMR1 duplications. We identified four rearrangements considered as causative or potentially pathogenic, corresponding to a detection rate of 8%. Two CNVs affected known XLID genes and were therefore considered as causative (IL1RAPL1 and OPHN1 intragenic deletions). Two new CNVs were considered as potentially pathogenic as they affected interesting candidates for ID. The first CNV is a deletion of the first exon of the TRPC5 gene, encoding a cation channel implicated in dendrite growth and patterning, in a child presenting with ID and an autism spectrum disorder (ASD). The second CNV is a partial deletion of KLHL15, in a patient with severe ID, epilepsy, and anomalies of cortical development. In both cases, in spite of strong arguments for clinical relevance, we were not able at this stage to confirm pathogenicity of the mutations, and the causality of the variants identified in XLID remains to be confirmed. © 2014 Wiley Periodicals, Inc.

Adaptive laser link reconfiguration using constraint propagation

NASA Technical Reports Server (NTRS)

Crone, M. S.; Julich, P. M.; Cook, L. M.

1993-01-01

This paper describes Harris AI research performed on the Adaptive Link Reconfiguration (ALR) study for Rome Lab, and focuses on the application of constraint propagation to the problem of link reconfiguration for the proposed space based Strategic Defense System (SDS) Brilliant Pebbles (BP) communications system. According to the concept of operations at the time of the study, laser communications will exist between BP's and to ground entry points. Long-term links typical of RF transmission will not exist. This study addressed an initial implementation of BP's based on the Global Protection Against Limited Strikes (GPALS) SDI mission. The number of satellites and rings studied was representative of this problem. An orbital dynamics program was used to generate line-of-site data for the modeled architecture. This was input into a discrete event simulation implemented in the Harris developed COnstraint Propagation Expert System (COPES) Shell, developed initially on the Rome Lab BM/C3 study. Using a model of the network and several heuristics, the COPES shell was used to develop the Heuristic Adaptive Link Ordering (HALO) Algorithm to rank and order potential laser links according to probability of communication. A reduced set of links based on this ranking would then be used by a routing algorithm to select the next hop. This paper includes an overview of Constraint Propagation as an Artificial Intelligence technique and its embodiment in the COPES shell. It describes the design and implementation of both the simulation of the GPALS BP network and the HALO algorithm in COPES. This is described using a 59 Data Flow Diagram, State Transition Diagrams, and Structured English PDL. It describes a laser communications model and the heuristics involved in rank-ordering the potential communication links. The generation of simulation data is described along with its interface via COPES to the Harris developed View Net graphical tool for visual analysis of communications

Discrete typing units of Trypanosoma cruzi identified in rural dogs and cats in the humid Argentinean Chaco

PubMed Central

ENRIQUEZ, G.F.; CARDINAL, M.V.; OROZCO, M.M.; LANATI, L.; SCHIJMAN, A.G.; GÜRTLER, R.E.

2013-01-01

SUMMARY The discrete typing units (DTUs) of Trypanosoma cruzi that infect domestic dogs and cats have rarely been studied. With this purpose we conducted a cross-sectional xenodiagnostic survey of dog and cat populations residing in two infested rural villages in Pampa del Indio, in the humid Argentine Chaco. Parasites were isolated by culture from 44 dogs and 12 cats with a positive xenodiagnosis. DTUs were identified from parasite culture samples using a strategy based on multiple polymerase-chain reactions. TcVI was identified in 37 of 44 dogs and in 10 of 12 cats, whereas TcV was identified in five dogs and in two cats –a new finding for cats. No mixed infections were detected. The occurrence of two dogs infected with TcIII –classically found in armadillos– suggests a probable link with the local sylvatic transmission cycle involving Dasypus novemcinctus armadillos and a potential risk of human infection with TcIII. Our study reinforces the importance of dogs and cats as domestic reservoir hosts and sources of various DTUs infecting humans, and suggests a link between dogs and the sylvatic transmission cycle of TcIII. PMID:23058180

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

PubMed Central

Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

2013-01-01

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

Hopf-link topological nodal-loop semimetals

NASA Astrophysics Data System (ADS)

Zhou, Yao; Xiong, Feng; Wan, Xiangang; An, Jin

2018-04-01

We construct a generic two-band model which can describe topological semimetals with multiple closed nodal loops. All the existing multi-nodal-loop semimetals, including the nodal-net, nodal-chain, and Hopf-link states, can be examined within the same framework. Based on a two-nodal-loop model, the corresponding drumhead surface states for these topologically different bulk states are studied and compared with each other. The connection of our model with Hopf insulators is also discussed. Furthermore, to identify experimentally these topologically different semimetal states, especially to distinguish the Hopf-link from unlinked ones, we also investigate their Landau levels. It is found that the Hopf-link state can be characterized by the existence of a quadruply degenerate zero-energy Landau band, regardless of the direction of the magnetic field.

The intersubjective links in perversion.

PubMed

Eiguer, Alberto

2007-10-01

The author studies the intersubjective links which the pervert maintains with analyst or partner, attempting to indicate the differences between the investments in each case. Rather than accepting that empathy towards these patients is impossible to achieve and disturbs the countertransference profoundly, it attempts to show that these difficulties may be overcome if they are reinterpreted in the light of the theory of the intersubjective link. The author examines the theories and the practice of intersubjectivity and gives a definition of his approach to the link between two subjects. He applies these ideas to the case of a sexually masochistic female patient. The countertransference is marked successively by indifference, rejection and smothering. The analysis of the analyst's dream allows the situation to evolve. Failures in primary identification can result in domination over others and utilitarianism. The author examines the place of the challenge to the 'Law' and the father (in the attempt by the patient to put a theory to the test) in order to identify the figure of the witness in the pervert's intersubjective links. The desire of the transference would be marked by the figure of the witness rather than by that of the analyst as accomplice.

Cross-linking Chemistry of Squid Beak*

PubMed Central

Miserez, Ali; Rubin, Daniel; Waite, J. Herbert

2010-01-01

In stark contrast to most aggressive predators, Dosidicus gigas (jumbo squids) do not use minerals in their powerful mouthparts known as beaks. Their beaks instead consist of a highly sclerotized chitinous composite with incremental hydration from the tip to the base. We previously reported l-3,4-dihydroxyphenylalanine (dopa)-histidine (dopa-His) as an important covalent cross-link providing mechanical strengthening to the beak material. Here, we present a more complete characterization of the sclerotization chemistry and describe additional cross-links from D. gigas beak. All cross-links presented in this report share common building blocks, a family of di-, tri-, and tetra-histidine-catecholic adducts, that were separated by affinity chromatography and high performance liquid chromatography (HPLC) and identified by tandem mass spectroscopy and proton nuclear magnetic resonance (1H NMR). The data provide additional insights into the unusually high cross-link density found in mature beaks. Furthermore, we propose both a low molecular weight catechol, and peptidyl-dopa, to be sclerotization agents of squid beak. This appears to represent a new strategy for forming hard tissue in animals. The interplay between covalent cross-linking and dehydration on the graded properties of the beaks is discussed. PMID:20870720

Cross-linking chemistry of squid beak.

PubMed

Miserez, Ali; Rubin, Daniel; Waite, J Herbert

2010-12-03

In stark contrast to most aggressive predators, Dosidicus gigas (jumbo squids) do not use minerals in their powerful mouthparts known as beaks. Their beaks instead consist of a highly sclerotized chitinous composite with incremental hydration from the tip to the base. We previously reported l-3,4-dihydroxyphenylalanine (dopa)-histidine (dopa-His) as an important covalent cross-link providing mechanical strengthening to the beak material. Here, we present a more complete characterization of the sclerotization chemistry and describe additional cross-links from D. gigas beak. All cross-links presented in this report share common building blocks, a family of di-, tri-, and tetra-histidine-catecholic adducts, that were separated by affinity chromatography and high performance liquid chromatography (HPLC) and identified by tandem mass spectroscopy and proton nuclear magnetic resonance ((1)H NMR). The data provide additional insights into the unusually high cross-link density found in mature beaks. Furthermore, we propose both a low molecular weight catechol, and peptidyl-dopa, to be sclerotization agents of squid beak. This appears to represent a new strategy for forming hard tissue in animals. The interplay between covalent cross-linking and dehydration on the graded properties of the beaks is discussed.

A piloted simulation study of data link ATC message exchange

NASA Technical Reports Server (NTRS)

Waller, Marvin C.; Lohr, Gary W.

1989-01-01

Data link Air Traffic Control (ATC) and Air Traffic Service (ATS) message and data exchange offers the potential benefits of increased flight safety and efficiency by reducing communication errors and allowing more information to be transferred between aircraft and ground facilities. Digital communication also presents an opportunity to relieve the overloading of ATC radio frequencies which hampers message exchange during peak traffic hours in many busy terminal areas. A piloted simulation study to develop pilot factor guidelines and assess potential flight crew benefits and liabilities from using data link ATC message exchange was completed. The data link ATC message exchange concept, implemented on an existing navigation computer Control Display Unit (CDU) required maintaining a voice radio telephone link with an appropriate ATC facility. Flight crew comments, scanning behavior, and measurements of time spent in ATC communication activities for data link ATC message exchange were compared to similar measures for simulated conventional voice radio operations. The results show crew preference for the quieter flight deck environment and a perception of lower communication workload.

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

PubMed

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

2017-01-16

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

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

PubMed

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

2015-06-01

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

Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.

PubMed

Marigorta, Urko M; Denson, Lee A; Hyams, Jeffrey S; Mondal, Kajari; Prince, Jarod; Walters, Thomas D; Griffiths, Anne; Noe, Joshua D; Crandall, Wallace V; Rosh, Joel R; Mack, David R; Kellermayer, Richard; Heyman, Melvin B; Baker, Susan S; Stephens, Michael C; Baldassano, Robert N; Markowitz, James F; Kim, Mi-Ok; Dubinsky, Marla C; Cho, Judy; Aronow, Bruce J; Kugathasan, Subra; Gibson, Greg

2017-10-01

Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease. We show that TRSs based on genes regulated by variants linked to inflammatory bowel disease (IBD) not only outperform genetic risk scores (GRSs) in distinguishing Crohn's disease from healthy samples, but also serve to identify patients who in time will progress to complicated disease. Our dissection of eQTL effects may be used to distinguish genes whose association with disease is through promotion versus protection, thereby linking statistical association to biological mechanism. The TRS approach constitutes a potential strategy for personalized medicine that enhances inference from static genotypic risk assessment.

[Detection and prenatal diagnosis for RS1 gene mutations in two Chinese families with X-linked juvenile retinoschisis].

PubMed

Chu, Yan; Fang, Dong; Hou, Qiao-fang; Wang, Li-ya; Guo, Xi-rang; Wang, Ying-tai; Liao, Shi-xiu

2013-04-01

To identify potential mutations of retinoschisis 1 (RS1) gene responsible for X-linked retinoschisis (XLRS) in two Chinese families. The 6 exons and flanking intronic regions were analyzed with PCR and direct sequencing. Two RS1 mutations were identified in the two families, which included 1 frameshift mutation (c.573delG, p.Pro192fs) and 1 missense mutation (c.626G>A, p.Arg209His). Two RS1 mutations have been identified, among which Pro192fs mutation is discovered for the first time in Chinese population. Above results may enrich our understanding of the clinical manifestations of XLRS and facilitated early diagnosis and genetic counseling for the disease.

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

PubMed Central

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

2006-01-01

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

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

PubMed

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

2018-01-01

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

Potential link between plant and fungal distributions in a dipterocarp rainforest: community and phylogenetic structure of tropical ectomycorrhizal fungi across a plant and soil ecotone.

PubMed

Peay, Kabir G; Kennedy, Peter G; Davies, Stuart J; Tan, Sylvester; Bruns, Thomas D

2010-01-01

*Relatively little is known about diversity or structure of tropical ectomycorrhizal communities or their roles in tropical ecosystem dynamics. In this study, we present one of the largest molecular studies to date of an ectomycorrhizal community in lowland dipterocarp rainforest. *We sampled roots from two 0.4 ha sites located across an ecotone within a 52 ha forest dynamics plot. Our plots contained > 500 tree species and > 40 species of ectomycorrhizal host plants. Fungi were identified by sequencing ribosomal RNA genes. *The community was dominated by the Russulales (30 species), Boletales (17), Agaricales (18), Thelephorales (13) and Cantharellales (12). Total species richness appeared comparable to molecular studies of temperate forests. Community structure changed across the ecotone, although it was not possible to separate the role of environmental factors vs host plant preferences. Phylogenetic analyses were consistent with a model of community assembly where habitat associations are influenced by evolutionary conservatism of functional traits within ectomycorrhizal lineages. *Because changes in the ectomycorrhizal fungal community parallel those of the tree community at this site, this study demonstrates the potential link between the distribution of tropical tree diversity and the distribution of tropical ectomycorrhizal diversity in relation to local-scale edaphic variation.

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

PubMed Central

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

2013-01-01

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

Fetal alcohol-spectrum disorders: identifying at-risk mothers

PubMed Central

Montag, Annika C

2016-01-01

Fetal alcohol-spectrum disorders (FASDs) are a collection of physical and neurobehavioral disabilities caused by prenatal exposure to alcohol. To prevent or mitigate the costly effects of FASD, we must identify mothers at risk for having a child with FASD, so that we may reach them with interventions. Identifying mothers at risk is beneficial at all time points, whether prior to pregnancy, during pregnancy, or following the birth of the child. In this review, three approaches to identifying mothers at risk are explored: using characteristics of the mother and her pregnancy, using laboratory biomarkers, and using self-report assessment of alcohol-consumption risk. At present, all approaches have serious limitations. Research is needed to improve the sensitivity and specificity of biomarkers and screening instruments, and to link them to outcomes as opposed to exposure. Universal self-report screening of all women of childbearing potential should ideally be incorporated into routine obstetric and gynecologic care, followed by brief interventions, including education and personalized feedback for all who consume alcohol, and referral to treatment as indicated. Effective biomarkers or combinations of biomarkers may be used during pregnancy and at birth to determine maternal and fetal alcohol exposure. The combination of self-report and biomarker screening may help identify a greater proportion of women at risk for having a child with FASD, allowing them to access information and treatment, and empowering them to make decisions that benefit their children. PMID:27499649

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

Probing structures of large protein complexes using zero-length cross-linking.

PubMed

Rivera-Santiago, Roland F; Sriswasdi, Sira; Harper, Sandra L; Speicher, David W

2015-11-01

Structural mass spectrometry (MS) is a field with growing applicability for addressing complex biophysical questions regarding proteins and protein complexes. One of the major structural MS approaches involves the use of chemical cross-linking coupled with MS analysis (CX-MS) to identify proximal sites within macromolecules. Identified cross-linked sites can be used to probe novel protein-protein interactions or the derived distance constraints can be used to verify and refine molecular models. This review focuses on recent advances of "zero-length" cross-linking. Zero-length cross-linking reagents do not add any atoms to the cross-linked species due to the lack of a spacer arm. This provides a major advantage in the form of providing more precise distance constraints as the cross-linkable groups must be within salt bridge distances in order to react. However, identification of cross-linked peptides using these reagents presents unique challenges. We discuss recent efforts by our group to minimize these challenges by using multiple cycles of LC-MS/MS analysis and software specifically developed and optimized for identification of zero-length cross-linked peptides. Representative data utilizing our current protocol are presented and discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

ZIKV – CDB: A Collaborative Database to Guide Research Linking SncRNAs and ZIKA Virus Disease Symptoms

PubMed Central

Morais, Daniel Kumazawa; Cuadros-Orellana, Sara; Pais, Fabiano Sviatopolk-Mirsky; Medeiros, Julliane Dutra; Geraldo, Juliana Assis; Gilbert, Jack; Volpini, Angela Cristina; Fernandes, Gabriel Rocha

2016-01-01

Background In early 2015, a ZIKA Virus (ZIKV) infection outbreak was recognized in northeast Brazil, where concerns over its possible links with infant microcephaly have been discussed. Providing a causal link between ZIKV infection and birth defects is still a challenge. MicroRNAs (miRNAs) are small noncoding RNAs (sncRNAs) that regulate post-transcriptional gene expression by translational repression, and play important roles in viral pathogenesis and brain development. The potential for flavivirus-mediated miRNA signalling dysfunction in brain-tissue development provides a compelling hypothesis to test the perceived link between ZIKV and microcephaly. Methodology/Principal Findings Here, we applied in silico analyses to provide novel insights to understand how Congenital ZIKA Syndrome symptoms may be related to an imbalance in miRNAs function. Moreover, following World Health Organization (WHO) recommendations, we have assembled a database to help target investigations of the possible relationship between ZIKV symptoms and miRNA-mediated human gene expression. Conclusions/Significance We have computationally predicted both miRNAs encoded by ZIKV able to target genes in the human genome and cellular (human) miRNAs capable of interacting with ZIKV genomes. Our results represent a step forward in the ZIKV studies, providing new insights to support research in this field and identify potential targets for therapy. PMID:27332714

Linking exposures and health outcomes to a large population-based longitudinal study: the Millennium Cohort Study.

PubMed

Smith, Tyler C

2011-07-01

To describe current efforts and future potential for understanding long-term health of military service members by linking the Millennium Cohort Study data to exposures and health outcomes. The Millennium Cohort Study launched in 2001, before September 11 and the start of combat operations in Afghanistan and Iraq. Other substantial Department of Defense (DoD) health, personnel, and exposure databases are maintained in electronic form and may be linked by personal identifiers. More than 150,000 consenting members comprise the Millennium Cohort from all services, and include active duty, Reserve, and National Guard current and past members, and represent demographic, occupational, military, and health characteristics of the U.S. military. These prospective data offer symptom assessment, behavioral health, and self-reported exposures that may complement and fill gaps in capability presented by other DoD electronic health and exposure data. In conjunction with Millennium Cohort survey data, prospective individual-level exposure and health outcome assessment is crucial to understand and quantify any long-term health outcomes potentially associated with unique military occupational exposures.

Coding/modulation trade-offs for Shuttle wideband data links

NASA Technical Reports Server (NTRS)

Batson, B. H.; Huth, G. K.; Trumpis, B. D.

1974-01-01

This paper describes various modulation and coding schemes which are potentially applicable to the Shuttle wideband data relay communications link. This link will be capable of accommodating up to 50 Mbps of scientific data and will be subject to a power constraint which forces the use of channel coding. Although convolutionally encoded coherent binary PSK is the tentative signal design choice for the wideband data relay link, FM techniques are of interest because of the associated hardware simplicity and because an FM system is already planned to be available for transmission of television via relay satellite to the ground. Binary and M-ary FSK are considered as candidate modulation techniques, and both coherent and noncoherent ground station detection schemes are examined. The potential use of convolutional coding is considered in conjunction with each of the candidate modulation techniques.

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

PubMed

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

2015-07-01

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

Characterization of the Deoxyguanosine–Lysine Cross-Link of Methylglyoxal

PubMed Central

2015-01-01

Methylglyoxal is a mutagenic bis-electrophile that is produced endogenously from carbohydrate precursors. Methylglyoxal has been reported to induce DNA–protein cross-links (DPCs) in vitro and in cultured cells. Previous work suggests that these cross-links are formed between guanine and either lysine or cysteine side chains. However, the chemical nature of the methylglyoxal induced DPC have not been determined. We have examined the reaction of methylglyoxal, deoxyguanosine (dGuo), and Nα-acetyllysine (AcLys) and determined the structure of the cross-link to be the N2-ethyl-1-carboxamide with the lysine side chain amino group (1). The cross-link was identified by mass spectrometry and the structure confirmed by comparison to a synthetic sample. Further, the cross-link between methylglyoxal, dGuo, and a peptide (AcAVAGKAGAR) was also characterized. The mechanism of cross-link formation is likely to involve an Amadori rearrangement. PMID:24801980

Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis.

PubMed

Delgado, Diego; del Pozo-Rodríguez, Ana; Solinís, Maria Ángeles; Avilés-Triqueros, Marcelino; Weber, Bernhard H F; Fernández, Eduardo; Gascón, Alicia R

2012-04-01

The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases.

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

PubMed

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

2017-11-29

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

Geospatial analysis identifies critical mineral-resource potential in Alaska

USGS Publications Warehouse

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

2017-03-03

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

Combinatorial Approach for Large-scale Identification of Linked Peptides from Tandem Mass Spectrometry Spectra*

PubMed Central

Wang, Jian; Anania, Veronica G.; Knott, Jeff; Rush, John; Lill, Jennie R.; Bourne, Philip E.; Bandeira, Nuno

2014-01-01

The combination of chemical cross-linking and mass spectrometry has recently been shown to constitute a powerful tool for studying protein–protein interactions and elucidating the structure of large protein complexes. However, computational methods for interpreting the complex MS/MS spectra from linked peptides are still in their infancy, making the high-throughput application of this approach largely impractical. Because of the lack of large annotated datasets, most current approaches do not capture the specific fragmentation patterns of linked peptides and therefore are not optimal for the identification of cross-linked peptides. Here we propose a generic approach to address this problem and demonstrate it using disulfide-bridged peptide libraries to (i) efficiently generate large mass spectral reference data for linked peptides at a low cost and (ii) automatically train an algorithm that can efficiently and accurately identify linked peptides from MS/MS spectra. We show that using this approach we were able to identify thousands of MS/MS spectra from disulfide-bridged peptides through comparison with proteome-scale sequence databases and significantly improve the sensitivity of cross-linked peptide identification. This allowed us to identify 60% more direct pairwise interactions between the protein subunits in the 20S proteasome complex than existing tools on cross-linking studies of the proteasome complexes. The basic framework of this approach and the MS/MS reference dataset generated should be valuable resources for the future development of new tools for the identification of linked peptides. PMID:24493012

Scalable persistent identifier systems for dynamic datasets

NASA Astrophysics Data System (ADS)

Golodoniuc, P.; Cox, S. J. D.; Klump, J. F.

2016-12-01

Reliable and persistent identification of objects, whether tangible or not, is essential in information management. Many Internet-based systems have been developed to identify digital data objects, e.g., PURL, LSID, Handle, ARK. These were largely designed for identification of static digital objects. The amount of data made available online has grown exponentially over the last two decades and fine-grained identification of dynamically generated data objects within large datasets using conventional systems (e.g., PURL) has become impractical. We have compared capabilities of various technological solutions to enable resolvability of data objects in dynamic datasets, and developed a dataset-centric approach to resolution of identifiers. This is particularly important in Semantic Linked Data environments where dynamic frequently changing data is delivered live via web services, so registration of individual data objects to obtain identifiers is impractical. We use identifier patterns and pattern hierarchies for identification of data objects, which allows relationships between identifiers to be expressed, and also provides means for resolving a single identifier into multiple forms (i.e. views or representations of an object). The latter can be implemented through (a) HTTP content negotiation, or (b) use of URI querystring parameters. The pattern and hierarchy approach has been implemented in the Linked Data API supporting the United Nations Spatial Data Infrastructure (UNSDI) initiative and later in the implementation of geoscientific data delivery for the Capricorn Distal Footprints project using International Geo Sample Numbers (IGSN). This enables flexible resolution of multi-view persistent identifiers and provides a scalable solution for large heterogeneous datasets.

Creating a Linked Data Hub in the Geosciences

NASA Astrophysics Data System (ADS)

Narock, T. W.; Rozell, E. A.; Robinson, E. M.

2012-12-01

Linked data is a paradigm for publishing data on the Web by using, among other things, non-proprietary data formats and resolvable identifiers for things in your dataset. One linked data initiative, DBPedia, is widely used as a "crystallization point" for linked data on the Web. It serves as a hub for links from external datasets covering a broad variety of domains. Within the Earth Science Information Partnership (ESIP) efforts have begun to create a similar crystallization point for linked data in the geosciences. The initial project was created by converting more than 100,000 abstracts from the American Geophysical Union (AGU) into linked data using the Resource Description Framework. Like the Wikipedia data DBPedia is derived from, AGU publications have extremely broad coverage of topics in the geosciences. To better characterize the network, we have linked this AGU data to ESIP meeting and membership data, as well as to National Science Foundation-funded research projects. In doing so, we can visualize connections between different collaborative clusters like the ESIP Community or NSF grantees within the broader Geosciences communities that attend AGU conferences. Efforts to extend this project include - the ability to annotate abstracts, provide links to referenced tools or datasets, and the enabling of a crowd-sourcing approach to co-reference resolution.

LinkedOmics: analyzing multi-omics data within and across 32 cancer types.

PubMed

Vasaikar, Suhas V; Straub, Peter; Wang, Jing; Zhang, Bing

2018-01-04

The LinkedOmics database contains multi-omics data and clinical data for 32 cancer types and a total of 11 158 patients from The Cancer Genome Atlas (TCGA) project. It is also the first multi-omics database that integrates mass spectrometry (MS)-based global proteomics data generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) on selected TCGA tumor samples. In total, LinkedOmics has more than a billion data points. To allow comprehensive analysis of these data, we developed three analysis modules in the LinkedOmics web application. The LinkFinder module allows flexible exploration of associations between a molecular or clinical attribute of interest and all other attributes, providing the opportunity to analyze and visualize associations between billions of attribute pairs for each cancer cohort. The LinkCompare module enables easy comparison of the associations identified by LinkFinder, which is particularly useful in multi-omics and pan-cancer analyses. The LinkInterpreter module transforms identified associations into biological understanding through pathway and network analysis. Using five case studies, we demonstrate that LinkedOmics provides a unique platform for biologists and clinicians to access, analyze and compare cancer multi-omics data within and across tumor types. LinkedOmics is freely available at http://www.linkedomics.org. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

HowTo - Easy use of global unique identifier

NASA Astrophysics Data System (ADS)

Czerniak, A.; Fleischer, D.; Schirnick, C.

2013-12-01

The GEOMAR sample- and core repository covers several thousands of samples and cores and was collected over the last decades. In the actual project, we bring this collection up to the new generation and tag every sample and core with a unique identifier, in our case the International Geo Sample Number (ISGN). This work is done with our digital Ink and hand writing recognition implementation. The Smart Pen technology was save time and resources to record the information on every sample or core. In the procedure of recording, there are several steps systematical are done: 1. Getting all information about the core or sample, such as cruise number, responsible person and so on. 2. Tag with unique identifiers, in our case a QR-Code. 3. Wrote down the location of sample or core. After transmitting the information from Smart Pen, actually via USB but wireless is a choice too, into our server infrastructure the link to other information began. As it linked in our Virtual Research Environment (VRE) with the unique identifier (ISGN) sample or core can be located and the QR-Code was simply linked back from core or sample to ISGN with additional scientific information. On the QR-Code all important information are on it and it was simple to produce thousand of it.

Photocontrolled Cargo Release from Dual Cross-Linked Polymer Particles.

PubMed

Tan, Shereen; Cui, Jiwei; Fu, Qiang; Nam, Eunhyung; Ladewig, Katharina; Ren, Jing M; Wong, Edgar H H; Caruso, Frank; Blencowe, Anton; Qiao, Greg G

2016-03-09

Burst release of a payload from polymeric particles upon photoirradiation was engineered by altering the cross-linking density. This was achieved via a dual cross-linking concept whereby noncovalent cross-linking was provided by cyclodextrin host-guest interactions, and irreversible covalent cross-linking was mediated by continuous assembly of polymers (CAP). The dual cross-linked particles (DCPs) were efficiently infiltrated (∼80-93%) by the biomacromolecule dextran (molecular weight up to 500 kDa) to provide high loadings (70-75%). Upon short exposure (5 s) to UV light, the noncovalent cross-links were disrupted resulting in increased permeability and burst release of the cargo (50 mol % within 1 s) as visualized by time-lapse fluorescence microscopy. As sunlight contains UV light at low intensities, the particles can potentially be incorporated into systems used in agriculture, environmental control, and food packaging, whereby sunlight could control the release of nutrients and antimicrobial agents.

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

NASA Astrophysics Data System (ADS)

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

2014-04-01

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

Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer’s disease

PubMed Central

Li, Xinzhong; Long, Jintao; He, Taigang; Belshaw, Robert; Scott, James

2015-01-01

Previous studies have evaluated gene expression in Alzheimer’s disease (AD) brains to identify mechanistic processes, but have been limited by the size of the datasets studied. Here we have implemented a novel meta-analysis approach to identify differentially expressed genes (DEGs) in published datasets comprising 450 late onset AD (LOAD) brains and 212 controls. We found 3124 DEGs, many of which were highly correlated with Braak stage and cerebral atrophy. Pathway Analysis revealed the most perturbed pathways to be (a) nitric oxide and reactive oxygen species in macrophages (NOROS), (b) NFkB and (c) mitochondrial dysfunction. NOROS was also up-regulated, and mitochondrial dysfunction down-regulated, in healthy ageing subjects. Upstream regulator analysis predicted the TLR4 ligands, STAT3 and NFKBIA, for activated pathways and RICTOR for mitochondrial genes. Protein-protein interaction network analysis emphasised the role of NFKB; identified a key interaction of CLU with complement; and linked TYROBP, TREM2 and DOK3 to modulation of LPS signalling through TLR4 and to phosphatidylinositol metabolism. We suggest that NEUROD6, ZCCHC17, PPEF1 and MANBAL are potentially implicated in LOAD, with predicted links to calcium signalling and protein mannosylation. Our study demonstrates a highly injurious combination of TLR4-mediated NFKB signalling, NOROS inflammatory pathway activation, and mitochondrial dysfunction in LOAD. PMID:26202100

Review of Potential Characterization Techniques in Approaching Energy and Sustainability

DOE PAGES

LePoire, David

2014-03-20

Societal prosperity is linked to sustainable energy and a healthy environment. But, tough global challenges include increased demand for fossil fuels, while approaching peak oil production and uncertainty in the environmental impacts of energy generation. Recently, energy use was identified as a major component of economic productivity, along with capital and labor. Furthermore, other environmental resources and impacts may be nearing environmental thresholds as indicated by nine planetary environmental boundaries, many of which are linked to energy production and use. Foresight techniques could be applied to guide future actions which include emphasis on (1) energy efficiency to bridge the transitionmore » to a renewable energy economy, (2) continued research, development, and assessment of new technologies, (3) improved understanding of environment impacts including natural capital use and degradation, (4) exploration of GDP alternative measures that include both economic production and environmental impacts, and (5) international cooperation and awareness of longer-term opportunities and their associated potential scenarios. Examples from the U.S. and the international community illustrate challenges and potential.« less

Bacterial population and biodegradation potential in chronically crude oil-contaminated marine sediments are strongly linked to temperature.

PubMed

Bargiela, Rafael; Mapelli, Francesca; Rojo, David; Chouaia, Bessem; Tornés, Jesús; Borin, Sara; Richter, Michael; Del Pozo, Mercedes V; Cappello, Simone; Gertler, Christoph; Genovese, María; Denaro, Renata; Martínez-Martínez, Mónica; Fodelianakis, Stilianos; Amer, Ranya A; Bigazzi, David; Han, Xifang; Chen, Jianwei; Chernikova, Tatyana N; Golyshina, Olga V; Mahjoubi, Mouna; Jaouanil, Atef; Benzha, Fatima; Magagnini, Mirko; Hussein, Emad; Al-Horani, Fuad; Cherif, Ameur; Blaghen, Mohamed; Abdel-Fattah, Yasser R; Kalogerakis, Nicolas; Barbas, Coral; Malkawi, Hanan I; Golyshin, Peter N; Yakimov, Michail M; Daffonchio, Daniele; Ferrer, Manuel

2015-06-29

Two of the largest crude oil-polluted areas in the world are the semi-enclosed Mediterranean and Red Seas, but the effect of chronic pollution remains incompletely understood on a large scale. We compared the influence of environmental and geographical constraints and anthropogenic forces (hydrocarbon input) on bacterial communities in eight geographically separated oil-polluted sites along the coastlines of the Mediterranean and Red Seas. The differences in community compositions and their biodegradation potential were primarily associated (P < 0.05) with both temperature and chemical diversity. Furthermore, we observed a link between temperature and chemical and biological diversity that was stronger in chronically polluted sites than in pristine ones where accidental oil spills occurred. We propose that low temperature increases bacterial richness while decreasing catabolic diversity and that chronic pollution promotes catabolic diversification. Our results further suggest that the bacterial populations in chronically polluted sites may respond more promptly in degrading petroleum after accidental oil spills.

Bacterial population and biodegradation potential in chronically crude oil-contaminated marine sediments are strongly linked to temperature

PubMed Central

Bargiela, Rafael; Mapelli, Francesca; Rojo, David; Chouaia, Bessem; Tornés, Jesús; Borin, Sara; Richter, Michael; Del Pozo, Mercedes V.; Cappello, Simone; Gertler, Christoph; Genovese, María; Denaro, Renata; Martínez-Martínez, Mónica; Fodelianakis, Stilianos; Amer, Ranya A.; Bigazzi, David; Han, Xifang; Chen, Jianwei; Chernikova, Tatyana N.; Golyshina, Olga V.; Mahjoubi, Mouna; Jaouanil, Atef; Benzha, Fatima; Magagnini, Mirko; Hussein, Emad; Al-Horani, Fuad; Cherif, Ameur; Blaghen, Mohamed; Abdel-Fattah, Yasser R.; Kalogerakis, Nicolas; Barbas, Coral; Malkawi, Hanan I.; Golyshin, Peter N.; Yakimov, Michail M.; Daffonchio, Daniele; Ferrer, Manuel

2015-01-01

Two of the largest crude oil-polluted areas in the world are the semi-enclosed Mediterranean and Red Seas, but the effect of chronic pollution remains incompletely understood on a large scale. We compared the influence of environmental and geographical constraints and anthropogenic forces (hydrocarbon input) on bacterial communities in eight geographically separated oil-polluted sites along the coastlines of the Mediterranean and Red Seas. The differences in community compositions and their biodegradation potential were primarily associated (P < 0.05) with both temperature and chemical diversity. Furthermore, we observed a link between temperature and chemical and biological diversity that was stronger in chronically polluted sites than in pristine ones where accidental oil spills occurred. We propose that low temperature increases bacterial richness while decreasing catabolic diversity and that chronic pollution promotes catabolic diversification. Our results further suggest that the bacterial populations in chronically polluted sites may respond more promptly in degrading petroleum after accidental oil spills. PMID:26119183

Using Voronoi Tessellations to identify groups in N-body Simulation

NASA Astrophysics Data System (ADS)

Gonzalez, R. E.; Theuns, T.

Dark matter N-body simulations often use a friends-of-friends (FOF) group finder to link together particles above a specified density threshold. An over density of 200 picks-out objects that can be identified with virialised dark matter haloes, based on the spherical collapse model for the formation of structure. When the halo contains significant substructure, as is the case in very high resolution simulations, then FOF will simply link all substructure to the parent halo. Many cosmological simulations now also include gas and stars, and these are often distributed differently from the dark matter. It is then not clear whether the structures identified by FOF are very physical. Here we use Voronoi tesselations to identify structures in hydrodynamical cosmological simulations, that contain dark matter, gas and stars. This adaptive technique allows accurate estimates of densities, and density gradients, for a non-structured distribution of points. We discuss how these estimates allow us to identify structures in the dark matter that can be identified with haloes, and in the stars, to identify galaxies.

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

PubMed

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

2018-04-01

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

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

PubMed

Tsutsumi, Akizumi; Inoue, Akiomi; Eguchi, Hisashi

2017-07-27

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

Could occupational physical activity mitigate the link between moderate kidney dysfunction and coronary heart disease?

PubMed

Esquirol, Yolande; Tully, Mark; Ruidavets, Jean-Bernard; Fogarty, Damian; Ferrieres, Jean; Quinn, Michael; Hughes, Maria; Kee, Frank

2014-12-20

Chronic kidney disease is now regarded as a risk factor for cardiovascular disease. The impact of occupational or non-occupational physical activity (PA) on moderate decreases of renal function is uncertain. We aimed to identify the potential association of PA (occupational and leisure-time) on early decline of estimated glomerular filtration rate (eGFR) and to determine the potential mediating effect of PA on the relationship between eGFR and heart disease. From the PRIME study analyses were conducted in 1058 employed men. Energy expended during leisure, work and commuting was calculated. Linear regression analyses were used to determine the link between types of PA and moderate decrements of eGFR determined with the KDIGO guideline at the baseline assessment. Cox proportional hazards analyses were used to explore the potential effect of PA on the relationship between eGFR and heart disease, ascertained during follow-up over 10 years. For these employed men, and after adjustment for known confounders of GFR change, more time spent sitting at work was associated with increased risk of moderate decline in kidney function, while carrying objects or being active at work was associated with decreased risk. In contrast, no significant link with leisure PA was apparent. No potential mediating effect of occupational PA was found for the relationship between eGFR and coronary heart disease. Occupational PA (potential modifiable factors) could provide a dual role on early impairment of renal function, without influence on the relationship between early decrease of e-GFR and CHD risk. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Potential Anti-Atherosclerotic Properties of Astaxanthin.

PubMed

Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

2016-02-05

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed.

Potential Anti-Atherosclerotic Properties of Astaxanthin

PubMed Central

Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

2016-01-01

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. PMID:26861359

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia

PubMed Central

Yamada, Kazuo; Gerber, David J.; Iwayama, Yoshimi; Ohnishi, Tetsuo; Ohba, Hisako; Toyota, Tomoko; Aruga, Jun; Minabe, Yoshio; Tonegawa, Susumu; Yoshikawa, Takeo

2007-01-01

The calcineurin cascade is central to neuronal signal transduction, and genes in this network are intriguing candidate schizophrenia susceptibility genes. To replicate and extend our previously reported association between the PPP3CC gene, encoding the calcineurin catalytic γ-subunit, and schizophrenia, we examined 84 SNPs from 14 calcineurin-related candidate genes for genetic association by using 124 Japanese schizophrenic pedigrees. Four of these genes (PPP3CC, EGR2, EGR3, and EGR4) showed nominally significant association with schizophrenia. In a postmortem brain study, EGR1, EGR2, and EGR3 transcripts were shown to be down-regulated in the prefrontal cortex of schizophrenic, but not bipolar, patients. These findings raise a potentially important role for EGR genes in schizophrenia pathogenesis. Because EGR3 is an attractive candidate gene based on its chromosomal location close to PPP3CC within 8p21.3 and its functional link to dopamine, glutamate, and neuregulin signaling, we extended our analysis by resequencing the entire EGR3 genomic interval and detected 15 SNPs. One of these, IVS1 + 607A→G SNP, displayed the strongest evidence for disease association, which was confirmed in 1,140 independent case-control samples. An in vitro promoter assay detected a possible expression-regulatory effect of this SNP. These findings support the previous genetic association of altered calcineurin signaling with schizophrenia pathogenesis and identify EGR3 as a compelling susceptibility gene. PMID:17360599

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process.

PubMed

Whitstock, Margaret T; Pearce, Christopher M; Ridout, Stephen C; Eckermann, Elizabeth J

2011-05-21

The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably

Hypothetical link between infertility and genetically modified food.

PubMed

Gao, Mingxia; Li, Bin; Yuan, Wenzhen; Zhao, Lihui; Zhang, Xuehong

2014-01-01

It is speculated that genetically modified food (GMF)/genetically modified organism (GMO) is responsible for infertility development. The risk linked with a wide use of GMFs/GMOs offers the basic elements for social criticism. However, to date, it has not been justified whether the bad effects are directly resulted from products of genetic modifications or trans-genesis process. Extensive experience with the risk assessment of whole foods has been applied recently on the safety and nutritional testing of GMFs/GMOs. Investigations have tested the safety of GMFs including sub-acute, chronic, reproductive, multi-generation and carcinogenicity studies. We extrapolated the potential risks associated with GMFs/GMOs on reproduction, and analyzed the multi-aspect linked between infertility and GMFs/GMOs. It could be conjectured that GMFs/GMOs could be potential hazard on reproduction, linking to the development of infertility through influencing the endocrine metabolism, endometriosis. However, little evidence shows the impaction on embryo or reproductive related tumor due to the limited literatures, and needs further research. The article presents some related patents on GMFs/GMOs, and some methods for tracking GMOs.

Fear Potentiated Startle Increases Phospholipase D (PLD) Expression/Activity and PLD-Linked Metabotropic Glutamate Receptor Mediated Post-Tetanic Potentiation in Rat Amygdala

PubMed Central

Krishnan, Balaji; Scott, Michael T.; Pollandt, Sebastian; Schroeder, Bradley; Kurosky, Alexander; Shinnick-Gallagher, Patricia

2016-01-01

Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders. PMID:26748024

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

PubMed Central

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

2017-01-01

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

Heterogeneity of link weight and the evolution of cooperation

NASA Astrophysics Data System (ADS)

Iwata, Manabu; Akiyama, Eizo

2016-04-01

In this paper, we investigate the effect of heterogeneity of link weight, heterogeneity of the frequency or amount of interactions among individuals, on the evolution of cooperation. Based on an analysis of the evolutionary prisoner's dilemma game on a weighted one-dimensional lattice network with intra-individual heterogeneity, we confirm that moderate level of link-weight heterogeneity can facilitate cooperation. Furthermore, we identify two key mechanisms by which link-weight heterogeneity promotes the evolution of cooperation: mechanisms for spread and maintenance of cooperation. We also derive the corresponding conditions under which the mechanisms can work through evolutionary dynamics.

Mammalian cell-transforming potential of traffic-linked ultrafine particulate matter PM0.056 in urban roadside atmosphere.

PubMed

Verma, Mukesh K; Poojan, Shiv; Sultana, Sarwat; Kumar, Sushil

2014-09-01

We examined the clastogenic and cell-transforming potential of ultrafine particulate matter fraction PM0.056 of urban ambient aerosol using mammalian cells. PM1.0, PM0.56 and PM0.056 fractions were sampled from roadside atmosphere of an urban area using the cascade impactor MOUDI-NR-110. The potential to induce cytotoxicity, DNA damage and micronuclei formation was examined at the test concentrations of 3, 6, 12.5, 25, 50 and 100 μg/ml using the 3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the plasmid relaxation assay and the C3H10T1/2 (10T1/2) cells. The cell-transforming potential was investigated in vitro using 10T1/2 cell transformation assay and the soft agar assay. PM1, PM0.56 and PM0.056 fractions were found to be toxic in dose-dependent manner. These induced cytotoxicity at five test concentrations, the ultrafine particle fraction PM0.056 showed greater cytotoxic potential. PM0.056 induced micronucleus formation in 10T1/2 cells. The effect was statistically significant. The DNA-damaging potential was measured in a plasmid relaxation assay. Both fine and ultrafine particle fraction PM0.56 and PM0.056 displayed greater effect as compared to larger PM1 fraction. DNA damage was found to be dependent on particulate matter intrinsic pro-oxidant chemicals. The ability of the ultrafine particle fraction PM0.056 to induce morphological cell transformation was demonstrated by significant and dose-dependent increases in type III focus formation by morphologically transformed cells in culture flasks and their clonal expansion in soft agar. It is concluded that the traffic-linked ultrafine particle fraction PM0.056 in the atmosphere by the roadside of an urban area is clastogenic and able to induce morphological transformation of mammalian cells. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions

Linked health data for pharmacovigilance in children: perceived legal and ethical issues for stakeholders and data guardians.

PubMed

Hopf, Yvonne Marina; Bond, Christine B; Francis, Jill J; Haughney, John; Helms, Peter J

2014-02-12

The inclusion of the Community Health Index in the recording of National Health Service (NHS) contacts in Scotland facilitates national linkage of data such as prescribing and healthcare utilisation. This linkage could be the basis for identification of adverse drug reactions. The aim of this article is to report the views of healthcare professionals on data sharing, ownership and the legal and other applicable frameworks relevant to linkage of routinely collected paediatric healthcare data. Qualitative study using semistructured face-to-face interviews addressing the study aims. Purposive sample of professional stakeholders (n=25) including experts on ethics, data protection, pharmacovigilance, data linkage, legal issues and prescribing. Interviews were audio-recorded, transcribed and thematically analysed using a framework approach. Participants identified existing data sharing systems in the UK. Access to healthcare data should be approved by the data owners. The definition of data ownership and associated legal responsibilities for linked healthcare data were seen as important factors to ensure accountability for the use of linked data. Yet data owners were seen as facilitators of the proposed data linkage. Twelve frameworks (legal, regulatory and governance) applicable to the linkage of healthcare data were identified. A large number of potentially relevant legal and regulatory frameworks were identified. Ownership of the linked data was seen as an extension of responsibility for, or guardianship of, the source datasets. The consensus emerging from the present study was that clarity is required on the definition of data sharing, data ownership and responsibilities of data owners.

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

PubMed

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

2016-05-01

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

Validation and discovery of genotype-phenotype associations in chronic diseases using linked data.

PubMed

Pathak, Jyotishman; Kiefer, Richard; Freimuth, Robert; Chute, Christopher

2012-01-01

This study investigates federated SPARQL queries over Linked Open Data (LOD) in the Semantic Web to validate existing, and potentially discover new genotype-phenotype associations from public datasets. In particular, we report our preliminary findings for identifying such associations for commonly occurring chronic diseases using the Online Mendelian Inheritance in Man (OMIM) and Database for SNPs (dbSNP) within the LOD knowledgebase and compare them with Gene Wiki for coverage and completeness. Our results indicate that Semantic Web technologies can play an important role for in-silico identification of novel disease-gene-SNP associations, although additional verification is required before such information can be applied and used effectively.

The link between rapid enigmatic amphibian decline and the globally emerging chytrid fungus.

PubMed

Lötters, Stefan; Kielgast, Jos; Bielby, Jon; Schmidtlein, Sebastian; Bosch, Jaime; Veith, Michael; Walker, Susan F; Fisher, Matthew C; Rödder, Dennis

2009-09-01

Amphibians are globally declining and approximately one-third of all species are threatened with extinction. Some of the most severe declines have occurred suddenly and for unknown reasons in apparently pristine habitats. It has been hypothesized that these "rapid enigmatic declines" are the result of a panzootic of the disease chytridiomycosis caused by globally emerging amphibian chytrid fungus. In a Species Distribution Model, we identified the potential distribution of this pathogen. Areas and species from which rapid enigmatic decline are known significantly overlap with those of highest environmental suitability to the chytrid fungus. We confirm the plausibility of a link between rapid enigmatic decline in worldwide amphibian species and epizootic chytridiomycosis.

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

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

Fear and decision-making in narcissistic personality disorder-a link between psychoanalysis and neuroscience.

PubMed

Ronningstam, Elsa; Baskin-Sommers, Arielle R

2013-06-01

Linking psychoanalytic studies with neuroscience has proven increasingly productive for identifying and understanding personality functioning. This article focuses on pathological narcissism and narcissistic personality disorder (NPD), with the aim of exploring two clinically relevant aspects of narcissistic functioning also recognized in psychoanalysis: fear and decision-making. Evidence from neuroscientific studies of related conditions, such as psychopathy, suggests links between affective and cognitive functioning that can influence the sense of self-agency and narcissistic self-regulation. Attention can play a crucial role in moderating fear and self-regulatory deficits, and the interaction between experience and emotion can be central for decision-making. In this review we will explore fear as a motivating factor in narcissistic personality functioning, and the impact fear may have on decision-making in people with pathological narcissism and NPD. Understanding the processes and neurological underpinnings of fear and decision-making can potentially influence both the diagnosis and treatment of NPD.

Fear and decision-making in narcissistic personality disorder—a link between psychoanalysis and neuroscience

PubMed Central

Ronningstam, Elsa; Baskin-Sommers, Arielle R.

2013-01-01

Linking psychoanalytic studies with neuroscience has proven increasingly productive for identifying and understanding personality functioning. This article focuses on pathological narcissism and narcissistic personality disorder (NPD), with the aim of exploring two clinically relevant aspects of narcissistic functioning also recognized in psychoanalysis: fear and decision-making. Evidence from neuroscientific studies of related conditions, such as psychopathy, suggests links between affective and cognitive functioning that can influence the sense of self-agency and narcissistic self-regulation. Attention can play a crucial role in moderating fear and self-regulatory deficits, and the interaction between experience and emotion can be central for decision-making. In this review we will explore fear as a motivating factor in narcissistic personality functioning, and the impact fear may have on decision-making in people with pathological narcissism and NPD. Understanding the processes and neurological underpinnings of fear and decision-making can potentially influence both the diagnosis and treatment of NPD. PMID:24174893

Assessing crown fire potential by linking models of surface and crown fire behavior

Treesearch

Joe H. Scott; Elizabeth D. Reinhardt

2001-01-01

Fire managers are increasingly concerned about the threat of crown fires, yet only now are quantitative methods for assessing crown fire hazard being developed. Links among existing mathematical models of fire behavior are used to develop two indices of crown fire hazard-the Torching Index and Crowning Index. These indices can be used to ordinate different forest...

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

PubMed Central

Loughman, James; Wildsoet, Christine F.; Williams, Cathy; Guggenheim, Jeremy A.

2018-01-01

Purpose To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. Methods Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests. Results Pathway analysis identified several biological processes already implicated in refractive error development through prior GWAS analyses and animal studies, including extracellular matrix remodeling, focal adhesion, and axon guidance, supporting the research hypothesis. Novel pathways also implicated in myopia development included mannosylation, glycosylation, lens development, gliogenesis, and Schwann cell differentiation. Hyperopia was found to be linked to a different pattern of biological processes, mostly related to organogenesis. Comparison with GWAS findings further confirmed that syndromic myopia genes were enriched for genetic variants that influence refractive errors in the general population. Gene-based analyses implicated 21 novel candidate myopia genes (ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1

Strengthening the dementia care triad: identifying knowledge gaps and linking to resources.

PubMed

Jensen, Christine J; Inker, Jennifer

2015-05-01

This article describes a project to identify the needs of family caregivers and health care providers caring for persons with dementia. Participants included 128 caregivers, who completed a survey, and 27 health care providers, who participated in a focus group and completed a survey. Caregivers reported their primary source of information about the disease was the doctor; however, the majority also reported they were primarily informed of medications and not about needed resources. Health care providers identified limited time with patients and families, and lack of awareness of community services, as their main challenges. Recommendations include strengthening the partnership between physicians, patients, and caregivers (the dementia care triad) through additional support and training for physicians and caregivers, increasing awareness of the Alzheimer's Association, and utilization of technology for families and professionals to track the needs of persons with dementia. © The Author(s) 2014.

A Checklist for Identifying Funding Sources for Assistive Technology.

ERIC Educational Resources Information Center

Menlove, Martell

1996-01-01

This article offers a systematically organized series of questions to identify funding sources for assistive technology for students with disabilities. A decision tree links the questions with funding sources. (DB)

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Pathways to the Future: Linking Environmental Scanning to Strategic Management.

ERIC Educational Resources Information Center

Mecca, Thomas V.; Morrison, James L.

1988-01-01

Describes an ED QUEST (Quick Environmental Scanning Technique) workshop demonstrating the links between an environmental scanning/forecasting process and formulation of institutional strategy. Explains ED QUEST's use in identifying and analyzing critical trends and events, and identifying the nature of the organization; developing alternative…

Correlations between Community Structure and Link Formation in Complex Networks

PubMed Central

Liu, Zhen; He, Jia-Lin; Kapoor, Komal; Srivastava, Jaideep

2013-01-01

Background Links in complex networks commonly represent specific ties between pairs of nodes, such as protein-protein interactions in biological networks or friendships in social networks. However, understanding the mechanism of link formation in complex networks is a long standing challenge for network analysis and data mining. Methodology/Principal Findings Links in complex networks have a tendency to cluster locally and form so-called communities. This widely existed phenomenon reflects some underlying mechanism of link formation. To study the correlations between community structure and link formation, we present a general computational framework including a theory for network partitioning and link probability estimation. Our approach enables us to accurately identify missing links in partially observed networks in an efficient way. The links having high connection likelihoods in the communities reveal that links are formed preferentially to create cliques and accordingly promote the clustering level of the communities. The experimental results verify that such a mechanism can be well captured by our approach. Conclusions/Significance Our findings provide a new insight into understanding how links are created in the communities. The computational framework opens a wide range of possibilities to develop new approaches and applications, such as community detection and missing link prediction. PMID:24039818

A Visual Analytics Framework for Identifying Topic Drivers in Media Events.

PubMed

Lu, Yafeng; Wang, Hong; Landis, Steven; Maciejewski, Ross

2017-09-14

Media data has been the subject of large scale analysis with applications of text mining being used to provide overviews of media themes and information flows. Such information extracted from media articles has also shown its contextual value of being integrated with other data, such as criminal records and stock market pricing. In this work, we explore linking textual media data with curated secondary textual data sources through user-guided semantic lexical matching for identifying relationships and data links. In this manner, critical information can be identified and used to annotate media timelines in order to provide a more detailed overview of events that may be driving media topics and frames. These linked events are further analyzed through an application of causality modeling to model temporal drivers between the data series. Such causal links are then annotated through automatic entity extraction which enables the analyst to explore persons, locations, and organizations that may be pertinent to the media topic of interest. To demonstrate the proposed framework, two media datasets and an armed conflict event dataset are explored.

Genome-wide study of resistant hypertension identified from electronic health records.

PubMed

Dumitrescu, Logan; Ritchie, Marylyn D; Denny, Joshua C; El Rouby, Nihal M; McDonough, Caitrin W; Bradford, Yuki; Ramirez, Andrea H; Bielinski, Suzette J; Basford, Melissa A; Chai, High Seng; Peissig, Peggy; Carrell, David; Pathak, Jyotishman; Rasmussen, Luke V; Wang, Xiaoming; Pacheco, Jennifer A; Kho, Abel N; Hayes, M Geoffrey; Matsumoto, Martha; Smith, Maureen E; Li, Rongling; Cooper-DeHoff, Rhonda M; Kullo, Iftikhar J; Chute, Christopher G; Chisholm, Rex L; Jarvik, Gail P; Larson, Eric B; Carey, David; McCarty, Catherine A; Williams, Marc S; Roden, Dan M; Bottinger, Erwin; Johnson, Julie A; de Andrade, Mariza; Crawford, Dana C

2017-01-01

Resistant hypertension is defined as high blood pressure that remains above treatment goals in spite of the concurrent use of three antihypertensive agents from different classes. Despite the important health consequences of resistant hypertension, few studies of resistant hypertension have been conducted. To perform a genome-wide association study for resistant hypertension, we defined and identified cases of resistant hypertension and hypertensives with treated, controlled hypertension among >47,500 adults residing in the US linked to electronic health records (EHRs) and genotyped as part of the electronic MEdical Records & GEnomics (eMERGE) Network. Electronic selection logic using billing codes, laboratory values, text queries, and medication records was used to identify resistant hypertension cases and controls at each site, and a total of 3,006 cases of resistant hypertension and 876 controlled hypertensives were identified among eMERGE Phase I and II sites. After imputation and quality control, a total of 2,530,150 SNPs were tested for an association among 2,830 multi-ethnic cases of resistant hypertension and 876 controlled hypertensives. No test of association was genome-wide significant in the full dataset or in the dataset limited to European American cases (n = 1,719) and controls (n = 708). The most significant finding was CLNK rs13144136 at p = 1.00x10-6 (odds ratio = 0.68; 95% CI = 0.58-0.80) in the full dataset with similar results in the European American only dataset. We also examined whether SNPs known to influence blood pressure or hypertension also influenced resistant hypertension. None was significant after correction for multiple testing. These data highlight both the difficulties and the potential utility of EHR-linked genomic data to study clinically-relevant traits such as resistant hypertension.

Using link analysis to explore the impact of the physical environment on pharmacist tasks.

PubMed

Lester, Corey A; Chui, Michelle A

2016-01-01

National community pharmacy organizations have been redesigning pharmacies to better facilitate direct patient care. However, evidence suggests that changing the physical layout of a pharmacy prior to understanding how the environment impacts pharmacists' work may not achieve the desired benefits. This study describes an objective method to understanding how the physical layout of the pharmacy may affect how pharmacists perform tasks. Link analysis is a systems engineering method used to describe the influence of the physical environment on task completion. This study used a secondary data set of field notes collected from 9 h of direct observation in one mass-merchandise community pharmacy in the U.S. State, Wisconsin. A node is an individual location in the environment. A link is the movement between two nodes. Tasks were inventoried and task themes identified. The mean, minimum, and maximum number of links needed to complete each task were then determined and used to construct a link table. A link diagram is a graphical display showing the links in conjunction with the physical layout of the pharmacy. A total of 92 unique tasks were identified resulting in 221 links. Tasks were sorted into five themes: patient care activities, insurance issues, verifying prescriptions, filling prescriptions, and other. Insurance issues required the greatest number of links with a mean of 4.75. Verifying prescriptions and performing patient care were the most commonly performed tasks with 36 and 30 unique task occurrences, respectively. Link analysis provides an objective method for identifying how a pharmacist interacts with the physical environment to complete tasks. This method provides designers with useful information to target interventions to improve the effectiveness of pharmacist work. Analysis beyond link analysis should be considered for large scale system redesign. Copyright © 2015 Elsevier Inc. All rights reserved.

Identifying failure in a tree network of a parallel computer

DOEpatents

Archer, Charles J.; Pinnow, Kurt W.; Wallenfelt, Brian P.

2010-08-24

Methods, parallel computers, and products are provided for identifying failure in a tree network of a parallel computer. The parallel computer includes one or more processing sets including an I/O node and a plurality of compute nodes. For each processing set embodiments include selecting a set of test compute nodes, the test compute nodes being a subset of the compute nodes of the processing set; measuring the performance of the I/O node of the processing set; measuring the performance of the selected set of test compute nodes; calculating a current test value in dependence upon the measured performance of the I/O node of the processing set, the measured performance of the set of test compute nodes, and a predetermined value for I/O node performance; and comparing the current test value with a predetermined tree performance threshold. If the current test value is below the predetermined tree performance threshold, embodiments include selecting another set of test compute nodes. If the current test value is not below the predetermined tree performance threshold, embodiments include selecting from the test compute nodes one or more potential problem nodes and testing individually potential problem nodes and links to potential problem nodes.

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

PubMed

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

2014-01-01

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

IDENTIFYING POTENTIAL SOURCES OF BACKGROUND CONTAMINATION IN RT-PCR

EPA Science Inventory

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

Mixed-Isotope Labeling with LC-IMS-MS for Characterization of Protein–Protein Interactions by Chemical Cross-Linking

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

Merkley, Eric D.; Baker, Erin S.; Crowell, Kevin L.

2013-02-20

Chemical cross-linking of proteins followed by proteolysis and mass spectrometric analysis of the resulting cross-linked peptides can provide insights into protein structure and protein-protein interactions. However, cross-linked peptides are by necessity of low stoichometry and have different physicochemical properties than linear peptides, routine unambiguous identification of the cross-linked peptides has remained difficult. To address this challenge, we demonstrated the use of liquid chromatography and ion mobility separations coupled with mass spectrometry in combination with a heavy-isotope labeling method. The combination of mixed-isotope cross-linking and ion mobility provided unique and easily interpretable spectral multiplet features for the intermolecular cross-linked peptides. Applicationmore » of the method to two different homodimeric proteins - SrfN, a virulence factor from Salmonella Typhimurium and SO_2176, a protein of unknown function from Shewanella oneidensis- revealed several cross-linked peptides from both proteins that were identified with a low false discovery rate (estimated using a decoy approach). A greater number of cross-linked peptides were identified using ion mobility drift time information in the analysis than when the data were summed across the drift time dimension before analysis. The identified cross-linked peptides migrated more quickly in the ion mobility drift tube than the unmodified peptides.« less

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

PubMed

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

2015-05-14

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

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

PubMed

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

2014-11-01

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

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

USDA-ARS?s Scientific Manuscript database

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

New genetic loci link adipose and insulin biology to body fat distribution.

PubMed

Shungin, Dmitry; Winkler, Thomas W; Croteau-Chonka, Damien C; Ferreira, Teresa; Locke, Adam E; Mägi, Reedik; Strawbridge, Rona J; Pers, Tune H; Fischer, Krista; Justice, Anne E; Workalemahu, Tsegaselassie; Wu, Joseph M W; Buchkovich, Martin L; Heard-Costa, Nancy L; Roman, Tamara S; Drong, Alexander W; Song, Ci; Gustafsson, Stefan; Day, Felix R; Esko, Tonu; Fall, Tove; Kutalik, Zoltán; Luan, Jian'an; Randall, Joshua C; Scherag, André; Vedantam, Sailaja; Wood, Andrew R; Chen, Jin; Fehrmann, Rudolf; Karjalainen, Juha; Kahali, Bratati; Liu, Ching-Ti; Schmidt, Ellen M; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bragg-Gresham, Jennifer L; Buyske, Steven; Demirkan, Ayse; Ehret, Georg B; Feitosa, Mary F; Goel, Anuj; Jackson, Anne U; Johnson, Toby; Kleber, Marcus E; Kristiansson, Kati; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Peters, Marjolein J; Prokopenko, Inga; Stančáková, Alena; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Van Vliet-Ostaptchouk, Jana V; Yengo, Loïc; Zhang, Weihua; Albrecht, Eva; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Böhringer, Stefan; Bonnet, Fabrice; Böttcher, Yvonne; Bruinenberg, Marcel; Carba, Delia B; Caspersen, Ida H; Clarke, Robert; Daw, E Warwick; Deelen, Joris; Deelman, Ewa; Delgado, Graciela; Doney, Alex Sf; Eklund, Niina; Erdos, Michael R; Estrada, Karol; Eury, Elodie; Friedrich, Nele; Garcia, Melissa E; Giedraitis, Vilmantas; Gigante, Bruna; Go, Alan S; Golay, Alain; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grewal, Jagvir; Groves, Christopher J; Haller, Toomas; Hallmans, Goran; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heikkilä, Kauko; Herzig, Karl-Heinz; Helmer, Quinta; Hillege, Hans L; Holmen, Oddgeir; Hunt, Steven C; Isaacs, Aaron; Ittermann, Till; James, Alan L; Johansson, Ingegerd; Juliusdottir, Thorhildur; Kalafati, Ioanna-Panagiota; Kinnunen, Leena; Koenig, Wolfgang; Kooner, Ishminder K; Kratzer, Wolfgang; Lamina, Claudia; Leander, Karin; Lee, Nanette R; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Mach, François; Magnusson, Patrik Ke; Mahajan, Anubha; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Moayyeri, Alireza; Monda, Keri L; Mooijaart, Simon P; Mühleisen, Thomas W; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nalls, Michael A; Narisu, Narisu; Glorioso, Nicola; Nolte, Ilja M; Olden, Matthias; Rayner, Nigel W; Renstrom, Frida; Ried, Janina S; Robertson, Neil R; Rose, Lynda M; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Sennblad, Bengt; Seufferlein, Thomas; Sitlani, Colleen M; Smith, Albert Vernon; Stirrups, Kathleen; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorand, Barbara; Thorleifsson, Gudmar; Tomaschitz, Andreas; Troffa, Chiara; van Oort, Floor Va; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Wennauer, Roman; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Zhang, Qunyuan; Zhao, Jing Hua; Brennan, Eoin P; Choi, Murim; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Gharavi, Ali G; Hedman, Åsa K; Hivert, Marie-France; Huang, Jinyan; Kanoni, Stavroula; Karpe, Fredrik; Keildson, Sarah; Kiryluk, Krzysztof; Liang, Liming; Lifton, Richard P; Ma, Baoshan; McKnight, Amy J; McPherson, Ruth; Metspalu, Andres; Min, Josine L; Moffatt, Miriam F; Montgomery, Grant W; Murabito, Joanne M; Nicholson, George; Nyholt, Dale R; Olsson, Christian; Perry, John Rb; Reinmaa, Eva; Salem, Rany M; Sandholm, Niina; Schadt, Eric E; Scott, Robert A; Stolk, Lisette; Vallejo, Edgar E; Westra, Harm-Jan; Zondervan, Krina T; Amouyel, Philippe; Arveiler, Dominique; Bakker, Stephan Jl; Beilby, John; Bergman, Richard N; Blangero, John; Brown, Morris J; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chines, Peter S; Claudi-Boehm, Simone; Collins, Francis S; Crawford, Dana C; Danesh, John; de Faire, Ulf; de Geus, Eco Jc; Dörr, Marcus; Erbel, Raimund; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Forouhi, Nita G; Forrester, Terrence; Franco, Oscar H; Gansevoort, Ron T; Gieger, Christian; Gudnason, Vilmundur; Haiman, Christopher A; Harris, Tamara B; Hattersley, Andrew T; Heliövaara, Markku; Hicks, Andrew A; Hingorani, Aroon D; Hoffmann, Wolfgang; Hofman, Albert; Homuth, Georg; Humphries, Steve E; Hyppönen, Elina; Illig, Thomas; Jarvelin, Marjo-Riitta; Johansen, Berit; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kooner, Jaspal S; Kooperberg, Charles; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lyssenko, Valeriya; Männistö, Satu; Marette, André; Matise, Tara C; McKenzie, Colin A; McKnight, Barbara; Musk, Arthur W; Möhlenkamp, Stefan; Morris, Andrew D; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Palmer, Lyle J; Penninx, Brenda W; Peters, Annette; Pramstaller, Peter P; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Ridker, Paul M; Ritchie, Marylyn D; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter Eh; Shuldiner, Alan R; Staessen, Jan A; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Strauch, Konstantin; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Vohl, Marie-Claude; Völker, Uwe; Vollenweider, Peter; Wilson, James F; Witteman, Jacqueline C; Adair, Linda S; Bochud, Murielle; Boehm, Bernhard O; Bornstein, Stefan R; Bouchard, Claude; Cauchi, Stéphane; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Cooper, Richard S; Dedoussis, George; Ferrucci, Luigi; Froguel, Philippe; Grabe, Hans-Jörgen; Hamsten, Anders; Hui, Jennie; Hveem, Kristian; Jöckel, Karl-Heinz; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; März, Winfried; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin Na; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Rivadeneira, Fernando; Saaristo, Timo E; Saleheen, Danish; Sinisalo, Juha; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Stefansson, Kari; Stumvoll, Michael; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; van der Harst, Pim; Veronesi, Giovanni; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Abecasis, Goncalo R; Assimes, Themistocles L; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; Franke, Lude; Frayling, Timothy M; Groop, Leif C; Hunter, David J; Kaplan, Robert C; O'Connell, Jeffrey R; Qi, Lu; Schlessinger, David; Strachan, David P; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Willer, Cristen J; Visscher, Peter M; Yang, Jian; Hirschhorn, Joel N; Zillikens, M Carola; McCarthy, Mark I; Speliotes, Elizabeth K; North, Kari E; Fox, Caroline S; Barroso, Inês; Franks, Paul W; Ingelsson, Erik; Heid, Iris M; Loos, Ruth Jf; Cupples, L Adrienne; Morris, Andrew P; Lindgren, Cecilia M; Mohlke, Karen L

2015-02-12

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

New genetic loci link adipose and insulin biology to body fat distribution

PubMed Central

Strawbridge, Rona J; Pers, Tune H; Fischer, Krista; Justice, Anne E; Workalemahu, Tsegaselassie; Wu, Joseph M.W.; Buchkovich, Martin L; Heard-Costa, Nancy L; Roman, Tamara S; Drong, Alexander W; Song, Ci; Gustafsson, Stefan; Day, Felix R; Esko, Tonu; Fall, Tove; Kutalik, Zoltán; Luan, Jian’an; Randall, Joshua C; Scherag, André; Vedantam, Sailaja; Wood, Andrew R; Chen, Jin; Fehrmann, Rudolf; Karjalainen, Juha; Kahali, Bratati; Liu, Ching-Ti; Schmidt, Ellen M; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bragg-Gresham, Jennifer L; Buyske, Steven; Demirkan, Ayse; Ehret, Georg B; Feitosa, Mary F; Goel, Anuj; Jackson, Anne U; Johnson, Toby; Kleber, Marcus E; Kristiansson, Kati; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Peters, Marjolein J; Prokopenko, Inga; Stančáková, Alena; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Van Vliet-Ostaptchouk, Jana V; Yengo, Loïc; Zhang, Weihua; Albrecht, Eva; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Böhringer, Stefan; Bonnet, Fabrice; Böttcher, Yvonne; Bruinenberg, Marcel; Carba, Delia B; Caspersen, Ida H; Clarke, Robert; Daw, E Warwick; Deelen, Joris; Deelman, Ewa; Delgado, Graciela; Doney, Alex SF; Eklund, Niina; Erdos, Michael R; Estrada, Karol; Eury, Elodie; Friedrich, Nele; Garcia, Melissa E; Giedraitis, Vilmantas; Gigante, Bruna; Go, Alan S; Golay, Alain; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grewal, Jagvir; Groves, Christopher J; Haller, Toomas; Hallmans, Goran; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heikkilä, Kauko; Herzig, Karl-Heinz; Helmer, Quinta; Hillege, Hans L; Holmen, Oddgeir; Hunt, Steven C; Isaacs, Aaron; Ittermann, Till; James, Alan L; Johansson, Ingegerd; Juliusdottir, Thorhildur; Kalafati, Ioanna-Panagiota; Kinnunen, Leena; Koenig, Wolfgang; Kooner, Ishminder K; Kratzer, Wolfgang; Lamina, Claudia; Leander, Karin; Lee, Nanette R; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Mach, François; Magnusson, Patrik KE; Mahajan, Anubha; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Moayyeri, Alireza; Monda, Keri L; Mooijaart, Simon P; Mühleisen, Thomas W; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nalls, Michael A; Narisu, Narisu; Glorioso, Nicola; Nolte, Ilja M; Olden, Matthias; Rayner, Nigel W; Renstrom, Frida; Ried, Janina S; Robertson, Neil R; Rose, Lynda M; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Sennblad, Bengt; Seufferlein, Thomas; Sitlani, Colleen M; Smith, Albert Vernon; Stirrups, Kathleen; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorand, Barbara; Thorleifsson, Gudmar; Tomaschitz, Andreas; Troffa, Chiara; van Oort, Floor VA; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Wennauer, Roman; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Zhang, Qunyuan; Zhao, Jing Hua; Brennan, Eoin P.; Choi, Murim; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Gharavi, Ali G; Hedman, Åsa K; Hivert, Marie-France; Huang, Jinyan; Kanoni, Stavroula; Karpe, Fredrik; Keildson, Sarah; Kiryluk, Krzysztof; Liang, Liming; Lifton, Richard P; Ma, Baoshan; McKnight, Amy J; McPherson, Ruth; Metspalu, Andres; Min, Josine L; Moffatt, Miriam F; Montgomery, Grant W; Murabito, Joanne M; Nicholson, George; Nyholt, Dale R; Olsson, Christian; Perry, John RB; Reinmaa, Eva; Salem, Rany M; Sandholm, Niina; Schadt, Eric E; Scott, Robert A; Stolk, Lisette; Vallejo, Edgar E.; Westra, Harm-Jan; Zondervan, Krina T; Amouyel, Philippe; Arveiler, Dominique; Bakker, Stephan JL; Beilby, John; Bergman, Richard N; Blangero, John; Brown, Morris J; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chines, Peter S; Claudi-Boehm, Simone; Collins, Francis S; Crawford, Dana C; Danesh, John; de Faire, Ulf; de Geus, Eco JC; Dörr, Marcus; Erbel, Raimund; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Forouhi, Nita G; Forrester, Terrence; Franco, Oscar H; Gansevoort, Ron T; Gieger, Christian; Gudnason, Vilmundur; Haiman, Christopher A; Harris, Tamara B; Hattersley, Andrew T; Heliövaara, Markku; Hicks, Andrew A; Hingorani, Aroon D; Hoffmann, Wolfgang; Hofman, Albert; Homuth, Georg; Humphries, Steve E; Hyppönen, Elina; Illig, Thomas; Jarvelin, Marjo-Riitta; Johansen, Berit; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kooner, Jaspal S; Kooperberg, Charles; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lyssenko, Valeriya; Männistö, Satu; Marette, André; Matise, Tara C; McKenzie, Colin A; McKnight, Barbara; Musk, Arthur W; Möhlenkamp, Stefan; Morris, Andrew D; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Palmer, Lyle J; Penninx, Brenda W; Peters, Annette; Pramstaller, Peter P; Raitakari, Olli T; Rankinen, Tuomo; Rao, DC; Rice, Treva K; Ridker, Paul M; Ritchie, Marylyn D.; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter EH; Shuldiner, Alan R; Staessen, Jan A; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Strauch, Konstantin; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Vohl, Marie-Claude; Völker, Uwe; Vollenweider, Peter; Wilson, James F; Witteman, Jacqueline C; Adair, Linda S; Bochud, Murielle; Boehm, Bernhard O; Bornstein, Stefan R; Bouchard, Claude; Cauchi, Stéphane; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Cooper, Richard S; Dedoussis, George; Ferrucci, Luigi; Froguel, Philippe; Grabe, Hans-Jörgen; Hamsten, Anders; Hui, Jennie; Hveem, Kristian; Jöckel, Karl-Heinz; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; März, Winfried; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin NA; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Rivadeneira, Fernando; Saaristo, Timo E; Saleheen, Danish; Sinisalo, Juha; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Stefansson, Kari; Stumvoll, Michael; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; van der Harst, Pim; Veronesi, Giovanni; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Abecasis, Goncalo R; Assimes, Themistocles L; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; Franke, Lude; Frayling, Timothy M; Groop, Leif C; Hunter, David J.; Kaplan, Robert C; O’Connell, Jeffrey R; Qi, Lu; Schlessinger, David; Strachan, David P; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Willer, Cristen J; Visscher, Peter M; Yang, Jian; Hirschhorn, Joel N; Zillikens, M Carola; McCarthy, Mark I; Speliotes, Elizabeth K; North, Kari E; Fox, Caroline S; Barroso, Inês; Franks, Paul W; Ingelsson, Erik; Heid, Iris M; Loos, Ruth JF; Cupples, L Adrienne; Morris, Andrew P; Lindgren, Cecilia M; Mohlke, Karen L

2014-01-01

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10−8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms. PMID:25673412

Bflinks: Reliable Bugfix Links via Bidirectional References and Tuned Heuristics

PubMed Central

2014-01-01

Background. Data from software version archives and defect databases can be used for defect insertion circumstance analysis and defect prediction. The first step in such analyses is identifying defect-correcting changes in the version archive (bugfix commits) and enriching them with additional metadata by establishing bugfix links to corresponding entries in the defect database. Candidate bugfix commits are typically identified via heuristic string matching on the commit message. Research Questions. Which filters could be used to obtain a set of bugfix links? How to tune their parameters? What accuracy is achieved? Method. We analyze a modular set of seven independent filters, including new ones that make use of reverse links, and evaluate visual heuristics for setting cutoff parameters. For a commercial repository, a product expert manually verifies over 2500 links to validate the results with unprecedented accuracy. Results. The heuristics pick a very good parameter value for five filters and a reasonably good one for the sixth. The combined filtering, called bflinks, provides 93% precision and only 7% results loss. Conclusion. Bflinks can provide high-quality results and adapts to repositories with different properties. PMID:27433506

Indoor communications networks realized through hybrid free-space optical and Wi-Fi links

NASA Astrophysics Data System (ADS)

Liverman, Spencer; Wang, Qiwei; Chu, Yu-Chung; Borah, Anindita; Wang, Songtao; Natarajan, Arun; Nguyen, Thinh; Wang, Alan X.

2018-01-01

Recently, free-space optical (FSO) networks have been investigated as a potential replacement for traditional WiFi networks due to their large bandwidth potentials. However, FSO networks often suffer from a lack of mobility. We present a hybrid free-space optical and radio frequency (RF) system that we have named WiFO, which seamlessly integrates free-space optical links with pre-existing WiFi networks. The free-space optical link in this system utilizes infrared LEDs operating at a wavelength of 850nm and is capable of transmitting 50Mbps over a three-meter distance. In this hybrid system, optical transmitters are embedded periodically throughout the ceiling of a workspace. Each transmitter directs an optical signal downward in a diffuse light cone, establishing a line of sight optical link. Line of sight communications links have an intrinsic physical layer of security due to the fact that a user must be directly in the path of transmission to access the link; however, this feature also poses a challenge for mobility. In our system, if the free-space optical link is interrupted, a control algorithm redirects traffic over a pre-existing WiFi link ensuring uninterrupted transmissions. After data packets are received, acknowledgments are sent back to a central access point via a WiFi link. As the demand for wireless bandwidth continues to increase exponentially, utilizing the unregulated bandwidth contained within optical spectrum will become necessary. Our fully functional hybrid free-space optical and WiFi prototype system takes full advantage of the untapped bandwidth potential in the optical spectrum, while also maintaining the mobility inherent in WiFi networks.

Comparison of the university hospital and county hospitals in western Sweden to identify potential weak links in the early chain of care for acute stroke: results of an observational study

PubMed Central

Wireklint Sundström, Birgitta; Herlitz, Johan; Hansson, Per Olof; Brink, Peter

2015-01-01

Objective To identify weak links in the early chain of care for acute stroke. Setting 9 emergency hospitals in western Sweden, each with a stroke unit, and the emergency medical services (EMS). Participants All patients hospitalised with a first and a final diagnosis of stroke−between 15 December 2010 and 15 April 2011. The university hospital in the city of Gothenburg was compared with 6 county hospitals. Primary and secondary measures (1) The system delay, that is, median delay time from call to the EMS until diagnosis was designated as the primary end point. Secondary end points were: (2) the system delay time from call to the EMS until arrival in a hospital ward, (3) the use of the EMS, (4) priority at the dispatch centre and (5) suspicion of stroke by the EMS nurse. Results In all, 1376 acute patients with stroke (median age 79 years; 49% women) were included. The median system delay from call to the EMS until (1) diagnosis (CT scan) and (2) arrival in a hospital ward was 3 h and 52 min and 4 h and 22 min, respectively. The system delay (1) was significantly shorter in county hospitals. (3) The study showed that 76% used the EMS (Gothenburg 71%; the county 79%; p<0.0001). (4) Priority 1 was given at the dispatch centre in 54% of cases. (5) Stroke was suspected in 65% of cases. A prenotification was sent in 32% (Gothenburg 52%; the county 20%; p<0.0001). Conclusions System delay is still long and only a small fraction of patients received thrombolysis. Three of four used the EMS (more frequent in the county). They were given the highest priority at the dispatch centre in half of the cases. Stroke was suspected in two-thirds of the cases, but a prenotification was seldom sent to the hospital. PMID:26351184

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

Cancer.gov

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

Use of employer administrative databases to identify systematic causes of injury in aluminum manufacturing.

PubMed

Pollack, Keshia M; Agnew, Jacqueline; Slade, Martin D; Cantley, Linda; Taiwo, Oyebode; Vegso, Sally; Sircar, Kanta; Cullen, Mark R

2007-09-01

Employer administrative files are an underutilized source of data in epidemiologic studies of occupational injuries. Personnel files, occupational health surveillance data, industrial hygiene data, and a real-time incident and injury management system from a large multi-site aluminum manufacturer were linked deterministically. An ecological-level measure of physical job demand was also linked. This method successfully created a database containing over 100 variables for 9,101 hourly employees from eight geographically dispersed U.S. plants. Between 2002 and 2004, there were 3,563 traumatic injuries to 2,495 employees. The most common injuries were sprain/strains (32%), contusions (24%), and lacerations (14%). A multivariable logistic regression model revealed that physical job demand was the strongest predictor of injury risk, in a dose dependent fashion. Other strong predictors of injury included female gender, young age, short company tenure and short time on current job. Employer administrative files are a useful source of data, as they permit the exploration of risk factors and potential confounders that are not included in many population-based surveys. The ability to link employer administrative files with injury surveillance data is a valuable analysis strategy for comprehensively studying workplace injuries, identifying salient risk factors, and targeting workforce populations disproportionately affected. (c) 2007 Wiley-Liss, Inc.

Network inference analysis identifies an APRR2-like gene linked to pigment accumulation in tomato and pepper fruits.

PubMed

Pan, Yu; Bradley, Glyn; Pyke, Kevin; Ball, Graham; Lu, Chungui; Fray, Rupert; Marshall, Alexandra; Jayasuta, Subhalai; Baxter, Charles; van Wijk, Rik; Boyden, Laurie; Cade, Rebecca; Chapman, Natalie H; Fraser, Paul D; Hodgman, Charlie; Seymour, Graham B

2013-03-01

Carotenoids represent some of the most important secondary metabolites in the human diet, and tomato (Solanum lycopersicum) is a rich source of these health-promoting compounds. In this work, a novel and fruit-related regulator of pigment accumulation in tomato has been identified by artificial neural network inference analysis and its function validated in transgenic plants. A tomato fruit gene regulatory network was generated using artificial neural network inference analysis and transcription factor gene expression profiles derived from fruits sampled at various points during development and ripening. One of the transcription factor gene expression profiles with a sequence related to an Arabidopsis (Arabidopsis thaliana) ARABIDOPSIS PSEUDO RESPONSE REGULATOR2-LIKE gene (APRR2-Like) was up-regulated at the breaker stage in wild-type tomato fruits and, when overexpressed in transgenic lines, increased plastid number, area, and pigment content, enhancing the levels of chlorophyll in immature unripe fruits and carotenoids in red ripe fruits. Analysis of the transcriptome of transgenic lines overexpressing the tomato APPR2-Like gene revealed up-regulation of several ripening-related genes in the overexpression lines, providing a link between the expression of this tomato gene and the ripening process. A putative ortholog of the tomato APPR2-Like gene in sweet pepper (Capsicum annuum) was associated with pigment accumulation in fruit tissues. We conclude that the function of this gene is conserved across taxa and that it encodes a protein that has an important role in ripening.

Issues using linkage of hospital records and death certificate data to determine the size of a potential palliative care population.

PubMed

Brameld, Kate; Spilsbury, Katrina; Rosenwax, Lorna; Murray, Kevin; Semmens, James

2017-06-01

Studies aiming to identify palliative care populations have used data from death certificates and in some cases hospital records. The size and characteristics of the identified populations can show considerable variation depending on the data sources used. It is important that service planners and researchers are aware of this. To illustrate the differences in the size and characteristics of a potential palliative care population depending on the differential use of linked hospital records and death certificate data. Retrospective cohort study. The cohort consisted of 23,852 people aged 20 years and over who died in Western Australia between 1 January 2009 and 31 December 2010 after excluding deaths related to pregnancy or trauma. Within this cohort, the number, proportion and characteristics of people who died from one or more of 10 medical conditions considered amenable to palliative care were identified using linked hospital records and death certificate data. Depending on the information source(s) used, between 43% and 73% of the 23,852 people who died had a condition potentially amenable to palliative care identified. The median age at death and the sex distribution of the decedents by condition also varied with the information source. Health service planners and researchers need to be aware of the limitations when using hospital records and death certificate data to determine a potential palliative care population. The use of Emergency Department and other administrative data sources could further exacerbate this variation.

Link between the potentially hazardous Asteroid (86039) 1999 NC43 and the Chelyabinsk meteoroid tenuous

NASA Astrophysics Data System (ADS)

Reddy, Vishnu; Vokrouhlický, David; Bottke, William F.; Pravec, Petr; Sanchez, Juan A.; Gary, Bruce L.; Klima, Rachel; Cloutis, Edward A.; Galád, Adrián; Guan, Tan Thiam; Hornoch, Kamil; Izawa, Matthew R. M.; Kušnirák, Peter; Le Corre, Lucille; Mann, Paul; Moskovitz, Nicholas; Skiff, Brian; Vraštil, Jan

2015-05-01

We explored the statistical and compositional link between Chelyabinsk meteoroid and potentially hazardous Asteroid (86039) 1999 NC43 to investigate their proposed relation proposed by Borovička et al. (Borovička, J., et al. [2013]. Nature 503, 235-237). First, using a slightly more detailed computation we confirm that the orbit of the Chelyabinsk impactor is anomalously close to the Asteroid 1999 NC43. We find ∼(1-3) × 10-4 likelihood of that to happen by chance. Taking the standpoint that the Chelyabinsk impactor indeed separated from 1999 NC43 by a cratering or rotational fission event, we run a forward probability calculation, which is an independent statistical test. However, we find this scenario is unlikely at the ∼(10-3-10-2) level. Secondly, we note that efforts to conclusively prove separation of the Chelyabinsk meteoroid from (86039) 1999 NC43 in the past needs to meet severe criteria: relative velocity ≃1-10 m/s or smaller, and ≃100 km distance (i.e. about the Hill sphere distance from the parent body). We conclude that, unless the separation event was an extremely recent event, these criteria present an insurmountable difficulty due to the combination of strong orbital chaoticity, orbit uncertainty and incompleteness of the dynamical model with respect to thermal accelerations. This situation leaves the link of the two bodies unresolved and calls for additional analyses. With that goal, we revisit the presumed compositional link between (86039) 1999 NC43 and the Chelyabinsk body. Borovička et al. (Borovička, J., et al. [2013]. Nature 503, 235-237) noted that given its Q-type taxonomic classification, 1999 NC43 may pass this test. However, here we find that while the Q-type classification of 1999 NC43 is accurate, assuming that all Q-types are LL chondrites is not. Our experiment shows that not all ordinary chondrites fall under Q-taxonomic type and not all LL chondrites are Q-types. Spectral curve matching between laboratory spectra of

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

PubMed

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

2010-08-18

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

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

PubMed

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

2017-05-24

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

The ChEMBL database as linked open data

PubMed Central

2013-01-01

Background Making data available as Linked Data using Resource Description Framework (RDF) promotes integration with other web resources. RDF documents can natively link to related data, and others can link back using Uniform Resource Identifiers (URIs). RDF makes the data machine-readable and uses extensible vocabularies for additional information, making it easier to scale up inference and data analysis. Results This paper describes recent developments in an ongoing project converting data from the ChEMBL database into RDF triples. Relative to earlier versions, this updated version of ChEMBL-RDF uses recently introduced ontologies, including CHEMINF and CiTO; exposes more information from the database; and is now available as dereferencable, linked data. To demonstrate these new features, we present novel use cases showing further integration with other web resources, including Bio2RDF, Chem2Bio2RDF, and ChemSpider, and showing the use of standard ontologies for querying. Conclusions We have illustrated the advantages of using open standards and ontologies to link the ChEMBL database to other databases. Using those links and the knowledge encoded in standards and ontologies, the ChEMBL-RDF resource creates a foundation for integrated semantic web cheminformatics applications, such as the presented decision support. PMID:23657106

Phenotype-genotype correlations in X linked retinitis pigmentosa.

PubMed Central

Kaplan, J; Pelet, A; Martin, C; Delrieu, O; Aymé, S; Bonneau, D; Briard, M L; Hanauer, A; Larget-Piet, L; Lefrançois, P

1992-01-01

Retinitis pigmentosa (RP) represents a group of clinically heterogeneous retinal degenerations in which all modes of inheritance have been described. We have previously found two different clinical profiles in X linked RP as a function of age and mode of onset. The first clinical form has very early onset with severe myopia. The second form starts later with night blindness with mild myopia or none. At least two genes have been identified in X linked forms, namely RP2 (linked to DXS7, DXS255, and DXS14) and RP3 (linked to DXS84 and OTC) on the short arm of the X chromosome. In order to contribute to phenotype-genotype correlations in X linked RP, we tested the hypothesis that the two clinical profiles could be accounted for by the two different gene loci. The present study provides evidence for linkage of the clinical form with early myopia as the onset symptom with the RP2 gene (pairwise linkage to DXS255: Z = 3.13 at theta = 0), while the clinical form with later night blindness as the onset symptom is linked to the RP3 gene (pairwise linkage to OTC: Z = 4.16 at theta = 0). Images PMID:1357178

Library Screen Identifies Enterococcus faecalis CcpA, the Catabolite Control Protein A, as an Effector of Ace, a Collagen Adhesion Protein Linked to Virulence

PubMed Central

Gao, Peng; Pinkston, Kenneth L.; Bourgogne, Agathe; Cruz, Melissa R.; Garsin, Danielle A.; Murray, Barbara E.

2013-01-01

The Enterococcus faecalis cell wall-anchored protein Ace is an important virulence factor involved in cell adhesion and infection. Expression of Ace on the cell surface is affected by many factors, including stage of growth, culture temperature, and environmental components, such as serum, urine, and collagen. However, the mechanisms that regulate or modulate Ace display are not well understood. With interest in identifying genes associated with Ace expression, we utilized a whole-cell enzyme-linked immunosorbent assay (ELISA)-based screening method to identify mutants from a transposon insertion mutant library which exhibited distinct Ace surface expression profiles. We identified a ccpA insertion mutant which showed significantly decreased levels of Ace surface expression at early growth phase versus those of wild-type OG1RF. Confirmation of the observation was achieved through flow cytometry and complementation analysis. Compared to the wild type, the E. faecalis ccpA mutant had an impaired ability to adhere to collagen when grown to early exponential phase, consistent with the lack of Ace expression in the early growth phase. As a key component of carbon catabolite regulation, CcpA has been previously reported to play a critical role in regulating expression of proteins involved in E. faecalis carbohydrate uptake and utilization. Our discovery is the first to associate CcpA with the production of a major E. faecalis virulence factor, providing new insights into the regulation of E. faecalis pathogenesis. PMID:23974022

Recovery and Growth Potential of Listeria monocytogenes in Temperature Abused Milkshakes Prepared from Naturally Contaminated Ice Cream Linked to a Listeriosis Outbreak

DOE PAGES

Chen, Yi; Allard, Emma; Wooten, Anna; ...

2016-05-18

The recovery and growth potential of Listeria monocytogenes was evaluated in three flavors of milkshakes (vanilla, strawberry, and chocolate) that were prepared from naturally contaminated ice cream linked to a listeriosis outbreak in the U.S. in 2015, and were subsequently held at room temperature for 14 h. The average lag phase duration of L. monocytogenes was 9.05 h; the average generation time was 1.67 h; and the average population level increase per sample at 14 h was 1.14 log CFU/g. Milkshake flavors did not significantly affect these parameters. The average lag phase duration of L. monocytogenes in milkshakes with initialmore » contamination levels ≤ 3 CFU/g (9.50 h) was significantly longer (P < 0.01) than that with initial contamination levels > 3 CFU/g (8.60 h). The results highlight the value of using samples that are contaminated with very low levels of L. monocytogenes for recovery and growth evaluations. The behavior of L. monocytogenes populations in milkshakes prepared from naturally contaminated ice cream linked to the listeriosis outbreak should be taken into account when performing risk based analysis using this outbreak as a case study.« less

Recovery and Growth Potential of Listeria monocytogenes in Temperature Abused Milkshakes Prepared from Naturally Contaminated Ice Cream Linked to a Listeriosis Outbreak.

PubMed

Chen, Yi; Allard, Emma; Wooten, Anna; Hur, Minji; Sheth, Ishani; Laasri, Anna; Hammack, Thomas S; Macarisin, Dumitru

2016-01-01

The recovery and growth potential of Listeria monocytogenes was evaluated in three flavors of milkshakes (vanilla, strawberry, and chocolate) that were prepared from naturally contaminated ice cream linked to a listeriosis outbreak in the U.S. in 2015, and were subsequently held at room temperature for 14 h. The average lag phase duration of L. monocytogenes was 9.05 h; the average generation time was 1.67 h; and the average population level increase per sample at 14 h was 1.14 log CFU/g. Milkshake flavors did not significantly affect these parameters. The average lag phase duration of L. monocytogenes in milkshakes with initial contamination levels ≤ 3 CFU/g (9.50 h) was significantly longer (P < 0.01) than that with initial contamination levels > 3 CFU/g (8.60 h). The results highlight the value of using samples that are contaminated with very low levels of L. monocytogenes for recovery and growth evaluations. The behavior of L. monocytogenes populations in milkshakes prepared from naturally contaminated ice cream linked to the listeriosis outbreak should be taken into account when performing risk based analysis using this outbreak as a case study.

Recovery and Growth Potential of Listeria monocytogenes in Temperature Abused Milkshakes Prepared from Naturally Contaminated Ice Cream Linked to a Listeriosis Outbreak

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

Chen, Yi; Allard, Emma; Wooten, Anna

The recovery and growth potential of Listeria monocytogenes was evaluated in three flavors of milkshakes (vanilla, strawberry, and chocolate) that were prepared from naturally contaminated ice cream linked to a listeriosis outbreak in the U.S. in 2015, and were subsequently held at room temperature for 14 h. The average lag phase duration of L. monocytogenes was 9.05 h; the average generation time was 1.67 h; and the average population level increase per sample at 14 h was 1.14 log CFU/g. Milkshake flavors did not significantly affect these parameters. The average lag phase duration of L. monocytogenes in milkshakes with initialmore » contamination levels ≤ 3 CFU/g (9.50 h) was significantly longer (P < 0.01) than that with initial contamination levels > 3 CFU/g (8.60 h). The results highlight the value of using samples that are contaminated with very low levels of L. monocytogenes for recovery and growth evaluations. The behavior of L. monocytogenes populations in milkshakes prepared from naturally contaminated ice cream linked to the listeriosis outbreak should be taken into account when performing risk based analysis using this outbreak as a case study.« less

Recovery and Growth Potential of Listeria monocytogenes in Temperature Abused Milkshakes Prepared from Naturally Contaminated Ice Cream Linked to a Listeriosis Outbreak

PubMed Central

Chen, Yi; Allard, Emma; Wooten, Anna; Hur, Minji; Sheth, Ishani; Laasri, Anna; Hammack, Thomas S.; Macarisin, Dumitru

2016-01-01

The recovery and growth potential of Listeria monocytogenes was evaluated in three flavors of milkshakes (vanilla, strawberry, and chocolate) that were prepared from naturally contaminated ice cream linked to a listeriosis outbreak in the U.S. in 2015, and were subsequently held at room temperature for 14 h. The average lag phase duration of L. monocytogenes was 9.05 h; the average generation time was 1.67 h; and the average population level increase per sample at 14 h was 1.14 log CFU/g. Milkshake flavors did not significantly affect these parameters. The average lag phase duration of L. monocytogenes in milkshakes with initial contamination levels ≤ 3 CFU/g (9.50 h) was significantly longer (P < 0.01) than that with initial contamination levels > 3 CFU/g (8.60 h). The results highlight the value of using samples that are contaminated with very low levels of L. monocytogenes for recovery and growth evaluations. The behavior of L. monocytogenes populations in milkshakes prepared from naturally contaminated ice cream linked to the listeriosis outbreak should be taken into account when performing risk based analysis using this outbreak as a case study. PMID:27242775

Media Reports of Links between MMR and Autism: A Discourse Analysis

ERIC Educational Resources Information Center

O'Dell, Lindsay; Brownlow, Charlotte

2005-01-01

This paper details an analysis of BBC reporting of the proposed links between MMR and autism. The study aimed to identify main issues arising from the media reports into the link between MMR and the development of autism, and how these contribute to common understandings about people with autism. The study employed a form of discourse analysis to…

Evaluation of commercial enzyme-linked immunosorbent assays to identify psychedelic phenethylamines.

PubMed

Kerrigan, Sarah; Mellon, Monica Brady; Banuelos, Stephanie; Arndt, Crystal

2011-09-01

The 2C, 2C-T, and DO series of designer drugs pose a number of challenges to forensic toxicology laboratories. Although these drugs are seized by law enforcement agencies throughout the United States, they are not readily detected in forensic toxicology laboratories. A systematic evaluation of the cross-reactivity of 9 commercial enzyme-linked immunosorbent assays (ELISAs) was conducted using 11 designer drugs. Cross-reactivity was measured towards 2,5-dimethoxy-4-bromophenethylamine (2C-B), 2,5-dimethoxyphenethylamine (2C-H), 2,5-dimethoxy4-iodophenethylamine (2C-I), 2,5-dimethoxy-4ethylthiophenethylamine (2C-T-2), 2,5-dimethoxy-4isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4bromoamphetamine (DOB), 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5-dimethoxy-4-methylamphetamine (DOM), and 4methylthioamphetamine (4-MTA). Cross-reactivity towards the 2C, 2C-T, and DO series of psychedelic amphetamines was < 0.4%. Concentrations as high as 50,000 ng/mL in urine, which greatly exceed those expected in forensic case samples, were not sufficient to produce a positive result. The only substance to produce any measurable cross-reactivity was 4-MTA. Cross-reactivities of 5 and 7% were obtained using four methamphetamine/MDMA directed assays, 25 and 200% using two amphetamine-directed assays. The absence of any measurable cross-reactivity towards the 10 2C, 2C-T, and DO psychedelic phenethylamines makes it harder to detect these drugs using routine screening. As a consequence, laboratories that rely upon immunoassay rather than more broad spectrum chromatographic screening techniques, may fail to detect these powerful psychedelic substances.

Linking quality indicators to clinical trials: an automated approach

PubMed Central

Coiera, Enrico; Choong, Miew Keen; Tsafnat, Guy; Hibbert, Peter; Runciman, William B.

2017-01-01

Abstract Objective Quality improvement of health care requires robust measurable indicators to track performance. However identifying which indicators are supported by strong clinical evidence, typically from clinical trials, is often laborious. This study tests a novel method for automatically linking indicators to clinical trial registrations. Design A set of 522 quality of care indicators for 22 common conditions drawn from the CareTrack study were automatically mapped to outcome measures reported in 13 971 trials from ClinicalTrials.gov. Intervention Text mining methods extracted phrases mentioning indicators and outcome phrases, and these were compared using the Levenshtein edit distance ratio to measure similarity. Main Outcome Measure Number of care indicators that mapped to outcome measures in clinical trials. Results While only 13% of the 522 CareTrack indicators were thought to have Level I or II evidence behind them, 353 (68%) could be directly linked to randomized controlled trials. Within these 522, 50 of 70 (71%) Level I and II evidence-based indicators, and 268 of 370 (72%) Level V (consensus-based) indicators could be linked to evidence. Of the indicators known to have evidence behind them, only 5.7% (4 of 70) were mentioned in the trial reports but were missed by our method. Conclusions We automatically linked indicators to clinical trial registrations with high precision. Whilst the majority of quality indicators studied could be directly linked to research evidence, a small portion could not and these require closer scrutiny. It is feasible to support the process of indicator development using automated methods to identify research evidence. PMID:28651340

Imprinted and X-linked non-coding RNAs as potential regulators of human placental function

PubMed Central

Buckberry, Sam; Bianco-Miotto, Tina; Roberts, Claire T

2014-01-01

Pregnancy outcome is inextricably linked to placental development, which is strictly controlled temporally and spatially through mechanisms that are only partially understood. However, increasing evidence suggests non-coding RNAs (ncRNAs) direct and regulate a considerable number of biological processes and therefore may constitute a previously hidden layer of regulatory information in the placenta. Many ncRNAs, including both microRNAs and long non-coding transcripts, show almost exclusive or predominant expression in the placenta compared with other somatic tissues and display altered expression patterns in placentas from complicated pregnancies. In this review, we explore the results of recent genome-scale and single gene expression studies using human placental tissue, but include studies in the mouse where human data are lacking. Our review focuses on the ncRNAs epigenetically regulated through genomic imprinting or X-chromosome inactivation and includes recent evidence surrounding the H19 lincRNA, the imprinted C19MC cluster microRNAs, and X-linked miRNAs associated with pregnancy complications. PMID:24081302

Social thermoregulation as a potential mechanism linking sociality and fitness: Barbary macaques with more social partners form larger huddles.

PubMed

Campbell, Liz A D; Tkaczynski, Patrick J; Lehmann, Julia; Mouna, Mohamed; Majolo, Bonaventura

2018-04-17

Individuals with more or stronger social bonds experience enhanced survival and reproduction in various species, though the mechanisms mediating these effects are unclear. Social thermoregulation is a common behaviour across many species which reduces cold stress exposure, body heat loss, and homeostatic energy costs, allowing greater energetic investment in growth, reproduction, and survival, with larger aggregations providing greater benefits. If more social individuals form larger thermoregulation aggregations due to having more potential partners, this would provide a direct link between sociality and fitness. We conducted the first test of this hypothesis by studying social relationships and winter sleeping huddles in wild Barbary macaques (Macaca sylvanus), wherein individuals with more social partners experience greater probability of winter survival. Precipitation and low temperature increased huddle sizes, supporting previous research that huddle size influences thermoregulation and energetics. Huddling relationships were predicted by social (grooming) relationships. Individuals with more social partners therefore formed larger huddles, suggesting reduced energy expenditure and exposure to environmental stressors than less social individuals, potentially explaining how sociality affects survival in this population. This is the first evidence that social thermoregulation may be a direct proximate mechanism by which increased sociality enhances fitness, which may be widely applicable across taxa.

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

PubMed

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

2016-10-01

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

Review Recent progress in identification and characterization of loci associated with sex-linked congenital cataract.

PubMed

Zhang, D D; Du, J Z; Topolewski, J; Wang, X M

2016-07-29

Congenital cataract is a common cause of blindness in children; however, its pathogenesis remains unclear. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract. The current genetic models of congenital cataract include autosomal dominant, autosomal recessive, and sex-linked inheritance. Sex-linked congenital cataract could be inherited through the X or Y chromosome. Congenital cataract is a symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-Hünermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome. On the other hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified. Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients. In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract. This could help identify novel approaches for the prevention, early diagnosis, and comprehensive disease treatment.

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

PubMed Central

Agaba, Morris; Cavener, Douglas R.

2017-01-01

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