bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the JMJD3 (KDM6B) histone demethylase in glioblastoma stem cells by STAT3
Authors: Sherry-Lynes Maureen M. , Sengupta Sejuti , Kulkarni Shreya , Cochran Brent H. 
Published: July 2016

SUMMARYThe growth factor and cytokine regulated transcription factor STAT3 is required for the self-renewal of several stem cell types including tumor stem cells from glioblastoma. Here we show that STAT3 inhibition leads to the upregulation of the histone H3K27me2/3 demethylase Jmjd3 (KDM6B), which can reverse polycomb complex-mediated repression of tissue specific genes. STAT3 binds to the Jmjd3 promoter, suggesting that Jmjd3 is a direct target of STAT3. Overexpression of Jmjd3 slows glioblastoma stem cell growth and neurosphere formation, whereas knockdown of Jmjd3 rescues the STAT3 inhibitor-induced neurosphere formation defect. Consistent with this observation, STAT3 inhibition leads to histone H3K27 demethylation of neural differentiation genes, such as Myt1, FGF21, and GDF15. These results demonstrate that the regulation of Jmjd3 by STAT3 maintains repression of differentiation specific genes and is therefore important for the maintenance of self-renewal of normal neural and glioblastoma stem cells.
RNA sequencing-based cell proliferation analysis across 19 cancers identifies a subset of proliferation-informative cancers with a common survival signature
Authors: Ramaker Ryne C. , Lasseigne Brittany N. , Hardigan Andrew A. , Palacio Laura , Gunther David S. , Kirby Marie K. , Myers Richard M. , Cooper Sara J. 
Published: July 2016

AbstractDespite advances in cancer diagnosis and treatment strategies, robust prognostic signatures remain elusive in most cancers. Cell proliferation has long been recognized as a prognostic marker in cancer, but it has not been thoroughly investigated across multiple cancers. Here we explore the role of cell proliferation across 19 cancers (n=6,581 patients) using tissue-based RNA sequencing from The Cancer Genome Atlas project by employing a ‘proliferative index’ derived from gene expression associated withPCNAexpression. This proliferative index is significantly associated with patient survival (Cox, p-value<0.05) in 7/19 cancers, which we have defined as ‘proliferation-informative cancers’ (PICs). In PICs the proliferative index is strongly correlated with tumor stage and nodal invasion. PICs paradoxically demonstrate reduced baseline expression of proliferation machinery relative to non-PICs suggesting that non-PICs saturate their proliferative capacity early in tumor development and allow other factors to dictate prognostic outcomes. We also identify chemotherapies whose efficacy is correlated with proliferation index and highlight drugs capable of inhibiting proliferation associated expression. Additionally, we find that proliferative index is significantly associated with gross somatic mutation burden (Spearman, p=1.76×10−23) as well mutations in individual driver genes. This analysis provides a comprehensive characterization of tumor proliferation rates and their association with disease progression and prognosis across cancer types and highlights specific cancers that may be particularly susceptible to improved targeting of this classic cancer hallmark.
Measuring experimental cyclohexane-water distribution coefficients for the SAMPL5 challenge
Authors: Rustenburg Ariën S. , Dancer Justin , Lin Baiwei , Feng Jianwen A. , Ortwine Daniel F. , Mobley David L. , Chodera John D. 
Published: July 2016

Small molecule distribution coefficients between immiscible nonaqueuous and aqueous phases—such as cyclohexane and water—measure the degree to which small molecules prefer one phase over another at a given pH. As distribution coefficients capture both thermodynamic effects (the free energy of transfer between phases) and chemical effects (protonation state and tautomer effects in aqueous solution), they provide an exacting test of the thermodynamic and chemical accuracy of physical models without the long correlation times inherent to the prediction of more complex properties of relevance to drug discovery, such as protein-ligand binding affinities. For the SAMPL5 challenge, we carried out a blind prediction exercise in which participants were tasked with the prediction of distribution coefficients to assess its potential as a new route for the evaluation and systematic improvement of predictive physical models. These measurements are typically performed for octanol-water, but we opted to utilize cyclohexane for the nonpolar phase. Cyclohexane was suggested to avoid issues with the high water content and persistent heterogeneous structure of water-saturated octanol phases, since it has greatly reduced water content and a homogeneous liquid structure. Using a modified shake-flask LC-MS/MS protocol, we collected cyclohexane/water distribution coefficients for a set of 53 druglike compounds at pH 7.4. These measurements were used as the basis for the SAMPL5 Distribution Coefficient Challenge, where 18 research groups predicted these measurements before the experimental values reported here were released. In this work, we describe the experimental protocol we utilized for measurement of cyclohexane-water distribution coefficients, report the measured data, propose a new bootstrap-based data analysis procedure to incorporate multiple sources of experimental error, and provide insights to help guide future iterations of this valuable exercise in predictive modeling.Abbreviations used in this paperSAMPLStatistical Assessment of the Modeling of Proteins and Ligandslog Plog10partition coefficientlog Dlog10distribution coefficientLC-MS/MSLiquid chromatography - tandem mass spectrometryHPLCHigh-pressure liquid chromatographyMRMMultiple reaction monitoringDMSODimethyl sulfoxidePBSPhosphate buffered salineRPMRevolutions per minuteCVCoefficient of variationMAPMaximuma posterioriMCMCMarkov chain Monte Carlo
Deconvolution model for cytometric microbial subgroups along a freshwater hydrologic continuum
Authors: Amalfitano Stefano , Fazi Stefano , Romani Anna M. , Andrea Butturini 
Published: July 2016

AbstractFlow cytometry is suitable to discriminate and quantify aquatic microbial cells within a spectrum of fluorescence and light scatter signals. Using fixed operational and gating settings, a mixture model, coupled to Laplacian operator and Nelder-Mead optimization algorithm, allowed deconvolving bivariate cytometric profiles into single cell subgroups. This procedure was applied to outline recurrent patterns and quantitative changes of the aquatic microbial community along a river hydrologic continuum. We found five major persistent subgroups within each of the commonly retrieved populations of cells with Low and High content of Nucleic Acids (namely, LNA and HNA cells). Moreover, we assessed changes of the cytometric community profile over-imposed by water inputs from a wastewater treatment plant. Our approach for multiparametric data deconvolution confirmed that flow cytometry could represent a prime candidate technology for assessing microbial community patterns in flowing waters.
Coordinates and Intervals in Graph-based Reference Genomes
Authors: Rand Knut D. , Grytten Ivar , Nederbragt Alexander J. , Storvik Geir O. , Glad Ingrid K. , Sandve Geir K. 
Published: July 2016

AbstractMotivationIt has been proposed that future reference genomes should be graph structures in order to better represent the sequence diversity present in a species. However, there is currently no standard method to represent genomic intervals, such as positions of genes, on graph-based reference genomes.ResultsWe formalize offset-based coordinate systems on graph-based reference genomes and introduce a method for representing intervals on these reference structures. We show the advantage of our method by representing genes on a graph-based representation of the GRCh38 version of the human genome and its alternative loci for regions that are highly variable.ConclusionMore complex reference genomes, containing alternative loci, require methods to represent genomic data on these structures. Our proposed notation for genomic intervals makes it possible to fully utilize the alternative loci of GRCh38 and potential future graph-based reference genomes. We illustrate our notation for genomic intervals, as well as the offset-based coordinate systems, through a web tool at:https://github.com/uio-cels/gen-graph-coords.
Shared predation: positive effects of predator distraction
Authors: Teixeira Alves Mickaël , Grognard Frédéric , Calcagno Vincent , Mailleret Ludovic 
Published: July 2016

AbstractSimple rules based on population equilibria can characterize indirect interactions in three-species systems but fail to predict them when considering behavioral mechanisms. In this paper, we revisit the effects of shared predation,i.e. the situation in which two prey are consumed by a common predator. Such predation usually induces negative indirect interactions between prey, or apparent competition, through an increase of predator density and thus of predation pressure. Two mechanisms can however weaken apparent competition and lead to equivocal signs of indirect interactions. On the one hand, predator distraction, which stems from the difficulty to efficiently forage for different prey at the same moment in time and diminishes the number of prey capturedperpredator. On the other hand, predator negative density dependence limits predator growth. To get further insights into simple rules describing indirect interactions brought about by shared predation, we studied two classes of one-predator-two-prey models exhibiting these two mechanisms. We found robust simple rules derived from predator equilibria which state that at least one prey is favored by the presence of the other when the predators partition their foraging effort between them. These rules thus characterize a surprising wide range of indirect effects including apparent predation, apparent commensalism and apparent mutualism. They also highlight different situations in which larger predator populations do not entail smaller prey populations and in which neither prey species can be negatively affected by the other.
Benzoate and Salicylate Tolerant Strains Lose Antibiotic Resistance during Laboratory Evolution ofEscherichia coliK-12
Authors: Creamer Kaitlin E. , Ditmars Frederick S. , Basting Preston J. , Kunka Karina S. , Hamdallah Issam N. , Bush Sean P. , Scott Zachary , He Amanda , Penix Stephanie R. , Gonzales Alexandra S. , Eder Elizabeth K. , Camperchioli Dominic , Berndt Adama , Clark Michelle W. , Rouhier Kerry A. , Slonczewski Joan L. 
Published: July 2016

ABSTRACTEscherichia coliK-12 W3110 grows in the presence of membrane-permeant organic acids that can depress cytoplasmic pH and accumulate in the cytoplasm. We conducted experimental evolution by daily diluting cultures in increasing concentrations of benzoic acid (up to 20 mM) buffered at external pH 6.5, a pH at which permeant acids concentrate in the cytoplasm. By 2,000 generations, clones isolated from evolving populations showed increasing tolerance to benzoate but were sensitive to chloramphenicol and tetracycline. Sixteen clones grew to stationary phase in 20 mM benzoate, whereas the ancestral strain W3110 peaked and declined. Similar growth occurred in 10 mM salicylate. Benzoate-evolved strains grew like W3110 in the absence of benzoate; in media buffered at pH 4.8, pH 7.0, or pH 9.0; or in 20 mM acetate or sorbate at pH 6.5. Genomes of 16 strains revealed over 100 mutations including SNPs, large deletions, and insertion knockouts. Most strains acquired deletions in the benzoate-induced multiple antibiotic resistance (Mar) regulon or in associated regulators such asrobandcpxA, as well as MDR efflux pumpsemrA,emrY, andmdtA. Strains also lost or down-regulated the Gad acid fitness regulon. In 5 mM benzoate, or in 2 mM salicylate (2-hydroxybenzoate), most strains showed increased sensitivity to the antibiotics chloramphenicol and tetracycline; some strains were more sensitive than amarAknockout. Thus, our benzoate-evolved strains may reveal additional unknown drug resistance components. Benzoate or salicylate selection pressure may cause general loss of MDR genes and regulators.IMPORTANCEBenzoate is a common food preservative, and salicylate is the primary active metabolite of aspirin. In the gut microbiome, genetic adaptation to salicylate may involve loss or downregulation of inducible multidrug resistance systems. This discovery implies that aspirin therapy may modulate the human gut microbiome to favor salicylate tolerance at the expense of drug resistance. Similar aspirin-associated loss of drug resistance might occur in bacterial pathogens found in arterial plaques.
Opposing influences on construction plant and machinery health and safety innovations
Authors: Holt Gary D. 
Published: July 2016

Purpose
This paper aims to consider opposing influences on workplace plant and machinery health and safety (PMH&S) innovations, highlight examples of these to model PMH&S innovations’ effectiveness at the workplace, develop guidance for improvement of same and for construction of health and safety (H&S) performance.

Design/methodology/approach
This study is a qualitative meta-analysis of data distributed among a sample of published research in the field, and it uses inductive reasoning based on informal, qualitative and interpretative analysis.

Findings
Nearly all PMH&S innovations (positive influences) originate from original equipment manufacturers and specialist companies throughout the supply chain. Negative influences that can counter these potential H&S benefits result mainly from human (in) action(s) at the workplace. These are classified (and analysed) in terms of “error”, “indifference” and “lack of training”. “Tolerant” H&S management is another negative influence found among these classifications.

Originality/value
The study draws from a targeted meta-sample of research in the field, a model of positive and negative influences on PMH&S innovations that emphasises workers’ (in) action(s).
Right-time vs real-time pro-active construction safety and health system architecture
Authors: Teizer Jochen 
Published: July 2016

Purpose
The purpose of this paper is to investigate the critical time window for pro-active construction accident prevention and response. Large to small organisations throughout the entire construction supply chain continue to be challenged to adequately prevent accidents. Construction worker injuries and fatalities represent significant waste of resources. Although the five C’s (culture, competency, communication, controls and contractors) have been focusing on compliance, good practices and best-in-class strategies, even industry leaders have only marginal improvements in recorded safety statistics for many years.

Design/methodology/approach
Right-time vs real-time construction safety and health identifies three major focus areas to aid in the development of a strategic, as opposed to tactical, response. Occupational safety and health by design, real-time safety and health monitoring and alerts and education, training and feedback leveraging state-of-the-art technology provide meaningful predictive, quantitative and qualitative measures to identify, correlate and eliminate hazards before workers get injured or incidents cause collateral damage.

Findings
The current state and development of existing innovative initiatives in the occupational construction safety and health domain are identified. A framework for right-time vs real-time construction safety and health presents the specific focus on automated safety and health data gathering, analysis and reporting to achieve better safety performance. The developed roadmap for right-time vs real-time safety and health is finally tested in selected application scenarios of high concern in the construction industry.

Originality/value
A strategic roadmap to eliminate hazards and accidents through right-time vs real-time automation is presented that has practical as well as social implications on conducting a rigorous safety culture and climate in a construction business and its entire supply chain.
Librarians and scientists partner to address data management
Authors: Medina-Smith Andrea , Tryka Kimberly A. , Silcox Barbara , Hanisch Robert J. 
Published: July 2016

Purpose
This study aims to look at the changing way in which the Information Services Office (ISO) at the National Institute of Standards and Technology (NIST) provides services to NIST scientific and technical staff throughout their research and publishing cycles. These services include the more traditional services of a research library and publishing NIST technical reports and The Journal of Research of NIST and preserving and exhibiting scientific instruments and other artifacts. ISO has always prided itself on having a close relationship with its customers, providing a high level of service and developing new services to stay in front of NIST researcher needs. Through a concerted, strategic effort since the late 1990s, ISO has developed and promoted relationships with its key customers through its Lab Liaison Program.

Design/methodology/approach
This paper discusses the relationship ISO has developed with the Office of Data and Informatics (ODI), how this relationship was forged and how this collaboration will serve as a model for working with the other labs and programs at NIST. It will also discuss the risks and opportunities of this new collaborative service model, how ISO positioned itself to become an equal partner with ODI in the exploration of solutions to data management issues and the benefits of the relationship from ODI’s perspective.

Findings
A pattern of strategic changes to the services and activities offered by the Lab Liaison program has put ISO in the position to collaborate as peers with researchers at NIST.

Originality/value
This study provides an overview of how ISO made strategic decisions to incorporate non-traditional services to support data management at NIST.
The impact of managerial commitment and Kaizen benefits on companies
Authors: Oropesa Vento Midiala , García Alcaraz Jorge  Luis , Maldonado Macías Aidé  Aracely , Martínez Loya Valeria 
Published: July 2016

Purpose
– The purpose of this paper is to analyze the effects of both managerial commitment and the professional development of human resources on the benefits obtained from Kaizen implementation at the planning stage in Mexican maquiladora companies.

Design/methodology/approach
– As part of the methodology, a questionnaire is validated and administered to 423 workers in different companies from the states of Tabasco, Baja California, Sinaloa and Chihuahua. Moreover, a structural equation model is proposed to relate four latent variables: two concerning managerial commitment and the professional development of human resources, and two more related to the kinds of benefits obtained (economic and for human resources).

Findings
– Results demonstrate that managerial commitment has a direct and positive impact on economic benefits and those for human resources. The major contribution of this study is, however, the determination of dependency measures between these variables.

Practical implications
– This research contributes to the improvement and change, since the results of the research can be extended to the sustainability of other improvement activities, presenting additional areas for future research, such understanding will increase the likelihood that the results of application of Kaizen are sustained, eliminating waste and improving support within the organization. Finally, this research makes contributions to the field of industrial engineering and management disciplines of engineering and operations management, as it focusses on the improvement of integrated systems of people, materials, information, equipment and energy, these systems they are integral to the modeling of this investigation.

Originality/value
– This study tests the hypotheses and their relation to the sustainability of Kaizen in time for them to use the analysis technique of structural equations. For the author, this is the first study to determine the causal relationships between the critical success factors and benefits of Kaizen, determining a measure of dependence between them.
Understanding research students’ behavioural intention in the adoption of digital libraries
Authors: Khan Asad , Qutab Saima 
Published: July 2016

Purpose
The purpose of this study is to investigate the factors that influence the adoption of Higher Education Commission (HEC) National Digital Library among research students in different universities of Pakistan.

Design/methodology/approach
The study framework was based on technology acceptance model (TAM). A sample of Pakistani university students completed the questionnaire measuring the effects of extraneous stimuli through cognitive responses on adoption of the HEC digital library. To test the research hypotheses, multiple regression analysis was used.

Findings
The findings revealed that: cognitive responses predicted students’ intention of using HEC digital library; extraneous variables significantly influenced cognitive responses; system characteristics directly influenced usefulness and ease of use; interface characteristics directly influenced cognitive responses; and individual differences significantly affected the ease of use. Similarly, system quality was identified with the highest direct effect on usefulness, whereas navigation had the highest influence on easy use of the HEC digital library of Pakistan. In addition, usefulness was explored with the highest effect on intention to use the HEC digital library of Pakistan. The findings revealed that individual behaviours influence the use of digital libraries which imply that acceptance of an information system (IS) involve cognitive idiosyncrasies. Findings of the study are useful for Pakistani academic librarians to enhance adoption and usability of the HEC digital library of Pakistan. The study extended cross-cultural validation of TAM and explored how that Pakistani university students utilize HEC digital library.

Research limitations/implications
These findings have significant implications for librarians in developing countries, such as to evaluate usability of digital libraries from individuals’ perspective, create awareness, customize users’ interface and train students in navigational techniques. It may also facilitate librarians to improve their current levels of library assistance and emphasize the usefulness of digital libraries towards academic excellence. The findings equally suggest that individual behaviours influence the use of digital libraries because acceptance of an information system involves cognitive idiosyncrasies. This study explored all possible links between the study constructs and emphasized that findings are useful to enhance the adoption and usability of digital library in the developing countries.

Originality/value
This study is the first attempt that empirically assessed the adoption of digital libraries in terms of Pakistani research students. The study validated TAM in the context of Pakistani university librarianship that extended the cross-cultural validation of TAM. Furthermore, the study focused on real constructs instead of dummy variables and predicted significant effects on acceptance and rejection of digital libraries.