bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graphical interface design for children seeking information in a digital library
Authors: Wu Ko-chiu , Tang Yun-meng , Tsai Cheng-yu 
Published: May 2014

Abstract
Background
Children are very curious. They like to play games but lack reading fluency. Conventional interfaces for information-seeking in digital libraries are unsuitable for children because they are rigid, text-based, and task-oriented. Thus, this study developed a customized interface for a digital library. To facilitate children in online searches, the design concepts included user-friendly target icons, icon recognition, and way-finding in a two-dimensional visualized environment.

Methods
In this study, the criteria used to develop visualization tools that children can use for information retrieval were based on theories of human perception related to graphical interfaces for information visualization systems, including iconic representations and information density on visualized displays. Databases widely used by children in the National Library of Public Information were linked to the suggested database frame. The database frame was classified into five major subject categories: Natural Sciences, Fine Arts and Music, Health and Athletics, History and Culture, and Treasure of Knowledge. The web interface was designed according to way-finding concepts and map-structure hierarchies. Information searches in the main frame, sub-frames, and linked database were designed to be simple and intuitive for use by children.

Results
Information search efficiency was measured in 104 children assigned to search the virtual environment for icons (databases) that adequately supported their studies. Statistical analyses showed that, compared to the text-lined interface, the graphical interface improved the success and speed of searches by children.

Conclusions
Incorporating theories of spatial memory and representative icons in designs for visualized retrieval systems helps children to recognize different categories of knowledge content and improves their efficiency in information retrieval. To improve database search efficiency in children, information recommendation issues require further study. However, further research is also needed to identify factors that affect patterns of information-seeking behavior in children.
Survivin family proteins as novel molecular determinants of doxorubicin resistance in organotypic human breast tumors
Authors: Faversani Alice , Vaira Valentina , Moro Giacomina P , Tosi Delfina , Lopergolo Alessia , Schultz David C , Rivadeneira Dayana , Altieri Dario C , Bosari Silvano 
Published: May 2014

Abstract
Introduction
The molecular determinants of breast cancer resistance to first-line anthracycline-containing chemotherapy are unknown.

Methods
We examined the response to doxorubicin of organotypic cultures of primary human breast tumors ex vivo with respect to cell proliferation, DNA damage and modulation of apoptosis. Samples were analyzed for genome-wide modulation of cell death pathways, differential activation of p53, and the role of survivin family molecules in drug resistance. Rational drug combination regimens were explored by high-throughput screening, and validated in model breast cancer cell types.

Results
Doxorubicin treatment segregated organotypic human breast tumors into distinct Responder or Non Responder groups, characterized by differential proliferative index, stabilization of p53, and induction of apoptosis. Conversely, tumor histotype, hormone receptor or human epidermal growth factor receptor-2 (HER2) status did not influence chemotherapy sensitivity. Global analysis of cell death pathways identified survivin and its alternatively spliced form, survivin-ΔEx3 as uniquely overexpressed in Non Responder breast tumors. Forced expression of survivin-ΔEx3 preserved cell viability and prevented doxorubicin-induced apoptosis in breast cancer cell types. High-throughput pharmacologic targeting of survivin family proteins with a small-molecule survivin suppressant currently in the clinic (YM155) selectively potentiated the effect of doxorubicin, but not other chemotherapeutics in breast cancer cell types, and induced tumor cell apoptosis.

Conclusions
Survivin family proteins are novel effectors of doxorubicin resistance in chemotherapy-naive breast cancer. The incorporation of survivin antagonist(s) in anthracycline-containing regimens may have improved clinical activity in these patients.
Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death
Authors: Kim Jinhee , Ghasemzadeh Nima , Eapen Danny J , Chung Neo Christopher , Storey John D , Quyyumi Arshed A , Gibson Greg 
Published: May 2014

Abstract
Background
Genetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.

Methods
Peripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followed for a mean 2.4 years for cardiovascular death. Gene expression was measured on Illumina HT-12 microarrays with two different normalization procedures to control technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Analysis of variance was combined with receiver operating curve and survival analysis to define a transcriptional signature of cardiovascular death.

Results
In both phases, there was significant differential expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. Expression quantitative trait loci analysis provided evidence for altered local genetic regulation of transcript abundance in AMI samples. On follow-up there were 31 cardiovascular deaths. A principal component (PC1) score capturing covariance of 238 genes that were differentially expressed between deceased and survivors in the discovery phase significantly predicted risk of cardiovascular death in the replication and combined samples (hazard ratio = 8.5, P < 0.0001) and improved the C-statistic (area under the curve 0.82 to 0.91, P = 0.03) after adjustment for traditional covariates.

Conclusions
A specific blood gene expression profile is associated with a significant risk of death in Caucasian subjects with CAD. This comprises a subset of transcripts that are also altered in expression during acute myocardial infarction.
Genome-Wide Analyses of ChIP-Seq Derived FOXA2 DNA Occupancy in Liver Points to Genetic Networks Underpinning Multiple Complex Traits
Authors: Johnson Matthew E. , Schug Jonathan , Wells Andrew D. , Kaestner Klaus H. , Grant Struan F. A. 
Published: May 2014

Background:Forkhead Box A2 (FOXA2) exerts an influence on glucose homeostasis via activity in the liver. In addition, a key genome-wide association study (GWAS) recently demonstrated that genetic variation, namely rs6048205, at the FOXA2 locus is robustly associated with fasting glucose levels. Our hypothesis was that this DNA-binding protein regulates the expression of a set of molecular pathways critical to endocrine traits.Methods:Drawing on our laboratory and bioinformatic experience with chromatin immunoprecipitation followed by massively parallel sequencing, we analyzed our existing FOXA2 chromatin immunoprecipitation followed by massively parallel sequencing data generated in human liver, using the algorithm hypergeometric optimization of motif enrichment, to gain insight into its global genomic binding pattern from a disease perspective.Results:We performed a pathway analysis of the gene list using the gene set enrichment analysis algorithm, which yielded a number of significant annotations. Motivated by the fact that the FOXA2 locus has been implicated by GWAS, we cross-referenced the occupancy sites with the National Institutes of Health GWAS catalog and found strong evidence for the enrichment of loci implicated in endocrine, neuropsychiatric, cardiovascular, and cancer trait categories, but interestingly there was no evidence for enrichment for inflammation related traits. Intriguingly, a FOXA2 occupancy site coincided with rs6048205, suggesting that this variant confers its effect, at least partially, via a perturbation of a FOXA2 feedback mechanism.Conclusion:Our data strongly suggest that FOXA2 is acting as a master regulator of key pathways that are enriched for loci implicated by GWAS for most trait categories, with the clear exception of inflammation, suggesting that this factor exerts its effect in this context via noninflammatory processes.
Teprotumumab, an IGF-1R Blocking Monoclonal Antibody Inhibits TSH and IGF-1 Action in Fibrocytes
Authors: Chen Hong , Mester Tünde , Raychaudhuri Nupur , Kauh Courtney Y. , Gupta Shivani , Smith Terry J. , Douglas Raymond S. 
Published: May 2014

Context:
Thyroid-associated ophthalmopathy (TAO) is the component of Graves' disease characterized by orbital inflammation and connective tissue remodeling. The IGF-1 receptor (IGF-1R) and TSH receptor (TSHR) form a physical and functional complex in orbital fibroblasts. A subset of these fibroblasts is derived from infiltrating CD34+ fibrocytes. Teprotumumab (RV 001, R1507) is a human monoclonal anti-IGF-1R blocking antibody currently undergoing a phase 2 clinical trial in patients with active TAO.

Objective:
To determine whether teprotumumab inhibits the induction by TSH of IL-6 and IL-8 in fibrocytes.

Design:
Fibrocytes were treated without or with teprotumumab in combination with IGF-1 or TSH.

Main Outcome Measures:
IL-6 and IL-8 mRNA expression and protein production were analyzed by real-time PCR and Luminex, respectively. Phosphorylated Akt (S473) levels were analyzed by Western blot. TSHR and IGF-1R display was assessed by flow cytometry.

Results:
Fibrocyte display of IGF-1R and TSHR was reduced with teprotumumab, as were IGF-1- and TSH-dependent phosphorylated Akt levels. TSH induction of IL-6 and IL-8 mRNA and protein was also reduced by the monoclonal antibody.

Conclusions:
Teprotumumab attenuates the actions of both IGF-1 and TSH in fibrocytes. Specifically, it blocks the induction of proinflammatory cytokines by TSH. These results provide, at least in part, the molecular rationale for interrogating the therapeutic efficacy of this antibody in TAO.
Bällchen is required for self-renewal of germline stem cells in Drosophila melanogaster
Authors: Herzig Bettina , Yakulov Toma A. , Klinge Kathrin , Günesdogan Ufuk , Jäckle Herbert , Herzig Alf 
Published: May 2014

ABSTRACT
Self-renewing stem cells are pools of undifferentiated cells, which are maintained in cellular niche environments by distinct tissue-specific signalling pathways. In Drosophila melanogaster, female germline stem cells (GSCs) are maintained in a somatic niche of the gonads by BMP signalling. Here we report a novel function of the Drosophila kinase Bällchen (BALL), showing that its cell autonomous role is to maintain the self-renewing capacity of female GSCs independent of BMP signalling. ball mutant GSCs are eliminated from the niche and subsequently differentiate into mature eggs, indicating that BALL is largely dispensable for differentiation. Similar to female GSCs, BALL is required to maintain self-renewal of male GSCs, suggesting a tissue independent requirement of BALL for self-renewal of germline stem cells.
Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter
Authors: Nakashima Akio , Kamada Shinji , Tamanoi Fuyuhiko , Kikkawa Ushio 
Published: May 2014

ABSTRACT
The Tsc1–Tsc2 complex homologous to human tuberous sclerosis complex proteins governs amino acid uptake by regulating the expression and intracellular distribution of amino acid transporters in Schizosaccharomyces pombe. Here, we performed a genetic screening for molecules that are involved in amino acid uptake and found Arn1 (also known as Any1). Arn1 is homologous to ART1, an arrestin-related trafficking adaptor (ART) in Saccharomyces cerevisiae, and contains a conserved arrestin motif, a ubiquitination site, and two PY motifs. Overexpression of arn1+ confers canavanine resistance on cells, whereas its disruption causes hypersensitivity to canavanine. We also show that Arn1 regulates endocytosis of the Cat1 amino acid transporter. Furthermore, deletion of arn1+ suppresses a defect of amino acid uptake and the aberrant Cat1 localization in tsc2Δ. Arn1 interacts with and is ubiquitinated by the Pub1 ubiquitin ligase, which is necessary to regulate Cat1 endocytosis. Cat1 undergoes ubiquitinations on lysine residues within the N-terminus, which are mediated, in part, by Arn1 to determine Cat1 localization. Correctively, Arn1 is an ART in S. pombe and contributes to amino acid uptake through regulating Cat1 endocytosis in which Tsc2 is involved.
Cenp-meta is required for sustained spindle checkpoint
Authors: Rubin Thomas , Karess Roger E. , Rahmani Zohra 
Published: May 2014

ABSTRACT
Cenp-E is a kinesin-like motor protein required for efficient end-on attachment of kinetochores to the spindle microtubules. Cenp-E immunodepletion in Xenopus mitotic extracts results in the loss of mitotic arrest and massive chromosome missegregation, whereas its depletion in mammalian cells leads to chromosome segregation defects despite the presence of a functional spindle assembly checkpoint (SAC). Cenp-meta has previously been reported to be the Drosophila homolog of vertebrate Cenp-E. In this study, we show that cenp-metaΔ mutant neuroblasts arrest in mitosis when treated with colchicine. cenp-metaΔ mutant cells display a mitotic delay. Yet, despite the persistence of the two checkpoint proteins Mad2 and BubR1 on unattached kinetochores, these cells eventually enter anaphase and give rise to highly aneuploid daughter cells. Indeed, we find that cenp-metaΔ mutant cells display a slow but continuous degradation of cyclin B, which eventually triggers the mitotic exit observed. Thus, our data provide evidence for a role of Cenp-meta in sustaining the SAC response.
Cdk5 activity in the brain – multiple paths of regulation
Authors: Shah Kavita , Lahiri Debomoy K. 
Published: May 2014

ABSTRACTCyclin dependent kinase-5 (Cdk5), a family member of the cyclin-dependent kinases, plays a pivotal role in the central nervous system. During embryogenesis, Cdk5 is indispensable for brain development and, in the adult brain, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation. However, Cdk5 activity becomes deregulated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, which leads to neurotoxicity. Therefore, precise control over Cdk5 activity is essential for its physiological functions. This Commentary covers the various mechanisms of Cdk5 regulation, including several recently identified protein activators and inhibitors of Cdk5 that control its activity in normal and diseased brains. We also discuss the autoregulatory activity of Cdk5 and its regulation at the transcriptional, post-transcriptional and post-translational levels. We finally highlight physiological and pathological roles of Cdk5 in the brain. Specific modulation of these protein regulators is expected to provide alternative strategies for the development of effective therapeutic interventions that are triggered by deregulation of Cdk5.
A Tight 2-Approximation for Preemptive Stochastic Scheduling
Authors: Megow Nicole , Vredeveld Tjark 
Published: May 2014

We consider dynamic stochastic scheduling of preemptive jobs with processing times that follow independent discrete probability distributions. We derive a policy with a guaranteed performance ratio of 2 for the problem of minimizing the sum of weighted completion times on identical parallel machines subject to release dates. The analysis is tight. Our policy as well as their analysis applies also to the more general model of stochastic online scheduling.In contrast to previous results for nonpreemptive stochastic scheduling, our preemptive policy yields an approximation guarantee that is independent of the processing time distributions. However, our policy extensively utilizes information on the distributions other than the first (and second) moments. We also introduce a new nontrivial lower bound on the expected value of an unknown optimal policy. It relies on a relaxation to the basic problem on a single machine without release dates, which is known to be solved optimally by the Gittins index priority rule. This dynamic priority index is crucial to the analysis and also inspires the design of our policy.
Mobile phone and adolescents- addiction a mindful check in!
Authors: Sumesh Kumar Sudhen 
Published: May 2014

Mobile phones, one of the greatest inventions in the late 20th century, now have become the newest addiction in the world. Even though it has given us convenient and comfort, it doesn’t mean it has no adverse effect. It is something that is going to affect everyone on day to day basis. The concept and ideas of the adolescents with mobile phone use and mental health generated a possible pathway for personnel dependency and also for the direct sources of stress, depression, sleep disturbances, aggression, and to a list of risky behaviors. However, studies on the association between problematic mobile phone use and psychological problems have been relatively few until now. The impact of mobile phone in adolescents in different domains of mental health should be considered for epidemiological and interventional studies. Keywords: Adolescents, Cell Phone Use [CPU], Mobile Phone, Mobile Phone Use [MPU], Psychological Problems.
Monitoring the Aging of Industrial Motors by Geometric Trending of Frequency Domain Signatures
Authors: Bayram Duygu , Şeker Serhat , Upadhyaya Belle R. 
Published: May 2014

Abstract
The characterization of the aging of electric motors using vibration measurements and a geometric interpretation of spectral domain signatures is presented. For comparison, two vibration signal records from a three-phase induction motor were acquired during degradation due to bearing fluting, following thermal and chemical aging sequences. Power spectral densities (PSD) of the vibration signals were calculated and linear approximations to the spectral signatures were used to observe the overall trend. The intersection point and slopes of these linear representations were used to extract certain critical frequencies in order to define convex regions (CR) and convex hulls (CH) as representatives of the aging (degradation) process. Furthermore, using these CRs and CHs, the functional readiness of motors could be determined by comparison of the signatures for initial and aged conditions.
Validation of Six Genetic Determinants of Susceptibility to Estrogen-Induced Mammary Cancer in the Rat and Assessment of Their Relevance to Breast Cancer Risk in Humans
Authors: Colletti John A , Leland-Wavrin Kristin M , Kurz Scott G , Hickman Maureen Peters , Seiler Nicole L , Samanas Nyssa Becker , Eckert Quincy A , Dennison Kirsten L , Ding Lina , Schaffer Beverly S , Shull James D 
Published: May 2014

Abstract
When treated with 17β-estradiol, female ACI rats (Rattus norvegicus) rapidly develop mammary cancers that share multiple phenotypes with luminal breast cancers. Seven distinct quantitative trait loci that harbor genetic determinants of susceptibility to 17β-estradiol−induced mammary cancer have been mapped in reciprocal intercrosses between susceptible ACI rats and resistant Brown Norway (BN) rats. A panel of unique congenic rat strains has now been generated and characterized to confirm the existence of these quantitative trait loci, designated Emca3 through Emca9, and to quantify their individual effects on susceptibility to 17β-estradiol−induced mammary cancer. Each congenic strain carries BN alleles spanning an individual Emca locus, introgressed onto the ACI genetic background. Data presented herein indicate that BN alleles at Emca3, Emca4, Emca5, Emca6, and Emca9 reduce susceptibility to 17β-estradiol−induced mammary cancer, whereas BN alleles at Emca7 increase susceptibility, thereby confirming the previous interval mapping data. All of these Emca loci are orthologous to regions of the human genome that have been demonstrated in genome-wide association studies to harbor genetic variants that influence breast cancer risk. Moreover, four of the Emca loci are orthologous to loci in humans that have been associated with mammographic breast density, a biomarker of breast cancer risk. This study further establishes the relevance of the ACI and derived congenic rat models of 17β-estradiol−induced mammary cancer for defining the genetic bases of breast cancer susceptibility and elucidating the mechanisms through which 17β-estradiol contributes to breast cancer development.
Essential Domains ofSchizosaccharomyces pombeRad8 Required for DNA Damage Response
Authors: Ding Lin , Forsburg Susan L 
Published: May 2014

AbstractSchizosaccharomyces pombe Rad8 is a conserved protein homologous to S. cerevisiaeRad5 and human HLTF that is required for error-free postreplication repair by contributing to polyubiquitylation of PCNA. It has three conserved domains: an E3 ubiquitin ligase motif, a SNF2-family helicase domain, and a family-specific HIRAN domain. Data from humans and budding yeast suggest that helicase activity contributes to replication fork regression and template switching for fork restart. We constructed specific mutations in the three conserved domains and found that both the E3 ligase and HIRAN domains are required for proper response to DNA damage caused by a variety of agents. In contrast, mutations in the helicase domain show no phenotypes in a wild-type background. To determine whether Rad8 functionally overlaps with other helicases, we compared the phenotypes of single and double mutants with a panel of 23 nonessential helicase mutants, which we categorized into five phenotypic groups. Synthetic phenotypes with rad8∆ were observed for mutants affecting recombination, and a rad8 helicase mutation affected the HU response of a subset of recombination mutants. Our data suggest that the S. pombe Rad8 ubiquitin ligase activity is important for response to a variety of damaging agents, while the helicase domain plays only a minor role in modulating recombination-based fork restart during specific forms of replication stress.
A Roadmap for Functional Structural Variants in the Soybean Genome
Authors: Anderson Justin E , Kantar Michael B , Kono Thomas Y , Fu Fengli , Stec Adrian O , Song Qijian , Cregan Perry B , Specht James E , Diers Brian W , Cannon Steven B , McHale Leah K , Stupar Robert M 
Published: May 2014

Abstract
Gene structural variation (SV) has recently emerged as a key genetic mechanism underlying several important phenotypic traits in crop species. We screened a panel of 41 soybean (Glycine max) accessions serving as parents in a soybean nested association mapping population for deletions and duplications in more than 53,000 gene models. Array hybridization and whole genome resequencing methods were used as complementary technologies to identify SV in 1528 genes, or approximately 2.8%, of the soybean gene models. Although SV occurs throughout the genome, SV enrichment was noted in families of biotic defense response genes. Among accessions, SV was nearly eightfold less frequent for gene models that have retained paralogs since the last whole genome duplication event, compared with genes that have not retained paralogs. Increases in gene copy number, similar to that described at the Rhg1 resistance locus, account for approximately one-fourth of the genic SV events. This assessment of soybean SV occurrence presents a target list of genes potentially responsible for rapidly evolving and/or adaptive traits.