bluuebunny/crossref_metadata_2025_split huggingface dataset:
cit: hypothesis testing software for mediation analysis in genomic applications
Authors: Millstein Joshua , Chen Gary K. , Breton Carrie V. 
Published: March 2016

Abstract
Motivation: The challenges of successfully applying causal inference methods include: (i) satisfying underlying assumptions, (ii) limitations in data/models accommodated by the software and (iii) low power of common multiple testing approaches.
Results: The causal inference test (CIT) is based on hypothesis testing rather than estimation, allowing the testable assumptions to be evaluated in the determination of statistical significance. A user-friendly software package provides P-values and optionally permutation-based FDR estimates (q-values) for potential mediators. It can handle single and multiple binary and continuous instrumental variables, binary or continuous outcome variables and adjustment covariates. Also, the permutation-based FDR option provides a non-parametric implementation.
Conclusion: Simulation studies demonstrate the validity of the cit package and show a substantial advantage of permutation-based FDR over other common multiple testing strategies.
Availability and implementation: The cit open-source R package is freely available from the CRAN website (https://cran.r-project.org/web/packages/cit/index.html) with embedded C ++ code that utilizes the GNU Scientific Library, also freely available (http://www.gnu.org/software/gsl/).
Contact: joshua.millstein@usc.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Giant pandas use odor cues to discriminate kin from nonkin
Authors: Gilad Oranit , Swaisgood Ronald R. , Owen Megan A. , Zhou Xiaoping 
Published: March 2016

Abstract
Sociality is an important factor in both the mechanism and function of kin recognition, yet it is little explored in solitary species. While there may be future opportunities for nepotistic functions of kin discrimination among solitary species, the ability to discriminate kin from nonkin may still have important roles in social regulation. The solitary giant panda Ailuropoda melanoleuca offers a good model system to explore kin discrimination in a solitary mammal. As kin discrimination in many other mammals is olfactorily mediated, we investigated whether giant pandas are able to discriminate odor cues from daughters even after months and years of separation. Our results indicate that giant pandas are capable of discriminating between kin and nonkin using odor cues available in urine and body odor. Daughters preferentially investigated the odors of unrelated adult female pandas over the odors of their mothers, and mothers spent more time investigating the odors of unrelated age-matched female pandas over those from their daughters. Because these studies were conducted months or years after the mother–daughter period of dependency ended, it is still unclear what mechanism is used for recognition. Long-term olfactory memories and phenotype matching should both be considered, and further studies are required for such determination.
Greek Literature, the Digital Humanities, and the Shifting Technologies of Reading
Authors: Barker Elton , Terras Melissa 
Published: March 2016

Abstract
Contrary perhaps to expectation, Classical studies is at the vanguard of the latest technological developments for using digital tools and computational techniques in research. This article outlines its pioneering adoption of digital tools and methods, and investigates how the digital medium is helping to transform the study of Greek and Latin literature. It discusses the processes and consequences of digitization, explaining how technologies like multispectral imaging are increasing the textual corpus, while examining how annotation, engagement, and reuse are changing the way we think about “the text”. It also considers how the digital turn is reinvigorating textual analysis, by exploring the broader ecosystem, within which the digital text can now be studied, and which provides enriched contexts for understanding that are constantly shifting and expanding. Classical literature in the digital age has the potential to both challenge dominant modes of thinking about antiquity and disrupt traditional ways of doing research.
Role of MiR-126a-3p in Endothelial Injury in Endotoxic Mice
Authors: Chu Maoping , Qin Shanshan , Wu Rongzhou , Zhou Xiangyu , Tang Xiaojun , Zhang Shuo , Zhao Qifeng , Wang Huating , Liu Ying , Han Xiaohua , Xiao Jian , Li Xiaokun , Zhang Chunxiang 
Published: March 2016

Objective:
Sepsis poses a serious global health problem with an overall mortality rate of 30%, in which the vascular injury is a major contributor. The study is to determine the expression profile of micro-RNAs in endotoxic vascular walls and their potential roles in sepsis-related vascular injury.

Design:
Prospective randomized study.

Setting:
Laboratory investigation.

Subjects:
Male C57BL/6 mice, average weight 26.5 ± 1.8 g.

Interventions:
Endotoxemia was induced in mice via lipopolysaccharide injection (20 mg/kg, intraperitoneal) (Sigma, St. Louis, MO). The control mice were injected with the same amount of saline (500 μL, intraperitoneal). In a subgroup of mice, a high dose of lipopolysaccharide (30 mg/kg, intraperitoneal) was applied to induce endotoxin-related death.

Measurements and Main Results:
The mi-RNA expression profiles in aortas from lipopolysaccharide-induced endotoxic mice were determined. The result demonstrated that some micro-RNAs were aberrantly expressed in endotoxic mouse arteries. Among them, the endothelial cell–enriched/endothelial cell–specific miR-126a-3p was significantly down-regulated in endotoxic mouse arteries, septic human vessels, as well as vascular endothelial cells isolated from endotoxic mice or treated with lipopolysaccharide. The down-regulation of miR-126a-3p occurred at transcriptional level via the decreased expression of Krüppel-like factor 2, which could be inhibited by Krüppel-like factor 2 over-expression via adenovirus expressing Krüppel-like factor 2. The down-regulation of miR-126a-3p in endothelial cells resulted in the increased apoptosis, and decreased proliferation and migration, which were inhibited by miR-126a-3p mimics. In vivo, over-expression of miR-126a-3p via lentivirus attenuated endotoxemia-induced injuries on endothelial function and vascular permeability. We found that SPRED1 and VCAM-1 were two direct target genes of miR-126a-3p related to miR-126a-3p–mediated effects in endotoxemia. Finally, the survival rate of endotoxic mice was significantly increased by the over-expression of miR-126a-3p.

Conclusions:
The results suggest that vascular micro-RNAs such as miR-126a-3p may represent novel mechanisms and new therapeutic targets for endotoxemia-induced vascular injury and endotoxic mortality.
EGFR Exon 19 Deletion is Associated With Favorable Overall Survival After First-line Gefitinib Therapy in Advanced Non–Small Cell Lung Cancer Patients
Authors: Choi Yong Won , Jeon So Yeon , Jeong Geum Sook , Lee Hyun Woo , Jeong Seong Hyun , Kang Seok Yun , Park Joon Seong , Choi Jin-Hyuk , Koh Young Wha , Han Jae Ho , Sheen Seung Soo 
Published: March 2016

Objectives:
Exon 19 deletion and L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are both common mutations that predict a good response to EGFR tyrosine kinase inhibitors in non–small cell lung cancer (NSCLC). However, the existence of clinically significant difference in sensitivity to EGFR tyrosine kinase inhibitors among different EGFR mutation subtypes is still a matter of debate.

Materials and Methods:
The outcome of 60 EGFR mutation-positive advanced NSCLC patients who received first-line gefitinib therapy (250 mg/d) was retrospectively analyzed according to EGFR mutation subtypes.

Results:
The median progression-free survival (PFS) and overall survival (OS) after the initiation of gefitinib therapy for all patients was 11 and 26 months, respectively. Univariate analysis showed that patients with exon 19 deletion (n=28) had significantly longer median PFS (20 vs. 8 mo, P=0.004) and OS (36 vs. 22 mo, P=0.001) compared with those with L858R mutation (n=25) and uncommon or dual mutations (n=7). Multivariate analysis revealed that exon 19 deletion (P=0.007) was an independent prognostic factor of favorable PFS, with an independent association with poor PFS of male sex (P=0.049). Exon 19 deletion was also independently associated with favorable OS (P<0.0001), whereas male sex (P=0.004) and primary metastatic disease (P=0.032) were independent prognostic factors of poor OS.

Conclusions:
The EGFR exon 19 deletion was associated with favorable PFS and OS in patients receiving first-line gefitinib treatment. The EGFR mutation subtype should be considered when making treatment decision or designing clinical trials for chemotherapy-naive, EGFR mutation-positive advanced NSCLC patients.
Incidence and Management of Glaucoma in Vogt Koyanagi Harada Disease
Authors: Pandey Amit , Balekudaru Shantha , Venkatramani Devendra V. , George Amala E. , Lingam Vijaya , Biswas Jyotirmay 
Published: March 2016

Purpose:
To analyse the prevalence, incidence, and risk factors of glaucoma in Vogt Koyanagi Harada (VKH) disease and study the changes in visual acuity and intraocular pressure (IOP) with treatment.

Materials and Methods:
Retrospective chart analysis of 448 eyes of 224 patients of Indian origin diagnosed with VKH disease from January 1990 to December 2013, who had a minimum follow-up of 3 months was performed.

Results:
Seventy-one eyes (15.8%) developed sustained elevation in IOP. The prevalence of glaucoma at presentation was 15.8% and the cumulative incidence of glaucoma was 11.7%. The mechanisms of glaucoma were open-angle glaucoma in 46 eyes, (64.8%), angle closure in 21 eyes (29.6%), and of combined mechanisms in the remainder (4 eyes, 5.6%). Acute angle-closure crisis developed in 9 eyes (12.6%). Uveal effusion (odds ratio 9.47; confidence interval, 4.08-20.03) and increased number of recurrences (odds ratio 1.31; confidence interval, 1.13-1.53) were found to be significant risk factors for the development of glaucoma. Successful control of IOP was achieved in 64% at 12 months using medical/ laser treatment for glaucoma and was 50 % at 12 months following surgical management.

Conclusions:
Glaucoma is a frequent complication of uveitis in VKH disease. Presence of uveal effusion and increased number of recurrences of inflammation are significant risk factors.
Antimicrobial functions of lactoferrin promote genetic conflicts in ancient primates and modern humans
Authors: Barber Matthew F. , Kronenberg Zev , Yandell Mark , Elde Nels C. 
Published: March 2016

ABSTRACTLactoferrin is a multifunctional mammalian immunity protein that limits microbial growth through sequestration of nutrient iron. Additionally, lactoferrin possesses cationic protein domains that directly bind and inhibit diverse microbes. The implications for these dual functions on lactoferrin evolution and genetic conflicts with pathogens remain unclear. Here we show that lactoferrin has been subject to recurrent episodes of positive selection during primate divergence predominately at antimicrobial peptide surfaces consistent with long-term antagonism by pathogens. An abundant lactoferrin polymorphism in human populations and Neanderthals also exhibits signatures of positive selection across primates, linking ancient host-microbe conflicts to modern human genetic variation. Rapidly evolving sites in lactoferrin further correspond to molecular interfaces with pathogenic bacteria causing meningitis, pneumonia, and sepsis. Because microbes actively target lactoferrin to acquire iron, we propose that the emergence of antimicrobial activity provided a pivotal mechanism of adaptation sparking evolutionary conflicts via acquisition of new protein functions.AUTHOR SUMMARYImmunity genes can evolve rapidly in response to antagonism by microbial pathogens, but how the emergence of new protein functions impacts such evolutionary conflicts remains unclear. Here we have traced the evolutionary history of the lactoferrin gene in primates, which in addition to an ancient iron-binding function, acquired antimicrobial peptide activity in mammals. We show that, in contrast to the related gene transferrin, lactoferrin has rapidly evolved at protein domains that mediate iron-independent antimicrobial functions. We also find evidence of natural selection acting on lactoferrin in human populations, suggesting that lactoferrin genetic diversity has impacted the evolutionary success of both ancient primates and humans. Our work demonstrates how the emergence of new host immune protein functions can drastically alter evolutionary conflicts with microbes.
A method to exploit the structure of genetic ancestry space to enhance case-control studies
Authors: Bodea Corneliu A. , Neale Benjamin M. , Ripke Stephan ,   The International IBD Genetics Consortium, Daly Mark J. , Devlin Bernie , Roeder Kathryn 
Published: March 2016

AbstractOne goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in cases are contrasted with those from population-based samples used as controls. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of controls from studies of Crohn’s disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful and convenient genetic association analyses without access to the individual level data.
Programming of Plant Leaf Senescence with Temporal and Inter-Organellar Coordination of Transcriptome in Arabidopsis1
Authors: Woo Hye Ryun , Koo Hee Jung , Kim Jeongsik , Jeong Hyobin , Yang Jin Ok , Lee Il Hwan , Jun Ji Hyung , Choi Seung Hee , Park Su Jin , Kang Byeongsoo , Kim You Wang , Phee Bong-Kwan , Kim Jin Hee , Seo Chaehwa , Park Charny , Kim Sang Cheol , Park Seongjin , Lee Byungwook , Lee Sanghyuk , Hwang Daehee , Nam Hong Gil , Lim Pyung Ok 
Published: March 2016

Abstract
Plant leaves, harvesting light energy and fixing CO2, are a major source of foods on the earth. Leaves undergo developmental and physiological shifts during their lifespan, ending with senescence and death. We characterized the key regulatory features of the leaf transcriptome during aging by analyzing total- and small-RNA transcriptomes throughout the lifespan of Arabidopsis (Arabidopsis thaliana) leaves at multidimensions, including age, RNA-type, and organelle. Intriguingly, senescing leaves showed more coordinated temporal changes in transcriptomes than growing leaves, with sophisticated regulatory networks comprising transcription factors and diverse small regulatory RNAs. The chloroplast transcriptome, but not the mitochondrial transcriptome, showed major changes during leaf aging, with a strongly shared expression pattern of nuclear transcripts encoding chloroplast-targeted proteins. Thus, unlike animal aging, leaf senescence proceeds with tight temporal and distinct interorganellar coordination of various transcriptomes that would be critical for the highly regulated degeneration and nutrient recycling contributing to plant fitness and productivity.
The effects of lucky draw sales promotion on brand loyalty in mobile telecommunication industry
Authors: Yeboah-Asiamah Eric , Quaye Daniel M. , Nimako Simon Gyasi 
Published: March 2016

Purpose
– The purpose of this paper is to empirically examine the relationship between lucky draw sales promotion (LDSP) and the four phases of brand loyalty in the telecommunication industry.

Design/methodology/approach
– A self-administered structure questionnaire was used to collect primary data from conveniently sampled 338 lucky draw winners in the Ghanaian telecommunication industry. A response rate of 67.1 percent was obtained for data analysis using structural equation modeling approach.

Findings
– It was found that LDSP positively relate to cognitive brand loyalty, and to behavioral brand loyalty through affective and conative brand loyalty. All hypothesized relationships among the sequential four-stage loyalty were confirmed, except the direct relationship between LDSP and behavioral brand loyalty.

Research limitations/implications
– The findings are limited to lucky draw winners in the telecommunication industry.

Practical implications
– Marketers can increase brand loyalty and profit more from their customers through targeted programs with hedonic benefits to build strong commitment level (conative brand loyalty), strong favoritism (affective brand loyalty) and strong beliefs about the superiority (cognitive brand loyalty) of a brand.

Originality/value
– Theoretically, this study fills the void of empirical studies on non-price sales promotion techniques of lucky draw and customer brand loyalty in the telecommunication sector in developing economy context, and contributes to the body of knowledge in the area of customer brand loyalty and LDSP.
Equivalent stator slot model of temperature field for high torque-density permanent magnet synchronous in-wheel motors accounting for winding type
Authors: Liang Peixin , Pei Yulong , Chai Feng , Cheng Shukang 
Published: March 2016

Purpose
– For high torque-density permanent magnet synchronous in-wheel motor, service life and electromagnetic performance are related directly to winding temperature. The purpose of this paper is to investigate the equivalent stator slot model to calculate the temperature of winding accurately.

Design/methodology/approach
– This paper analyzes the the law of heat flux transfer in slot, which points the main influence factors of equivalent stator slot model. Thermal network model is used to investigate the drawbacks of conventional equivalent model. Based on the law of heat transfer in stator slot, a new layered winding model is put forward. According to winding type and property of impregnations, detailed method and equivalent principle of the new model are presented. The accuracy of this new method has been verified experimentally.

Findings
– An accurate equivalent stator slot model should be built according to the low of heat transfer. According to theory analysis, the drawbacks of conventional equivalent stator slot model are pointed: it cannot reflect the temperature gradient of winding; the maximum and the average temperature of winding are much higher than actual value. For the new layered model, equivalent principle is related to winding type and property of impregnations, which makes the new model widely used.

Originality/value
– This paper presents a new layered model, and shows detailed method, which is more meaningful for designers. The new layered model takes winding type and property of impregnations into account, which makes the new model widely used. It is verified experimentally that layered model is applicable to not only steady-state temperature field but also transient temperature field.
Linear induction motor drive for woodworking machine application
Authors: Miao Dong-Min , Wang Shuai , Shen Jian-Xin 
Published: March 2016

Purpose
– The purpose of this paper is to study a woodworking machine, in which a linear induction motor (LIM) is applied to feed the wood to be processed into the cutting saw. The LIM is optimally designed and the whole drive system is controlled by a programmable logic controller (PLC) to meet the industrial demands.

Design/methodology/approach
– Since the operation range is short, the LIM mainly works at the transient state of quick start and quick brake. Hence, the thrust force with a large slip ratio (hereafter called the starting thrust) is one of the most important issues in the LIM design. Finite element method is used to optimize the starting thrust while taking a specific variable voltage variable frequency (VVVF) drive into account.

Findings
– The LIM system directly drives the machine workbench where the wood is placed, eliminating the requirement of manpower to push the wood through the cutting saw, hence, greatly reduces the operation hazard. It has a higher reliability and longer service life than the conventional drive system employing a rotary motor with a ball screw mechanism.

Originality/value
– The LIM is an attractive candidate for the woodworking machine application, which can replace the complicated and relatively low-efficiency mechanism of rotary motor and ball screw. High starting thrust can be achieved by optimizing the LIM design, whilst the specific VVVF control is essential to ensure a good drive performance. The PLC is competent for both human-machine interface (HMI) and control of the inverter-fed LIM system, and is of high reliability in industrial environment.
Influence of end-effect on torque-speed characteristics of various switched flux permanent magnet machine topologies
Authors: Al-ani M,M.J, , Zhu Z.Q. 
Published: March 2016

Purpose– The purpose of this paper is to investigate and compare the influence of end-effect on the torque-speed characteristics of three conventional switched flux permanent magnet (SFPM) machines having different stator/rotor pole combinations, i.e. 12/10, 12/13 and 12/14 as well as three novel topologies with less permanent magnets (PMs), i.e. multi-tooth, E-core and C-core.Design/methodology/approach– SFPM machines combine the advantages of simple and robust rotor and easy management of the temperature due to the location of the PMs and armature windings on the stator. However, due to spoke location of the PMs a large flux leakage in the end region, i.e. end-effect, can be observed which could result in a large reduction in the electromagnetic performance. Therefore, the influence of end-effect on the torque-speed characteristics is investigated. 3D-finite element analyses (FEA) results are compared with their 2D-FEA counterparts in order to account for the end-effect influence.Findings– It has been concluded that due to end flux leakage, lower torque capability in the constant torque region is observed in the six machines. However, improved flux-weakening capability in the conventional machines can be exhibited at high current levels, whereas due to the large inductance lower power capability in the multi-tooth, E-core and C-core machines is obtained.Research limitations/implications– The influence of temperature rise on the performance is not included.Originality/value– This paper has analysed the influence of end-effect on the torque-speed characteristics of several SFPM machines.