bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association analyses of chronotype in 697,828 individuals provides new insights into circadian rhythms in humans and links to disease
Authors: Jones Samuel E. , Lane Jacqueline M. , Wood Andrew R. , van Hees Vincent T. , Tyrrell Jessica , Beaumont Robin N. , Jefferies Aaron , Dashti Hassan S. , Hillsdon Melvyn , Ruth Katherine S. , Tuke Marcus A. , Yaghootkar Hanieh , Sharp Seth , Jie Yingjie , Thompson William D. , Harrison Jamie W. , Dawes Amy , Byrne Enda M. , Tiemeier Henning , Allebrandt Karla V. , Bowden Jack , Ray David W. , Freathy Rachel M. , Murray Anna , Mazzotti Diego R. , Gehrman Philip R. ,   the 23andMe Research Team, Lawlor Debbie A. , Frayling Timothy M. , Rutter Martin K. , Hinds David , Saxena Richa , Weedon Michael N. 
Published: April 2018

AbstractUsing genome-wide data from 697,828 research participants from 23andMe and UK Biobank, we increase the number of identified loci associated with being a morning person, a behavioural indicator of a person’s underlying circadian rhythm, from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we show that the chronotype loci influence sleep timing: the mean sleep timing of the 5% of individuals carrying the most “morningness” alleles was 25 minutes earlier than the 5% carrying the fewest. The loci were enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. We provide evidence that being a morning person is causally associated with better mental health but does not appear to affect BMI or Type 2 diabetes. This study offers new insights into the biology of circadian rhythms and links to disease in humans.
Overlapping neural processes for stopping and economic choice in orbitofrontal cortex
Authors: Balasubramani Pragathi Priyadharsini , Hayden Benjamin Y. 
Published: April 2018

ABSTRACTEconomic choice and stopping are not traditionally treated as related phenomena. However, we were motivated by foraging models of economic choice to hypothesize that they may reflect similar neural processes occurring in overlapping brain circuits. We recorded neuronal activity in orbitofrontal cortex (OFC), while macaques performed a stop signal task interleaved with a structurally matched economic choice task. Decoding analyses show that OFC ensembles predict successful versus failed stopping both before the trial and immediately after the stop signal, even after controlling for value predictions. These responses indicate that OFC contributes both proactively and reactively to stopping. Moreover, OFC neurons’ engagement in one task positively predicted their engagement in the other. Finally, firing patterns that distinguished low from high value offers in the economic task distinguished failed and successful trials in the stopping task. These results endorse the idea that economic choice and inhibition may be subject to theoretical unification.
Intact memory for local and distal cues in male and female rats that lack adult neurogenesis
Authors: Seib Desiree R , Chahley Erin , Princz-Lebel Oren , Snyder Jason S 
Published: April 2018

ABSTRACTThe dentate gyrus is essential for remembering the fine details of experiences that comprise episodic memory. Dentate gyrus granule cells receive highly-processed sensory information and are hypothesized to perform a pattern separation function, whereby similar sensory inputs are transformed into orthogonal neural representations. Behaviorally, this is believed to enable distinct memory for highly interfering stimuli. Since the dentate gyrus is comprised of a large number of adult-born neurons, which have unique synaptic wiring and neurophysiological firing patterns, it has been proposed that neurogenesis may contribute to this process in unique ways. Some behavioral evidence exists to support this role, whereby neurogenesis-deficient rodents are impaired at discriminating the fine visuospatial details of experiences. However, the extent to which newborn neurons contribute to dentate gyrus-dependent learning tasks is unclear. Furthermore, since most studies of dentate gyrus function are conducted in male rats, little is known about how females perform in similar situations, and whether there might be sex differences in the function of adult neurogenesis. To address these issues, we examined spatial discrimination memory in transgenic male and female rats that lacked adult neurogenesis. The first task probed memory for the position of local objects in an open field, assessed by behavioral responses to novel object locations. The second task examined memory for distal environmental cues. All rats were able to successfully discriminate local and distal cue changes. Males and females also performed comparably, although females displayed higher levels of rearing and locomotion. Collectively, our results indicate that rats are capable of learning about local and distal cues in the absence of adult neurogenesis.
Generative Adversarial Networks Conditioned on Brain Activity Reconstruct Seen Images
Authors: St-Yves Ghislain , Naselaris Thomas 
Published: April 2018

AbstractWe consider the inference problem of reconstructing a visual stimulus from brain activity measurements (e.g. fMRI) that encode this stimulus. Recovering a complete image is complicated by the fact that neural representations are noisy, high-dimensional, and contain incomplete information about image details. Thus, reconstructions of complex images from brain activity require a strong prior. Here we propose to train generative adversarial networks (GANs) to learn a generative model of images that is conditioned on measurements of brain activity. We consider two challenges of this approach: First, given that GANs require far more data to train than is typically collected in an fMRI experiment, how do we obtain enough samples to train a GAN that is conditioned on brain activity? Secondly, how do we ensure that our generated samples are robust against noise present in fMRI data? Our strategy to surmount both of these problems centers around the creation of surrogate brain activity samples that are generated by an encoding model. We find that the generative model thus trained generalizes to real fRMI data measured during perception of images and is able to reconstruct the basic outline of the stimuli.
Cis- and Trans-Acting Expression Quantitative Trait Loci Differentially Regulate Gamma-Globin Gene Expression
Authors: Shaikho Elmutaz M. , Farrell John J. , Chui David H. K. , Sebastiani Paola , Steinberg Martin H. 
Published: April 2018

ABSTRACTGenetic association studies have detected two trans-acting quantitative trait loci (QTL) on chromosomes 2, 6 and one cis-acting QTL on chromosome 11 that were associated with fetal hemoglobin (HbF) levels. In these studies, HbF was expressed as a percentage of total hemoglobin or the number of erythrocytes that contain HbF (F-cells). As theγ-globin chains of HbF are encoded by two non-allelic genes(HBG2, HBG1)that are expressed at different levels we used normalized gene expression and genotype data from The Genotype-Tissue Expression (GTEx)-project to study the effects of cis- and trans-acting HbF expression or eQTL. This allowed us to examine mRNA expression ofHBG2and HBG1individually. In addition to studying eQTL for globin genes we examined genes co-expressed withHBG1, studied upstream regulators ofHBG1co-expressed genes and performed a correlation analysis betweenHBG2andHBG1and known HbF regulators. Our results suggest differential effect of cis and trans-acting QTL onHBGandHBG1expression. Trans-acting eQTLs have the same magnitude of effect on the expression of bothHBG2andHBG1while the sole cis-acting eQTL affected onlyHBG2. Furthermore, the analysis of upstream regulators and the correlation analysis suggested thatBCL2L1might be a new potential trans-acting HbF activator. HbF is the major modulator of the phenotype of sickle cell anemia and β thalassemia. Depending on the effect size, modification of trans-acting elements might have a greater impact on HbF levels than cis-acting elements alone.
Preliminary study on the application of PspA as carrier
Authors: Lichan-Wang  , Yajun-Tan  , Chen-Wei  , Huajie-Zhang  , Peng-Luo  , Shumin-Zhang  , Xiao-Ma  
Published: April 2018

AbstractThe aim of the study is to research the feasibility of pneumococcal surface protein A (PspA) using as carrier protein. Three recombinant pneumococcal surface proteins A (come from family1 and family 2) were expressed by prokaryotic expression system and were conjugated to group A meningococcal polysaccharide (GAMP) to make three polysaccharide-protein conjugates. The conjugates, un-conjugated proteins, GAMP and GAMP-TT vaccine bulk (used as positive control) were immunized to mice and their immune effects were evaluated by the method of ELISA, FCM and SBA. The results showed that the polysaccharide-protein conjugates can produce higher levels of anti-GAMP IgG titers (P < 0.05), higher ratios of Th1/Th2 (P < 0.05) and higher levels of serum bactericidal activity (P < 0.05) compared with the un-conjugated GAMP. The conjugation of PspAs to GAMP also enhanced the anti-PspA responses compared with un-conjugated PspAs except PspA3. In conclusion, all the results indicated that three PspAs were suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the GAMP, and would protect against group A of epidemic cerebrospinal meningitis and also have the potential to provide broad protection from Streptococcus pneumonia.
Biphasic recruitment of TRF2 to DNA damage sites promotes non-sister chromatid homologous recombination repair
Authors: Kong Xiangduo , Saquilabon Cruz Gladys Mae , Trinh Sally Loyal , Zhu Xu-Dong , Berns Michael W. , Yokomori Kyoko 
Published: April 2018

AbstractTRF2 binds to telomeric repeats and is critical for telomere integrity. Evidence suggests that it also localizes to non-telomeric DNA damage sites. However, this recruitment appears to be precarious and functionally controversial. We find that TRF2 recruitment to damage sites occurs by a two-step mechanism: the initial rapid recruitment (phase I) and stable and prolonged association with damage sites (phase II). Phase I is poly(ADP-ribose) polymerase (PARP)-dependent and requires the N-terminal basic domain. The phase II recruitment requires the C-terminal MYB/SANT domain and the iDDR region in the hinge domain, which is mediated by the MRE11 complex and is stimulated by hTERT. PARP-dependent recruitment of intrinsically disordered proteins contributes to transient displacement of TRF2 that separates two phases. TRF2 binds to the I-PpoI-induced DNA double-strand break sites, which is enhanced by the presence of complex damage and is dependent on PARP and the MRE11 complex. TRF2 depletion affects non-sister chromatid homologous recombination (HR) repair, but not HR between sister chromatids or non-homologous endjoining pathways. Our results demonstrate a unique recruitment mechanism and function of TRF2 at non-telomeric DNA damage sites.Summary StatementTRF2 is recruited to DNA double-strand break damage sites by a two-step mechanism and functions in non-sister chromatid homologous recombination repair
Dissecting bacterial resistance and resilience in antibiotic responses
Authors: Meredith Hannah R. , Andreani Virgile , Lopatkin Allison J. , Lee Anna J. , Anderson Deverick J. , Batt Gregory , You Lingchong 
Published: April 2018

AbstractAn essential property of microbial communities is the ability to survive a disturbance. Survival can be achieved throughresistance, the ability to absorb effects of a disturbance without a significant change, orresilience, the ability to recover after being perturbed by a disturbance. These concepts have long been applied to the analysis of ecological systems, though their interpretations are often subject to debate. Here we show that this framework readily lends itself to the dissection of the bacterial response to antibiotic treatment, where both terms can be unambiguously defined. The ability to tolerate the antibiotic treatment in the short term corresponds to resistance, which primarily depends on traits associated with individual cells. In contrast, the ability to recover after being perturbed by an antibiotic corresponds to resilience, which primarily depends on traits associated with the population. This framework effectively reveals the phenotypic signatures of bacterial pathogens expressing extended spectrum β-lactamases (ESBLs), when treated by a β-lactam antibiotic. Our analysis has implications for optimizing treatment of these pathogens using a combination of a β-lactam and a β-lactamase (Bla) inhibitor. In particular, our results underscore the need to dynamically optimize combination treatments based on the quantitative features of the bacterial response to the antibiotic or the Bla inhibitor.
Development Defects of Hydroxy-Fatty Acid-Accumulating Seeds Are Reduced by Castor Acyltransferases
Authors: Lunn Daniel , Smith Gracen A. , Wallis James G. , Browse John 
Published: April 2018

Abstract
Researchers have long endeavored to produce modified fatty acids in easily managed crop plants where they are not natively found. An important step toward this goal has been the biosynthesis of these valuable products in model oilseeds. The successful production of such fatty acids has revealed barriers to the broad application of this technology, including low seed oil and low proportion of the introduced fatty acid and reduced seed vigor. Here, we analyze the impact of producing hydroxy-fatty acids on seedling development. We show that germinating seeds of a hydroxy-fatty acid-accumulating Arabidopsis (Arabidopsis thaliana) line produce chlorotic cotyledons and suffer reduced photosynthetic capacity. These seedlings retain hydroxy-fatty acids in polar lipids, including chloroplast lipids, and exhibit decreased fatty acid synthesis. Triacylglycerol mobilization in seedling development also is reduced, especially for lipids that include hydroxy-fatty acid moieties. These developmental defects are ameliorated by increased flux of hydroxy-fatty acids into seed triacylglycerol created through the expression of either castor (Ricinus communis) acyltransferase enzyme ACYL-COA:DIACYLGLYCEROL ACYLTRANSFERASE2 or PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE1A. Such expression increases both the level of total stored triacylglycerol and the rate at which it is mobilized, fueling fatty acid synthesis and restoring photosynthetic capacity. Our results suggest that further improvements in seedling development may require the specific mobilization of triacylglycerol-containing hydroxy-fatty acids. Understanding the defects in early development caused by the accumulation of modified fatty acids and providing mechanisms to circumvent these defects are vital steps in the development of tailored oil crops.
Managing operations in customer-intensive services with forward-looking customers
Authors: Li Chengzhang , Jiang Minghui , Yuan Xuchuan 
Published: April 2018

Purpose
This paper aims to investigate the optimal price and service rate decisions in a customer-intensive service, where customers’ perceived service quality decreases in the service speed. Customers are assumed to be forward-looking in purchase decision-making and heterogeneous in their reservation utilities. The purpose of this paper is to study the impact of customers’ forward-looking behavior and the heterogeneity on the operational decisions in a customer-intensive context.

Design/methodology/approach
The service is delivered through an M/M/1 queue system with unobservable queues. Customers are forward-looking in queue joining decisions, where the purchase decisions are made when the expected utility is greater than the reservation utility. The optimal price and service rate decisions are analyzed with both homogeneous and heterogeneous customers, where homogenous customers have the same reservation utility in purchase decision-making, while heterogeneous customers have different reservation utilities, which are captured by a random variable.

Findings
The optimal price and service rate decisions with forward-looking customers depend on the customer intensity, potential market size and customers’ reservation utility distribution. The results suggest that customers’ heterogeneity in terms of their reservation utilities affects the optimal decisions, market coverage and the expected revenue. Service providers need to take customers’ heterogeneity and the forward-looking behavior into operational decision-making.

Originality/value
This paper extends previous studies in customer-intensive service and contribute to the service operations management area by explicitly incorporating customers’ forward-looking behavior and heterogeneity in purchase decision-making. Assuming customers are forward-looking and heterogeneous is more realistic and practical. The results highlight that knowing customers’ behavioral characteristics can better improve decision-making in service operations, which is critical for enhancing customers’ satisfaction and loyalty, thus critical to a firm’s success in the market with intensive competition.
Problem-based learning
Authors: Silva Anielson Barbosa Da , Bispo Ana Carolina Kruta de Araújo , Rodriguez Danilo Goncalves , Vasquez Francisco Ialyson Felipe 
Published: April 2018

Purpose
The purpose of this paper is to present a proposal for structuring the use of problem-based learning (PBL) as an active teaching strategy and assess PBL’s implications for student learning in the undergraduate management degree program of a federal university in Northeastern Brazil. PBL can turn students into active subjects in their own learning and promote the development of decision-making abilities through the identification and analysis of real problems.

Design/methodology/approach
The study follows the assumptions of qualitative research and uses the action research approach. The data were collected through reflective reports (texts freely written by students describing their experiences in a course) and through interviews. The collected material formed the basis for analysis and discussion of the results using content analysis.

Findings
The results indicate that the PBL teaching strategy has positive implications for student learning in that it promotes the integration of theory and practice, which enhances the motivation to learn. The students perceived the practical aspect, teamwork and presence of an entrepreneur/manager in the PBL classes as factors facilitating learning. By contrast, teamwork and the time involved were seen as factors limiting learning.

Practical implications
The use of PBL demonstrates its potential for learning through the integration of students’ cognitive, behavioral and social dimensions, fostering closer integration with the context of professional activity. The presence of entrepreneurs/managers who present real problems to be analyzed by the students in the classroom can contribute significantly to the promotion of learning and reflection by undergraduate management students.

Originality/value
The results of this study reveals its originality and value to management education in Brazil because it defines a framework for the implementation of PBL as an active learning strategy in a management program, it indicates the potential of PBL for the development of students’ competencies, it increases the potential for integrating theory with professional practice and it can aid the process of training teachers as they assess the implications of PBL for student learning.
Treatment of ankylosing spondylitis with co‐amoxiclav
Authors: Öğrendik Mesut 
Published: April 2018

SummaryThis article presents the efficacy of co‐amoxiclav in two patients with ankylosing spondylitis. Both patients were administered oral co‐amoxiclav for 7 days. The primary efficacy variable was the ankylosing spondylitis activity index. Secondary outcome measures were the ankylosing spondylitis functional index and spinal mobility. We detected a marked improvement in all symptoms and physical examination parameters. Co‐amoxiclav has been shown to be effective against ankylosing spondylitis.
Translating value‐based health care: an experiment into healthcare governance and dialogical accountability
Authors: Bonde Morten , Bossen Claus , Danholt Peter 
Published: April 2018

AbstractThis article analyses an experiment into healthcare governance in Denmark inspired by principles of value‐based health care and intended to re‐orient the focus of healthcare governance from ‘productivity’ to ‘value for the patient’. The region in charge of the experiment exempted nine hospital departments from activity‐based financing and accountability based on diagnosis‐related groups, which allegedly incentivised hospitals in ‘perverse’ and counterproductive ways. Instead, the departments were to develop new indicators from their local practices to support and account for quality and value for the patient. Drawing on the actor‐network theory concept of ‘translation’, this article analyses how the experiment was received and put into practice in the nine departments, and how it established new kinds of accountability relations. We argue that the experiment provides fruitful inspiration for future governance schemes in healthcare to embrace the local complexities of clinical practices. In particular, we argue that the locally developed indicators facilitated what we call ‘dialogical accountability’, and we discuss whether this represents a feasible way forward for value‐based health care.
Challenge of Firearms Control in a Free Society
Authors: Cook Philip J. 
Published: April 2018

AbstractChapter 10 of   The Challenge of Crime in a Free Society, titled “Control of Firearms,” is a brief but strong statement in support of regulating gun transactions, possession, and carrying, with several specific recommendations, including the adoption of universal gun registration and permit‐to‐purchase requirements. The U.S. President's Commission on Law Enforcement and Administration of Justice, when writing the chapter, had no systematic research to draw on. Since its publication in 1967, the field of gun violence has become an active area of research, and much has been learned. But the nation has become far more polarized politically during the last 50 years, and gun policy has become a rigidly partisan issue. A new commission would have great difficulty reaching consensus, although there may be common ground on regulating guns vis‐à‐vis mental illness and domestic violence.
Addressing Juvenile Crime
Authors: Lane Jodi 
Published: April 2018

AbstractAt‐risk and offending juveniles remain the most promising target group for crime reduction efforts. Many of the problems these youths faced in the 1960s remain or have intensified, and policies to address them have shifted. Yet, research on the causes, consequences, and best responses to juvenile crime has advanced considerably and provides important lessons for policy makers and practitioners moving forward. These include (a) help don't hurt; (b) provide better procedural protections; (c) continue to build, implement, and refine evidence‐based programming; (d) tailor services; (e) tackle community‐level problems; (f) really listen and work together; (g) build better data systems; and (h) invest resources in children and teens. Providing a retrospective on the 1967 U.S. President's Commission on Law Enforcement and Administration of Justice report, I briefly summarize and update the Commission's findings on factors related to juvenile delinquency, outline the Commission's policy recommendations, review the research on policy and practice changes since the report, and consider current implications for policy and practice.