bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased melanocortin‐4 receptor function conferred by an infrequent variant at the human melanocortin receptor accessory protein 2 gene
Authors: Schonnop Laura , Kleinau Gunnar , Herrfurth Nikolas , Volckmar Anna‐Lena , Cetindag Cigdem , Müller Anne , Peters Triinu , Herpertz Stephan , Antel Jochen , Hebebrand Johannes , Biebermann Heike , Hinney Anke 
Published: August 2016

ObjectiveThe melanocortin receptor accessory protein 2 (MRAP2) is relevant for weight regulation in mice and humans. This function is likely mediated by regulation of the melanocortin‐4 receptor (MC4R). Functional implications of human MRAP2 mutations have not been described yet.MethodsA mutation screen was conducted in MRAP2 in 184 children and adolescents with (extreme) obesity and in 184 lean controls. Detected nonsynonymous variants were genotyped in larger independent study groups (300 people with obesity and 436 individuals with normal weight). The influence of mutant MRAP2 on MC4R signaling was analyzed in vitro.Results(1) Three (two novel) nonsynonymous MRAP2 variants were detected: p.Ala137Thr, p.Gln174Arg, p.Arg125His (rs115655382), two synonymous variants, and three intronic variants. (2) The impact of MRAP2 on MC4R function was dependent on the ratio between the two co‐expressed proteins. Increased MC4R signaling was detected at MRAP2/MC4R ratios of 2 + 1 and above. (3) The function of MC4R was reduced with the infrequent allele at the MRAP2 p.Gln174Arg variant. (4) The three nonsynonymous mutations were each only detected once among the 484 people with obesity and not among 620 individuals with normal weight.ConclusionsThis was the first study describing an effect of a MRAP2 mutation on MC4R function.
A randomized pilot study comparing zero‐calorie alternate‐day fasting to daily caloric restriction in adults with obesity
Authors: Catenacci Victoria A. , Pan Zhaoxing , Ostendorf Danielle , Brannon Sarah , Gozansky Wendolyn S. , Mattson Mark P. , Martin Bronwen , MacLean Paul S. , Melanson Edward L. , Troy Donahoo William 
Published: August 2016

ObjectiveTo evaluate the safety and tolerability of alternate‐day fasting (ADF) and to compare changes in weight, body composition, lipids, and insulin sensitivity index (Si) with those produced by a standard weight loss diet, moderate daily caloric restriction (CR).MethodsAdults with obesity (BMI ≥30 kg/m2, age 18‐55) were randomized to either zero‐calorie ADF (n = 14) or CR (−400 kcal/day, n = 12) for 8 weeks. Outcomes were measured at the end of the 8‐week intervention and after 24 weeks of unsupervised follow‐up.ResultsNo adverse effects were attributed to ADF, and 93% completed the 8‐week ADF protocol. At 8 weeks, ADF achieved a 376 kcal/day greater energy deficit; however, there were no significant between‐group differences in change in weight (mean ± SE; ADF −8.2 ± 0.9 kg, CR −7.1 ± 1.0 kg), body composition, lipids, or Si. After 24 weeks of unsupervised follow‐up, there were no significant differences in weight regain; however, changes from baseline in % fat mass and lean mass were more favorable in ADF.ConclusionsADF is a safe and tolerable approach to weight loss. ADF produced similar changes in weight, body composition, lipids, and Si at 8 weeks and did not appear to increase risk for weight regain 24 weeks after completing the intervention.
Combined effect of education and reproductive history on weight trajectories of young Australian women: A longitudinal study
Authors: Holowko Natalie , Jones Mark , Koupil Ilona , Tooth Leigh , Mishra Gita 
Published: August 2016

ObjectiveTo investigate the combined effect of education and reproductive history on weight trajectory.MethodsThe association of education with weight trajectory (1996–2012) in relation to reproductive history was analyzed among 9,336 women (born 1973–1978) from the Australian Longitudinal Study on Women's Health using random effects models.ResultsCompared with women with a university degree/higher, lower‐educated women were 2 kg heavier at baseline and gained an additional 0.24 kg/year. Giving birth was associated with an increase in weight which was more pronounced among women having their first birth <26 years of age (2.1 kg, 95% CI: 1.5–2.7), compared with 26 to 32 years or >32 years. While younger first‐time mothers had a steeper weight trajectory (∼+0.16 kg/year, 95% CI: 0.1–0.3), this was less steep among lower‐educated women. High‐educated women with a second birth between 26 and 32 years had 0.9 kg decreased weight after this birth, while low‐educated women gained 0.9 kg.ConclusionsWhile the effect of having children on weight in young adulthood was minimal, women having their first birth <26 years of age had increased risk of weight gain, particularly primiparous women. Educational differences in weight persisted after accounting for reproductive history, suggesting a need to explore alternative mechanisms through which social differences in weight are generated.
Seven‐day cumulative effects of air pollutants increase respiratory ER visits up to threefold
Authors: Schvartsman Cláudio , Pereira Luiz Alberto Amador , Braga Alfésio Luiz Ferreira , Farhat Sylvia Costa Lima 
Published: August 2016

SummaryObjective: Children are especially vulnerable to respiratory injury induced by exposure to air pollutants. In the present study, we investigate periods of up to 7 days, and evaluate the lagged effects of exposure to air pollutants on the daily number of children and adolescents visiting the emergency room (ER) for the treatment of lower respiratory obstructive diseases (LROD), in the city of São Paulo, Brazil. Methods: Daily records of LROD‐related ER visits by children and adolescents under the age of 19, from January 2000 to December 2007 (2,922 days) were included in the study. Time‐series regression models (generalized linear Poisson) were used to control for short‐ and long‐term trends, as well as for temperature and relative humidity. Third‐degree polynomial lag models were used to estimate both lag structures and the cumulative effects of air pollutants. Effects of air pollutants were expressed as the percentage increase in LROD‐related ER visits. Results: We observed an acute effect at the same day of exposure to air pollutants; however, the cumulative effects of air pollutants on the number of LROD‐related ER visits was almost threefold greater than the one observed at the same day of exposure to PM10, SO2, and NO2 mainly in children aged 5 years and under. The 7‐day cumulative effect of SO2 reached 11.0% (95% CI: 5.0–16.7) increase in visits. Conclusion and Relevance: This study highlights the effects of intermediate‐term exposure to air pollutants on LROD in children. Pediatr Pulmonol. 2017;52:205–212. © 2016 Wiley Periodicals, Inc.
Loss of Pink1 modulates synaptic mitochondrial bioenergetics in the rat striatum prior to motor symptoms: concomitant complex I respiratory defects and increased complex II‐mediated respiration
Authors: Stauch Kelly L. , Villeneuve Lance M. , Purnell Phillip R. , Ottemann Brendan M. , Emanuel Katy , Fox Howard S. 
Published: August 2016

PurposeMutations in PTEN‐induced putative kinase 1 (Pink1), a mitochondrial serine/threonine kinase, cause a recessive inherited form of Parkinson's disease (PD). Pink1 deletion in rats results in a progressive PD‐like phenotype, characterized by significant motor deficits starting at 4 months of age. Despite the evidence of mitochondrial dysfunction, the pathogenic mechanism underlying disease due to Pink1‐deficiency remains obscure.Experimental designStriatal synaptic mitochondria from 3‐month‐old Pink1‐deficient rats were characterized using bioenergetic and mass spectroscopy (MS)‐based proteomic analyses.ResultsStriatal synaptic mitochondria from Pink1‐deficient rats exhibit decreased complex I‐driven respiration and increased complex II‐mediated respiration compared with wild‐type rats. MS‐based proteomics revealed 69 of the 811 quantified mitochondrial proteins were differentially expressed between Pink1‐deficient rats and controls. Down‐regulation of several electron carrier proteins, which shuttle electrons to reduce ubiquinone at complex III, in the Pink1‐knockouts suggests disruption of the linkage between fatty acid, amino acid, and choline metabolism and the mitochondrial respiratory system.Conclusions and clinical relevanceThese results suggest that complex II activity is increased to compensate for loss of electron transfer mechanisms due to reduced complex I activity and loss of electron carriers within striatal nerve terminals early during disease progression. This may contribute to the pathogenesis of PD.
A network of allosterically coupled residues in the bacteriophage T4 Mre11–Rad50 complex
Authors: Gao Yang , Meyer Jennifer R. , Nelson Scott W. 
Published: August 2016

AbstractThe Mre11–Rad50 (MR) protein complex, made up of a nuclease and ATPase, respectively, is involved in the processing of double‐strand breaks as part of an intricate mechanism for their repair. Although it is clear that the MR complex is subject to allosteric regulation and that there is communication between the nuclease and ATPase active sites, the underlying mechanisms are poorly understood. We performed statistical coupling analysis on Mre11 and Rad50 to predict linked residues based on their evolutionary correlation. This analysis predicted a coevolving sector of six residues that may be allosterically coupled. The prediction was tested using double‐mutant cycle analysis of nuclease and ATPase activity. The results indicate that a tyrosine residue located near the active site of Mre11 is allosterically coupled to several Rad50 residues located over 40 Å away. This allosteric coupling may be the basis for the reciprocal regulation of the ATPase and nuclease activities of the complex.
Rational design of TNFα binding proteins based on the de novo designed protein DS119
Authors: Zhu Cheng , Zhang Changsheng , Zhang Tao , Zhang Xiaoling , Shen Qi , Tang Bo , Liang Huanhuan , Lai Luhua 
Published: August 2016

AbstractDe novo protein design offers templates for engineering tailor‐made protein functions and orthogonal protein interaction networks for synthetic biology research. Various computational methods have been developed to introduce functional sites in known protein structures. De novo designed protein scaffolds provide further opportunities for functional protein design. Here we demonstrate the rational design of novel tumor necrosis factor alpha (TNFα) binding proteins using a home‐made grafting program AutoMatch. We grafted three key residues from a virus 2L protein to a de novo designed small protein, DS119, with consideration of backbone flexibility. The designed proteins bind to TNFα with micromolar affinities. We further optimized the interface residues with RosettaDesign and significantly improved the binding capacity of one protein Tbab1‐4. These designed proteins inhibit the activity of TNFα in cellular luciferase assays. Our work illustrates the potential application of the de novo designed protein DS119 in protein engineering, biomedical research, and protein sequence‐structure‐function studies.
Effects of Y incorporation in TaON gate dielectric on electrical performance of GaAs metal–oxide–semiconductor capacitor
Authors: Liu Li Ning , Choi Hoi Wai , Xu Jing Ping , Lai Pui To 
Published: August 2016

In this study, GaAs metal–oxide–semiconductor (MOS) capacitors using Y‐incorporated TaON as gate dielectric have been investigated. Experimental results show that the sample with a Y/(Y + Ta) atomic ratio of 27.6% exhibits the best device characteristics: high k value (22.9), low interfacestate density (9.0 × 1011 cm–2 eV–1), small flatband voltage (1.05 V), small frequency dispersion and low gate leakage current (1.3 × 10–5A/cm2 at Vfb + 1 V). These merits should be attributed to the complementary properties of Y2O3 and Ta2O5:Y can effectively passivate the large amount of oxygen vacancies in Ta2O5, while the positively‐charged oxygen vacancies in Ta2O5 are capable of neutralizing the effects of the negative oxide charges in Y2O3. This work demonstrates that an appropriate doping of Y content in TaON gate dielectric can effectively improve the electrical performance for GaAs MOS devices.
Capacitance–voltage characteristic of the GaAs MOS capacitor with TaYON gate dielectric (Y content = 27.6%) proposed in this work with the cross sectional structure and dielectric surface morphology as insets.magnified imageCapacitance–voltage characteristic of the GaAs MOS capacitor with TaYON gate dielectric (Y content = 27.6%) proposed in this work with the cross sectional structure and dielectric surface morphology as insets.
Counter anion in Li+‐encapsulated C60 can further enhance the rate of Diels–Alder reaction: A DFT study
Authors: Zhang Dawei , Li Haisheng , Wang Huixian , Li Liben 
Published: August 2016

AbstractDensity functional theory calculations were carried out to investigate the Diels–Alder cycloaddition between cyclopentadiene and C60 after the encapsulation of Li+ ion with transition states identified and confirmed by intrinsic reaction coordinate calculations. Our results showed that the Li+‐encapsulation results in a lower energy barrier and the presence of counter anion
can further reduce the energy barrier, making the trend in agreement with the experimental results. In addition, the influencing factors on the reactivity of Li+‐encapsulated fullerenes such as counter anion and the position of Li+ in C60 were discussed. This study aims to provide a better understanding of Diels–Alder reaction with Endohedral Metallofullerenes to allow more efficient functionalization of fullerenes.
Towards a Design Pattern for Adaptive Systems Inspired by the Neocortex
Authors: Phillips Brian J. , Blackburn Mark 
Published: August 2016

ABSTRACTThis paper discusses a general design pattern that can provide systems engineering guidance for building adaptive systems. The Neocortex Adaptive System Pattern (NASP) architecture is an adaptive decision‐making architecture. It is derived from the physical architecture observed within the neocortex. It allows different adaptive system components with diverse methodologies and techniques to coexist and cooperate within a single system. A literature review of relevant neuroscience literature is provided. An architectural view, along with a taxonomy of architecture features, is explained in detail. Experiment results that compare an implemented NASP system, a non‐NASP adaptive system, and rule‐based systems within a combative simulation are presented. The NASP design pattern unifies the diverse set of algorithms and technologies found across the spectrum of adaptive systems. Evidence from this study indicates that multiple methods and time windows for adaptation can result in superior performance of the overall system. The implications of this result infer a clear preference for Bayesian‐based adaptive systems over neural network–based adaptive systems when the system faces time‐sensitive problems. This paper supports the claim of a design pattern by providing an example system that shares the same architectural features as NASP.
Empirical Validation of Structural Complexity Metric and Complexity Management for Engineering Systems
Authors: Sinha Kaushik , de Weck Olivier L. 
Published: August 2016

ABSTRACTQuantitative assessment of structural complexity is essential for characterization of engineered complex systems. In this paper, we describe a quantitative measure for structural complexity, conduct an empirical validation study of the structural complexity metric, and introduce a complexity management framework for engineering system development. We perform empirical validation of the proposed complexity metric using simple experiments using ball and stick models and show that the development effort increases superlinearly with increasing structural complexity. The standard deviation of the build time for ball and stick models is observed to vary superlinearly with structural complexity. We also describe a generic statistical procedure for building such cost estimation relationships with structural complexity as the independent variable. We distinguish the notion of perception of complexity as an observer‐dependent property and contrast that with complexity, which is a property of the system architecture. Finally, we introduce the notion of system value based on performance‐complexity trade space and introduce a complexity management framework for system development.
Stress-induced galectin-1 influences immune tolerance in the spleen and thymus by modulating CD45 immunoreactive lymphocytes
Authors: Sasaguri Kenichi , Yamada Kentaro , Narimatsu Yuri , Oonuki Masami , Oishi Azusa , Koda Koyo , Kubo Kin-ya , Yamamoto Toshiharu , Kadoya Toshihiko 
Published: August 2016

Abstract
Galectin-1 (Gal-1) is differentially expressed in normal and pathological tissues and regulates immune cell homeostasis. Restraint stress increases serum Gal-1 in rats. However, the function of stress-induced Gal-1 in serum is unknown. We determined if stress-induced Gal-1 in serum accumulates in immunocompetent organs as protection from physiological and/or psychological stress. Western blotting showed that the intensity of Gal-1 bands in stressed groups was significantly higher than that in controls. RT–PCR analysis indicated that the Gal-1 mRNA level did not increase after restraint stress. The numbers of Gal-1 immunoreactive cells in the splenic periarterial lymphatic sheath (PLS) and the thymus medulla of the stressed group were increased compared with those in controls. Furthermore, stress-induced Gal-1 immunoreactive cells corresponded to CD45 immunoreactive lymphocytes (CD45+) in the PLS of the spleen and the medulla of the thymus. Thus, stress-induced Gal-1 immediately accumulates in the spleen and thymus, and may modulate the immune response through apoptosis by binding to CD45+ lymphocytes in immune organs following physiological and/or psychological stress.
Einflussfaktoren auf die Arbeitsbelastung in der stationären Behindertenhilfe
Authors: Habermann-Horstmeier L. , Limbeck K. 
Published: August 2016

ZusammenfassungBislang gab es nur wenige Hinweise darauf, dass sich die Beschäftigten im Bereich der Behindertenbetreuung – ähnlich wie in der Pflege – durch ihre Arbeit besonders stark belastet fühlen. Im Rahmen der BMBD-Studie wurden nun bundesweit 400 Betreuungskräfte aus der stationären Behindertenhilfe u. a. zu ihrer Arbeitssituation befragt. Für die vorliegende Untersuchung wurden erstmals verschiedene Faktoren betrachtet, die dabei mitwirken, dass Betreuungskräfte ihre Tätigkeit als belastend empfinden. Die entsprechenden Daten wurden mithilfe uni- und bivariater Verfahren analysiert, mögliche statistische Zusammenhänge wurden im Rahmen einer Regressionsanalyse überprüft. Es zeigte sich, dass sich mehr als die Hälfte (56,1%) der Betreuungskräfte in der stationären Behindertenhilfe in Deutschland durch ihre berufliche Situation belastet fühlen. In diesem Zusammenhang konnten zahlreiche Faktoren ermittelt werden, die dabei mitwirken, dass ein Betreuer seine Arbeit als belastend empfindet. Hierzu gehören neben der Trägerschaft der Einrichtung z. B. auch Alter, Geschlecht, Beschäftigungsdauer, Arbeitsumfang und Hierarchieebene der Betreuer. So beurteilten männliche Leitungskräfte ihren Job als deutlich weniger belastend als ihre weiblichen Kollegen, männliche Betreuer in nicht-leitender Funktion tendierten jedoch dazu, ihre Arbeit als belastender einzuschätzen als ihre Kolleginnen. Am stärksten belastet fühlten sich die 25- bis 34-jährigen sowie die 45- bis 65-jährigen nicht-leitenden Fachkräfte. In der Gruppe 25- bis 34-Jährigen waren es insbesondere die Frauen, die sich stark belastet fühlten. Besonders stark belastet fühlten sich auch Beschäftigte, die schon mehr als 20 Jahre in einer Einrichtung tätig waren. Wenn zum Schicht- bzw. Wochenenddienst noch Überstunden hinzukamen, wurde dies von allen Betreuungskräften - besonders jedoch von den jüngeren Frauen – als erhebliche Belastung wahrgenommen. Die detaillierte Betrachtung von Faktoren, die dabei mitwirken, dass Betreuungskräfte ihre Tätigkeit als belastend empfinden, konnte damit z. T. erhebliche Unterschiede im Grad der Arbeitsbelastung zwischen Frauen und Männern, Leitungskräften und nicht-leitenden Fachkräften sowie zwischen Jungen und Älteren aufzeigen. Dies sollte bei der Planung von Maßnahmen zur Senkung der Arbeitsbelastung von Betreuern in der stationären Behindertenhilfe berücksichtigt werden.
Resilient Provision of Ecosystem Services from Agricultural Landscapes: Trade‐offs Involving Means and Variances of Water Quality Improvements
Authors: Rabotyagov Sergey S. , Valcu‐Lisman Adriana M. , Kling Catherine L. 
Published: August 2016

AbstractWe assess the trade‐offs and synergies involved in reducing agriculture‐generated nutrient loads with different levels of resilience. We optimize the selection of least‐cost patterns of agricultural conservation practices for both the expected performance of the conservation actions and its variance. Securing nutrient loads with a higher level of resilience is costly, with marginal costs of resilience generally declining with lower loads. We find that the main trade‐off dimension is between cost of conservation investments and ecosystem service objectives, as opposed to pronounced mean‐variance or between‐nutrient objectives trade‐offs. We find relative synergies in agricultural conservation investments aimed at nutrient reductions.
Variation in high-priority drug-drug interaction alerts across institutions and electronic health records
Authors: McEvoy Dustin S , Sittig Dean F , Hickman Thu-Trang , Aaron Skye , Ai Angela , Amato Mary , Bauer David W , Fraser Gregory M , Harper Jeremy , Kennemer Angela , Krall Michael A , Lehmann Christoph U , Malhotra Sameer , Murphy Daniel R , O’Kelley Brandi , Samal Lipika , Schreiber Richard , Singh Hardeep , Thomas Eric J , Vartian Carl V , Westmorland Jennifer , McCoy Allison B , Wright Adam 
Published: August 2016

Objective: The United States Office of the National Coordinator for Health Information Technology sponsored the development of a “high-priority” list of drug-drug interactions (DDIs) to be used for clinical decision support. We assessed current adoption of this list and current alerting practice for these DDIs with regard to alert implementation (presence or absence of an alert) and display (alert appearance as interruptive or passive).Materials and methods: We conducted evaluations of electronic health records (EHRs) at a convenience sample of health care organizations across the United States using a standardized testing protocol with simulated orders.Results: Evaluations of 19 systems were conducted at 13 sites using 14 different EHRs. Across systems, 69% of the high-priority DDI pairs produced alerts. Implementation and display of the DDI alerts tested varied between systems, even when the same EHR vendor was used. Across the drug pairs evaluated, implementation and display of DDI alerts differed, ranging from 27% (4/15) to 93% (14/15) implementation.Discussion: Currently, there is no standard of care covering which DDI alerts to implement or how to display them to providers. Opportunities to improve DDI alerting include using differential displays based on DDI severity, establishing improved lists of clinically significant DDIs, and thoroughly reviewing organizational implementation decisions regarding DDIs.Conclusion: DDI alerting is clinically important but not standardized. There is significant room for improvement and standardization around evidence-based DDIs.