bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structures of the human neurokinin 1 receptor in complex with clinically used antagonists
Authors: Schöppe Jendrik , Ehrenmann Janosch , Klenk Christoph , Rucktooa Prakash , Schütz Marco , Doré Andrew S. , Plückthun Andreas 
Published: December 2018

AbstractNeurokinins (or tachykinins) are peptides that modulate a wide variety of human physiology through the neurokinin G protein-coupled receptor family, implicated in a diverse array of pathological processes. Here we report high-resolution crystal structures of the human NK1receptor (NK1R) bound to two small-molecule antagonist therapeutics – aprepitant and netupitant and the progenitor antagonist CP-99,994. The structures reveal the detailed interactions between clinically approved antagonists and NK1R, which induce a distinct receptor conformation resulting in an interhelical hydrogen-bond network that cross-links the extracellular ends of helices V and VI. Furthermore, the high-resolution details of NK1R bound to netupitant establish a structural rationale for the lack of basal activity in NK1R. Taken together, these co-structures provide a comprehensive structural basis of NK1R antagonism and will facilitate the design of new therapeutics targeting the neurokinin receptor family.
Dissociable cognitive strategies for sensorimotor learning
Authors: McDougle Samuel D. , Taylor Jordan A. 
Published: December 2018

AbstractComputations underlying cognitive strategies in human motor learning are poorly understood. Here we investigate such strategies in a common sensorimotor transformation task. We show that strategies assume two forms, likely reflecting distinct working memory representations: discrete caching of stimulus-response contingencies, and time-consuming parametric computations. Reaction times and errors suggest that both strategies are employed during learning, and trade off based on task complexity. Experiments using pressured preparation time further support dissociable strategies: In response caching, time pressure elicits multi-modal distributions of movements; during parametric computations, time pressure elicits a shifting distribution of movements between visual targets and distal goals, consistent with analog re-computing of a movement plan. A generalization experiment reveals that discrete and parametric strategies produce, respectively, more localized or more global transfer effects. These results describe how qualitatively distinct cognitive representations are leveraged for motor learning and produce downstream consequences for behavioral flexibility.
A region-resolved mucosa proteome of the human stomach
Authors: Ni Xiaotian , Tan Zhaoli , Ding Chen , Zhang Chunchao , Song Lan , Yang Shuai , Liu Mingwei , Jia Ru , Zhao Chuanhua , Song Lei , Liu Wanlin , Zhou Quan , Gong Tongqing , Li Xianju , Tai Yanhong , Zhu Weimin , Shi Tieliu , Wang Yi , Xu Jianming , Zhen Bei , Qin Jun 
Published: December 2018

AbstractThe human gastric mucosa is the most active layer of the stomach wall, involved in food digestion, metabolic processes and gastric carcinogenesis. Anatomically, the human stomach is divided into seven regions, but the protein basis for cellular specialization is not well understood. Here we present a global analysis of protein profiles of 82 apparently normal mucosa samples obtained from living individuals by endoscopic stomach biopsy. We identify 6,258 high-confidence proteins and estimate the ranges of protein expression in the seven stomach regions, presenting a region-resolved proteome reference map of the near normal, human stomach. Furthermore, we measure mucosa protein profiles of tumor and tumor nearby tissues (TNT) from 58 gastric cancer patients, enabling comparisons between tumor, TNT, and normal tissue. These datasets provide a rich resource for the gastrointestinal tract research community to investigate the molecular basis for region-specific functions in mucosa physiology and pathology including gastric cancer.
Acto-myosin force organization modulates centriole separation and PLK4 recruitment to ensure centriole fidelity
Authors: Vitiello Elisa , Moreau Philippe , Nunes Vanessa , Mettouchi Amel , Maiato Helder , Ferreira Jorge G. , Wang Irène , Balland Martial 
Published: December 2018

AbstractThe presence of aberrant number of centrioles is a recognized cause of aneuploidy and hallmark of cancer. Hence, centriole duplication needs to be tightly regulated. It has been proposed that centriole separation limits centrosome duplication. The mechanism driving centriole separation is poorly understood and little is known on how this is linked to centriole duplication. Here, we propose that actin-generated forces regulate centriole separation. By imposing geometric constraints via micropatterns, we were able to prove that precise acto-myosin force arrangements control direction, distance and time of centriole separation. Accordingly, inhibition of acto-myosin contractility impairs centriole separation. Alongside, we observed that organization of acto-myosin force modulates specifically the length of S-G2 phases of the cell cycle, PLK4 recruitment at the centrosome and centriole fidelity. These discoveries led us to suggest that acto-myosin forces might act in fundamental mechanisms of aneuploidy prevention.
The conformational changes coupling ATP hydrolysis and translocation in a bacterial DnaB helicase
Authors: Wiegand Thomas , Cadalbert Riccardo , Lacabanne Denis , Timmins Joanna , Terradot Laurent , Böckmann Anja , Meier Beat H. 
Published: December 2018

AbstractDnaB helicases are motor proteins that couple ATP-hydrolysis to the loading of the protein onto DNA at the replication fork and to translocation along DNA to separate double-stranded DNA into single strands during replication. Using a network of conformational states, arrested by nucleotide mimics, we herein characterize the reaction coordinates for ATP hydrolysis, DNA loading and DNA translocation using solid-state NMR spectroscopy. AMP-PCP is used as pre-hydrolytic, ADP:AlF4− as transition state, and ADP as post-hydrolytic ATP mimic. 31P and 13C NMR spectra reveal conformational and dynamic responses to ATP hydrolysis and the resulting DNA loading and translocation with single amino-acid resolution. This allows us to identify residues guiding the DNA translocation process and to explain the high binding affinities for DNA observed for ADP:AlF4−, which turns out to be optimally preconfigured to bind DNA.
pH effects on the electrochemical reduction of CO(2) towards C2 products on stepped copper
Authors: Liu Xinyan , Schlexer Philomena , Xiao Jianping , Ji Yongfei , Wang Lei , Sandberg Robert B. , Tang Michael , Brown Kristopher S. , Peng Hongjie , Ringe Stefan , Hahn Christopher , Jaramillo Thomas F. , Nørskov Jens K. , Chan Karen 
Published: December 2018

AbstractWe present a microkinetic model for CO(2) reduction (CO(2)R) on Cu(211) towards C2 products, based on energetics estimated from an explicit solvent model. We show that the differences in both Tafel slopes and pH dependence for C1 vs C2 activity arise from differences in their multi-step mechanisms. We find the depletion in C2 products observed at high overpotential and high pH to arise from the 2nd order dependence of C-C coupling on CO coverage, which decreases due to competition from the C1 pathway. We further demonstrate that CO(2) reduction at a fixed pH yield similar activities, due to the facile kinetics for CO2 reduction to CO on Cu, which suggests C2 products to be favored for CO2R under alkaline conditions. The mechanistic insights of this work elucidate how reaction conditions can lead to significant enhancements in selectivity and activity towards higher value C2 products.
Uncovering electron scattering mechanisms in NiFeCoCrMn derived concentrated solid solution and high entropy alloys
Authors: Mu Sai , Samolyuk German D. , Wimmer Sebastian , Troparevsky Maria C. , Khan Suffian N. , Mankovsky Sergiy , Ebert Hubert , Stocks George M. 
Published: December 2018

AbstractWhilst it has long been known that disorder profoundly affects transport properties, recent measurements on a series of solid solution 3d-transition metal alloys reveal two orders of magnitude variations in the residual resistivity. Using ab initio methods, we demonstrate that, while the carrier density of all alloys is as high as in normal metals, the electron mean-free-path can vary from ~10 Å (strong scattering limit) to ~103 Å (weak scattering limit). Here, we delineate the underlying electron scattering mechanisms responsible for this disparate behavior. While site-diagonal, spin dependent, potential scattering is always dominant, for alloys containing only Fe, Co, and Ni the majority-spin channel experiences negligible disorder scattering, thereby providing a short circuit, while for Cr/Mn containing alloys both spin channels experience strong disorder scattering due to an electron filling effect. Somewhat surprisingly, other scattering mechanisms—including displacement, or size effect, scattering which has been shown to strongly correlate with such diverse properties as yield strength—are found to be relatively weak in most cases.
Strain engineering of electro-optic constants in ferroelectric materials
Authors: Paillard Charles , Prokhorenko Sergei , Bellaiche Laurent 
Published: December 2018

AbstractElectro-optic effects allow control of the ow of light using electric fields, and are of utmost importance for today’s information and communication technologies, such as TV displays and fiber optics. The search for large electro-optic constants in films is essential to the miniaturization and increased efficiency of electro-optic devices. In this work, we demonstrate that strain-engineering in PbTiO3 films allows to selectively choose which electro-optic constant to improve. Unclamped electro-optic constants larger than 100 pm V−1 are predicted, either by driving the softening of an optical phonon mode at a phase transition boundary under tensile strain, or by generating the equivalent of a negative pressure via compressive strain to obtain large piezoelectric constants. In particular, a r13 electro-optic coefficient twice as large as the one of the commonly used LiNbO3 electro-optic material is found here when growing PbTiO3 on the technologicallyimportant Si substrate.
Learning to predict single-wall carbon nanotube-recognition DNA sequences
Authors: Yang Yoona , Zheng Ming , Jagota Anand 
Published: December 2018

AbstractDNA/single-wall carbon nanotube (SWCNT) hybrids have enabled many applications because of their special ability to disperse and sort SWCNTs by their chirality and handedness. Much work has been done to discover sequences which recognize specific chiralities of SWCNT, and significant progress has been made in understanding the underlying structure and thermodynamics of these hybrids. Nevertheless, de novo prediction of recognition sequences remains essentially impossible and the success rate for their discovery by search of the vast single-stranded DNA library is very low. Here, we report an effective way of predicting recognition sequences based on machine learning analysis of existing experimental sequence data sets. Multiple input feature construction methods (position-specific, term-frequency, combined or segmented term frequency vector, and motif-based feature) were used and compared. The transformed features were used to train several classifier algorithms (logistic regression, support vector machine, and artificial neural network). Trained models were used to predict new sets of recognition sequences, and consensus among a number of models was used successfully to counteract the limited size of the data set. Predictions were tested using aqueous two-phase separation. New data thus acquired were used to retrain the models by adding an experimentally tested new set of predicted sequences to the original set. The frequency of finding correct recognition sequences by the trained model increased to >50% from the ~10% success rate in the original training data set.
Comparison of Bacillus subtilis transcriptome profiles from two separate missions to the International Space Station
Authors: Morrison Michael D. , Fajardo-Cavazos Patricia , Nicholson Wayne L. 
Published: December 2018

AbstractThe human spaceflight environment is notable for the unique factor of microgravity, which exerts numerous physiologic effects on macroscopic organisms, but how this environment may affect single-celled microbes is less clear. In an effort to understand how the microbial transcriptome responds to the unique environment of spaceflight, the model Gram-positive bacteriumBacillus subtiliswas flown on two separate missions to the International Space Station in experiments dubbed BRIC-21 and BRIC-23. Cells were grown to late-exponential/early stationary phase, frozen, then returned to Earth for RNA-seq analysis in parallel with matched ground control samples. A total of 91 genes were significantly differentially expressed in both experiments; 55 exhibiting higher transcript levels in flight samples and 36 showing higher transcript levels in ground control samples. Genes upregulated in flight samples notably included those involved in biofilm formation, biotin and arginine biosynthesis, siderophores, manganese transport, toxin production and resistance, and sporulation inhibition. Genes preferentially upregulated in ground control samples notably included those responding to oxygen limitation, e.g., fermentation, anaerobic respiration, subtilosin biosynthesis, and anaerobic regulatory genes. The results indicated differences in oxygen availability between flight and ground control samples, likely due to differences in cell sedimentation and the toroidal shape assumed by the liquid cultures in microgravity.
Insulin signaling in Drosophila melanogaster mediates Aβ toxicity
Authors: Huang Yunpeng , Wan Zhihui , Wang Zhiqing , Zhou Bing 
Published: December 2018

AbstractAlzheimer’s disease (AD) and diabetes are clinically positively correlated. However, the connection between them is not clarified. Here, using Drosophila as a model system, we show that reducing insulin signaling can effectively suppress the toxicity from Aβ (Amyloid beta 42) expression. On the other hand, Aβ accumulation led to the elevation of fly insulin-like peptides (ILPs) and activation of insulin signaling in the brain. Mechanistically, these observations are attributed to a reciprocal competition between Drosophila insulin-like peptides and Aβ for the activity of insulin-degrading enzyme (IDE). Intriguingly, peripheral insulin signaling is decreased despite its heightened activity in the brain. While many upstream factors may modify Aβ toxicity, our results suggest that insulin signaling is the main downstream executor of Aβ damage, and thus may serve as a promising target for Alzheimer’s treatment in non-diabetes patients. This study explains why more Alzheimer’s cases are found in diabetes patients.
Weiterbildung zum eHealth-Berater und Vernetzung im eHealthWerk
Authors: Kokelmann Christoph , Stumpf Paul 
Published: December 2018

ZUSAMMENFASSUNGDie Digitalisierung im Gesundheitswesen ist aus gesundheitspolitischer wie wirtschaftlicher Sicht hochaktuell. Das technisch Machbare steht jedoch der Herausforderung gegenüber, dass sowohl Patienten als auch professionelle Gesundheitsakteure in der Anwendung entsprechend geschult sein müssen. Mitunter kann der Arzt diese Beratungsleistung jedoch gar nicht leisten, weil er selbst zu unerfahren ist. Damit steigt die Wahrscheinlichkeit, dass sich der Patient die eHealth-Tools eigenständig und unsystematisch zu erschließen versucht und dass das Selbstmanagement seiner Krankheit nachteilig beeinflusst wird. Die Weiterbildung zum eHealth-Berater greift diese Diskrepanz auf und fördert die digitale Gesundheitskompetenz der Gesundheitsakteure zielgerichtet. Die Evaluation der Pilotphase konnte bestätigen, dass das Konzept der Weiterbildung dieses Ziel erreicht. Ergänzt durch aktuelle Inhalte aus dem Online-Netzwerk sind die Teilnehmer optimal für die Digitalisierung im Gesundheitswesen gerüstet.
Möglichkeiten moderner Diabetestechnologie
Authors: Thomas Andreas 
Published: December 2018

ZUSAMMENFASSUNGIn Form von Spritzen und Kanülen zur Insulininjektion stehen den Patienten prinzipiell seit Beginn der Diabetestherapie technologische Anwendungen bereit. An dieser Situation änderte sich über viele Jahrzehnte wenig, bis in den 1980er-Jahren eine rasante Entwicklung einsetzte, welche die Diabetestherapie revolutionierte. Das betraf 2 grundsätzliche Bereiche: Einerseits standen Insulinpens und feinere Insulinkanülen zur Verfügung, dies förderte die Bereitschaft der Patienten für eine physiologischere, aber auch mehr Injektionen erforderlich machende Insulintherapie. Dazu gehören auch die zu dieser Zeit aufkommenden Insulinpumpen. Andererseits gelang es, kleine, transportable Blutzuckermessgeräte und Teststreifen mit vertretbar geringen notwendigen Blutmengen zur Messung bereitzustellen, was die Patienten in die Lage versetzte, ihre Therapie im Alltag selbst zu führen. Diese Entwicklung ist in den letzten Jahren immer rasanter geworden. Ein Meilenstein war das kontinuierliche Glukosemonitoring (CGM), ein wichtiger Bestandteil in Systemen für eine automatisierte Insulinabgabe und die Zusammenführung von Messung und Insulinabgabe. Weiterhin können durch die kontinuierliche Glukosemessung auch Blutzuckermessungen einschränkt bzw. ganz verzichtbar werden. Mit den Errungenschaften der modernen Informationstechnologie ergeben sich völlig neue Möglichkeiten, die unter den gebräuchlichen Begriff „Digitalisierung“ fallen. Wurde zunächst nur Software zur Analyse von Glukosewerten entwickelt, so lassen sich mittlerweile Daten auch über eine Cloud einem Computer zuführen, der sie analysiert und dem Patienten im Alltag unterstützende Verhaltenshinweise gibt (Patienten-Entscheidungs-Systeme). Die Möglichkeiten der modernen Diabetestechnologie betreffen nicht mehr nur Patienten mit Typ-1-, sondern zunehmend auch die mit Typ-2-Diabetes. Generell führt dies zu einem veränderten Verhältnis zwischen Arzt und Patient, wobei beide Seiten wirkungsvoll unterstützt werden.
Characteristics and Management of Patients with Venous Thromboembolism: The GARFIELD-VTE Registry
Authors: Ageno Walter , Haas Sylvia , Weitz Jeffrey I. , Goldhaber Samuel Z. , Turpie Alexander G. G. , Goto Shinya , Angchaisuksiri Pantep , Nielsen Joern Dalsgaard , Kayani Gloria , Pieper Karen S. , Schellong Sebastian , Bounameaux Henri , Mantovani Lorenzo G. , Prandoni Paolo , Kakkar Ajay K. ,   on behalf of the GARFIELD-VTE investigators
Published: December 2018

Background Management of venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), varies worldwide.
Methods The Global Anticoagulant Registry in the FIELD – Venous Thromboembolism (GARFIELD-VTE) is a prospective, observational study of 10,685 patients with objectively diagnosed VTE recruited from May 2014 to January 2017 at 417 sites in 28 countries. All patients are followed for at least 3 years. We describe the baseline characteristics of the study population and their management within 30 days of diagnosis.
Results The median age was 60.2 years; 50.4% were male; 61.7% had DVT and 38.3% had PE ± DVT; and 32.3% were obese (body mass index ≥ 30 kg/m2). The most common risk factors were surgery (12.5%), hospitalization (12.0%) and trauma to the lower limbs (7.8%). At the time of VTE diagnosis, 10.1% had active cancer and 5.7% were chronically immobilized. Treatment for VTE was anticoagulant (AC) therapy alone in 90.9% of patients; 5.1% received thrombolytic and/or surgical/mechanical therapy ± AC and 4.0% received no therapy. Pre-diagnosis, 12.8% received AC therapy alone and 0.2% received thrombolytic and/or surgical/mechanical therapy ± AC. After diagnosis, parenteral AC therapy alone was administered in 17.6% of patients, and it was followed by a direct oral AC (DOAC) in 16.4% or a vitamin K antagonist (VKA) in 26.8%. DOACs alone were prescribed to 32.3% of patients, while 5.9% received VKA alone.
Conclusion The initial findings from this global registry highlight the heterogeneity in characteristics and management of VTE patients. Prospective follow-up will reveal the impact of this heterogeneity on outcomes.
Updating a Perinatal Risk Scoring System to Predict Infant Mortality
Authors: Umer Amna , Lilly Christa , Hamilton Candice , Cottrell Lesley , Lefeber Timothy , Hulsey Thomas , John Collin 
Published: December 2018

Objective The Birth Score Project (Project WATCH) began in the rural state of West Virginia (WV) in the United States in 1984. The project is intended to identify newborns with a greater risk of infant mortality. The primary objective of this study was to update the current Birth Score based on current literature and rigorous statistical methodology.
Study Design The study merged data from the Birth Score, Birth Certificate (birth years 2008–2013), and Infant Mortality Data (N = 121,640). The merged data were randomly divided into developmental (N = 85,148) and validation (N = 36,492) datasets. Risk scoring system was developed using the weighted multivariate risk score functions and consisted of infant and maternal factors.
Results The updated score ranged from 0 to 86. Infants with a score of ≥17 were categorized into the high score group (n = 15,387; 18.1%). The odds of infant mortality were 5.6 times higher (95% confidence interval: 4.4, 7.1) among those who had a high score versus low score.
Conclusion The updated score is a better predictor of infant mortality than the current Birth Score. This score has practical relevance for physicians in WV to identify newborns at the greatest risk of infant mortality and refer the infants to primary pediatric services and case management for close follow-up.
Passive Ceiling Light Disinfection System to Reduce Bioburden in an Intensive Care Unit
Authors: Rohan Annie , Khan Imraan , Yin Donglei , Yang Jie 
Published: December 2018

AbstractA ceiling-installed narrow spectrum (402–420 nm) bactericidal blue light disinfection system was installed in a large suburban medical intensive care unit (ICU) and evaluated for implementation feasibility and effectiveness in reducing environmental bioburden. Installation of 54 ceiling devices was accomplished at low cost and with minimal ICU process disruption. Postinstallation high-touch surface colony counts were significantly lower than preinstallation. Linear mixed modeling demonstrated a 21% average overall decrease in colony count after installation, with consistent reduction in colony counts starting from week 4 postinstallation. Automated technology is potentially more efficient in reducing environmental bioburden in the acute care setting compared with other bioburden reducing methods or can provide a robust compliment to manual cleaning.