bluuebunny/crossref_metadata_2025_split huggingface dataset:
From therapeutic antibodies to immune complex vaccines
Authors: Wang Xuan-Yi , Wang Bin , Wen Yu-Mei 
Published: January 2019

AbstractIn recent years, therapeutic monoclonal antibodies have made impressive progress, providing great benefit by successfully treating malignant and chronic inflammatory diseases. Monoclonal antibodies with broadly neutralizing effects against specific antigens, or that target specific immune regulators, manifest therapeutic effects via their Fab fragment specificities. Subsequently therapeutic efficacy is mediated mostly by interactions of the Fc fragments of the antibodies with their receptors (FcR) displayed on cells of the immune system. These interactions can trigger a series of immunoregulatory responses, involving both innate and adaptive immune systems and including cross-presentation of antigens, activation of CD8+T cells and CD4+T cells, phagocytosis, complement-mediated antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The nature of the triggered effector functions of the antibodies is markedly affected by the glycosylation patterns of the Fc fragments. These can cause differences in the conformation of the heavy chains of antibodies, with resultant changes in antibody binding affinity and activation of the complement system. Studies of the Fc glycosylation profiles together with the associated Fc effector functions and FcR/CR interactions promoted interest and progress in engineering therapeutic antibodies. Furthermore, because antigen–antibody immune complexes (ICs) have shown similar actions, in addition to certain novel immunoregulatory mechanisms that also reshape immune responses, the properties of ICs are being explored in new approaches for prevention and therapy of diseases. In this review, both basic studies and experimental/clinical applications of ICs leading to the development of preventive and therapeutic vaccines are presented.
The impact of cigarette smoke exposure, COPD, or asthma status on ABC transporter gene expression in human airway epithelial cells
Authors: Aguiar Jennifer A. , Tamminga Andrea , Lobb Briallen , Huff Ryan D. , Nguyen Jenny P. , Kim Yechan , Dvorkin-Gheva Anna , Stampfli Martin R. , Doxey Andrew C. , Hirota Jeremy A. 
Published: January 2019

AbstractABC transporters are conserved in prokaryotes and eukaryotes, with humans expressing 48 transporters divided into 7 classes (ABCA, ABCB, ABCC, ABCD, ABDE, ABCF, and ABCG). Throughout the human body, ABC transporters regulate cAMP levels, chloride secretion, lipid transport, and anti-oxidant responses. We used a bioinformatic approach complemented with in vitro experimental methods for validation of the 48 known human ABC transporters in airway epithelial cells using bronchial epithelial cell gene expression datasets available in NCBI GEO from well-characterized patient populations of healthy subjects and individuals that smoke cigarettes, or have been diagnosed with COPD or asthma, with validation performed in Calu-3 airway epithelial cells. Gene expression data demonstrate that ABC transporters are variably expressed in epithelial cells from different airway generations, regulated by cigarette smoke exposure (ABCA13, ABCB6, ABCC1, and ABCC3), and differentially expressed in individuals with COPD and asthma (ABCA13, ABCC1, ABCC2, ABCC9). An in vitro cell culture model of cigarette smoke exposure was able to recapitulate select observed in situ changes. Our work highlights select ABC transporter candidates of interest and a relevant in vitro model that will enable a deeper understanding of the contribution of ABC transporters in the respiratory mucosa in lung health and disease.
Contact-dependent growth inhibition systems in Acinetobacter
Authors: De Gregorio Eliana , Zarrilli Raffaele , Di Nocera Pier Paolo 
Published: January 2019

AbstractIn bacterial contact-dependent growth inhibition (CDI) systems, CdiA proteins are exported to the outer membrane by cognate CdiB proteins. CdiA binds to receptors on susceptible bacteria and subsequently delivers its C-terminal toxin domain (CdiA-CT) into neighbouring target cells. Whereas self bacteria produce CdiI antitoxins, non-self bacteria lack antitoxins and are therefore inhibited in their growth by CdiA. In silico surveys of pathogenic Acinetobacter genomes have enabled us to identify >40 different CDI systems, which we sorted into two distinct groups. Type-II CdiAs are giant proteins (3711 to 5733 residues) with long arrays of 20-mer repeats. Type-I CdiAs are smaller (1900–2400 residues), lack repeats and feature central heterogeneity (HET) regions, that vary in size and sequence and can be exchanged between CdiA proteins. HET regions in most type-I proteins confer the ability to adopt a coiled-coil conformation. CdiA-CT and pretoxin modules differ significantly between type-I and type-II CdiAs. Moreover, type-II genes only have remnants of genes in their 3′ end regions that have been displaced by the insertion of novel cdi sequences. Type-I and type-II CDI systems are equally abundant in A. baumannii, whereas A. pittii and A. nosocomialis predominantly feature type-I and type-II systems, respectively.
Using backbone-cyclized Cys-rich polypeptides as molecular scaffolds to target protein–protein interactions
Authors: Chaudhuri Dipankar , Aboye Teshome , Camarero Julio A. 
Published: January 2019

Abstract
The use of disulfide-rich backbone-cyclized polypeptides, as molecular scaffolds to design a new generation of bioimaging tools and drugs that are potent and specific, and thus might have fewer side effects than traditional small-molecule drugs, is gaining increasing interest among the scientific and in the pharmaceutical industries. Highly constrained macrocyclic polypeptides are exceptionally more stable to chemical, thermal and biological degradation and show better biological activity when compared with their linear counterparts. Many of these relatively new scaffolds have been also found to be highly tolerant to sequence variability, aside from the conserved residues forming the disulfide bonds, able to cross cellular membranes and modulate intracellular protein–protein interactions both in vitro and in vivo. These properties make them ideal tools for many biotechnological applications. The present study provides an overview of the new developments on the use of several disulfide-rich backbone-cyclized polypeptides, including cyclotides, θ-defensins and sunflower trypsin inhibitor peptides, in the development of novel bioimaging reagents and therapeutic leads.
Advancing the Delivery of Communication Sciences and Disorders Services Through Research: The Promise of Health Services Research
Authors: Morris Megan A. , Oshita Jennifer Y. , Stransky Michelle 
Published: January 2019

Purpose
Traditional efficacy research, or research that studies interventions in controlled settings, can be difficult to translate to real-world clinical settings. In this article, we introduce the field of health services research (HSR) as 1 possible tool to aid this translation. HSR is a field of research that examines and intervenes in the use, cost, quality, delivery, organization, and outcomes of clinical interventions and services in the real-world setting. The complexity of the world outside the clinic walls is accounted for in HSR methods and data sources. As such, HSR often requires collaboration of stakeholders, including patients, caregivers, clinicians, and policy makers. These stakeholders are often engaged throughout the research process, from selecting research questions to disseminating results. HSR brings together researchers from multiple disciplines, including sociology, health economics, epidemiology, and implementation science, among others. The outcomes of HSR can inform policy changes both locally and nationally. To clarify the scope and impact of HSR, we present examples of HSR-based research on communication between patients with communication disorders and health care providers.

Conclusions
HSR is a critical tool for clinicians and researchers in the discipline of communication sciences and disorders who are committed to improving the lives and health of persons with communication disorders.
Experimental study of the penetration of oxygen and deuterium atoms into porous water ice
Authors: Minissale M. , Nguyen T. , Dulieu F. 
Published: January 2019

Context. Many interstellar molecules are thought to form on dust grains. In particular, hydrogenation is one of the major mechanisms of the formation of mantle ice. To date it is not clear if H atoms can penetrate the bulk of the ice mantle or if it only has chemical activity on the accessible surface of grains.
Aims. We wish to study the efficiency of atoms deposited on the outer surface of the amorphous solid water to penetrate into the ice bulk.
Methods. NO molecules react with O and H atoms. They are easily detected by infrared (IR) spectroscopy. These two properties make this molecule an ideal chemical tracer for the penetration of O and H atoms through water ice. In our experiments we first deposited a NO undercoat and covered this layer (at 40 K) with a variable amount of water ice. Then, we exposed this undercoat to D (10 K) or O (40 K) atoms, and we followed the NO consumption and the products that appeared via IR signatures, and we finally analyzed the desorption of all species through a temperature-programmed desorption technique. We experimentally characterize the accessible surface of the ice and provide a model to interpret quantitatively our measurements.
Results. Water ice limits the destruction of tracer NO molecules. The thicker the ice, the more NO remains unreacted. H and O atoms lead to the same amount of NO consumption, pointing out that access to reactants for these two different atoms is identical. We discuss different possible scenarios of NO localization (in and/or on the ice) and determine how this affects our observables (IR data and desorption profiles).
Conclusions. In our experimental conditions, it is not possible to measure any atom penetration through the bulk of the ice. The surface diffusion followed by reaction with NO or by self-reaction (i.e., H + H → H2) is faster than bulk diffusion. We propose lower limit values for penetration barriers. Therefore the building of astrophysical ice mantles should be mostly driven by surface reactivity.
Constraining models of activity on comet 67P/Churyumov-Gerasimenko with Rosetta trajectory, rotation, and water production measurements
Authors: Attree N. , Jorda L. , Groussin O. , Mottola S. , Thomas N. , Brouet Y. , Kührt E. , Knapmeyer M. , Preusker F. , Scholten F. , Knollenberg J. , Hviid S. , Hartogh P. , Rodrigo R. 
Published: January 2019

Aims.We use four observational data sets, mainly from the Rosetta mission, to constrain the activity pattern of the nucleus of comet 67P/Churyumov-Gerasimenko (67P).Methods.We developed a numerical model that computes the production rate and non-gravitational acceleration of the nucleus of comet 67P as a function of time, taking into account its complex shape with a shape model reconstructed from OSIRIS imagery. We used this model to fit three observational data sets: the trajectory data from flight dynamics; the rotation state as reconstructed from OSIRIS imagery; and the water production measurements from ROSINA of 67P. The two key parameters of our model, adjusted to fit the three data sets all together, are the activity pattern and the momentum transfer efficiency (i.e., the so-calledηparameter of the non-gravitational forces).Results.We find an activity pattern that can successfully reproduce the three data sets simultaneously. The fitted activity pattern exhibits two main features: a higher effective active fraction in two southern super-regions (~10%) outside perihelion compared to the northern regions (<4%), and a drastic rise in effective active fraction of the southern regions (~25−35%) around perihelion. We interpret the time-varying southern effective active fraction by cyclic formation and removal of a dust mantle in these regions. Our analysis supports moderate values of the momentum transfer coefficientηin the range 0.6–0.7; valuesη≤ 0.5 orη≥ 0.8 significantly degrade the fit to the three data sets. Our conclusions reinforce the idea that seasonal effects linked to the orientation of the spin axis play a key role in the formation and evolution of dust mantles, and in turn, they largely control the temporal variations of the gas flux.
The effects of prestige on collective performance and information flow in a strictly hierarchical institution
Authors: Offord Matt , Gill Roger , Kendal Jeremy 
Published: January 2019

AbstractInstitutions such as the military aim to respond efficiently to complex logistical challenges using a strictly hierarchical structure, where leaders are assigned a rank by senior colleagues and team members are trained to obey leader commands. Anthropologists have observed that leadership status outside of these top-down hierarchical institutions is often affected by the attribution of prestige by non-leaders. Here we show that even in the strictly hierarchical institutional context of the Royal Navy, informal prestige networks play a functional role in leadership efficacy and group-level dynamics. Specifically, a team leader’s informal prestige is a far stronger predictor of team performance and rate of information transmission during training exercises at sea than their formal rank. We find that the more decentralised the prestige network the more efficient it is for disseminating information. The implications of our findings for traditional conceptions of leadership in hierarchical institutions and the effects of prestige on group-level behaviour are discussed.
Gender influences in agricultural production: the dynamic role of the female farmer.
Authors: Lange K. , Tewari Rachna , Zivkovic S. , McCallister D. 
Published: January 2019

Abstract
Women have played an integral role in agricultural production for centuries. This article reviews multiple perspectives on women's involvement in US agricultural production, including economics, rural sociology, geography, gender ethnography and similarly related fields. We focus on studies surrounding women's roles in US agriculture over time, recent trends of US female farm operators and farm sector gender influences of women.
A simple convolutional neural network for prediction of enhancer–promoter interactions with DNA sequence data
Authors: Zhuang Zhong , Shen Xiaotong , Pan Wei 
Published: January 2019

Abstract

Motivation
Enhancer–promoter interactions (EPIs) in the genome play an important role in transcriptional regulation. EPIs can be useful in boosting statistical power and enhancing mechanistic interpretation for disease- or trait-associated genetic variants in genome-wide association studies. Instead of expensive and time-consuming biological experiments, computational prediction of EPIs with DNA sequence and other genomic data is a fast and viable alternative. In particular, deep learning and other machine learning methods have been demonstrated with promising performance.

Results
First, using a published human cell line dataset, we demonstrate that a simple convolutional neural network (CNN) performs as well as, if no better than, a more complicated and state-of-the-art architecture, a hybrid of a CNN and a recurrent neural network. More importantly, in spite of the well-known cell line-specific EPIs (and corresponding gene expression), in contrast to the standard practice of training and predicting for each cell line separately, we propose two transfer learning approaches to training a model using all cell lines to various extents, leading to substantially improved predictive performance.

Availability and implementation
Computer code is available at https://github.com/zzUMN/Combine-CNN-Enhancer-and-Promoters.

Supplementary information
Supplementary data are available at Bioinformatics online.
Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive–Compulsive Disorder
Authors: Pujol Jesus , Blanco-Hinojo Laura , Maciá Dídac , Alonso Pino , Harrison Ben J , Martínez-Vilavella Gerard , Deus Joan , Menchón José M , Cardoner Narcís , Soriano-Mas Carles 
Published: January 2019

AbstractWe mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive–compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.
Misuse of Discharge Antimicrobial Prescription in the Emergency Department: An Observational Study at a Tertiary Care Center
Authors: Tagashira Yasuaki , Yamane Naofumi , Miyahara Satoshi , Orihara Azusa , Uehara Yuki , Hiramatsu Keiichi , Honda Hitoshi 
Published: January 2019

Abstract
We conducted a restrospective cohort study of patients discharged from the emergency department at a tertiary care center with an antimicrobial prescription. More than half of the prescribed antimicrobials were misused and frequently inappropriate for various infectious diseases. In this study, we analyzed the physician-related and environment-related factors predicting misuse.
Real Exchange Rates and Currency Risk Premiums
Authors: Balduzzi Pierluigi , Chiang I-Hsuan Ethan 
Published: January 2019

Abstract
Standard finite horizon tests uncover only weak evidence of the predictive power of the real exchange rate for excess currency returns. On the other hand, in long-horizon tests, the real exchange rate strongly and negatively predicts future excess currency returns. Conversely, we can attribute most of the variability in real exchange rates to changes in currency risk premiums. The “habit” and “long-run risks” models replicate the predictive power of the real exchange rate for excess currency returns, but substantially overstate the fraction of the volatility of the real exchange rate due to risk premiums.
Received December 14, 2017; Editorial decision October 14, 2018 by Editor: Raman Uppal. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Building a botanical foundation for perennial agriculture: Global inventory of wild, perennial herbaceous Fabaceae species
Authors: Ciotir Claudia , Applequist Wendy , Crews Timothy E. , Cristea Neculai , DeHaan Lee R. , Frawley Emma , Herron Sterling , Magill Robert , Miller James , Roskov Yury , Schlautman Brandon , Solomon James , Townesmith Andrew , Van Tassel David , Zarucchi James , Miller Allison J. 
Published: January 2019

SummaryConcerns about soil health and stability are focusing attention on crops that deliver both agricultural products and ecological services. Deep rooted, perennial plants that build soil organic matter, support diverse below-ground microbial communities, and produce edible seeds are key components underpinning ecological intensification; however few perennial, herbaceous crops have been domesticated for food.To facilitate development of edible, perennial, herbaceous crops, including perennial grains, we constructed an online resource of wild, perennial, herbaceous species – the Perennial Agriculture Project Global Inventory (PAPGI; http://www.tropicos.org/Project/PAPGI). The first component of this project focuses on wild, perennial, herbaceous Fabaceae species. We extracted taxonomic names and descriptors from the International Legume Database and Information Service. Names were added to PAPGI, a special project within the botanical database TROPICOS, where they link to specimen records and ethnobotanical and toxicological data. PAPGI includes 6,644 perennial, herbaceous Fabaceae species. We built a searchable database of more than 60 agriculturally important traits. Here we highlight food and forage uses for 314 legume species, and toxicological data for 278 species.The novel contribution of PAPGI is its focus on wild, perennial herbaceous species that generally have not entered the domestication process but that hold promise for development as perennial food crops. By extracting botanical information relevant for agriculture we provide a dynamic resource for breeders and plant scientists working to advance ecological intensification of agriculture, and for conservation managers working to preserve wild species of potential agricultural importance.Societal Impact StatementAgroecosystems are constantly evolving to meet the needs of a growing population in a sustainable manner. Perennial, herbaceous crops deliver both agricultural products and ecological services. Until recently, edible, perennial, herbaceous crops, including perennial grains, were absent from agriculture. Perennial, herbaceous crops can be developed through wide hybridization between annual crops and perennial relatives or by de novo domestication of wild species. The diversity of wild, perennial, herbaceous legume species documented by the PAPGI increases resources available to breeders of perennial, herbaceous legumes, and raises awareness about previously untapped wild plant diversity in future crop development.