bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformance test development with the Java modeling language
Authors: Søndergaard Hans , Korsholm Stephan E. , Ravn Anders P. 
Published: February 2017

SummaryIn order to claim conformance with a Java Specification Request, a Java implementation has to pass all tests in an associated Technology Compatibility Kit. This paper presents a model‐based development of a Technology Compatibility Kit test suite and a test execution tool for the draft safety‐critical Java profile specification. The Java Modeling Language is used to model conformance constraints for the profile. Java Modeling Language annotations define contracts for classes and interfaces. The annotations are translated by a tool into runtime assertion checks. Hereby, the design and elaboration of the concrete test cases are simplified, because the expected results are derived from contracts and thus do not need to be provided explicitly. Bottom‐up testing is applied for testing methods of the safety‐critical Java classes, whereas top‐down testing is applied for testing global properties, such as protocols, memory management, and real‐time properties, including scheduling. The tests are executed using a simplified version of JUnit, which makes the test suite executable on resource‐constrained platforms. Copyright © 2017 John Wiley & Sons, Ltd.
Characterization of Protein Content Present in Exosomes Isolated from Conditioned Media and Urine
Authors: Sinha Ankit , Alfaro Javier , Kislinger Thomas 
Published: February 2017

AbstractCells secrete biomolecules into the extracellular space as a way of intercellular communication. Secreted proteins can act as ligands that engage specific receptors—on the same cell, nearby cells, or distant cells—and induce defined signaling pathways. Proteins and other biomolecules can also be packaged as cargo molecules within vesicles that are released to the extracellular space (termed extracellular vesicles or EVs). A subclass of such EVs, exosomes have been shown to horizontally transfer information. In recent years, exosomes have sparked tremendous interest in biological research, both for the discovery of novel biomarkers and for the identification of signaling molecules, as part of their cargo. Although multiple methods have been described for the isolation of exosomes, described here is a simple differential centrifugation approach that is well suited for the isolation of exosomes from conditioned cell culture media and urine. Mass spectrometry provides an ideal method to comprehensively analyze the protein cargo of exosomes. © 2017 by John Wiley & Sons, Inc.
Reprogramming of Pancreatic Acinar Cells to Functional Beta Cells by In Vivo Transduction of a Polycistronic Construct Containing Pdx1, Ngn3, MafA in Mice
Authors: Cavelti‐Weder C. , Zumsteg A. , Li W. , Zhou Q. 
Published: February 2017

AbstractTo generate new beta cells after birth is a key focus of regenerative medicine, which could greatly aid the major health burden of diabetes. Beta‐cell regeneration has been described using four different approaches: (1) the development of beta cells from putative precursor cells of the adult pancreas, which is termed neogenesis, (2) replication of existing beta cells, (3) differentiation from embryonic or induced pluripotent stem cells, and (4) reprogramming of non‐beta cells to beta cells. Studies from the authors’ laboratory have shown that beta‐cell reprogramming can be achieved by transduction of adult pancreatic tissues with viral constructs containing the three developmentally important transcription factors Pdx1, Ngn3, and MafA. This protocol outlines the generation of a polycistronic construct containing the three transcription factors, the expansion and purification of the polycistronic virus, and in vivo transduction for acinar to beta‐cell reprogramming in adult mice. The ultimate goal is to generate beta‐like cells that resemble as closely as possible endogenous beta cells in phenotype and function for potential translational applications. © 2017 by John Wiley & Sons, Inc.
Magnetic Nanoparticle‐Mediated Gene Delivery to Two‐ and Three‐Dimensional Neural Stem Cell Cultures: Magnet‐Assisted Transfection and Multifection Approaches to Enhance Outcomes
Authors: Pickard Mark R. , Adams Christopher F. , Chari Divya M. 
Published: February 2017

AbstractNeural stem cells (NSCs) have high translational potential in transplantation therapies for neural repair. Enhancement of their therapeutic capacity by genetic engineering is an important goal for regenerative neurology. Magnetic nanoparticles (MNPs) are major non‐viral vectors for safe bioengineering of NSCs, offering critical translational benefits over viral vectors, including safety, scalability, and ease of use. This unit describes protocols for the production of suspension (neurosphere) and adherent (monolayer) murine NSC cultures. Genetic engineering of NSCs with MNPs and the application of ‘magnetofection’ (magnetic fields) or ‘multifection’ (repeat transfection) approaches to enhance gene delivery are described. Magnetofection of monolayer cultures achieves optimal transfection, but neurospheres offer key advantages for neural graft survival post‐transplantation. A protocol is presented which allows the advantageous features of each approach to be combined into a single procedure for transplantation. The adaptation of these protocols for other MNP preparations is considered, with emphasis on the evaluation of procedural safety. © 2017 by John Wiley & Sons, Inc.
Utility of computed diffusion‐weighted MRI for predicting aggressiveness of prostate cancer
Authors: Waseda Yuma , Yoshida Soichiro , Takahara Taro , Kwee Thomas Christian , Matsuoka Yoh , Saito Kazutaka , Kihara Kazunori , Fujii Yasuhisa 
Published: February 2017

PurposeTo investigate the value of computed (c) diffusion‐weighted imaging (DWI) in assessing prostate cancer aggressiveness.Materials and MethodsFifty‐five patients with peripheral zone prostate cancer who underwent prebiopsy 1.5T magnetic resonance imaging (including native DWI at b‐values of 0 and 1000 s/mm2) were included. cDWI signal intensities of peripheral zone prostate cancer and nonmalignant prostate tissue were measured. Association between changes in monoexponentially calculated cDWI signals according to different b‐values and primary Gleason grades were assessed.ResultsThe cDWI signal intensity of prostate cancer was lower at b = 0 s/mm2 and higher at b = 1000 s/mm2 compared to nonmalignant prostate tissue. The b‐value at which the signal intensities of prostate cancer and nonmalignant prostate tissue were equal was defined as the “iso‐b‐value.” On multivariate analysis, only the iso‐b‐value was a significant predictor of primary Gleason grade 4/5 cancer (P = 0.001). The area under the curve (AUC) of the iso‐b‐value for diagnosing primary Gleason grade 4/5 cancer was 0.94, and significantly higher than that of the tumor apparent diffusion coefficient (ADC) value with an AUC of 0.68 (P < 0.001).ConclusioncDWI with iso‐b‐value‐based semiquantitative analysis was found to be useful for predicting the aggressiveness of prostate cancer and may potentially outperform tumor ADC measurements in this setting.Level of Evidence: 3Technical Efficacy: Stage 2J. MAGN. RESON. IMAGING 2017;46:490–496
Axonal sprouting in commissurally projecting parvalbumin‐expressing interneurons
Authors: Christenson Wick Zoé , Leintz Caara H. , Xamonthiene Casey , Huang Bin H. , Krook‐Magnuson Esther 
Published: February 2017

AbstractPrevious research has shown that in vivo on‐demand optogenetic stimulation of inhibitory interneurons expressing parvalbumin (PV) is sufficient to suppress seizures in a mouse model of temporal lobe epilepsy (TLE). Surprisingly, this intervention was capable of suppressing seizures when PV‐expressing interneurons were stimulated ipsilateral or contralateral to the presumed seizure focus, raising the possibility of commissural inhibition in TLE. There are mixed reports regarding commissural PV interneuron projections in the healthy hippocampus, and it was previously unknown whether these connections would be maintained or modified following the network reorganization associated with TLE. Using retrograde labeling and viral vector technology in both sexes and the intrahippocampal kainate mouse model of TLE, we therefore examined these issues. Our results reveal that healthy controls possess a population of commissurally projecting hippocampal PV interneurons. Two weeks post kainate injection, we observed a slight, but not statistically significant decrease in retrogradely labeled PV interneurons in the hippocampus contralateral to kainate and tracer injection. By 6 months post kainate, however, there was a significant increase in retrogradely labeled PV interneurons, suggesting commissural inhibitory axonal sprouting. Using viral green fluorescent protein expression selectively in PV neurons, we demonstrated sprouting of commissural PV projections in the dentate gyrus of the kainate‐injected hippocampus 6 months post kainate. These findings indicate that PV interneurons supply direct inhibition to the contralateral hippocampus and undergo sprouting in a mouse model of TLE. © 2017 Wiley Periodicals, Inc.
Addressing wild turkey population declines using structured decision making
Authors: Robinson Kelly F. , Fuller Angela K. , Schiavone Michael V. , Swift Bryan L. , Diefenbach Duane R. , Siemer William F. , Decker Daniel J. 
Published: February 2017

ABSTRACTWe present a case study from New York, USA, of the use of structured decision making (SDM) to identify fall turkey harvest regulations that best meet stakeholder objectives, in light of recent apparent declines in abundance of wild turkeys in the northeastern United States. We used the SDM framework to incorporate the multiple objectives associated with turkey hunting, stakeholder desires, and region‐specific ecological and environmental factors that could influence fall harvest. We identified a set of 4 fall harvest regulations, composed of different season lengths and bag limits, and evaluated their relative achievement of the objectives. We used a stochastic turkey population model, statistical modeling, and expert elicitation to evaluate the consequences of each harvest regulation on each of the objectives. We conducted a statewide mail survey of fall turkey hunters in New York to gather the necessary information to evaluate tradeoffs among multiple objectives associated with hunter satisfaction. The optimal fall harvest regulation was a 2‐week season and allowed for the harvest of 1 bird/hunter. This regulation was the most conservative of those evaluated, reflecting the concerns about recent declines in turkey abundance among agency wildlife biologists and the hunting public. Depending on the region of the state, the 2‐week, 1‐bird regulation was predicted to result in 7–32% more turkeys on the landscape after 5 years. The SDM process provided a transparent framework for setting fall turkey harvest regulations and reduced potential stakeholder conflict by explicitly taking the multiple objectives of different stakeholder groups into account. © 2017 The Wildlife Society.
Spectral characteristics of semisolid protons in human brain white matter at 7 T
Authors: Jiang Xu , van Gelderen Peter , Duyn Jeff H. 
Published: February 2017

PurposeTo inform the quantification of MRI magnetization transfer contrast at high field by measuring the spectral characteristics of 1H protons in semisolids in human brain at 7 T, while avoiding prohibitive radiofrequency (RF) tissue heating and confounding effects from chemical exchange.MethodsSaturation‐recovery type experiments were performed using brief, frequency‐specific RF pulses that saturate semisolid proton magnetization. Analysis of the subsequent recovery of water proton magnetization with a two‐pool model of exchange allowed the study of spectral characteristics of semisolid protons.ResultsWe show that in white matter, the semisolid proton spectrum can be approximated with a symmetric, super‐Lorentzian line at −2.58 ± 0.05 ppm from the water resonance and an average transverse relaxation time constant (T2) of 9.6 ± 0.6 μs.ConclusionsThese results are consistent with studies at lower field that have indicated a major contribution from methylene protons to magnetization transfer contrast, and will facilitate the design and quantification of magnetization transfer studies at 7 T. Magn Reson Med 78:1950–1958, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Structural, thermodynamic, and phosphatidylinositol 3‐phosphate binding properties of Phafin2
Authors: Tang Tuo‐Xian , Jo Ami , Deng Jingren , Ellena Jeffrey F. , Lazar Iulia M. , Davis Richey M. , Capelluto Daniel G. S. 
Published: February 2017

AbstractPhafin2 is a phosphatidylinositol 3‐phosphate (PtdIns(3)P) binding protein involved in the regulation of endosomal cargo trafficking and lysosomal induction of autophagy. Binding of Phafin2 to PtdIns(3)P is mediated by both its PH and FYVE domains. However, there are no studies on the structural basis, conformational stability, and lipid interactions of Phafin2 to better understand how this protein participates in signaling at the surface of endomembrane compartments. Here, we show that human Phafin2 is a moderately elongated monomer of ∼28 kDa with an intensity‐average hydrodynamic diameter of ∼7 nm. Circular dichroism (CD) analysis indicates that Phafin2 exhibits an α/β structure and predicts ∼40% random coil content in the protein. Heteronuclear NMR data indicates that a unique conformation of Phafin2 is present in solution and dispersion of resonances suggests that the protein exhibits random coiled regions, in agreement with the CD data. Phafin2 is stable, displaying a melting temperature of 48.4°C. The folding‐unfolding curves, obtained using urea‐ and guanidine hydrochloride‐mediated denaturation, indicate that Phafin2 undergoes a two‐state native‐to‐denatured transition. Analysis of these transitions shows that the free energy change for urea‐ and guanidine hydrochloride‐induced Phafin2 denaturation in water is ∼4 kcal mol−1. PtdIns(3)P binding to Phafin2 occurs with high affinity, triggering minor conformational changes in the protein. Taken together, these studies represent a platform for establishing the structural basis of Phafin2 molecular interactions and the role of the two potentially redundant PtdIns(3)P‐binding domains of the protein in endomembrane compartments.
Interactions of glyphosate use with farm characteristics and cropping patterns in Central Europe
Authors: Wiese Armin , Schulte Michael , Theuvsen Ludwig , Steinmann Horst‐Henning 
Published: February 2017

AbstractBACKGROUNDAlthough glyphosate is the most widely used herbicide in the European Union, little is known about the patterns of its usage in arable farming. Therefore, a nationwide survey of 2026 German farmers was analysed to obtain further knowledge about glyphosate applications in conventional European arable farming. Given its broad range of agri‐environmental and farm‐type conditions, Germany can be regarded as a suitable study region to represent Central European farming. The growing season 2013/2014 was set as a reference.RESULTSFarmers who participated in the survey employ diverse patterns of glyphosate use. While 23% stated that they did not use glyphosate in the season in question, others applied glyphosate to their total arable area. However, most applications occurred on specific parts of the farm. Application patterns of oilseed rape, winter wheat, maize and sugar beet were studied in detail, and U‐shaped distributions of glyphosate use intensity were observed. The effects of farm type and management practices on glyphosate use patterns were mixed in the various crops.CONCLUSIONMotivation for glyphosate use differs widely within the farming community. Agricultural researchers, extension services and policy makers are recommended to mitigate vulnerabilities associated with glyphosate use, such as routine spraying and practices that increase selection pressure for the evolution of glyphosate‐resistant weeds. © 2017 Society of Chemical Industry
Impaired maternal hemodynamics in morbidly obese women: a case–control study
Authors: Vinayagam D. , Gutierrez J. , Binder J. , Mantovani E. , Thilaganathan B. , Khalil A. 
Published: February 2017

ABSTRACTObjectiveMaternal obesity is associated with significant pregnancy complications and is a risk factor for the development of hypertensive disorders of pregnancy as well as other adverse outcomes. There are few data regarding the hemodynamic aberrations observed in maternal obesity. The aim of this study was to investigate maternal hemodynamics in morbidly obese women.MethodsThis was a prospective, case–control study of morbidly obese women (body mass index (BMI) ≥ 40 kg/m2) and controls (BMI 20–29.9 kg/m2). The control population was matched for maternal age and gestational age. BMI was calculated based on maternal height and weight at the time of recruitment to the study, which occurred on the same day as the hemodynamic assessment. Pregnant women in the second or third trimester of pregnancy were included. Women who were found to be hypertensive at any time were excluded from the study. A USCOM‐1A® device was used to assess hemodynamic parameters (heart rate, stroke volume (SV), cardiac output and systemic vascular resistance (SVR)). The parameters were corrected for body surface area (BSA) to provide the SV index (SVI), cardiac index (CI) and SVR index (SVRI). Mann–Whitney U‐test was used to compare the medians of the hemodynamic variables between the two groups.ResultsIn total, 23 morbidly obese women and 327 controls were included in the analysis. There was no difference in maternal (P = 0.506) or gestational (P = 0.693) age at recruitment between the groups. Mean arterial pressure was higher both at pregnancy booking (90 vs 80 mmHg, P < 0.001) and study recruitment (91 vs 85 mmHg, P < 0.001) in the obese group compared with the controls. Heart rate was higher in the obese group (P = 0.003), but there was no difference in SV (P = 0.271), cardiac output (P = 0.238) or SVR (P = 0.635). Following correction of these parameters for BSA, compared with the control group, SVI (34 vs 45 mL/m2, P < 0.001) and CI (2.96 vs 3.64 L/min/m2, P < 0.001) were significantly reduced in the obese group, whereas SVRI was significantly higher (2354 vs 1840 dynes × s/cm5, P < 0.001).ConclusionsThe findings of our study suggest that cardiac function is significantly altered in morbidly obese pregnant women. In order to make appropriate comparisons between individuals, it is imperative that hemodynamic parameters are indexed for BSA, as is standard practice in pediatric cardiology. The novel finding of reduced CI in morbidly obese pregnant women may explain the predisposition to pre‐eclampsia and other adverse outcomes in this population and warrants further investigation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
The 3-Sweep Approach: A Standardized Technique for Fetal Anatomic Assessment in the Limited Resource Setting
Authors: Abu-Rustum Reem S. , Ziade M. Fouad 
Published: February 2017

AbstractThis retrospective study aims to describe a standardized screening technique “the 3-sweep approach” for fetal anatomic assessment in the outreach setting. The study was carried out on 1396 pregnant women referred for an obstetric ultrasound for pregnancy dating and detection of abnormalities in a limited resource setting in Lebanon. All pregnancies were scanned utilizing a previously described standardized 6-step approach and the 3-sweep approach for fetal anatomic assessment. The first sweep examines the fetal head and face, the second examines the spine, and the third examines the chest, abdomen, and pelvis. Positive findings were referred for a detailed ultrasound examination at a referral center. There were a total of 1157 women, at >14 weeks gestation, included in the study. The median gestational age was 24 weeks 4 days (14 weeks 0 day–41 weeks 1 day). The 3-sweep approach was completed in all pregnancies with a total time of under 1 min. A total of 33/1157 (2.9%) fetuses had structural abnormalities detected. Confirmation of the 3-sweep findings was made by comprehensive imaging at a referral center (8/33 = 24.2%) or thorough review of 3-sweep images (25/33 = 75.8%). We found the 3-sweep approach to be an effective mode of screening for structural fetal abnormalities. Though it requires skill in probe manipulation and knowledge of fetal anatomy, its incorporation into routine evaluation in the outreach setting will help identify at-risk fetuses. Depending on the available facilities, this may facilitate proper referral and management to optimize neonatal outcomes and minimize maternal risks. Based on our experience, it is a time-efficient and complementary technique to the 6-step approach.
Creating the competitive edge: A new relationship between operations management and industrial policy
Authors: Spring Martin , Hughes Alan , Mason Katy , McCaffrey Paul 
Published: February 2017

AbstractPolicy interventions by governments to alter the structure of economic activity have either been dismissed or ignored by operations management (OM) scholars. However, in recent years, such ‘industrial policy’ measures have gained increasing support in developed economies, particularly in relation to manufacturing. This paper argues that contemporary manufacturing in high‐cost economies is rooted in technological innovation. As such, it can be enhanced by industrial policy interventions that prevent systems failures in the process of turning technological innovation into commercially viable products. In particular, we argue that this can be achieved by establishing non‐firm, intermediate research organizations and by other measures to change the institutional architecture of an economy. We disagree with claims in earlier OM literature that industrial policy is all but irrelevant to manufacturing firms and to OM. Instead, we argue that OM must broaden its conceptual scope so as to encompass active engagement with non‐firm network participants such as government‐supported intermediate research organizations, and that, as well as learning to be effective users of industrial policy, OM practitioners and academics should engage actively in the development of industrial policy. In this way, high‐value, high‐productivity manufacturing can be viable in high‐cost economic environments.
Solutions of elliptic equations with indefinite nonlinearities via Morse theory and linking
Authors: Del Pino Manuel , Alama Stanley 
Published: February 2017

We consider the Dirichlet problem for the equation

−∆u = λu + h(x)f(u)

, with

h

changing sign. In particular, we study existence of nontrivial solutions in the case where

f

has superlinear growth, but is not assumed to be odd. Two different approaches are used: one involving Morse theory and one using min-max methods.

Résumé

Nous étudions le problème de Dirichlet pour l’équation

−∆u = λu + h(x)f(u)

, où

h

est une fonction qui change de signe. En particulier, nous établissons l’existence de solutions non triviales quand

f

est surlinéaire, mais pas nécessairement impair. Nous nous servons de deux approches différentes, l’une basée sur la théorie de Morse, et l’autre sur les méthodes d’enlacement.