bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proline‐Rich Tyrosine Kinase 2 Downregulates Peroxisome Proliferator–Activated Receptor Gamma to Promote Hypoxia‐Induced Pulmonary Artery Smooth Muscle Cell Proliferation
Authors: Bijli Kaiser M. , Kang Bum‐Yong , Sutliff Roy L. , Hart C. Michael 
Published: February 2016

Hypoxia stimulates pulmonary hypertension (PH), in part by increasing the proliferation of human pulmonary artery smooth muscle cells (HPASMCs) via sustained activation of mitogen‐activated protein kinase, extracellular signal–regulated kinases 1 and 2 (ERK 1/2), and nuclear factor‐kappa B (NF‐κB); elevated expression of NADPH oxidase 4 (Nox4); and downregulation of peroxisome proliferator–activated receptor gamma (PPARγ) levels. However, the upstream mediators that control these responses remain largely unknown. We hypothesized that proline‐rich tyrosine kinase 2 (Pyk2) plays a critical role in the mechanism of hypoxia‐induced HPASMC proliferation. To test this hypothesis, HPASMCs were exposed to normoxia or hypoxia (1% O2) for 72 hours. Hypoxia activated Pyk2 (detected as Tyr402 phosphorylation), and inhibition of Pyk2 with small interfering RNA (siRNA) or tyrphostin A9 attenuated hypoxia‐induced HPASMC proliferation. Pyk2 inhibition attenuated ERK 1/2 activation as early as 24 hours after the onset of hypoxia, suggesting a proximal role for Pyk2 in this response. Pyk2 inhibition also attenuated hypoxia‐induced NF‐κB activation, reduced HPASMC PPARγ messenger RNA levels and activity, and increased NF‐κB‐mediated Nox4 levels. The siRNA‐mediated PPARγ knockdown enhanced Pyk2 activation, whereas PPARγ overexpression reduced Pyk2 activation in HPASMCs, confirming a reciprocal relationship between Pyk2 and PPARγ. Pyk2 depletion also attenuated hypoxia‐induced NF‐κB p65 activation and reduced PPARγ protein levels in human pulmonary artery endothelial cells. These in vitro findings suggest that Pyk2 plays a central role in the proliferative phenotype of pulmonary vascular wall cells under hypoxic conditions. Coupled with recent reports that hypoxia‐induced PH is attenuated in Pyk2 knockout mice, these findings suggest that Pyk2 may represent a novel therapeutic target in PH.
Self-assembled 3D-hierarchical structure Cu2ZnSnS4 photocathodes by tuning anion ratios in precursor solution
Authors: Wen Xin , Luo Wenjun , Guan Zhongjie , Shao Hansen , Fu Gao , Zhou Yong , Zou Zhigang 
Published: February 2016

Abstract
Cu2ZnSnS4 (CZTS) is one of the most promising light capture materials for solar cells or solar fuels. Construction of 3D hierarchical structure is very important for efficient optoelectronic devices. It is challenging to directly fabricate 3D hierarchical structure CZTS film by a facile solution method. Herein, we present a one-step sol–gel method for fabrication of CZTS thin films with 3D hierarchical structures. For the first time, it is found that the morphologies of thin films can be adjusted between dense, porous and 3D hierarchical structures by tuning anion ratios of Cl−/Ac− in precursor solution. Further analysis suggests the formation of intermediate phases of SnO2 nanoparticles and SnS2 nanosheets by tuning ratios of Cl−/Ac− in precursor solution, which has important effects on the formation of different nanostructures of CZTS. This study can deepen understanding of anion’ effect on morphologies of samples using a solution method and forms a reference to prepare novel nanostructures of other materials.
Thermally activated tunneling in porous silicon nanowires with embedded Si quantum dots
Authors: Rezvani S J , Pinto N , Enrico E , D’Ortenzi L , Chiodoni A , Boarino L 
Published: February 2016

Abstract
Electronic transport properties of porous Si nanowires either with embedded Si quantum dots or with a percolative crystalline path are studied as a function of the temperature for the first time. We show that unlike bulk porous Si, the predesigned structure of the wires results in a single distinct conduction mechanism such as tunneling in the former case and variable range hopping in the latter case. We demonstrate that the geometry of the systems with a large internal surface area and high density of the Si quantum dots have a significant conduction enhancement compared to bulk porous silicon. These results can also improve the understanding of the basis of the different electronic transport mechanisms reported in bulk porous silicon.
Modelling cathode spots in glow discharges in the cathode boundary layer geometry
Authors: Bieniek M S , Almeida P G C , Benilov M S 
Published: February 2016

Abstract
Self-organized patterns of cathode spots in glow discharges are computed in the cathode boundary layer geometry, which is the one employed in most of the experiments reported in the literature. The model comprises conservation and transport equations of electrons and a single ion species, written in the drift-diffusion and local-field approximations, and Poisson’s equation. Multiple solutions existing for the same value of the discharge current and describing modes with different configurations of cathode spots are computed by means of a stationary solver. The computed solutions are compared to their counterparts for plane-parallel electrodes, and experiments. All of the computed spot patterns have been observed in the experiment.
Reply to Comment on ‘Molecular structure-dependent deformations in boron nitride nanostructures subject to an electrical field’
Authors: Zhang Jin , Wang Chengyuan , Adhikari Sondipon 
Published: February 2016

Abstract
A large scattering of effective atomic charge distribution was found in the literature for hexagonal boron nitride nanostructures (BNNSs). In our paper (Zhang J, Wang C Y and Sondipon A 2013 J. Phys. D: Appl. Phys. 46 235303) ‘±3e’ was chosen as a rough approximation for the effective atomic charge in BNNSs as it gave the piezoelectric coefficient of BNNSs close to the values in the literature.
Effects of flowering phenology and synchrony on the reproductive success of a long-flowering shrub
Authors: Rodríguez-Pérez Javier , Traveset Anna 
Published: February 2016

AbstractFlowering phenology and synchrony with biotic and abiotic resources are crucial traits determining the reproductive success in insect-pollinated plants. In seasonal climates, plants flowering for long periods should assure reproductive success when resources are more predictable. In this work, we evaluated the relationship between flowering phenology and synchrony and reproductive success in Hypericum balearicum , a shrub flowering all year round but mainly during spring and summer. We studied two contrasting localities (differing mostly in rainfall) during 3 years, and at different biological scales spanning from localities to individual flowers and fruits. We first monitored (monthly) flowering phenology and reproductive success (fruit and seed set) of plants, and assessed whether in the locality with higher rainfall plants had longer flowering phenology and synchrony and relatively higher reproductive success within or outside the flowering peak. Secondly, we censused pollinators on H. balearicum individuals and measured reproductive success along the flowering peak of each locality to test for an association between (i) richness and abundance of pollinators and (ii) fruit and seed set, and seed weight. We found that most flowers (∼90 %) and the highest fruit set (∼70 %) were produced during the flowering peak of each locality. Contrary to expectations, plants in the locality with lower rainfall showed more relaxed flowering phenology and synchrony and set more fruits outside the flowering peak. During the flowering peak of each locality, the reproductive success of early-flowering individuals depended on a combination of both pollinator richness and abundance and rainfall; by contrast, reproductive success of late-flowering individuals was most dependent on rainfall. Plant species flowering for long periods in seasonal climates, thus, appear to be ideal organisms to understand how flowering phenology and synchrony match with biotic and abiotic resources, and how this ultimately influences plant reproductive success.
Interloper bias in future large-scale structure surveys
Authors: Pullen Anthony R. , Hirata Christopher M. , Doré Olivier , Raccanelli Alvise 
Published: February 2016

Abstract
Next-generation spectroscopic surveys will map the large-scale structure of the observable universe, using emission line galaxies as tracers. While each survey will map the sky with a specific emission line, interloping emission lines can masquerade as the survey's intended emission line at different redshifts. Interloping lines from galaxies that are not removed can contaminate the power spectrum measurement, mixing correlations from various redshifts and diluting the true signal. We assess the potential for power spectrum contamination, finding that an interloper fraction worse than 0.2% could bias power spectrum measurements for future surveys by more than 10% of statistical errors, while also biasing power spectrum inferences. We also construct a formalism for predicting cosmological parameter measurement bias, demonstrating that a 0.15%–0.3% interloper fraction could bias the growth rate by more than 10% of the error, which can affect constraints on gravity from upcoming surveys. We use the COSMOS Mock Catalog (CMC), with the emission lines rescaled to better reproduce recent data, to predict potential interloper fractions for the Prime Focus Spectrograph (PFS) and the Wide-Field InfraRed Survey Telescope (WFIRST). We find that secondary line identification, or confirming galaxy redshifts by finding correlated emission lines, can remove interlopers for PFS. For WFIRST, we use the CMC to predict that the 0.2% target can be reached for the WFIRST Hα survey, but sensitive optical and near-infrared photometry will be required. For the WFIRST [O iii] survey, the predicted interloper fractions reach several percent and their effects will have to be estimated and removed statistically (e.g., with deep training samples). These results are optimistic as the CMC does not capture the full set of correlations of galaxy properties in the real Universe, and they do not include blending effects. Mitigating interloper contamination will be crucial to the next generation of emission line surveys.
Unexpected superoutburst and rebrightening of AL Comae Berenices in 2015
Authors: Kimura Mariko , Kato Taichi , Imada Akira , Ikuta Kai , Isogai Keisuke , Dubovsky Pavol A. , Kiyota Seiichiro , Pickard Roger D. , Miller Ian , Pavlenko Elena P. , Sosnovskij Aleksei A. , Dvorak Shawn , Nogami Daisaku 
Published: February 2016

AbstractIn 2015 March, the notable WZ Sge-type dwarf nova AL Com exhibited an unusual outburst with a recurrence time of ∼ 1.5 yr, which is the shortest interval of superoutbursts among WZ Sge-type dwarf novae. Early superhumps in the superoutburst light curve were absent, and a precursor was observed at the onset of the superoutburst for the first time in WZ Sge-type dwarf novae. The present superoutburst can be interpreted as a result of the condition that the disk radius barely reached the 3:1 resonance radius, but did not reach the 2:1 resonance one. Ordinary superhumps immediately grew following the precursor. The initial part of the outburst is indistinguishable from those of superoutbursts of ordinary SU UMa-type dwarf novae. This observation supports the interpretation that the 2:1 resonance suppresses a growth of ordinary superhumps. The estimated superhump period and superhump period derivative are Psh = 0.0573185(11) d and Pdot = +1.5(3.1) × 10−5, respectively. These values indicate that the evolution of ordinary superhumps is the same as that in past superoutbursts with much larger extent. Although the light curve during the plateau stage was typical for an SU UMa-type dwarf nova, this superoutburst showed a rebrightening, together with a regrowth of the superhumps. The overall light curve of the rebrightening was the almost the same as those observed in previous rebrightenings. This implies that the rebrightening type is inherent in the system.
Getting (Along) With the Guidelines: Reconciling Patient Autonomy and Quality Improvement Through Shared Decision Making
Authors: Xu Yan , Wells Philip S. 
Published: February 2016

In past decades, stark differences in practice pattern, cost, and outcomes of care across regions with similar health demographics have prompted calls for reform. As health systems answer the growing call for accountability in the form of quality indices, while responding to increased scrutiny on practice variation in the form of pay for performance (P4P), a rift is widening between the system and individual patients. Currently, three areas are inadequately considered by P4P structures based largely on physician adherence to guidelines: diversity of patient values and preferences; time and financial burden of therapy in the context of multimorbidity; and narrow focus on quantitative measures that distract clinicians from providing optimal care. As health care reform efforts place greater emphasis on value-for-money of care delivered, they provide an opportunity to consider the other “value”—the values of each patient and care delivery that aligns with them.
The inherent balance of risks and benefits in every treatment, especially those involving chronic conditions, calls for engagement of patients in decision-making processes, recognizing the diversity of preferences at the individual level. Shared decision making (SDM) is an attractive option and should be an essential component of quality health care rather than its adjunct. Four interwoven steps toward the meaningful implementation of SDM in clinical practice—embedding SDM as a health care quality measure, “real-world” evaluation of SDM effectiveness, pursuit of an SDM-favorable health system, and patient-centered medical education—are proposed to bring focus back to the beneficiary of health care accountability, the patient.
Equitable Imagery in the Preclinical Medical School Curriculum: Findings From One Medical School
Authors: Martin Glenna C. , Kirgis Julianne , Sid Eric , Sabin Janice A. 
Published: February 2016

Purpose
The unequal representation of women and people of color compared with men and whites in medical school textbooks has been well documented, as have health care inequities, and biases—both overt and implicit—by health care providers and in access to care. The authors investigated whether this bias exists in PowerPoint slides used in didactic material for preclinical students at one medical school.

Method
The authors analyzed 747 “decks” of slides from 33 preclinical courses in the medical school curriculum at the University of Washington School of Medicine in the years spanning 2009 to 2011. The authors coded the human images into various sex- and race-specific classifications and evaluated the distribution of images into these categories.

Results
Of the 4,033 images that could be coded by sex, 39.6% (1,595) were female and 60.5% (2,438) were male. Of the 5,230 images that could be coded by race/ethnicity, 78.4% (4,100) were white and 21.6% (1,130) were persons of color. Thus, images of whites and males predominated.

Conclusions
The proportion of images used in didactic courses at one school of medicine is not representative of the U.S. population in terms of race or sex. The authors discuss the potential sources and impact of this bias, make a case for sex and race diversity in didactic imagery, and propose possible avenues for further research and curricular reform in an era when the population is becoming increasingly racially and ethnically diverse.
ISSLS Prize Winner: Consensus on the Clinical Diagnosis of Lumbar Spinal Stenosis
Authors: Tomkins-Lane Christy , Melloh Markus , Lurie Jon , Smuck Matt , Battié Michele C. , Freeman Brian , Samartzis Dino , Hu Richard , Barz Thomas , Stuber Kent , Schneider Michael , Haig Andrew , Schizas Constantin , Cheung Jason Pui Yin , Mannion Anne F. , Staub Lukas , Comer Christine , Macedo Luciana , Ahn Sang-ho , Takahashi Kazuhisa , Sandella Danielle 
Published: February 2016

Study Design.
Delphi.

Objective.
The aim of this study was to obtain an expert consensus on which history factors are most important in the clinical diagnosis of lumbar spinal stenosis (LSS).

Summary of Background Data.
LSS is a poorly defined clinical syndrome. Criteria for defining LSS are needed and should be informed by the experience of expert clinicians.

Methods.
Phase 1 (Delphi Items): 20 members of the International Taskforce on the Diagnosis and Management of LSS confirmed a list of 14 history items. An online survey was developed that permits specialists to express the logical order in which they consider the items, and the level of certainty ascertained from the questions. Phase 2 (Delphi Study) Round 1: Survey distributed to members of the International Society for the Study of the Lumbar Spine. Round 2: Meeting of 9 members of Taskforce where consensus was reached on a final list of 10 items. Round 3: Final survey was distributed internationally. Phase 3: Final Taskforce consensus meeting.

Results.
A total of 279 clinicians from 29 different countries, with a mean of 19 (±SD: 12) years in practice participated. The six top items were “leg or buttock pain while walking,” “flex forward to relieve symptoms,” “feel relief when using a shopping cart or bicycle,” “motor or sensory disturbance while walking,” “normal and symmetric foot pulses,” “lower extremity weakness,” and “low back pain.” Significant change in certainty ceased after six questions at 80% (P < .05).

Conclusion.
This is the first study to reach an international consensus on the clinical diagnosis of LSS, and suggests that within six questions clinicians are 80% certain of diagnosis. We propose a consensus-based set of “seven history items” that can act as a pragmatic criterion for defining LSS in both clinical and research settings, which in the long term may lead to more cost-effective treatment, improved health care utilization, and enhanced patient outcomes.

Level of Evidence: 2
Gadobutrol-Enhanced Magnetic Resonance Imaging of the Breast in the Preoperative Setting
Authors: Sardanelli Francesco , Newstead Gillian M. , Putz Barbara , Jirakova Trnkova Zuzana , Trimboli Rubina M. , Abe Hiroyuki , Haverstock Daniel , Rosenberg Martin 
Published: February 2016

Objectives
The aim of this study was to evaluate the diagnostic efficacy of gadobutrol enhanced preoperative breast magnetic resonance imaging (MRI) in 2 prospective studies.

Materials and Methods
Approval of ethics committees and informed consent from patients were obtained. Both Gadobutrol-Enhanced MR Mammography (GEMMA) trials followed a standardized protocol using 1.5 T scanners. After unenhanced scans, patients received 0.1 mmol/kg of gadobutrol for the dynamic study. Six independent blinded readers, 3 for GEMMA1 and 3 for GEMMA2, assessed unenhanced images and, 2 or more weeks apart, contrast-enhanced plus unenhanced breast MRI images (CE-BMRI), using a standard 5-region scheme. Another 6 independent readers (3 for each study) evaluated mammograms alone. Sensitivity was calculated taking into account the identification of regions harboring malignancies (within-patient sensitivity), whereas specificity was based on cancer-free breasts. The first patient from each center was used for site qualification and blinded reader training and excluded from the efficacy analyses. Reference standard was pathology for regions harboring malignancy and a combination of negative pathology, mammography, and ultrasound for cancer-free regions.

Results
Of 906 breast cancer patients enrolled in 13 countries in the 2 studies, 865 received gadobutrol and 787 were evaluated for diagnostic performance (390 in GEMMA1 and 397 in GEMMA2). Within-patient sensitivity, that is, the detection rate of malignant disease extent per patient, ranged from 80% to 89% for CE-BMRI and was significantly superior to unenhanced breast MRI alone (37%–73%) and to mammography alone (68%–73%) for all readers in both trials. Specifity of the CE-BMRI ranged from 83% to 95%.

Conclusion
In a very large multicenter preoperative setting, gadobutrol-enhanced breast MRI demonstrated high levels of sensitivity and specificity, consistent with published data on breast MRI.
Application of new informatics tools for identifying allosteric lead ligands of the c-Src kinase
Authors: Peng Lili X. , Lawrenz Morgan , Shukla Diwakar , Tang Grace W. , Pande Vijay S. , Altman Russ B. 
Published: February 2016

ABSTRACTRecent molecular dynamics (MD) simulations of the catalytic domain of the c-Src kinase revealed intermediate conformations with a potentially druggable allosteric pocket adjacent to the C-helix, bound by 8-anilino-1-naphthalene sulfonate. Towards confirming the existence of this pocket, we have developed a novel lead enrichment protocol using new target and lead enrichment software to identify sixteen allosteric lead ligands of the c-Src kinase. First, Markov State Models analysis was used to identify the most statistically significant c-Src target conformations from all MD-simulated conformations. The most statistically relevant candidate MSM targets were then prioritized by assessing how well each reproduced binding poses of ligands specific to the ATP-competitive and allosteric pockets. The top-performing MSM targets, identified by receiver-operating curve analysis, were then used to screen the ZINC library of 13 million ‘clean, drug-like’’ ligands, all of which prioritized based on their empirical scoring function, binding pose consistency across MSM targets, and strong hydrogen bonding and hydrophobic interactions with Src residues. The FragFEATURE knowledgebase of fragment-protein pocket interactions was then used to identify fragments specific to the ATP-competitive and allosteric pockets. This information was used to identify seven Type II and nine Type III lead ligands with binding poses supported by fragment predictions. Of these, Type II lead ligands, ZINC13037947 and ZINC09672647, and Type III lead ligands, ZINC12530852 and ZINC30012975, exhibited the most favorable fragment profiles and are recommended for further experimental testing for the existence of the allosteric pocket in Src.