bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-1/PD-L1 Blockade Enhances T-cell Activity and Antitumor Efficacy of Imatinib in Gastrointestinal Stromal Tumors
Authors: Seifert Adrian M. , Zeng Shan , Zhang Jennifer Q. , Kim Teresa S. , Cohen Noah A. , Beckman Michael J. , Medina Benjamin D. , Maltbaek Joanna H. , Loo Jennifer K. , Crawley Megan H. , Rossi Ferdinand , Besmer Peter , Antonescu Cristina R. , DeMatteo Ronald P. 
Published: July 2016

Abstract
Purpose: Tyrosine kinase inhibitors are effective in gastrointestinal stromal tumors (GISTs) but often are of transient benefit as resistance commonly develops. Immunotherapy, particularly blockade of the inhibitory receptor programmed death 1 (PD-1) or the ligand programmed death ligand 1 (PD-L1), has shown effectiveness in a variety of cancers. The functional effects of PD-1/PD-L1 blockade are unknown in GISTs.
Experimental Design: We analyzed tumor and matched blood samples from 85 patients with GISTs and determined the expression of immune checkpoint molecules using flow cytometry. We investigated the combination of imatinib with PD-1/PD-L1 blockade in KitV558Δ/+ mice that develop GISTs.
Results: The inhibitory receptors PD-1, lymphocyte activation gene 3, and T-cell immunoglobulin mucin-3 were upregulated on tumor-infiltrating T cells compared with T cells from matched blood. PD-1 expression on T cells was highest in imatinib-treated human GISTs. Meanwhile, intratumoral PD-L1 expression was variable. In human GIST cell lines, treatment with imatinib abrogated the IFNγ-induced upregulation of PD-L1 via STAT1 inhibition. In KitV558Δ/+ mice, imatinib downregulated IFNγ-related genes and reduced PD-L1 expression on tumor cells. PD-1 and PD-L1 blockade in vivo each had no efficacy alone but enhanced the antitumor effects of imatinib by increasing T-cell effector function in the presence of KIT and IDO inhibition.
Conclusions: PD-1/PD-L1 blockade is a promising strategy to improve the effects of targeted therapy in GISTs. Collectively, our results provide the rationale to combine these agents in human GISTs. Clin Cancer Res; 23(2); 454–65. ©2016 AACR.
PD-1 Axis Inhibitors in EGFR- and ALK-Driven Lung Cancer: Lost Cause?
Authors: Gettinger Scott , Politi Katerina 
Published: July 2016

Abstract
Programmed death axis 1 (PD-1) inhibitors have ushered in a new error of cancer immunotherapeutics for advanced smoking-associated non–small cell lung cancer. Their role in treating EGFR-mutant and ALK-rearranged lung cancer has yet to be determined. Clin Cancer Res; 22(18); 4539–41. ©2016 AACR.
See related article by Gainor et al., p. 4585
Interaction Between HIV-1 Nef and Calnexin
Authors: Hunegnaw Ruth , Vassylyeva Marina , Dubrovsky Larisa , Pushkarsky Tatiana , Sviridov Dmitri , Anashkina Anastasia A. , Üren Aykut , Brichacek Beda , Vassylyev Dmitry G. , Adzhubei Alexei A. , Bukrinsky Michael 
Published: July 2016

Objective—
HIV-infected patients are at an increased risk of developing atherosclerosis, in part because of downmodulation and functional impairment of ATP-binding cassette A1 (ABCA1) cholesterol transporter by the HIV-1 protein Nef. The mechanism of this effect involves Nef interacting with an ER chaperone calnexin and disrupting calnexin binding to ABCA1, leading to ABCA1 retention in ER, its degradation and resulting suppression of cholesterol efflux. However, molecular details of Nef–calnexin interaction remained unknown, limiting the translational impact of this finding.

Approach and Results—
Here, we used molecular modeling and mutagenesis to characterize Nef–calnexin interaction and to identify small molecule compounds that could block it. We demonstrated that the interaction between Nef and calnexin is direct and can be reconstituted using recombinant proteins in vitro with a binding affinity of 89.1 nmol/L measured by surface plasmon resonance. The cytoplasmic tail of calnexin is essential and sufficient for interaction with Nef, and binds Nef with an affinity of 9.4 nmol/L. Replacing lysine residues in positions 4 and 7 of Nef with alanines abrogates Nef–calnexin interaction, prevents ABCA1 downregulation by Nef, and preserves cholesterol efflux from HIV-infected cells. Through virtual screening of the National Cancer Institute library of compounds, we identified a compound, 1[(7-oxo-7H-benz[de]anthracene-3-yl)amino]anthraquinone, which blocked Nef–calnexin interaction, partially restored ABCA1 activity in HIV-infected cells, and reduced foam cell formation in a culture of HIV-infected macrophages.

Conclusion—
This study identifies potential targets that can be exploited to block the pathogenic effect of HIV infection on cholesterol metabolism and prevent atherosclerosis in HIV-infected subjects.
Incidence of Transient Ischemic Attack in Auckland, New Zealand, in 2011 to 2012
Authors: Barber P. Alan , Krishnamurthi Rita , Parag Varsha , Anderson Neil E. , Ranta Annemarei , Kilfoyle Dean , Wong Edward , Green Geoff , Arroll Bruce , Bennett Derrick A. , Witt Emma , Rush Elaine , Minsun Suh Flora , Theadom Alice , Rathnasabapathy Yogini , Te Ao Braden , Parmar Priyakumari , Feigin Valery L. 
Published: July 2016

Background and Purpose—
There have been few recent population-based studies reporting the incidence (first ever) and attack rates (incident and recurrent) of transient ischemic attack (TIA).

Methods—
The fourth Auckland Regional Community Stroke study (ARCOS IV) used multiple overlapping case ascertainment methods to identify all hospitalized and nonhospitalized cases of TIA that occurred in people ≥16 years of age usually resident in Auckland (population ≥16 years of age is 1.12 million), during the 12 months from March 1, 2011. All first-ever and recurrent new TIAs (any new TIA 28 days after the index event) during the study period were recorded.

Results—
There were 785 people with TIA (402 [51.2%] women, mean [SD] age 71.5 [13.8] years); 614 (78%) of European origin, 84 (11%) Māori/Pacific, and 75 (10%) Asian/Other. The annual incidence of TIA was 40 (95% confidence interval, 36–43), and attack rate was 63 (95% confidence interval, 59–68), per 100 000 people, age standardized to the World Health Organization world population. Approximately two thirds of people were known to be hypertensive or were being treated with blood pressure–lowering agents, half were taking antiplatelet agents and just under half were taking lipid-lowering therapy before the index TIA. Two hundred ten (27%) people were known to have atrial fibrillation at the time of the TIA, of whom only 61 (29%) were taking anticoagulant therapy, suggesting a failure to identify or treat atrial fibrillation.

Conclusions—
This study describes the burden of TIA in an era of aggressive primary and secondary vascular risk factor management. Education programs for medical practitioners and patients around the identification and management of atrial fibrillation are required.
Inhibition of Thrombin-Activatable Fibrinolysis Inhibitor and Plasminogen Activator Inhibitor-1 Reduces Ischemic Brain Damage in Mice
Authors: Denorme Frederik , Wyseure Tine , Peeters Miet , Vandeputte Nele , Gils Ann , Deckmyn Hans , Vanhoorelbeke Karen , Declerck Paul J. , De Meyer Simon F. 
Published: July 2016

Background and Purpose—
Cerebral ischemia and reperfusion is associated with activation of the coagulation cascade and fibrin deposition in cerebral microvessels. Both thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) attenuate fibrinolysis and are therefore attractive targets for the treatment of ischemic stroke.

Methods—
TAFI and PAI-1 were inhibited by monoclonal antibodies in a mouse model of transient middle cerebral artery occlusion. Twenty-four hours after stroke, mice were neurologically scored, cerebral thrombotic burden was assessed, and brain infarct sizes were calculated.

Results—
Inhibition of TAFI or PAI-1 significantly decreased cerebral infarct sizes by 50% 24 hours after stroke. This reduction in cerebral damage was associated with a significant decrease in fibrin(ogen) deposition in the ischemic brain. Concurrently, functional recovery of the animals was improved. Interestingly, combined targeting of TAFI and PAI-1 using low, and by themselves inactive, doses of antibodies improved cerebral blood flow and reduced cerebral fibrin(ogen) deposition and infarct sizes by 50%. When dual treatment was delayed to 1 hour after the start of reperfusion, it still reduced brain injury; however, this was not statistically significant.

Conclusions—
Targeting of PAI-1 and TAFI is protective in an ischemic stroke model by attenuating fibrin(ogen) deposition, thereby improving reperfusion. Combined inhibition has a co-operative effect that could become useful in ischemic stroke therapy.
Terror on Trial
Authors: Steinberg Ronen 
Published: July 2016

AbstractThis article discusses the question of accountability after the Terror through a close analysis of the case of Joseph Le Bon, a public official who was put on trial for his role in the repression. This trial has often been seen as reactionary in essence. In contrast, this article argues that it derived from the democratizing impulses of the French Revolution. The Revolution enshrined accountability as a fundamental principle in the new political order. After the Terror, this gave rise to an unpredictable dilemma: how to hold individuals accountable for a mass crime. The article shows how both the case against Le Bon and his defense were shaped by the same democratizing impulses. In this sense, the Thermidorian struggle with justice was continuous with the Revolution. In making its case, the article relies on the concept of transitional justice.
The Culture of Reaction
Authors: Mason Laura 
Published: July 2016

AbstractReactionary culture helped shape Thermidor's retreat from the ideologies, social policies, and political practices of the Terror. This article explains how it did so by examining the most popular newspaper of the French Revolution's Year III (1794–95), L'orateur du peuple, and editor Stanislas Fréron's appropriation of revolutionary inventiveness to discredit revolutionary activism. Between Robespierre's defeat in July 1794 and the adoption of a new constitution in late summer 1795, Fréron used radical language to condemn first the Terror and then radical republicanism, progressing from attacks on specific legislators to an assault on social welfare, political militancy, and universal suffrage. Elaborating a right-wing ideology that was neither Catholic nor royalist, L'orateur du peuple illuminates the conservative uses of revolutionary political culture. Fréron and the reactionary polemicists among whom he worked forged a virulent reactionary populism in the Year III whose legacy endures today.
Circuits of Practical Knowledge
Authors: Bond Elizabeth Andrews 
Published: July 2016

AbstractLetters to the editor were published in the thousands during the 1770s and 1780s, shaping a forum that constituted an eighteenth-century information network. Such letters serve as a powerful touchstone for ideas that circulated among the French reading public, shedding new light on the cultural history of the Enlightenment. Drawing on world history and digital history approaches, this article analyzes a subset of letters that were exchanged and reprinted among provincial papers (affiches) throughout France. By visualizing the exchange of such reprinted letters as a network, it becomes clear that provincial readers did not read their local papers in isolation but instead were connected to a larger community that often included published missives from the surrounding généralité and the capital. The content of such letters communicated an optimism about the possibility of ameliorating daily life through incremental, practical changes, fostering a notion of a practical Enlightenment.
Beautiful Lemons: Adverse Selection in Durable-Goods Markets with Sorting
Authors: Peterson Jonathan R. , Schneider Henry S. 
Published: July 2016

We document a basic characteristic of adverse selection in secondhand markets for durable goods: goods with higher observed quality may have more adverse selection and hence lower unobserved quality. We provide a simple theoretical model to demonstrate this result, which is a consequence of the interaction of sorting between drivers over observed quality and adverse selection over unobserved quality. We then offer empirical support using data on secondhand prices and repair rates of used cars from the Consumer Expenditure Survey, and discuss a number of implications for everyday advertising and consumer questions. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2016.2495 . This paper was accepted by J. Miguel Villas-Boas, marketing.
Leisure times of their children from mother’s percpective: The effect of rural and urban life<p>Anne perspektifinden çocuklarının serbest zamanları: Kırsal ve kentsel yaşamın etkisi
Authors: Ertüzün Ezgi , Gökçe Hüseyin , Alabay Erhan 
Published: July 2016

The aim of this study was to evaluate the leisure time activities of the children from mothers’ perspective dwelling in rural and urban area. Totally 23 mothers from rural and urban life formed the sample of the study. It was a qualitative research in terms of the techniques used in the resolution of the obtained data. Semi-structured observation form developed by the researchers was used in the study. The matters of semi-structured interview consisted of some questions evaluating the perception of mothers’ leisure time concept and the leisure time activities of the children from mothers’ perspective. Sub-themes were formed from the each question and these themes were supported by mother’s opinion. In both areas children spend their leisure times with their mothers the most. After that, children mostly spend time with their friends in rural areas, and fathers in urban areas secondly. It is stated that none of the urban based children spend time with their friends. ÖzetYaşamın ilk dönemi olan çocukluk döneminde serbest zaman aktiviteleri çocuklara oyun kavramı ile yansır. Oyunun çocuk üzerindeki etkisi açıktır ve buna bağlı olarak kırsal ve kentsel alanlarda yaşayan annelerin bakış açılarının çocuklarının serbest zaman aktivitelerine nasıl yansıdığı merak uyandırmaktadır. Bu nedenle çalışmada kırsal ve kentsel yaşam süren annelerin, kendilerinin çocukluk dönemine ilişkin ve çocuklarının serbest zaman etkinliklerinin değerlendirilmesine ilişkin görüşleri incelenmiştir. Araştırmanın örneklemini kırsal ve kentsel yaşam süren toplam 23 anne oluşturmaktadır. Araştırma elde edilen verilerin çözümlenmesi açısından nitel bir çalışmadır. Araştırmada araştırmacılar tarafından geliştirilmiş yarı yapılandırılmış gözlem formu kullanılmıştır. Yarı yapılandırılmış görüşme maddeleri, annelerin serbest zaman kavramı algılarını ve anne perspektifinden çocuklarının serbest zaman etkinliklerini değerlendiren sorulardan oluşmuştur. Her bir sorudan alt temalar oluşturulmuş ve bu temalar anne görüşleri ile desteklenmiştir. Her iki bölgede yaşam süren çocukların serbest zamanlarını en çok anneleri ile geçirdikleri, daha sonrasında ise kırsal bölgelerde arkadaşlarla, kentsel bölgelerde babalarla vakit geçirildiği tespit edilmiştir. Kentsel bölgedeki çocukların hiç birinin serbest zamanlarını arkadaşlarıyla geçirmedikleri tespit edilmiştir.
On the control of the difference between two
Brownian motions: an application to energy
markets modeling
Authors: Deschatre Thomas 
Published: July 2016

Abstract
We derive a model based on the structure of dependence between a Brownian motion and its reflection
according to a barrier. The structure of dependence presents two states of correlation: one of comonotonicity
with a positive correlation and one of countermonotonicity with a negative correlation. This model
of dependence between two Brownian motions B1 and B2 allows for the value of
to be higher than 1/2 when x is close to 0, which is not the case when the dependence is modeled by a constant correlation.
It can be used for risk management and option pricing in commodity energy markets. In particular, it allows
to capture the asymmetry in the distribution of the difference between electricity prices and its combustible
prices.
IRE-1α regulates expression of ubiquitin specific peptidases during hypoxic response in U87 glioma cells
Authors: Minchenko Oleksandr H. , Tsymbal Dariia O. , Minchenko Dmytro O. , Riabovol Olena O. , Halkin Oleh V. , Ratushna Oksana O. 
Published: July 2016

AbstractIRE-1α (inositol requiring enzyme-1α), the most evolutionarily conserved of the endoplasmic reticulum stress signaling pathways, is highly implicated in sustaining the proliferation of glioma cells and subsequent tumor growth, which is decreased by the inhibition of IRE-1α. To explore the IRE-1α mediated regulation of ubiquitin system in glioma cells, the expression of a subset of ubiquitin specific peptidases (USP) and of ubiquitin activating enzyme E1-like protein/autophagy related 7 (GSA7/ATG7) genes was studied, during hypoxic stress in wild type and U87 glioma cells with inhibited IRE-1α. Hypoxic treatment of wild type glioma cells leads to the up-regulation of USP25 and the concomitant downregulation of USP1, USP10, USP14, and GSA7 genes. USP4 and USP22 genes expression did not significantly change with hypoxic treatment. Inhibition of IRE-1α activity led to up-regulation of USP1, USP4, USP10, USP22, and USP25, while USP14 and GSA7 genes were down-regulated. Therefore, IRE-1α activity modifies substrate-targeting specificity to proteasome during hypoxic stress, which in turn can affect cell survival. Inhibition of IRE-1α correlates directly with deregulation of ubiquitin specific peptidases and GSA7 in a fashion that ultimately slows tumor growth.
Characteristics of Subcritical Water Extraction and Kinetics of Pentacyclic Triterpenoids from Dry Loquat (Eriobotrya japonica) Leaves
Authors: Mlyuka Erasto , Zhang Shuang , Wang Linxiang , Zheng Zongping , Chen Jie 
Published: July 2016

Abstract
In this study, pentacyclic triterpenoids (PTTs) were extracted from loquat leaves by subcritical water extraction (SWE) technique in a dynamic mode. The results revealed that PTTs yield increased up to 5.38±0.12 mg/g with the increasing temperature at 180 °C for corosolic acid (CA) and up to 7.20±0.11 mg/g at 200 °C for ursolic acid (UA) within experimental times. The optimum flow rates to obtain concentrated CA and UA extracts were found to be 33.33 and 41.67 mL/min, respectively. Furthermore, extraction temperatures strongly influenced the extraction rate as demonstrated by the rate constant of each temperature tested. Moreover, the kinetic rate constant decreased as the function of temperature indicating the yield of both CA and UA were significantly influenced by subcritical temperatures and extraction times.
Laplace homotopy perturbation method for Burgers equation with space- and time-fractional order
Authors: Johnston S. J. , Jafari H. , Moshokoa S. P. , Ariyan V. M. , Baleanu D. 
Published: July 2016

AbstractThe fractional Burgers equation describes the physical processes of unidirectional propagation of weakly nonlinear acoustic waves through a gas-filled pipe. The Laplace homotopy perturbation method is discussed to obtain the approximate analytical solution of space-fractional and time-fractional Burgers equations. The method used combines the Laplace transform and the homotopy perturbation method. Numerical results show that the approach is easy to implement and accurate when applied to partial differential equations of fractional orders.
Rotational surfaces in isotropic spaces satisfying weingarten conditions
Authors: Öğrenmiş Alper Osman 
Published: July 2016

AbstractIn this paper, we study the rotational surfaces in the isotropic 3-space 𝕀3satisfying Weingarten conditions in terms of the relative curvatureK(analogue of the Gaussian curvature) and the isotropic mean curvatureH. In particular, we classify such surfaces of linear Weingarten type in 𝕀3.
Application of kinetic approach to porous medium flow simulation in environmental hydrology problems on high-performance computing systems
Authors: Chetverushkin Boris N. , Churbanova Natalia G. , Kuleshov Andrey A. , Lyupa Anastasiya A. , Trapeznikova Marina A. 
Published: July 2016

AbstractA kinetically-based system of equations for three-phase porous media flow simulation is considered. A simple case with the following assumptions is discussed: phase transitions are absent, phases do not dissolve and do not mix, the rock compressibility is negligible. Such systems are under consideration in applied problems when the pressure changes slightly and thermal processes are absent, for example, in environmental problems. The continuity equation is modified via introduction of the regularizing term and the second-order time derivative. Due to conversion to the hyperbolic type the corresponding difference equation stability is improved. An explicit algorithm is developed and adapted to high-performance computing systems. High parallelization efficiency is achieved on a classical cluster as well as on a hybrid cluster with graphics accelerators.
Weighted statistical modelling algorithms with branching and extension of a model ensemble of interacting particles
Authors: Rogasinsky Sergey V. 
Published: July 2016

AbstractA modification of the weighted statistical modelling of the evolution of an ensemble of interacting particles is constructed for approximate solution of a nonlinear kinetic equation. If the auxiliary weight exceeds one, we propose to use randomized branching of trajectory of the model ensemble of particles or its corresponding extension. Numerical analysis of constructed algorithms is performed for specifically formulated model problem on relaxation of a mixture of two gases with very different concentrations.
Una aproximación al transmedia, el storytelling y los nuevos modelos narrativos electorales actuales en la comunicación política actual.
Authors: Cárcar Benito Jesús Esteban 
Published: July 2016

El fenómeno de las narrativas transmediáticas se ha convertido en uno de los temas de investigación más interesantes en el mundo de la comunicación política. Su impacto ha superado otros ámbitos (la ficción, el periodismo y la comunicación comercial) para convertirse en una práctica de la comunicación política/estratégica hasta dar lugar a la "transpolítica”. En las narraciones transmedia, se deben tener en cuenta a las audiencias (entendidas como prosumidores) para construir las historias formando parte de ese proceso expansivo del relato., que ayudan a la conformación del propio storytelling de la campaña. El trabajo aborda una aproximación a la consistencia de los universos políticos narrativos transmedia con su poderoso efecto de engagement sobre los electores y ciudadanos. Por último, bucea en los casos sobre las narrativas transmedia, relativas a universos ficcionales del mundo político actual, nuevos modelos.