bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the Specific Retention Volume of the Probe Volume and the Effects on the Polymer-Probe System by Inverse Gas Chromatography
Authors: Karagöz Mustafa Hamdi 
Published: May 2019

In this study, the effects of probe quantities on retention volume and the physical and thermodynamic results of polymer-probe systems were investigated. For this purpose, by using inverse gas chromatographic method. Alcohols and alkanes with different chemical and physical properties were injected as probes on homopolymer (2-cyclohexylidene-1,3-dioxolane-4-yl-methyl methacrylate) (CHMMA). Probe quantities of 0.3, 0.6, and 0.9 μl were selected, and an injection was made at every 10°C between 40 and 150°C. In addition, 3 μl volume probes were tried but reproducible results were not obtained in these volumes and the detector was observed to be out of order after several injections. It has been observed that the specific retention volume of alcohols and alkanes partially increased by increasing the injection amount. A linear relationship was observed between probe quantities and specific retention volume. This linear relationship is apparent from the specific retention volume values, where the probes are independent of the physical and chemical structures. It was observed that the results obtained in all three injections were close to each other and within acceptable limits. The glass transition temperature of the polymer was determined to be a Tg of 60°C. The thermodynamic data calculated for the injection of different amounts of probes were close to each other.
Arginine Starvation and Docetaxel Induce c-Myc–Driven hENT1 Surface Expression to Overcome Gemcitabine Resistance in ASS1-Negative Tumors
Authors: Prudner Bethany C. , Rathore Richa , Robinson Anthony M. , Godec Abigail , Chang Samuel F. , Hawkins William G. , Hirbe Angela C. , Van Tine Brian A. 
Published: May 2019

Abstract

Purpose:
The response to acute and long-term arginine starvation results in a conditional adaptive metabolic reprogramming that can be harnessed for therapeutic opportunities in ASS1-negative tumors. Here, we investigate the underlying biology of priming ASS1− tumors with arginine deiminase (ADI-PEG20) before treatment with gemcitabine (GEM) and docetaxel (DTX) in sarcoma, pancreatic cancer, and melanoma cell lines.

Experimental Design:
ASS1− tumor cell lines were treated to create LTAT (long-term ADI treated) cell lines (ASS1+) and used for drug combination studies. Protein expression of ASS1, dCK, RRM2, E2F1, c-MYC, and hENT1 was measured. c-MYC activity was determined, live-cell immunofluorescent studies for hENT1, uptake assays of FITC-cytosine probe, and rescue studies with a c-MYC inhibitor were all determined in the presence or absence of the ADI-PEG20:GEM:DTX.

Results:
In examining modulations within the pyrimidine pathway, we identified that the addition of DTX to cells treated with ADI-PEG20 resulted in translocation of stabilized c-Myc to the nucleus. This resulted in an increase of hENT1 cell-surface expression and rendered the cells susceptible to GEM. In vivo studies demonstrate that the combination of ADI-PEG20:GEM:DTX was optimal for tumor growth inhibition, providing the preclinical mechanism and justification for the ongoing clinical trial of ADI-PEG20, GEM, and DTX in sarcoma.

Conclusions:
The priming of tumors with ADI-PEG20 and DTX results in the stabilization of c-MYC potentiating the effect of GEM treatment via an increase in hENT1 expression. This finding is applicable to ASS1-deficient cancers that are currently treated with GEM.
Targeting the YB-1/PD-L1 Axis to Enhance Chemotherapy and Antitumor Immunity
Authors: Tao Zhen , Ruan Hailong , Sun Lin , Kuang Dong , Song Yongchun , Wang Qi , Wang Tao , Hao Yi , Chen Ke 
Published: May 2019

Abstract
Tumor cells can escape immune destruction in tumor chemoresistance, but the mechanism for this phenomenon remains unclear. Y-box binding protein 1 (YB-1), which is upregulated in chemoresistant tumor cells, plays a role in the acquisition of multidrug resistance. Here, we demonstrate that chemotherapy induced an immunosuppressive microenvironment in the tumor and induced immune evasion through YB-1–mediated programmed death-1 ligand 1 (PD-L1) upregulation. Examination of the YB-1 protein and mRNA showed an increase in YB-1 expression in hepatocellular carcinoma (HCC). High YB-1 expression negatively correlated with the overall survival of HCC patients. YB-1 expression positively correlated with PD-L1, and YB-1 induced PD-L1 expression by binding a PD-L1 promoter motif. YB-1 expression was upregulated in chemoresistant HCC cells, and YB-1 knockdown reversed chemoresistance via T-cell activation in the tumor microenvironment due to blocked PD-L1 expression. We also found that inhibition of the tumor immunosuppressive environment and immune evasion was accompanied by proliferation of functional cytotoxic CD8+ T cells and inhibition of myeloid-derived suppressor cells and regulatory T cells in the tumor environment. Our data indicate that targeting the YB-1 signaling axis, which simultaneously reverses both tumor immune evasion and multidrug resistance, may improve the antitumor response. This finding suggests a treatment modality against tumor chemoresistance.
An Artificial Antigen-Presenting Cell Delivering 11 Immune Molecules Expands Tumor Antigen–Specific CTLs in Ex Vivo and In Vivo Murine Melanoma Models
Authors: Zhang Lei , Song Shilong , Jin Xiaoxiao , Wan Xin , Shahzad Khawar Ali , Pei Weiya , Zhao Chen , Shen Chuanlai 
Published: May 2019

Abstract
Antigen-presenting cells expand antigen-specific T cells ex vivo and in vivo for tumor immunotherapy, but are time-consuming to generate and, as live cells, raise biosafety concerns. An alternative is found in cell-free artificial antigen-presenting cells (aAPC), but these only present two or three kinds of immune molecules. Here, we describe a multipotent artificial antigen-presenting cell (MaAPC) that delivered 11 kinds of immune moleclues. This MaAPC simulated natural APCs through the concurent coupling of target antigens (H-2Kb/TRP2180–188-Ig dimers and H-2Db/gp10025–33-Ig dimers), costimulatory molecules (anti-CD28, anti–4-1BB, and anti-CD2), and “self-marker” CD47-Fc onto surface-modified polylactic-co-glycolic acid microparticles (PLGA-MP). These PLGA-MPs also encapsulated cytokines (IL2 and IL15), a chemokine (CCL21), and checkpoint inhibitors (anti–CTLA-4 and anti–PD-1). Culture of MaAPCs with naïve T cells for 1 week elevated the frequencies of TRP2180–188–specific and gp10025–33–specific CTLs to 51.0% and 43.3%, respectively, with enhanced cytotoxicity. Three infusions of MaAPCs inhibited subcutaneous melanoma growth in a mouse model and expanded TRP2180–188 and gp10025–33–specific CTLs 59–86-fold in peripheral blood, 76–77-fold in spleen, and 205–212-fold in tumor tissue, in an antigen-specific manner. Compared with conventional aAPCs carrying two or three immune molecules, the 11-signal MaAPCs exerted greater impact on T cells, including activation, proliferation, cytotoxicity, differentiation to memory CTLs or regulatory T cells and cytokines profiles, without detected side effects. Such MaAPCs could be used to individualize tumor immunotherapy.
Subphonemic Variation and Lexical Processing: Social and Stylistic Factors
Authors: Jones Zack , Clopper Cynthia G. 
Published: May 2019

Abstract
Different pronunciation variants of the same word can facilitate lexical access, but they may be more or less effective primes depending on their phonological form, stylistic appropriateness, familiarity, and social prestige, suggesting that multiple phonological variants are encoded in the lexicon with varying strength. The current study investigated how subphonemic variation is encoded using a lexical decision task with cross-modal form priming. The results revealed that the magnitude of priming was mediated by stylistic and social properties of the auditory primes, including speaking style, talker dialect, and duration. These interactions provide evidence that phonetically reduced forms and forms that are not socially prestigious are not as robustly encoded in the lexicon as canonical forms and forms produced in prestigious varieties.
Phonetic Realisation and Phonemic Categorisation of the Final Reduced Corner Vowels in the Finnic Languages of Ingria
Authors: Kuznetsova Natalia , Verkhodanova Vasilisa 
Published: May 2019

Abstract
Individual variability in sound change was explored at three stages of final vowel reduction and loss in the endangered Finnic varieties of Ingria (subdialects of Ingrian, Votic and Ingrian Finnish). The correlation between the realisation of reduced vowels and their phonemic categorisation by speakers was studied. The correlated results showed that if V was pronounced >70%, its starting loss was not yet perceived, apart from certain frequent elements, but after >70% loss, V was not perceived any more. A split of 50/50 between V and loss in production correlated with the same split in categorisation. At the beginning of a sound change, production is, therefore, more innovative, but after reanalysis, categorisation becomes more innovative and leads the change. The vowel a was the most innovative in terms of loss, u/o were the most conservative, and i was in the middle, while consonantal palatalisation was more salient than labialisation. These differences are based on acoustics, articulation and perception.
Gran Canarian Spanish Non-Continuant Voicing: Gradiency, Sex Differences and Perception
Authors: Broś Karolina , Lipowska Katarzyna 
Published: May 2019

AbstractBackground/Aims:This paper examines the process of postvocalic voicing in the Spanish of Gran Canaria from the point of view of language change. A perception-production study was designed to measure the extent of variation in speaker productions, explore the degree to which production is affected by perception and identify variables that can be considered markers of sound change in progress.Methods:20 native speakers of the dialect were asked to repeat auditory input data containing voiceless non-continuants with and without voicing.Results:Input voicing has no effect on output pronunciations, but voicing is highly variable, with both phonetic and social factors involved. Most importantly, a clear lenition pattern was identified based on such indicators as consonant duration, intensity ratio, absence of burst and presence of formants, with the velar /k/ as the most affected segment. Furthermore, strong social implications were identified: voicing degrees and rates depend both on the level of education and on the gender of the speaker.Conclusion:The results of the study suggest that the interplay of external and internal factors must be investigated more thoroughly to better address the question of phonetic variation and phonologisation of contrasts in the context of language change.
The Goldilocks Zone of Perceptual Learning
Authors: Babel Molly , McAuliffe Michael , Norton Carolyn , Senior Brianne , Vaughn Charlotte 
Published: May 2019

Abstract

Background/Aims:
Lexically guided perceptual learning in speech is the updating of linguistic categories based on novel input disambiguated by the structure provided in a recognized lexical item. We test the range of variation that allows for perceptual learning by presenting listeners with items that vary from subtle within-category variation to fully remapped cross-category variation.
Methods:
Experiment 1 uses a lexically guided perceptual learning paradigm with words containing noncanonical /s/ realizations from s/ʃ continua that correspond to “typical,” “ambiguous,” “atypical,” and “remapped” steps. Perceptual learning is tested in an s/ʃ categorization task. Experiment 2 addresses listener sensitivity to variation in the exposure items using AX discrimination tasks.
Results:
Listeners in experiment 1 showed perceptual learning with the maximally ambiguous tokens. Performance of listeners in experiment 2 suggests that tokens which showed the most perceptual learning were not perceptually salient on their own.
Conclusion:
These results demonstrate that perceptual learning is enhanced with maximally ambiguous stimuli. Excessively atypical pronunciations show attenuated perceptual learning, while typical pronunciations show no evidence for perceptual learning. AX discrimination illustrates that the maximally ambiguous stimuli are not perceptually unique. Together, these results suggest that perceptual learning relies on an interplay between confidence in phonetic and lexical predictions and category typicality.
Genome-Wide Association Study–Driven Gene-Set Analyses, Genetic, and Functional Follow-Up Suggest
GLIS1
as a Susceptibility Gene for Mitral Valve Prolapse
Authors: Yu Mengyao , Georges Adrien , Tucker Nathan R. , Kyryachenko Sergiy , Toomer Katelyn , Schott Jean-Jacques , Delling Francesca N. , Fernandez-Friera Leticia , Solis Jorge , Ellinor Patrick T. , Levine Robert A. , Slaugenhaupt Susan A. , Hagège Albert A. , Dina Christian , Jeunemaitre Xavier , Milan David J. , Norris Russell A. , Bouatia-Naji Nabila 
Published: May 2019

Background
Mitral valve prolapse (MVP) is a common heart valve disease, the most frequent indication for valve repair or replacement. MVP is characterized by excess extracellular matrix secretion and cellular disorganization, which leads to bulky valves that are unable to coapt correctly during ventricular systole resulting in mitral regurgitation, and it is associated with sudden cardiac death. Here we aim to characterize globally the biological mechanisms underlying genetic susceptibility to MVP to better characterize its triggering mechanisms.

Methods

We applied
i
-GSEA4GWAS and DEPICT, two pathway enrichment tools to MVP genome-wide association studies. We followed-up the association with MVP in an independent dataset of cases and controls. This research was conducted using the UK Biobank Resource. Immunohistochemistry staining for Glis1 (GLIS family zinc finger 1) was conducted in developing heart of mice. Knockdown of
Glis1
using morpholinos was performed in zebrafish animals 72 hours postfertilization.

Results

We show that genes at risk loci are involved in biological functions relevant to actin filament organization, cytoskeleton biology, and cardiac development. The enrichment for positive regulation of transcription, cell proliferation, and migration motivated the follow-up of
GLIS1
, a transcription factor from the Krüppel-like zinc finger family. In combination with previously available data, we now report a genome-wide significant association with MVP (odds ratio, 1.20;
P
=4.36×10
-10
), indicating that
Glis1
is expressed during embryonic development predominantly in nuclei of endothelial and interstitial cells of mitral valves in mouse. We also show that
Glis1
knockdown causes atrioventricular regurgitation in developing hearts in zebrafish.

Conclusions

Our findings define globally molecular and cellular mechanisms underlying common genetic susceptibility to MVP and implicate established and unprecedented mechanisms. Through the
GLIS1
association and function, we point at regulatory functions during cardiac development as common mechanisms to mitral valve degeneration.
Assessment and Validation of a Phenotype-Enhanced Variant Classification Framework to Promote or Demote
RYR2
Missense Variants of Uncertain Significance
Authors: Giudicessi John R. , Lieve Krystien V.V. , Rohatgi Ram K. , Koca Faruk , Tester David J. , van der Werf Christian , Martijn Bos J. , Wilde Arthur A.M. , Ackerman Michael J. 
Published: May 2019

Background

Many rare, potentially pathogenic,
RYR2
variants identified in individuals with clinically definite catecholaminergic polymorphic ventricular tachycardia are classified ambiguously as variants of uncertain significance (VUS). We aimed to determine if a phenotype-enhanced variant classification approach could reduce the burden of
RYR2
VUS encountered during clinical genetic testing.

Methods

This retrospective study was conducted in 84
RYR2
-positive individuals from the Mayo Clinic (Rochester, MN) and validated in 149
RYR2
-positive individuals from Amsterdam University Medical Center (Amsterdam, NL). Using a newly developed diagnostic scorecard, the pretest clinical probability of catecholaminergic polymorphic ventricular tachycardia was determined for all
RYR2
-positive individuals. Each
RYR2
variant was then readjudicated using a phenotype-enhanced American College of Medical Genetics approach that incorporates new criteria that reflect the phenotypic strength associated with each individual
RYR2
variant.

Results

Overall, 72 distinct
RYR2
variants were identified among the 84 Mayo Clinic (39 unique) and 149 Amsterdam University Medical Center (30 unique) cases. Three variants were present in both cohorts. American College of Medical Genetics guidelines classified 47% of all
RYR2
variants as VUS. In the Mayo Clinic cohort, readjudication using amended phenotype-enhanced American College of Medical Genetics standards dropped the VUS rate significantly (20/42 [48%] versus 3/42 [7%];
P
<0.001) with 13/20 (65%)
RYR2
VUS promoted to likely pathogenic and 4/20 (20%) demoted to likely benign. A similar drop in VUS rate (14/33 [42%] versus 3/33 [9%];
P
=0.001) was observed in the Amsterdam University Medical Center validation cohort with 10/14 (71%)
RYR2
VUS promoted to likely pathogenic and 1/14 (7%) demoted to likely benign.

Conclusions
This multicenter study illustrates the potential utility of phenotype-enhanced variant classification in catecholaminergic polymorphic ventricular tachycardia.
Left Ventricular Flow Analysis
Authors: Stoll Victoria M. , Hess Aaron T. , Rodgers Christopher T. , Bissell Malenka M. , Dyverfeldt Petter , Ebbers Tino , Myerson Saul G. , Carlhäll Carl-Johan , Neubauer Stefan 
Published: May 2019

Background:
Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity.

Methods
Thirty-four dilated cardiomyopathy patients, 30 ischemic cardiomyopathy patients, and 36 controls underwent magnetic resonance including 4-dimensional flow, BNP (brain-type natriuretic peptide) measurement, functional capacity assessment (6-minute walk test), and symptom quantification. A subgroup of dilated cardiomyopathy and control subjects underwent cardiac energetic assessment. Left ventricular flow was separated into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average KE throughout the cardiac cycle was calculated.

Results:

Patients had reduced direct flow proportion and direct-flow average KE compared with controls (
P
<0.0001). The residual volume proportion and residual volume average KE were increased in patients (
P
<0.0001). Importantly, in a multiple linear regression model to predict the patient’s 6-minute walk test, the independent predictors were age (β=−0.3015;
P
=0.019) and direct-flow average KE (β=0.280,
P
=0.035; R
2
model, 0.466,
P
=0.002). In contrast, neither ejection fraction nor left ventricular volumes were independently predictive.

Conclusions:
This study demonstrates an independent predictive relationship between the direct-flow average KE and a prognostic measure of functional capacity. Intracardiac 4-dimensional flow parameters are novel biomarkers in heart failure and may provide additive value in monitoring new therapies and predicting prognosis.
Buddhist Vegetarianism Views on Equivalent Reduction of Greenhouse Gas Emissions in China from 2017 to 2027
Authors: Tseng Ampere A. 
Published: May 2019

AbstractThe impact of Buddhist vegetarianism views on the equivalent reduction of greenhouse gas emissions (GHGE s) is evaluated. The vegetarianism views from three major Buddhist schools in China are first presented, since different views on vegetarianism can dictate the assessment of the equivalent of GHGE reduction. The populations of Chinese Buddhists in these three Buddhist schools are then estimated. A correlation formula is used to evaluate the equivalent GHGE reductions attributed to the vegan and vegetarian populations in the Chinese Buddhists from 2017 to 2027. The reduction results enable us to conclude that Chinese Buddhists with vegan or vegetarian diets account for the equivalent GHGE reduction of 54.560 MtCO2e in 2017 and 60.927 MtCO2e in 2027 with an average annual growth rate of 1.11 %. The reductions of 54.560 and 60.927 MtCO2e equal to 11.66 % and 13.02 % of the total GHGE s from the United Kingdom in 2016, respectively.
On Tools Making Minds: an Archaeological Perspective on Human Cognitive Evolution
Authors: Overmann Karenleigh A. , Wynn Thomas 
Published: May 2019

AbstractUsing a model of cognition as extended and enactive, we examine the role of materiality in making minds as exemplified by lithics and writing, forms associated with conceptual thought and meta-awareness of conceptual domains. We address ways in which brain functions may change in response to interactions with material forms, the attributes of material forms that may cause such change, and the spans of time required for neurofunctional reorganization. We also offer three hypotheses for investigating co-influence and change in cognition and material culture.
Cultural Models of Substance Misuse Risk and Moral Foundations: Cognitive Resources Underlying Stigma Attribution
Authors: Henderson Nicole Lynn , Dressler William W. 
Published: May 2019

AbstractThis study examines the cognitive resources underlying the attribution of stigma in substance use and misuse. A cultural model of substance misuse risk was elicited from students at a major U.S. state university. We found a contested cultural model, with some respondents adopting a model of medical risk while others adopted a model of moral failure; agreeing that moral failure primarily defined risk led to greater attribution of stigma. Here we incorporate general beliefs about moral decision-making, assessed through Moral Foundations Theory. Specifically, we examined commitment to each moral foundation in relation to stigma attribution while controlling for the specific model of substance misuse risk. We found an interaction between the purity moral foundation and the cultural model of risk. This suggests that broad moral orientations, along with more specific understandings of substance misuse risk, combine to orient an individual with respect to stigma attribution.