bluuebunny/crossref_metadata_2025 huggingface dataset:
Habitual Weakness
Authors: Silver Kenneth ,   Philosophy Documentation Center
Published: August 2019

The standard case of weakness of will involves a strong temptation leading us to reconsider or act against our judgments. Here, however, I consider cases of what I call ‘habitual weakness’, where we resolve to do one thing yet do another not to satisfy any grand desire, but out of habit. After giving several examples, I suggest that habitual weakness has been under-discussed in the literature and explore why. These cases are worth highlighting for their ubiquity, and I show three further advantages of appreciating habitual weakness as a kind of weakness: It challenges purportedly necessary conditions on akrasia, it side-steps outstanding skeptical concerns, and it provides a new model for considering the weak-willed behavior of group agents. I conclude by arguing that cases of habitual weakness are genuine cases of akrasia and weakness of will. Rather than lacking strength of will, habitual weakness involves lacking diligence, vigilance, or fortitude.
Anaerobic digestion, mixing, environmental fate, and transport
Authors: Chang Chein‐Chi , Kuo‐Dahab Camilla , Chapman Tom , Mei Ying
Published: August 2019

This section covers research published during the calendar year 2018 on mixing and transport processes. The review covers mixing of anaerobic digesters, mixing of heat transfer, and environmental fate and transport.
Assessment of contrafreeloading preferences in giraffe (Giraffa camelopardalis)
Authors: Sasson‐Yenor Jacinthe , Powell David M.
Published: August 2019

Contrafreeloading is an intriguing phenomenon in which animals will work to obtain resources, such as food, when the same resource is simultaneously freely available. Multiple hypotheses exist for why animals might choose to contrafreeload. In this study, we assessed preferences for contrafreeloading in giraffe at the Bronx Zoo to determine whether they actually preferred to contrafreeload or were simply demonstrating a willingness to contrafreeload. Food was presented in a range of distributions between an easily accessed feeding device and a more challenging one and the giraffes’ feeding behavior at these two types of feeding devices was recorded. As the experiments progressed, more giraffe used these more challenging feeders. There was significant individual variation in the expression of preference for contrafreeloading and willingness to contrafreeload. Individual, phase of the experiment, and an interaction between these factors were significant predictors of challenge feeder use. Three foraging strategies emerged among the giraffe that we termed “freeloaders,” “contrafreeloaders,” and “opportunists.” The results of this study demonstrate that multiple indices of preference are necessary when assessing contrafreeloading behavior, and that giraffe are affected to different degrees by the factors that stimulate contrafreeloading. These results may shed light on why different individuals use complex feeding enrichment devices to varying extents.
On the spectrum and spacetime supersymmetry of heterotic ambitwistor string
Authors: Flores Henrique , Lize Matheus
Published: August 2019

Abstract

We analyse the BRST cohomology of the Ramond sector of heterotic ambitwistor theory. We also write the free string field theory action and compute the supersymmetry transformations.
The Hillary Hypotheses: Testing Candidate Views of Loss
Authors: Lewis-Beck Michael S. , Quinlan Stephen
Published: August 2019

The surprising election of Donald Trump to the presidency calls for a comprehensive assessment of what motivated voters to opt for a controversial political novice rather than a provocative but experienced political veteran. Our study provides a novel exploration of the Trump victory through the prism of the defeated candidate—Hillary Rodham Clinton (HRC). Losing candidates’ perceptions are usually not subject to academic analyses. Nevertheless, these people often hold substantial sway in their parties and thus understanding their views on the loss is essential, especially as a party regroups after defeat. Using HRC’s memoirWhat Happened, we devise the HillaryHypotheses, her rationale for her electoral defeat. Using the 2016 American National Election Study (ANES), we provide the first systematic test of a losing candidate’s rationale for their defeat. We show that more often than not, HRC’s assumptions are supported. However, we find little evidence to support HRC’s most crucial assertion, namely that the e-mail scandal and specifically James Comey’s intervention ten days before Election Day cost her the presidency. Our findings have implications for understanding why Donald Trump won, but more broadly the contribution explores an understudied aspect of elections—a defeated candidate’s impression of their loss.
Adversaries or Allies? Donald Trump’s Republican Support in Congress
Authors: Amira Karyn , Johnson Lauren , McCray Deon , Ragusa Jordan
Published: August 2019

Donald Trump’s first year in office received unprecedented media coverage, with many wondering whether congressional Republicans were “adversaries” or “allies” of the president’s legislative positions. We explore this issue from two vantage points. First, we place Trump’s presidency in historical context by forecasting his Republican support with data from 1969 to 2016. We find that Republicans supported Trump’s legislative positions in 2017 at levels consistent with expectations, contrary to the views of some. Second, we explore the factors that explain why Republican lawmakers supported or opposed their party’s president. We find that conservative and establishment Republicans were more likely to support Trump, contrary to some claims, while female Republicans and those representing affluent, non-white districts were more likely to oppose Trump. We conclude by discussing the broader implications of these results, including the role of identity in contemporary American politics and the possible realignment of the GOP.
The Role of Whiteness in the 2016 Presidential Primaries
Authors: Lopez Bunyasi Tehama
Published: August 2019

Donald Trump initiated his run for president by framing the United States as a nation in descent. Adopting the slogan “Make America Great Again,” he set his campaign against a backdrop of loss and declared a mission for reclamation. Numerous analysts claim that his candidacy and rhetoric galvanized white voters who feel left behind by changing times, but few have been able to provide direct evidence of a racialized sense of disadvantage, and most polls were not prepared to ask such specific questions prior to the Iowa Caucus. Using data from the National Study of Color-Blindness and Race-Consciousness—a unique nationally-sampled dataset fielded two weeks before the beginning of the 2016 primary election season—I demonstrate that Trump was not only the most popular candidate among white voters, but that he was especially supported by whites who think that their racial group fares worse in the job market than do black Americans, who feel that being white has been personally detrimental to their job prospects; who believe that there are generally more disadvantages to being white than there are advantages; and who disagree with the notion that systematic racism mainly benefits whites. My analysis argues that how whites think about whiteness mattered for their likelihood to support Donald Trump.
A Discussion of Jessica Blatt's Race and the Making of American Political Science
Authors: Fraga Luis Ricardo
Published: August 2019

In Race and the Making of American Political Science, Jessica Blatt argues that the professionalization of the discipline was deeply entwined with ideas about racial difference, and the concomitant attempt by leading scholars to define and defend a system of racial hierarchy in the United States and beyond. Although it focuses on the period from the late nineteenth century through the 1930s, the book also raises fundamental questions about the historical legacy of racialist arguments for professional political science, the extent of their continuing resonance, and contemporary implications for both academic and broader civic discourse. We have asked a range of leading political scientists to consider and respond to Professor Blatt’s important call for scholarly self-reflexivity.
A Discussion of Jessica Blatt's Race and the Making of American Political Science
Authors: Hancock Alfaro Ange-Marie
Published: August 2019

In Race and the Making of American Political Science, Jessica Blatt argues that the professionalization of the discipline was deeply entwined with ideas about racial difference, and the concomitant attempt by leading scholars to define and defend a system of racial hierarchy in the United States and beyond. Although it focuses on the period from the late nineteenth century through the 1930s, the book also raises fundamental questions about the historical legacy of racialist arguments for professional political science, the extent of their continuing resonance, and contemporary implications for both academic and broader civic discourse. We have asked a range of leading political scientists to consider and respond to Professor Blatt’s important call for scholarly self-reflexivity.
Legacy Atmospheric Profiles and Derived Products From GOES‐16: Validation and Applications
Authors: Schmit Timothy J. , Li Jun , Lee Su Jeong , Li Zhenglong , Dworak Richard , Lee Yong‐Keun , Bowlan Michael , Gerth Jordan , Martin Graeme D. , Straka William , Baggett Kevin C. , Cronce Lee
Published: August 2019

The Geostationary Operational Environmental Satellite‐R (GOES‐R) series started a new era for the U.S. geostationary satellite observing system. The Advanced Baseline Imager (ABI) onboard the GOES‐R series has fine temporal (30 s to 10 min) and spatial resolutions (0.5–2 km), and 16 spectral bands. However, due to the lack of an infrared sounder, the ABI is used to continue the legacy atmospheric profile (LAP) products that the previous GOES Sounder has, including the legacy atmospheric moisture profile, legacy atmospheric temperature profile, total precipitable water, layered precipitable water, and derived atmospheric stability indices. The ABI LAP retrieval algorithms have been developed under the GOES‐R series Algorithm Working Group (AWG) program funded by the GOES‐R Program Office. The LAP products from GOES‐16 have been operational and validated with a series of reference data sets including radiosonde observations, the Global Positioning System from SuomiNet, the Advanced Microwave Scanning Radiometer 2 total precipitable water measurements, as well as global operational analysis from National Oceanic and Atmospheric Administration and European Centre for Medium‐Range Weather Forecasts models, for almost a year (from 2017 to 2018) to assure the data quality for applications. In addition, the LAP products have been successfully demonstrated at the Hazardous Weather Testbed experiments in the summer of 2017 and the spring of 2018. Both validation results and Hazardous Weather Testbed demonstrations indicate that the GOES‐R series LAP products meet the product requirements and provide added value over NWP short‐range forecasts, especially for middle‐upper tropospheric moisture, in situation awareness and nowcasting.
Analytical Identification and Characterization of the Major Geochemical Terranes of Mercury's Northern Hemisphere
Authors: Peplowski Patrick N. , Stockstill‐Cahill Karen
Published: August 2019

Principal component analysis of Mercury chemical composition maps provide analytically robust identification of distinct geochemical terranes on Mercury. The results reveal a wide diversity of terrane types, including previously identified terranes like the high‐Mg terrane and northern terranes, as well as a new terrane not identified in prior studies, the intermediate composition, high‐K (IHK) terrane. We propose that the IHK is material excavated from beneath the Borealis planitia by the Rustaveli‐basin‐forming impact. In addition to the new IHK terrane, Caloris‐basin‐like materials are recognized outside of the basin rim for the first time. This indicates that the terrane type found within the Caloris basin is not a unique consequence of the Caloris impact event. Geochemical modeling of terrane compositions facilitates interpretation of the principal components in terms of mineral end‐members, making the individual principal component maps also a measure of the relative variability of pyroxenes, olivine, and plagioclase. Our mineralogical modeling also confirms the low‐viscosity nature of the lava that flooded Mercury's surface to produce the present‐day crust, consistent with the geomorphology of Mercury's extensive volcanic plains units.
Friction in Cold Ice Within Outer Solar System Satellites With Reference to Thermal Weakening at High Sliding Velocities
Authors: Sleep Norman H.
Published: August 2019

The icy shells of Enceladus and Europa consist from top down of cold (~100 K) ice at low (<0.1 MPa) pressure, cold ice at high pressure up to ~10 MPa, and warm ice near 273 K the base. The pressure ~10 MPa and temperature near 273 K of basal ice within Enceladus and Europa are similar to that within terrestrial glaciers that are known to have seismicity (icequakes). Warm ice easily melts during sliding so its icequakes are qualitatively explained and expected on these satellites if the macroscopic strain rates are comparable to those within terrestrial glaciers subjected to oceanic tides. However, cold ice at high pressures does not readily macroscopically melt during sliding. A dynamic weakening mechanism for crustal faults in rock may be applicable to Enceladus and Europa. Micron‐scale real contacts support ~0.4‐GPa shear tractions and normal tractions on rapidly sliding ice faults. At sliding velocities above ~0.1 m/s, the asperity tips of the contacts become hot and weak in ice. The macroscopic friction depends on the average strength of the asperity tips during the lifetimes of contact. The strength of the asperity tips self‐organizes so that frictional heating balances the heat lost from the asperity tip by conduction. The macroscopic coefficient of friction at coseismic sliding velocities decreases to a modest fraction of the low‐velocity coefficient of friction, but does not approach zero. This velocity‐weakening mechanism likely allows major icequakes within the cold interiors of Europa and Enceladus.
Revealing Hidden Climate Indices from the Occurrence of Hydrologic Extremes
Authors: Renard Benjamin , Thyer Mark
Published: August 2019

Describing the space‐time variability of hydrologic extremes in relation to climate is important for scientific and operational purposes. Many studies demonstrated the role of large‐scale modes of climate variability such as the El Niño–Southern Oscillation (ENSO) or the North Atlantic Oscillation (NAO), among many others. Climate indices have hence frequently been used as predictors in probabilistic models describing hydrologic extremes. However, standard climate indices such as ENSO/NAO are poor predictors in some regions. Consequently, this paper describes an innovative method to avoid relying on standard climate indices, based on the following idea: the relevant climate indices are effectively unknown (they are hidden), and they should therefore be estimated directly from hydrologic data. In statistical terms, this corresponds to a Bayesian hierarchical model describing extreme occurrences, with hidden climate indices treated as latent variables. This approach is illustrated using three case studies. A synthetic case study first shows that identifying hidden climate indices from occurrence data alone is feasible. A second case study using flood occurrences at 42 east Australian sites confirms that the model correctly identifies their ENSO‐related climate driver. The third case study is based on 207 sites in France, where standard climate indices poorly predict flood occurrence. The hidden climate indices model yields a reliable description of flood occurrences, in particular their clustering in space and their large interannual variability. Moreover, some hidden climate indices are linked with specific patterns in atmospheric variables, making them interpretable in terms of climate variability and opening the way for predictive applications.
Major depression and enhanced molecular senescence abnormalities in young and middle-aged adults
Authors: Diniz Breno S. , Reynolds III Charles F. , Sibille Etienne , Bot Mariska , Penninx Brenda W. J. H
Published: August 2019

Recent evidence suggests a significant overlap in biological changes between major depression and aging across the lifespan. We aim to evaluate the impact of a major depressive episode on the Senescence-Associated Secretory Phenotype (SASP) index, a dynamic secretory molecular pattern indicative of cellular senescence. We also tested the potential moderators of the association between major depression and the SASP index. We included 1165 young and middle-aged adults (527 with a current major depressive episode (cMDE) and 638 with no lifetime history of depression) from a community-based cohort from the Netherlands. We calculated the SASP index based on a previously developed composite index involving 19 biomarkers. cMDE had higher SASP index values (t(1163) = 2.93, p = 0.003) compared to controls in the univariate analysis. After controlling for sociodemographic and somatic health covariates, there was no significant association between cMDE and SASP index (F(1,1158) = 1.09, p = 0.29). Those with the most severe depressive episodes had significantly higher SASP indices compared to those with mild-to-moderate cMDE and controls (F(2,1162) = 6.73, p = 0.001). We found a significant interaction between cMDE and overweight (F(1,1164) = 5.1, p = 0.028): those with comorbid cMDE and overweight had the highest SASP index. Our study demonstrated a complex interaction between cMDE and medical morbidity, especially overweight, on the SASP index, suggesting that their coexistence aggravate age-related biological processes. Moreover, higher SASP index can be a biomarker for more severe depressive episodes.
Two pedigrees with arrhythmogenic right ventricular cardiomyopathy linked with R49H and F531C mutation in DSG2
Authors: Chen Xuepin , Peng Hui , Zheng Chenqing , Zhang Hongmei , Yan Chao , Ma Huihui , Dai Xiafei , Li Xiaoping
Published: August 2019

Arrhythmogenic right ventricular cardiomyopathy (ARVC) presents as the progressive fibrofatty replacement of the cardiomyocytes particularly in the right ventricular wall. Here, we report two cases with ARVC. In family A, the proband carries a Desmoglein2 (DSG2) gene complex heterozygous mutation NM_001943.4:c.146G>A/p.(Arg49His)and NM_001943.3:c.1592T>G/p.(Phe531Cys). In family B, the proband carries a homozygous mutation NM_001943.3:c.1592T>G/p.(Phe531Cys).
Bell’s theorem for temporal order
Authors: Zych Magdalena , Costa Fabio , Pikovski Igor , Brukner Časlav
Published: August 2019

Time has a fundamentally different character in quantum mechanics and in general relativity. In quantum theory events unfold in a fixed order while in general relativity temporal order is influenced by the distribution of matter. When matter requires a quantum description, temporal order is expected to become non-classical—a scenario beyond the scope of current theories. Here we provide a direct description of such a scenario. We consider a thought experiment with a massive body in a spatial superposition and show how it leads to entanglement of temporal orders between time-like events. This entanglement enables accomplishing a task, violation of a Bell inequality, that is impossible under local classical temporal order; it means that temporal order cannot be described by any pre-defined local variables. A classical notion of a causal structure is therefore untenable in any framework compatible with the basic principles of quantum mechanics and classical general relativity.
Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model
Authors: Spangenberg Elizabeth , Severson Paul L. , Hohsfield Lindsay A. , Crapser Joshua , Zhang Jiazhong , Burton Elizabeth A. , Zhang Ying , Spevak Wayne , Lin Jack , Phan Nicole Y. , Habets Gaston , Rymar Andrey , Tsang Garson , Walters Jason , Nespi Marika , Singh Parmveer , Broome Stephanie , Ibrahim Prabha , Zhang Chao , Bollag Gideon , West Brian L. , Green Kim N.
Published: August 2019

Many risk genes for the development of Alzheimer’s disease (AD) are exclusively or highly expressed in myeloid cells. Microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for their survival. We designed and synthesized a highly selective brain-penetrant CSF1R inhibitor (PLX5622) allowing for extended and specific microglial elimination, preceding and during pathology development. We find that in the 5xFAD mouse model of AD, plaques fail to form in the parenchymal space following microglial depletion, except in areas containing surviving microglia. Instead, Aβ deposits in cortical blood vessels reminiscent of cerebral amyloid angiopathy. Altered gene expression in the 5xFAD hippocampus is also reversed by the absence of microglia. Transcriptional analyses of the residual plaque-forming microglia show they exhibit a disease-associated microglia profile. Collectively, we describe the structure, formulation, and efficacy of PLX5622, which allows for sustained microglial depletion and identify roles of microglia in initiating plaque pathogenesis.
Genotoxic stress-triggered β-catenin/JDP2/PRMT5 complex facilitates reestablishing glutathione homeostasis
Authors: Cao Lixue , Wu Geyan , Zhu Jinrong , Tan Zhanyao , Shi Dongni , Wu Xingui , Tang Miaoling , Li Ziwen , Hu Yameng , Zhang Shuxia , Yu Ruyuan , Mo Shuang , Wu Jueheng , Song Erwei , Li Mengfeng , Song Libing , Li Jun
Published: August 2019

The mechanisms underlying how cells subjected to genotoxic stress reestablish reduction-oxidation (redox) homeostasis to scavenge genotoxic stress-induced reactive oxygen species (ROS), which maintains the physiological function of cellular processes and cell survival, remain unclear. Herein, we report that, via a TCF-independent mechanism, genotoxic stress induces the enrichment of β-catenin in chromatin, where it forms a complex with ATM phosphorylated-JDP2 and PRMT5. This elicits histone H3R2me1/H3R2me2s-induced transcriptional activation by the recruitment of the WDR5/MLL methyltransferase complexes and concomitant H3K4 methylation at the promoters of multiple genes in GSH-metabolic cascade. Treatment with OICR-9429, a small-molecule antagonist of the WDR5-MLL interaction, inhibits the β-catenin/JDP2/PRMT5 complex-reestablished GSH metabolism, leading to a lethal increase in the already-elevated levels of ROS in the genotoxic-agent treated cancer cells. Therefore, our results unveil a plausible role for β-catenin in reestablishing redox homeostasis upon genotoxic stress and shed light on the mechanisms of inducible chemotherapy resistance in cancer.
Tumor-targeted silencing of the peptide transporter TAP induces potent antitumor immunity
Authors: Garrido Greta , Schrand Brett , Rabasa Ailem , Levay Agata , D’Eramo Francesca , Berezhnoy Alexey , Modi Shrey , Gefen Tal , Marijt Koen , Doorduijn Elien , Dudeja Vikas , van Hall Thorbald , Gilboa Eli
Published: August 2019

Neoantigen burden is a major determinant of tumor immunogenicity, underscored by recent clinical experience with checkpoint blockade therapy. Yet the majority of patients do not express, or express too few, neoantigens, and hence are less responsive to immune therapy. Here we describe an approach whereby a common set of new antigens are induced in tumor cells in situ by transient downregulation of the transporter associated with antigen processing (TAP). Administration of TAP siRNA conjugated to a broad-range tumor-targeting nucleolin aptamer inhibited tumor growth in multiple tumor models without measurable toxicity, was comparatively effective to vaccination against prototypic mutation-generated neoantigens, potentiated the antitumor effect of PD-1 antibody or Flt3 ligand, and induced the presentation of a TAP-independent peptide in human tumor cells. Treatment with the chemically-synthesized nucleolin aptamer-TAP siRNA conjugate represents a broadly-applicable approach to increase the antigenicity of tumor lesions and thereby enhance the effectiveness of immune potentiating therapies.
Outcomes from deep brain stimulation targeting subthalamic nucleus and caudal zona incerta for Parkinson’s disease
Authors: Mostofi Abteen , Evans Julian M. , Partington-Smith Lucy , Yu Kenny , Chen Cliff , Silverdale Monty A.
Published: August 2019

Both subthalamic nucleus (STN) and caudal zona incerta (cZI) have been implicated as the optimal locus for deep brain stimulation (DBS) in Parkinson’s disease (PD). We present a retrospective clinico-anatomical analysis of outcomes from DBS targeting both STN and cZI. Forty patients underwent bilateral DBS using an image-verified implantable guide tube/stylette technique. Contacts on the same quadripolar lead were placed in both STN and cZI. After pulse generator programming, contacts yielding the best clinical effect were selected for chronic stimulation. OFF-medication unified PD rating scale (UPDRS) part III scores pre-operatively and ON-stimulation at 1–2 year follow up were compared. Active contacts at follow-up were anatomically localised from peri-operative imaging. Overall, mean UPDRS part III score improvement was 55 ± 9% (95% confidence interval), with improvement in subscores for rigidity (59 ± 13%), bradykinesia (58 ± 13%), tremor (71 ± 24%) and axial features (36 ± 19%). Active contacts were distributed in the following locations: (1) within posterior/dorsal STN (50%); (2) dorsal to STN (24%); (3) in cZI (21%); and (4) lateral to STN (5%). When contacts were grouped by location, no significant differences between groups were seen in baseline or post-operative improvement in contralateral UPDRS part III subscores. We conclude that when both STN and cZI are targeted, active contacts are distributed most commonly within and immediately dorsal to STN. In a subgroup of cases, cZI contacts were selected for chronic stimulation in preference. Dual targeting of STN and cZI is feasible and may provide extra benefit compared with conventional STN DBS is some patients.
Systematic identification and characterization of Aedes aegypti long noncoding RNAs (lncRNAs)
Authors: Azlan Azali , Obeidat Sattam M. , Yunus Muhammad Amir , Azzam Ghows
Published: August 2019

Long noncoding RNAs (lncRNAs) play diverse roles in biological processes. Aedes aegypti (Ae. aegypti), a blood-sucking mosquito, is the principal vector responsible for replication and transmission of arboviruses including dengue, Zika, and Chikungunya virus. Systematic identification and developmental characterisation of Ae. aegypti lncRNAs are still limited. We performed genome-wide identification of lncRNAs, followed by developmental profiling of lncRNA in Ae. aegypti. We identified a total of 4,689 novel lncRNA transcripts, of which 2,064, 2,076, and 549 were intergenic, intronic, and antisense respectively. Ae. aegypti lncRNAs share many characteristics with other species including low expression, low GC content, short in length, and low conservation. Besides, the expression of Ae. aegypti lncRNAs tend to be correlated with neighbouring and antisense protein-coding genes. A subset of lncRNAs shows evidence of maternal inheritance; hence, suggesting potential role of lncRNAs in early-stage embryos. Additionally, lncRNAs show higher tendency to be expressed in developmental and temporal specific manner. The results from this study provide foundation for future investigation on the function of Ae. aegypti lncRNAs.
Divalent cations can control a switch-like behavior in heterotypic and homotypic RNA coacervates
Authors: Onuchic Paulo L. , Milin Anthony N. , Alshareedah Ibraheem , Deniz Ashok A. , Banerjee Priya R.
Published: August 2019

Liquid-liquid phase separation (LLPS) of RNA-protein complexes plays a major role in the cellular function of membraneless organelles (MLOs). MLOs are sensitive to changes in cellular conditions, such as fluctuations in cytoplasmic ion concentrations. To investigate the effect of these changes on MLOs, we studied the influence of divalent cations on the physical and chemical properties of RNA coacervates. Using a model system comprised of an arginine-rich peptide and RNA, we predicted and observed that variations in signaling cations exert interaction-dependent effects on RNA LLPS. Changing the ionic environment has opposing effects on the propensity for heterotypic peptide-RNA and homotypic RNA LLPS, which results in a switch between coacervate types. Furthermore, divalent ion variations continuously tune the microenvironments and fluid properties of heterotypic and homotypic droplets. Our results may provide a general mechanism for modulating the biochemical environment of RNA coacervates in a cellular context.
Randomized clinical trial: the effect of probiotic Bacillus coagulans Unique IS2 vs. placebo on the symptoms management of irritable bowel syndrome in adults
Authors: Madempudi Ratna Sudha , Ahire Jayesh J. , Neelamraju Jayanthi , Tripathi Anirudh , Nanal Satyavrat
Published: August 2019

The therapeutic effects of B. coagulans Unique IS2 have been well established in children with irritable bowel syndrome (IBS), but its efficacy in adults remain under reported. Thus, in this study the efficacy of B. coagulans Unique IS2 in the management of IBS symptoms in adults was investigated. Patients (n = 153) fulfilling Rome III criteria were provided placebo capsules for a 2 weeks run-in period. Only patients satisfying compliance criteria (n = 136) were randomized (double blind) to receive either B. coagulans Unique IS2 (2 billion CFU) or placebo capsules daily for 8 weeks. Reduction of abdominal discomfort/pain intensity and increase in complete spontaneous bowel movements were analyzed as primary end points. Other clinical symptoms of IBS and serum cytokines were also evaluated. B. coagulans Unique IS2 showed significant improvement in primary and secondary endpoints, as compared to placebo. Haematology of both the arms remained normal. No significant changes in pro- (IL-6, IL-12, TNF-α, INF- γ) and anti-inflammatory cytokine (IL-10) levels were detected at the end of B. coagulans treatment (8 weeks) as compared to placebo. B. coagulans was well tolerated with no severe adverse events to report. Overall, the results demonstrate that B. coagulans Unique IS2 is efficacious in the management of IBS symptoms in adults (18–60 years).
Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series
Authors: Vallon-Christersson Johan , Häkkinen Jari , Hegardt Cecilia , Saal Lao H. , Larsson Christer , Ehinger Anna , Lindman Henrik , Olofsson Helena , Sjöblom Tobias , Wärnberg Fredrik , Ryden Lisa , Loman Niklas , Malmberg Martin , Borg Åke , Staaf Johan
Published: August 2019

Multigene expression signatures provide a molecular subdivision of early breast cancer associated with patient outcome. A gap remains in the validation of such signatures in clinical treatment groups of patients within population-based cohorts of unselected primary breast cancer representing contemporary disease stages and current treatments. A cohort of 3520 resectable breast cancers with RNA sequencing data included in the population-based SCAN-B initiative (ClinicalTrials.gov ID NCT02306096) were selected from a healthcare background population of 8587 patients diagnosed within the years 2010–2015. RNA profiles were classified according to 19 reported gene signatures including both gene expression subtypes (e.g. PAM50, IC10, CIT) and risk predictors (e.g. Oncotype DX, 70-gene, ROR). Classifications were analyzed in nine adjuvant clinical assessment groups: TNBC-ACT (adjuvant chemotherapy, n = 239), TNBC-untreated (n = 82), HER2+/ER− with anti-HER2+ ACT treatment (n = 110), HER2+/ER+ with anti-HER2 + ACT + endocrine treatment (n = 239), ER+/HER2−/LN− with endocrine treatment (n = 1113), ER+/HER2−/LN− with endocrine + ACT treatment (n = 243), ER+/HER2−/LN+ with endocrine treatment (n = 423), ER+/HER2−/LN+ with endocrine + ACT treatment (n = 433), and ER+/HER2−/LN− untreated (n = 200). Gene signature classification (e.g., proportion low-, high-risk) was generally well aligned with stratification based on current immunohistochemistry-based clinical practice. Most signatures did not provide any further risk stratification in TNBC and HER2+/ER– disease. Risk classifier agreement (low-, medium/intermediate-, high-risk groups) in ER+ assessment groups was on average 50–60% with occasional pair-wise comparisons having <30% agreement. Disregarding the intermediate-risk groups, the exact agreement between low- and high-risk groups was on average ~80–95%, for risk prediction signatures across all assessment groups. Outcome analyses were restricted to assessment groups of TNBC-ACT and endocrine treated ER+/HER2−/LN− and ER+/HER2−/LN+ cases. For ER+/HER2− disease, gene signatures appear to contribute additional prognostic value even at a relatively short follow-up time. Less apparent prognostic value was observed in the other groups for the tested signatures. The current study supports the usage of gene expression signatures in specific clinical treatment groups within population-based breast cancer. It also stresses the need of further development to reach higher consensus in individual patient classifications, especially for intermediate-risk patients, and the targeting of patients where current gene signatures and prognostic variables provide little support in clinical decision-making.
Bone sarcoma patient-derived xenografts are faithful and stable preclinical models for molecular and therapeutic investigations
Authors: Nanni Patrizia , Landuzzi Lorena , Manara Maria Cristina , Righi Alberto , Nicoletti Giordano , Cristalli Camilla , Pasello Michela , Parra Alessandro , Carrabotta Marianna , Ferracin Manuela , Palladini Arianna , Ianzano Marianna L. , Giusti Veronica , Ruzzi Francesca , Magnani Mauro , Donati Davide Maria , Picci Piero , Lollini Pier-Luigi , Scotlandi Katia
Published: August 2019

Standard therapy of osteosarcoma (OS) and Ewing sarcoma (EW) rests on cytotoxic regimes, which are largely unsuccessful in advanced patients. Preclinical models are needed to break this impasse. A panel of patient-derived xenografts (PDX) was established by implantation of fresh, surgically resected osteosarcoma (OS) and Ewing sarcoma (EW) in NSG mice. Engraftment was obtained in 22 of 61 OS (36%) and 7 of 29 EW (24%). The success rate in establishing primary cell cultures from OS was lower than the percentage of PDX engraftment in mice, whereas the reverse was observed for EW; the implementation of bothin vivoandin vitroseeding increased the proportion of patients yielding at least one workable model. The establishment ofin vitrocultures from PDX was highly efficient in both tumor types, reaching 100% for EW. Morphological and immunohistochemical (SATB2, P-glycoprotein 1, CD99, caveolin 1) studies and gene expression profiling showed a remarkable similarity between patient’s tumor and PDX, which was maintained over several passages in mice, whereas cell cultures displayed a lower correlation with human samples. Genes differentially expressed between OS original tumor and PDX mostly belonged to leuykocyte-specific pathways, as human infiltrate is gradually replaced by murine leukocytes during growth in mice. In EW, which contained scant infiltrates, no gene was differentially expressed between the original tumor and the PDX. A novel therapeutic combination of anti-CD99 diabody C7 and irinotecan was tested against two EW PDX; both drugs inhibited PDX growth, the addition of anti-CD99 was beneficial when chemotherapy alone was less effective. The panel of OS and EW PDX faithfully mirrored morphologic and genetic features of bone sarcomas, representing reliable models to test therapeutic approaches.
Magnetized suspended carbon nanotubes based nanofluid flow with bio-convection and entropy generation past a vertical cone
Authors: Ramzan Muhammad , Mohammad Mutaz , Howari Fares
Published: August 2019

The captivating attributes of carbon nanotubes (CNT) comprising chemical and mechanical steadiness, outstanding electrical and thermal conductivities, featherweight, and physiochemical consistency make them coveted materials in the manufacturing of electrochemical devices. Keeping in view such exciting features of carbon nanotubes, our objective in the present study is to examine the flow of aqueous based nanofluid comprising single and multi-wall carbon nanotubes (CNTs) past a vertical cone encapsulated in a permeable medium with convective heat and solutal stratification. The impacts of heat generation/absorption, gyrotactic-microorganism, thermal radiation, and Joule heating with chemical reaction are added features towards the novelty of the erected model. The coupled differential equations are attained from the partial differential equations by exercising the local similarity transformation technique. The set of conservation equations supported by the associated boundary conditions are worked out numerically by employing bvp4c MATLAB function. The sway of numerous appearing parameters in the analysis on the allied distributions is scrutinized and the fallouts are portrayed graphically. The physical quantities of interest including Skin friction coefficient, the rate of heat and mass transfers are assessed versus essential parameters and their outcomes are demonstrated in tabulated form. It is witnessed that the velocity of the fluid decreases for boosting values of the magnetic and suction parameters in case of both nanotubes. Moreover, the density of motile microorganism is decreased versus larger estimates of bio-convection constant. A notable highlight of the presented model is the endorsement of the results by matching them to an already published material in the literature. A venerable harmony in this regard is achieved.
A non-linear mathematical model using optical sensor to predict heart decellularization efficacy
Authors: Pereira Rayssa Helena Arruda , Prado Adilson Ribeiro , Caro Luiz Felipe Castello Del , Zanardo Tadeu Ériton Caliman , Alencar Airlane Pereira , Nogueira Breno Valentim
Published: August 2019

One of the main problems of the decellularization technique is the subjectivity of the final evaluation of its efficacy in individual organs. This problem can result in restricted cell repopulation reproducibility and worse responses to transplant tissues. Our proposal is to analyze the optical profiles produced by hearts during perfusion decellularization, as an additional method for evaluating the decellularization process of each individual organ. An apparatus comprised of a structured LED source and photo detector on an adjustable base was developed to capture the relationship between transmitted light during the perfusion of murine hearts, and residual DNA content. Voltage-time graphic records were used to identify a nonlinear mathematical model to discriminate between decellularizations with remaining DNA above (Incomplete Decellularization) and below (Complete Decellularization) the standardized limits. The results indicate that temporal optical evaluation of the process enables inefficient cell removal to be predicted in the initial stages, regardless of the apparent transparency of the organ. Our open system also creates new possibilities to add distinct photo detectors, such as for specific wavelengths, image acquisition, and physical-chemical evaluation of the scaffold, in order to collect different kinds of information, from dozens of studies. These data, when compiled and submitted to machine learning techniques, have the potential to initiate an exponential advance in tissue bioengineering research.
Resveratrol Targets Urokinase-Type Plasminogen Activator Receptor Expression to Overcome Cetuximab-Resistance in Oral Squamous Cell Carcinoma
Authors: Uzawa Katsuhiro , Amelio Antonio L. , Kasamatsu Atsushi , Saito Tomoaki , Kita Akihiro , Fukamachi Megumi , Sawai Yuki , Toeda Yuriko , Eizuka Keitaro , Hayashi Fumihiko , Kato-Kase Ikuko , Sunohara Masataka , Iyoda Manabu , Koike Kazuyuki , Nakashima Dai , Ogawara Katsunori , Endo-Sakamoto Yosuke , Shiiba Masashi , Takiguchi Yuichi , Yamauchi Mitsuo , Tanzawa Hideki
Published: August 2019

Drug resistance to anti-cancer agents is a major concern regarding the successful treatment of malignant tumors. Recent studies have suggested that acquired resistance to anti-epidermal growth factor receptor (EGFR) therapies such as cetuximab are in part caused by genetic alterations in patients with oral squamous cell carcinoma (OSCC). However, the molecular mechanisms employed by other complementary pathways that govern resistance remain unclear. In the current study, we performed gene expression profiling combined with extensive molecular validation to explore alternative mechanisms driving cetuximab-resistance in OSCC cells. Among the genes identified, we discovered that a urokinase-type plasminogen activator receptor (uPAR)/integrin β1/Src/FAK signal circuit converges to regulate ERK1/2 phosphorylation and this pathway drives cetuximab-resistance in the absence of EGFR overexpression or acquired EGFR activating mutations. Notably, the polyphenolic phytoalexin resveratrol, inhibited uPAR expression and consequently the signaling molecules ERK1/2 downstream of EGFR thus revealing additive effects on promoting OSCC cetuximab-sensitivity in vitro and in vivo. The current findings indicate that uPAR expression plays a critical role in acquired cetuximab resistance of OSCC and that combination therapy with resveratrol may provide an attractive means for treating these patients.
Filtration-based water treatment system embedded with black phosphorus for NIR-triggered disinfection
Authors: Li Dengyu , Zhao Qing , Zhang Siyu , Wu Fengchang , Yu Xuefeng , Xiong Zhiqiang , Ma Wei , Wang Dongsheng , Zhang Xuejiao , Xing Baoshan
Published: August 2019

A sandwich-structured filter system embedded with black phosphorus was efficient for NIR-triggered water disinfection.
The cytotoxic potential of cationic triangulenes against tumour cells
Authors: Leung Euphemia , Pilkington Lisa I. , Naiya Mohinder M. , Barker David , Zafar Ayesha , Eurtivong Chatchakorn , Reynisson Jóhannes
Published: August 2019

Close-shelled carbocations DNA intercalators Pr-ADOTA and Pr-DAOTA are very cytotoxic against the cancer cell lines MDA-MB-231 (breast) and HCT116 (colon).
A general low-temperature synthesis route to polyanionic vanadium phosphate fluoride cathode materials: AVPO4F (A = Li, Na, K) and Na3V2(PO4)2F3
Authors: Goubard-Bretesché Nicolas , Kemnitz Erhard , Pinna Nicola
Published: August 2019

A versatile wet chemistry route is reported for the synthesis of highly pure (Li, Na, K)VPO4F and Na3V2(PO4)2F3 cathode materials.
A free-radical-promoted stereospecific denitro silylation of β-nitroalkenes with silanes
Authors: Zhang Xi , Liu Ming-Xia , Wang Tong-Lin , Wang Yong-Qing , Wang Xi-Cun , Quan Zheng-Jun
Published: August 2019

A novel Cu-promoted approach for the stereospecific synthesis of (E)-vinylsilanes through the denitro C–Si coupling reaction of β-nitroalkenes with silanes.
Optimization of the synthesis of quinoline-based neutral cyclometalated iridium complexes via microwave irradiation: design of light harvesting and emitting complexes using bulky quinolines
Authors: Echeverry-Gonzalez Carlos A. , Puerto-Galvis Carlos E. , Borca Carlos H. , Mosquera Martín A. , Luis-Robles Andrés F. , Kouznetsov Vladimir V.
Published: August 2019

We report a fast, simple, and robust microwave methodology for the synthesis of quinoline-based neutral heteroleptic cyclometalated iridium complexes: photophysical and computational characterization of the new complexes.
Solvent-controlled chemoselective N-dealkylation-N-nitrosation or C-nitration of N-alkyl anilines with tert-butyl nitrite
Authors: Guo Xuanhua , Lv Chengdong , Mahmood Qaiser , Zhou Li , Xu Guangqiang , Wang Qinggang
Published: August 2019

A metal-free, acid-free and chemoselective N-dealkylation-N-nitrosation or C-nitration of N-alkyl anilines has been developed.
Structure confirmation and thermal kinetics of the inclusion of cis-jasmone in β-cyclodextrin
Authors: Ai Lvye , Hu Jingyan , Ji Xiaoming , Zhao Huaxin
Published: August 2019

In this study, inclusion complex of cis-jasmone in β-CD (β-CD-CJ) was synthesized to improve cis-jasmone stability.
Isomeric triazines exhibit unique profiles of bioorthogonal reactivity
Authors: Kamber David N. , Nguyen Sean S. , Liu Fang , Briggs Jeffrey S. , Shih Hui-Wen , Row R. David , Long Zane G. , Houk K. N. , Liang Yong , Prescher Jennifer A.
Published: August 2019

Isomeric triazines can be tuned to exhibit unique reaction profiles with biocompatible strained alkenes and alkynes.
High-performance poly(acrylic acid) hydrogels formed with a block copolymer crosslinker containing amino-acid derivatives
Authors: Zhang Rui , Ruan Hengzhi , Zhou Tianxu , Fu Qionglong , Peng Hongwei , Zhu Xuedong , Yao Yuan
Published: August 2019

Two block copolymers containing amino-acid derivatives were employed as a macro-crosslinker to prepare high performance PAA hydrogels concluding desirable mechanical properties and self-healing abilities, as well as notch-insensitivity.
Atomic-scale view of stability and degradation of single-crystal MAPbBr3 surfaces
Authors: Choi Joong Il Jake , Khan Muhammad Ejaz , Hawash Zafer , Kim Ki Jeong , Lee Hyunhwa , Ono Luis K. , Qi Yabing , Kim Yong-Hoon , Park Jeong Young
Published: August 2019

MAPbBr3 (MA: CH3NH3+) undergoes surface degradation under dark and vacuum conditions that leads to the formation of surface PbBr2 species.
A monocrystal Fe3O4@ultrathin N-doped carbon core/shell structure: from magnetotactic bacteria to Li storage
Authors: Su Yibo , Wang Fangxu , Zhang Jian , Tong Rong-Ao , Chong Shaokun , Wang Wei (Alex) , Wang Chang-An , Chen Chuanfang
Published: August 2019

Research on magnetotactic bacteria has attracted much attention in recent years because this kind of bacteria can produce magnetosome chains, which are composed of several Fe3O4(or Fe3S4) monocrystals enveloped by a lipid bilayer.
Determination of partial conductivities and computational analysis of the theoretical power density of BaZr0.1Ce0.7Y0.1Yb0.1O3−δ(BZCYYb1711) electrolyte under various PCFC conditions
Authors: Kim In-Ho , Lim Dae-Kwang , Bae Hohan , Bhardwaj Aman , Park Jun-Young , Song Sun-Ju
Published: August 2019

This work provides performance limits based on the transport properties of electrolyte as a guideline for the further development of suitable electrode materials for PCFCs.
Nanocellulose-based materials as components of polymer electrolyte fuel cells
Authors: Vilela Carla , Silvestre Armando J. D. , Figueiredo Filipe M. L. , Freire Carmen S. R.
Published: August 2019

The present review article ventures into the question “Do the nanoscale forms of cellulose have potential in fuel cell systems?”
Graphene quantum dot/Co(OH)2electrode on nanoporous Au–Ag alloy for superior hybrid micro-supercapacitors
Authors: Xia Qiuyu , Zeng Wen , Ji Fengzhen , Chen Xinman , Zhang Yong , Ling Faling , Hu Wei , Fang Liang , Khisro Said Nasir , Zhou Miao
Published: August 2019

Graphene quantum dot (GQD)/Co(OH)2composite based wire-shaped, quasi-solid-state hybrid supercapacitor device exhibits enhanced specific capacitance, a high capacitance retention rate and superior device stability.