bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical calculus of the mechanical strength of binary oxide glasses
Authors: Eftimie M , Filip A , Banu A
Published: November 2019

The mechanical strength of the glasses is determined by the strength of the established bonds between the different macro-anionic species, these bonds being the weaker compared to the covalent ones inside the macro-anionic species. In this paper is proposed a probabilistic relationship to calculate the theoretical mechanical strength of the SiO2 glass and of some compositions in the Na2O⋅Si2 system, in good agreement with literature data.
Applications of piezoelectric MFC type transducers in mechatronic measurement systems - the impact of a mechanical subsystem damage on a system operation
Authors: Placzek M
Published: November 2019

The work include a report of research works concerning applications of non-classical piezoelectric transducers in mechatronic measuring systems. Composite piezoelectric transducers called Macro Fiber Composite (MFC) are considered. Characteristics of considered transducers were made, indicating their advantages and disadvantages, as well as the results of carried out laboratory tests are presented, in which MFC transducers were used as sensors for mechatronic measurement systems. A series of laboratory tests was carried out on the created laboratory stand to determine the impact on the measured values of damage of the mechanical subsystem on which the MFC-type piezoelectric transducer was glued. Results of measurements are presented and analysed in relation to different applications of the piezoelectric MFC sensors.
Distance-aware Data Forwarding Protocol for Named Data Mobile Ad-hoc Network (NDMANET)
Authors: Lai Junyu , Chen Zhongwei , Li Chengkang , Sun Yingbing , Xiao Han
Published: November 2019

Information Centric Network (ICN) is a promising future networking architecture, while Named Data Networking (NDN) is regarded as ICN’s representative and authoritative scheme. In the recent past, applying ICN/NDN concept in mobile ad-hoc network (MANET), i.e. Named Data Mobile Ad-hoc Network (NDMANET), has attracted a plenty of research efforts. Compared to legacy IP protocol, NDN scheme is considered to be more robust and profitable to the node mobility and the dynamically changed topologies in the MANET domain. This paper focuses on NDMANET’s packet forwarding protocols, which to a large extent decides the efficiency of data dissemination and is a vital module of NDMANET. Firstly, the paper investigates and analyzes some existing packet forwarding protocols, which are widely accepted in NDMANET. On that basis, an innovative distance-aware data forwarding (DDF) protocol is elaborated for NDMANET, with the purpose of further enhancing its network performance. Comprehensive simulation experiments have been conducted and the results illustrate that the proposed DDF protocol can introduce considerable reduction in bandwidth and in energy consumption, with only slightly degrading the response ratio.
Modeling and Simulation of Bow Wave in Aerial Refueling
Authors: Zhai Kunxian , Zhou Suiping , Li Xiaoping , Liu Yanming
Published: November 2019

In a probe-and-drogue aerial refueling system, the tanker docking system consists of a hose and a drogue. When the receiver approaches the drogue, the dynamics of the drogue may be seriously disturbed by the aerodynamic effect from the receiver which is commonly known as the bow wave effect. In this paper, a numerical simulation method based on potential flow theory is proposed to investigate the bow wave effect. The proposed method is efficient and can be conveniently used in the modelling and simulation of autonomous aerial refuelling system. The results of this method are highly consistent with the CFD results, which demonstrates the effectiveness of the proposed method.
Based on MATLAB Simulation to Analyze the Online Source Interaction of the Photovoltaic Power Grid
Authors: Luo Lin Qing , Ma Zhao Xing
Published: November 2019

Firstly, the influence of voltage fluctuation and power loss on power flow distribution is analyzed by theoretical formula. Then, under the simulation experiment of MATLAB, the related problems arising from the power quality of the distribution network when the distributed photovoltaic power generation is connected to the power grid are studied, and the influence of voltage fluctuations and harmonics on it is analyzed. Through simulation test, the corresponding voltage, current and power waveforms are obtained. To study the effects of the waveform, and incorporate FFT analysis tools to observe harmonic content. The simulation results show that the node voltage will increase with the reverse current phenomenon of pv and netease. In the process of grid-connection, a large number of higher harmonics are difficult to filter completely.
Study on the Forecasting of the Hot Corrosion Resistance of Typical Superalloys for Aeroengines
Authors: Bingxiu Guo , Wang Xiaohui , Wang Yanyan , Shao Yue
Published: November 2019

The high-temperature components of aeroengines are in contact with gas flow for a long time, making them susceptible to hot corrosion, which can affect the reliability and lifespan of aeroengines. In this study, five types of superalloys commonly used in the high-temperature components of Aeroengines are selected for gas-based hot corrosion tests, and the corrosion rates are calculated using the weight loss method. Gradient Boosting Regression Tree (GBRT) machine learning algorithm is utilized to establish a corrosion rate forecasting model. The evaluation results show the predictability of this method. The effect of input parameters, including main alloy chemical composition and corrosion time, on the corrosion rate was discussed using GBRT and critical factors are obtained. These results provide a reference for the protection of aeroengines from hot corrosion.
Analysis of IGS Data Based on Military Action Prediction
Authors: Fu Qiang , Shi Guowei , Fu Wentao , Ji Yuanfa , Sun Xiyan
Published: November 2019

In order to verify that the analysis of satellite navigation signal observation data can be used as a means of predicting military operations, this paper combines the recent Iranian shooting down of UAV event, using RTKLIB software to analyze the parameter of visible satellite numbers, SNR(signal-to-noise ratio), and accuracy factor, multipath error, positioning accuracy and other indicators in order to avoid errors in the analysis results of a single type of receiver data analysis, further IGS in the vicinity of Iran and around the world according to the type of receiver, antenna type, and firmware version used. Observe the data for analysis. The analysis shows that the signal power of the GPS L2 frequency is enhanced in the United States from 15:00 on June 20, 2019 to 9:00 on June 21, 2019. The enhancement range is global. The analysis system of this paper can as an effective means of accurately predicting and judging military operations.
The Political Economy of the Developmental State in Latin America
Authors: Orihuela José Carlos
Published: November 2019

The role of the state in economic development is broad, old, and metamorphic. Drawing on historical political economy and a critical reading of new institutional scholarship, our understanding of the developmental state is contextual and complex. Successful developmental state formation is the result of stable political-economic environments, cultural legacies of earlier state-making functioning as mental maps for new statecraft, coherent institutional and policy entrepreneurship, and sustained growth that gives positive feedback in state-making. Latin American state developmentalism has always been diverse, before and after the debt crisis. In the era of state-led industrialization, the Latin American developmental state “failed” because, with domestic and regional markets small and dependence on foreign markets and financial capital high, macroeconomic policymaking did not learn to deal with crises and cyclical external conditions. Developmental state success in the 21st century depends on undertaking less volatile political-economic pathways to facilitate organizational learning by doing. In exclusionary Latin America more than in other corners of the world, developmental state success also means reconciling economic and social goals.
The gap problem made easy?
Authors: Lo Tien-Chun
Published: November 2019

Byerly recently developed a new solution to the gap problem for cosmological arguments. His idea is that the best explanation for why the necessary being is found to have necessary existence is that it is a perfect being. I raise an objection to Byerly’s solution on the ground that there is some rival naturalistic explanation that is as good as Byerly s theistic explanation.
The function of secondary metabolites in plant carnivory
Authors: Hatcher Christopher R , Ryves David B , Millett Jonathan
Published: November 2019

Background

Carnivorous plants are an ideal model system for evaluating the role of secondary metabolites in plant ecology and evolution. Carnivory is a striking example of convergent evolution to attract, capture and digest prey for nutrients to enhance growth and reproduction and has evolved independently at least ten times. Though the roles of many traits in plant carnivory have been well studied, the role of secondary metabolites in the carnivorous habit is considerably less understood.

Scope

This review provides the first synthesis of research in which secondary plant metabolites have been demonstrated to have a functional role in plant carnivory. From these studies we identify key metabolites for plant carnivory and their functional role, and highlight biochemical similarities across taxa. From this synthesis we provide new research directions for integrating secondary metabolites into understanding of the ecology and evolution of plant carnivory.

Conclusions

Carnivorous plants use secondary metabolites to facilitate prey attraction, capture, digestion and assimilation. We found ~170 metabolites for which a functional role in carnivory has been demonstrated. Of these, 26 compounds are present across genera that independently evolved a carnivorous habit, suggesting convergent evolution. Some secondary metabolites have been co-opted from other processes, such as defence or pollinator attraction. Secondary metabolites in carnivorous plants provide a potentially powerful model system for exploring the role of metabolites in plant evolution. They also show promise for elucidating how the generation of novel compounds, as well as the co-option of pre-existing metabolites, provides a strategy for plants to occupy different environments.
ADDO: a comprehensive toolkit to detect, classify and visualize additive and non-additive quantitative trait loci
Authors: Cui Leilei , Yang Bin , Pontikos Nikolas , Mott Richard , Huang Lusheng
Published: November 2019

Motivation

During the past decade, genome-wide association studies (GWAS) have been used to map quantitative trait loci (QTLs) underlying complex traits. However, most GWAS focus on additive genetic effects while ignoring non-additive effects, on the assumption that most QTL act additively. Consequently, QTLs driven by dominance and other non-additive effects could be overlooked.

Results

We developed ADDO, a highly efficient tool to detect, classify and visualize QTLs with additive and non-additive effects. ADDO implements a mixed-model transformation to control for population structure and unequal relatedness that accounts for both additive and dominant genetic covariance among individuals, and decomposes single-nucleotide polymorphism effects as either additive, partial dominant, dominant or over-dominant. A matrix multiplication approach is used to accelerate the computation: a genome scan on 13 million markers from 900 individuals takes about 5 h with 10 CPUs. Analysis of simulated data confirms ADDO’s performance on traits with different additive and dominance genetic variance components. We showed two real examples in outbred rat where ADDO identified significant dominant QTL that were not detectable by an additive model. ADDO provides a systematic pipeline to characterize additive and non-additive QTL in whole genome sequence data, which complements current mainstream GWAS software for additive genetic effects.

Availability and implementation

ADDO is customizable and convenient to install and provides extensive analytics and visualizations. The package is freely available online at https://github.com/LeileiCui/ADDO.

Supplementary information

Supplementary data are available at Bioinformatics online.
Blood-based protein mediators of senility with replications across biofluids and cohorts
Authors: Royall Donald R , Palmer Raymond F ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: November 2019

Dementia severity can be quantitatively described by the latent dementia phenotype ‘δ’ and its various composite ‘homologues’. We have explored δ’s blood-based protein biomarkers in the Texas Alzheimer’s Research and Care Consortium. However, it would be convenient to replicate them in the Alzheimer’s Disease Neuroimaging Initiative. To that end, we have engineered a δ homologue from the observed cognitive performance measures common to both projects [i.e. ‘d:Texas Alzheimer’s Research and Care Consortium to Alzheimer’s Disease Neuroimaging Initiative’ (dT2A)]. In this analysis, we confirm 13/22 serum proteins as partial mediators of age’s effect on dementia severity as measured by dT2A in the Texas Alzheimer’s Research and Care Consortium and then replicate 4/13 in the Alzheimer’s Disease Neuroimaging Initiative’s plasma data. The replicated mediators of age-specific effects on dementia severity are adiponectin, follicle-stimulating hormone, pancreatic polypeptide and resistin. In their aggregate, the 13 confirmed age-specific mediators suggest that ‘cognitive frailty’ pays a role in dementia severity as measured by δ. We provide both discriminant and concordant support for that hypothesis. Weight, calculated low-density lipoprotein and body mass index are partial mediators of age’s effect in the Texas Alzheimer’s Research and Care Consortium. Biomarkers related to other disease processes (e.g. cerebrospinal fluid Alzheimer’s disease-specific biomarkers in the Alzheimer’s Disease Neuroimaging Initiative) are not. It now appears that dementia severity is the sum of multiple independent processes impacting δ. Each may have a unique set of mediating biomarkers. Age’s unique effect appears to be at least partially mediated through proteins related to frailty. Age-specific mediation effects can be replicated across cohorts and biofluids. These proteins may offer targets for the remediation of age-specific cognitive decline (aka ‘senility’), help distinguish it from other determinants of dementia severity and/or provide clues to the biology of Aging Proper.
Sexually Transmitted Infection Screening Among Gay, Bisexual, and Other Men Who Have Sex With Men Prescribed Pre-exposure Prophylaxis in Baltimore City, Maryland
Authors: Schumacher Christina , Wu Linxuan , Chandran Aruna , Fields Errol , Price Ashley , Greenbaum Adena , Jennings Jacky M ,   IMPACT Partner Collaborative, Page Kathleen , Davis Maisha , Ryscavage Patrick , Leitch Jones Joyce , Farley Jason , Arrington-Sanders Renata , Tepper Vicki , Demissew Mimi
Published: November 2019

Background

Human immunodeficiency virus pre-exposure prophylaxis (PrEP) clinical guidelines recommend men who have sex with men (MSM) PrEP users be screened biannually for syphilis and gonorrhea/chlamydia at all anatomic sites. We sought to determine the proportion screened and positive by STI and anatomic site at PrEP initiation and PrEP-care visits and patient-level characteristics associated with screening among MSM PrEP users in Baltimore City, Maryland.

Methods

Medical records among MSM initiating PrEP between 30 September 2015 and 31 March 2018 were abstracted. STI screening (syphilis and gonorrhea/chlamydia at all anatomic sites) and positivity at PrEP visits ≤12 months following initiation were calculated. Poisson regression with cluster robust SEs was used to assess associations with STI screening.

Results

Among 290 MSM initiating PrEP, 43.1% (n = 125) were screened per guidelines at PrEP initiation; 79.3% (230), 69.3% (201), 55.9% (162), and 69.3% (201) were screened for syphilis, urogenital, rectal, and oropharyngeal gonorrhea/chlamydia, respectively. Positivity among those screened was syphilis, 7.8% (n = 18/230); gonorrhea, 5.0% urogenital (10/201), 11.1% rectal (18/162), and 7.5% oropharyngeal (15/201); chlamydia, 5.0% urogenital (10/201), 11.7% rectal (19/162), and 1.5% oropharyngeal (3/201). Reported anal and oral sex (vs neither) was independently associated with STI screening (aPR, 2.11; 1.05–4.27) at PrEP initiation. At biannual PrEP-care visits, STI screening was lower and syphilis and rectal gonorrhea/chlamydia positivity was higher.

Conclusions

Observed STI screening levels and disease burden suggest the effectiveness of STI screening in PrEP care for STI prevention may be limited. Our results suggest providers may be offering screening based on sexual practices; clarification of STI screening guidelines for PrEP users is needed.
O100 WORLDWIDE TECHNIQUES AND OUTCOMES OF ROBOT-ASSISTED MINIMALLY INVASIVE ESOPHAGECTOMY (RAMIE): RESULTS FROM THE INTERNATIONAL UGIRA REGISTRY
Authors: Kingma B F , Grimminger P P , van Det M J , Chao Y K , Chiu P , Sallum R A , Egberts J H , Chaudry A , Luketich J D , Ruurda J P , van Hillegersberg R ,   UGIRA Study Group
Published: November 2019

Aim

The aim of this study was to gain insight in the techniques and outcomes of RAMIE worldwide.

Background & Methods

Although robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted. The current literature on RAMIE mainly consists of single-center case series with considerable variation in reported techniques and outcomes. To gain an overview of the worldwide practice in RAMIE, an online registry was established by the Upper GI International Robotic Association (UGIRA). The collected data involve patient- and treatment characteristics, as well as postoperative outcomes that include complications as defined by the Esophageal Complications Consensus Group, length of stay, re-admissions (i.e. <30 days after discharge), mortality (i.e. in-hospital or <30 days after surgery), and pathological results. The outcomes were descriptively analyzed for this interim report.

Results

A total of 434 patients who underwent RAMIE for esophageal cancer between 2016-2019 were included in this interim analysis. The mean age was 63 years (SD ±9.7), the majority was male (n=359, 83%), and nearly all patients had an ASA score ≥2 (n=398, 92%). Adenocarcinoma (n=253, 58%) and squamous cell carcinoma (n=162, 37%) were most prevalent. The usual surgical approach was transthoracic (n=428, 99%) with the patient in semiprone position (n=393, 91%). Gastric conduit reconstruction was performed in all except one patient, who received a colonic interposition. The anastomosis was created by hand-sewing (n=207, 48%), circular stapling (n=142, 32%), or linear stapling (n=85, 20%). The median intraoperative blood loss was 120 milliliters (IQR 70-280) and the median operating time was 392 minutes (IQR 353-455). Postoperative complications occurred in 251 patients (59%) and mainly involved pulmonary complications (n=138, 32%), anastomotic leakage (n=80, 18%), and cardiac complications (n=55, 13%). Mortality occurred in 9 patients (2%) and re-admission because of complications was required in 57 patients (14%). A median of 28 lymph nodes (IQR 21-35) were removed and a radical resection was achieved in 400 patients (92%).

Conclusion

The presented results are the first to provide an overview of the techniques that are commonly used in RAMIE. By demonstrating results that are in line with recent benchmarking literature, this study demonstrates the safety and feasibility of RAMIE.
O187 ANASTOMOTIC TECHNIQUES AND ASSOCIATED MORBIDITY IN TOTAL MINIMALLY-INVASIVE TRANSTHORACIC ESOPHAGECTOMY – RESULTS FROM THE ESOBENCHMARK DATABASE
Authors: Schroeder W , Raptis D , Schmidt H , Gisbertz S , Moons J , Asti E , Luyer M , Hoelscher A , Schneider P , van Berge Henegouwen M , Nafteux P , Nilsson M , Räsanen J , Palazzo F , Mercer S , Bonavina L , Nieuwenhuijzen G , Wijjnhoven B , Pattyn P , Grimminger P , Bruns C , Gutschow C
Published: November 2019

Background

Total minimally-invasive transthoracic esophagectomy (ttMIE) faces increasing application in surgical treatment of esophageal cancer. For esophago-gastric reconstruction, different anastomotic techniques are currently used, but their impact on postoperative anastomotic leakage and morbidity has not been investigated. The aim of this retrospective multicenter analysis was to describe anastomotic techniques used for ttMIE and to analyze the associated morbidity.

Patients and Methods

Patients were selected from a basic dataset, collected over a 5-year period from 13 international surgical high-volume centers. Endpoints were anastomotic leakage rate and postoperative morbidity in correlation to anastomotic techniques, measured by the CD classification and the Comprehensive Complication Index® (CCI).

Results

Five anastomotic techniques were identified in 966 patients after ttMIE: Intrathoracic end-to-side circular-stapled technique in 427 patients (double-stapling n=90, purse-string n=337), intrathoracic (n=109) or cervical (n=255) side-to-side linear-stapled, and cervical end-to-side hand-sewn (n=175). Leakage rates were similar in intrathoracic and cervical anastomoses (15.9% vs. 17.2%, P=0.601), but overall complications (56.7%% vs. 63.7%, P=0.029) and median 90-day CCI (21 (IQR 0-36) vs. 29 (IQR 0-40), P=0.019) favored intrathoracic reconstructions. Leakage rates after intrathoracic end-to-side double-stapling (23.3%) and cervical end-to-side hand-sewn (25.1%) techniques were significantly higher compared with intrathoracic side-to-side linear (15.6%), end-to-side purse-string (13.9%) and cervical side-to-side linear-stapled esophago-gastrostomies (11.8%) (P<0.001). Multivariable analysis confirmed anastomotic technique as independent predictor of leakage after ttMIE.

Conclusion

Results of this analysis present the current status of the technical evolution of ttMIE with anastomotic leakage as predominant surgical complication. However, technique-related morbidity requires cautious interpretation considering the long learning curve of this complex surgical procedure.
Death of a Child Prior to Midlife, Dementia Risk, and Racial Disparities
Authors: Umberson Debra , Donnelly Rachel , Xu Minle , Farina Matthew , Garcia Michael A
Published: November 2019

Objectives

This study considers whether experiencing the death of a child prior to midlife (by parental age 40) is associated with subsequent dementia risk, and how such losses, which are more common for black than for white parents, may add to racial disparities in dementia risk.

Methods

We use discrete-time event history models to predict dementia incidence among 9,276 non-Hispanic white and 2,182 non-Hispanic black respondents from the Health and Retirement Study, 2000–2014.

Results

Losing a child prior to midlife is associated with increased risk for later dementia, and adds to disparities in dementia risk associated with race. The death of a child is associated with a number of biosocial variables that contribute to subsequent dementia risk, helping to explain how the death of child may increase risk over time.

Discussion

The death of a child prior to midlife is a traumatic life course stressor with consequences that appear to increase dementia risk for both black and white parents, and this increased risk is explained by biosocial processes likely activated by bereavement. However, black parents are further disadvantaged in that they are more likely than white parents to experience the death of a child, and such losses add to the already substantial racial disadvantage in dementia risk.
Body Appreciation and Health Care Avoidance: A Brief Report
Authors: Cook Mackenzie , Ramseyer Winter Virginia , O’Neill Elizabeth A
Published: November 2019

Research suggests that body image is related to health behaviors and health care use, but possible mechanisms for this relationship remain unclear. The current study examined the presence of a relationship between body appreciation and avoiding the doctor to avoid being weighed, using a diverse sample of women (N = 499). Controlling for body size and determinants of health care utilization, logistic regression results suggested that women with higher body appreciation were less likely to avoid health care to avoid being weighed (odds ratio = 0.38, p < .001). In addition, differences in avoiding the doctor to avoid being weighed were found for the covariates (that is, age, race, body mass index, and socioeconomic status). These results inform knowledge regarding barriers to health care use and the relationship between body image and health care use. The article concludes with a discussion of the implications for future research, social work interventions, and social work education to promote women’s health and well-being.
The Role of Bacteria and Its Derived Metabolites in Chronic Pain and Depression: Recent Findings and Research Progress
Authors: Li Shan , Hua Dongyu , Wang Qiaoyan , Yang Ling , Wang Xinlei , Luo Ailin , Yang Chun
Published: November 2019

Background

Chronic pain is frequently comorbid with depression in clinical practice. Recently, alterations in gut microbiota and metabolites derived therefrom have been found to potentially contribute to abnormal behaviors and cognitive dysfunction via the “microbiota–gut–brain” axis.

Methods

PubMed was searched and we selected relevant studies before October 1, 2019. The search keyword string included “pain OR chronic pain” AND “gut microbiota OR metabolites”; “depression OR depressive disorder” AND “gut microbiota OR metabolites”. We also searched the reference lists of key articles manually.

Results

This review systematically summarized the recent evidence of gut microbiota and metabolites in chronic pain and depression in animal and human studies. The results showed the pathogenesis and therapeutics of chronic pain and depression might be partially due to gut microbiota dysbiosis. Importantly, bacteria-derived metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and secondary bile acids, offer new insights into the potential linkage between key triggers in gut microbiota and potential mechanisms of depression.

Conclusion

Studying gut microbiota and its metabolites has contributed to the understanding of comorbidity of chronic pain and depression. Consequently, modulating dietary structures or supplementation of specific bacteria may be an available strategy for treating chronic pain and depression.
Analytic Extensions of Representations of *-Subsemigroups Without Polar Decomposition
Authors: Oeh Daniel
Published: November 2019

Let $(G,\tau )$ be a finite-dimensional Lie group with an involutive automorphism $\tau $ of $G$ and let ${{\mathfrak {g}}} = {{\mathfrak {h}}} \oplus {{\mathfrak {q}}}$ be its corresponding Lie algebra decomposition. We show that every nondegenerate strongly continuous representation on a complex Hilbert space ${\mathcal {H}}$ of an open $^\ast $-subsemigroup $S \subset G$, where $s^{\ast } = \tau (s)^{-1}$, has an analytic extension to a strongly continuous unitary representation of the 1-connected Lie group $G_1^c$ with Lie algebra $[{{\mathfrak {q}}},{{\mathfrak {q}}}] \oplus i{{\mathfrak {q}}}$. We further examine the minimal conditions under which an analytic extension to the 1-connected Lie group $G^c$ with Lie algebra ${{\mathfrak {h}}} \oplus i{{\mathfrak {q}}}$ exists. This result generalizes the Lüscher–Mack theorem and the extensions of the Lüscher–Mack theorem for $^\ast $-subsemigroups satisfying $S = S(G^\tau )_0$ by Merigon, Neeb, and Ólafsson. Finally, we prove that nondegenerate strongly continuous representations of certain $^\ast $-subsemigroups $S$ can even be extended to representations of a generalized version of an Olshanski semigroup.
Pharmacokinetics and antiviral activity of cabotegravir and rilpivirine in cerebrospinal fluid following long-acting injectable administration in HIV-infected adults
Authors: Letendre Scott L , Mills Anthony , Hagins Debbie , Swindells Susan , Felizarta Franco , Devente Jerome , Bettacchi Christopher , Lou Yu , Ford Susan , Sutton Kenneth , Shaik Jafar Sadik , Crauwels Herta , D’Amico Ronald , Patel Parul
Published: November 2019

Background

Long-acting (LA) formulations of cabotegravir, an HIV integrase inhibitor, and rilpivirine, an NNRTI, are in development as monthly or 2 monthly intramuscular (IM) injections for maintenance of virological suppression.

Objectives

To evaluate cabotegravir and rilpivirine CSF distribution and HIV-1 RNA suppression in plasma and CSF in HIV-infected adults participating in a substudy of the Phase 2b LATTE-2 study (NCT02120352).

Methods

Eighteen participants receiving cabotegravir LA 400 mg + rilpivirine LA 600 mg IM [every 4 weeks (Q4W), n = 3] or cabotegravir LA 600 mg + rilpivirine LA 900 mg IM [every 8 weeks (Q8W), n = 15] with plasma HIV-1 RNA <50 copies/mL enrolled. Paired steady-state CSF and plasma concentrations were evaluable in 16 participants obtained 7 (±3) days after an injection visit. HIV-1 RNA in CSF and plasma were assessed contemporaneously using commercial assays.

Results

Median total CSF concentrations in Q4W and Q8W groups, respectively, were 0.011 μg/mL and 0.013 μg/mL for cabotegravir (0.30% and 0.34% of the paired plasma concentrations) and 1.84 ng/mL and 1.67 ng/mL for rilpivirine (1.07% and 1.32% of paired plasma concentrations). Cabotegravir and rilpivirine total CSF concentrations exceeded their respective in vitro EC50 for WT HIV-1 (0.10 ng/mL and 0.27 ng/mL, respectively). All 16 participants had HIV-1 RNA <50 copies/mL in plasma and CSF, and 15 of 16 participants had HIV-1 RNA <2 copies/mL in CSF.

Conclusions

A dual regimen of cabotegravir LA and rilpivirine LA achieved therapeutic concentrations in the CSF resulting in effective virological control in CSF.
Toward the Interpretation of Positive Testing for Fentanyl and Its Analogs in Real Hair Samples: Preliminary Considerations
Authors: Salomone A , Bigiarini R , Palamar J J , McKnight C , Vinsick L , Amante E , Di Corcia D , Vincenti M
Published: November 2019

The detection of new psychoactive substances (NPS) in hair has become extensively researched in recent years. Although most NPS fall into the classes of synthetic cannabinoids and designer cathinones, novel synthetic opioids (NSO) have appeared with increasing frequency in the illicit drug supply. While the detection of NSO in hair is now well documented, interpretation of results presents several controversial issues, as is quite common in hair analysis. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry method able to detect 13 synthetic opioids (including fentanyl analogs) and metabolites in hair was applied to 293 real samples. Samples were collected in the USA between November 2016 and August 2018 from subjects who had reported heroin use in the past year or had already tested positive to hair testing for common opiates. The range, mean and median concentrations were calculated for each analyte, in order to draw a preliminary direction for a possible cut-off to discriminate between exposure to either low or high quantities of the drug. Over two-thirds (68%) of samples tested positive for fentanyl at concentrations between LOQ and 8600 pg/mg. The mean value was 382 pg/mg and the median was 95 pg/mg. The metabolites norfentanyl and 4-ANPP were also quantified and were found between LOQ and 320 pg/mg and between LOQ and 1400 pg/mg, respectively. The concentration ratios norfentanyl/fentanyl, 4-ANPP/fentanyl and norfentanyl/4-ANPP were also tested as potential markers of active use and to discriminate the intake of fentanyl from other analogs. The common occurrence of samples positive for multiple drugs may suggest that use is equally prevalent among consumers, which is not the case, as correlations based on quantitative results demonstrated. We believe this set of experimental observations provides a useful starting point for a wide discussion aimed to better understand positive hair testing for fentanyl and its analogs in hair samples.
Influence of in-situ rock stress on the stability of roadway surrounding rock: a case study
Authors: Ji Ming , Guo Hongjun
Published: November 2019

In-situ rock stress was measured in the development roadway of Gucheng coal mine at +420 m level by using the stress relief method of hollow inclusion. The results show that the first principal stress was the vertical stress, the maximum horizontal principal stresses were distributed in the range of N10°E and N20°E, and the average side pressure coefficient was 0.83. There was a large difference between the maximum horizontal principal stress and the minimum horizontal principal stress, and the calculated average ratio was 2.02. A spatial stress conversion model of the horizontal roadway based on the measured in-situ rock stresses was built, and the distribution laws of stress and displacement of the surrounding rock of the roadway were analyzed in depth along the changing radial direction. According to the Mohr–Coulomb failure criterion, an asymmetric surrounding rock plastic zone was obtained and the plastic failure radius was 5.0 m. Considering the roadway-surrounding rock differential control, the stronger support in the risk areas was practiced and validated. The work in this paper would provide some ideas for the design and optimization of the support parameters for roadway engineering.
Black to Ireland: Circum-Atlantic Double Exposure and Racialized Jump Cuts in The Emperor Jones
Authors: Johnson Katie N
Published: November 2019

The Emperor Jones (1933) was a film aimed at critiquing empire while also evoking the black diaspora. Yet the film was created by a team of Irish-American artists (playwright Eugene O’Neill, director Dudley Murphy, and actor Dudley Digges). Their work on The Emperor Jones came from a commitment to the idea that the colonization of Ireland was of a piece with the results of anti-black racism, colonialism and imperialism (although not similar), and as a way of negotiating their own contested relationship with legitimating structures in white, US culture. The film’s racial politics, which have been debated since its premiere, repeatedly interlink a range of global and circum-Atlantic legacies of white imperialism. The Emperor Jones abounds with contradictions: it both shattered racial constraints in American film while also articulating racial anxieties. We can see this manifested in two ways. First, the film’s anti-imperialist, antiracist ambitions are visible in the director’s attempt to overlay different cartographies, memories, and experiences of racial violation with a technique that I call “circum-Atlantic double exposure.” The second characteristic, which I call the “racialized jump cut,” is the mark of state censors and local projectionists who spliced out potentially inflammatory material from the film. Central to my argument is that double-exposure works together with racialized jump cuts in The Emperor Jones: the cut points to the doubling; the dissolve highlights the (w)hole. These two strikingly divergent and paradoxical features of the film—the director’s accretions and the state’s depletions—expose the problematics of representing imperial violence.
The growth of brightest cluster galaxies and intracluster light over the past 10 billion years
Authors: DeMaio Tahlia , Gonzalez Anthony H , Zabludoff Ann , Zaritsky Dennis , Aldering Greg , Brodwin Mark , Connor Thomas , Donahue Megan , Hayden Brian , Mulchaey John S , Perlmutter Saul , Stanford S A
Published: November 2019

We constrain the evolution of the brightest cluster galaxy plus intracluster light (BCG + ICL) using an ensemble of 42 galaxy groups and clusters that span redshifts of z = 0.05−1.75 and masses of M500,c= 2 × 1013−1015 M⊙. Specifically, we measure the relationship between the BCG + ICL stellar mass M⋆ and M500,c at projected radii 10 < r < 100 kpc for three different epochs. At intermediate redshift ($\bar{z}=0.40$), where we have the best data, we find M⋆ ∝ M500,c0.48 ± 0.06. Fixing the exponent of this power law for all redshifts, we constrain the normalization of this relation to be 2.08 ± 0.21 times higher at $\bar{z}=0.40$ than at high redshift ($\bar{z}=1.55$). We find no change in the relation from intermediate to low redshift ($\bar{z}=0.10$). In other words, for fixed M500,c, M⋆ at 10 < r < 100 kpc increases from $\bar{z}=1.55$ to $\bar{z}=0.40$ and not significantly thereafter. Theoretical models predict that the physical mass growth of the cluster from z = 1.5 to z = 0 within r500,c is 1.4×, excluding evolution due to definition of r500,c. We find that M⋆ within the central 100 kpc increases by ∼3.8× over the same period. Thus, the growth of M⋆ in this central region is more than a factor of 2 greater than the physical mass growth of the cluster as a whole. Furthermore, the concentration of the BCG + ICL stellar mass, defined by the ratio of stellar mass within 10 kpc to the total stellar mass within 100 kpc, decreases with increasing M500,c at all z. We interpret this result as evidence for inside–out growth of the BCG + ICL over the past 10 Gyr, with stellar mass assembly occurring at larger radii at later times.
Oxidative damage diminishes mitochondrial DNA polymerase replication fidelity
Authors: Anderson Andrew P , Luo Xuemei , Russell William , Yin Y Whitney
Published: November 2019

Mitochondrial DNA (mtDNA) resides in a high ROS environment and suffers more mutations than its nuclear counterpart. Increasing evidence suggests that mtDNA mutations are not the results of direct oxidative damage, rather are caused, at least in part, by DNA replication errors. To understand how the mtDNA replicase, Pol γ, can give rise to elevated mutations, we studied the effect of oxidation of Pol γ on replication errors. Pol γ is a high fidelity polymerase with polymerase (pol) and proofreading exonuclease (exo) activities. We show that Pol γ exo domain is far more sensitive to oxidation than pol; under oxidative conditions, exonuclease activity therefore declines more rapidly than polymerase. The oxidized Pol γ becomes editing-deficient, displaying a 20-fold elevated mutations than the unoxidized enzyme. Mass spectrometry analysis reveals that Pol γ exo domain is a hotspot for oxidation. The oxidized exo residues increase the net negative charge around the active site that should reduce the affinity to mismatched primer/template DNA. Our results suggest that the oxidative stress induced high mutation frequency on mtDNA can be indirectly caused by oxidation of the mitochondrial replicase.
Sam68 binds Alu-rich introns in SMN and promotes pre-mRNA circularization
Authors: Pagliarini Vittoria , Jolly Ariane , Bielli Pamela , Di Rosa Valentina , De la Grange Pierre , Sette Claudio
Published: November 2019

The Spinal Muscular Atrophy (SMA) gene SMN was recently duplicated (SMN1 and SMN2) in higher primates. Furthermore, invasion of the locus by repetitive elements almost doubled its size with respect to mouse Smn, in spite of an almost identical protein-coding sequence. Herein, we found that SMN ranks among the human genes with highest density of Alus, which are evolutionary conserved in primates and often occur in inverted orientation. Inverted repeat Alus (IRAlus) negatively regulate splicing of long introns within SMN, while promoting widespread alternative circular RNA (circRNA) biogenesis. Bioinformatics analyses revealed the presence of ultra-conserved Sam68 binding sites in SMN IRAlus. Cross-link-immunoprecipitation (CLIP), mutagenesis and silencing experiments showed that Sam68 binds in proximity of intronic Alus in the SMN pre-mRNA, thus favouring circRNA biogenesis in vitro and in vivo. These findings highlight a novel layer of regulation in SMN expression, uncover the crucial impact exerted by IRAlus and reveal a role for Sam68 in SMN circRNA biogenesis.
A single amino acid switch converts the Sleeping Beauty transposase into an efficient unidirectional excisionase with utility in stem cell reprogramming
Authors: Kesselring Lisa , Miskey Csaba , Zuliani Cecilia , Querques Irma , Kapitonov Vladimir , Laukó Andrea , Fehér Anita , Palazzo Antonio , Diem Tanja , Lustig Janna , Sebe Attila , Wang Yongming , Dinnyés András , Izsvák Zsuzsanna , Barabas Orsolya , Ivics Zoltán
Published: November 2019

The Sleeping Beauty (SB) transposon is an advanced tool for genetic engineering and a useful model to investigate cut-and-paste DNA transposition in vertebrate cells. Here, we identify novel SB transposase mutants that display efficient and canonical excision but practically unmeasurable genomic re-integration. Based on phylogenetic analyses, we establish compensating amino acid replacements that fully rescue the integration defect of these mutants, suggesting epistasis between these amino acid residues. We further show that the transposons excised by the exc+/int− transposase mutants form extrachromosomal circles that cannot undergo a further round of transposition, thereby representing dead-end products of the excision reaction. Finally, we demonstrate the utility of the exc+/int− transposase in cassette removal for the generation of reprogramming factor-free induced pluripotent stem cells. Lack of genomic integration and formation of transposon circles following excision is reminiscent of signal sequence removal during V(D)J recombination, and implies that cut-and-paste DNA transposition can be converted to a unidirectional process by a single amino acid change.
The human HELLS chromatin remodelling protein promotes end resection to facilitate homologous recombination and contributes to DSB repair within heterochromatin
Authors: Kollárovič Gabriel , Topping Caitríona E , Shaw Edward P , Chambers Anna L
Published: November 2019

Efficient double-strand break repair in eukaryotes requires manipulation of chromatin structure. ATP-dependent chromatin remodelling enzymes facilitate different DNA repair pathways, during different stages of the cell cycle and in varied chromatin environments. The contribution of remodelling factors to double-strand break repair within heterochromatin during G2 is unclear. The human HELLS protein is a Snf2-like chromatin remodeller family member and is mutated or misregulated in several cancers and some cases of ICF syndrome. HELLS has been implicated in the DNA damage response, but its mechanistic function in repair is not well understood. We discover that HELLS facilitates homologous recombination at two-ended breaks and contributes to repair within heterochromatic regions during G2. HELLS promotes initiation of HR by facilitating end-resection and accumulation of CtIP at IR-induced foci. We identify an interaction between HELLS and CtIP and establish that the ATPase domain of HELLS is required to promote DSB repair. This function of HELLS in maintenance of genome stability is likely to contribute to its role in cancer biology and demonstrates that different chromatin remodelling activities are required for efficient repair in specific genomic contexts.
RTHP-43 (LTBK-02). MULTI-TIME POINT EVALUATION OF PERIPHERAL BLOOD MYELOID-DERIVED SUPPRESSOR CELL AND LYMPHOCYTE POPULATIONS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA RECEIVING ADJUVANT THERAPY
Authors: Sloan Lindsey , Sen Rupashree , Doucet Michele , Blosser Lee , Shpitser Ilya , Sherman Eli , San Numair , Cheng Zhi , Katulis Lisa , Wemmer Jan , Kamson David , Jackson Christina , Hu Chen , McNutt Todd , Grossman Stuart , Holdhoff Matthias , Lim Michael , Redmond Kristin J , Eberhart Charles , Quon Harry , Pardoll Drew , Ganguly Sudipto , Kleinberg Lawrence
Published: November 2019

Alterations in peripheral blood cell populations, including myeloid cell subsets and lymphocytes, have been associated with poor prognostic outcomes in patients with glioblastoma (GBM). To date, evaluation of these populations has largely been on freeze-thawed samples at a limited number of time points. The purpose of our study is to identify the frequency and activation status of tumor-supportive myeloid and lymphocyte subsets during the course of standard adjuvant therapy in patients with GBM in fresh peripheral blood samples. We hypothesize that dysfunctional myeloid and lymphocyte populations expand during standard care temozolomide (TMZ)/radiation therapy (RT). We prospectively enrolled 16 patients with a new diagnosis of GBM that underwent maximal safe surgical resection. Twelve received standard adjuvant therapy consisting of six weeks of TMZ/RT. Four received alternative therapies: one experimental chemotherapeutic/three alternative radiation schemes. Peripheral blood was obtained seven times over the course of adjuvant therapy: prior to starting adjuvant therapy, five during treatment, and once one month after completion of therapy. Eleven patients completed all seven time points. Peripheral blood samples were analyzed by flow cytometry, focusing on immune checkpoints and critical markers of activation of systemic immunity. Available preliminary data demonstrate a median increase of 2.1% (-21.2–27.4%) in the frequency (%fx) of myeloid-derived suppressor cells (MDSC) after commencement of adjuvant therapy at time point 2 (TP2), compared to baseline. To date, 7/16 patients are alive and without evidence of recurrent disease on imaging. The majority of these patients had a decrease in %fx of MDSC at TP2, after starting adjuvant therapy, compared to baseline. The %fx of CD8+ T cells was greatest at TP7 (range: 21.7%-67.0%), one month after TMZ/RT, for most patients. PD-1 and FOXP3 expression by lymphocytes was variable across time points, suggesting the importance of additional factors which will be explored through future analyses. These early findings suggest that the immune response changes throughout the course of TMZ/RT. An understanding of these changes in the peripheral blood, termed immunodynamics in the context of our studies, may be valuable future tool to aid in optimizing immunity in patients with GBM.
Publication Bias and the Cross-Section of Stock Returns
Authors: Chen Andrew Y , Zimmermann Tom
Published: November 2019

We develop an estimator for publication bias-adjusted returns and apply it to 156 published long-short portfolios. Our adjustment uses only in-sample data and provides sharper inferences than out-of-sample tests. Bias-adjusted returns are only 12.3% smaller than in-sample returns with a standard error of 1.7 percentage points. The small bias comes from the dispersion of returns across predictors, which is too large to be explained by data-mined noise. The bias is much smaller than post-publication decay (p-value ¡.0001), suggesting mispricing is important. Our results offer a different perspective about recent papers that find most published predictors are likely false.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.