bluuebunny/crossref_metadata_2025 huggingface dataset:
Industrial integrated energy system optimization with considering thermal power transferring process
Authors: Yuan Weideng , Duan Mengyong , Chen Weihong , Qiu Zejian , Dong Wenjie , Yang Benzhi
Published: April 2020

In the regional integrated energy system, multiple resources on the demand side and supply side should be considered in integrated planning. In particular, how to realize measuring heat energy grade as well as considering thermal energy transferring medium characteristics in the integrated energy system optimization operation and resource allocation is a urgent research area to explore. In this paper, a typical industrial park integrated energy system considering thermal energy transferring process is established. In the beginning, multi-energy flows complementary characteristics of the industrial park have been introduced, which could improve energy usage efficiency by energy conversion, energy storage and energy substitution. Then the models of storage battery, micro-turbine and other resources have been established. In addition, the model of heat energy pipe network has been built considering thermal energy unidirectional transmission and various heat grade. Based on the previous models, the objective function of industrial park economic operation. Finally, the simulation results show that the proposed multi-energy flows model could satisfy the economical operation as well as energy supply balance while obeying energy conservation law and transferring process limit.
A way to improve the performance of the integrated maintenance system in new generation dispatching control system
Authors: Xu Pan , Sun Mingyang , Zhuang Weijin , Zhang Hong , Pan Jiajia
Published: April 2020

As the structural complexity and application relevance of the new generation dispatching control system are increased due to the architecture changes, this paper analyses the actual requirements of integrated maintenance system of the control system and the performance problems in the data collection and analysis processes, introduces the application scenario of distributed memory technology in the integrated maintenance system of the new generation dispatching control system, presents an integrated solution to meet the maintenance performance requirements of the new generation dispatching control system.
Study on eutrophication characteristics of rainy and dry season in Shenzhen Bay
Authors: Huang Xu , Luo Huan , Wu Qiong , Li Zhaoxu , Chen Xiuhong , Hei Liang
Published: April 2020

Firstly, the eutrophication of five monitoring points in Shenzhen Bay was analyzed by using the nutritional status quality index method, and the eutrophication of the entire Shenzhen Bay was analyzed by the results of the eutrophication model simulation. The results showed that the maximum of the nutritional status quality index(NQI) in the dry season was 22, the minimum was 3;the maximum NQI in the rainy season was 23, the minimum was 4, and when NQI is greater than 3, the water is eutrophication level, so whether it was the dry season or the rainy season, Shenzhen Bay is basically eutrophic, and the eutrophication of the Shenzhen Bay in the rainy season is more serious than that in the dry season. Regardless of the dry season or the rainy season, the NQI of the Shenzhen Bay outer area is basically around 5, while the NQI of the interior area is basically larger than that of the outer area. The degree of eutrophication is more serious than that of the outer area;the maximum NQI is 22 in the high tide during the dry season, and the maximum NQI is 23 in the rainy season;the maximum NQI is 21 in the ebb during the dry season, and the maximum NQI in the rainy season is 22, so the eutrophication of Shenzhen Bay is more serious than the ebb when the high tide.
The impact of access to clean water on health of the elderly: Evidence from China
Authors: Liu Chenxi
Published: April 2020

Access to clean water is a crucial part for the health of humans. Many present and previous studies have found that drinking water quality affects people’s health. Our study aims to find the association between drinking water and health of the elderly in China. Through regression analysis, the results show significant association between water facility (access to tap water) and old people’s depression level, difficulties to do daily activities and self-assessed health. The harmful chemicals in unsanitary water bring health risks to the old people. We suggest the government that investing more money on drinking water facilities is necessary to improve both physical and mental health of the elderly.
A study on the characteristics of Ozone Weekend Effect and reaction sensitivity in Chengdu
Authors: Liu Hefan , Deng Ye , Huang Fengxia , Zhang Tianyue , Yang Xinyue , Zhang Xin , Song Danlin , Chen Yan
Published: April 2020

This study improved the computation theory “Ozone Weekend Effect Method” (OWEM) and analyzed the 2016 observation data from the state-controlled ambient air quality monitoring sites in Chengdu using the OWEM theory. The improved OWEM theory is then applied to processing large sample data and making a judgment on photochemical reaction sensitivity in Chengdu. The result of applying the OWEM theory to Chengdu shows 1) that the VOCs-limited period, the NOx-limited period and the photochemical reaction steady-state period, Rt, accounted for 66.06%, 33.64% and 0.30%, respectively; 2) that on a seasonal basis, i.e. in the ozone photochemical reaction occurring in spring, summer, autumn and winter 2016 in Chengdu, the VOCs-limited period accounted for 59.40%, 72.49%, 63.85% and 68.49% of the 2016 observed data, respectively, and the NOx-limited period accounted for 39.70%, 27.51%, 36.15% and 31.19%respectively; 3) that in the VOCs-limited period and the NOx-limited period of August 2016, the month when the most serious ozone pollution of that year occurred in Chengdu, Rt accounted for 70.0% and 30.0%, respectively, and that there was no photochemical reaction steady-state zone period that month; 4) and that through estimation, it is suggested that as for the ozone pollution control of Chengdu, the ratio of VOCs emission reduction to NOx emission reduction should be around 3:1.
Present situation of hazardous waste generation in China and grey model prediction
Authors: Yan Jinchuan , Liu Yi , Li Zhi
Published: April 2020

According to the 2008-2017 China Environmental Statistics Yearbook data, combined with GIS heat map, the current situation and regional distribution characteristics of hazardous waste generation and disposal in China were analyzed, and the GM gray model was constructed to predict its output in the next five years. The results show that it is predicted that by the end of 2023, hazardous waste production of China will reach 157,889,300 tons. It is suggested that take the government as the guidance, the production and disposal enterprises will jointly promote the development of hazardous waste resources, improve the existing treatment methods and strengthen the hazardous waste management system, thus breaking the deadlock of geographical mismatch.
Adsorption of ampicillin sodium on activated carbons with different surface chemistries
Authors: Li Xin , Zhang Nannan , Yang Liyan
Published: April 2020

BACKGROUND: The adsorption of ampicillin from aqueous solution by three types of activated carbon was investigated. The first was a commercial activated carbon (AC), the second (AAC) was AC modified by HNO3 oxidation and the third (HAAC) was AAC modified through thermal treatment. The surface properties of the activated carbon samples were characterized and the effects of pH and contact time on the adsorption were determined. The adsorption isotherms, adsorption kinetics and adsorption mechanism are discussed. RESULTS: Compared to AC, HNO3 oxidation increased the number of acid functional groups on the surface of AAC, which hindered the adsorption of ampicillin. For HAAC, thermal treatment removed surface oxygen groups and then improved the adsorption ability. The adsorption processes was greatly affected by pH and acidic conditions were favorable for adsorption. With an initial ampicillin sodium concentration of 200 mg/L, 9 h was needed for adsorption to reach equilibrium. The Langmuir isotherm provides a better fit for the adsorption than the Freundlich isotherm and the maximum adsorption capacities for AC, AAC and HAAC were 90.6, 59.8, 140.9 mg/g, respectively. The sorption kinetics can be described by a pseudo-second order model. CONCLUSION: The functional groups on activated carbon greatly affect its adsorption ability. The adsorption of ampicillin can be improved by increasing the number of basic functional groups on the activated carbon. Chemisorption was the dominant adsorption process and pH was an important factor affecting ampicillin adsorption.
Evaluation of the old residential area modification by applying improved fuzzy comprehensive evaluation
Authors: Li Xiufang , Huang Mingqiang
Published: April 2020

In order to make a global assessment on the modification effect of existing old residential areas in hot summer and warmer winter zone, an improved fuzzy comprehensive evaluation (FCE) model of old residential building modification is established based on the aspects of structural safety and architectural appearance, indoor comfort system, outdoor environment, public service facilities, building equipment efficiency and operation management, etc. Analytic hierarchy process is used to determine the weights of evaluation factors at all levels. And the model is used to evaluate the modification effect of the old residential buildings in Xiamen city. The evaluation result shows feasibility of this modification method on the old residential building. The evaluation grade of this area’s modification can be assessed as “Good”, which can provide a reference for the modification of the old residential areas with hot summer and warm winter. Measures, such as increasing government financial input, institutionalized ways to tracking energy consumption, popularization of energy-saving awareness, should be taken for the modification.
Problems and corrective measures of promoting the green construction of high-quality settlement buildings
Authors: Huang Mingqiang , Lin Ruijuan , Wang Weiwei , Song Zixin , Xia Xumei
Published: April 2020

The green construction of high-quality settlement buildings is related to the people’s life, the integrity of the government and social stability. Accelerating the construction of high-quality settlement buildings is helpful to promote the harmonious development of society. This study first expounds the significance of promoting the green construction of high-quality settlement buildings, then analyzes three major problems in the construction process of settlement buildings based on the data of previous research, and on this basis puts forward corresponding countermeasures and suggestions to promote the sustainable development of high-quality settlement buildings construction.
Growth period trend analysis both Triticum aestivum L. and Zea mays L. in Eastern Henan Province: Case study of NDVI3g (1982-2013) in Yongcheng and Xiayi experiment areas
Authors: Cui Zhenzhen , Ma Chao , Huang Shanshan
Published: April 2020

Long-term GIMMS AVHRR NDVI3g (1982∼2013) remote sensing image was used to obtain the equivalent biomass of winter wheat and summer maize in Xiayi and Yongcheng experimental sites as well as the change trend of vegetation SOS, EOS and LOS by regression analysis, Gaussian fitting and NDVI volume integration, and combined with climate driving factors (precipitation, temperature) to analyze the correlation between these trends and vegetation index changes. The results showed that (1) The vegetation index of 32a in the study areas showed an increasing trend, the vegetation growth of Yongcheng was better than that of Xiayi, and the NDVI equivalent biomass was higher than that of Xiayi; (2) The SOS of the Yongxia experimental sites was significantly advanced, and the EOS was slightly advanced, resulting in a significant increase in the vegetation growth period in the two study areas, and the increase of vegetation LOS in Yongcheng experimental area was about 3 times that of summer maize. The advancement of LOS was the main way to respond to climate change by vegetation activities in Yongxia areas; (3) The NDVI in the study areas was significantly positively correlated with temperature and had no significant correlation with precipitation.
The Development of Solar-Powered Gas Metering Units Equipped with Radio or 3G Based Telemetry Systems
Authors: Velichko M A , Gladkikh Yu P , Kostina I B
Published: April 2020

In this article we have described the development of solar-powered gas metering units including modern ultrasonic and vortex flowmeters for volume and mass measurement of natural gas, associated petroleum gases, inert gases, oxygen, hydrogen, air, nitrogen, carbon dioxide and any other single and multicomponent gases that are not aggressive to the flowmeter materials. We have shown implementation of such units in the existing gas producing stations in the desert of Kara-Kum. Confirmed was the ability of our gas metering units to operate more than a year without network power supply and staff intervention. Also pictured was creation of telemetry system for collecting and transmitting metrological information, including gas flow rate, temperature, pressure, humidity to the central terminal. Different physical layers have been used to transfer data from the metering units, including radio channels at 433 MHz frequency between units and central station. This telemetry system implemented selfmaintenance and self-monitoring features, facilitating remote control of metering unit, so important in rigid conditions of solar-rich deserts and semi-deserts.
Microstructures and mechanical properties of Ni/Fe dissimilar butt joint welded using the cold metal transfer
Authors: Tang YunLong , Ye Xin , Ding LongCan , Zhang PeiLei , Yu ZhiShui , Wu Di
Published: April 2020

In this study, dissimilar butt joints were formed between as-rolled Inconel 718 and SUS 316 using cold metal transfer (CMT) with ERNiFeCr-2 filler metal at a welding speed of 5 mm s−1 and three different welding currents (130, 160 and 190 A). The morphology, microstructure, and mechanical properties of the joints and the mechanism by which the joint interface formed were studied. The results indicate that CMT welding parameters have an effect on the weld appearance and that the weld metal exhibits better wettability and spreadability at a welding current of 160 A. The interface between the weld metal and SUS 316 base metal was characterized by applying an optical microscopy (OM) and scanning electron microscopy (SEM) equipped with energy-dispersive X-ray spectrometry (EDS). The results revealed that no obvious diffusion of Ni and Fe ions was identified across the joint interface. The fractures that initiated in the joints during the tension testing formed in the heat-affected zone (HAZ) of the SUS 316 base metal, and the high-temperature tensile strength of the joint was observed to be 424 MPa, which is approximately 87.06% of that of SUS 316 base metal (487 MPa) and 67.19% of that of Inconel 718 base metal (631 MPa). In terms of the elongation, the joint (21.9%), Inconel 718 base metal (21.2%) and SUS 316 base metal (22.3%) elongations were similar. For comparison, the joint also was tested at room temperature, resulting in a tensile strength and elongation of 511 MPa and 27.5%, respectively. A spherical elemental Ni segregation morphology was clearly observed at the high-temperature fracture. Hardness studies demonstrated that the weld metal hardness is higher than that of the SUS 316 base metal.
Functionalization of silk fabric using hyperbranched polymer coated attapulgite nanoparticles for prospective UV-resistance and antibacterial applications
Authors: Liu Yan , Gao Xiaoliang , Zhang Guangyu , Xiao Yao
Published: April 2020

Herein, the Attapulgite nanoparticles (ATP NPs) coated silk fabric was prepared by impregnation method using hyperbranched polymer as addition agent. The ATP NPs and prepared silk fabrics were characterized by means of scanning electron microscope (SEM), ultraviolet-visible (UV–Vis) spectroscopy, Fourier transform infrared spectrophotometer (FTIR), X-ray diffraction (XRD), Energy Dispersive Spectrometer (EDS). The results of SEM, EDS, FTIR and XRD confirmed that ATP NPs were successfully coated on the surface of silk fabric. Not only did the treated silk fabrics possess excellent antibacterial property and antibacterial resistance, but also exhibited outstanding anti-ultraviolet performance, which can meet the requirements of multifunctional products.
Global PPPs and the Choice of Law Challenge
Authors: Lin Tan Yock
Published: April 2020

Positing the public-private partnership as an important optional legal structure in the delivery of infrastructural services in the Belt and Road Initiative (BRI), this exploratory article discusses the crucial, but formidable, problems of risks in management or governance. It considers whether traditional common law conflict of laws as applied in Singapore courts can contribute principles that recognize shared expectations and commitment or foster solidarity, mutuality, and trust—values regarded as essential to their effective resolution. Arguing that traditional conflicts distinctions between State and non-State law as well as between public and private law are unhelpful in this respect, it concludes that modern critical developments contain promising prospects for developing such principles. These principles will predicate a role for foreign State substantive public policies and, if there is relevant ‘relational distance’, implement them in BRI choice-of-law disputes, thereby reconciling private efficiency and public accountability beyond borders.
On the Stabilization of the Betti Numbers of the Moduli Space of Sheaves on ℙ2
Authors: Mandal Sayanta
Published: April 2020

Let $r \geq 2$ be an integer, and let $a$ be an integer coprime to $r$. We show that if $c_2 \geq n + \left \lfloor \frac{r-1}{2r}a^2 + \frac{1}{2}(r^2 + 1) \right \rfloor $, then the $2n$th Betti numbers of the moduli space $M_{\mathbb{P}^2,H}(r,aH,c_2)$ stabilize where $H = c_1(\mathcal{O}_{\mathbb{P}^2}(1))$.
The Unified Medical Language System SPECIALIST Lexicon and Lexical Tools: Development and applications
Authors: Lu Chris J , Payne Amanda , Mork James G
Published: April 2020

Natural language processing (NLP) plays a vital role in modern medical informatics. It converts narrative text or unstructured data into knowledge by analyzing and extracting concepts. A comprehensive lexical system is the foundation to the success of NLP applications and an essential component at the beginning of the NLP pipeline. The SPECIALIST Lexicon and Lexical Tools, distributed by the National Library of Medicine as one of the Unified Medical Language System Knowledge Sources, provides an underlying resource for many NLP applications. This article reports recent developments of 3 key components in the Lexicon. The core NLP operation of Unified Medical Language System concept mapping is used to illustrate the importance of these developments. Our objective is to provide generic, broad coverage and a robust lexical system for NLP applications. A novel multiword approach and other planned developments are proposed.
Infectious Complications Following CD19 Chimeric Antigen Receptor T-cell Therapy for Children, Adolescents, and Young Adults
Authors: Vora Surabhi B , Waghmare Alpana , Englund Janet A , Qu Pingping , Gardner Rebecca A , Hill Joshua A
Published: April 2020

Background

Infectious complications of chimeric antigen receptor (CAR) T-cell immunotherapy in children and young adults have not been well described.

Methods

Medical records of patients ≤26 years old receiving CD19 CAR T-cell infusion (CTI) at a single institution between 2014 and 2017 were reviewed. The number of infections per 100 days-at-risk (infection density) in the 90 days preceding and 0–28 and 29–90 days after CTI was calculated. Poisson regression and Cox analyses were utilized to identify risk factors for infections.

Results

Eighty-three patients received CTI during the study period. Most patients (98%) had refractory or relapsed acute lymphoblastic leukemia (ALL). Infections occurred in 54% of patients in the 90 days before CTI (infection density, 1.23) and in 40% of patients in the first 28 days following CTI (infection density, 2.89). Infection density decreased to 0.55 in the 29–90 days post-CTI. Most infections were bacteremias (39%) or respiratory viral infections (43%). Pre-CTI risk factors associated with infection included prior hematopoietic cell transplantation (HCT), immunoglobulin G (IgG) level <400 mg/dL, and lymphodepletion other than cyclophosphamide plus fludarabine; post-CTI risk factors included higher-severity CRS and IgG <400 mg/dL.

Conclusions

Infection rates in children and young adults receiving CD19 CAR T-cell therapy increase in the first month and then decline. Understanding types and timing of infections and contributing risk factors may help inform prophylactic and monitoring strategies. Specific attention should be given to patients with prior HCT, severe hypogammaglobulinemia, and severe CRS.
Duration of topical steroid application after photorefractive keratectomy with mitomycin C
Authors: Pakbin Mojgan , Khabazkhoob Mehdi , Pakravan Mohammad , Fotouhi Akbar , Jafarzadehpour Ebrahim , Aghamirsalim Mohamadreza , Seyedian Mohammad Amin , Hashemi Hassan
Published: April 2020

Contradictory results of postoperative steroid application in photorefractive keratectomy (PRK) led to a meta-analysis of the existing data to achieve a definite conclusion on the optimum dosage and duration of corticosteroid therapy after PRK. The overall pooled unstandardized mean difference (PUMD) of the corneal haze score was −0.20 (95% CI, −0.29 to −0.12). In subgroup analysis, the PUMD of the corneal haze score was statistically significant in 2 subgroups, −0.57 (−0.85 to −0.30) for 3 to 6 months postoperatively and −0.13 (−0.23 to −0.04) for ≤ 3 months postoperatively. Analysis of the PUMD of postoperative spherical equivalent in participants with low to moderate myopia (≥−6.00 D) and high myopia (<−6.00 D) showed positive effects of steroids on prevention of myopia regression. In conclusion, long-term topical steroid application after PRK seems unnecessary in low and moderate myopia. New randomized clinical trials using current technologies are recommended for postoperative treatments.
Updates in Pediatric Malignant Gliomas
Authors: Gonçalves Fabrício Guimarães , Alves César Augusto Pinheiro Ferreira , Vossough Arastoo
Published: April 2020

Malignant gliomas constitute a smaller portion of brain tumors in children compared with adults. Nevertheless, they can be devastating tumors with poor prognosis. Recent advances and improved understanding of the genetic and molecular characterization of pediatric brain tumors, including those of malignant gliomas, have led to the reclassification of many pediatric brain tumors and new entities have been defined. In this paper, we will present some of the more recent characterization and pertinent changes in pediatric high-grade gliomas, along with the conventional and advanced imaging features associated with these entities. Implications of the recent changes in pediatric malignant glioma classifications will also be discussed.
Integrative and Conjugative Elements (ICE) and Associated Cargo Genes within and across Hundreds of Bacterial Genera
Authors: Kaufman James H , Terrizzano Ignacio , Nayar Gowri , Seabolt Ed , Agarwal Akshay , Slizovskiy Ilya B , Noyes Noelle
Published: April 2020

Horizontal gene transfer mediated by integrative and conjugative elements (ICE) is considered an important evolutionary mechanism of bacteria. It allows organisms to quickly evolve new phenotypic properties including antimicrobial resistance (AMR) and virulence. The rate of ICE-mediated cargo gene exchange has not yet been comprehensively studied within and between bacterial taxa. In this paper we report a big data analysis of ICE and associated cargo genes across over 200,000 bacterial genomes representing 1,345 genera. Our results reveal that half of bacterial genomes contain one or more known ICE features (“ICE genomes”), and that the associated genetic cargo may play an important role in the spread of AMR genes within and between bacterial genera. We identify 43 AMR genes that appear only in ICE genomes and never in non-ICE genomes. A further set of 95 AMR genes are found >5x more often in ICE versus non-ICE genomes. In contrast, only 29 AMR genes are observed more frequently (at least 5:1) in non-ICE genomes compared to ICE genomes. Analysis of NCBI antibiotic susceptibility assay data reveals that ICE genomes are also over-represented amongst phenotypically resistant isolates, suggesting that ICE processes are critical for both genotypic and phenotypic AMR. These results, as well as the underlying big data resource, are important foundational tools for understanding bacterial evolution, particularly in relation to important bacterial phenotypes such as AMR.
State-dependent regulation of cortical processing speed via gain modulation
Authors: Wyrick David , Mazzucato Luca
Published: April 2020

Abstract

To thrive in dynamic environments, animals must be capable of rapidly and flexibly adapting behavioral responses to a changing context and internal state. Examples of behavioral flexibility include faster stimulus responses when attentive and slower responses when distracted. Contextual or state-dependent modulations may occur early in the cortical hierarchy and may be implemented via top-down projections from cortico-cortical or neuromodulatory pathways. However, the computational mechanisms mediating the effects of such projections are not known. Here, we introduce a theoretical framework to classify the effects of cell-type specific top-down perturbations on the information processing speed of cortical circuits. Our theory demonstrates that perturbation effects on stimulus processing can be predicted by intrinsic gain modulation, which controls the timescale of the circuit dynamics. Our theory leads to counter-intuitive effects such as improved performance with increased input variance. We tested the model predictions using large-scale electrophysiological recordings from the visual hierarchy in freely running mice, where we found that a decrease in single-cell intrinsic gain during locomotion led to an acceleration of visual processing. Our results establish a novel theory of cell-type specific perturbations, applicable to top-down modulation as well as optogenetic and pharmacological manipulations. Our theory links connectivity, dynamics, and information processing via gain modulation.
Genetics of Smoking and Risk of Atherosclerotic Cardiovascular Diseases: A Mendelian Randomization Study
Authors: Levin Michael G. , Klarin Derek , Assimes Themistocles L. , Freiberg Matthew S. , Ingelsson Erik , Lynch Julie , Natarajan Pradeep , O’Donnell Christopher , Rader Daniel J. , Tsao Philip S. , Chang Kyong-Mi , Voight Benjamin F. , Damrauer Scott M.
Published: April 2020

Importance

Smoking is associated with atherosclerotic cardiovascular disease, but the relative contribution to each subtype (coronary artery disease [CAD], peripheral artery disease [PAD], and large-artery stroke) remains less well understood.

Objective

To determine the effect of smoking on risk of coronary artery disease, peripheral artery disease, and large-artery stroke.

Design

Mendelian randomization study using summary statistics from genome-wide associations of smoking (up to 462,690 individuals), coronary artery disease (up to 60,801 cases, 123,504 controls), peripheral artery disease (up to 24,009 cases, 150,983 controls), and large-artery stroke (up to 4,373 cases, 406,111 controls)

Setting

Population-based study of primarily European-ancestry individuals

Participants

Participants in genome-wide association studies of smoking, coronary artery disease, peripheral artery disease, and stroke.

Exposures

Genetic liability to smoking defined by lifetime smoking index: an integrated measure of smoking status, age at initiation, age at cessation, number of cigarettes smoked per day, and declining effect of smoking on health outcomes).

Main Outcome Measure

Risk of coronary artery disease, peripheral artery disease, and large-artery stroke.

Results

Genetic liability to smoking was associated with increased risk of PAD (OR 2.13; 95% CI 1.78-2.56; P = 3.6 × 10−16), CAD (OR 1.48; 95% CI 1.25-1.75; P = 4.4 × 10−6), and stroke (OR 1.4; 95% CI 1.02-1.92; P = 0.036). Risk of PAD in smokers was greater than risk of large-artery stroke (pdifference= 0.025) or CAD (pdifference= 0.0041). The effect of smoking on ASCVD remained independent from the effects of smoking on traditional cardiovascular risk factors.

Conclusions and Relevance

Genetic liability to smoking is a strong, causal risk factor for CAD, PAD, and stroke, although the effect of smoking is strongest for PAD. The effect of smoking is independent of traditional cardiovascular risk factors.
HAPPI GWAS: Holistic Analysis with Pre and Post Integration GWAS
Authors: Slaten Marianne L. , Chan Yen On , Shrestha Vivek , Lipka Alexander E. , Angelovici Ruthie
Published: April 2020

Motivation

Advanced publicly available sequencing data from large populations have enabled in-formative genome-wide association studies (GWAS) that associate SNPs with phenotypic traits of interest. Many publicly available tools able to perform GWAS have been developed in response to increased demand. However, these tools lack a comprehensive pipeline that includes both pre-GWAS analysis such as outlier removal, data transformation, and calculation of Best Linear Unbiased Predictions (BLUPs) or Best Linear Unbiased Estimates (BLUEs). In addition, post-GWAS analysis such as haploblock analysis and candidate gene identification are lacking.

Results

Here, we present HAPPI GWAS, an open-source GWAS tool able to perform pre-GWAS, GWAS, and post-GWAS analysis in an automated pipeline using the command-line interface.

Availability

HAPPI GWAS is written in R for any Unix-like operating systems and is available on GitHub (https://github.com/Angelovici-Lab/HAPPI.GWAS.git).

Contact

angelovicir@missouri.edu
Polygenic scores for height in admixed populations
Authors: Bitarello Bárbara D. , Mathieson Iain
Published: April 2020

Polygenic risk scores (PRS) use the results of genome-wide association studies (GWAS) to predict quantitative phenotypes or disease risk at an individual level. This provides a potential route to the use of genetic data in personalized medical care. However, a major barrier to the use of PRS is that the majority of GWAS come from cohorts of European ancestry. The predictive power of PRS constructed from these studies is substantially lower in non-European ancestry cohorts, although the reasons for this are unclear. To address this question, we investigate the performance of PRS for height in cohorts with admixed African and European ancestry, allowing us to evaluate ancestry-related differences in PRS predictive accuracy while controlling for environment and cohort differences. We first show that that the predictive accuracy of height PRS increases linearly with European ancestry and is largely explained by European ancestry segments of the admixed genomes. We show that differences in allele frequencies, recombination rate, and marginal effect sizes across ancestries all contribute to the decrease in predictive power, but none of these effects explain the decrease on its own. Finally, we demonstrate that prediction for admixed individuals can be improved by using a linear combination of PRS that includes ancestry-specific effect sizes, although this approach is at present limited by the small size of non-European ancestry discovery cohorts.
Repeated parallel losses of inflexed stamens in Moraceae: phylogenomics and generic revision of the tribe Moreae and the reinstatement of the tribe Olmedieae (Moraceae)
Authors: Gardner Elliot M. , Garner Mira , Cowan Robyn , Dodsworth Steven , Epitawalage Niroshini , Arifiani Deby , Sahromi S. , Baker William J. , Forest Felix , Maurin Olivier , Zerega Nyree J.C. , Monro Alexandre , Hipp Andrew L.
Published: April 2020

We present a densely-sampled phylogenomic study of the mulberry tribe (Moreae, Moraceae), an economically important clade with a global distribution, revealing multiple losses of inflexed stamens, a character traditionally used to circumscribe Moreae. Inflexed stamens facilitate ballistic pollen release and are associated with wind pollination, and the results presented here suggest that losses of this character state may have evolved repeatedly in Moraceae. Neither Moreae nor several of its major genera (Morus,Streblus,Trophis) were found to be monophyletic. A revised system for a monophyletic Moreae is presented, including the reinstatement of the generaAmpalis, Maillardia, Taxotrophis,andParatrophis, and the recognition of the new genusAfromorus, based onMorussubgenusAfromorus.Pseudostreblusis reinstated and transferred to the Parartocarpeae, andSloetiopsisis reinstated and transferred to the Dorstenieae. The tribe Olmediae is reinstated, replacing the Castilleae, owing to the reinstatement of the type genusOlmedia,and its exclusion from Moreae.Strebluss.s. is excluded from Moreae and transferred to the Olmediae, which is characterized primarily by involucrate inflorescences without regard to stamen position. Eight new combinations are made.
Functional characterization of germline variants in theTMEM127tumor suppressor reveals novel insights into its membrane topology and trafficking
Authors: Flores Shahida K. , Deng Yilun , Cheng Ziming , Zhang Xingyu , Tao Sifan , Saliba Afaf , Chu Irene , Wang Exing , Aguiar Ricardo C. T. , Dahia Patricia L. M.
Published: April 2020

Purpose

To better understand the function of the transmembrane protein TMEM127, a poorly known tumor suppressor gene associated with pheochromocytomas, paragangliomas and renal carcinomas, we evaluated patient-derived germline variants.

Methods

Subcellular localization and steady-state levels of 21 tumor-associated, transiently expressedTMEM127variants were compared to the wild-type protein using immunofluorescence and immunoblot analysis, respectively, in cells genetically modified to lack endogenous TMEM127. Membrane topology and endocytic mechanisms were also assessed.

Results

We identified three subgroups of mutations and determined that 15 of the 21 variants (71%), including 9 of 15 missense variants (60%), are pathogenic or likely pathogenic, through loss of membrane binding ability, stability and/or internalization capability. Investigation into an N-terminal cluster of missense variants uncovered a previously unrecognized transmembrane domain, indicating that TMEM127 is a four-, not a three-, transmembrane domain-containing protein. Additionally, a C-terminal variant with predominant plasma membrane localization revealed an atypical, extended acidic, dileucine-based motif required for TMEM127 internalization through clathrin-mediated endocytosis.

Conclusion

We characterized the functional deficits of several germlineTMEM127variants and identified novel structure-function features of TMEM127, namely, a fourth transmembrane domain and an endocytic motif. These findings will assist inTMEM127variant interpretation and will help guide future studies investigating the cellular role of TMEM127.
Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia
Authors: Yoon Jin-Hui , Shin Paul , Joo Jongyoon , Kim Gaon S. , Oh Wang-Yuhl , Jeong Yong
Published: April 2020

Proper regulation and patency of cerebral microcirculation is crucial for maintaining a healthy brain. Capillary stalling, i.e., the brief interruption of microcirculation mainly by leukocytes, has been observed in several diseases and contributes to disease pathogenesis or progression. However, the underpinning mechanism for leukocyte capillary plugging remains elusive. Therefore, we investigated the mechanism of capillary stalling in mice during the development of subcortical vascular dementia (SVaD), the most common type of vascular dementia characterized by impaired microcirculation and associated pathological features. Longitudinal optical coherence tomography angiography showed increased number of stalled segments as the disease progressed, while two-photon microscopy indicated a less extensive endothelial glycocalyx (EG) in the stalled segments. We also found that increased gliosis and blood-brain barrier leakage were correlated with the increased number of stalled segments. Based on the above, we conclude that EG potentially mediates capillary stalling and can be a therapeutic target of SVaD.
Determining the interaction status and evolutionary fate of duplicated homomeric proteins
Authors: Mallik Saurav , Tawfik Dan S
Published: April 2020

Oligomeric proteins are central to life. Duplication and divergence of their genes is a key evolutionary driver, also because duplications can yield very different outcomes. Given a homomeric ancestor, duplication can yield two paralogs that form two distinct homomeric complexes, or a heteromeric complex comprising both paralogs. Alternatively, one paralog remains a homomer while the other acquires a new partner. However, so far, conflicting trends have been noted with respect to which fate dominates, primarily because different methods and criteria are being used to assign the interaction status of paralogs. Here, we systematically analyzed allSaccharomyces cerevisiaeandEscherichia colioligomeric complexes that include paralogous proteins. We found that the proportions of homo-hetero duplication fates strongly depend on a variety of factors, yet that nonetheless, rigorous filtering gives a consistent picture. InE. coliabout 50%, of the paralogous pairs appear to have retained the ancestral homomeric interaction, whereas inS. cerevisiaeonly ∼10% retained a homomeric state. This difference was also observed when unique complexes were counted instead of paralogous gene pairs. We further show that this difference is accounted for by multiple cases of heteromeric yeast complexes that share common ancestry with homomeric bacterial complexes. Our analysis settles contradicting trends and conflicting previous analyses, and provides a systematic and rigorous pipeline for delineating the fate of duplicated oligomers in any organism for which protein-protein interaction data are available.
Multiple Myeloma: Combination Therapy of BET Proteolysis Targeting Chimeric Molecule with CDK9 Inhibitor
Authors: Lim Su-Lin , Xu Liang , Han Bing-Chen , Shyamsunder Pavithra , Chng Wee-Joo , Koeffler H. Phillip
Published: April 2020

Cyclin Dependent Kinase 9 (CDK9) associates with Bromodomain and Extra-Terminal Domain (BET) proteins to promote transcriptional elongation by phosphorylation of serine 2 of RNAP II C-terminal domain. We examined the therapeutic potential of selective CDK9 inhibitors (AZD 4573 and MC180295) against human multiple myeloma cellsin vitro.Short-hairpin RNA silencing of CDK9 in Multiple Myeloma (MM) cell lines reduced cell viability compared to control cells showing the dependency of MM cells on CDK9. In order to explore synergy with the CDK9 inhibitor, proteolysis targeting chimeric molecule (PROTAC) ARV 825 was added. This latter drug causes ubiquitination of BET proteins resulting in their rapid and efficient degradation. Combination treatment of MM cells with ARV 825 and AZD 4573 markedly reduced their protein expression of BRD 2, BRD 4, MYC and phosphorylated RNA pol II as compared to each single agent alone. Combination treatment synergistically inhibited multiple myeloma cells bothin vitroandin vivowith insignificant weight loss. The combination also resulted in marked increase of apoptotic cells at low dose compared to single agent alone. Taken together, our studies show for the first time that the combination of a BET PROTAC (ARV 825) plus AZD 4573 (CDK9 inhibitor) is effective against MM cells.
Deep evolutionary origin of gamete-directed zygote activation by KNOX/BELL transcription factors in green plants
Authors: Hisanaga Tetsuya , Fujimoto Shota , Cui Yihui , Sato Katsutoshi , Sano Ryosuke , Yamaoka Shohei , Kohchi Takayuki , Berger Frédéric , Nakajima Keiji
Published: April 2020

KNOX and BELL transcription factors regulate distinct steps of diploid development in the green lineages. In the green alga Chlamydomonas reinhardtii, KNOX and BELL proteins are inherited by gametes of the opposite mating types, and heterodimerize in zygotes to activate diploid development. By contrast, in land plants such as Physcomitrella and Arabidopsis, KNOX and BELL proteins function in meristem maintenance and organogenesis during the later stages of diploid development. However, whether the contrasting functions of KNOX and BELL were acquired independently in algae and land plants is currently unknown. Here we show that in the basal land plant species Marchantia polymorpha, gamete-expressed KNOX and BELL are required to initiate zygotic development by promoting nuclear fusion in a manner strikingly similar to that of C. reinhardtii. Our results indicate that zygote activation is the ancestral role of KNOX/BELL transcription factors, which shifted toward meristem maintenance as land plants evolved.
SERRATE interacts with the nuclear exosome targeting (NEXT) complex to degrade primary miRNA precursors in Arabidopsis
Authors: Bajczyk Mateusz , Lange Heike , Bielewicz Dawid , Szewc Lukasz , Bhat Susheel Sagar , Dolata Jakub , Kuhn Lauriane , Szweykowska-Kulinska Zofia , Gagliardi Dominique , Jarmolowski Artur
Published: April 2020

SERRATE/ARS2 is a conserved RNA effector protein involved in transcription, processing and export of different types of RNAs. In Arabidopsis, the best-studied function of SERRATE (SE) is to promote miRNA processing. Here, we report that SE interacts with the Nuclear Exosome Targeting (NEXT) complex, comprising the RNA helicase HEN2, the RNA binding protein RBM7 and one of the two zinc-knuckle proteins ZCCHC8A/ZCCHC8B. The identification of common targets of SE and HEN2 by RNA-seq supports the idea that SE cooperates with NEXT for RNA surveillance by the nuclear exosome. Among the RNA targets accumulating in absence of SE or NEXT are miRNA precursors. Loss of NEXT components results in the accumulation of pri-miRNAs without affecting levels of miRNAs, indicating that NEXT is, unlike SE, not required for miRNA processing. As compared tose-2,se-2 hen2-2double mutants showed increased accumulation of pri-miRNAs, but partially restored levels of mature miRNAs and attenuated developmental defects. We propose that the slow degradation of pri-miRNAs caused by loss of HEN2 compensates for the poor miRNA processing efficiency inse-2mutants, and that SE regulates miRNA biogenesis through its double contribution in promoting miRNA processing but also pri-miRNA degradation through the recruitment of the NEXT complex.
MicroHapDB: a portable and extensible database of all published microhaplotype marker and frequency data
Authors: Standage Daniel , Mitchell Rebecca
Published: April 2020

Microhaplotypes are the subject of significant interest in the forensics community as a promising multi-purpose forensic DNA marker for human identification. Microhaplotype markers are composed of multiple SNPs in close proximity, such that a single NGS read can simultaneously genotype the individual SNPs and phase them in aggregate to determine the associated donor haplotype. Abundant throughout the human genome, numerous recent studies have sought to discover and rank microhaplotype markers according to allelic diversity within and among populations. Microhaplotypes provide an appealing alternative to STR markers for human identification and mixture deconvolution, but can also be optimized for ancestry inference or combined with phenotype SNPs for prediction of externally visible characteristics in a multiplex NGS assay. Designing and evaluating panels of microhaplotypes is complicated by the lack of a convenient database of all published data, as well as the lack of population allele frequency data spanning disparate marker collections. We present MicroHapDB, a comprehensive database of published microhaplotype marker and frequency data, as a tool to advance the development of microhaplotype-based human forensics capabilities. We also present population allele frequencies derived from 26 global population samples for all microhaplotype markers published to date, facilitating the design and interpretation of custom multi-source panels. We submit MicroHapDB as a resource for community members engaged in marker discovery, population studies, assay development, and panel and kit design.
Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and secondary effects
Authors: Arnesen Spencer , Blanchard Zannel , Williams Michelle M , Berrett Kristofer C , Li Zheqi , Oesterreich Steffi , Richer Jennifer K , Gertz Jason
Published: April 2020

While breast cancer patients with tumors that express estrogen receptor α (ER) generally respond well to hormone therapies that block ER activity, a significant number of patients relapse. Approximately 30% of these recurrences harbor activating mutations in the ligand binding domain (LBD) of ER, which have been shown to confer ligand-independent function. However, much is still unclear regarding the effect of mutant ER beyond its estrogen independence. To investigate the molecular effects of mutant ER, we developed multiple isogenic ER mutant cell lines for the most common LBD mutations, Y537S and D538G. These mutations induced differential expression of thousands of genes, the majority of which were mutant allele-specific and were not observed upon estrogen treatment of wildtype cells. These mutant-specific genes showed consistent differential expression across ER mutant lines developed in other laboratories. Wildtype cells with long-term estrogen exposure only exhibited some of these transcriptional changes, suggesting that mutant ER causes novel regulatory effects that are not simply due to constant activity. While ER mutations exhibited minor effects on ER genomic binding, with the exception of ligand independence, ER mutations conferred substantial differences in chromatin accessibility. Mutant ER was bound to approximately a quarter of mutant-enriched accessible regions that were enriched for other DNA binding factors including FOXA1, CTCF, and OCT1. Overall, our findings indicate that mutant ER causes several consistent effects on gene expression, both indirectly and through constant activity.