bluuebunny/crossref_metadata_2025 huggingface dataset:
Lumbar Disc Herniation Automatic Detection in Magnetic Resonance Imaging Based on Deep Learning
Authors: Tsai Jen-Yung , Hung Isabella Yu-Ju , Guo Yue Leon , Jan Yih-Kuen , Lin Chih-Yang , Shih Tiffany Ting-Fang , Chen Bang-Bin , Lung Chi-Wen
Published: August 2021

Background: Lumbar disc herniation (LDH) is among the most common causes of lower back pain and sciatica. The causes of LDH have not been fully elucidated but most likely involve a complex combination of mechanical and biological processes. Magnetic resonance imaging (MRI) is a tool most frequently used for LDH because it can show abnormal soft tissue areas around the spine. Deep learning models may be trained to recognize images with high speed and accuracy to diagnose LDH. Although the deep learning model requires huge numbers of image datasets to train and establish the best model, this study processed enhanced medical image features for training the small-scale deep learning dataset.

Methods: We propose automatic detection to assist the initial LDH exam for lower back pain. The subjects were between 20 and 65 years old with at least 6 months of work experience. The deep learning method employed the YOLOv3 model to train and detect small object changes such as LDH on MRI. The dataset images were processed and combined with labeling and annotation from the radiologist’s diagnosis record.

Results: Our method proves the possibility of using deep learning with a small-scale dataset with limited medical images. The highest mean average precision (mAP) was 92.4% at 550 images with data augmentation (550-aug), and the YOLOv3 LDH training was 100% with the best average precision at 550-aug among all datasets. This study used data augmentation to prevent under- or overfitting in an object detection model that was trained with the small-scale dataset.

Conclusions: The data augmentation technique plays a crucial role in YOLOv3 training and detection results. This method displays a high possibility for rapid initial tests and auto-detection for a limited clinical dataset.
Assessing the Role of Cyberbiosecurity in Agriculture: A Case Study
Authors: Drape Tiffany , Magerkorth Noah , Sen Anuradha , Simpson Joseph , Seibel Megan , Murch Randall Steven , Duncan Susan E.
Published: August 2021

Agriculture has adopted the use of smart technology to help meet growing food demands. This increased automation and associated connectivity increases the risk of farms being targeted by cyber-attacks. Increasing frequency of cybersecurity breaches in many industries illustrates the need for securing our food supply chain. The uniqueness of biological data, the complexity of integration across the food and agricultural system, and the importance of this system to the U.S. bioeconomy and public welfare suggests an urgency as well as unique challenges that are not common across all industries. To identify and address the gaps in awareness and knowledge as well as encourage collaborations, Virginia Tech hosted a virtual workshop consisting of professionals from agriculture, cybersecurity, government, and academia. During the workshop, thought leaders and influencers discussed 1) common food and agricultural system challenges, scenarios, outcomes and risks to various sectors of the system; 2) cyberbiosecurity strategies for the system, gaps in workforce and training, and research and policy needs. The meeting sessions were transcribed and analyzed using qualitative methodology. The most common themes that emerged were challenges, solutions, viewpoints, common vocabulary. From the results of the analysis, it is evident that none of the participating groups had available cybersecurity training and resources. Participants were uncertain about future pathways for training, implementation, and outreach related to cyberbiosecurity. Recommendations include creating training and education, continued interdisciplinary collaboration, and recruiting government involvement to speed up better security practices related to cyberbiosecurity.
Interactions Between Genes From Aging Pathways May Influence Human Lifespan and Improve Animal to Human Translation
Authors: Ukraintseva Svetlana , Duan Matt , Arbeev Konstantin , Wu Deqing , Bagley Olivia , Yashkin Arseniy P. , Gorbunova Galina , Akushevich Igor , Kulminski Alexander , Yashin Anatoliy
Published: August 2021

A major goal of aging research is identifying genetic targets that could be used to slow or reverse aging – changes in the body and extend limits of human lifespan. However, majority of genes that showed the anti-aging and pro-survival effects in animal models were not replicated in humans, with few exceptions. Potential reasons for this lack of translation include a highly conditional character of genetic influence on lifespan, and its heterogeneity, meaning that better survival may be result of not only activity of individual genes, but also gene–environment and gene–gene interactions, among other factors. In this paper, we explored associations of genetic interactions with human lifespan. We selected candidate genes from well-known aging pathways (IGF1/FOXO growth signaling, P53/P16 apoptosis/senescence, and mTOR/SK6 autophagy and survival) that jointly decide on outcomes of cell responses to stress and damage, and so could be prone to interactions. We estimated associations of pairwise statistical epistasis between SNPs in these genes with survival to age 85+ in the Atherosclerosis Risk in Communities study, and found significant (FDR < 0.05) effects of interactions between SNPs in IGF1R, TGFBR2, and BCL2 on survival 85+. We validated these findings in the Cardiovascular Health Study sample, with P < 0.05, using survival to age 85+, and to the 90th percentile, as outcomes. Our results show that interactions between SNPs in genes from the aging pathways influence survival more significantly than individual SNPs in the same genes, which may contribute to heterogeneity of lifespan, and to lack of animal to human translation in aging research.
Loss of PIKfyve Causes Transdifferentiation of Dictyostelium Spores Into Basal Disc Cells
Authors: Yamada Yoko , Forbes Gillian , Du Qingyou , Kawata Takefumi , Schaap Pauline
Published: August 2021

The 1-phosphatidylinositol-3-phosphate 5-kinase PIKfyve generates PtdIns3,5P2 on late phagolysosomes, which by recruiting the scission protein Atg18, results in their fragmentation in the normal course of endosome processing. Loss of PIKfyve function causes cellular hypervacuolization in eukaryotes and organ failure in humans. We identified pikfyve as the defective gene in a Dictyostelium mutant that failed to form spores. The amoebas normally differentiated into prespore cells and initiated spore coat protein synthesis in Golgi-derived prespore vesicles. However, instead of exocytosing, the prespore vesicles fused into the single vacuole that typifies the stalk and basal disc cells that support the spores. This process was accompanied by stalk wall biosynthesis, loss of spore gene expression and overexpression of ecmB, a basal disc and stalk-specific gene, but not of the stalk-specific genes DDB_G0278745 and DDB_G0277757. Transdifferentiation of prespore into stalk-like cells was previously observed in mutants that lack early autophagy genes, like atg5, atg7, and atg9. However, while autophagy mutants specifically lacked cAMP induction of prespore gene expression, pikfyve− showed normal early autophagy and prespore induction, but increased in vitro induction of ecmB. Combined, the data suggest that the Dictyostelium endosomal system influences cell fate by acting on cell type specific gene expression.
Interplay Between Notch and YAP/TAZ Pathways in the Regulation of Cell Fate During Embryo Development
Authors: Engel-Pizcueta Carolyn , Pujades Cristina
Published: August 2021

Cells in growing tissues receive both biochemical and physical cues from their microenvironment. Growing evidence has shown that mechanical signals are fundamental regulators of cell behavior. However, how physical properties of the microenvironment are transduced into critical cell behaviors, such as proliferation, progenitor maintenance, or differentiation during development, is still poorly understood. The transcriptional co-activators YAP/TAZ shuttle between the cytoplasm and the nucleus in response to multiple inputs and have emerged as important regulators of tissue growth and regeneration. YAP/TAZ sense and transduce physical cues, such as those from the extracellular matrix or the actomyosin cytoskeleton, to regulate gene expression, thus allowing them to function as gatekeepers of progenitor behavior in several developmental contexts. The Notch pathway is a key signaling pathway that controls binary cell fate decisions through cell–cell communication in a context-dependent manner. Recent reports now suggest that the crosstalk between these two pathways is critical for maintaining the balance between progenitor maintenance and cell differentiation in different tissues. How this crosstalk integrates with morphogenesis and changes in tissue architecture during development is still an open question. Here, we discuss how progenitor cell proliferation, specification, and differentiation are coordinated with morphogenesis to construct a functional organ. We will pay special attention to the interplay between YAP/TAZ and Notch signaling pathways in determining cell fate decisions and discuss whether this represents a general mechanism of regulating cell fate during development. We will focus on research carried out in vertebrate embryos that demonstrate the important roles of mechanical cues in stem cell biology and discuss future challenges.
GADD45B Is a Potential Diagnostic and Therapeutic Target Gene in Chemotherapy-Resistant Prostate Cancer
Authors: Wang Qiong , Wu Wanhua , Gao Ze , Li Kaiwen , Peng Shirong , Fan Huiyang , Xie Zhongqiu , Guo Zhenghui , Huang Hai
Published: August 2021

Background

Chemoresistance is the major cause of death in advanced prostate cancer (PCa), especially in metastatic PCa (mPCa). However, the molecular mechanisms underlying the chemoresistance of PCa remain unclear. Understanding the reason behind the drug resistance would be helpful in developing new treatment approaches.

Methods

The Cancer Genome Atlas, Gene Expression Omnibus datasets, and clinical samples were used to examine the correlation between growth arrest and DNA damage-inducible 45 beta (GADD45B) with clinical characteristics and prognosis. Lentiviral transfection was used to construct GADD45B overexpression cell lines. Hypoxic incubator, low serum medium, or docetaxel was used to build environmental stress model or chemotherapy cell model. The MTS assay and colony formation assay were used to test cell viability. Apoptosis and cell cycle were detected by flow cytometry. The RNA and protein levels of related biomarkers were tested by Western blotting and quantitative polymerase chain reaction. Bioinformatics analysis after RNA sequencing was performed to identify the possible mechanism of how GADD45B regulates chemotherapy resistance.

Results

GADD45B was related to distant metastasis but not to Gleason score, prostate-specific antigen level, T stage, or lymph node metastasis and indicated a good prognosis. The level of GADD45B increased significantly in PCa cells that faced environmental stress. It was found that a high level of GADD45B significantly enhanced the chemosensitivity. Furthermore, high GADD45B promoted cell apoptosis via mitogen-activated protein kinase (MAPK) pathway.

Conclusion

GADD45B promoted chemosensitivity of prostate cancer through MAPK pathway. GADD45B could serve as a diagnostic biomarker and therapeutic target for mPCa or chemotherapy-resistant patients.
Defining the Structural Stability Field of Disordered Fluorite Oxides
Authors: O’Quinn Eric C. , Drey Devon L. , Lang Maik K.
Published: August 2021

Fluorite-structured oxides constitute an important class of materials for energy technologies. Despite their high level of structural symmetry and simplicity, these materials can accommodate atomic disorder without losing crystallinity, making them indispensable for uses in environments with high temperature, changing chemical compositions, or intense radiation fields. In this contribution, we present a set of simple rules that predict whether a compound may adopt a disordered fluorite structure. This approach is closely aligned with Pauling’s rules for ionic crystal structures and Goldschmidt’s rules for ionic substitution.
Linking inherent O-Linked Protein Glycosylation of YghJ to Increased Antigen Potential
Authors: Thorsing Mette , Krogh Thøger Jensen , Vitved Lars , Nawrocki Arkadiusz , Jakobsen Rikke , Larsen Martin R. , Chakraborty Subhra , Bourgeois A. Louis , Andersen Ann Zahle , Boysen Anders
Published: August 2021

Enterotoxigenic Escherichia coli (ETEC) is a WHO priority pathogen and vaccine target which causes infections in low-income and middle-income countries, travelers visiting endemic regions. The global urgent demand for an effective preventive intervention has become more pressing as ETEC strains have become increasingly multiple antibiotic resistant. However, the vaccine development pipeline has been slow to address this urgent need. To date, vaccine development has focused mainly on canonical antigens such as colonization factors and expressed toxins but due to genomic plasticity of this enteric pathogen, it has proven difficult to develop effective vaccines. In this study, we investigated the highly conserved non-canonical vaccine candidate YghJ/SsLE. Using the mass spectrometry-based method BEMAP, we demonstrate that YghJ is hyperglycosylated in ETEC and identify 54 O-linked Set/Thr residues within the 1519 amino acid primary sequence. The glycosylation sites are evenly distributed throughout the sequence and do not appear to affect the folding of the overall protein structure. Although the glycosylation sites only constitute a minor subpopulation of the available epitopes, we observed a notable difference in the immunogenicity of the glycosylated YghJ and the non-glycosylated protein variant. We can demonstrate by ELISA that serum from patients enrolled in an ETEC H10407 controlled infection study are significantly more reactive with glycosylated YghJ compared to the non-glycosylated variant. This study provides an important link between O-linked glycosylation and the relative immunogenicity of bacterial proteins and further highlights the importance of this observation in considering ETEC proteins for inclusion in future broad coverage subunit vaccine candidates.
Machine Learning Approach Identified Multi-Platform Factors for Caries Prediction in Child-Mother Dyads
Authors: Wu Tong Tong , Xiao Jin , Sohn Michael B. , Fiscella Kevin A. , Gilbert Christie , Grier Alex , Gill Ann L. , Gill Steve R.
Published: August 2021

Untreated tooth decays affect nearly one third of the world and is the most prevalent disease burden among children. The disease progression of tooth decay is multifactorial and involves a prolonged decrease in pH, resulting in the demineralization of tooth surfaces. Bacterial species that are capable of fermenting carbohydrates contribute to the demineralization process by the production of organic acids. The combined use of machine learning and 16s rRNA sequencing offers the potential to predict tooth decay by identifying the bacterial community that is present in an individual’s oral cavity. A few recent studies have demonstrated machine learning predictive modeling using 16s rRNA sequencing of oral samples, but they lack consideration of the multifactorial nature of tooth decay, as well as the role of fungal species within their models. Here, the oral microbiome of mother–child dyads (both healthy and caries-active) was used in combination with demographic–environmental factors and relevant fungal information to create a multifactorial machine learning model based on the LASSO-penalized logistic regression. For the children, not only were several bacterial species found to be caries-associated (Prevotella histicola, Streptococcus mutans, and Rothia muciloginosa) but also Candida detection and lower toothbrushing frequency were also caries-associated. Mothers enrolled in this study had a higher detection of S. mutans and Candida and a higher plaque index. This proof-of-concept study demonstrates the significant impact machine learning could have in prevention and diagnostic advancements for tooth decay, as well as the importance of considering fungal and demographic–environmental factors.
A Framework for Estimating Human-Wildlife Conflict Probabilities Conditional on Species Occupancy
Authors: Warrier Rekha , Noon Barry R. , Bailey Larissa L.
Published: August 2021

Managing human-wildlife conflicts (HWCs) is an important conservation objective for the many terrestrial landscapes dominated by humans. Forecasting where future conflicts are likely to occur and assessing risks to lives and livelihoods posed by wildlife are central to informing HWC management strategies. Existing assessments of the spatial occurrence patterns of HWC are based on either understanding spatial patterns of past conflicts or patterns of species distribution. In the former case, the absence of conflicts at a site cannot be attributed to the absence of the species. In the latter case, the presence of a species may not be an accurate measure of the probability of conflict occurrence. We present a Bayesian hierarchical modeling framework that integrates conflict reporting data and species distribution data, thus allowing the estimation of the probability that conflicts with a species are reported from a site, conditional on the species being present. In doing so, our model corrects for both false-positive and false-negative conflict reporting errors. We provide study design recommendations using simulations that explore the performance of the model under a range of conflict reporting probabilities. We applied the model to data on wild boar (Sus scrofa) space use and conflicts collected from the Central Terai Landscape (CTL), an important tiger conservation landscape in India. We found that tolerance for wildlife was a predictor of the probability with which farmers report conflict with wild boars from sites not used by the species. We also discuss useful extensions of the model when conflict data are verified for potential false-positive errors and when landscapes are monitored over multiple seasons.
Post-release Movement Behaviour and Survival of Kulan Reintroduced to the Steppes and Deserts of Central Kazakhstan
Authors: Kaczensky Petra , Salemgareyev Albert , Linnell John D. C. , Zuther Steffen , Walzer Chris , Huber Nikolaus , Petit Thierry
Published: August 2021

Asiatic wild ass, or kulan (Equus hemionus kulan) were once a key species of the Eurasian steppes and deserts. In Kazakhstan they went extinct by the 1930s. Early reintroductions have reestablished the species in two protected areas, but the species has reclaimed <1% of their former range and remained absent from central Kazakhstan. To initiate restoration in this vast region, we captured and transported a first group of nine wild kulan to a large pre-release enclosure in the Torgai region in 2017, and two more in 2019. We used direct observations and post-release movement data of four kulan equipped with GPS-Iridium collars to document their adaptation process in a vast novel habitat without conspecifics. For comparison with movements in the source populations, we additionally equipped two kulan in Altyn Emel National Park and six in Barsa Kelmes State Nature Reserve. The nine transported kulan formed a cohesive group with very high movement correlation in the enclosure. After release, the group initially stayed tightly together but started to break up by mid-May and all kulan travelled independently by mid-August. With 48,680–136,953 km2, the 95% Autocorrelated Kernel Density Estimation ranges of the reintroduced kulan were huge and about 10–100 times larger than those in the source populations. The reintroduced mares never reconnected, there was no evidence of successful reproduction, and two of the four collared mares were killed by poachers and one died of natural causes. At least one stallion survived in the wild, but the fate of the other uncollared animals remains unclear. We speculate that the fission-fusion dynamics and low movement correlation of kulan societies and the need for migratory movements harbours the risk that animals released into a novel environment loose contact with each other. This risk is likely enhanced in steppe habitats where movement constraining factors are absent. Further kulan reintroductions to the steppes and deserts of central Kazakhstan should aim to release larger groups and build up the free-ranging population quickly to reach a critical mass, increasing the chance of kulan encountering conspecifics to successfully breed and increase their chances of survival.
Perivascular Adipose-Derived Exosomes Reduce Foam Cell Formation by Regulating Expression of Cholesterol Transporters
Authors: Liu Yan , Sun Yan , Lin Xuze , Zhang Dai , Hu Chengping , Liu Jinxing , Zhu Yong , Gao Ang , Han Hongya , Chai Meng , Zhang Jianwei , Zhou Yujie , Zhao Yingxin
Published: August 2021

Background: Accumulating evidence demonstrates that perivascular adipose tissue (PVAT) plays an important role in maintaining vascular homeostasis. The formation of macrophage foam cells is a central feature of atherosclerosis. This study aimed to evaluate the effect of PVAT-derived exosomes (EXOs) on the lipid accumulation of macrophages and verify the anti-atherogenic characteristics of PVAT.

Methods and Results: We extracted EXOs from the PVAT and subcutaneous adipose tissue (SCAT) of wild-type C57BL/6J mice. After coincubation, the EXOs were taken up by RAW264.7 cells. Oil Red O staining revealed that macrophage foam cell formation and intracellular lipid accumulation were ameliorated by PVAT-EXOs. Flow cytometry showed that PVAT-EXOs significantly reduced macrophage uptake of fluorescence-labelled oxidised low-density lipoprotein (ox-LDL). In addition, high-density lipoprotein-induced cholesterol efflux was promoted by PVAT-EXOs. Western blot analysis showed the downregulation of macrophage scavenger receptor A and the upregulation of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which could be mediated by the overexpression of peroxisome proliferator-activated receptor γ and was independent of liver X receptor α.

Conclusion: Our findings suggest that PVAT-EXOs reduce macrophage foam cell formation by regulating the expression of cholesterol transport proteins, which provides a novel mechanism by which PVAT protects the vasculature from atherosclerosis.
The Fluid Evolution of Ancient Carbonate Reservoirs in Sichuan Basin and Its Implication for Shale Gas Exploration
Authors: Zhou Zhenzhu , Chen Xiaolan , Xia Haiyang
Published: August 2021

Sichuan Basin is the only successful basin for shale gas exploration in China. In addition to the main shale in the Lower Silurian Longmaxi formation, the lower Cambrian Qiongzhusi shale is an important potential formation. However, it was once considered that shale gas is difficult to enrich because of its poor sealing conditions and hydrocarbon migration to adjacent reservoirs. With the increasing research on hydrocarbon generation and reservoir in shale of Qiongzhusi Formation in recent years, it has become an important exploration target in Sichuan Basin. The enrichment of oil and gas is closely related to fluid activities. Limited by the degree of exploration, there is little analysis of fluid activities in Qiongzhusi Formation, and there is little analysis of shale gas enrichment potential from the perspective of fluid. The hydrocarbon generated from Qiongzhusi shale in the rift could migrate laterally to the uplift area and form a reservoir in Dengying Formation. The fluid activities from source rock to reservoir are basically the same. Therefore, this paper reconstructed the history of hydrocarbon activities in Dengying reservoirs based on fluid inclusion analysis. Then the fluid activity process in Qiongzhusi shale was studied, and its enrichment conditions of shale gas was discussed. The results show that the hydrocarbon activities of Dengying Formation can be divided into three stages: 1) oil charging stage, 2) oil cracking gas generation stage and 3) gas reservoir adjustment stage. The first stage is under normal pressure, and the second and third stages developed overpressure with pressure coefficients of 1.3 and 1.2, respectively. High pressure coefficient is an important indicator of shale gas enrichment. Because the source rock of Qiongzhusi Formation has always been the main source rock of Dengying Formation, it can supply hydrocarbon to Dengying Formation only with overpressure in gas generation stage. Therefore, overpressure in the last two stages of gas generation indeed existed. As long as the sealing condition of shale itself is not particularly poor, shale gas “sweet points” would be formed. Therefore, the thick shale in Deyang-Anyue rift is the focus of shale gas exploration in Qiongzhusi Formation.
Observations of the Effects of Maternal Fasting Plasma Glucose Changes in Early Pregnancy on Fetal Growth Profiles and Birth Outcomes
Authors: Guo Fei , Liu Yindi , Ding Zheng , Zhang Yong , Zhang Chen , Fan Jianxia
Published: August 2021

Introduction

Although the role of maternal hyperglycemia on birth outcomes is clear, literature regarding fetal growth is scarce. We examined the possible associations between maternal fasting plasma glucose (FPG) and fetal growth.

Materials and Methods

A total of 35,981 singleton-pregnant women with FPG in the first trimester were included. Fetal growth parameters were measured during pregnancy by ultrasound at mid and late pregnancy. Information on birth characteristics was retrieved from medical records. We used multivariable linear and logistic regression to determine the associations between FPG and z-scores of fetal parameters and risks of birth outcomes and to assess effect modification by maternal characteristics.

Results

A per-unit increase in FPG levels was negatively associated with fetal parameters in mid pregnancy but positively correlated with those in late pregnancy and with birth characteristics. The effect estimates in late pregnancy were attenuated by maternal pre-pregnancy body mass index (BMI). A significant relationship between FPG and abdominal circumference (AC), an indicator of fetal adiposity, was sustained in subgroups of women with advanced age, positive family history of diabetes, and multiparity in fully adjusted models. After stratification by BMI, high FPG was associated with accelerated AC only in normal controls (0.044 SD; 95% CI: 0.010, 0.079) and overweight/obese women (0.069 SD; 95% CI: -0.002, 0.140) but not in underweight women. High FPG was an independent risk factor for large-for-gestational age in the whole group and stratified subgroups.

Conclusions

Increased FPG in early pregnancy is closely related to fetal growth. Maternal characteristics may modify the associations between FPG and fetal adiposity in late pregnancy.
Simulation-Based Evaluation of Treatment Adjustment to Exercise in Type 1 Diabetes
Authors: Deichmann Julia , Bachmann Sara , Burckhardt Marie-Anne , Szinnai Gabor , Kaltenbach Hans-Michael
Published: August 2021

Regular exercise is beneficial and recommended for people with type 1 diabetes, but increased glucose demand and changes in insulin sensitivity require treatment adjustments to prevent exercise-induced hypoglycemia. Several different adjustment strategies based on insulin bolus reductions and additional carbohydrate intake have been proposed, but large inter- and intraindividual variability and studies using different exercise duration, intensity, and timing impede a direct comparison of their effects. In this study, we use a mathematical model of the glucoregulatory system and implement published guidelines and strategies in-silico to provide a direct comparison on a single ‘typical’ person on a standard day with three meals. We augment this day by a broad range of exercise scenarios combining different intensity and duration of the exercise session, and different timing with respect to adjacent meals. We compare the resulting blood glucose trajectories and use summary measures to evaluate the time-in-range and risk scores for hypo- and hyperglycemic events for each simulation scenario, and to determine factors that impede prevention of hypoglycemia events. Our simulations suggest that the considered strategies and guidelines successfully minimize the risk for acute hypoglycemia. At the same time, all adjustments substantially increase the risk of late-onset hypoglycemia compared to no adjustment in many cases. We also find that timing between exercise and meals and additional carbohydrate intake during exercise can lead to non-intuitive behavior due to superposition of meal- and exercise-related glucose dynamics. Increased insulin sensitivity appears as a major driver of non-acute hypoglycemic events. Overall, our results indicate that further treatment adjustment might be required both immediately following exercise and up to several hours later, but that the intricate interplay between different dynamics makes it difficult to provide generic recommendations. However, our simulation scenarios extend substantially beyond the original scope of each model component and proper model validation is warranted before applying our in-silico results in a clinical setting.
Research on the Parametric Modelling Approach of Vortex Generator on Wind Turbine Airfoil
Authors: Chen Ming , Zhao Zhenzhou , Liu Huiwen , Wang Tongguang , Meng Lingyu , Feng Junxin , Jiang Ruifang , Wang Dingding
Published: August 2021

Counter-rotating vortex generators (VGs) are typically employed to delay airflow separation on wind turbine blades. Large-size wind turbine blades equipped with small size VGs make the computational fluid dynamics (CFD) researches require a great deal of computational resources. Parametric models of VGs can effectively improve the numerical research efficiency of wind turbine blades with VGs. In order to improve the accuracy of such parametric models, this study proposed a series of modeling approaches to determine the positions of the adding source term in Cartesian coordinates, the VG vortex core radius, etc., on the wind turbine airfoils. These techniques are integrated with a maximum circulation algorithm by considering the interactions between VG pairs to predict the performance of a DU91-W2-250 blade section with VGs. The proposed parametric model and an entity model at different angles of attack (AoAs) are implemented on the blade section. Our approach is validated using experimental data. Comparisons demonstrate a strong agreement between the modelled and experimental results, proving the high accuracy of the two models. The numerical results of the models are then compared and analyzed at different incoming flow velocities and AoAs to verify the universality of the proposed parametric approaches. The results reveal a high consistency between the vortex structure, the velocity profile above the blade surface and the distribution of the pressure coefficient calculated by the two models. This proves the high universality of the proposed approaches and demonstrates the potential of the parametric model in replacing the VG entity model. The VG parametric model expresses VG parameters by program, which can improve the research efficiency of VG arrangement on wind turbine blades.
Towards Good E-Flows Practices in the Small-Scale Hydropower Sector in Uganda
Authors: O’Brien G. C. , Dickens C. W. S. , Mor C. , England M. I.
Published: August 2021

Stakeholders of the small-scale (<50 MW generation capacity) hydropower sector in Uganda recognise the importance of sustainable development of the resources that have social and ecological importance. Uganda is experiencing a boom in hydropower projects resulting in over generation of electricity and its exportation to neighbouring nations. Limited policies are currently available in Uganda to direct the sustainable development of this sector. Environmental flows (e-flows) practices established for the Nile Basin region and international good e-flows practices can contribute to sustainable management of hydropower developments in Uganda. The paper defines and explains e-flows, identifies water resource attributes of importance for e-flows determination associated with hydropower and threat associated with this activity in Uganda, and provides good e-flows determination and management practices based on regional and international information. The determination and management of e-flows in the hydropower sector in Uganda is largely dependent on the availability of and quality of hydrology, hydraulic and flow-ecosystem and flow-ecosystem service relationship information. This review of good-practice e-flows practice for the small hydropower sector in Uganda provides guidance to support multiple stakeholders of water resources in Uganda for a better future for all of its vulnerable communities and the environments they depend on.
Co-Designing Urban Carbon Sink Parks: Case Carbon Lane in Helsinki
Authors: Tammeorg Priit , Soronen Päivi , Riikonen Anu , Salo Esko , Tikka Suvi , Koivunen Minja , Salonen Anna-Reetta , Kopakkala Topi , Jalas Mikko
Published: August 2021

In order to achieve the goals of carbon (C) neutrality within next 20 year, municipalities worldwide need to increasingly apply negative emission technologies. We focus on the main principles of urban demonstration areas using biochars for C sequestration and explore the lessons learned from a co-creation process of one such park, Hyväntoivonpuisto in Helsinki, Finland. Demonstration sites of urban C sinks in public parks must be safe, visible and scientifically sound for reliable and cost-effective verification of carbon sequestration. We find that different interests can be arbitrated and that synergy that emerges from co-creation of urban C sink parks between stakeholders (scientists, city officials, companies, and citizens) can result in demo areas with maximized potential for impact, dissemination and consideration of principles of scientific experimentation.
Asymmetric Risk Spillover of the International Crude Oil Market in the Perspective of Crude Oil Dual Attributes
Authors: Jia Shuaishuai , Dong Hao , Yang Haowen
Published: August 2021

The heterogeneity of investor sentiment plays a key role in causing the asymmetry of information transmission patterns and transmission intensity between markets. This paper analyzes the asymmetric risk spillover between the international crude oil market and other markets, including commodity market and financial market, using monthly data from June 2006 to October 2020. The risk from the international crude oil market is separated into upside and downside risks. The empirical results suggest that, first, from the perspective of static spillover, the risk spillover between the international oil market and commodity market or financial market enhances significantly in response to rising return; second, from the perspective of dynamic spillover, the asymmetric risk spillover of international crude oil market manifests the key roles played by important events happening in the crude oil market and alternating attributes of crude oil. Some policy suggestions are proposed in light of these empirical results.
Immune-Related Genes Are Prognostic Markers for Prostate Cancer Recurrence
Authors: Fu Min , Wang Qiang , Wang Hanbo , Dai Yun , Wang Jin , Kang Weiting , Cui Zilian , Jin Xunbo
Published: August 2021

Background

Prostate cancer (PCa) is an immune-responsive disease. The current study sought to explore a robust immune-related prognostic gene signature for PCa.

Methods

Data were retrieved from the tumor Genome Atlas (TCGA) database and GSE46602 database for performing the least absolute shrinkage and selection operator (LASSO) cox regression model analysis. Immune related genes (IRGs) data were retrieved from ImmPort database.

Results

The weighted gene co-expression network analysis (WGCNA) showed that nine functional modules are correlated with the biochemical recurrence of PCa, including 259 IRGs. Univariate regression analysis and survival analysis identified 35 IRGs correlated with the prognosis of PCa. LASSO Cox regression model analysis was used to construct a risk prognosis model comprising 18 IRGs. Multivariate regression analysis showed that risk score was an independent predictor of the prognosis of PCa. A nomogram comprising a combination of this model and other clinical features showed good prediction accuracy in predicting the prognosis of PCa. Further analysis showed that different risk groups harbored different gene mutations, differential transcriptome expression and different immune infiltration levels. Patients in the high-risk group exhibited more gene mutations compared with those in the low-risk group. Patients in the high-risk groups showed high-frequency mutations in TP53. Immune infiltration analysis showed that M2 macrophages were significantly enriched in the high-risk group implying that it affected prognosis of PCa patients. In addition, immunostimulatory genes were differentially expressed in the high-risk group compared with the low-risk group. BIRC5, as an immune-related gene in the prediction model, was up-regulated in 87.5% of prostate cancer tissues. Knockdown of BIRC5 can inhibit cell proliferation and migration.

Conclusion

In summary, a risk prognosis model based on IGRs was developed. A nomogram comprising a combination of this model and other clinical features showed good accuracy in predicting the prognosis of PCa. This model provides a basis for personalized treatment of PCa and can help clinicians in making effective treatment decisions.
High-Frequency Homologous Recombination Occurred Preferentially in Populus
Authors: Geng Xining , Xia Yufei , Chen Hao , Du Kang , Yang Jun , Kang Xiangyang
Published: August 2021

Homologous recombination (HR), the most significant event in meiosis, has important implications for genetic diversity and evolution in organisms. Heteroduplex DNA (hDNA), the product of HR, can be captured by artificially induced chromosome doubling during the development of the embryo sac to inhibit postmeiotic segregation, subsequently, and hDNAs are directly detected using codominant simple sequence repeat (SSR) markers. In the present study, two hybrid triploid populations derived from doubling the chromosomes of the embryo sac induced by high temperature in Populus tomentosa served as starting materials. Eighty-seven, 62, and 79 SSR markers on chromosomes 01, 04, and 19, respectively, that were heterozygous in the maternal parent and different from the paternal parent were screened to detect and characterize the hDNA in P. tomentosa. The results showed that the hDNA frequency patterns on chromosomes changed slightly when the number of SSR primers increased. The highest hDNA frequency occurred at the adjacent terminal on chromosomes, which was slightly higher than those at the terminals in the two genotypic individuals, and the hDNA frequency gradually decreased as the locus-centromere distance decreased. With the increase in the number of SSR markers employed for detection, the number of recombination events (REs) detected significantly increased. In regions with high methylation or long terminal repeat (LTR) retrotransposon enrichment, the frequency of hDNA was low, and high frequencies were observed in regions with low sequence complexity and high gene density. High-frequency recombination occurring at high gene density regions strongly affected the association between molecular markers and quantitative trait loci (QTLs), which was an important factor contributing to the difficulty encountered by MAS in achieving the expected breeding results.
Convalescent COVID-19 Patients Without Comorbidities Display Similar Immunophenotypes Over Time Despite Divergent Disease Severities
Authors: Chu Chang-Feng , Sabath Florian , Fibi-Smetana Silvia , Sun Shan , Öllinger Rupert , Noeßner Elfriede , Chao Ying-Yin , Rinke Linus , Winheim Elena , Rad Roland , Krug Anne B. , Taher Leila , Zielinski Christina E.
Published: August 2021

COVID-19, the disease caused by SARS-CoV-2 infection, can assume a highly variable disease course, ranging from asymptomatic infection, which constitutes the majority of cases, to severe respiratory failure. This implies a diverse host immune response to SARS-CoV-2. However, the immunological underpinnings underlying these divergent disease courses remain elusive. We therefore set out to longitudinally characterize immune signatures of convalescent COVID-19 patients stratified according to their disease severity. Our unique convalescent COVID-19 cohort consists of 74 patients not confounded by comorbidities. This is the first study of which we are aware that excludes immune abrogations associated with non-SARS-CoV-2 related risk factors of disease severity. Patients were followed up and analyzed longitudinally (2, 4 and 6 weeks after infection) by high-dimensional flow cytometric profiling of peripheral blood mononuclear cells (PBMCs), in-depth serum analytics, and transcriptomics. Immune phenotypes were correlated to disease severity. Convalescence was overall associated with uniform immune signatures, but distinct immune signatures for mildly versus severely affected patients were detectable within a 2-week time window after infection.
The Role of Regulatory T Cells in Pulmonary Arterial Hypertension
Authors: Tian Wen , Jiang Shirley Y. , Jiang Xinguo , Tamosiuniene Rasa , Kim Dongeon , Guan Torrey , Arsalane Siham , Pasupneti Shravani , Voelkel Norbert F. , Tang Qizhi , Nicolls Mark R.
Published: August 2021

Pulmonary arterial hypertension (PAH) is a chronic, incurable condition characterized by pulmonary vascular remodeling, perivascular inflammation, and right heart failure. Regulatory T cells (Tregs) stave off autoimmunity, and there is increasing evidence for their compromised activity in the inflammatory milieu of PAH. Abnormal Treg function is strongly correlated with a predisposition to PAH in animals and patients. Athymic Treg-depleted rats treated with SU5416, an agent causing pulmonary vascular injury, develop PAH, which is prevented by infusing missing CD4+CD25highFOXP3+ Tregs. Abnormal Treg activity may also explain why PAH disproportionately affects women more than men. This mini review focuses on the role of Tregs in PAH with a special view to sexual dimorphism and the future promise of Treg therapy.
Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia
Authors: Shelyakin Pavel V. , Lupyr Ksenia R. , Egorov Evgeny S. , Kofiadi Ilya A. , Staroverov Dmitriy B. , Kasatskaya Sofya A. , Kriukova Valeriia V. , Shagina Irina A. , Merzlyak Ekaterina M. , Nakonechnaya Tatiana O. , Latysheva Elena A. , Manto Irina A. , Khaitov Musa R. , Lukyanov Sergey A. , Chudakov Dmitriy M. , Britanova Olga V.
Published: August 2021

The interplay between T- and B-cell compartments during naïve, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. Here we investigated characteristics of naïve and effector T cell subsets in XLA patients, revealing prominent alterations in the corresponding T-cell receptor (TCR) repertoires. We observed immunosenescence in terms of decreased diversity of naïve CD4+and CD8+TCR repertoires in XLA donors. The most substantial alterations were found within naïve CD4+subsets, and we have investigated these in greater detail. In particular, increased clonality and convergence, along with shorter CDR3 regions, suggested narrower focused antigen-specific maturation of thymus-derived naïve Treg(CD4+CD45RA+CD27+CD25+) in the absence of B cells - normally presenting diverse self and commensal antigens. The naïve Tregproportion among naïve CD4 T cells was decreased in XLA patients, supporting the concept of impaired thymic naïve Tregselection. Furthermore, the naïve Tregsubset showed prominent differences at the transcriptome level, including increased expression of genes specific for antigen-presenting and myeloid cells. Altogether, our findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naïve Treg TCR repertoire that enables better control of self-reactive T cells.
Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking
Authors: Bromberger Thomas , Klapproth Sarah , Rohwedder Ina , Weber Jasmin , Pick Robert , Mittmann Laura , Min-Weißenhorn Soo Jin , Reichel Christoph A. , Scheiermann Christoph , Sperandio Markus , Moser Markus
Published: August 2021

β2 integrins mediate key processes during leukocyte trafficking. Upon leukocyte activation, the structurally bent β2 integrins change their conformation towards an extended, intermediate and eventually high affinity conformation, which mediate slow leukocyte rolling and firm arrest, respectively. Translocation of talin1 to integrin adhesion sites by interactions with the small GTPase Rap1 and the Rap1 effector Riam precede these processes. Using Rap1 binding mutant talin1 and Riam deficient mice we show a strong Riam-dependent T cell homing process to lymph nodes in adoptive transfer experiments and by intravital microscopy. Moreover, neutrophils from compound mutant mice exhibit strongly increased rolling velocities to inflamed cremaster muscle venules compared to single mutants. Using Hoxb8 cell derived neutrophils generated from the mutant mouse strains, we show that both pathways regulate leukocyte rolling and adhesion synergistically by inducing conformational changes of the β2 integrin ectodomain. Importantly, a simultaneous loss of both pathways results in a rolling phenotype similar to talin1 deficient neutrophils suggesting that β2 integrin regulation primarily occurs via these two pathways.
Protectins PCTR1 and PD1 Reduce Viral Load and Lung Inflammation During Respiratory Syncytial Virus Infection in Mice
Authors: Walker Katherine H. , Krishnamoorthy Nandini , Brüggemann Thayse R. , Shay Ashley E. , Serhan Charles N. , Levy Bruce D.
Published: August 2021

Viral pneumonias are a major cause of morbidity and mortality, owing in part to dysregulated excessive lung inflammation, and therapies to modulate host responses to viral lung injury are urgently needed. Protectin conjugates in tissue regeneration 1 (PCTR1) and protectin D1 (PD1) are specialized pro-resolving mediators (SPMs) whose roles in viral pneumonia are of interest. In a mouse model of Respiratory Syncytial Virus (RSV) pneumonia, intranasal PCTR1 and PD1 each decreased RSV genomic viral load in lung tissue when given after RSV infection. Concurrent with enhanced viral clearance, PCTR1 administration post-infection, decreased eosinophils, neutrophils, and NK cells, including NKG2D+ activated NK cells, in the lung. Intranasal PD1 administration post-infection decreased lung eosinophils and Il-13 expression. PCTR1 increased lung expression of cathelicidin anti-microbial peptide and decreased interferon-gamma production by lung CD4+ T cells. PCTR1 and PD1 each increased interferon-lambda expression in human bronchial epithelial cells in vitro and attenuated RSV-induced suppression of interferon-lambda in mouse lung in vivo. Liquid chromatography coupled with tandem mass spectrometry of RSV-infected and untreated mouse lungs demonstrated endogenous PCTR1 and PD1 that decreased early in the time course while cysteinyl-leukotrienes (cys-LTs) increased during early infection. As RSV infection resolved, PCTR1 and PD1 increased and cys-LTs decreased to pre-infection levels. Together, these results indicate that PCTR1 and PD1 are each regulated during RSV pneumonia, with overlapping and distinct mechanisms for PCTR1 and PD1 during the resolution of viral infection and its associated inflammation.