bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards the Myoelectric Digital Twin: Ultra Fast and Realistic Modelling for Deep Learning
Authors: Maksymenko Kostiantyn , Clarke Alexander Kenneth , Guerra Irene Mendez , Deslauriers-Gauthier Samuel , Farina Dario 
Published: June 2021

AbstractMuscle electrophysiology has emerged as a powerful tool to drive human machine interfaces, with many new recent applications outside the traditional clinical domains. It is currently a crucial component of control systems in robotics and virtual reality. However, more sophisticated, functional, and robust decoding algorithms are required to meet the fine control requirements of these new applications. Deep learning approaches have shown the highest potential in this regard. To be effective, deep learning requires a large amount of high-quality annotated data for training; the only option today is the use of experimental electromyography data. Yet the acquisition and labelling of training data is time-consuming and expensive. Moreover, the high-quality annotation of this data is often not possible because the ground truth labels are hidden. Data augmentation using simulations, a strategy applied in other deep learning applications, has never been attempted in electromyography due to the absence of computationally efficient and realistic models. Here, we present a new highly realistic and ultra-fast computational model tailored for the training of deep learning algorithms. For the first time, we are able to simulate arbitrary large datasets of realistic electromyography signals with high internal variability and leverage it to train deep learning algorithms. Because the computational model provides access to all the hidden parameters of the simulation, it also allows us to use some annotation strategies that are impossible with experimental data. We believe that this concept of Myoelectric Digital Twin allows new unprecedented approaches to muscular signals decoding and will accelerate the development of human-machine interfaces.
T helper 2 transcriptional profile predicts single-cell HIV envelope-specific polyfunctional CD4+ T cells correlated with reduced risk of infection in RV144 trial
Authors: Cohen Kristen W. , Tian Yuan , Thayer Casey , Seese Aaron , Amezquita Robert , McElrath M. Juliana , De Rosa Stephen C. , Gottardo Raphael 
Published: June 2021

AbstractDespite the critical role antigen-specific T cells play in responding to viral infections, their aggregate frequencies in peripheral blood have not correlated with clinical protection during HIV infection. However, a subset of HIV-specific CD4+ T cells, termed polyfunctional T cells, can produce multiple effector cytokines simultaneously. In the RV144 HIV vaccine trial, polyfunctional T cells correlated with reduced risk of HIV infection. Little is known about what differentiates polyfunctional T cells from other vaccine-elicited T cells. Therefore, we developed a novel live-cell multiplexed cytokine capture assay, to identify and transcriptionally profile vaccine-specific polyfunctional CD4+ T cells. We applied these methods to samples from the HVTN 097 clinical trial of the same vaccine regimen as RV144. We discovered two surface receptors that were enriched among polyfunctional CD4+ T cells and a Th2-biased signature (IL-4, IL-5, and IL-13) that specifically predicted the envelope-specific polyfunctional CD4+ T cells that were correlated with reduced risk of HIV infection in RV144. By linking single-cell transcriptional and functional profiles, we may be able to further define the role of vaccine-elicited polyfunctional T cells in contributing to effective immunity.Key PointsNovel ex vivo multiplexed cytokine capture assay to enumerate and single-cell sort polyfunctional T cells for downstream analysesPolyfunctional T cells were specifically detected among the HIV envelope-stimulated CD4+ T cellsSingle-cell RNA sequencing identified novel surface markers enriched among vaccine-specific polyfunctional CD4+ T cellsTh2 transcriptional signature predicted polyfunctional CD4+ T cell profile that had correlated with reduced risk of HIV infection in the RV144 HIV efficacy trial
B1L regulates lateral root development by exocytic vesicular trafficking-mediated polar auxin transport in Arabidopsis
Authors: Yang Gang , Chen Bi-xia , Chen Tao , Chen Jia-hui , Sun Rui , Liu Cong-cong , Jia Jiao , Yue Xiu-le , An Li-zhe , Zhang Hua 
Published: June 2021

SUMMARYAuxin and auxin-mediated signaling pathways involved in the regulation of lateral root development are well documented. Although exocytic vesicle trafficking plays an important role in auxin efflux carriers PIN recycling, and polar auxin transport during lateral root formation, however, the mechanistic details of these processes are not well understood. Here, we demonstrate that BYPASS1-LIKE (B1L) regulate lateral root development via exocytic vesicular trafficking-mediated polar auxin transport in Arabidopsis. In b1l mutants, the number of lateral roots increased significantly, and the phenotypes were mainly attributed to lateral root primordium initiation but not to the defects in lateral root primordium development. Furthermore, the auxin signal was stronger in the lateral root primordium of the b1l mutant at stage I than those observed in the wild-type (WT). Moreover, exogenous auxin and auxin transport inhibitory treatments indicated that the phenotype of lateral roots in b1l mutants can be attributed to higher auxin levels and that B1L regulates auxin efflux. Consistently, auxin efflux carriers PIN1-GFP and PIN3-GFP were expressed at higher levels in the lateral root primordium of the b1l mutants. Interestingly, we found that B1L interacted with the exocyst and b1l mutant showed a defect in PIN2 exocytosis. Finally, we found that B1L cooperated with EXO70B1 to regulate lateral root formation. Our findings reveal an essential regulatory mechanism of B1L that interacts with the exocyst to regulate PIN-mediated polar auxin transport and lateral root initiation.
Droplets of amyotrophic lateral sclerosis-associated p62/SQSTM1 mutants show slower inner fluidity
Authors: Omar Faruk Mohammad , Ichimura Yoshinobu , Kageyama Shun , El-Gowily Afnan H. , Sou Yu-shin , Koike Masato , Noda Nobuo N , Komatsu Masaaki 
Published: June 2021

SummaryA series of amyotrophic lateral sclerosis (ALS)-related proteins such as FUS, TDP-43 and hnRNPA1 has an ability to be liquid-liquid phase separation, and their disease-related mutations cause the transition of their responsible liquid droplets to aggregates. Missense mutations in SQSTM1/p62, which have been identified throughout the gene, are associated with ALS, frontotemporal degeneration (FTD) and Paget’s disease of bone. SQSTM1/p62 protein forms liquid-droplets through the interaction with ubiquitinated proteins, and the droplet serves as a platform of autophagosome formation and anti-oxidative stress response via the LC3-interacting region (LIR) and Keap1-interacting region (KIR), respectively. However, it remains unclear whether ALS/FTD-related p62 mutations in LIR and KIR form aberrant liquid droplets, cause defective autophagy and stress response or both. To evaluate the effects of ALS/FTD-related p62 mutations in LIR and KIR on a major oxidative stress system, the Keap1-Nrf2 pathway and the autophagic turnover, we developed systems that enable to monitor them with high sensitivity. These systems revealed that some mutants but not all have their less abilities on the Nrf2-activation and show the delayed turnover. By contrast, while the sufficient ability to form liquid droplets, all droplets consisting of p62 mutants showed slower inner fluidity. These results indicate that like other ALS-related mutant proteins, a primary defect in ALS/FTD with p62 missense mutations is a qualitative change of p62-liquid droplets.
FXa cleaves the SARS-CoV-2 spike protein and blocks cell entry to protect against infection with inferior effects in B.1.1.7 variant
Authors: Dong Wenjuan , Wang Jing , Tian Lei , Zhang Jianying , Mead Heather , Jaramillo Sierra A. , Li Aimin , Zumwalt Ross E. , Whelan Sean P.J. , Settles Erik W. , Keim Paul S. , Barker Bridget Marie , Caligiuri Michael A. , Yu Jianhua 
Published: June 2021

AbstractThe ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human natural defense mechanisms against SARS-CoV-2 are largely unknown. Serine proteases (SPs) including furin and TMPRSS2 cleave SARS-CoV-2 spike protein, facilitating viral entry. Here, we show that FXa, a SP for blood coagulation, is upregulated in COVID-19 patients compared to non-COVID-19 donors and exerts anti-viral activity. Mechanistically, FXa cleaves the SARS-CoV-2 spike protein, which prevents its binding to ACE2, and thus blocks viral entry. Furthermore, the variant B.1.1.7 with several mutations is dramatically resistant to the anti-viral effect of FXa compared to wild-type SARA-CoV-2 in vivo and in vitro. The anti-coagulant rivaroxaban directly inhibits FXa and facilitates viral entry, whereas the indirect inhibitor fondaparinux does not. In a lethal humanized hACE2 mouse model of SARS-CoV-2, FXa prolonged survival while combination with rivaroxaban but not fondaparinux abrogated this protection. These preclinical results identify a previously unknown SP function and associated anti-viral host defense mechanism and suggest caution in considering direct inhibitors for prevention or treatment of thrombotic complications in COVID-19 patients.
A screen of covalent inhibitors in Mycobacterium tuberculosis identifies serine hydrolases involved in lipid metabolism as potential therapeutic targets
Authors: Babin Brett M. , Keller Laura J. , Pinto Yishay , Li Veronica L. , Eneim Andrew , Vance Summer E. , Terrell Stephanie M. , Bhatt Ami , Long Jonathan Z. , Bogyo Matthew 
Published: June 2021

SummaryThe increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their importance for the synthesis of the mycobacterial cell envelope. We screened a library of small molecules containing serine-reactive electrophiles and identified narrow spectrum inhibitors of M. tuberculous growth. Using these lead molecules, we performed competitive activity-based protein profiling and identified multiple SH targets, including enzymes with uncharacterized functions. Lipidomic analyses of compound-treated cultures revealed an accumulation of free lipids and a substantial decrease in lipooligosaccharides, linking SH inhibition to defects in cell envelope biogenesis. Mutant analysis revealed a path to resistance via the synthesis of mycocerates, but not through mutations to target enzymes. Our results suggest that simultaneous inhibition of multiple SH enzymes is likely to be an effective therapeutic strategy for the treatment of M. tuberculosis infections.
Viral Evasion of the Integrated Stress Response Through Antagonistic eIF2-P Mimicry
Authors: Schoof Michael , Wang Lan , Zachery Cogan J , Lawrence Rosalie , Boone Morgane , Wuerth Jennifer Deborah , Frost Adam , Walter Peter 
Published: June 2021

AbstractViral infection triggers activation of the integrated stress response (ISR). In response to viral double-stranded RNA (dsRNA), RNA-activated protein kinase (PKR) phosphorylates the translation initiation factor eIF2, converting it from a translation initiator into a potent translation inhibitor and this restricts the synthesis of viral proteins. Phosphorylated eIF2 (eIF2-P) inhibits translation by binding to eIF2’s dedicated, heterodecameric nucleotide exchange factor eIF2B and conformationally inactivating it. We show that the NSs protein of Sandfly Fever Sicilian virus (SFSV) allows the virus to evade the ISR. Mechanistically, NSs tightly binds to eIF2B (KD= 43 nM), blocks eIF2-P binding, and rescues eIF2B GEF activity. Cryo-EM structures demonstrate that SFSV NSs and eIF2-P directly compete, with the primary NSs contacts to eIF2Bα mediated by five ‘aromatic fingers’. NSs binding preserves eIF2B activity by maintaining eIF2B’s conformation in its active A-State.
Peer presence and familiarity as key factors to reduce cocaine intake: an effect mediated by the Subthalamic Nucleus
Authors: Giorla E , Nordmann S , Vielle C , Pelloux Y , Roux P , Protopopescu C , Manrique C , Davranche K , Montanari C , Giorgi L , Vilotitch A , Huguet P , Carrieri P , Baunez C 
Published: June 2021

AbstractStimulant use, including cocaine, often occurs in a social context whose influence is important to understand to decrease intake and reduce associated harms. Given the regulatory role of the subthalamic nucleus (STN) on cocaine intake and emotions, we investigate its role on such influence of social context on cocaine intake. We explored the influence of peer presence and familiarity on the frequency of self-administered cocaine and its neurobiological basis. We first compared cocaine intake in various conditions (alone or with peers with different characteristics: observing or self-administering, familiar or not, cocaine-naive or not, dominant or subordinate) in rats (n=90). The risk of drug consumption was reduced when a peer was present, observing or self-administering as well, and further diminished when the peer was unfamiliar (vs familiar). The presence of a cocaine-naive peer further decreased cocaine consumption. The presence of a non-familiar and drug-naive peer represents thus key conditions to diminish cocaine intake. We tested the effects of STN lesions in these various conditions and also conducted social experiments to validate the role of STN in social cognition. The STN lesion by itself reduced cocaine intake to the level reached in presence of a stranger naïve peer and affected social cognition, positioning the STN as one neurobiological substrate of social influence on drug intake. Finally, with a translational research approach, we compared the drug intake in these conditions in human drug users (n=77). This human study confirmed the beneficial effect of social presence, especially of strangers. Our results indirectly support the use of social interventions and harm reduction strategies, in particular supervised consumption rooms for stimulant users.
Seed microbiota revealed by a large-scale meta-analysis including 50 plant species
Authors: Simonin Marie , Briand Martial , Chesneau Guillaume , Rochefort Aude , Marais Coralie , Sarniguet Alain , Barret Matthieu 
Published: June 2021

ABSTRACTSeed microbiota constitutes a primary inoculum for plants that is gaining attention due to its role for plant health and productivity. Here, we performed a meta-analysis on 63 seed microbiota studies covering 50 plant species to synthesize knowledge on the diversity of this habitat. Seed microbiota are diverse and extremely variable, with taxa richness varying from one to thousands of taxa. Hence, seed microbiota presents a variable (i.e flexible) microbial fraction but we also identified a stable (i.e. core) fraction across samples. Around 30 bacterial and fungal taxa are present in most plant species and in samples from all over the world. Core taxa, such asPantoea agglomerans, Pseudomonas viridiflava, P. fluorescens, Cladosporium perangustumandAlternaria sp., are dominant seed taxa. The characterization of the core and flexible seed microbiota provided here will help uncover seed microbiota roles for plant health and design effective microbiome engineering.
ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling
Authors: Hancock-Cerutti William , Wu Zheng , Tharkeshwar Arun , Ferguson Shawn M. , Shadel Gerald S. , De Camilli Pietro 
Published: June 2021

ABSTRACTMutations in VPS13C cause early onset, autosomal recessive Parkinson’s Disease (PD). We have established that VPS13C encodes a lipid transfer protein localized to contact sites between the endoplasmic reticulum (ER) and late endosomes/lysosomes. In the current study, we demonstrate that depleting VPS13C in HeLa cells causes an accumulation of lysosomes with an altered lipid profile, including an accumulation of di-22:6-BMP, a biomarker of the PD-associated leucine-rich repeat kinase 2 (LRRK2) G2019S mutation. In addition, the DNA-sensing cGAS/STING pathway, which was recently implicated in PD pathogenesis, is activated in these cells. This activation results from a combination of elevated mitochondrial DNA in the cytosol and a defect in the degradation of activated STING, a lysosome-dependent process. These results suggest a link between ER-lysosome lipid transfer and innate immune activation and place VPS13C in pathways relevant to PD pathogenesis.
Initial sizing of a roadable personal air vehicle using design of experiments for various engine types
Authors: Cha Jaeyoung , Yun Juyeol , Hwang Ho-Yon 
Published: June 2021

Purpose
The purpose of this paper is to analyze and compare the performances of novel roadable personal air vehicle (PAV) concepts that meet established operational requirements with different types of engines.

Design/methodology/approach
The vehicle configuration was devised considering the dimensions and operational restrictions of the roads, runways and parking lots in South Korea. A folding wing design was adopted for road operations and parking. The propulsion designs considered herein use gasoline, diesel and hybrid architectures for longer-range missions. The sizing point of the roadable PAV that minimizes the wing area was selected, and the rate of climb, ground roll distance, cruise speed and service ceiling requirements were met. For various engine types and mission profiles, the performances of differently sized PAVs were compared with respect to the MTOW, wing area, wing span, thrust-to-weight ratio, wing loading, power-to-weight ratio, brake horsepower and fuel efficiency.

Findings
Unlike automobiles, the weight penalty of the hybrid system because of the additional electrical components reduced the fuel efficiency considerably. When the four engine types were compared, matching the total engine system weight, the internal combustion (IC) engine PAVs had better fuel efficiency rates than the hybrid powered PAVs. Finally, a gasoline-powered PAV configuration was selected as the final design because it had the lowest MTOW, despite its slightly worse fuel efficiency compared to that of the diesel-powered engine.

Research limitations/implications
Although an electric aircraft powered only by batteries most capitalizes on the operating cost, noise and emissions benefits of electric propulsion, it also is most hampered by range limitations. Air traffic integration or any safety, and noise issues were not accounted in this study.

Practical implications
Aircraft sizing is a critical aspect of a system-level study because it is a prerequisite for most design and analysis activities, including those related to the internal layout as well as cost and system effectiveness analyses. The results of this study can be implemented to design a PAV.

Social implications
This study can contribute to the establishment of innovative PAV concepts that can alleviate today’s transportation problems.

Originality/value
This study compared the sizing results of PAVs with hybrid engines with those having IC engines.
Adoption of rural bank credit programs among smallholder farmers in Ghana: an average treatment effect estimation of rates of exposure and adoption and their determinants
Authors: Missiame Arnold , Irungu Patrick , Nyikal Rose Adhiambo , Appiah-Kubi Grace Darko 
Published: June 2021

PurposeThe study aims to estimate the rates of exposure to, and adoption of, rural bank credit programs by smallholder farmers in rural Ghana and the factors responsible for those rates.Design/methodology/approachThe study used a random sample of 300 smallholder farmers in the Fanteakwa District of Ghana, obtained through the multistage sampling technique. The study also employed the average treatment effects approach to estimate the average treatment effect of farmers’ exposure to rural bank credit programs, on their adoption of such programs.FindingsThe actual adoption rate is approximately 41%, and the potential, conditional on the whole population being aware of rural bank credit programs, is approximately 61%. Accordingly, there is a gap of about 20% in the adoption of rural bank credit programs, and is due to the incomplete exposure of smallholder farmers to the rural bank credit programs. Age of the household head, access to extension services, membership in farmer-based organizations and active savings accounts with a rural bank are the major contributors to smallholder farmer exposure to and the adoption of rural bank credit programs.Originality/valueThe current study is the first of its kind to be conducted in Ghana on rural bank credit programs. It takes into account the extent to which smallholder farmers are exposed to such credit programs and how it influences their decisions to access or adopt.
Re-structuring library resources and services in IIT Delhi library: analytical study from users' perspective
Authors: Kumar Rajender , Gupta Dinesh K. 
Published: June 2021

Purpose
This study aims to assess users' satisfaction from the re-structured library resources and services due to technological innovations in the Indian Institute of Technology Delhi library. It also identifies and suggests potential improvement areas.

Design/methodology/approach
The study adopts a survey research method to collect data from the end-users of the library. Data were collected through a structured questionnaire. In total, 100 copies of questionnaires were distributed to the students, and out of the filled received questionnaires, 92 were found dully completed and useable. Collected data were analyzed by using percentage and chi-square test for testing of hypothesis.

Findings
This study shows that users' usage and preference for e-resources and e-services are increasing as there is a general trend to overlook traditional print resources where e-resources are available in the first place. The study recommends that a radical rethinking is required to strengthen the electronic collection and improve the library services.

Practical implications
The paper has a direct practical implication. It suggests that as technology continues to evolve, it is likely that academic institutes find themselves identifying appropriate areas to redesign library activities and services regularly. This paper reveals the practice of re-engineering in academic library services and knowing students' specific preferences of resources and services to enhance library usage.

Originality/value
The study is based on the self-designed structured questionnaire. Primary data has been collected from the IIT Delhi library users, thus providing original information and informative inputs to the existing literature.