Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain

COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. ABSTRACT The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model in vivo. The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the “ridge” of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both “up” and “down” conformations of S-RBD. In vitro mutagenesis assays show that mutant residues found in the emerging new lineage B.1. 1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. IMPORTANCE COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies’ neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.
Application of Non-Viral Vectors in Drug Delivery and Gene Therapy

Vectors and carriers play an indispensable role in gene therapy and drug delivery. Non-viral vectors are widely developed and applied in clinical practice due to their low immunogenicity, good biocompatibility, easy synthesis and modification, and low cost of production. This review summarized a variety of non-viral vectors and carriers including polymers, liposomes, gold nanoparticles, mesoporous silica nanoparticles and carbon nanotubes from the aspects of physicochemical characteristics, synthesis methods, functional modifications, and research applications. Notably, non-viral vectors can enhance the absorption of cargos, prolong the circulation time, improve therapeutic effects, and provide targeted delivery. Additional studies focused on recent innovation of novel synthesis techniques for vector materials. We also elaborated on the problems and future research directions in the development of non-viral vectors, which provided a theoretical basis for their broad applications.
Modeling of human T cell development in vitro as a read-out for hematopoietic stem cell multipotency

Hematopoietic stem cells (HSCs) reside in distinct sites throughout fetal and adult life and give rise to all cells of the hematopoietic system. Because of their multipotency, HSCs are capable of curing a wide variety of blood disorders through hematopoietic stem cell transplantation (HSCT). However, due to HSC heterogeneity, site-specific ontogeny and current limitations in generating and expanding HSCs in vitro, their broad use in clinical practice remains challenging. To assess HSC multipotency, evaluation of their capacity to generate T lymphocytes has been regarded as a valid read-out. Several in vitro models of T cell development have been established which are able to induce T-lineage differentiation from different hematopoietic precursors, although with variable efficiency. Here, we review the potential of human HSCs from various sources to generate T-lineage cells using these different models in order to address the use of both HSCs and T cell precursors in the clinic.
Electrospinning of a Copolymer PVDF-co-HFP Solved in DMF/Acetone: Explicit Relations among Viscosity, Polymer Concentration, DMF/Acetone Ratio and Mean Nanofiber Diameter

The process of electrospinning polymer solutions depends on many entry parameters, with each having a significant impact on the overall process and where complexity prevents the expression of their interplay. However, under the assumption that most parameters are fixed, it is possible to evaluate the mutual relations between pairs or triples of the chosen parameters. In this case, the experiments were carried out with a copolymer poly(vinylidene-co-hexafluoropropylene) solved in mixed N,N’-dimethylformamide (DMF)/acetone solvent for eight polymer concentrations (8, 10, 12, 15, 18, 21, 24, and 27 wt.%) and five DMF/acetone ratios (1/0, 4/1, 2/1, 1/1, 1/2). Processing of the obtained data (viscosity, mean nanofiber diameter) aimed to determine algebraic expressions relating both to viscosity and a mean nanofiber diameter with polymer concentration, as well as DMF/acetone ratio. Moreover, a master curve relating these parameters with no fitting factors was proposed continuously covering a sufficiently broad range of concentration as well as DMF/acetone ratio. A comparison of algebraic evaluation with the experimental data seems to be very good (the mean deviation for viscosity was about 2%, while, for a mean nanofiber diameter was slightly less than 10%).
The Evidence of the Bystander Effect after Bleomycin Electrotransfer and Irreversible Electroporation

One of current applications of electroporation is electrochemotherapy and electroablation for local cancer treatment. Both of these electroporation modalities share some similarities with radiation therapy, one of which could be the bystander effect. In this study, we aimed to investigate the role of the bystander effect following these electroporation-based treatments. During direct CHO-K1 cell treatment, cells were electroporated using one 100 µs duration square wave electric pulse at 1400 V/cm (for bleomycin electrotransfer) or 2800 V/cm (for irreversible electroporation). To evaluate the bystander effect, the medium was taken from directly treated cells after 24 h incubation and applied on unaffected cells. Six days after the treatment, cell viability and colony sizes were evaluated using the cell colony formation assay. The results showed that the bystander effect after bleomycin electrotransfer had a strong negative impact on cell viability and cell colony size, which decreased to 2.8% and 23.1%, respectively. On the contrary, irreversible electroporation induced a strong positive bystander effect on cell viability, which increased to 149.3%. In conclusion, the results presented may serve as a platform for further analysis of the bystander effect after electroporation-based therapies and may ultimately lead to refined application of these therapies in clinics.
Hemostatic Electrospun Nanocomposite Containing Poly(lactic acid)/ Halloysite Nanotube Functionalized by Poly(amidoamine) Dendrimer for Wound Healing Application: in Vitro and in Vivo Assays.

The main challenge in treating injuries is excessive bleeding whereas intervention is required if the body's hemostatic systems fail to control the bleeding. Herein, a novel nanocomposite consisting of poly(lactic acid) (PLA) and poly(amidoamine) (PAMAM) dendrimer functionalized halloysite nanotube (HNT) with a highly porous structure via electrospinning is developed. HNT was functionalized by PAMAM via divergent synthetic routes from zero to third-generation numbers. The effect of different percentages and generation numbers of PAMAM dendrimer (G1, G2, and G3) functionalized HNT on PLA is studied using physicochemical nanocomposites characteristics. These resultant nanocomposites provide a nanofibrous structure with appropriate physicochemical characteristics such as mechanical properties, surface wettability and water permeability. The hemostatic assays indicate that nanocomposite with PAMAM G3 functionalized HNT have the quickest blood clotting time due to the abundant amino functional group. Furthermore, the nanocomposites with 10wt% of nanoparticles significantly promote cellular behavior in vitro. The in vivo study demonstrates that PLA/PAMAM G3 functionalized HNT promotes angiogenesis, collagen deposition, and re-epithelialization in the wound sites of the rat model, as well as inhibiting inflammatory response. Our findings indicate that nanofibrous structure and the presence of dendrimer functionalized HNT have a synergetic effect on the enhanced nanocomposite wound healing performance. This article is protected by copyright. All rights reserved.
Uncertainty-Aware Knowledge Distillation for Collision Identification of Collaborative Robots

Human-robot interaction has received a lot of attention as collaborative robots became widely utilized in many industrial fields. Among techniques for human-robot interaction, collision identification is an indispensable element in collaborative robots to prevent fatal accidents. This paper proposes a deep learning method for identifying external collisions in 6-DoF articulated robots. The proposed method expands the idea of CollisionNet, which was previously proposed for collision detection, to identify the locations of external forces. The key contribution of this paper is uncertainty-aware knowledge distillation for improving the accuracy of a deep neural network. Sample-level uncertainties are estimated from a teacher network, and larger penalties are imposed for uncertain samples during the training of a student network. Experiments demonstrate that the proposed method is effective for improving the performance of collision identification.
Leader-Following Consensus of Heterogeneous Linear Multiagent Systems With Communication Time-Delays via Adaptive Distributed Observers

This article investigates the leader-following consensus problem of heterogeneous linear multiagent systems under switching and directed topologies. It is assumed that the communication between agents suffers from time-varying delays and only the neighboring agents of the leader are able to get access to the information of the leader agent, including its agent matrices. A key technical lemma on the input to state stability of time-delayed systems is first established with which the main results of this article can be obtained. An adaptive distributed observer, taking into consideration of communication time delays, is proposed for each follower to estimate the leader’s system matrices and its state. Then, a distributed controller based on this adaptive observer is developed. We show that the resulting closed-loop multiagent system achieves the leader-following output consensus. Two examples are finally given to illustrate the effectiveness of the proposed controller.
Smartphone-Based Human Sitting Behaviors Recognition Using Inertial Sensor

At present, people spend most of their time in passive rather than active mode. Sitting with computers for a long time may lead to unhealthy conditions like shoulder pain, numbness, headache, etc. To overcome this problem, human posture should be changed for particular intervals of time. This paper deals with using an inertial sensor built in the smartphone and can be used to overcome the unhealthy human sitting behaviors (HSBs) of the office worker. To monitor, six volunteers are considered within the age band of 26 ± 3 years, out of which four were male and two were female. Here, the inertial sensor is attached to the rear upper trunk of the body, and a dataset is generated for five different activities performed by the subjects while sitting in the chair in the office. Correlation-based feature selection (CFS) technique and particle swarm optimization (PSO) methods are jointly used to select feature vectors. The optimized features are fed to machine learning supervised classifiers such as naive Bayes, SVM, and KNN for recognition. Finally, the SVM classifier achieved 99.90% overall accuracy for different human sitting behaviors using an accelerometer, gyroscope, and magnetometer sensors.
Fragmented blind docking: a novel protein–ligand binding prediction protocol

Abstract In the present paper we propose a novel blind docking protocol based on Autodock-Vina. The developed docking protocol can provide binding site identification and binding pose prediction at the same time, by a systematical exploration of the protein volume performed with several preliminary docking calculations. In our opinion, this protocol can be successfully applied during the first steps of the virtual screening pipeline, because it provides binding site identification and binding pose prediction at the same time without visual evaluation of the binding site. After the binding pose prediction, MM/GBSA re-scoring rescoring procedures has been applied to improve the accuracy of the protein–ligand bound state. The FRAD protocol has been tested on 116 protein–ligand complexes of the Heat Shock Protein 90 – alpha, on 176 of Human Immunodeficiency virus protease 1, and on more than 100 protein–ligand system taken from the PDBbind dataset. Overall, the FRAD approach combined to MM/GBSA re-scoring can be considered as a powerful tool to increase the accuracy and efficiency with respect to other standard docking approaches when the ligand-binding site is unknown. Communicated by Ramaswamy H. Sarma
Rhythmic sampling revisited: Experimental paradigms and neural mechanisms

Sampling of information is thought to be an important aspect of explorative behaviour. Evidence for it has been gained in behavioural assessments of a variety of overt and covert cognitive domains, including sensation, attention, memory, eye movements and dexterity. A common aspect across many findings is that sampling tends to exhibit a rhythmicity at low frequencies (theta, 4–8 Hz; alpha, 9–12 Hz). Neurophysiological investigations in a wide range of species, including rodents, non‐human primates and humans have demonstrated the presence of sampling related neural oscillations in a number of brain areas ranging from early sensory cortex, hippocampus to high‐level cognitive areas. However, to assess whether rhythmic sampling represents a general aspect of exploratory behaviour one must critically evaluate the task parameters, and their potential link with neural oscillations. Here we focus on sampling during attentive vision to present an overview on the experimental conditions that are used to investigate rhythmic sampling and associated oscillatory brain activity in this domain. This review aims to (1) provide guidelines to efficiently quantify behavioural rhythms, (2) compare results from human and non‐human primate studies and (3) argue that the underlying neural mechanisms of sampling can co‐occur in both sensory and high‐level areas.
Rapid evolution of post-zygotic reproductive isolation is widespread in Arctic plant lineages

Abstract Background and Aims The Arctic tundra, with its extreme temperatures and short growing season, is evolutionarily young and harbours one of the most species-poor floras on Earth. Arctic species often show little phenotypic and genetic divergence across circumpolar ranges. However, strong intraspecific post-zygotic reproductive isolation (RI) in terms of hybrid sterility has frequently evolved within selfing Arctic species of the genus Draba. Here we assess whether incipient biological species are common in the Arctic flora. Methods We conducted an extensive crossing experiment including six species representing four phylogenetically distant families collected across the circumpolar Arctic. We crossed conspecific parental populations representing different spatial scales, raised 740 F1 hybrids to maturity and measured fertility under laboratory conditions. We examined genetic divergence between populations for two of these species (Cardamine bellidifolia and Ranunculus pygmaeus). Key Results In five of the six species, we find extensive reduction in pollen fertility and seed set in F1 hybrids; 219 (46 %) of the 477 F1 hybrids generated between parents separated by ≥427 km had <20 % pollen fertility. Isolation with migration (IM) and *BEAST analyses of sequences of eight nuclear genes in C. bellidifolia suggests that reproductively isolated populations of this species diverged during, or even after, the last glaciation. Likewise, Arctic populations of R. pygmaeus were genetically very similar despite exhibiting strongly reduced fertility in crosses, suggesting that RI evolved recently also in this species. Conclusion We show that post-zygotic RI has developed multiple times within taxonomically recognized Arctic species belonging to several distantly related lineages, and that RI may have developed over just a few millennia. Rapid and widespread evolution of incipient biological species in the Arctic flora might be associated with frequent bottlenecks due to glacial cycles, and/or selfing mating systems, which are common in the harsh Arctic environment where pollinators are scarce.
Elucidating the Association Between Military Sexual Trauma Types and Different Types of Risky Behaviors

ABSTRACT Military sexual harassment (MSH) and assault (MSA) are associated with serious mental and physical health outcomes among military personnel and veterans. However, less is known about how these experiences relate to risky, impulsive, and health-compromising behaviors. The goal of the current study was to assess MSH and MSA in relation to a wide range of risky behaviors. Participants were 512 veterans in the community (M age = 41.36, 71.3% male, 71.3% white) who completed an online survey via Amazon’s Mechanical Turk (MTurk). Compared to veterans who reported MSH only or no history of MST, veterans with a MSA history reported greater past-month risky behavior engagement, both overall and for specific behaviors, including problematic use of alcohol, drugs, gambling, technology, risky sexual behaviors, eating behaviors, illegal behaviors, reckless spending, physically aggressive behaviors, verbally aggressive behaviors, property destruction, reckless driving, non-suicidal self-injury, and suicidal behavior. Our findings emphasize the importance of differentiating between MSH and MSA when detecting and intervening with veterans at risk for engaging in risky behaviors.
Microglia‐specific ApoE knock‐out does not alter Alzheimer's disease plaque pathogenesis or gene expression

Previous studies suggest that microglial‐expressed Apolipoprotein E (ApoE) is necessary to shift microglia into a neurodegenerative transcriptional state in Alzheimer's disease (AD) mouse models. On the other hand, elimination of microglia shifts amyloid beta (Aβ) accumulation from parenchymal plaques to cerebral amyloid angiopathy (CAA), mimicking the effects of global APOE*4 knock‐in. Here, we specifically knock‐out microglial‐expressed ApoE while keeping astrocytic‐expressed ApoE intact. When microglial‐specific ApoE is knocked‐out of a 5xFAD mouse model of AD, we found a ~35% increase in average Aβ plaque size, but no changes in plaque load, microglial number, microglial clustering around Aβ plaques, nor the formation of CAA. Immunostaining revealed ApoE protein present in plaque‐associated microglia in 5xFAD mice with microglial‐specific ApoE knockout, suggesting that microglia can take up ApoE from other cellular sources. Mice with Apoe knocked‐out of microglia had lower synaptic protein levels than control mice, indicating that microglial‐expressed ApoE may have a role in synapse maintenance. Surprisingly, microglial‐specific ApoE knock‐out resulted in few differentially expressed genes in both 5xFAD and control mice; however, some rescue of 5xFAD associated neuronal networks may occur with microglial‐specific ApoE knock‐out as shown by weighted gene co‐expression analysis. Altogether, our data indicates that microglial‐expressed ApoE may not be necessary for plaque formation or for the microglial transcriptional shift into a Disease Associated Microglia state that is associated with reactivity to plaques but may be necessary for plaque homeostasis in disease and synaptic maintenance under normal conditions.
Peritransplant glucocorticoids redistribute donor T cells to the bone marrow and prevent relapse after haploidentical SCT

Patients with acute leukemia who are unable to achieve complete remission prior to allogeneic hematopoietic stem cell transplantation (SCT) have dismal outcomes, with relapse rates well in excess of 60%. Haplo-identical SCT (haplo-SCT) may allow enhanced graft-versus-leukemia (GVL) effects by virtue of HLA class I/II donor-host disparities, but it typically requires intensive immunosuppression with posttransplant cyclophosphamide (PT-Cy) to prevent lethal graft-versus-host disease (GVHD). Here, we demonstrate in preclinical models that glucocorticoid administration from days –1 to +5 inhibits alloantigen presentation by professional recipient antigen presenting cells in the gastrointestinal tract and prevents donor T cell priming and subsequent expansion therein. In contrast, direct glucocorticoid signaling of donor T cells promotes chemokine and integrin signatures permissive of preferential circulation and migration into the BM, promoting donor T cell residency. This results in significant reductions in GVHD while promoting potent GVL effects; relapse in recipients receiving glucocorticoids, vehicle, or PT-Cy was 12%, 56%, and 100%, respectively. Intriguingly, patients with acute myeloid leukemia not in remission who received unmanipulated haplo-SCT and peritransplant glucocorticoids also had an unexpectedly low relapse rate at 1 year (32%; 95% CI, 18%–47%) with high overall survival at 3 years (58%; 95% CI, 38%–74%). These data highlight a potentially simple and effective approach to prevent relapse in patients with otherwise incurable leukemia that could be studied in prospective randomized trials.