Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure Determination by Single-Particle Cryo-Electron Microscopy: Only the Sky (and Intrinsic Disorder) is the Limit

Traditionally, X-ray crystallography and NMR spectroscopy represent major workhorses of structural biologists, with the lion share of protein structures reported in protein data bank (PDB) being generated by these powerful techniques. Despite their wide utilization in protein structure determination, these two techniques have logical limitations, with X-ray crystallography being unsuitable for the analysis of highly dynamic structures and with NMR spectroscopy being restricted to the analysis of relatively small proteins. In recent years, we have witnessed an explosive development of the techniques based on Cryo-electron microscopy (Cryo-EM) for structural characterization of biological molecules. In fact, single-particle Cryo-EM is a special niche as it is a technique of choice for the structural analysis of large, structurally heterogeneous, and dynamic complexes. Here, sub-nanometer atomic resolution can be achieved (i.e., resolution below 10 Å) via single-particle imaging of non-crystalline specimens, with accurate 3D reconstruction being generated based on the computational averaging of multiple 2D projection images of the same particle that was frozen rapidly in solution. We provide here a brief overview of single-particle Cryo-EM and show how Cryo-EM has revolutionized structural investigations of membrane proteins. We also show that the presence of intrinsically disordered or flexible regions in a target protein represents one of the major limitations of this promising technique.
A Dengue Virus Type 2 (DENV-2) NS4B-Interacting Host Factor, SERP1, Reduces DENV-2 Production by Suppressing Viral RNA Replication

Host cells infected with dengue virus (DENV) often trigger endoplasmic reticulum (ER) stress, a key process that allows viral reproduction, without killing the host cells until the late stage of the virus life-cycle. However, little is known regarding which DENV viral proteins interact with the ER machinery to support viral replication. In this study, we identified and characterized a novel host factor, stress-associated ER protein 1 (SERP1), which interacts with the DENV type 2 (DENV-2) NS4B protein by several assays, for example, yeast two-hybrid, subcellular localization, NanoBiT complementation, and co-immunoprecipitation. A drastic increase (34.5-fold) in the SERP1 gene expression was observed in the DENV-2-infected or replicon-transfected Huh7.5 cells. The SERP1 overexpression inhibited viral yields (37-fold) in the DENV-2-infected Huh7.5 cells. In contrast, shRNAi-knockdown and the knockout of SERP1 increased the viral yields (3.4- and 16-fold, respectively) in DENV-2-infected HEK-293 and Huh7.5 cells, respectively. DENV-2 viral RNA replication was severely reduced in stable SERP1-expressing Huh7.5 cells transfected with DENV-2 replicon plasmids. The overexpression of DENV-2 NS4B alleviated the inhibitory effect of SERP1 on DENV-2 RNA replication. Taking these results together, we hypothesized that SERP1 may serve as an antiviral player during ER stress to restrict DENV-2 infection. Our studies revealed novel anti-DENV drug targets that may facilitate anti-DENV drug discovery.
Multicenter study of lumbar discectomy with Barricaid annular closure device for prevention of lumbar disc reherniation in US patients

Abstract Background: Patients with large defects in the annulus fibrosus following lumbar discectomy have high rates of symptomatic reherniation. The Barricaid annular closure device provides durable occlusion of the annular defect and has been shown to significantly lower the risk of symptomatic reherniation in a large European randomized trial. However, the performance of the Barricaid device in a United States (US) population has not been previously reported. Design and methods: This is a historically controlled post-market multicenter study to determine the safety and efficacy of the Barricaid device when used in addition to primary lumbar discectomy in a US population. A total of 75 patients with large annular defects will receive the Barricaid device following lumbar discectomy at up to 25 sites in the US and will return for clinical and imaging follow-up at 4 weeks, 3 months, and 1 year. Trial oversight will be provided by a data safety monitoring board and imaging studies will be read by an independent imaging core laboratory. Patients treated with the Barricaid device in a previous European randomized trial with comparable eligibility criteria, surgical procedures, and outcome measures will serve as historical controls. Main outcomes will include back pain severity, leg pain severity, Oswestry Disability Index, health utility on the EuroQol-5 Dimension questionnaire, complications, symptomatic reherniation, and reoperation. Propensity score adjustment using inverse probability of treatment weighting will be used to adjust for differences in baseline patient characteristics between the US trial participants and European historical controls. Ethics and dissemination: This study was approved by a central institutional review board. The study results of this trial will be widely disseminated at conference proceedings and published in peer-reviewed journals. The outcomes of this study will have important clinical and economic implications for all stakeholders involved in treating patients with lumbar discectomy in the US. Study registration: ClinicalTrials.gov (https://clinicaltrials.gov): NCT03986580. Level of evidence: 3.
Insulin-and-Glucagon Artificial Pancreas Versus Insulin-Alone Artificial Pancreas: A Short Review

IN BRIEF The advantage of the insulin-and-glucagon artificial pancreas is based on the rapid effect of subcutaneous glucagon delivery in preventing hypoglycemia compared to suspension of insulin delivery. In short-term studies, the dual-hormone artificial pancreas reduced daytime hypoglycemia, especially during exercise, compared to the insulin-alone artificial pancreas, but the insulin-alone system seemed sufficient in eliminating nocturnal hypoglycemia. The comparative benefits of the single- and dual-hormone systems for improving A1C and preventing severe hypoglycemia remain unknown.
Information Bottleneck Method and Deep Learning

For my STATS 385 paper I chose to review Alex Alemi et al.’s recently published (July, 2017) paper “Deep Variational Information Bottleneck” in the context of recent work around the Information Bottleneck Method. The Information Bottleneck (IB) Method is an Information Theory based approach to understanding deep learning that has recently garnered more attention. Alex Alemi et al.’s recent paper has addressed some of the greatest challenges to the IB method, significantly improving the practicality of the theory, but at the same time has failed to adequately set up future experiments. Before diving into the paper I will first summarize the context of the current discourse on the Information Bottleneck Method and its application to deep learning.
Human CAP cells represent a novel source for functional, miRNA-loaded exosome production

Exosomes represent a promising delivery tool for nucleic acid-based pharmaceuticals. They are highly suitable for transporting therapeutic miRNAs to tumor cells, due to their natural membrane components. Further, exosomes are capable of effectively protecting nucleic acids against ribonucleases and enable the delivery of their content through cell membranes. However, no suitable production host for miRNA containing exosomes of non-tumorigenic origin has yet been identified. In this study we engineered an immortalised human amniocyte cell line (CAP® cells), whose exosomes were enriched and characterised. The cell line modifications not only enabled the production of GFP-labelled but also pro-apoptotic miRNA containing exosomes without negative influence on host cell growth. Furthermore, we demonstrated that pro-apoptotic miRNA containing CAP exosomes are taken up by ovarian cancer cells. Strikingly, delivery of functional exosomal miRNA led to downregulation of several reported target genes in the treated tumor cells. In summary, we revealed CAP cells of non-tumorigenic origin as a novel and efficient exosome production host with the potential to produce functional miRNA-loaded exosomes.
Goodput Modelling and Optimisation of Channel Assignment For Planning IEEE 802.11Wireless Backhaul Networks

IEEE 802.11Wireless backhaul networks (WBNs) provide scalable and cost-effective solutions for interconnecting small-cell networks and backbone networks or Internet. With newer and farther reaching applications being developed in IEEE 802.11 WBNs, such as smart grids and intelligent transportation systems, users expect high goodput and better fairness. However, some performance issues in IEEE 802.11 protocols such as border effect, exposed nodes and hidden nodes are exacerbated as network densification occurs, leading to goodput degradation and severe unfairness such as flow starvation (extreme low goodput). These issues may cause an IEEE 802.11 WBN to form a bottleneck and impact the overall network performance. Therefore, in-depth study is required in order to improve the IEEE 802.11 WBN planning to achieve better goodput and fairness. This research aims to improve IEEE 802.11 WBN planning through goodput modelling and optimising channel assignment. A novel simple goodput distribution model is proposed to predict goodput and fairness in IEEE 802.11 WBNs. Simulation results show that the proposed goodput model accurately predicts goodput with consideration of carrier sensing effect and traffic demands. Based on this goodput model, a new interference model is proposed to more realistically reflect both local and global interference in IEEE 802.11 WBNs. With the proposed interference model, two anti-starvation channel assignments have been developed to prevent flow starvation. Simulation validations show that the new anti-starvation channel assignments effectively prevent flow starvation and improve network fairness in IEEE 802.11 WBNs. This research also optimises channel assignment to achieve desired fairness and goodput. A multi-objective optimisation problem is formulated and a new fitness function is designed to evaluate a channel allocation with accurate prediction of goodput and fairness. Utilising the new fitness function, two multi-objective channel assignments have been developed to achieve both fairness and goodput. Compared with existing channel assignments through simulation, the proposed multi-objective channel assignments provide a set of feasible solutions that meet desired fairness and goodput. This research helps network planners or service providers to improve the IEEE 802.11 WBN planning from predicting network performance to optimising goodput and fairness. The proposed goodput model, interference model, and fitness function are also useful for node placement, and optimising routing and scheduling in IEEE 802.11 WBNs.
Molecular Simulation of Liquids and Gels

The combination of long range structural disorder and strong interactions means the liquid phase is not as well understood as the other principle states of matter. The development of liquid state theory has been slow as a consequence [1]. The internal structure of a liquid is random when viewed on a large scale, but also displays ordering on a local scale. In particular the importance of energetically favourable clusters of particles called locally favoured structures (LFS) to local ordering was discussed by Sir Charles Frank in 1952 [2]. I simulate a fluid of Lennard-Jones particles [3] to examine the internal structure near the phase boundary using molecular dynamics [4] A novel method called topological cluster classification [5] is used to identify LFS in the bulk. I disprove a 1952 conjecture by Frank regarding the populations of icosahedral LFS in liquids, but find encouraging signals coupling LFS to the process of crystallization and dynamical arrest. Colloidal dispersions are ensembles of microscopic particles suspended in a solvent which display dynamics with similar phase behaviour to simple atomic and molecular systems. Under certain conditions they form metastable solids such as glasses, gels and crystals. I simulate the formation of colloidal gels in experimental dispersions [6] using a basic model for inter-colloidal interactions [7, 8] and Brownian dynamics [9]. I find the simulation results do not match the gelation witnessed in the experiments and discuss why this discrepancy arises.
Is Access to Care Associated With Stage at Presentation and Survival for Melanoma Patients?

Background Melanoma incidence increases with socioeconomic status but the effect of rurality and access to primary care or dermatology on patient outcomes is unclear. Objectives The objectives of this study were to determine whether access to care, rurality, or socioeconomic status are associated with melanoma stage at presentation and prognosis. Methods Linked administrative databases from Ontario, Canada, were retrospectively analyzed to identify a population-based cohort of patients diagnosed with melanoma between 2004 and 2012. Rurality was assessed using the rural index of Ontario (RIO) score, and the number of visits to dermatology and primary care was used to evaluate access to care. Results We identified 18 776 melanoma patients, of whom 9591 had completed pathological staging. Patients with higher RIO scores, living further from a cancer center or in a rural community, were less likely to see a dermatologist in the year prior to diagnosis (P < .001 for all). Patients seen by a dermatologist within 365 days prior to diagnosis were less likely to present with stage III or IV disease (odds ratio 0.63, P < .001) and had improved overall survival (hazard ratio [HR] for death 0.77, P < .001). There was a nonlinear association between number of family physician visits and melanoma prognosis, with patients who had 3 to 5 visits per year having the best overall survival (HR 0.88, P = .003). Conclusion Our findings strengthen the known association between access to dermatology and melanoma outcomes by linking individual patients’ prediagnosis access to care to pathological stage at diagnosis and overall survival.
A novel strategy to visualize vesicle‐bound kinesins reveals the diversity of kinesin‐mediated transport

In mammals, 15 to 20 kinesins are thought to mediate vesicle transport. Little is known about the identity of vesicles moved by each kinesin or the functional significance of such diversity. To characterize the transport mediated by different kinesins, we developed a novel strategy to visualize vesicle‐bound kinesins in living cells. We applied this method to cultured neurons and systematically determined the localization and transport parameters of vesicles labeled by different members of the Kinesin‐1, ‐2, and ‐3 families. We observed vesicle labeling with nearly all kinesins. Only six kinesins bound vesicles that undergo long‐range transport in neurons. Of these, three had an axonal bias (KIF5B, KIF5C and KIF13B), two were unbiased (KIF1A and KIF1Bβ), and one transported only in dendrites (KIF13A). Overall, the trafficking of vesicle‐bound kinesins to axons or dendrites did not correspond to their motor domain preference, suggesting that on‐vesicle regulation is crucial for kinesin targeting. Surprisingly, several kinesins were associated with populations of somatodendritic vesicles that underwent little long‐range transport. This assay should be broadly applicable for investigating kinesin function in many cell types.
Neuroinflammatory Reactions in the Brain of 1,2-DCE-Intoxicated Mice during Brain Edema

We previously reported that expression of matrix metalloproteinase-9 (MMP-9) mRNA and protein was upregulated during 1,2-dichloroethane (1,2-DCE) induced brain edema in mice. We also found that the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway resulted in MMP-9 overexpression and nuclear factor-κB (NF-κB) activation in mice treated with 1,2-DCE. In this study, we further hypothesized that inflammatory reactions mediated by the p38 MAPK/ NF-κB signaling pathway might be involved in MMP-9 overexpression, blood-brain barrier (BBB) disruption and edema formation in the brain of 1,2-DCE-intoxicated mice. Our results revealed that subacute poisoning by 1,2-DCE upregulates protein levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and p-p65 in mouse brains. Pretreatment with an inhibitor against p38 MAPK attenuates these changes. Moreover, pretreatment with an inhibitor against NF-κB attenuates alterations in brain water content, pathological indications notable in brain edema, as well as mRNA and protein expression on levels of MMP-9, VCAM-1, ICAM-1, iNOS, and IL-1β, tight junction proteins (TJs), GFAP and Iba-1 in the brain of 1,2-DCE-intoxicated mice. Furthermore, pretreatment with an inhibitor against MMP-9 obstructs the decrease of TJs in the brain of 1,2-DCE-intoxicated mice. Lastly, pretreatment with an antagonist against the IL-1β receptor also attenuates changes in protein levels of p-p38 MAPK, p-p65, p-IκB, VCAM -1, ICAM-1, IL-1β, and Iba-1 in the brain of 1,2-DCE-intoxicated-mice. Taken together, findings from the current study indicate that the p38 MAPK/ NF-κB signaling pathway might be involved in the activation of glial cells, and the overproduction of proinflammatory factors, which might induce inflammatory reactions in the brain of 1,2-DCE-intoxicated mice that leads to brain edema.
Efficacy of fasudil for the treatment of aneurysmal subarachnoid hemorrhage

Abstract Background: This study aims to systematically assess the efficacy and safety of fasudil for the treatment of aneurysmal subarachnoid hemorrhage (ASH). Methods: This study will include all of randomized controlled trials on the efficacy and safety of fasudil for the treatment of ASH. Ten electronic databases of PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, Ovid, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched from inception to the May 1, 2019 without language restrictions. We will also search gray literatures to avoid missing any other potential studies. Two authors will independently perform study selection, data extraction and management, and methodologic quality assessment. The primary outcome is limbs function. The secondary outcomes comprise of muscle strength, muscle tone, quality of life, and adverse events. Results: This study will provide a comprehensive literature search on the current evidence of fasudil for the treatment of ASH from primary and secondary outcomes. Conclusion: The results of this study will present evidence to determine whether fasudil is an effective and safety treatment for patients with ASH. Systematic review registration: PROSPERO CRD42019136215.
CRISPR-Cas12a Coupled with Platinum Nano-Reporter for Visual Quantification of SNVs on a Volumetric Bar-Chart Chip.

Methods that can detect and quantify single nucleotide variations (SNVs)/single nucleotide polymorphisms (SNPs) are greatly needed in bioanalysis measuring gene mutations and polymorphisms. Herein, a visual and instrument-free SNV quantification platform is developed. Platinum nanoparticles tethered to magnetic beads by single-stranded DNAs are designed as quantitative readout reporters for CRISPR-Cas12a nucleic acid detection system. The integration of platinum nano-reporter and the CRISPR-Cas system with a volumetric bar chart chip realizes volumetric quantification of nucleic acids. This platform enables quantification of multiple cancer mutations in pure DNA samples and mock cell-free DNA samples in serum, with allelic fractions as low as 0.01%. This platform could have great potential in quantification of SNVs/SNPs as well as other types of nucleic acid targets at the point of care.
Recombinant N-acyl homoserine lactone-Lactonase AiiAQSI-1 Attenuates Aeromonas hydrophila Virulence Factors, Biofilm Formation and Reduces Mortality in Crucian Carp

Quorum quenching (QQ) is a promising alternative infection-control strategy to antibiotics that controls quorum-regulated virulence without killing the pathogens. Aeromonas hydrophila is an opportunistic gram-negative pathogen living in freshwater and marine environments. A. hydrophila possesses an N-acyl homoserine lactone (AHL)-based quorum-sensing (QS) system that regulates virulence, so quorum signal-inactivation (i.e., QQ) may represent a new way to combat A. hydrophila infection. In this study, an AHL lactonase gene, aiiA was cloned from Bacillus sp. strain QSI-1 and expressed in Escherichia coli strain BL21(DE3). The A. hydrophila hexanoyl homoserine lactone (C6-HSL) QS signal molecule was degraded by AiiAQSI-1, which resulted in a decrease of bacterial swimming motility, reduction of extracellular protease and hemolysin virulence factors, and inhibited the biofilm formation of A. hydrophila YJ-1 in a microtiter assay. In cell culture studies, AiiAQSI-1 decreased the ability of A. hydrophila adherence to and internalization by Epithelioma papulosum cyprini (EPC) cells. During in vivo studies, oral administration of AiiAQSI-1 via feed supplementation attenuated A. hydrophila infection in Crucian Carp. Results from this work indicate that feed supplementation with AiiAQSI-1 protein has potential to control A. hydrophila aquaculture disease via QQ.
Self-Repairing Composites for Corrosion Protection: A Review on Recent Strategies and Evaluation Methods

The use of self-healing coatings to protect metal substrates, such as aluminum alloys, stainless steel, carbon steel, and Mg alloys from corrosion is an important aspect for protecting metals and for the economy. During the past decade, extensive transformations on self-healing strategies were introduced in protective coatings, including the use of green components. Scientists used extracts of henna leaves, aloe vera, tobacco, etc. as corrosion inhibitors, and cellulose nanofibers, hallyosite nanotubes, etc. as healing agent containers. This review gives a concise description on the need for self-healing protective coatings for metal parts, the latest extrinsic self-healing strategies, and the techniques used to follow-up the self-healing process to control the corrosion of metal substrates. Common techniques, such as accelerated salt immersion test and electrochemical impedance spectroscopy (EIS), for evaluating the self-healing process in protective coatings are explained. We also show recent advancements procedures, such as scanning vibrating electrode technique (SVET) and scanning electrochemical microscopy (SECM), as successful techniques in evaluating the self-healing process in protective coatings.
The sonic instructor: A music-based biofeedback system for improving weightlifting technique

In this study, we assumed that correct functional movements for weightlifting can be learned with the help of a music-based biofeedback system. We compared musical feedback with verbal feedback from experienced trainers using two independent groups. The focus was on one specific movement called deadlift. Physical parameters under considerations were the spine (i.e. loss of midline stability resulting in flexion) and the forward displacement of the barbell during the repetitions relative to the mid-foot. We recruited 31 recreational weight lifters (21-42 years of age). Results revealed that both feedback types are effective in improving the movements for deadlift. No significant differences were found across the two feedback types, neither in terms of movement, nor in terms of clarity and motivation. The results suggest that the proposed feedback system is a valid tool for technology-aided training and self-training practices.