Miracle-dz/UniFAR-FTUs huggingface dataset:
Munc13-1 MUN domain and Munc18-1 cooperatively chaperone SNARE assembly through a tetrameric complex

Significance Neurons in the brain communicate with each other by release of neurotransmitters. Neurotransmitter release is mediated by 3 membrane-anchored SNARE proteins and various regulatory proteins, including Munc13-1 and Munc18-1. SNAREs couple their folding and assembly to membrane fusion in a regulatory protein-dependent manner. The physiological pathway of the regulated SNARE assembly, however, is unclear. We found that the MUN domain of Munc13-1, Munc18-1, and 2 SNAREs—syntaxin 1 and VAMP2—associate into a weak tetrameric complex. The third SNARE protein, SNAP-25B, rapidly binds the 2 SNAREs in the complex to form a ternary SNARE complex likely with a displacement of the regulatory proteins. Therefore, Munc13-1 and Munc18-1 cooperatively chaperone SNARE assembly, a process required for neurotransmitter release. Munc13-1 is a large multifunctional protein essential for synaptic vesicle fusion and neurotransmitter release. Its dysfunction has been linked to many neurological disorders. Evidence suggests that the MUN domain of Munc13-1 collaborates with Munc18-1 to initiate SNARE assembly, thereby priming vesicles for fast calcium-triggered vesicle fusion. The underlying molecular mechanism, however, is poorly understood. Recently, it was found that Munc18-1 catalyzes neuronal SNARE assembly through an obligate template complex intermediate containing Munc18-1 and 2 SNARE proteins—syntaxin 1 and VAMP2. Here, using single-molecule force spectroscopy, we discovered that the MUN domain of Munc13-1 stabilizes the template complex by ∼2.1 kBT. The MUN-bound template complex enhances SNAP-25 binding to the templated SNAREs and subsequent full SNARE assembly. Mutational studies suggest that the MUN-bound template complex is functionally important for SNARE assembly and neurotransmitter release. Taken together, our observations provide a potential molecular mechanism by which Munc13-1 and Munc18-1 cooperatively chaperone SNARE folding and assembly, thereby regulating synaptic vesicle fusion.
Typical and Aberrant Functional Brain Flexibility: Lifespan Development and Aberrant Organization in Traumatic Brain Injury and Dyslexia

Intrinsic functional connectivity networks derived from different neuroimaging methods and connectivity estimators have revealed robust developmental trends linked to behavioural and cognitive maturation. The present study employed a dynamic functional connectivity approach to determine dominant intrinsic coupling modes in resting-state neuromagnetic data from 178 healthy participants aged 8–60 years. Results revealed significant developmental trends in three types of dominant intra- and inter-hemispheric neuronal population interactions (amplitude envelope, phase coupling, and phase-amplitude synchronization) involving frontal, temporal, and parieto-occipital regions. Multi-class support vector machines achieved 89% correct classification of participants according to their chronological age using dynamic functional connectivity indices. Moreover, systematic temporal variability in functional connectivity profiles, which was used to empirically derive a composite flexibility index, displayed an inverse U-shaped curve among healthy participants. Lower flexibility values were found among age-matched children with reading disability and adults who had suffered mild traumatic brain injury. The importance of these results for normal and abnormal brain development are discussed in light of the recently proposed role of cross-frequency interactions in the fine-grained coordination of neuronal population activity.
Expression profile of HLA‐B*38:55Q allele

The identification of null or questionably expressed HLA allelic variants is a major issue in HLA diagnostics, because the mistyping of the aberrant expression of such alleles can have a major impact on the outcome of both hematopoietic stem cell transplantation (HSCT) and solid organ transplants. It is debated how questionable (Q) alleles, because of their unknown expression profile, should be considered in an allogenic HSCT setting. The HLA‐B*38:55Q allele was detected as an HLA‐B blank specificity; DNA sequencing identified a single polymorphism at position 373 in exon 3 (TGC > CGC), which results in the replacement of cysteine 101 with an arginine in the HLA‐B heavy chain, thus, impairing disulfide bridge formation in the alpha‐2 domain, essential for the normal expression of the HLA molecules. In order to determine the RNA and protein expression profile of this allelic variant, we analyzed antigenic expression at different levels, transcriptional and transductional, using a combination of cellular methods, such as serological testing and flow cytometric analysis, polymerase chain reaction (PCR) sequence‐specific primer (SSP) cDNA group‐specific amplification and immunocytochemical assay, demonstrating the prevalent cytoplasmatic distribution of the HLA‐B*38:55Q protein. Our findings suggest that in matching process the HLA‐B*38:55Q allele needs to be considered as a low expressed allele, able to elicit an allogenic T‐cell response in vivo and impair the transplant outcome.
Aspiration thrombectomy for the management of acute deep venous thrombosis in the setting of venous thoracic outlet syndrome

Objectives Venous thoracic outlet syndrome, known by the eponym Paget–Schroetter syndrome, is seen in healthy, young individuals with “effort-induced thrombosis. ” Endovascular therapies, including catheter-directed thrombolysis, have been described in the acute management of the upper extremity deep venous thrombosis; however, we assessed the technical success of treating this entity using a mechanical aspiration thrombectomy system. Methods This was a multi-center retrospective review of patients with venous thoracic outlet syndrome with acute thrombosis treated with the Indigo continuous aspiration mechanical thrombectomy system. Charts from patients with venous thoracic outlet syndrome and acute deep venous thrombosis treated with this system at our institution along with three data sharing locations were reviewed for demographics, deep venous thrombosis risk factors, imaging modalities used for diagnosis, extent of axillosubclavian deep venous thrombosis, treatment details, adjunctive therapies, and complications. The primary outcome was technical success (resolution of >70% of thrombus). Results There were 16 patients (50% male) with a mean age of 33 years (range 17–69 years). Six patients had underlying venous thromboembolism risk factors including use of contraceptives (n = 2), prior deep venous thrombosis (n = 3), and known thrombophilia (n = 1). Fifteen patients had complete venous occlusion, and the extent of venous involvement included subclavian (n = 14), axillary (n = 16), and brachial (n = 7). The majority (81.25%) of patients were treated in a single setting, and technical success was achieved in all cases with the use of adjunctive therapies. Only three patients required additional overnight thrombolytic therapy. Conclusions The Penumbra Indigo system, often in combination with adjunctive catheter-directed thrombolysis and venoplasty, is a safe and effective device for the treatment of acute upper extremity deep venous thrombosis in the setting of Paget–Schroetter syndrome. No patients experienced central embolization or post-operative renal insufficiency. One-third of patients avoided any additional catheter-directed thrombolysis exposure, and technical success was achieved in all cases. A single bleeding complication was observed in a patient undergoing overnight adjunctive catheter-directed thrombolysis. All patients maintained patency until time of first rib resection.
Complement and Complement Targeting Therapies in Glomerular Diseases

The complement cascade is part of the innate immune system whose actions protect hosts from pathogens. Recent research shows complement involvement in a wide spectrum of renal disease pathogenesis including antibody-related glomerulopathies and non-antibody-mediated kidney diseases, such as C3 glomerular disease, atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. A pivotal role in renal pathogenesis makes targeting complement activation an attractive therapeutic strategy. Over the last decade, a growing number of anti-complement agents have been developed; some are approved for clinical use and many others are in the pipeline. Herein, we review the pathways of complement activation and regulation, illustrate its role instigating or amplifying glomerular injury, and discuss the most promising novel complement-targeting therapies.
Radiofrequency ablation of primary and metastatic liver tumors. Where are we and where we are going

Artigo recebido em 02/12/2009 Aprovado em 18/12/2009 1. Professor Titular da Disciplina de Cirurgia Geral, Chefe do Núcleo de Clínica Cirúrgica e Coordenador do Curso de Medicina da Universidade de Santo Amaro UNISA. Professor de Habilidades Cirúrgicas da Universidade Cidade de São Paulo – UNICID. 2. Acadêmica do 6o ano do Curso de Medicina da Universidade Cidade de São Paulo – UNICID. 3. Residente do Programa de Cirurgia Geral da Universidade de Santo Amaro UNISA. 4. Professor Assistente da Disciplina de Cirurgia Geral da Universidade de Santo Amaro UNISA. 5. Livre Docente e Diretor do Laboratório de Investigação Médica da Disciplina de Transplante e Cirurgia do Fígado do Departamento de Gastroenterologia da Faculdade de Medicina da Universidade de São Paulo. Former Honorary Registrar Department of Surgery, Addenbrookes Hospital, University of Cambridge, England , UK. PONTO DE VISTA
Toxic Comment Detection and Classification

This project aims to build models that detect and classify comments as toxic. In this project, I made use of various models on the data such as Logistic Regression, XGBboost, SVM and a bidirectional LSTM(Long Short Term Memory). The SVM, XGBboost and Logistic regression implementations achieved very similar levels of accuracy whereas the LSTM implementation achieved the best accuracy out of all of the models.
Receptor Tyrosine Kinases in Development: Insights from Drosophila

Cell-to-cell communication mediates a plethora of cellular decisions and behaviors that are crucial for the correct and robust development of multicellular organisms. Many of these signals are encoded in secreted hormones or growth factors that bind to and activate cell surface receptors, to transmit the cue intracellularly. One of the major superfamilies of cell surface receptors are the receptor tyrosine kinases (RTKs). For nearly half a century RTKs have been the focus of intensive study due to their ability to alter fundamental aspects of cell biology, such as cell proliferation, growth, and shape, and because of their central importance in diseases such as cancer. Studies in model organisms such a Drosophila melanogaster have proved invaluable for identifying new conserved RTK pathway components, delineating their contributions, and for the discovery of conserved mechanisms that control RTK-signaling events. Here we provide a brief overview of the RTK superfamily and the general mechanisms used in their regulation. We further highlight the functions of several RTKs that govern distinct cell-fate decisions in Drosophila and explore how their activities are developmentally controlled.
Insights into fungal diversity of a shallow-water hydrothermal vent field at Kueishan Island, Taiwan by culture-based and metabarcoding analyses

This paper reports the diversity of fungi associated with substrates collected at a shallow hydrothermal vent field at Kueishan Island, Taiwan, using both culture-based and metabarcoding methods. Culture of fungi from yellow sediment (with visible sulfur granules), black sediment (no visible sulfur granules), the vent crab Xenograpsus testudinatus, seawater and, animal egg samples resulted in a total of 94 isolates. Species identification based on the internal transcribed spacer regions of the rDNA revealed that the yellow sediment samples had the highest species richness with 25 species, followed by the black sediment (23) and the crab (13). The Ascomycota was dominant over the Basidiomycota; the dominant orders were Agaricales, Capnodiales, Eurotiales, Hypocreales, Pleosporales, Polyporales and Xylariales. Hortaea werneckii was the only common fungus isolated from the crab, seawater, yellow and black sediment samples. The metabarcoding analysis amplifying a small fragment of the rDNA (from 18S to 5.8S) recovered 7–27 species from the black sediment and 12–27 species from the yellow sediment samples and all species belonged to the Ascomycota and the Basidiomycota. In the yellow sediments, the dominant order was Pleosporales and this order was also dominant in the black sediment together with Sporidiobolales. Based on the results from both methods, 54 and 49 species were found in the black and yellow sediments, respectively. Overall, a higher proportion of Ascomycota (~70%) over Basidiomycota was recovered in the yellow sediment and the two phyla were equally abundant in the black sediment. The top five dominant fungal orders in descending order based on species richness were Pleosporales>Eurotiales>Polyporales>Hypocreales>Capnodiales in the black sediment samples, and Polyporales>Pleosporales>Eurotiales>Capnodiales>Hypocreales in the yellow sediment samples. This study is the first to observe a high diversity of fungi associated with various substrates at a marine shallow water hydrothermal vent ecosystem. While some fungi found in this study were terrestrial species and their airborne spores might have been deposited into the marine sediment, several pathogenic fungi of animals, including Acremonium spp. , Aspergillus spp. , Fusarium spp. , Malassezia spp. , Hortaea werneckii, Parengyodontium album, and Westerdykella dispersa, were recovered suggesting that these fungi may be able to cause diseases of marine animals.
Diet and feeding strategy of Northeast Atlantic mackerel (Scombrus scomber) in Icelandic waters

Predator-prey relations, as well as the trophic ecology of highly migratory marine species, is important to understand their impact on the ecosystem. Conventional methods were used to study the diet composition and feeding strategy of the Northeast Atlantic mackerel (Scombrus scomber), during their summer feeding migration to Icelandic waters in 2009–2014. In addition, generalised additive modelling (GAM) was used to determine which biological and environmental factors contribute to the variation of their stomach weight in the years 2011–2014. From the dietary analysis, we found that calanoid copepods (especially Calanus finmarchicus) were the most important contributor to the overall diet of mackerel in the years studied. Although in some years and areas, they also preyed heavily on larger prey items such as euphausiids, amphipods and megalopa larvae of crab and shrimp. The GAM showed that temperature and the time the day of sampling were significant explanatory variables for the stomach weight, while zooplankton biomass did not seem to have much influence. The Northeast Atlantic mackerel are ferocious feeders upon copepods, as well as exhibiting an overall opportunistic feeding strategy. During their feeding migration in Icelandic waters, they were found to feed on the most dominant species available to them.
Immune Parameters for Diagnosis and Treatment Monitoring in Invasive Mold Infection

Infections caused by invasive molds, including Aspergillus spp. , can be difficult to diagnose and remain associated with high morbidity and mortality. Thus, early diagnosis and targeted systemic antifungal treatment remains the most important predictive factor for a successful outcome in immunocompromised individuals with invasive mold infections. Diagnosis remains difficult due to low sensitivities of diagnostic tests including culture and other mycological tests for mold pathogens, particularly in patients on mold-active antifungal prophylaxis. As a result, antifungal treatment is rarely targeted and reliable markers for treatment monitoring and outcome prediction are missing. Thus, there is a need for improved markers to diagnose invasive mold infections, monitor response to treatment, and assist in determining when antifungal therapy should be escalated, switched, or can be stopped. This review focuses on the role of immunologic markers and specifically cytokines in diagnosis and treatment monitoring of invasive mold infections.
A Review of Orbital Involvementin Patients with Primary ParanasalSinus Space Occupying Lesions ina South-East Asian Tertiary Centre

A Review of Orbital Involvement in Patients with Primary Paranasal Sinus Space Occupying Lesions in a South-East Asian Tertiary Centre Objective: To study the ophthalmic symptoms, signs and the outcomes after therapeutic intervention in patients with various space occupying lesions (SOL) of paranasal sinuses (PNS) in a tertiary referral centre in South-East Asia. Patients and Methods: Retrospective review of all the cases with primary sinus SOL presenting with orbital involvement seen at the ophthalmic plastic service between January 1, 2000 and December 31, 2011. Results: There were a total of 22 cases. Mean age was 51.5 years and male to female ratio was 2:1. Presenting ophthalmic signs were proptosis (77.3%), palpable mass (63.6%), ophthalmoplegia (54.6%), pain (36.4%) and poor vision (13.6%). All cases were co-managed by Eye and ENT surgeons, with 15 cases first detected by ophthalmologists and 7cases by otolaryngologists. Of the 22 cases, 10 (45.5%) cases were neoplasms, 9 (40.9%) were paranasal sinus mucoceles and 3 cases were dysplastic lesions. Mean follow up period was 23 months (3 months to 69 months). Conclusion: PNS SOL cases can present with ophthalmic signs and symptoms to the ophthalmologists and often may be the first presentation. Diplopia and ophthalmoplegia are the most common ophthalmic disorders signifying orbital involvement by a PNS SOL. The outcome largely depends upon the primary etiology of the sinus lesion and efficacy of the multi-disciplinary approach.
ENTREPRENEURSHIP AND POSTMATERIALISTIC VALUES. An individual-based analysis

Research theme and hypothesis. From Schumpeter right up to today research on entrepreneurship has mainly demonstrated that entrepreneurs constitute a key factor in a country's economic development, in creating employment and in innovation. However, there is still no definitive answer to the question: What makes a person an entrepreneur? The hypothesis of this study is based on the tenet that materialistic people seek material security and that postmaterialistic people seek to satisfy needs such as independence and fulfilling personal objectives in life and that for this reason the latter tend to set up less companies than the materialists. Hypothesis: People who are more postmaterialistic tend to start up less companies than people who are more materialistic. Data. A model was drawn up to explore the predictive capacity of postmaterialism in entrepreneurship at the individual level. The measure of postmaterialism was taken from Inglehart's 4-item postmaterialism index. The model uses the socio demographic variables of age, gender, education and income level as control variables. Data from about twenty thousand subjects from 25 OECD countries is used in the 1999-2004 database of the World Value Survey to measure all these variables. Results. Results were obtained using logistic regression. There is significant statistical evidence that postmaterialism decreases a person ́s likelihood of becoming an entrepreneur, although its impact varies depending on the country and on the variables incorporated into the models.
Indigenous Knowledge and Farmer Perceptions of Climate and Ecological Changes in the Bamenda Highlands of Cameroon: Insights from the Bui Plateau

Anticipating seasonal and shorter time scale dynamics to farming practices is primordial for indigenous farmers’ resilience under extreme environmental conditions, where climate change is a menace to agro-hydro-ecological systems. This paper assesses the effectiveness of indigenous farmers’ knowledge and aptitude to read weather signs for informed decisions on their daily and seasonal activities. Such climate-proof development is anchored on indigenous people’s knowledge and perceptions in circumstances where the dearth of scientific evidence or information exists as in Cameroon. The study is based on eight focus group discussions and a survey of 597 farming households in seven agro-ecological basins on the Bui Plateau of the Bamenda Highlands. The results indicate that indigenous smallholder farmers value their ability to accurately observe and anticipate local conditions in various ways to serve their local realities more aptly than outside forecasts. Such local knowledge should thus exercise a complementary role weave in a local climate information understanding system that replicates ecological variability.
SELF-GOVERNMENT FOR ABORIGINAL PEOPLE IN URBAN AREAS: A LITERATURE REVIEW AND SUGGESTIONS FOR RESEARCH

Resume The author reviews much of the literature on Aboriginal people in terms of self-government and suggests avenues of further research. The paper considers both self-government arrangements and the demographic structure of the urban Aboriginal population. L'auteur étudie nombre d'écrits sur les Autochtones sur le plan de l'autonomie et suggère des possibilités d'autres recherches. L'article examine les règlements pour l'autonomie et la structure démographique de la population urbaine autochtone.
USING MODIFIED INDUSTRIAL ROBOTS TO EMULATE THE CONTACT DYNAMICS BEHAVIOR OF A SPACE MANIPULATOR

The most challenging and risky operations for a space manipulator are those involving physical contact. To ensure safe and reliable contact operations, each such robotic task must be carefully designed and verified before it is performed in space. This paper provides an overview of a hardware-in-the-loop (HIL) simulation system which is designed for verification of general contact tasks of a space manipulator. The system uses two industrial robots to emulate the dynamic behavior of the space manipulator and a payload handled by the space manipulator. Due to special requirements for HIL simulation, industrial robots cannot be used as is. The paper focuses on the discussion regarding how to modify the industrial robots to meet the basic requirements of HIL simulation. The proposed modifications are being implemented right now. The test work completed so far indicates that the alternated robots will meet the proposed requirements for HIL simulation.
Exploring feature visualization: how optimized images range across networks and approaches

In the last year or so, a flurry of papers have come out which probe the nature of neural computations in visual cortex by using convolutional neural networks to optimize images for neurons in macaque [1] [2] or mouse visual cortex [3]. An especially exciting example of this line of research found a linear mapping from CNN features to neurons in macaque visual area V4 and then used gradient ascent to synthesize images which optimally drive neuronal responses, achieving remarkable specificity and control of the neuronal sub-populations within this cortical area [1]. Of particular interest is whether such an approach would be feasible for human fMRI to characterize ventral temporal cortex (VTC) which is responsible for highlevel visual categorization in humans. For example, to what extent would the images optimized for VTC reveal a modularity, with images of buildings optimized for known place-selective regions or images of body parts optimized for limb-selective regions? Or how might the ideal stimuli differ for the different face-selective areas in VTC? We know from previous research that there are different face-selective areas in ventral cortex that appear to be specialized for different tasks but fully characterizing these differences and their purpose has proved elusive. However, before instantiating this approach for human fMRI can even be attempted, we need to explore the space of potential visualizations, namely: