Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of Mendelian sleep and circadian genetic variants in a population setting

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants of these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. We found no association of any of these variants with extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P=4x10-8; and had a 57-minute earlier midpoint sleep, P=5x10-7). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.
Personal Resilience, Social Support, and Organizational Support Impact Burnout among Nurses During COVID-19

Background: Nurses have been under heavy workloads since the outbreak of COVID-19 and are at a high risk of infection, leading to a high level of psychosocial risk. This can adversely affect nurses both psychologically and physically. Burnout is caused by prolonged stress during work. In the nursing profession, burnout is common, potentially affecting the well-being of nurses and their productivity. The identification of factors that may contribute to maintaining mental health and reducing burnout among frontline nurses during a pandemic is essential. Purpose: The purpose of this study was to explore how personal resilience, social support, and organizational support impact burnout among frontline staff nurses. Methods: This study involved 129 registered nurses from a COVID-19 designated hospital using four standardized scales. Results: The mean age of the respondents was 29.46 years (standard deviation = 4.89). The mean number of years respondents worked in this organization was 5.60 years and the nursing profession was 4.16 years. Most of the respondents were female and held a bachelor's degree in nursing. Multiple regression analysis was performed to predict burnout. Burnout was statistically significantly predicted by the multiple regression model (R2 = .420, F (3, 125) = 10.941, p < . 0001; adjusted R2 = . 406). Personal resilience, social support, and organizational support added statistically significantly to the prediction of burnout (p < .05). Conclusion: Findings from multiple regression analysis showed that nurses with low resilience and those who perceived inadequate social and organizational support had a higher risk of reporting more burnout. As a result of a bivariate analysis, there was no significant correlation between nurse variables and burnout level, except for age, which was negatively correlated with burnout level. Accordingly, young nurses tend to experience burnout, and nurse directors and managers must address this problem.
Timing of Breakthrough Infection Risk After Vaccination Against SARS-CoV-2

Background: Provision of safe and effective vaccines has been a remarkable public health achievement during the SARS-CoV-2 pandemic. The effectiveness and durability of protection of the first two doses of SARS-CoV-2 vaccines is an important area for study, as are questions related to optimal dose combinations and dosing intervals. Methods: We performed a case-cohort study to generate real-world evidence on efficacy of first and second dose of SARS-CoV-2 vaccines, using a population-based case line list and vaccination database for the province of Ontario, Canada between December 2020 and October 2021. Risk of infection after vaccination was evaluated in all laboratory-confirmed vaccinated SARS-CoV-2 cases, and a 2% sample of vaccinated controls, evaluated using survival analytic methods, including construction of Cox proportional hazards models. Vaccination status was treated as a time-varying covariate. Results: First and second doses of SARS-CoV-2 vaccine markedly reduced risk of infection (first dose efficacy 68%, 95% CI 67% to 69%; second dose efficacy 88%, 95% CI 87 to 88%). In multivariable models, extended dosing intervals were associated with lowest risk of breakthrough infection (HR for redosing 0.64 (95% CI 0.61 to 0.67) at 6-8 weeks). Heterologous vaccine schedules that mixed viral vector vaccine first doses with mRNA second doses were significantly more effective than mRNA only vaccines. Risk of infection largely vanished during the time period 4-6 months after the second vaccine dose, but rose markedly thereafter. Interpretation: A case-cohort design provided an efficient means to identify strong protective effects associated with SARS-CoV-2 vaccination, particularly after the second dose of vaccine. However, this effect appeared to wane once more than 6 months had elapsed since vaccination. Heterologous vaccination and extended dosing intervals improved the durability of immune response.
Phylogeography of hepatitis B: The role of Portugal in the early dissemination of HBV worldwide

In Portugal, the genetic diversity, origin of HBV, and the Portuguese role in the dissemination of HBV worldwide were never investigated. In this work, we studied the epidemic history and transmission dynamics of HBV genotypes that are endemic in Portugal. HBV pol gene was sequenced from 130 patients followed in Lisbon. HBV genotype A (HBV/A) was the most prevalent (n=54, 41.5%), followed by D [HBV/D; (n=44, 33.8%)], and E [HBV/E; (n=32, 24.6%)]. Spatio-temporal evolutionary dynamics was reconstructed in BEAST using a Bayesian Markov Chain Monte Carlo method, with a GTR nucleotide substitution model, an uncorrelated lognormal relaxed molecular clock model, a Bayesian skyline plot, and a continuous diffusion model. HBV/D4 was the first subgenotype to be introduced in Portugal around 1857 (HPD 95% 1699-1931) followed by HBV/D3 and A2 a few decades later. HBV/E and HBV/A1 were introduced in Portugal later, almost simultaneously. Our results also indicate a very important role of Portugal in the exportation of HBV/D4 and A2 to Brazil and Cape Verde, respectively, at the beginning of the XX century. This work clarifies the epidemiological history of HBV in Portugal and shows that Portugal had an important role in the global spread of this virus.
Digital Literacy Training in Canada, Part 2: Defining and Measuring Success

This study explores how public libraries and other local community organizations can best deliver and evaluate the digital literacy initiatives they provide to the communities they serve; this article focuses on program evaluation. Interviews with 14 administrators of digital literacy programs revealed that administrators espouse idealistic intentions for digital literacy programs, particularly to give marginalized people increased educational and vocational opportunities. These administrators are also confident in the success of these programs, despite little formal assessment of outcomes for learners. Success is measured by numbers of program participants and anecdotal evidence of positive outcomes for learners, such as increased confidence or an intention to move forward with career goals. This limited approach to measuring the success of digital literacy programs reveals significant opportunity to more fully and systematically evaluate the outcomes of these programs and to assess whether program goals are being met and ongoing investment of resources is merited.
Improving Quality Control Plan of Flexible Printed Circuit

Smart phone market has been growing larger and larger in recent years. This fact makes enormous competitiveness in its supply chain. Therefore, the product quality is the most importance part to improve business competitiveness, especially a flexible printed circuit which is a main assembly component in smart phones. This paper presents the approach to improve the quality control plan of the flexible printed circuit backend process. Failure Mode Effective Analysis (FMEA) was adopted to prioritize the defective and analyze weak points in the original quality control plan. Then, Statistical Process Control (SPC), optimizing inspection method and working procedure of inspection process, were introduced to improve the detection ability of the quality control plan. The results showed that the implementation of the new quality control plan could reduce escaped defective parts and the expense of escaped defect parts significantly.
Aspects of Design and Analysis of Cognitive Radios and Networks

Recent survey campaigns have shown a tremendous under utilization of the bandwidth allocated to various wireless services. Motivated by this and the ever increasing demand for wireless applications, the concept of cognitive radio (CR) systems has rendered hope to end the so called spectrum scarcity. This thesis presents various different facets related to the design and analysis of CR systems in a unified way. We begin the thesis by presenting an information theoretic study of cognitive systems working in the so called low interference regime of the overlay mode. We show that as long as the coverage area of a CR is less than that of a primary user (PU) device, the probability of the cognitive terminal inflicting small interference at the PU is overwhelmingly high. We have also analyzed the effect of a key parameter governing the amount of power allocated to relaying the PU message in the overlay mode of operation in realistic environments by presenting a simple and accurate approximation. Then, we explore the possibilities of statistical modeling of the cumulative interference due to multiple interfering CRs. We show that although it is possible to obtain a closed form expression for such an interference due a single CR, the problem is particularly difficult when it comes to the total CR interference in lognormally faded environments. In particular, we have demonstrated that fitting a two or three parameter lognormal is not a feasible option for all scenarios. We also explore the second-order characteristics of the cumulative interference by evaluating its level crossing rate (LCR) and average exceedance duration (AED) in Rayleigh and Rician channel conditions. We show that the LCRs in both these cases can be evaluated by modeling the interference process with gamma and noncentral χ processes, respectively. By exploiting radio environment map (REM) information,
Seed-competent tau monomer initiates pathology in PS19 tauopathy mice

Tau aggregation into ordered assemblies causes myriad neurodegenerative tauopathies. We previously reported that tau monomer exists in either inert (Mi) or seed-competent (Ms) conformational ensembles, and that Ms encodes strains, which are biologically active, self-propagating assemblies. We have previously isolated Ms from tauopathy brains, but it is unknown if disease begins with Ms formation followed by fibril assembly, or if Ms derives from fibrils and is an epiphenomenon. Consequently, we studied a tauopathy mouse model (PS19) that expresses full-length human (1N4R) tau containing a disease-associated mutation (P301S). Using tau repeat domain biosensor cells, we detected insoluble tau seeding activity at 2 months. We found insoluble tau protein assemblies by immunoblot at 3 months. We next immunopurified monomer from mice aged 1-6 weeks using size exclusion chromatography. We detected soluble seeding activity at 4 weeks, before insoluble material or larger assemblies, with assemblies ranging from n=1-3 tau units. By 5 and 6 weeks, large soluble assemblies had formed. This indicated the first detectable pathological forms of tau were Ms. We next tested for post-translational modifications of tau monomer from 1-6 weeks. We detected no phosphorylation unique to Ms in PS19 or Alzheimer’s disease brain. We conclude that tauopathy begins with formation of Ms monomer, whose activity is phosphorylation-independent. Ms self-assembles to form oligomers before it forms insoluble fibrils. The conversion of tau monomer from Mi to Ms thus constitutes the first detectable step in the initiation of tauopathy in this mouse model, with obvious implications for origins of disease in humans.
Phosphoantigens are Molecular Glues that Promote Butyrophilin 3A1/2A1 Association Leading to Vγ9Vδ2 T Cell Activation

Tumor cells and pathogen-infected cells are presented to human γδ T cells based on “inside-out” signaling in which metabolites called phosphoantigens (pAgs) inside target cells are recognized by the intracellular domain of a butyrophilin protein (BTN3A1), leading to an extracellular conformational change. Here, we report that pAgs function as molecular “glues” that initiate a heteromeric association between the intracellular domains of BTN3A1 and the structurally similar BTN2A1. Working with both exogenous and endogenous pAgs, we used x-ray crystallography, mutational studies, cellular assays, synthetic probe as well as molecular dynamics investigations to determine how pAgs glue intracellular BTN3A1 and BTN2A1 together for the “inside-out” signaling that triggers γδ T cell activation. This γδ T cell-specific mode of antigen sensing creates opportunities for the development of alternative immunotherapies against cancer and infectious diseases that do not involve αβ T cells. One Sentence Summary The responses of gamma-delta T cells to cancer cells or pathogens are initiated via the intracellular association of heteromeric butyrophilins that are glued together by isoprenoid metabolites.
Wetland loss in the Ñeembucú Wetlands Complex, Paraguay, using remote sensing

South American wetlands are of global importance, yet limited delineation and monitoring restricts informed decision-making around the drivers of wetland loss. A growing human population and increasing demand for agricultural products has driven wetland loss and degradation in the Neotropics. Understanding of wetland dynamics and land use change can be gained through wetland monitoring. The Ñeembucú Wetlands Complex is the largest wetland in Paraguay, lying within the Paraguay-Paraná-La Plata River system. This study aims to use remotely sensed data to map land cover between 2006 and 2021, quantify wetland change over the 15-year study period and thus identify land cover types vulnerable to change in the Ñeembucú Wetlands Complex. Forest, dryland vegetation, vegetated wetland and open water were identified using Random Forest supervised classifications trained on visual inspection data and field data. Annual change of −0.34, 4.95, −1.65, 0.40 was observed for forest, dryland, vegetated wetland and open water, respectively. Wetland and forest conversion is attributed to agricultural and urban expansion. With ongoing pressures on wetlands, monitoring will be a key tool for addressing change and advising decision-making around development and conservation of valuable ecosystem goods and services in the Ñeembucú Wetlands Complex.
Revealing genomic changes responsible for cannabinoid receptor loss in parrots: mechanism and functional effects

In vertebrates, an ancient duplication in the genes for cannabinoid receptors (CNRs) allowed the evolution of specialised endocannabinoid receptors expressed in the brain (CNR1) and the periphery (CNR2). While dominantly conserved throughout vertebrate phylogeny, our comparative genomic analysis suggests that certain taxa may have lost either the CNR1 regulator of neural processes or, more frequently, the CNR2 involved in immune regulation. Focussing on conspicuous CNR2 pseudogenization in parrots (Psittaciformes), a diversified crown lineage of cognitively-advanced birds, we highlight possible functional effects of such a loss. Parrots appear to have lost the CNR2 gene at at least two separate occasions due to chromosomal rearrangement. Using gene expression data from the brain and periphery of birds with experimentally-induced sterile inflammation, we compare CNR and inflammatory marker (interleukin 1 beta, IL1B) expression patterns in CNR2-deficient parrots (represented by the budgerigar, Melopsittacus undulatus and five other parrot species) with CNR2-intact passerines (represented by the zebra finch, Taeniopygia guttata). Though no significant changes in CNR expression were observed in either parrots or passerines during inflammation of the brain or periphery, we detected a significant up-regulation of IL1B expression in the brain after stimulation with lipopolysaccharide (LPS) only in parrots. As our analysis failed to show evidence for selection on altered CNR1 functionality in parrots, compared to other birds, CNR1 is unlikely to be involved in compensation for CNR2 loss in modulation of the neuroimmune interaction. Thus, our results provide evidence for the functional importance of CNR2 pseudogenization for regulation of neuroinflammation.
Abnormal metabolic brain network in behavioral variant of frontotemporal dementia

The increasing number of patients with neurodegenerative dementia is a major public health issue. While clinical features of neurodegenerative disorders causing dementia are overlapping, accurate diagnosis is a prerequisite for an effective drug development. Besides the need for a better biomarker of Alzheimer’s disease (AD), development of non‐AD biomarkers is necessary. Behavioral variant of frontotemporal dementia (bvFTD) is the second most common neurodegenerative dementia in patients younger than 65 years. The aim of our study was to identify and validate bvFTD specific metabolic brain pattern using voxel‐based spatial covariance analysis according to the scaled subprofile model (SSM/PCA) on a new cohort of European patients and to study its biologic significance.
New concepts for normally-off power Gallium Nitride (GaN) High Electron Mobility Transistor (HEMT)

AlGaN/GaN HEMTs are very promising candidates for high frequency applications with high power and low noise. While switching applications strongly demand normally-off operation, conventional HEMTs attain a channel populated with electrons at zero gate voltage making them normally-on. For the sake of achieving normally-off HEMTs, several structures have been proposed such as recessed gate structures, fluorine ion treatment, pn junction gate structures, thin AlGaN barrier and Gate Injection transistor. The effectiveness of the agent used to obtain normally-off, whether it is recessing the gate, introducing a cap layer or implanting fluorine, increases as the agent comes closer to the AlGaN/GaN interface. Unfortunately, when introducing a cap layer or recessing the gate, coming closer to the interface means decreasing the barrier thickness, which strongly affects the density of the 2DEG. In the case of fluorine implantation, getting closer will increase the probability of fluorine ions getting into the channel and hence degrade the mobility of the 2DEG. In this work we propose two new concepts to achieve normally-off operation. We suggest the introduction of negative fluorine ions on one hand or a p-GaN region on the other hand, below the channel, under the AlGaN/GaN interface and away from high current density regions. After calibrating the simulator using experimental results from a normally-on HEMT device, we have shown that our proposed structures are more effective: the concentration required to achieve normally-off operation is lower than in the other existing solutions and the confinement of the two dimensional electron gas below the gate is better. The proposed ideas were also applied to Metal Insulator Semiconductor HEMT (MIS-HEMT) and Gate Injection Transistor (GIT), giving rise to a normally-off HEMT with high controllable threshold voltage.
MECHANICS ANALYSIS OF ROTARY DRILLING RIG UNDER DRILLING-BUCKET-LIFTING CONDITIONS

Based on the detailed mechanics analysis of a rotary drilling rig under drilling-bucket-lifting conditions, a mathematics model was established. The factors influencing the loads of the mast hydraulic cylinder and the lift arm hydraulic cylinder were analyzed respectively. A simulation model based on MATLAB was built up and was simulated in Simulink. The results indicate that, under drilling-bucket-lifting conditions, the load of the lift arm hydraulic cylinder has nothing to do with the acting line of all other external loads except the weights of the connecting rod and the lift arm; the change of lift arm angle has the most impact on both of the loads of lift arm hydraulic cylinder and the support reaction force of the hinge connecting lift arm and swing platform. The simulation data are basically consistent with the experimental ones, which show that the mathematics and simulation model can well describe the mechanics behaviors of the rotary drilling rig.
Automated design of bandpass filters based on open complementary split ring resonators (OCSRRs) using aggressive space mapping (ASM) optimization

This paper is focused on the design of bandpass filters based on open complementary split ring resonators (OCSRRs) in microstrip technology. The filters are obtained by coupling the corresponding shunt resonators (OCSRRs) through admittance inverters (quarter wavelength transmission line sections). Different undesirable effects derived from the chosen topology are taken into account and are compensated at the design level. These effects include the reduction in bandwidth (caused by the narrowband functionality of the line sections acting as admittance inverters), and the presence of a spurious band above the filter passband. The proposed technique is based on the well‐known aggressive space mapping algorithm, which is a powerful tool for the synthesis and design of microwave components. The design of the OCSRR‐based filter is provided in a fully automated way as the main result of this paper. Copyright © 2015 John Wiley & Sons, Ltd.
Applying an Improved DBSCAN Clustering Algorithm to Network Intrusion Detection

Density-Based Spatial Clustering of Application with Noise (DBSCAN) is a typical density clustering algorithm, which defines a cluster as the maximum set of densities connected points. It can divide regions with sufficient density of clusters, and can find clusters of any shape of the spatial database with noise. However, the data types it can deal with are limited, and the clustering quality is poor when the density of the sample set is not uniform and the clustering distance difference is large. To solve these problems, an improved DBSCAN algorithm based on K-prototypes and dissimilarity matrix is proposed to improve the quality of clustering and applied to network intrusion detection. The experimental results show that, the proposed algorithm improves the clustering quality of the KDD Cup 99 dataset for network intrusion detection.