Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Wide Surveillance of Genital Herpes Simplex Virus Type 1 From Multiple Anatomic Sites Over Time

Abstract Here we present genomic and in vitro analyses of temporally separated episodes of herpes simplex virus type 1 (HSV-1) shedding by an HSV-1–seropositive and human immunodeficiency virus (HIV)/HSV-2–seronegative individual who has frequent recurrences of genital HSV-1. Using oligonucleotide enrichment, we compared viral genomes from uncultured swab specimens collected on different days and from distinct genital sites. We found that viral genomes from 7 swab specimens and 3 cultured specimens collected over a 4-month period from the same individual were 98.5% identical. We observed a >2-fold difference in the number of minority variants between swab specimens from lesions, swab specimens from nonlesion sites, and cultured specimens. This virus appeared distinct in its phylogenetic relationship to other strains, and it contained novel coding variations in 21 viral proteins. This included a truncation in the UL11 tegument protein, which is involved in viral egress and spread. Normal immune responses were identified, suggesting that unique viral genomic features may contribute to the recurrent genital infection that this participant experiences.
PARP12 suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins

Interferon stimulates the ADP-ribosylation–dependent degradation of nonstructural Zika virus proteins necessary for viral replication. Ribosylation restricts infection Type I interferon signaling drives the expression of hundreds of interferon-stimulated genes (ISGs) that are critical for host and cellular defense against viral infection. To identify ISGs that limit Zika virus infection, Li et al. screened CRISPR knockout cell lines and found that loss of PARP12 increased viral replication. Truncation and pharmacological inhibition of PARP12 indicated that antiviral activity required the PARP domain–dependent ADP-ribosylation of required viral proteins, which led to their ubiquitylation and degradation. This work identifies a distinct antiviral mechanism and suggests that PARP agonists may have clinical utility if repurposed as treatments for Zika virus. Zika virus infection stimulates a type I interferon (IFN) response in host cells, which suppresses viral replication. Type I IFNs exert antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). To screen for antiviral ISGs that restricted Zika virus replication, we individually knocked out 21 ISGs in A549 lung cancer cells and identified PARP12 as a strong inhibitor of Zika virus replication. Our findings suggest that PARP12 mediated the ADP-ribosylation of NS1 and NS3, nonstructural viral proteins that are involved in viral replication and modulating host defense responses. This modification of NS1 and NS3 triggered their proteasome-mediated degradation. These data increase our understanding of the antiviral activity of PARP12 and suggest a molecular basis for the potential development of therapeutics against Zika virus.
G2D: from GTA to Data

This document describes G2D, a software that enables capturing videos from Grand Theft Auto V (GTA V), a popular role playing game set in an expansive virtual city. The target users of our software are computer vision researchers who wish to collect hyper-realistic computer-generated imagery of a city from the street level, under controlled 6DOF camera poses and varying environmental conditions (weather, season, time of day, traffic density, etc.). G2D accesses/calls the native functions of the game; hence users can directly interact with G2D while playing the game. Specifically, G2D enables users to manipulate conditions of the virtual environment on the fly, while the gameplay camera is set to automatically retrace a predetermined 6DOF camera pose trajectory within the game coordinate system. Concurrently, automatic screen capture is executed while the virtual environment is being explored. G2D and its source code are publicly available at this https URL In addition, we demonstrate an application of G2D to generate a large-scale dataset with groundtruth camera poses for testing structure-from-motion (SfM) algorithms. The dataset and generated 3D point clouds are also made available at this https URL
Using J-K-fold Cross Validation To Reduce Variance When Tuning NLP Models

K-fold cross validation (CV) is a popular method for estimating the true performance of machine learning models, allowing model selection and parameter tuning. However, the very process of CV requires random partitioning of the data and so our performance estimates are in fact stochastic, with variability that can be substantial for natural language processing tasks. We demonstrate that these unstable estimates cannot be relied upon for effective parameter tuning. The resulting tuned parameters are highly sensitive to how our data is partitioned, meaning that we often select sub-optimal parameter choices and have serious reproducibility issues. Instead, we propose to use the less variable J-K-fold CV, in which J independent K-fold cross validations are used to assess performance. Our main contributions are extending J-K-fold CV from performance estimation to parameter tuning and investigating how to choose J and K. We argue that variability is more important than bias for effective tuning and so advocate lower choices of K than are typically seen in the NLP literature and instead use the saved computation to increase J. To demonstrate the generality of our recommendations we investigate a wide range of case-studies: sentiment classification (both general and target-specific), part-of-speech tagging and document classification.
Pre-α-pro-GDNF and Pre-β-pro-GDNF Isoforms Are Neuroprotective in the 6-hydroxydopamine Rat Model of Parkinson's Disease

Glial cell line-derived neurotrophic factor (GDNF) is one of the most studied neurotrophic factors. GDNF has two splice isoforms, full-length pre-α-pro-GDNF (α-GDNF) and pre-β-pro-GDNF (β-GDNF), which has a 26 amino acid deletion in the pro-region. Thus far, studies have focused solely on the α-GDNF isoform, and nothing is known about the in vivo effects of the shorter β-GDNF variant. Here we compare for the first time the effects of overexpressed α-GDNF and β-GDNF in non-lesioned rat striatum and the partial 6-hydroxydopamine lesion model of Parkinson's disease. GDNF isoforms were overexpressed with their native pre-pro-sequences in the striatum using an adeno-associated virus (AAV) vector, and the effects on motor performance and dopaminergic phenotype of the nigrostriatal pathway were assessed. In the non-lesioned striatum, both isoforms increased the density of dopamine transporter-positive fibers at 3 weeks after viral vector delivery. Although both isoforms increased the activity of the animals in cylinder assay, only α-GDNF enhanced the use of contralateral paw. Four weeks later, the striatal tyrosine hydroxylase (TH)-immunoreactivity was decreased in both α-GDNF and β-GDNF treated animals. In the neuroprotection assay, both GDNF splice isoforms increased the number of TH-immunoreactive cells in the substantia nigra but did not promote behavioral recovery based on amphetamine-induced rotation or cylinder assays. Thus, the shorter GDNF isoform, β-GDNF, and the full-length α-isoform have comparable neuroprotective efficacy on dopamine neurons of the nigrostriatal circuitry.
Polynomials with Surjective Arboreal Galois Representations Exist in Every Degree

Let~$E$ be a Hilbertian field of characteristic~$0$. R.W. K. Odoni conjectured that for every positive integer~$n$ there exists a polynomial~$f\in E[X]$ of degree~$n$ such that each iterate~$f^{\circ{k}}$ of~$f$ is irreducible and the Galois group of the splitting field of~$f^{\circ k}$ is isomorphic to the automorphism group of a regular,~$n$-branching tree of height~$k. $ We prove this conjecture when~$E$ is a number field.
RNA methylation in nuclear pre‐mRNA processing

Eukaryotic RNA can carry more than 100 different types of chemical modifications. Early studies have been focused on modifications of highly abundant RNA, such as ribosomal RNA and transfer RNA, but recent technical advances have made it possible to also study messenger RNA (mRNA). Subsequently, mRNA modifications, namely methylation, have emerged as key players in eukaryotic gene expression regulation. The most abundant and widely studied internal mRNA modification is N6‐methyladenosine (m6A), but the list of mRNA chemical modifications continues to grow as fast as interest in this field. Over the past decade, transcriptome‐wide studies combined with advanced biochemistry and the discovery of methylation writers, readers, and erasers revealed roles for mRNA methylation in the regulation of nearly every aspect of the mRNA life cycle and in diverse cellular, developmental, and disease processes. Although large parts of mRNA function are linked to its cytoplasmic stability and regulation of its translation, a number of studies have begun to provide evidence for methylation‐regulated nuclear processes. In this review, we summarize the recent advances in RNA methylation research and highlight how these new findings have contributed to our understanding of methylation‐dependent RNA processing in the nucleus.
Against all odds: exhaustive activation in lexical access of verb complementation options

ABSTRACT Various findings suggest that once a verb is accessed, all of its complementation options are activated. This fMRI study examined whether all the complementation options are activated even in contexts where this seems unnecessary. We examined whether introducing the selected complement prior to the verb (in topicalised sentences) still involves the activation of all complementation options. We performed ROI analyses in the left STG, a brain region that has been linked to the processing of argument structure and the number of complementation options. In this region, multiple-option verbs elicited greater activations compared with one-option verbs, both when the complement appeared after the verb and when it appeared pre-verbally. This suggests encapsulated lexical retrieval of the verb, which involves exhaustive activation of all its complementation options when the verb is accessed.
Quantitative Prediction of OATP‐Mediated Drug‐Drug Interactions With Model‐Based Analysis of Endogenous Biomarker Kinetics

Quantitative prediction of the magnitude of transporter‐mediated clinical drug‐drug interactions (DDIs) solely from in vitro inhibition data remains challenging. The objective of the present work was to analyze the kinetic profile of an endogenous biomarker for organic anion‐transporting polypeptides 1B (OATP1B), coproporphyrin I (CPI), and to predict clinical DDIs with a probe OATP1B substrate (pravastatin) based on “in vivo” inhibition constants (Ki). The CPI kinetics in the presence and absence of strong and weak OATP1B inhibitors (rifampin and GDC‐0810) were described well with a one‐compartment model, and in vivo Ki were estimated. Clinical DDIs between pravastatin and these inhibitors were predicted using physiologically based pharmacokinetic (PBPK) models coupled with the estimated in vivo Ki and predicted magnitude matched well with the observed DDIs. In conclusion, model‐based analysis of the CPI profile has the potential to quantitatively predict liability of a new molecular entity (NME) as an OATP1B inhibitor early in drug development.
Contribution of physician assistants/associates to secondary care: a systematic review

Objective To appraise and synthesise research on the impact of physician assistants/associates (PA) in secondary care, specifically acute internal medicine, care of the elderly, emergency medicine, trauma and orthopaedics, and mental health. Design Systematic review. Setting Electronic databases (Medline, Embase, ASSIA, CINAHL, SCOPUS, PsycINFO, Social Policy and Practice, EconLit and Cochrane), reference lists and related articles. Included articles Peer-reviewed articles of any study design, published in English, 1995–2017. Interventions Blinded parallel processes were used to screen abstracts and full text, data extractions and quality assessments against published guidelines. A narrative synthesis was undertaken. Outcome measures Impact on: patients’ experiences and outcomes, service organisation, working practices, other professional groups and costs. Results 5472 references were identified and 161 read in full; 16 were included—emergency medicine (7), trauma and orthopaedics (6), acute internal medicine (2), mental health (1) and care of the elderly (0). All studies were observational, with variable methodological quality. In emergency medicine and in trauma and orthopaedics, when PAs are added to teams, reduced waiting and process times, lower charges, equivalent readmission rate and good acceptability to staff and patients are reported. Analgesia prescribing, operative complications and mortality outcomes were variable. In internal medicine outcomes of care provided by PAs and doctors were equivalent. Conclusions PAs have been deployed to increase the capacity of a team, enabling gains in waiting time, throughput, continuity and medical cover. When PAs were compared with medical staff, reassuringly there was little or no negative effect on health outcomes or cost. The difficulty of attributing cause and effect in complex systems where work is organised in teams is highlighted. Further rigorous evaluation is required to address the complexity of the PA role, reporting on more than one setting, and including comparison between PAs and roles for which they are substituting. PROSPERO registration number CRD42016032895.
Body mass index and association with use of and distance from places for physical activity and active leisure among schoolchildren in Brazil. Cross-sectional study

ABSTRACT BACKGROUND: We evaluated associations between use of public places for physical activity and active leisure (PAAL) and their distances from subjects’ homes and indicators of overweight and obesity, among schoolchildren from different socioeconomic levels, in the city of Florianópolis, Brazil. DESIGN AND SETTING: Cross-sectional study conducted on a sample of 2,152 schoolchildren aged 7 to 14 years, enrolled at 30 public and private schools. METHODS: The exposure variables were the use of public places for PAAL in the neighborhood and their distance from schoolchildren’s homes. The outcomes were body mass index (BMI) and waist circumference (WC). Univariate and multivariate linear regression analyses were conducted according to income strata. RESULTS: Among the schoolchildren from low-income families, living closer to parks/playgrounds was associated with lower BMI (β = -2.15; 95% confidence interval, CI = -2.53; -1.77) and lower WC (β = -0.11 95% CI = -0.17; -0.05), while living at these distances from football pitches was associated with higher BMI (β = 1.73; 95% CI = 0.31; 3.15) and larger WC measurements (β = 0.03; 95% CI = 0.005; 0.14). Among the schoolchildren in low-income groups, living at an intermediate distance from beaches was associated with lower BMI (β = -1.10; 95% CI = -1.61; -0.59). CONCLUSION: Living closer to parks/playgrounds was associated with lower BMI and WC among schoolchildren from low-income families. Living closer to football pitches was associated with higher BMI and WC among these schoolchildren. Living at intermediate distances from beaches was associated with lower BMI among these schoolchildren.
Making habitat connectivity a reality

Although a plethora of habitat‐connectivity plans exists, protecting and restoring connectivity through on‐the‐ground action has been slow. We identified challenges to and opportunities for connectivity conservation through a literature review of project implementation, a workshop with scientists and conservation practitioners, 3 case studies of connectivity projects, and interviews with conservation professionals. Connectivity challenges and solutions tended to be context specific, dependent on land‐ownership patterns, socioeconomic factors, and the policy framework. Successful connectivity implementation tended to be associated with development and promotion of a common vision among diverse sets of stakeholders, including nontraditional conservation actors, such as water districts and recreation departments, and with communication with partners and the public. Other factors that lead to successful implementation included undertaking empirical studies to prioritize and validate corridors and the identification of related co‐benefits of corridor projects. Engaging partners involved in land management and planning, such as nongovernmental conservation organizations, public agencies, and private landowners, is critical to effective strategy implementation. A clear regulatory framework, including unambiguous connectivity conservation mandates, would increase public resource allocation, and incentive programs are needed to promote private sector engagement. Connectivity conservation must move more rapidly from planning to implementation. We provide an evidence‐based solution composed of key elements for successful on‐the‐ground connectivity implementation. We identified the social processes necessary to advance habitat connectivity for biodiversity conservation and resilient landscapes under climate change.
Constructing Fast Network through Deconstruction of Convolution

Convolutional neural networks have achieved great success in various vision tasks; however, they incur heavy resource costs. By using deeper and wider networks, network accuracy can be improved rapidly. However, in an environment with limited resources (e.g., mobile applications), heavy networks may not be usable. This study shows that naive convolution can be deconstructed into a shift operation and pointwise convolution. To cope with various convolutions, we propose a new shift operation called active shift layer (ASL) that formulates the amount of shift as a learnable function with shift parameters. This new layer can be optimized end-to-end through backpropagation and it can provide optimal shift values. Finally, we apply this layer to a light and fast network that surpasses existing state-of-the-art networks.
Effects of group size and rank on mother–infant relationships and reproductive success in rhesus macaques (Macaca mulatta)

In the present study, we compared mother–infant relationships in 57 mother–infant dyads residing in two wild, semi‐provisioned (22 mother–infant dyads in 2014, 35 dyads in 2015) groups of rhesus macaques (Macaca mulatta) in the Nanwan Nature Reserve for Rhesus Macaques, Hainan, China. We also compared reproductive success between these two groups. The ecology and provisioning regime for each group was similar. These groups differed however, in size. Group 1 contained ∼35 individuals and Group 2 contained ∼120 individuals. Data were collected over a 2‐year period (2014–2015). We found that during the birth season, mother–infant relationships in the larger group were characterized by less time in contact and more time separated than in the smaller group. Mothers in the smaller group initiated more contact and proximity with their infants. During the mating season when infants were approximately 6 months old, mother–infant relationships in the smaller group were more rejecting. We also found that birth rates were significantly higher but infant survivorship (to 1‐year‐old) was significantly lower in the smaller group. Moreover, higher‐ranking mothers in the larger group were characterized by a higher reproductive output than females of lower rank. In the smaller group, female rank did not affect reproductive output. There was, however, no clear relationship between infant survivorship and maternal rank. We hypothesize that differences in reproductive success and changes in mother–infant relationships between the birth and mating seasons reflect differences in the costs and benefits of group size: females in the larger group faced (i) higher intragroup feeding competition leading to a reduction in birth rate but also (ii) lower predation risk, resulting in higher infant survival rate compared to females in the smaller group. The results of this study point to the tradeoffs that primate females face in living in smaller and larger social groups.
Metformin-attenuated sepsis-induced oxidative damages: a novel role for metformin

Objective(s): Sepsis can result in severe organ injury by provoking inflammatory cascades and oxidative stress. Several studies are currently underway to find a drug with anti-inflammatory effects to prevent mortality and morbidity during sepsis. The present study was undertaken to assess the effects of metformin on oxidative stress and antioxidant status in sepsis induced by the Cecal Ligation and Puncture (CLP) method. Materials and Methods: Male Wistar rats were divided into 4 groups (n=10): sham, CLP, and 50 and 100 mg/kg metformin-treated CLP groups. After 12 hr, blood samples were collected and lung tissue was removed for histopathological study to detect tissue damage and degree of inflammation based on neutrophil infiltration and assay of the oxidative stress biomarkers superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase (GPx), and plasminogen activator inhibitor-1 (PAI-1). Results: The MPO activity and MDA level were decreased in the metformin-treated groups (P<0.05). Moreover, the groups receiving metformin showed lower inflammation scores than the CLP group (P<0.05). No significant differences in SOD, GPx, or PAI in the different groups were observed. The TAC level was reduced in the CLP group compared to the sham group (P<0.05), and interestingly, this value was reduced even further in the metformin-treated groups (P<0.05 compared with the CLP group). Conclusion: It was concluded that metformin protects lung tissue against sepsis-induced oxidative damage, and this protective effect may be more related to its anti-inflammatory and reduced neutrophil accumulation and less to its anti-oxidative properties.
Nonpolar residues in the presumptive pore‐lining helix of mechanosensitive channel MSL10 influence channel behavior and establish a nonconducting function

Mechanosensitive (MS) ion channels provide a universal mechanism for sensing and responding to increased membrane tension. MscS-Like(MSL)10 is a relatively well-studied MS ion channel from Arabidopsis thaliana that is implicated in cell death signaling. The relationship between the amino acid sequence of MSL10 and its conductance, gating tension, and opening and closing kinetics remain unstudied. Here we identify several nonpolar residues in the presumptive pore-lining transmembrane helix of MSL10 (TM6) that contribute to these basic channel properties. F553 and I554 are essential for wild type channel conductance and the stability of the open state. G556, a glycine residue located at a predicted kink in TM6, is essential for channel conductance. The increased tension sensitivity of MSL10 compared to close homolog MSL8 may be attributed to F563, but other channel characteristics appear to be dictated by more global differences in structure. Finally, MSL10 F553V and MSL10 G556V provided the necessary tools to establish that MSL10’s ability to trigger cell death is independent of its ion channel function.