Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphoacceptors Threonine 162 and Serines 170 and 178 within the Carboxyl-Terminal RRRS/T Motif of the Hepatitis B Virus Core Protein Make Multiple Contributions to Hepatitis B Virus Replication

ABSTRACT Phosphorylation of serines 157, 164, and 172 within the carboxyl-terminal SPRRR motif of the hepatitis B virus (HBV) core (C) protein modulates HBV replication at multiple stages. Threonine 162 and serines 170 and 178, located within the carboxyl-terminal conserved RRRS/T motif of HBV C protein, have been proposed to be protein kinase A phosphorylation sites. However, in vivo phosphorylation of these residues has never been observed, and their contribution to HBV replication remains unknown. In this study, [32P]orthophosphate labeling of cells expressing C proteins followed by immunoprecipitation with anti-HBc antibody revealed that threonine 162 and serines 170 and 178 are phosphoacceptor residues. A triple-alanine-substituted mutant, mimicking dephosphorylation of all three residues, drastically decreased pregenomic RNA (pgRNA) encapsidation, thereby decreasing HBV DNA synthesis. In contrast, a triple-glutamate-substituted mutant, mimicking phosphorylation of these residues, decreased DNA synthesis without significantly decreasing encapsidation. Neither triple mutant affected C protein expression or core particle assembly. Individual alanine substitution of threonine 162 significantly decreased minus-strand, plus-strand, and relaxed-circular DNA synthesis, demonstrating that this residue plays multiple roles in HBV DNA synthesis. Double-alanine substitution of serines 170 and 178 reduced HBV replication at multiple stages, indicating that these residues also contribute to HBV replication. Thus, in addition to serines 157, 164, and 172, threonine 162 and serines 170 and 178 of HBV C protein are also phosphorylated in cells, and phosphorylation and dephosphorylation of these residues play multiple roles in modulation of HBV replication. IMPORTANCE Threonine 162, within the carboxyl-terminal end of the hepatitis B virus (HBV adw) core (C) protein, has long been ignored as a phosphoacceptor, even though it is highly conserved among mammalian hepadnaviruses and in the overlapping consensus RxxS/T, RRxS/T, and TP motifs. Here we show, for the first time, that in addition to the well-known phosphoacceptor serines 157, 164, and 172 in SPRRR motifs, threonine 162 and serines 170 and 178 in the RRRS/T motif are phosphorylated in cells. We also show that, like serines 157, 164, and 172, phosphorylated and dephosphorylated threonine 162 and serines 170 and 178 contribute to multiple steps of HBV replication, including pgRNA encapsidation, minus-strand and plus-strand DNA synthesis, and relaxed-circular DNA synthesis. Of these residues, threonine 162 is the most important. Furthermore, we show that phosphorylation of C protein is required for efficient completion of HBV replication.
Optimal design for longitudinal studies to estimate pubertal height growth in individuals

Abstract Background: The SITAR model expresses individual pubertal height growth in terms of mean size, peak height velocity (PHV) and age at PHV. Aim: To use SITAR to identify the optimal time interval between measurements to summarise individual pubertal height growth. Subjects and methods: Heights in 3172 boys aged 9–19 years from Christ’s Hospital School measured on 128 679 occasions (a median of 42 heights per boy) were analysed using the SITAR (SuperImposition by Translation And Rotation) mixed effects growth curve model, which estimates a mean curve and three subject-specific random effects. Separate models were fitted to sub-sets of the data with measurement intervals of 2, 3, 4, 6, 12 and 24 months, and the different models were compared. Results: The models for intervals 2–12 months gave effectively identical results for the residual standard deviation (0.8 cm), mean spline curve (6 degrees of freedom) and random effects (correlations >0.9), showing there is no benefit in measuring height more often than annually. The model for 2-year intervals fitted slightly less well, but needed just four-to-five measurements per individual. Conclusions: Height during puberty needs to be measured only annually and, with slightly lower precision, just four biennial measurements can be sufficient.
Effectiveness of omega-3 polyunsaturated fatty acids against microbial pathogens

Microorganisms provide both beneficial and harmful effects to human beings. Beneficial effects come from the symbiotic relationship that exists between humans and microbiota, but then several human illnesses have turned some friendly microbes into opportunistic pathogens, causing several microbial-related diseases. Various efforts have been made to create and utilize antimicrobial agents in the treatment and prevention of these infections, but such efforts have been hampered by the emergence of antimicrobial resistance. Despite extensive studies on drug discovery to alleviate this problem, issues with the toxicity and tolerance of certain compounds and continuous microbial evolution have forced researchers to focus on screening various phytochemical dietary compounds for antimicrobial activity. Linolenic acid and its derivatives (eicosapentaenoic acid and docosahexaenoic acid) are omega-3 fatty acids that have been studied due to their role in human health, being important for the brain, the eye, the cardiovascular system, and general human growth. However, their utilization as antimicrobial agents has not been widely appreciated, perhaps due to a lack of understanding of antimicrobial mechanisms, toxicity, and route of administration. Therefore, this review focuses on the efficacy, mechanism, and toxicity of omega-3 fatty acids as alternative therapeutic agents for treating and preventing diseases associated with pathogenic microorganisms.
Polymorphisms of the Ras-Association Domain Family 1 Isoform A (RASSF1A) Gene are Associated with Ovarian Cancer, and with the Prognostic Factors of Grade and Stage, in Women in Southern China

Background The aim of this study was to determine whether polymorphisms of the Ras-association domain family 1 isoform A (RASSF1A) gene were associated with ovarian cancer and with tumor grade and stage, which affect the prognosis of ovarian cancer, in women in Southern China. Material/Methods Women from Southern China with histologically confirmed, graded and staged ovarian cancer (n=1,375), and cancer-free controls (n=1,227), provided samples of peripheral blood. DNA was extracted from the blood samples, and five tagging single nucleotide polymorphisms (SNPs) (rs4688728G>T, rs72932987C>T, rs1989839C>T, rs2073497A>C, and rs2236947A>C) were evaluated using an online assay-by-design platform. Polymerase chain reaction (PCR) DNA amplification was performed and computational haplotyping analysis of genetic associations between the five tagging SNPs was performed to identify frequent haplotypes in women with ovarian cancer, and the associations with tumor grade and stage. Results In women in Southern China, the CT genotype of rs1989839 was associated with the patients with ovarian cancer (P=0.001), and was significantly correlated with tumor grade and stage (P=0.008). One of the remaining four SNPs studied, rs2073497A>C showed an association with the prognostic factors of grade and stage, but this association did not reach statistical significance. Conclusions Polymorphisms of the RASSF1A gene, most significantly the CT genotype of rs1989839, might play a role in the development and prognosis of ovarian cancer in women in Southern China. To our knowledge, this is the first study to demonstrate an association between polymorphisms in the RASSF1A gene in ovarian cancer.
Revealing the effect of crumpling on the reinforcement efficiency of graphene in composites

A graphene/PMMA model composite has been studied primarily using Raman spectroscopy, as the characteristic Raman band positions are closely correlated to the strain in graphene. Different from the conventional work, in this work, the graphene/PMMA model composite has been annealed to induce a residual compression, which leads to the formation of crumples in the graphene. Our main target is to study how the structure of the crumples affects the stress transfer from the matrix to grapheme, and this has been achieved by comparing the strain applied to the substrate, with the strain in the graphene flake.
Early predictors of male delinquency: a review.

A systematic review is presented of prediction studies on delinquency. The main aim is to identify etiological variables for delinquency that, in different studies and across different populations, show good predictive validity. To achieve this goal, a measure of predictive efficiency was chosen that could be applied to studies from the United States and from abroad. The principal predictors of delinquency were the parents' family management and techniques (supervision and discipline), the child's conduct problems, parental criminality, and the child's poor academic performance. Data are presented to show the earliest age of the child at which these predictors have been measured. Results of the prediction data are used to demonstrate utility functions in which false positive and false negative errors are minimized. Recommendations are put forward to improve prediction studies in criminality.
Quantification of Age-Related Lung Tissue Mechanics under Mechanical Ventilation

Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator-induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator-induced lung injuries. Two age-related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50-year-old (normal) and second is for an 80-year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80-year-old as compared to the 50-year-old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80-year-old decreased by about 64% (three-fold) and 80% (four-fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80-year-old in comparison to the 50-year-old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.
“At My Age … ”: Defining Sexual Wellness in Mid- and Later Life

Sexual wellness is integral to quality of life across the life span, despite ageist stereotypes suggesting sexual expression ends at midlife. However, conceptualizing sexual wellness in mid- and later life is complicated by a dysfunction-based narrative, lack of a sex-positive aging framework, and existing measures that are age irrelevant and limited in scope. This study aimed to address these limitations by providing a conceptualization of sexual wellness grounded in definitions from midlife and older adults. A sample of 373 midlife and older adults (M = 60, SD = 5.84) in the United States provided a definition of sexual wellness. Using thematic analysis, multiple researchers coded qualitative responses, and results suggested a biopsychosocial-cultural framework. Findings reflect that midlife and older adults provide multifaceted definitions inclusive of various behavioral experiences, including disengaging from sex. They are also keenly aware of physical and psychological limitations and strengths, and emphasize mutual experiences and synchronicity. Midlife and older adults also reflect on age, drawing comparisons to different phases of life and often displaying adaptability in adjusting expectations. When conceptualizing sexual wellness in this population it is imperative to capture this multidimensionality, include those who are not actively engaging in sex, and be aware of the influence of ageist and dys/function narratives.
Transfer of clinical breast examination skills to female community health volunteers in Nepal.

OBJECTIVE To observe skill transfer for detection of clinical abnormalities in the breast by determining kappa agreement, sensitivity, specificity, positive predictive value and negative predictive value of clinical breast examination by female community health workers (FCHVs) considering surgeon findings as the gold standard. METHOD This cross-sectional study was conducted in Dharan Municipality, Eastern Nepal for period of one year from June 2008 to May 2009. A total of 1,238 women were examined by both a FCHV and the surgeon. RESULT The interobserver kappa agreement for the detection of clinical abnormalities in breast was 67% indicating a good agreement. Sensitivity, specificity, positive predictive value and negative predictive values of "FCHVs' clinical breast examination" to detect clinical abnormalities in breast in comparison to the surgeon's were 70%, 95%, 74% and 94% respectively. CONCLUSION In view of good clinical breast examination skill transfer to FCHVs for detection of clinical abnormalities in breast, we conclude effective training of FCHVs may be a feasble approach for diagnosis of breast abnormalities in rural Nepal.
High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development

The microtubule associated protein tau plays a critical role in the pathogenesis of neurodegenerative disease. Recent studies suggest that tau also plays a role in disorders of neuronal connectivity, including epilepsy and post-traumatic stress disorder. Animal studies have shown that the MAPT gene, which codes for the tau protein, undergoes complex pre-mRNA alternative splicing to produce multiple isoforms during brain development. Human data, particularly on temporal and regional variation in tau splicing during development are however lacking. In this study, we present the first detailed examination of the temporal and regional sequence of MAPT alternative splicing in the developing human brain. We used a novel computational analysis of large transcriptomic datasets (total n = 502 patients), quantitative polymerase chain reaction (qPCR) and western blotting to examine tau expression and splicing in post-mortem human fetal, pediatric and adult brains. We found that MAPT exons 2 and 10 undergo abrupt shifts in expression during the perinatal period that are unique in the canonical human microtubule-associated protein family, while exon 3 showed small but significant temporal variation. Tau isoform expression may be a marker of neuronal maturation, temporally correlated with the onset of axonal growth. Immature brain regions such as the ganglionic eminence and rhombic lip had very low tau expression, but within more mature regions, there was little variation in tau expression or splicing. We thus demonstrate an abrupt, evolutionarily conserved shift in tau isoform expression during the human perinatal period that may be due to tau expression in maturing neurons. Alternative splicing of the MAPT pre-mRNA may play a vital role in normal brain development across multiple species and provides a basis for future investigations into the developmental and pathological functions of the tau protein.
Journal of Occupational Medicine and Toxicology High Abundances of Neurotrophin 3 in Atopic Dermatitis Mast Cell

Background: Neurotrophin 3 (NT-3) is a member of the neurotrophin family, a group of related proteins that are known to regulate neuro-immune interactions in allergic diseases. Their cellular sources and role in the recruitment of mast cell precursors in atopic dermatitis have not been characterized in detail so far.
Information Systems Projects and Individual Developer Outcomes: Role of Project Managers and Process Control

We integrate control theory and the information systems IS project management literature using a multilevel lens to theorize the cross-level effects of technical IS project risk on individual developer outcomes-performance and psychological stress-and the mechanisms by which IS project managers' project-related knowledge attenuates this relationship. We argue that IS project managers with project-related knowledge mitigate technical IS project risk by facilitating the enactment of internal and external process controls in their IS projects. Our empirical study involves data collected from 1,230 individual developers embedded in 130 IS project teams that are managed by 20 IS project managers. Our results provide strong support for the three-level model and its set of a cross-level main effects of technical IS project risk on individual developer outcomes; b cross-level main effects of IS project manager project-related knowledge on enacted internal and external process controls; and c cross-level moderation of the relationship between technical IS project risk and individual developer outcomes by IS project manager project-related knowledge through internal and external process controls. Our study provides insights on how IS project management, IS project process controls, and technical IS project risk must be managed as a system of multilevel dependencies to achieve the desired developer outcomes. The online appendix is available at https://doi.org/10.1287/isre.2017. 0723 .
Diagnostic Performance and Safety of Positron Emission Tomography Using 18F-Fluciclovine in Patients with Clinically Suspected High- or Low-grade Gliomas: A Multicenter Phase IIb Trial

Objective(s): The study objective was to assess the diagnostic performance of positron emission tomography (PET) for gliomas using the novel tracer 18F-fluciclovine (anti-[18F]FACBC) and to evaluate the safety of this tracer in patients with clinically suspected gliomas. Methods: Anti-[18F]FACBC was administered to 40 patients with clinically suspected high- or low-grade gliomas, followed by PET imaging. T1-weighted, contrast-enhanced T1-weighted, and fluid-attenuated inversion recovery (or T2-weighted) magnetic resonance imaging (MRI) scans were obtained to plan for the tissue collection. Tissues were collected from either “areas visualized using anti-[18F]FACBC PET imaging but not using contrast-enhanced T1-weighted imaging” or “areas visualized using both anti-[18F]FACBC-PET imaging and contrast-enhanced T1-weighted imaging” and were histopathologically examined to assess the diagnostic accuracy of anti-[18F]FACBC-PET for gliomas. Results: The positive predictive value of anti-[18F]FACBC-PET imaging for glioma in areas visualized using anti-[18F]FACBC-PET imaging, but not visualized using contrast-enhanced T1-weighted images, was 100.0% (26/26), and the value in areas visualized using both contrast-enhanced T1-weighted imaging and anti-[18F]FACBC-PET imaging was 87.5% (7/8). Twelve adverse events occurred in 7 (17.5%) of the 40 patients who received anti-[18F]FACBC. Five events in five patients were considered to be adverse drug reactions; however, none of the events were serious, and all except one resolved spontaneously without treatment. Conclusion: This Phase IIb trial showed that anti-[18F]FACBC-PET imaging was effective for the detection of gliomas in areas not visualized using contrast-enhanced T1-weighted MRI and the tracer was well tolerated.
Policy matrix evolution for generation of heuristics

Online bin-packing is a well-known problem in which immediate decisions must be made about the placement of items with various sizes into fixed capacity bins. The associated decisions can be based on an index policy in which each decision option is independently given a value and the highest value choice is selected. In this paper, we represent such heuristics for online bin packing as a simple matrix of scores. We then use a genetic algorithm to search for matrices giving good performance. This might be regarded as parameter tuning of the packing heuristic but in which a fine-grained representation is used and so the number of parameters is much larger than in standard parameter tuning. The evolved matrices perform better than the standard heuristics. They also reveal interesting structures and so have impact on questions of how heuristic score functions should be represented and what structure they might be expected to exhibit.
Learning to Extract Coherent Summary via Deep Reinforcement Learning

Coherence plays a critical role in producing a high-quality summary from a document. In recent years, neural extractive summarization is becoming increasingly attractive. However, most of them ignore the coherence of summaries when extracting sentences. As an effort towards extracting coherent summaries, we propose a neural coherence model to capture the cross-sentence semantic and syntactic coherence patterns. The proposed neural coherence model obviates the need for feature engineering and can be trained in an end-to-end fashion using unlabeled data. Empirical results show that the proposed neural coherence model can efficiently capture the cross-sentence coherence patterns. Using the combined output of the neural coherence model and ROUGE package as the reward, we design a reinforcement learning method to train a proposed neural extractive summarizer which is named Reinforced Neural Extractive Summarization (RNES) model. The RNES model learns to optimize coherence and informative importance of the summary simultaneously. The experimental results show that the proposed RNES outperforms existing baselines and achieves state-of-the-art performance in term of ROUGE on CNN/Daily Mail dataset. The qualitative evaluation indicates that summaries produced by RNES are more coherent and readable.
Application of Microencapsulation Technology for the Production of Vitamin-C Fortified Flavoured Milk

A research study was carried out to develop vitamin-C enriched flavoured milk by using vitamin-C microcapsules. Vitamin-C was encapsulated through extrusion technique using sodium alginate (stabilizer) as coating material. Standardization of sodium alginate was done by the formation of beads. The beads were found hard and of good quality with 2 g sodium alginate for carrying the vitamin-C. The level of addition of vitamin-C powder was standardized based on the encapsulation efficiency (EE). In the present study, 71 percentage EE level was used to prepare vitamin-C fortified flavoured milk. The developed flavoured milk (F1) and control flavoured milk (CF) were assessed for consumer acceptability through nine point’s hedonic rating scale. Among the samples, F1 had the highest rate of consumer acceptance next to the control sample (CF). The pH value of control (CF) and F1 were observed to be 5.65 and 5.32 respectively. The sterilization efficiency of CF and F1 samples was found positive. The vitamin-C encapsulated flavoured milk (F1) sample was observed better up to 30 days with the retained quantity of 92 ± 0.50 mg of vitamin-C.