Miracle-dz/UniFAR-FTUs huggingface dataset:
Signals in APOBEC3F N-terminal and C-terminal Deaminase Domains Each Contribute to Encapsidation in HIV-1 Virions and Are Both Required for HIV-1 Restriction*

Background: The antiretroviral activity of cellular proteins APOBEC3F and APOBEC3G requires their inclusion within HIV-1 virions. Results: Unlike APOBEC3G, signals in N- and C-terminal deaminase domains of APOBEC3F each contribute to virion encapsidation. Conclusion: A3F employs an additional mechanism for virion encapsidation that is absent in A3G. Significance: Elucidation of the mechanisms of APOBEC3F and APOBEC3G encapsidation may suggest new strategies to decrease HIV-1 replication. Human cytidine deaminases APOBEC3F (A3F) and APOBEC3G (A3G) inhibit human immunodeficiency virus type-1 (HIV-1) replication. In the absence of HIV-1 Vif, A3F and/or A3G are incorporated into assembling virions and exert antiviral functions in subsequently infected target cells. Encapsidation of A3F or A3G within the protease-matured virion core following their incorporation into virions is hypothesized to be important for the antiviral function of these proteins. In this report, we demonstrated that A3F was quantitatively encapsidated in the mature virion core. In distinct contrast, A3G was distributed both within and outside of the virion core. Analysis of a series of A3F-A3G chimeras comprised of exchanged N- and C-terminal deaminase domains identified a 14 amino acid segment in the A3F C-terminal deaminase domain that contributed to preferential encapsidation and anti-HIV activity. Amino acid residue L306 in this C-terminal segment was determined to be necessary, but not sufficient, for these effects. Amino acid residue W126 in the N-terminal deaminase domain was determined also to contribute to preferential encapsidation and antiviral activity of A3F. Analysis of the A3F (W126A L306A) double mutant revealed that both residues are required for full anti-HIV function. The results reported here advance our understanding of the mechanisms of A3F virion encapsidation and antiviral function and may lead to innovative strategies to inhibit HIV-1 replication.
Ethanol metabolism by HeLa cells transduced with human alcohol dehydrogenase isoenzymes: control of the pathway by acetaldehyde concentration.

BACKGROUND Human class I alcohol dehydrogenase 2 isoenzymes (encoded by the ADH1B locus) have large differences in kinetic properties; however, individuals inheriting the alleles for the different isoenzymes exhibit only small differences in alcohol elimination rates. This suggests that other cellular factors must regulate the activity of the isoenzymes. METHODS The activity of the isoenzymes expressed from ADH1B*1, ADH1B*2, and ADH1B*3 cDNAs was examined in stably transduced HeLa cell lines, including lines which expressed human low K(m) aldehyde dehydrogenase (ALDH2). The ability of the cells to metabolize ethanol was compared with that of HeLa cells expressing rat class I alcohol dehydrogenase (ADH) (HeLa-rat ADH cells), rat hepatoma (H4IIEC3) cells, and rat hepatocytes. RESULTS The isoenzymes had similar protein half-lives in the HeLa cells. Rat hepatocytes, H4IIEC3 cells, and HeLa-rat ADH cells oxidized ethanol much faster than the cells expressing the ADH1B isoenzymes. This was not explained by high cellular NADH levels or endogenous inhibitors; but rather because the activity of the β1 and β2 ADHs was constrained by the accumulation of acetaldehyde, as shown by the increased rate of ethanol oxidation by cell lines expressing β2 ADH plus ALDH2. CONCLUSION The activity of the human β2 ADH isoenzyme is sensitive to inhibition by acetaldehyde, which likely limits its activity in vivo. This study emphasizes the importance of maintaining a low steady-state acetaldehyde concentration in hepatocytes during ethanol metabolism.
Cardiac Valve Papillary Fibroelastoma: Surgical Excision for Revealed or Potential Embolization

Abstract Cardiac papillary fibroelastomas (CPF) are benign endocardial papillomas commonly formed from valve endothelium. The majority of tumors are found on the left side of the heart, with only a few case reports of pulmonary valve fibroelastomas. We report here a case of pulmonary valve papillary fibroelastoma that was successfully managed with simple excision of the mass.
“ Is it true ? ” – Deep Learning for Stance Detection in News

Stance detection is an important component of fake news detection. In this project we explore different neural net architectures for stance detection in news articles. In particular, we analyze the effectiveness of recurrent neural nets for this problem. We discover that a modified attentive reader model is well suited for the task. While our best deep learning model comfortably exceeds the baseline score set by Fake News Challenge, a simple feedforward network marginally outperforms it. As far as we are aware, our LSTM-based RNN model is the state of the art end-to-end deep learning model for this dataset.
Students' conceptions of subject matter: An aspect of learning and teaching in higher education

Summary Our intention is to outline a certain view of learning and teaching in higher education. In order to make our generalisations more concrete we have used, as an example, a research project concerned with ways of facilitating a deeper understanding of selected concepts in Economics at University level. This project can be seen as a continuation of previous research, especially within another project entitled ‘Study skill and learning˚s carried out during 1970–74—see, e.g. Svensson's (1976) work with the same title—whose conclusions related to qualitative differences in learning.
Nuclear factors that mediate intrathymic signals are developmentally regulated

Thymocytes mature through several stages of development, defined by cell surface markers such as CD3, CD4, and CD8, in response to environmental cues. Signal transduction resulting from lymphocyte- stromal cell interactions is likely to activate inducible transcription factors which in turn govern stage-specific gene expression. In this report we show that inducible transcription factors such as AP-1 and NF- AT are constitutively nuclear, in response to intrathymic signals, in freshly isolated thymocytes at all stages of maturation. In CD4+CD8+ double positive (DP), but not in the more immature CD4-CD8- double negative (DN) thymocytes, constant stimulus from the thymic environment is required to maintain nuclear AP-1. Thus, disruption of the thymus and incubation of thymocytes at 37 degrees C downregulates DNA binding by nuclear factors AP-1 and NF-AT. Similar treatment of thymocytes has previously been shown to downregulate CD3 zeta chain phosphorylation and increase T cell receptor CD3 expression on DP thymocytes, which is a feature of repertoire selection. Since mature T cells maintain inducible nuclear factors in an inactive form until an encounter with antigen, we propose that downregulation of nuclear DNA binding proteins may reflect another feature of this stage of T cell maturation.
Daily Variation in Global and Local DNA Methylation in Mouse Livers

DNA methylation is one of the best-characterized epigenetic modifications and has an important biological relevance. Here we showed that global DNA methylation level in mouse livers displayed a daily variation where the peak phases occurred during the end of the day and the lowest level at the beginning of the day in the light-dark or dark-dark cycles. Typical repeat sequence long interspersed nucleotide element-1 (LINE-1) had a similar methylation rhythm to global DNA. DNA methyltransferase 3A (DNMT3A) and ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) brought a relative forward daily variation to global DNA methylation, and the temporary change in ratio of SAM to SAH had no influence on the DNA methylation level. The rhythm of global DNA methylation was lost and DNA methylation level was increased in Per1-/-Per2-/- double knockout mice, which were in accordance with changes of Dnmt3a mRNA levels and its rhythm. Our results suggest that the daily variation in global DNA methylation was associated with the change of Dnmt3a expression rather than ratio of SAM to SAH.
Weighted Hypothesis Testing

The power of multiple testing procedures can be increased by using weighted p-values (Genovese, Roeder and Wasserman 2005). We derive the optimal weights and we show that the power is remarkably robust to misspecification of these weights. We consider two methods for choosing weights in practice. The first, external weighting, is based on prior information. The second, estimated weighting, uses the data to choose weights.
Energy Reduction in SRAM using Dynamic Voltage and Frequency Management

This paper describes a dynamic voltage frequency control scheme for a 256 X 64 SRAM block for reducing the energy in active mode and stand-by mode. The DVFM control system monitors the external clock and changes the supply voltage and the body bias so as to achieve a significant reduction in energy. The behavioral model of the proposed DVFM control system algorithm is described and simulated in HDL using delay and energy parameters obtained through SPICE simulation. The frequency range dictated by an external controller is 100 MHz to I GHz. The supply voltage of the complete memory system is varied in steps of 50 mV over the range of 500 mV to IV. The threshold voltage range of operation is plusmn100 mV around the nominal value, achieving 83.4% energy reduction in the active mode and 86.7% in the stand-by mode. This paper also proposes a energy replica that is used in the energy monitor subsystem of the DVFM system.
Historical and epistemological trends in public administration

Begins with a brief overview of how public administration emerged as the positivist theory and technocratic practice of the modern administrative state. The question then becomes: To what extent has public administration been affected by the societal shift toward postmodernism? The author argues that public administration has moved some distance away from its positivist origins; however, the transformation of public administration is still incomplete. The author concludes that public administration should pay more attention to the recent developments of post‐positivist methods of analysis rather than attempting to adopt all the tenets of postmodernism. Large bureaucratic organizations remain typically modern, but they should not be either conceptualized or managed as small machines.
Glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase IV inhibitors: new therapeutic agents for the treatment of type 2 diabetes

Purpose of reviewCurrent treatments for type 2 diabetes are effective, but a substantial number of patients continue to have difficulty in achieving and maintaining satisfactory control of blood glucose. The available data suggest that enhancing the action of glucagon-like peptide 1 through the use of glucagon-like peptide 1 receptor agonists, or by preventing the degradation of glucagon-like peptide 1 by inhibition of dipeptidyl peptidase IV, may be useful therapeutic approaches for the treatment of type 2 diabetes. Herein we focus on the status of current approaches, based on enhancement of incretin action, for the treatment of type 2 diabetes. Recent findingsDegradation-resistant glucagon-like peptide 1 receptor agonists acutely lower blood glucose in human beings by improvement in β cell function, inhibition of gastric emptying, and reduction of glucagon secretion. Treatment with these agents added to existing diabetes therapies, as exemplified by studies of the injectable glucagon-like peptide 1 receptor agonist exenatide, demonstrates significant reduction in HbA1c, together with prevention of weight gain and, in many individuals, significant weight loss over a 30-week study period. Dipeptidyl peptidase IV inhibitors are orally available effective antidiabetic agents that seem to be well tolerated but may not produce weight loss. Less information is currently available about the consequences of long-term treatment with Dipeptidyl peptidase IV inhibitors. SummaryBoth glucagon-like peptide 1receptor agonists and dipeptidyl peptidase IV inhibitors represent promising new approaches for the treatment of type 2 diabetes. The long-term safety and efficacy of these agents remain to be determined, but the available evidence suggests that these new drug classes will provide novel therapeutic alternatives for the management of diabetes.
Reliable Virtual Machine Placement and Routing in Clouds

In current cloud computing systems, when leveraging virtualization technology, the customer’s requested data computing or storing service is accommodated by a set of communicated virtual machines (VM) in a scalable and elastic manner. These VMs are placed in one or more server nodes according to the node capacities or failure probabilities. The VM placement availability refers to the probability that at least one set of all customer’s requested VMs operates during the requested lifetime. In this paper, we first study the problem of placing at most <inline-formula> <tex-math notation="LaTeX">$H$</tex-math><alternatives><inline-graphic xlink:href="yang-ieq1-2693273.gif"/> </alternatives></inline-formula> groups of <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives> <inline-graphic xlink:href="yang-ieq2-2693273.gif"/></alternatives></inline-formula> requested VMs on a minimum number of nodes, such that the VM placement availability is no less than <inline-formula><tex-math notation="LaTeX">$\delta$ </tex-math><alternatives><inline-graphic xlink:href="yang-ieq3-2693273.gif"/></alternatives></inline-formula>, and that the specified communication delay and connection availability for each VM pair under the same placement group are not violated. We consider this problem with and without Shared-Risk Node Group (SRNG) failures, and prove this problem is NP-hard in both cases. We subsequently propose an exact Integer Nonlinear Program (INLP) and an efficient heuristic to solve this problem. We conduct simulations to compare the proposed algorithms with two existing heuristics in terms of performance. Finally, we study the related reliable routing problem of establishing a connection over at most <inline-formula><tex-math notation="LaTeX">$w$</tex-math><alternatives> <inline-graphic xlink:href="yang-ieq4-2693273.gif"/></alternatives></inline-formula> link-disjoint paths from a source to a destination, such that the connection availability requirement is satisfied and each path delay is no more than a given value. We devise an exact algorithm and two heuristics to solve this NP-hard problem, and evaluate them via simulations.
Effects of Auricular Acupressure on Sleep Quality, Anxiety, and Depressed Mood in RN-BSN Students With Sleep Disturbance.

BACKGROUND Students in 2-year registered nurse to Bachelor of Science in nursing (RN-BSN) programs usually work full-time and study part-time. Sleep disturbance, anxiety, and depression are known to be common health problems among these students. Prior research has described the effectiveness of auricular acupressure (AA) in reducing sleep disturbance and improving mood. PURPOSE The aim of this study was to evaluate the effect of using a 4-week AA program that adheres to a magnetic pellet on the shenmen acupoint on sleep quality, anxiousness, and depressed moods in nursing students with sleep disturbance. METHODS This study used a one-group, quasi-experimental design with repeated measures. Eligible students were recruited from an RN-BSN program offered by a university in northern Taiwan, and all were currently experiencing sleep disturbance. A 4-week AA intervention that applied a magnetic pellet on the shenmen acupoint was used. The Pittsburgh Sleep Quality Index, Beck Anxiety Inventory, and Beck Depression Inventory-II were used to measure sleep quality and mood outcomes each week during the 4-week intervention. Improvements in sleep quality, anxiety, and depressed moods were analyzed using the generalized estimating equation. RESULTS Thirty-six participants with a mean age of 32 years were enrolled as participants. After adjusting for confounding factors, continuous and significant improvements in sleep quality, anxiety, and depressed mood (p < .05) were observed throughout the intervention, with 4-week improvements in sleep quality, anxiety, and depressed mood averaging 26.7%, 43.5%, and 25%, respectively. CONCLUSIONS/IMPLICATIONS FOR PRACTICE This study showed the efficacy of using a 4-week AA that applies a magnetic pellet on the shenmen acupoint in terms of improving sleep quality, anxiousness, and depressed mood in RN-BSN students experiencing sleep disturbances. Especially, the emotional mood of participants improved significantly as early as the first week. The 4-week AA for reducing sleep disturbance, and improving students' anxiety, and depressed moods may be applied on primary healthcare.
Three-dimensional structure of rhesus rotavirus by cryoelectron microscopy and image reconstruction

The structure of rhesus rotavirus was examined by cryoelectron microscopy and image analysis. Three-dimensional reconstructions of infectious virions were computed at 26- and 37-A resolution from electron micrographs recorded at two different levels of defocus. The major features revealed by the reconstructions are (a) both outer and inner capsids are constructed with T = 13l icosahedral lattice symmetry; (b) 60 spikelike projections, attributed to VP4, extend at least 100 A from the outer capsid surface; (c) the outer capsid, attributed primarily to VP7, has a smoothly rippled surface at a mean radius of 377 A and is perforated by 132 aqueous holes ranging from 40- 65 A in diameter; (d) the inner capsid has a "bristled" outer surface composed of 260 trimeric-shaped columns of density, attributed to VP6, which merge with a smooth, spherical shell of density at a lower, mean radius of 299 A, and which is perforated by holes in register with those in the outer capsid; (e) a "core" region contains a third, nonspherical shell of density at a mean radius of 225 A that encapsidates the double-stranded RNA genome; and (f) the space between the outer and inner capsids forms an open aqueous network that may provide pathways for the diffusion of ions and small regulatory molecules as well as the extrusion of RNA. The assignment of different viral structural proteins to specific features of the reconstruction has been tentatively made on the basis of excluded volume estimates and previous biochemical characterizations of rotavirus.
Assembly of Alphavirus Replication Complexes from RNA and Protein Components in a Novel trans-Replication System in Mammalian Cells

ABSTRACT For positive-strand RNA viruses, the viral genomic RNA also acts as an mRNA directing the translation of the replicase proteins of the virus. Replication takes place in association with cytoplasmic membranes, which are heavily modified to create specific replication compartments. Here we have expressed by plasmid DNA transfection the large replicase polyprotein of Semliki Forest virus (SFV) in mammalian cells from a nonreplicating mRNA and provided a separate RNA containing the replication signals. The replicase proteins were able to efficiently and specifically replicate the template in trans, leading to accumulation of RNA and marker gene products expressed from the template RNA. The replicase proteins and double-stranded RNA replication intermediates localized to structures similar to those seen in SFV-infected cells. Using correlative light electron microscopy (CLEM) with fluorescent marker proteins to relocate those transfected cells, in which active replication was ongoing, abundant membrane modifications, representing the replication complex spherules, were observed both at the plasma membrane and in intracellular endolysosomes. Thus, replication complexes are faithfully assembled and localized in the trans-replication system. We demonstrated, using CLEM, that the replication proteins alone or a polymerase-negative polyprotein mutant together with the template did not give rise to spherule formation. Thus, the trans-replication system is suitable for cell biological dissection and examination in a mammalian cell environment, and similar systems may be possible for other positive-strand RNA viruses.
PDK1 Regulates Vascular Remodeling and Promotes Epithelial-Mesenchymal Transition in Cardiac Development

ABSTRACT One essential downstream signaling pathway of receptor tyrosine kinases (RTKs), such as vascular endothelial growth factor receptor (VEGFR) and the Tie2 receptor, is the phosphoinositide-3 kinase (PI3K)-phosphoinositide-dependent protein kinase 1 (PDK1)-Akt/protein kinase B (PKB) cascade that plays a critical role in development and tumorigenesis. However, the role of PDK1 in cardiovascular development remains unknown. Here, we deleted PDK1 specifically in endothelial cells in mice. These mice displayed hemorrhage and hydropericardium and died at approximately embryonic day 11.5 (E11.5). Histological analysis revealed defective vascular remodeling and development and disrupted integrity between the endothelium and trabeculae/myocardium in the heart. The atrioventricular canal (AVC) cushion and valves failed to form, indicating a defect in epithelial-mesenchymal transition (EMT), together with increased endothelial apoptosis. Consistently, ex vivo AVC explant culture showed impeded mesenchymal outgrowth. Snail protein was reduced and was absent from the nucleus in AVC cells. Delivery of the Snail S6A mutant to the AVC explant effectively rescued EMT defects. Furthermore, adenoviral Akt delivery rescued EMT defects in AVC explant culture, and deletion of PTEN delayed embryonic lethality of PDK1 endothelial deletion mice by 1 day and rendered normal development of the AVC cushion in the PDK1-deficient heart. Taken together, these results have revealed an essential role of PDK1 in cardiovascular development through activation of Akt and Snail.
Family Relations Test: A Normative Study

Summary The Bene-Anthony Family Relations Test was administered to 190 eleven-year-old, sixth grade children (86 boys, 104 girls) by students under the supervision of the author. Means and standard deviations for the outgoing and incoming, positive and negative, categories were calculated for ‘Father’, ‘Mother’, ‘Nobody’, ‘Next Oldest Sibling’ and ‘Next Youngest Sibling’, boys and girls being treated separately. The ‘norms’ for boys are compared with “clinic”, “delinquent” and “non-reading” groups. Some important and statistically significant differences are noted between these groups.
Flies and Campylobacter Infection of Broiler Flocks

A total of 8.2% of flies caught outside a broiler house in Denmark had the potential to transmit Campylobacter jejuni to chickens, and hundreds of flies per day passed through the ventilation system into the broiler house. Our study suggests that flies may be an important source of Campylobacter infection of broiler flocks in summer.