Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Permissive Cell Lines for Complete Propagation of Hepatitis C Virus

ABSTRACT Hepatitis C virus (HCV) is a major etiologic agent of chronic liver diseases. Although the HCV life cycle has been clarified by studying laboratory strains of HCV derived from the genotype 2a JFH-1 strain (cell culture-adapted HCV [HCVcc]), the mechanisms of particle formation have not been elucidated. Recently, we showed that exogenous expression of a liver-specific microRNA, miR-122, in nonhepatic cell lines facilitates efficient replication but not particle production of HCVcc, suggesting that liver-specific host factors are required for infectious particle formation. In this study, we screened human cancer cell lines for expression of the liver-specific α-fetoprotein by using a cDNA array database and identified liver-derived JHH-4 cells and stomach-derived FU97 cells, which express liver-specific host factors comparable to Huh7 cells. These cell lines permit not only replication of HCV RNA but also particle formation upon infection with HCVcc, suggesting that hepatic differentiation participates in the expression of liver-specific host factors required for HCV propagation. HCV inhibitors targeting host and viral factors exhibited different antiviral efficacies between Huh7 and FU97 cells. Furthermore, FU97 cells exhibited higher susceptibility for propagation of HCVcc derived from the JFH-2 strain than Huh7 cells. These results suggest that hepatic differentiation participates in the expression of liver-specific host factors required for complete propagation of HCV. IMPORTANCE Previous studies have shown that liver-specific host factors are required for efficient replication of HCV RNA and formation of infectious particles. In this study, we screened human cancer cell lines for expression of the liver-specific α-fetoprotein by using a cDNA array database and identified novel permissive cell lines for complete propagation of HCVcc without any artificial manipulation. In particular, gastric cancer-derived FU97 cells exhibited a much higher susceptibility to HCVcc/JFH-2 infection than observed in Huh7 cells, suggesting that FU97 cells would be useful for further investigation of the HCV life cycle, as well as the development of therapeutic agents for chronic hepatitis C.
The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Nuclear Import Pathway and Nuclear Export Signal among Retroviral Rev/Rev-Like Proteins

ABSTRACT The Rev protein is essential for the replication of lentiviruses. Rev is a shuttling protein that transports unspliced and partially spliced lentiviral RNAs from the nucleus to the cytoplasm via the nucleopore. To transport these RNAs, the human immunodeficiency virus type 1 (HIV-1) Rev uses the karyopherin β family importin β and CRM1 proteins that interact with the Rev nuclear localization signal (NLS) and nuclear exportation signal (NES), respectively. Recently, we reported the presence of new types of bipartite NLS and nucleolar localization signal (NoLS) in the bovine immunodeficiency virus (BIV) Rev protein. Here we report the characterization of the nuclear import and export pathways of BIV Rev. By using an in vitro nuclear import assay, we showed that BIV Rev is transported into the nucleus by a cytosolic and energy-dependent importin α/β classical pathway. Results from glutathione S-transferase (GST) pulldown assays that showed the binding of BIV Rev with importins α3 and α5 were in agreement with those from the nuclear import assay. We also identified a leptomycin B-sensitive NES in BIV Rev, which indicates that the protein is exported via CRM1 like HIV-1 Rev. Mutagenesis experiments showed that the BIV Rev NES maps between amino acids 109 to 121 of the protein. Remarkably, the BIV Rev NES was found to be of the cyclic AMP (cAMP)-dependent protein kinase inhibitor (PKI) type instead of the HIV-1 Rev type. In summary, our data showed that the nuclear import mechanism of BIV Rev is novel among Rev proteins characterized so far in lentiviruses.
Interaction and Interdependent Packaging of Tegument Protein UL11 and Glycoprotein E of Herpes Simplex Virus

ABSTRACT The UL11 tegument protein of herpes simplex virus plays a critical role in the secondary envelopment; however, the mechanistic details remain elusive. Here, we report a new function of UL11 in the budding process in which it directs efficient acquisition of glycoprotein E (gE) via a direct interaction. In vitro binding assays showed that the interaction required only the first 28, membrane-proximal residues of the cytoplasmic tail of gE, and the C-terminal 26 residues of UL11. A second, weaker binding site was also found in the N-terminal half of UL11. The significance of the gE-UL11 interaction was subsequently investigated with viral deletion mutants. In the absence of the gE tail, virion packaging of UL11, but not other tegument proteins such as VP22 and VP16, was reduced by at least 80%. Reciprocally, wild-type gE packaging was also drastically reduced by about 87% in the absence of UL11, and this defect could be rescued in trans by expressing UL11 at the UL35 locus. Surprisingly, a mutant that lacks the C-terminal gE-binding site of UL11 packaged nearly normal amounts of gE despite its strong interaction with the gE tail in vitro, indicating that the interaction with the UL11 N terminus may be important. Mutagenesis studies of the UL11 N terminus revealed that the association of UL11 with membrane was not required for this function. In contrast, the UL11 acidic cluster motif was found to be critical for gE packaging and was not replaceable with foreign acidic clusters. Together, these results highlight an important role of UL11 in the acquisition of glycoprotein-enriched lipid bilayers, and the findings may also have important implications for the role of UL11 in gE-mediated cell-to-cell spread.
Identification of Autographa californica Nucleopolyhedrovirus ac93 as a Core Gene and Its Requirement for Intranuclear Microvesicle Formation and Nuclear Egress of Nucleocapsids

ABSTRACT Autographa californica nucleopolyhedrovirus (AcMNPV) orf93 (ac93) is a highly conserved uncharacterized gene that is found in all of the sequenced baculovirus genomes except for Culex nigripalpus NPV. In this report, using bioinformatics analyses, ac93 and odv-e25 (ac94) were identified as baculovirus core genes and thus p33-ac93-odv-e25 represent a cluster of core genes. To investigate the role of ac93 in the baculovirus life cycle, an ac93 knockout AcMNPV bacmid was constructed via homologous recombination in Escherichia coli. Fluorescence and light microscopy showed that the AcMNPV ac93 knockout did not spread by infection, and titration assays confirmed a defect in budded virus (BV) production. However, deletion of ac93 did not affect viral DNA replication. Electron microscopy indicated that ac93 was required for the egress of nucleocapsids from the nucleus and the formation of intranuclear microvesicles, which are precursor structures of occlusion-derived virus (ODV) envelopes. Immunofluorescence analyses showed that Ac93 was concentrated toward the cytoplasmic membrane in the cytoplasm and in the nuclear ring zone in the nucleus. Western blot analyses showed that Ac93 was associated with both nucleocapsid and envelope fractions of BV, but only the nucleocapsid fraction of ODV. Our results suggest that ac93, although not previously recognized as a core gene, is one that plays an essential role in the formation of the ODV envelope and the egress of nucleocapsids from the nucleus.
Gamma Interferon and Perforin Control the Strength, but Not the Hierarchy, of Immunodominance of an Antiviral CD8+ T Cell Response

ABSTRACT The two major antiviral effector mechanisms of CD8+ T cells are thought to be perforin (Prf)-mediated cell lysis and gamma interferon (IFN-γ)-mediated induction of an antiviral state. By affecting the expression of proteins involved in antigen presentation, IFN-γ is also thought to shape the magnitude and specificity of the CD8+ T cell response. Here we studied the roles of Prf and IFN-γ in shaping the effector and memory CD8+ T cell responses to vaccinia virus (VACV). IFN-γ deficiency resulted in increased numbers of anti-VACV effector and memory CD8+ T cells, which were partly dependent on increased virus loads. On the other hand, Prf-deficient mice showed an increase in the number of VACV-specific CD8+ T cells only in the memory phase. Treatment of the mice with the antiviral drug cidofovir reduced the numbers of effector and memory cells closer to wild-type levels in IFN-γ-deficient mice and reduced the numbers of memory CD8+ T cells to wild-type levels in Prf-deficient mice. These data suggest that virus loads are the main reason for the increased strength of the CD8 response in IFN-γ- and Prf-deficient mice. Neither Prf deficiency nor IFN-γ deficiency had an effect on the immunodominance hierarchy of five Kb-restricted CD8+ T cell determinants either during acute infection or after recovery. Thus, our work shows that CD8+ T cell immunodominance during VACV infection is not affected by the effects of IFN-γ on the antigen presentation machinery.
Robust Transceiver Design for Two-User MIMO Interference Channel With Simultaneous Wireless Information and Power Transfer

For two-user multiple-input-multiple-output interference channels with simultaneous wireless information and power transfer, we investigate robust transceiver design problem where channel uncertainties are modeled by worst case model. Our objective is to minimize worst case sum mean square error under individual transmit power constraints and worst case energy harvesting (EH) constraints. We propose to transform the quadratic EH constraints into linear matrix inequalities combined with two equality constraints. Furthermore, we propose to employ an algorithm based on constrained concave-convex procedure to alternatively optimize precoding matrices and postprocessing matrices. Simulation results demonstrate that our proposed robust transceiver design has significant performance gain over the nonrobust one.
Fixation of Oligosaccharides to a Surface May Increase the Susceptibility to Human Parainfluenza Virus 1, 2, or 3 Hemagglutinin-Neuraminidase

ABSTRACT The hemagglutinin-neuraminidase (HN) protein of human parainfluenza viruses (hPIVs) both binds (H) and cleaves (N) oligosaccharides that contain N-acetylneuraminic acid (Neu5Ac). H is thought to correspond to receptor binding and N to receptor-destroying activity. At present, N′s role in infection remains unclear: does it destroy only receptors, or are there other targets? We previously demonstrated that hPIV1 and 3 HNs bind to oligosaccharides containing the motif Neu5Acα2-3Galβ1-4GlcNAc (M. Amonsen, D. F. Smith, R. D. Cummings, and G. M. Air, J. Virol. 81:8341–8345, 2007). In the present study, we tested the binding specificity of hPIV2 on the Consortium for Functional Glycomics' glycan array and found that hPIV2 binds to oligosaccharides containing the same motif. We determined the specificities of N on red blood cells, soluble small-molecule and glycoprotein substrates, and the glycan array and compared them to the specificities of H. hPIV2 and -3, but not hPIV1, cleaved their ligands on red blood cells. hPIV1, -2, and -3 cleaved their NeuAcα2-3 ligands on the glycan array; hPIV2 and -3 also cleaved NeuAcα2-6 ligands bound by influenza A virus. While all three HNs exhibited similar affinities for all cleavable soluble substrates, their activities were 5- to 10-fold higher on small molecules than on glycoproteins. In addition, some soluble glycoproteins were not cleaved, despite containing oligosaccharides that were cleaved on the glycan array. We conclude that the susceptibility of an oligosaccharide substrate to N increases when the substrate is fixed to a surface. These findings suggest that HN may undergo a conformational change that activates N upon receptor binding at a cell surface.
Quetiapine versus aripiprazole in the management of schizophrenia

Objectives: Current evidence supports the use of various second-generation antipsychotics for pharmacotherapy of schizophrenia. While in a systematic review, generally no difference in efficacy was found between atypical antipsychotics, other studies have found quetiapine less effective than aripiprazole. This article reviews the efficacy and tolerability of aripiprazole versus quetiapine in the context of recommended management strategies for schizophrenia. Method: Fifty female inpatients, meeting the diagnosis of schizophrenia, were randomly entered into two groups (n = 25 in each group) to participate in a 12-week, double-blind study for random assignment to quetiapine or aripiprazole. The primary outcome measures were Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms. The schedule for Assessment of Insight (SAI), Clinical Global Impressions Severity Scale (CGI-S) and the Simpson Angus Scale (SAS) were also used as secondary measures. Results: Both quetiapine and aripiprazole showed significant effectiveness in the improvement of positive symptoms. The effectiveness for negative symptoms was also noteworthy with both drugs, although not to a significant level during this study. In addition, significant improvement was found on assessment with CGI-S and SAI for quetiapine and aripiprazole. SAS did not show any important increment in extrapyramidal side effects at the end of the examination. Conclusion: According to the findings, quetiapine and aripiprazole had similar effectiveness and tolerability with respect to management of schizophrenia.
Improvement of nonsuicidal self-injury following treatment with antipsychotics possessing strong D1 antagonistic activity: evidence from a report of three cases

Introduction: There is no drug treatment for nonsuicidal self-injury (NSSI), a highly prevalent and burdensome symptom of several psychiatric diseases like posttraumatic stress disorder (PTSD), personality disorders, and major depression (MD). Methods: Here, we present a retrospective series of three patients demonstrating a persistent remission in MD-associated NSSI in response to treatment with antipsychotics possessing marked D1 receptor antagonistic activity. Results: To the best of the authors’ knowledge, the case series presented is only the second clinical paper suggesting a role for D1 antagonists in NSSI drug therapy. Conclusions: Together with previously published data from rodent models, the findings suggest a role for D1 antagonists in NSSI drug therapy and hence for the D1 receptor in NSSI pathogenesis. This conclusion is limited by the facts that the patients presented here received polypharmacy and that the D1 receptor antagonistic antipsychotics suggested here as effective ‘anti-auto-aggressants’ do not address D1 receptors only but multiple neurotransmitter receptors/systems.
A Semiblind Tracking Algorithm for Joint Communication and Ranging With OFDM Signals

Range-based positioning by estimating the time of arrival (ToA) of the line-of-sight (LoS) path using orthogonal frequency-division multiplexing (OFDM) signals has gained remarkable attention. Multipath propagation significantly influences the ToA estimate, resulting in position errors. To mitigate these errors, the multipath channel needs to be accurately estimated, usually with a large number of known pilot symbols. A tradeoff between the data rate and the multipath channel estimation performance must be made for joint communication and positioning applications. This paper proposes a semiblind range tracking algorithm, which allows the reduction of the required number of pilot symbols significantly. For moving receivers, the algorithm needs, only in the beginning, an OFDM symbol with known pilot symbols, which increases the data rate dramatically. Instead of tracking the complex amplitude of individual subcarriers, the proposed algorithm directly tracks the multipath channel parameters, including the complex amplitude, delay, and angle of arrival (AoA) of individual multipath components. The estimated delay of the first arrived path, i.e., its ToA, is used to calculate the range between the transmitter and receiver antennas. Evaluations of the algorithm are provided by simulations in an artificial scenario and using channel sounder measurement data. The results show that the proposed tracking algorithm can effectively track the range between transmitter and receiver and detect the data.
Durable Protection from Vaginal Simian-Human Immunodeficiency Virus Infection in Macaques by Tenofovir Gel and Its Relationship to Drug Levels in Tissue

ABSTRACT A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/106 cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC95), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC95 in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.
Longitudinal change in pulmonary arterial capacitance as an indicator of prognosis and response to therapy and in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a chronic progressive disease that leads to right heart failure and death. Pulmonary arterial capacitance (PAC), defined as stroke volume divided by the pulmonary pulse pressure, has been identified as a prognostic factor in PAH. The impact of changes in PAC over time, however, is unclear. We evaluated changes in PAC over time to determine if such changes predicted transplant-free survival. A single-center retrospective study of consecutive group 1 PAH patients who had two or more right heart catheterizations (RHC) between January 2007 and June 2016 was undertaken. Hemodynamic data, clinical data, and outcomes were collected. Univariate and multivariate Cox proportional-hazards modelling to identify the contribution of risk factors for a composite outcome of death or lung transplantation was done. Mixed-effects logistic regression was performed to investigate the association between the change in PAC value over time and the composite outcome. A P value < 0.05 was considered significant. In total, 109 consecutive patients with a total of 300 RHC data were identified. PAC correlated inversely with functional status (P < 0.001) and inversely with pulmonary vascular resistance (P < 0.001). PAC values increased with the addition of new PAH-specific medications. Mixed effects logistic regression modeling using longitudinal data showed that a decrease in PAC over the study period was associated with increased mortality and transplantation (adjusted P = 0.039) over the study period. Change in PAC was a better predictor of outcome over the study period than baseline PAC or changes in other hemodynamic or clinical parameters. Decreases in PAC were predictive of increased mortality or transplantation in patients with group 1 PAH. There was a trend towards increased PAC in response to the addition of a PAH-specific medication. Our data support the use of PAC as a therapeutic target in PAH.
Validity of algorithm for estimating left sided filling pressures on echocardiography in a population referred for pulmonary arterial hypertension

The determination of LV filling pressure is integral to the diagnosis of pulmonary arterial hypertension (PAH). The American Society of Echocardiography (ASE) has devised algorithms for their estimation. We aimed to test these algorithms in a population referred for suspected PAH. In our retrospective study, we evaluated the accuracy of the ASE Algorithms compared to right heart catheterization done within three months, in patients seen during 2006–2014. All echocardiograms were classified as showing normal, elevated or indeterminate filling pressures. Those with indeterminate pressures were excluded. We evaluated the diagnostic properties of this algorithm to predict a pulmonary artery wedge pressure (PAWP) and left ventricular end diastolic pressure (LVEDP) >15 mmHg. A total of 94 patients were included. The ASE algorithms yielded indeterminate results in 50 (53.2%) patients. This occurred more commonly in older patients and patients with cardiovascular comorbidities. The algorithm had a high sensitivity for predicting an elevated PAWP at 89.5% (95% confidence interval [CI] = 66.9–98.7) and an elevated LVEDP at 100% (95% CI = 76.8–100). The algorithm had a negative predictive value of 81.8% and 100% for predicting an elevated PAWP (95% CI = 52.4–94.8) and LVEDP, respectively, but a poor positive predictive value. The ASE algorithm for predicting LV filling pressures often cannot be applied in populations with suspected PAH. When they are interpretable, they have a high negative predictive value for elevated PAWP and LVEDP. We recommend caution when using these algorithms in populations with suspected PAH.
Image classification based on the bagging-adaboost ensemble

In order to enable more effective image retrieval via keywords, automatic image annotation and categorization becomes an important problem in computer vision and content based image retrieval. Unfortunately, there exists a semantic gap between the low-level feature vectors and the high-level semantics or concepts. In this paper, we design a basic concept repertory to bridge this semantic gap. Specifically, a basic concept repertory, in the form of a dictionary, is first designed to store a set of classifiers, with each of these representing a concept and a set of rules which is used to distinguish concepts with similar characteristics. We propose a new classifier based on our proposed bagging-adaboosting ensemble (BAE) approach. The experiments demonstrate the good performance of our approaches.