Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-Dimensional Architecture of Tick-Borne Encephalitis Virus Replication Sites and Trafficking of the Replicated RNA

ABSTRACT Flavivirus replication is accompanied by the rearrangement of cellular membranes that may facilitate viral genome replication and protect viral components from host cell responses. The topological organization of viral replication sites and the fate of replicated viral RNA are not fully understood. We exploited electron microscopy to map the organization of tick-borne encephalitis virus (TBEV) replication compartments in infected cells and in cells transfected with a replicon. Under both conditions, 80-nm vesicles were seen within the lumen of the endoplasmic reticulum (ER) that in infected cells also contained virions. By electron tomography, the vesicles appeared as invaginations of the ER membrane, displaying a pore that could enable release of newly synthesized viral RNA into the cytoplasm. To track the fate of TBEV RNA, we took advantage of our recently developed method of viral RNA fluorescent tagging for live-cell imaging combined with bleaching techniques. TBEV RNA was found outside virus-induced vesicles either associated to ER membranes or free to move within a defined area of juxtaposed ER cisternae. From our results, we propose a biologically relevant model of the possible topological organization of flavivirus replication compartments composed of replication vesicles and a confined extravesicular space where replicated viral RNA is retained. Hence, TBEV modifies the ER membrane architecture to provide a protected environment for viral replication and for the maintenance of newly replicated RNA available for subsequent steps of the virus life cycle.
Drive Cycle Analysis of a Permanent-Magnet Traction Motor Based on Magnetostatic Finite-Element Analysis

This paper introduces a method for the drive cycle performance analysis of a permanent-magnet traction motor based on a fast magnetostatic finite-element analysis (FEA). The flux linkage and torque behavior of the permanent-magnet synchronous machine is studied by a nonlinear magnetostatic FEA as a function of direct- and quadrature-axis stator current components. In the analytical machine performance analysis, the current combinations producing the desired torque and minimizing the losses are determined. The iron loss is calculated with the time-transient FEA at no load. The maximum stator flux linkage, limited by the battery voltage, is taken into account. The drive cycle analysis, based on optimal current component surfaces, is carried out for a traction motor of an electric sports car. The results are compared with values measured for the drive cycle on a racetrack.
Anti-APOBEC3G Activity of HIV-1 Vif Protein Is Attenuated in Elite Controllers

ABSTRACT HIV-1-infected individuals who control viremia to below the limit of detection without antiviral therapy have been termed elite controllers (EC). Functional attenuation of some HIV-1 proteins has been reported in EC. The HIV-1 accessory protein Vif (virion infectivity factor) enhances viral infectivity through anti-retroviral factor apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) degradation; however, little is known regarding Vif function in EC. Here, the anti-APOBEC3G activities of clonal, plasma HIV RNA-derived Vif sequences from 46 EC, 46 noncontrollers (NC), and 44 individuals with acute infection (AI) were compared. Vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped viruses were generated by cotransfecting 293T cells with expression plasmids encoding patient-derived Vif, human APOBEC3G, VSV-G, and a vif/env-deficient luciferase-reporter HIV-1 proviral DNA clone. Viral stocks were used to infect 293T cells, and Vif anti-APOBEC3G activity was quantified in terms of luciferase signal. On average, the anti-APOBEC3G activities of EC-derived Vif sequences (median log10 relative light units [RLU], 4.54 [interquartile range {IQR}, 4.30 to 4.66]) were significantly lower than those of sequences derived from NC (4.75 [4.60 to 4.92], P < 0.0001) and AI (4.74 [4.62 to 4.94], P < 0.0001). Reduced Vif activities were not associated with particular HLA class I alleles expressed by the host. Vif functional motifs were highly conserved in all patient groups. No single viral polymorphism could explain the reduced anti-APOBEC3G activity of EC-derived Vif, suggesting that various combinations of minor polymorphisms may underlie these effects. These results further support the idea of relative attenuation of viral protein function in EC-derived HIV sequences. IMPORTANCE HIV-1 elite controllers (EC) are rare individuals who are able to control plasma viremia to undetectable levels without antiretroviral therapy. Understanding the pathogenesis and mechanisms underpinning this rare phenotype may provide important insights for HIV vaccine design. The EC phenotype is associated with beneficial host immunogenetic factors (such as HLA-B*57) as well as with functions of attenuated viral proteins (e.g., Gag, Pol, and Nef). In this study, we demonstrated that HIV-1 Vif sequences isolated from EC display relative impairments in their ability to counteract the APOBEC3G host restriction factor compared to Vif sequences from normal progressors and acutely infected individuals. This result extends the growing body of evidence demonstrating attenuated HIV-1 protein function in EC and, in particular, supports the idea of the relevance of viral factors in contributing to this rare HIV-1 phenotype.
Performance Analysis of a Generalized and Autonomous DRX Scheme

A generalized and autonomous discontinuous reception (DRX) scheme, which is applicable to both Third-Generation Partnership Project (3GPP) and IEEE 802.16e standards, is analyzed by two-level Markov chain modeling, along with the European Telecommunications Standards Institute (ETSI) packet traffic model. Numerical analysis showed that this scheme is capable of autonomously adjusting the DRX cycle to keep up with changing user equipment activity level with no signaling overhead increase, thus producing a better tuned DRX operation. Quantitative comparison with the power-saving schemes of 3GPP and 802.16e standards demonstrated that the autonomous DRX scheme is advantageous over these power-saving schemes.
Style Manual for Biological Journals

The Technical Writer, An Aid to the Presentation and Production of Technical Literature. J. W. Godfrey, F.S. R.A. , Editor, Technical Instructor, B.B.C., and G. Parr, M.I.E.E. , Director, Chapman & Hall, Ltd. Price, not stated. Pp. 340, with many illustrations. Chapman & Hall, Ltd., 37 Essex St., London, W.C. 2, England, 1959. There seems to be no end of books written about writing. The main trouble is that the people who need them never study them, and the people who may work hard over them probably don't need them or not very much. No one has ever figured out a way of correcting this problem of maldistribution. In an effort to standardize correct style, form, format, abbreviations, indexing, references, and the like, a Committee on Form and Style of the Conference of Biological Editors under the chairmanship of J. Roger Porter have gotten together a first-rate book on the style and mechanics
High-risk prescribing and monitoring in primary care: how common is it, and how can it be improved?

The safety of medication use in primary care is an area of increasing concern for health systems internationally. Systematic reviews estimate that 3–4% of all unplanned hospital admissions are due to preventable drug-related morbidity, the majority of which have been attributed to shortcomings in the prescribing and monitoring stages of the medication use process. We define high-risk prescribing as medication prescription by professionals, for which there is evidence of significant risk of harm to patients, and which should therefore either be avoided or (if avoidance is not possible) closely monitored and regularly reviewed for continued appropriateness. Although prevalence estimates vary depending on the instrument used, cross-sectional studies conducted in primary care equivocally show that it is common and there is evidence that it can be reduced. Quality improvement strategies, such as clinical decision support, performance feedback and pharmacist-led interventions have been shown to be effective in reducing prescribing outcomes but evidence of improved patient outcomes remains limited. The increasing implementation of electronic medical records in primary care offer new opportunities to combine different strategies to improve medication safety in primary care and to integrate services provided by different stakeholders. In this review article, we describe the spectrum of high-risk medication use in primary care, review approaches to its measurement and summarize research into its prevalence. Based on previously developed interventions to change professional practice, we propose a systematic approach to improve the safety of medication use in primary care and highlight areas for future research.
Routine deprescribing of chronic medications to combat polypharmacy

The positive benefit–risk ratio of most drugs is decreasing in correlation to very old age, the extent of comorbidity, dementia, frailty and limited life expectancy (VOCODFLEX). First, we review the extent of inappropriate medication use and polypharmacy (IMUP) globally and highlight its negative medical, nursing, social and economic consequences. Second, we expose the main clinical/practical and perceptual obstacles that combine to create the negative vicious circle that eventually makes us feel frustrated and hopeless in treating VOCODFLEX in general, and in our ‘war against IMUP’ in particular. Third, we summarize the main international approaches/methods suggested and tried in different countries in an attempt to improve the ominous clinical and economic outcomes of IMUP; these include a variety of clinical, pharmacological, computer-assisted and educational programs. Lastly, we suggest a new comprehensive perception for providing good medical practice to VOCODFLEX in the 21st century. This includes new principles for research, education and clinical practice guidelines completely different from the ‘single disease model’ research and clinical rules we were raised upon and somehow ‘fanatically’ adopted in the 20th century. This new perception, based on palliative, geriatric and ethical principle, may provide fresh tools for treating VOCODFLEX in general and reducing IMUP in particular.
Antibody-Mediated Enhancement of HIV-1 and HIV-2 Production from BST-2/Tetherin-Positive Cells

ABSTRACT BST-2/CD317/HM1.24/tetherin is a B-cell antigen overexpressed on the surface of myeloma cell lines and on neoplastic plasma cells of patients with multiple myeloma. Antibodies to BST-2 are in clinical trial for the treatment of multiple myeloma and are considered for the treatment of solid tumors with high BST-2 antigen levels. Functionally, BST-2 restricts the secretion of retroviruses, including human immunodeficiency virus type 1, as well as members of the herpesvirus, filovirus, and arenavirus families, presumably by tethering nascent virions to the cell surface. Here we report that BST-2 antibody treatment facilitates virus release from BST-2+ cells by interfering with the tethering activity of BST-2. BST-2 antibodies were unable to release already tethered virions and were most effective when added early during virus production. BST-2 antibody treatment did not affect BST-2 dimerization and did not reduce the cell surface expression of BST-2. Interestingly, BST-2 antibody treatment reduced the nonspecific shedding of BST-2 and limited the encapsidation of BST-2 into virions. Finally, flotation analyses indicate that BST-2 antibodies affect the distribution of BST-2 within membrane rafts. Our data suggest that BST-2 antibody treatment may enhance virus release by inducing a redistribution of BST-2 at the cell surface, thus preventing it from accumulating at the sites of virus budding.
Macromolecular Assembly-Driven Processing of the 2/3 Cleavage Site in the Alphavirus Replicase Polyprotein

ABSTRACT Semliki Forest virus (SFV) is a member of the Alphavirus genus, which produces its replicase proteins in the form of a nonstructural (ns) polyprotein precursor P1234. The maturation of the replicase occurs in a temporally controlled manner by protease activity of nsP2. The template preference and enzymatic capabilities of the alphaviral replication complex have a very important connection with its composition, which is irreversibly altered by proteolysis. The final cleavage of the 2/3 site in the ns polyprotein apparently leads to significant rearrangements within the replication complex and thus denotes the “point of no return” for viral replication progression. Numerous studies have devised rules for when and how ns protease acts, but how the alphaviral 2/3 site is recognized remained largely unexplained. In contrast to the other two cleavage sites within the ns polyprotein, the 2/3 site evidently lacks primary sequence elements in the vicinity of the scissile bond sufficient for specific protease recognition. In this study, we sought to investigate the molecular details of the regulation of the 2/3 site processing in the SFV ns polyprotein. We present evidence that correct macromolecular assembly, presumably strengthened by exosite interactions rather than the functionality of the individual nsP2 protease, is the driving force for specific substrate targeting. We conclude that structural elements within the macrodomain of nsP3 are used for precise positioning of a substrate recognition sequence at the catalytic center of the protease and that this process is coordinated by the exact N-terminal end of nsP2, thus representing a unique regulation mechanism used by alphaviruses.
Idiopathic Normal Pressure Hydrocephalus: Update and Practical Approach on Diagnosis and Management

The syndrome of idiopathic normal pressure hydrocephalus was first described in 1965, but 45 years later controversies still exist with regard to its cause, progression, differential diagnosis, and best treatment strategies. Its incidence may be underestimated and its importance increasing because of the aging population. The authors review current literature and offer an update on contemporary knowledge as well as a practical approach to diagnosis and management of the condition for the neurologists and neurosurgeons who encounter such patients.
Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review

Background: Nonadherence to medication is a recognized problem and may be the most challenging aspect of treatment. Methods: We performed a systematic review of factors that influence adherence and the consequences of nonadherence to the patient, healthcare system and society, in patients with schizophrenia. Particular attention was given to the effect of nonadherence on hospitalization rates, as a key driver of increased costs of care. A qualitative systematic literature review was conducted using a broad search strategy using disease and adherence terms. Due to the large number of abstracts identified, article selection was based on studies with larger sample sizes published after 2001. Thirty-seven full papers were included: 15 studies on drivers and 22 on consequences, of which 12 assessed the link between nonadherence and hospitalization. Results: Key drivers of nonadherence included lack of insight, medication beliefs and substance abuse. Key consequences of nonadherence included greater risk of relapse, hospitalization and suicide. Factors positively related to adherence were a good therapeutic relationship with physician and perception of benefits of medication. The most frequently reported driver and consequence were lack of insight and greater risk of hospitalization respectively. Conclusions: Improving adherence in schizophrenia may have a considerable positive impact on patients and society. This can be achieved by focusing on the identified multitude of factors driving nonadherence.
The Histone Deacetylase Inhibitor Valproic Acid Lessens NK Cell Action against Oncolytic Virus-Infected Glioblastoma Cells by Inhibition of STAT5/T-BET Signaling and Generation of Gamma Interferon

ABSTRACT Tumor virotherapy has been and continues to be used in clinical trials. One barrier to effective viral oncolysis, consisting of the interferon (IFN) response induced by viral infection, is inhibited by valproic acid (VPA) and other histone deacetylase inhibitors (HDACi). Innate immune cell recruitment and activation have been shown to be deleterious to the efficacy of oncolytic herpes simplex virus (oHSV) infection, and in this report we demonstrate that VPA limits this deleterious response. VPA, administered prior to oHSV inoculation in an orthotopic glioblastoma mouse model, resulted in a decline in NK and macrophage recruitment into tumor-bearing brains at 6 and 24 h post-oHSV infection. Interestingly, there was a robust rebound of recruitment of these cells at 72 h post-oHSV infection. The observed initial decline in immune cell recruitment was accompanied by a reduction in their activation status. VPA was also found to have a profound immunosuppressive effect on human NK cells in vitro. NK cytotoxicity was abrogated following exposure to VPA, consistent with downmodulation of cytotoxic gene expression of granzyme B and perforin at the mRNA and protein levels. In addition, suppression of gamma IFN (IFN-γ) production by VPA was associated with decreased STAT5 phosphorylation and dampened T-BET expression. Despite VPA-mediated immune suppression, mice were not at significantly increased risk for HSV encephalitis. These findings indicate that one of the avenues by which VPA enhances oHSV efficacy is through initial suppression of immune cell recruitment and inhibition of inflammatory cell pathways within NK cells.
Bit Depth Scalable Coding

In this paper, we propose an AVC compliant bit depth scalable coding solution based on MacroBlock level inter-layer prediction. This proposed coding solution is based on the current SVC platform and new decoding processes for bit depth upsampling are introduced. The proposed codec can give an 8-bit AVC main profile or high profile base layer coded bit-stream multiplexed with a high bit enhancement layer coded bit-stream generated by MacroBlock level inter-layer prediction and rate-distortion optimization. Compatibility to other types of scalability that are supported in current SVC standard is supported in our solution. The proposed bit depth scalable coding is implemented based on the up-to-date SVC reference software (JSVM7.12). Comparison results show that the proposed bit depth scalable coding outperforms simulcast by on average 5.2 dB for 8-bit to 10-bit scalability with the enhancement layer bitstream covering approximately 40% of the whole bitstream.
Inhibition of Latent Membrane Protein 1 Impairs the Growth and Tumorigenesis of Latency II Epstein-Barr Virus-Transformed T Cells

ABSTRACT Epstein-Barr virus (EBV) is a common human herpesvirus. Infection with EBV is associated with several human malignancies in which the virus expresses a set of latent proteins, among which is latent membrane protein 1 (LMP1). LMP1 is able to transform numerous cell types and is considered the main oncogenic protein of EBV. The mechanism of action is based on mimicry of activated members of the tumor necrosis factor (TNF) receptor superfamily, through the ability of LMP1 to bind similar adapters and to activate signaling pathways. We previously generated two unique models: a monocytic cell line and a lymphocytic (NC5) cell line immortalized by EBV that expresses the type II latency program. Here we generated LMP1 dominant negative forms (DNs), based on fusion between green fluorescent protein (GFP) and transformation effector site 1 (TES1) or TES2 of LMP1. Then we generated cell lines conditionally expressing these DNs. These DNs inhibit NF-κB and Akt pathways, resulting in the impairment of survival processes and increased apoptosis in these cell lines. This proapoptotic effect is due to reduced interaction of LMP1 with specific adapters and the recruitment of these adapters to DNs, which enable the generation of an apoptotic complex involving TRADD, FADD, and caspase 8. Similar results were obtained with cell lines displaying a latency III program in which LMP1-DNs decrease cell viability. Finally, we prove that synthetic peptides display similar inhibitory effects in EBV-infected cells. DNs derived from LMP1 could be used to develop therapeutic approaches for malignant diseases associated with EBV.
Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension

Few studies have examined the utility of serial echocardiography in the evaluation, management, and prognosis of patients with pulmonary arterial hypertension (PAH). Therefore, we sought to evaluate the prognostic significance of follow-up tricuspid annular plane systolic excursion (TAPSE) in PAH. We prospectively studied 70 consecutive patients with PAH who underwent baseline right heart catheterization (RHC) and transthoracic echocardiogram, who survived to follow-up echocardiogram after initiation of PAH therapy. Baseline TAPSE was 1.6 ± 0.5 cm which increased to 2.0 ± 0.4 cm on follow-up (P < 0.0001). The cohort was dichotomized by TAPSE at one-year follow-up: Group 1 (n = 37): follow-up TAPSE ≥ 2 cm; Group 2 (n = 33): follow-up TAPSE < 2 cm. Group 1 participants were significantly more likely to reach WHO functional class I–II status and achieve a higher six-minute walk distance on follow-up. Of the 68 patients who survived more than one year, 18 died (26.5%) over a median follow-up of 941 days (range, 3–2311 days), with significantly higher mortality in Group 2 versus Group 1 (41.9% vs. 13.5%; P = 0.003). While baseline TAPSE stratified at 2 cm did not predict survival in this cohort, TAPSE ≥ 2 cm at follow-up strongly predicted survival in bivariable models (hazard ratio, 0.21; 95% confidence interval, 0.08–0.60). In conclusion, follow-up TAPSE ≥ 2 cm is a prognostic marker and potential treatment target in a PAH population.
A Game-Based Mechanism for Avoiding Routing Hotspot in P2P Streaming Distribution

Today's P2P streaming application periodically suffers from routing hotspots, a.k. a. , flash crowds. A routing hotspot is typically created by an unanticipated new event that triggers an unanticipated surge of users which request streaming from some particular peers, temporarily overwhelming the peer's delivery capabilities. In this paper, we consider how to avoid the routing hotspot prior to a congestion event. Assume that the price for usage of each node is proportional to the congestion level at the node, we propose an incentive compatible pricing mechanism. It is shown that the users can enforce any operating point it deems efficient and avoid hotspot by offering the capacity of the various nodes at weight prices. The incentive compatible weight vector is shown to be unique to the extent of a multiplicative constant, and its structure is specified explicitly. In order to apply this mechanism in very-large-scale P2P streaming network, we propose an adaptive algorithm for distributed computation of the incentive compatible discount vector. The simulation results show that the incentive compatible pricing mechanism can avoid the routing hotspot efficiently.