Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcription of Subgenomic mRNA of Hepatitis Delta Virus Requires a Modified Hepatitis Delta Antigen That Is Distinct from Antigenomic RNA Synthesis

ABSTRACT Hepatitis delta virus (HDV) contains a viroid-like, 1.7-kb circular RNA genome, which replicates via a double-rolling-circle model. However, the exact mechanism involved in HDV genome RNA replication and subgenomic mRNA transcription is still unclear. Our previous studies have shown that the replications of genomic and antigenomic HDV RNA strands have different sensitivities to α-amanitin and are associated with different nuclear bodies, suggesting that these two strands are synthesized in different transcription machineries in the cells. In this study, we developed a unique quantitative reverse transcription-PCR (qRT-PCR) procedure for detection of various HDV RNA species from an RNA transfection system. Using this qRT-PCR procedure and a series of HDV mutants, we demonstrated that Arg-13 methylation, Lys-72 acetylation, and Ser-177 phosphorylation of small hepatitis delta antigen (S-HDAg) are important for HDV mRNA transcription. In addition, these three S-HDAg modifications are dispensable for antigenomic RNA synthesis but are required for genomic RNA synthesis. Furthermore, the three RNA species had different sensitivities to acetylation and deacetylation inhibitors, showing that the metabolic requirements for the synthesis of HDV antigenomic RNA are different from those for the synthesis of genomic RNA and mRNA. In sum, our data support the hypothesis that the cellular machinery involved in the synthesis of HDV antigenomic RNA is different from that of genomic RNA synthesis and mRNA transcription, even though the antigenomic RNA and the mRNA are made from the same RNA template. We propose that acetylation and deacetylation of HDAg may provide a molecular switch for the synthesis of the different HDV RNA species.
Lymphocytic Choriomeningitis Virus Infection Yields Overlapping CD4+ and CD8+ T-Cell Responses

ABSTRACT Activation of CD4+ T cells helps establish and sustain other immune responses. We have previously shown that responses against a broad set of nine CD4+ T-cell epitopes were present in the setting of lymphocytic choriomeningitis virus (LCMV) Armstrong infection in the context of H-2d. This is quite disparate to the H-2b setting, where only two epitopes have been identified. We were interested in determining whether a broad set of responses was unique to H-2d or whether additional CD4+ T-cell epitopes could be identified in the setting of the H-2b background. To pursue this question, we infected C57BL/6 mice with LCMV Armstrong and determined the repertoire of CD4+ T-cell responses using overlapping 15-mer peptides corresponding to the LCMV Armstrong sequence. We confirmed positive responses by intracellular cytokine staining and major histocompatibility complex (MHC)-peptide binding assays. A broad repertoire of responses was identified, consisting of six epitopes. These epitopes originate from the nucleoprotein (NP) and glycoprotein (GP). Out of the six newly identified CD4+ epitopes, four of them also stimulate CD8+ T cells in a statistically significant manner. Furthermore, we assessed these CD4+ T-cell responses during the memory phase of LCMV Armstrong infection and after infection with a chronic strain of LCMV and determined that a subset of the responses could be detected under these different conditions. This is the first example of a broad repertoire of shared epitopes between CD4+ and CD8+ T cells in the context of viral infection. These findings demonstrate that immunodominance is a complex phenomenon in the context of helper responses.
M94 Is Essential for the Secondary Envelopment of Murine Cytomegalovirus

ABSTRACT The gene M94 of murine cytomegalovirus (MCMV) as well as its homologues UL16 in alphaherpesviruses is involved in viral morphogenesis. For a better understanding of its role in the viral life cycle, a library of random M94 mutants was generated by modified transposon-based linker scanning mutagenesis. A comprehensive set of M94 mutants was reinserted into the MCMV genome and tested for their capacity to complement the M94 null mutant. Thereby, 34 loss-of-function mutants of M94 were identified, which were tested in a second screen for their capacity to inhibit virus replication. This analysis identified two N-terminal insertion mutants of M94 with a dominant negative effect. We compared phenotypes induced by the conditional expression of these dominant negative M94 alleles with the null phenotype of the M94 deletion. The viral gene expression cascade and the nuclear morphogenesis steps were not affected in either setting. In both cases, however, secondary envelopment did not proceed in the absence of functional M94, and capsids subsequently accumulated in the center of the cytoplasmic assembly complex. In addition, deletion of M94 resulted in a block of cell-to-cell spread. Moreover, the dominant negative mutant of M94 demonstrated a defect in interacting with M99, the UL11 homologue of MCMV.
Adapting the Right Measures for Pattern Discovery : A Unified View

This paper presents a unified view of interestingness measures for interesting pattern discovery. Specifically, we first provide three necessary conditions for interestingness measures being used for association pattern discovery. Then, we reveal one desirable property for interestingness measures: the supportascending conditional antimonotone property (SA-CAMP). Along this line, we prove that the measures possessing SA-CAMP are suitable for pattern discovery if the itemset-traversal structure is defined by a support-ascending set enumeration tree. In addition, we provide a thorough study on the family of the generalized mean (GM) measure and show their appealing properties, which are exploited for developing the GMiner algorithm for finding interesting association patterns. Finally, experimental results show that GMiner can efficiently identify interesting patterns based on SA-CAMP of the GM measure, even at an extremely low level of support.
Central venous catheter dressing durability: an evaluation

Background: Skin organisms at the insertion site are frequently implicated in central venous catheter blood stream infections (CVC BSIs) yet few studies have compared the durability of CVC dressings in critically ill patients. Aims: To undertake an evaluation of the durability and associated costs of different CVC dressings. Methods: Dressing duration was captured prospectively using a pro forma on four different dressings on five critical care units over a 12-month period. Staff received training on CVC dressing evidence-based practices and a ‘how to guide’ was implemented. Findings: A total of 1229 CVC dressings were observed from 590 CVCs. One dressing had a median (IQR) duration of 68.5 h (range, 32–105 h) compared to a median duration of 43.5, 46.0 and 40.5 h for the other dressings (P <0.001). The mean time to change a CVC dressing was 13.5 min and the cost of a dressing change was in the range of £1.97–4.97. During the 12-month study period we observed a downward trend in CVC BSIs. Discussion: Despite few dressings remaining adherent for 7 days, the low rates of CVC BSI observed suggests good dressing practices. Conclusions: One dressing appeared more durable than the others, although it was still below the recommended standard and more expensive.
A Genetic Variant of Hepatitis B Virus Divergent from Known Human and Ape Genotypes Isolated from a Japanese Patient and Provisionally Assigned to New Genotype J

ABSTRACT Hepatitis B virus (HBV) of a novel genotype (J) was recovered from an 88-year-old Japanese patient with hepatocellular carcinoma who had a history of residing in Borneo during the World War II. It was divergent from eight human (A to H) and four ape (chimpanzee, gorilla, gibbon, and orangutan) HBV genotypes, as well as from a recently proposed ninth human genotype I, by 9.9 to 16.5% of the entire genomic sequence and did not have evidence of recombination with any of the nine human genotypes and four nonhuman genotypes. Based on a comparison of the entire nucleotide sequence against 1,440 HBV isolates reported, HBV/J was nearest to the gibbon and orangutan genotypes (mean divergences of 10.9 and 10.7%, respectively). Based on a comparison of four open reading frames, HBV/J was closer to gibbon/orangutan genotypes than to human genotypes in the P and large S genes and closest to Australian aboriginal strains (HBV/C4) and orangutan-derived strains in the S gene, whereas it was closer to human than ape genotypes in the C gene. HBV/J shared a deletion of 33 nucleotides at the start of preS1 region with C4 and gibbon genotypes, had an S-gene sequence similar to that of C4, and expressed the ayw subtype. Efficient infection, replication, and antigen expression by HBV/J were experimentally established in two chimeric mice with the liver repopulated for human hepatocytes. The HBV DNA sequence recovered from infected mice was identical to that in the inoculum. Since HBV/J is positioned phylogenetically in between human and ape genotypes, it may help to trace the origin of HBV and merits further epidemiological surveys.
A Hybrid Learning Method for Constructing Compact Rule-Based Fuzzy Models

The Takagi-Sugeno-Kang-type rule-based fuzzy model has found many applications in different fields; a major challenge is, however, to build a compact model with optimized model parameters which leads to satisfactory model performance. To produce a compact model, most existing approaches mainly focus on selecting an appropriate number of fuzzy rules. In contrast, this paper considers not only the selection of fuzzy rules but also the structure of each rule premise and consequent, leading to the development of a novel compact rule-based fuzzy model. Here, each fuzzy rule is associated with two sets of input attributes, in which the first is used for constructing the rule premise and the other is employed in the rule consequent. A new hybrid learning method combining the modified harmony search method with a fast recursive algorithm is hereby proposed to determine the structure and the parameters for the rule premises and consequents. This is a hard mixed-integer nonlinear optimization problem, and the proposed hybrid method solves the problem by employing an embedded framework, leading to a significantly reduced number of model parameters and a small number of fuzzy rules with each being as simple as possible. Results from three examples are presented to demonstrate the compactness (in terms of the number of model parameters and the number of rules) and the performance of the fuzzy models obtained by the proposed hybrid learning method, in comparison with other techniques from the literature.
Apolipoprotein e gene polymorphism as a risk factor for ischemic cerebrovascular disease

Summary: The possible association of apolipoprotein E (apoE) DNA polymorphism with ischemic cerebrovascular disease was evaluated in 65 patients who had suffered completed stroke or transient ischemic attack and 330 healthy controls. ApoE genotypes were determined by restriction isotyping/MADGE analysis. Significant difference in apoE genotype frequencies between case and control group was observed (p<0.01). Patients affected by ischemic stroke had higher frequency of E4 allele and lower E2 allele than age-matched control subjects. Compared with persons without E4 allele, carriers of an E4 allele had 2.1 times higher risk of incident stroke. Our results indicate that the apoE gene polymorphism may be a risk factor for the development of ischemic cerebrovascular disease in Serbian population.
When ignorance is not bliss – a study of poor awareness of radiation exposure

Introduction and objective: Patient safety is at the forefront of quality of care. Radiation exposure secondary to diagnostic imaging is increasing rapidly. Coupled with clinicians’ lack of awareness concerning radiation, doses incurred during these common procedures mean patients are being exposed to substantial cumulative radiation. Recent publications have indicated a significant minority of cancers are secondary to medical ionising radiation. The purpose of this study was to establish physician knowledge of radiation dosages. Methods: Clinician knowledge of radiation doses was determined by a questionnaire distributed to 40 doctors across all specialties in a District General Hospital in England. Clinicians were asked to estimate the radiation dose incurred during common diagnostic investigations, environmental exposure and the relation to increased cancer risk. The results were correlated against seniority and previous formal education on ionising radiation. Results: Clinician knowledge of radiation doses was poor with a mean score of 17% (range 0–44%). There was, on average, more than a 12-fold underestimation of radiation exposure levels across all grades and specialties of doctors. Those with previous formal education outperformed those without, but not significantly (p > 0.05). Conclusions: Clinician awareness surrounding radiation doses of common diagnostic modalities is poor, grossly underestimating the true values. Increasing seniority or prior formal radiology training did not significantly alter the outcome. There is a need to educate clinicians, raise radiation dose awareness and avoid the financial, medico-legal and health delivery implications of unnecessary patient exposure to radiation.
Usability of photoplethysmography method in estimation of conduit artery stiffness

Three channel photoplethysmography (PPG) signal waveform studies of leg conduit arteries during a provocative occlusion test were performed. PPG waveform second derivative amplitude ratio and arterial pulse wave velocity values showed significant correlations with ultrasound (US) reference method of local and regional arterial stiffness (AS), showing the ability to use PPG for AS change quantitative assessment.
Intranasal Administration of Antibody-Bound Respiratory Syncytial Virus Particles Efficiently Primes Virus-Specific Immune Responses in Mice

ABSTRACT Infants are protected from a severe respiratory syncytial virus (RSV) infection in the first months of life by maternal antibodies or by prophylactically administered neutralizing antibodies. Efforts are under way to produce RSV-specific antibodies with increased neutralizing capacity compared to the currently licensed palivizumab. While clearly beneficial during primary infections, preexisting antibodies might affect the onset of adaptive immune responses and the ability to resist subsequent RSV infections. Therefore, we addressed the question of how virus neutralizing antibodies influence the priming of subsequent adaptive immune responses. To test a possible role of the neonatal Fc receptor (FcRn) in this process, we compared the responses in C57BL/6 wild-type (WT) and FcRn−/− mice. We observed substantial virus-specific T-cell priming and B-cell responses in mice primed with RSV IgG immune complexes resulting in predominantly Th1-type CD4+ T-cell and IgG2c antibody responses upon live-virus challenge. RSV-specific CD8+ T cells were primed as well. Activation of these adaptive immune responses was independent of FcRn. Thus, neutralizing antibodies that localize to the airways and prevent infection-related routes of antigen processing can still facilitate antigen presentation of neutralized virus particles and initiate adaptive immune responses against RSV.
Radionuclide Imaging in Patients with Ischemic Heart Failure

Nuclear imaging procedures are well-established diagnostic tools in clinical cardiology, providing noninvasive information about myocardial perfusion, cardiac function and metabolism. Scintigraphic parameters provide relevant information that aids in everyday clinical decision making for referring physicians. In patients with coronary artery disease, the presence of myocardial necrosis, postischemic stunning and hibernation can determine left ventricular dysfunction leading to ischemic heart failure. The prognosis of these patients is still poor and the long-term results of medical management remain discouraging. It is now well established that ventricular dysfunction is often a reversible process and ventricular function may improve following myocardial revascularization. Patients with extensive areas of hibernation treated medically have a worse prognosis as compared to those who undergo revascularization with a similar extent of viable myocardium. Therefore, an accurate non-invasive assessment of myocardial viability with the preoperative differentiation between hibernation and stunning and irreversibly necrotic tissue is important for clinical decision-making to select patients candidates for revascularization. Radionuclide imaging techniques evaluating myocardial perfusion, cell membrane integrity, ventricular function and cardiac metabolism have demonstrated clinical utility in the assessment of myocardial viability and in predicting improvement of ventricular function and prognosis after coronary revascularization. Under certain conditions, when viable myocytes are subject to ischemia, prolonged alterations in regional or global left ventricular function may occur and this dysfunction may be completely reversible. This condition may be related to two pathophysiological states: stunned and hibernating myocardium. Stunned myocardium refers to the state of persistent regional dysfunction after a transient period of ischemia that has been followed by reperfusion, and is mainly present in acute coronary syndromes. Myocardial hibernation refers to persistent regional left ventricular dysfunction secondary to prolonged, subacute or chronic myocardial hypoperfusion under resting conditions in which myocytes remain viable but regional contractility is reduced to match the reduced blood supply (1, 2). It has been suggested that during hibernation a new state of equilibrium is reached between blood flow (oxygen supply) and contraction (oxygen demand) whereby myocardial necrosis is prevented. Therefore, hibernation is considered a protective response of decrease oxygen demand in the setting of decrease oxygen availability (3). Early studies suggested that resting blood flow is severely reduced in hibernating myocardium. However, more recent data obtained with quantitative measurements of myocardial blood flow indicate that during hibernation resting blood flow may be normal or only moderately reduced, with a disproportiona l decline in contractile function (4, 5). These findings suggest that
Subjective Measures of Satisfaction and Benefit: Establishing Norms

The Collaborative Marketing Committee (CMC) has established as its primary objective the improvement of customer satisfaction with hearing instruments. The first series of MarkeTrak surveys conducted by Knowles Electronics demons t r a t ed that overall customer satisfaction with hearing instruments in the Uni ted States was 58%, whereas for new hea r ing ins t ruments satisfaction was 66% (Kochkin, 1992, 1993). MarkeTrak IV research (to be publ i shed) will show tha t overall satisfaction has declined to 52% while overall satisfaction with new hearing instruments has improved to 7 1 % . It is our belief that improvement in enduser satisfaction, benefit, and perceptions of hearing instrument value will have a positive long-term impact on market growth. Furthermore , th rough the systematic evaluation of satisfaction and benefit it is our belief that, as an industry, we can become wiser decisionmakers for our customers. To this end, this paper provides baseline measures of satisfaction and benefit for hearing healthcare professionals who simply want to know how their client population compares to a set of national norms. Subjective measures of satisfaction and benefit when normed to a meaningful referent group enable individual and group comparisons of performance of hearing instruments in a number of domains of function. Examples of potential applications in rout ine hear ing instrument fittings include:
Genome-Wide Analysis of Host mRNA Translation during Hepatitis C Virus Infection

ABSTRACT In the model of Huh-7.5. 1 hepatocyte cells infected by the JFH1 hepatitis C virus (HCV) strain, transcriptomic and proteomic studies have revealed modulations of pathways governing mainly apoptosis and cell cycling. Differences between transcriptomic and proteomic studies pointed to regulations occurring at the posttranscriptional level, including the control of mRNA translation. In this study, we investigated at the genome-wide level the translational regulation occurring during HCV infection. Sucrose gradient ultracentrifugation followed by microarray analysis was used to identify translationally regulated mRNAs (mRNAs associated with ribosomes) from JFH1-infected and uninfected Huh-7.5. 1 cells. Translationally regulated mRNAs were found to correspond to genes enriched in specific pathways, including vesicular transport and posttranscriptional regulation. Interestingly, the strongest translational regulation was found for mRNAs encoding proteins involved in pre-mRNA splicing, mRNA translation, and protein folding. Strikingly, these pathways were not previously identified, through transcriptomic studies, as being modulated following HCV infection. Importantly, the observed changes in host mRNA translation were directly due to HCV replication rather than to HCV entry, since they were not observed in JFH1-infected Huh-7.5. 1 cells treated with a potent HCV NS3 protease inhibitor. Overall, this study highlights the need to consider, beyond transcriptomic or proteomic studies, the modulation of host mRNA translation as an important aspect of HCV infection.
The Papillomavirus E1 Helicase Activates a Cellular DNA Damage Response in Viral Replication Foci

ABSTRACT The papillomavirus E1 and E2 proteins are essential for viral genome replication. E1 is a helicase that unwinds the viral origin and recruits host cellular factors to replicate the viral genome. E2 is a transcriptional regulator that helps recruit the E1 helicase to the origin and also plays a role in genome partitioning. We find that when coexpressed, the E1 and E2 proteins from several papillomavirus types localize to defined nuclear foci and result in growth suppression of the host cells. Growth suppression was due primarily to E1 protein function, and nuclear expression of E1 was accompanied by activation of a DNA damage response, resulting in phosphorylation of ATM, Chk2, and H2AX. Growth suppression and ATM activation required the ATPase and origin-specific binding functions of the E1 protein and resulted in active DNA repair, as evidenced by incorporation of nucleotide analogs and detection of free DNA ends. In the presence of the E2 protein, these activities became localized to nuclear foci. We postulate that these foci represent viral replication factories and that a cellular DNA damage response is activated to facilitate replication of viral DNA.