2,705 research outputs found
Effects of Graphene Coatings on hindering Space Charge injection in Epoxy Resin
The reliability of epoxy resins (and dielectrics in general) employed for HVDC applications is significantly affected by space charge accumulation in the insulating material. Several methods have been tested to limit the injection and accumulation of space charge. In this work, planar specimens featuring graphene coatings were tested. Measurements of space charge accumulation, conductivity and permittivity at different temperatures (from 30°C to 60°C) and fields (from 30 kV/mm to 50 kV/mm) were carried out on epoxy specimens with and without coatings. Results show accumulation of space charge for low fields and temperatures in the reference specimens, while a reduction can be noticed with a layer of graphene coating. On the other hand, at higher fields or temperatures, the effect is reversed
Actualités sur les co-infections VIH–VHC
Objectives
To evaluate the incidence of HIV–HCV co-infections and analyse the outcome in co-infected patients.
Epidemiology. Effects of antivirals
The prevalence of the co-infection by the HCV thus varies from 10 to 14% on subjects who have sexual behaviors at risk at 80 or 90% on users of drug IV. Numerous studies showed that the infection by the HIV made worse the natural history of the infection by the HCV [J Acquir Immune Defic Syndr 6 1993 602–610; J Hepatol 28 1998 945–950]. On the other hand, the studies which endeavoured to appreciate the effect of the antiretroviral therapeutics on the natural history of the chronic hepatitis C, on the co-infected patients, are more discussed. In cohorts of big size, it was demonstrated that the hepatic mortality increased with the exposure to antiretrovirals. However, the duration of the antiretroviral treatment also reports the more important survival of the patients, which distorts credibly the figures. The effect of the infection by the HCV on the progress of the disease with HIV is more discussed. The patients infected by the HIV, in any case, have to benefit from the research for a co-infection by the viruses of hepatitis B and C (HBV and HCV). This screening must be renewed every year, in particular on the drug addicts patients or presenting behaviors at risk.
Viral replication
The research of a viral replication, must be implemented for any confirmed positive HCV serology. The research of the HCV RNA needs ultrasensitive techniques of molecular biology which allow a qualitative detection andor a quantification of the viral genome (viral load). The techniques of last generation of real-time PCR combine both approaches (detection and quantification). The viral load HCV is not correlated to the degree of hepatic disease and does not predict the severity of the hepatic disease, contrary to the correlation demonstrated in the infection by the HIV. On the other hand, it can be a predictive factor in the response to the treatment. The pretherapeutic check-up also includes a determination of the viral genotype because a strong involvement in the response to the treatment was clearly demonstrated.
Hepatic fibrosis
The hepatic fibrosis must be estimated on patients having a chronic hepatitis because it conditions the prognosis and the treatment of the hepatitis. The anatomopathological study after hepatic biopsy (DHB) remains the reference method. Recently, the development of non invasive methods of measure of the hepatic fibrosis improved the care of hepatitis C, notably the blood tests (fibrotest BioPredictive Paris, fibrometer BLS Angers) and physical measures as the impulsional elastometry (Fibroscan® Echosens) which substitutes more and more in practice to the draining hepatic biopsy.
Treatment
Numerous studies now validated the treatment associating interferon pegilated and ribavirine as the reference treatment on the co-infected patients HIV/HCV. This treatment involves a high virological response going from 14 to 36% in the patients infected by a genotype 1 and 2 and from 43 to 73% in the patients infected by a genotype 2 or 3. The duration of the treatment is 48 weeks. As well as usual virological factors on the mono-infected patients (genotype, viral load), the rate of CD4 is one of the best predictive factors with a good response. Many hopes go towards the new molecules in development (inhibitors of protease), inhibitors of polymerase), with promising results on the mono-infected patients. However, the toxicity of these molecules is not very well known at the moment in the co-infected patients. It is thus necessary to perform trials in this group of patient, by watching very carefully the toxicity of the therapeutic associations
Analyse des mutations des domaines ISDR et V3 de la protéine NS5A du virus de l'hépatite C avant le traitement par l'interféron avec ou sans ribavirine
Aim of the study. – The hepatitis C virus (HCV) non-structural NS5A protein has been controversially implicated in the resistance of HCV to interferon therapy in clinical studies. In Japan, mutations in the interferon sensitivity-determining region (ISDR) in the NS5A gene were associated with response to interferon therapy in patients infected with genotype 1b. In contrast, studies from Europe did not confirm such association. More recently, it has been suggested that the V3 domain outside the putative ISDR might also have amino acids changes that may be involved in the resistance to IFN. In this study, the relationship between NS5A mutations in ISDR and V3 domains and virological response to therapy were investigated.
Materials and methods. – The NS5A gene was sequenced from 35 HCV genotype 1b infected patients at D0 of a prospective clinical trial of interferon therapy and interferon plus Ribavirin combination therapy.
Results. – In the ISDR domain, we did not observe any significant differences in amino acids changes between responders (1.7 ± 1.8, n = 19, range 0–6) and non-responders (1.1 ± 0.8, n = 14, range: 0–3), (P = 0.483), to therapy before the beginning of treatment. In the V3 domain, we found more mutations in responders (6.5 ± 1.9, range: 2–11) than in non-responders (4.7 ± 1.2, range: 3–8) (P = 0.0013), before the beginning of treatment.
Conclusion. – Our results confirm that, in Europe, the ISDR domain is not predictive for treatment success but suggest that the V3 domain have greater variability in responders than non-responders
Assessment of human influenza pandemic scenarios in Europe
The response to the emergence of the 2009 influenza A(H1N1) pandemic was the result of a decade of pandemic planning, largely centred on the threat of an avian influenza A(H5N1) pandemic. Based on a literature review, this study aims to define a set of new pandemic scenarios that could be used in case of a future influenza pandemic. A total of 338 documents were identified using a searching strategy based on seven combinations of keywords. Eighty-three of these documents provided useful information on the 13 virus-related and health-system-related parameters initially considered for describing scenarios. Among these, four parameters were finally selected (clinical attack rate, case fatality rate, hospital admission rate, and intensive care admission rate) and four different levels of severity for each of them were set. The definition of six most likely scenarios results from the combination of four different levels of severity of the four final parameters (256 possible scenarios). Although it has some limitations, this approach allows for more flexible scenarios and hence it is far from the classic scenarios structure used for pandemic plans until 2009
A 3D radiative transfer framework: I. non-local operator splitting and continuum scattering problems
We describe a highly flexible framework to solve 3D radiation transfer
problems in scattering dominated environments based on a long characteristics
piece-wise parabolic formal solution and an operator splitting method. We find
that the linear systems are efficiently solved with iterative solvers such as
Gauss-Seidel and Jordan techniques. We use a sphere-in-a-box test model to
compare the 3D results to 1D solutions in order to assess the accuracy of the
method. We have implemented the method for static media, however, it can be
used to solve problems in the Eulerian-frame for media with low velocity
fields.Comment: A&A, in press. 14 pages, 19 figures. Full resolution figures
available at ftp://phoenix.hs.uni-hamburg.de/preprints/3DRT_paper1.pdf HTML
version (low res figures) at
http://hobbes.hs.uni-hamburg.de/~yeti/PAPERS/3drt_paper1/index.htm
Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy
AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA-dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear.
METHODS: HCV quasispecies were studied by cloning and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-alpha2b for 3 mo followed by IFN-alpha2b alone or combined IFN-R therapy for 9 additional months. Patients were categorized into two groups based on their response to the treatments: 7 with sustained virological response (SVR) (quasispecies = 150) and 3 non-responders (NR) to IFN-R (quasispecies = 106).
RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispecies during therapy. Analysis of amino acids substitutions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate the two groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients.
CONCLUSION: These results suggest that detailed molecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection
Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Scleritis
Mutations within the hepatitis C virus genotype 1b E2-PePHD domain do not correlate with treatment outcome.
The hepatitis C virus (HCV) envelope protein 2 (E2) interacts in vitro with the interferon alpha (IFN-alpha)-inducible double-stranded RNA-activated protein kinase, suggesting a possible mechanism by which HCV may evade the antiviral effects of IFN-alpha. Variability in the part of the HCV E2 gene encoding the carboxy-terminal part of the protein, which includes the interaction domain (E2-PePHD), was explored in 25 patients infected with HCV genotype 1b and receiving IFN-alpha therapy. PCR products were generated and sequenced for 15 patients with a sustained response and for 10 patients with no virological response after treatment with IFN-alpha and ribavirin. PePHD amino acid sequences were obtained for isolates from serum collected before and during treatment, after 2 months in responders, and after 6 months in nonresponders. Quasispecies analysis of the pretreatment PePHD region was performed for isolates from patients displaying amino acid substitutions in this domain on direct sequencing. The E2-PePHD sequence was highly conserved in both resistant and susceptible genotype 1b strains and was identical to the prototype HCV type J sequence. No significant emergence of PePHD mutants during therapy was observed in our clonal analysis, and sporadic mutations and treatment outcomes were not found to be correlated. The PePHD sequence before or during treatment cannot be used to predict reliably the outcome of treatment in HCV type 1b-infected patients
- …