Linear B-cell epitopes of the NS3-NS4-NS5 proteins of the hepatitis C virusas modeled with synthetic peptides

AbstractA set of 150 synthetic peptides spanning the proteins NS3-NS4-NS5 of the hepatitis C virus (HCV) was synthesizedand tested with a panel of 20 sera obtained from HCV-infected patients. Of 62 peptides prepared from the NS3 region, none exhibited strong antigenic reactivity. Rather, five peptides from this region demonstrated specific reactivity with only 5–10% of anti-HCV-positive sera. Nonetheless, it is well known that the NS3 region contains strong antigenic epitopes. These epitopes appear to be modeled in a functionally active manner with recombinant proteins and cannot be mimicked properly with short synthetic peptides. This finding suggests that the major NS3 antigenic epitopes are conformationally dependent. Seven of 20 peptides prepared from the NS4 region were immunoreactive. Five peptides from this region demonstrated very strong HCV-specific antigenic reactivity. Four of the five peptides belong to the recognized immunoreactive 5-1-1 region located inside the C100-3 antigen. One peptide demonstrating immunoreactivity with approximately 90% of anti-HCV-positive sera was found outside the C100-3 region at the C-terminal part of the NS4 protein. Of 68 peptides synthesized from the NS5 protein, 30 were immunoreactive. Six of the 30 demonstrated immunoreactivity with 35–50% of anti-HCV-positive sera. Thus, the NS4 and NS5 regions of the HCV polyprotein contain a large number of specific, broadly reactive, linear antigenic epitopes. The highly antigenic reactivity of the NS5 region suggests that this protein may have significant diagnostic potential

Impact of tidal Poisson terms on nonrigid Earth rotation

Context. The tidal potential generated by bodies in the solar system contains Poisson terms, i.e., periodic terms with linearly time-dependent amplitudes. The influence of these terms on the Earth's rotation, although expected to be small, is of interest for high accuracy modeling. Aims. Therefore, we study their contribution to the rotation of a non-rigid Earth with an elastic mantle and liquid core. Methods. Starting from Liouville's equations, and following an analytical treatment, we obtain the relations accounting for Poisson terms in the forcing and providing the solution for the wobble. Results. We show that the transfer function between rigid and non rigid nutation amplitudes, as usually defined in the literature, must be supplemented by additional terms proportional to the amplitude of the Poisson term of the potential. These new terms are inversely proportional to (sigma - sigma(N))(2) where sigma is the forcing frequency and sigma(N) are the eigenfrequencies associated with the retrograde free core nutation and the Chandler wobble. The highest contribution to the nutation is 6 mu as (Delta psi) on the term 2l' - 2F + 2D - 2 Omega and remains below 1 mu as for the other terms. A contribution of 88 mu as/cy is found to the obliquity rate. We evaluate the variations of the third component of the wobble of the Earth and of the core in response to a zonal tidal potential, and show that there is no significant change

Improving newborn respiratory outcomes with a sustained inflation: a systematic narrative review of factors regulating outcome in animal and clinical studies

Respiratory support is critically important for survival of newborns who fail to breathe spontaneously at birth. Although there is no internationally accepted definition of a sustained inflation (SI), it has commonly been defined as a positive pressure inflation designed to establish functional residual capacity and applied over a longer time period than normally used in standard respiratory support (SRS). Outcomes vary distinctly between studies and to date there has been no comprehensive investigation of differences in SI approach and study outcome in both pre-clinical and clinical studies. A systematic literature search was performed and, after screening, identified 17 animal studies and 17 clinical studies evaluating use of a SI in newborns compared to SRS during neonatal resuscitation. Study demographics including gestational age, SI parameters (length, repetitions, pressure, method of delivery) and study outcomes were compared. Animal studies provide mechanistic understanding of a SI on the physiology underpinning the cardiorespiratory transition at birth. In clinical studies, there is considerable difference in study quality, delivery of SIs (number, pressure, length) and timing of primary outcome evaluation which limits direct comparison between studies. The largest difference is method of delivery, where the role of a SI has been observed in intubated animals, as the inflation pressure is directly applied to the lung, bypassing the obstructed upper airway in an apnoeic state. This highlights a potential limitation in clinical use of a SI applied non-invasively. Further research is required to identify if a SI may have greater benefits in subpopulations of newborns.Developmen

D-branes in 2d Lorentzian black hole

We study D-branes in the Lorentzian signature 2D black hole string theory. We use the technique of gauged WZW models to construct the associated boundary conformal field theories. The main focus of this work is to discuss the (semi-classical) world-volume geometries of the D-branes. We also discuss comparison of our work with results in related gauged WZW models.Comment: 24 pages, 5 figures, uses JHEP3.cl

False-negative results using Neisseria gonorrhoeae porA pseudogene PCR - a clinical gonococcal isolate with an N. meningitidis porA sequence, Australia, March 2011

The gonococcal porA pseudogene is a popular target for in-house Neisseria gonorrhoeae PCR methods. With this study we present two novel findings: the first case of an N. gonorrhoeae porA pseudogene PCR false-negative result caused by sequence variation, and in the same organism, the first description of a clinical N. gonorrhoeae strain harbouring an N. meningitidis porA sequence

The Shape of Gravity in a Warped Deformed Conifold

We study the spectrum of the gravitational modes in Minkowski spacetime due to a 6-dimensional warped deformed conifold, i.e., a warped throat, in superstring theory. After identifying the zero mode as the usual 4D graviton, we present the KK spectrum as well as other excitation modes. Gluing the throat to the bulk (a realistic scenario), we see that the graviton has a rather uniform probability distribution everywhere while a KK mode is peaked in the throat, as expected. Due to the suppressed measure of the throat in the wave function normalization, we find that a KK mode's probability in the bulk can be comparable to that of the graviton mode. We also present the tunneling probabilities of a KK mode from the inflationary throat to the bulk and to another throat. Due to resonance effect, the latter may not be suppressed as natively expected. Implication of this property to reheating after brane inflation is discussed

Links2HealthierBubs' cohort study: Protocol for a record linkage study on the safety, uptake and effectiveness of influenza and pertussis vaccines among pregnant Australian women

Introduction Pregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes. Methods and analysis ' Links2HealthierBubs' is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (∼607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers. Ethics and dissemination Ethical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women's Hospital, and the West Australian Aboriginal Health Ethics Committees. Research findings will be disseminated in peer-reviewed journals, at scientific meetings, and may be incorporated into communication materials for public health agencies and the public

Abelian and nonabelian vector field effective actions from string field theory

The leading terms in the tree-level effective action for the massless fields of the bosonic open string are calculated by integrating out all massive fields in Witten's cubic string field theory. In both the abelian and nonabelian theories, field redefinitions make it possible to express the effective action in terms of the conventional field strength. The resulting actions reproduce the leading terms in the abelian and nonabelian Born-Infeld theories, and include (covariant) derivative corrections.Comment: 49 pages, 1 eps figur

Evaluation of X chromosome inactivation with respect to HLA genetic susceptibility in rheumatoid arthritis and systemic sclerosis

Background: Autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc) are characterized by a strong genetic susceptibility from the Human Leucocyte Antigen (HLA) locus. Additionally, disorders of epigenetic processes, in particular non-random X chromosome inactivation (XCI), have been reported in many female-predominant autoimmune diseases. Here we test the hypothesis that women with RA or SSc who are strongly genetically predisposed are less susceptible to XCI bias. Methods: Using methylation sensitive genotyping of the androgen receptor (AR) gene, XCI profiles were performed in peripheral blood mononuclear cells from 161 women with RA, 96 women with SSc and 100 healthy women. HLA-DRB1 and DQB1 were genotyped. Presence of specific autoantibodies was documented for patients. XCI skewing was defined as having a ratio ≥ 80:20 of cells inactivating the same X chromosome. Results: 110 women with RA, 68 women with SSc, and 69 controls were informative for the AR polymorphism. Among them 40.9% of RA patients and 36.8% of SSc patients had skewed XCI compared to 17.4% of healthy women (P = 0.002 and 0.018, respectively). Presence of RA-susceptibility alleles coding for the "shared epitope" correlated with higher skewing among RA patients (P = 0.002) and such correlation was not observed in other women, healthy or with SSc. Presence of SSc-susceptibility alleles did not correlate with XCI patterns among SSc patients. Conclusion: Data demonstrate XCI skewing in both RA and SSc compared to healthy women. Unexpectedly, skewed XCI occurs more often in women with RA carrying the shared epitope, which usually reflects severe disease. This reinforces the view that loss of mosaicism in peripheral blood may be a consequence of chronic autoimmunity. © 2016 Kanaan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited