The clonal structure and dynamics of the human T cell response to an organic chemical hapten

Diphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis, and is used in treatment of warts, melanoma and alopecia areata. This therapeutic setting therefore provided an opportunity to study T cell receptor (TCR) repertoire changes in response to hapten sensitization in humans. Repeated exposure to DPC induced highly dynamic transient expansions of a polyclonal diverse T cell population. The number of TCRs expanded early after sensitization varies between individuals, and predicts the magnitude of the allergic reaction. The expanded TCRs show preferential TCR V and J gene usage, and consist of clusters of TCRs with similar sequences, two characteristic features of antigen-driven responses. The expanded TCRs share subtle sequence motifs that can be captured using a Dynamic Bayesian Network. These observations suggest the response to DPC is mediated by a polyclonal population of T cells recognizing a small number of dominant antigens

Raman Scattered He II λ\lambda 6545 Line in the Symbiotic Star V1016 Cygni

We present a spectrum of the symbiotic star V1016 Cyg observed with the 3.6 m Canada-France-Hawaii Telescope, in order to illustrate a method to measure the covering factor of the neutral scattering region around the giant component with respect to the hot emission region around the white dwarf component. In the spectrum, we find broad wings around H$\alpha$ and a broad emission feature around 6545${\rm \AA}$ that is blended with the [N II]$\lambda$ 6548 line. These two features are proposed to be formed by Raman scattering by atomic hydrogen, where the incident radiation is proposed to be UV continuum radiation around Ly$\beta$ in the former case and He II $\lambda$ 1025 emission line arising from $n=6\to n=2$ transitions for the latter feature. We remove the H$\alpha$ wings by a template Raman scattering wing profile and subtract the [N II] $\lambda$ 6548 line using the 3 times stronger [N II] $\lambda$ 6583 feature in order to isolate the He II Raman scattered 6545 \AA line. We obtain the flux ratio $F_{6545}/F_{6560}=0.24$ of the He II $\lambda$ 6560 emission line and the 6545 \AA feature for V1016 Cyg. Under the assumption that the He II emission from this object is isotropic, this ratio is converted to the ratio $\Phi_{6545}/\Phi_{1025}=0.17$ of the number of the incident photons and that of the scattered photons. This implies that the scattering region with H I column density $N_{HI}\ge 10^{20}{\rm cm^{-2}}$ covers 17 per cent of the emission region. By combining the presumed binary period $\sim 100$ yrs of this system we infer that a significant fraction of the slow stellar wind from the Mira component is ionized and that the scattering region around the Mira extends a few tens of AU, which is closely associated with the mass loss process of the Mira component.Comment: 12 pages, 6 figures, accepted for publication in Ap

The binary period and outburst behaviour of the SMC X-ray binary pulsar system SXP504

A probable binary period has been detected in the optical counterpart to the X-ray source CXOU J005455.6-724510 = RX J0054.9-7245 = AXJ0054.8-7244 = SXP504 in the Small Magellanic Cloud. This source was detected by Chandra on 04 Jul 2002 and subsequently observed by XMM-Newton on 18 Dec 2003. The source is coincident with an Optical Gravitational Lensing (OGLE) object in the lightcurves of which several optical outburst peaks are visible at ~ 268 day intervals. Timing analysis shows a period of 268.6 +/- 0.1 days at > 99% significance. Archival Rossi X-ray Timing Explorer (RXTE) data for the 504s pulse-period has revealed detections which correspond closely with predicted or actual peaks in the optical data. The relationship between this orbital period and the pulse period of 504s is within the normal variance found in the Corbet diagram.Comment: Accepted by MNRAS. 1 LATEX page. 4 figure

Strong Near-Infrared Emission Interior to the Dust-Sublimation Radius of Young Stellar Objects MWC275 and AB Aur

Using the longest optical-interferometeric baselines currently available, we have detected strong near-infrared (NIR) emission from inside the dust-destruction radius of Herbig Ae stars MWC275 and AB Aur. Our sub-milli-arcsecond resolution observations unambiguously place the emission between the dust-destruction radius and the magnetospheric co-rotation radius. We argue that this new component corresponds to hot gas inside the dust-sublimation radius, confirming recent claims based on spectrally-resolved interferometry and dust evaporation front modeling.Comment: 12 pages, 4 figures, Accepted for publication in ApJ

Raman-Scattering Wings of H alpha in Symbiotic Stars

Nussbaumer et al. (1989) proposed that broad H$\alpha$ wings can be formed through Raman scattering of Ly$\beta$ photons, and in this Letter we argue that the H$\alpha$ wings prevalently seen in symbiotic stars may be indeed formed in this way. Assuming a flat incident UV radiation around Ly$\beta$, we generate template wing profiles around H$\alpha$ that are formed through Raman scattering in a plane-parallel H~I region. We perform profile fitting analyses to show that the template wing profiles are in excellent agreement with the observed ones that are provided by van Winckel et al. (1993) and Ivison et al. (1994). The wing flux is determined by the scattering H~I column density and the incident Ly$\beta$ flux strength and profile. From our profile analysis it is proposed that the Raman scattering component may be identified with the neutral envelope with a column density ranging $10^{18-20} {\rm cm^{-2}}$ that surrounds the binary system. We briefly discuss alternative candidates for the wing formation mechanism and observational implications of Raman scattering in symbiotic stars and in other astronomical objects including planetary nebulae, post AGB stars and active galactic nuclei.Comment: 6 pages including 2 figures, to appear in the Astrophysical Journal Letter

Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer

<p>Abstract</p> <p>Background</p> <p>Genome wide association studies (GWAS) have identified several genetic variants that are associated with prostate cancer. Most of these variants, like other GWAS association signals, are located in non-coding regions of potential candidate genes, and thus could act at the level of the mRNA transcript.</p> <p>Methods</p> <p>We measured the expression and isoform usage of seven prostate cancer candidate genes in benign and malignant prostate by real-time PCR, and correlated these factors with cancer status and genotype at the GWAS risk variants.</p> <p>Results</p> <p>We determined that levels of <it>LMTK2 </it>transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 × 10^-7), and that an independent effect of genotype at variant rs6465657 on <it>LMTK2 </it>expression in benign (n = 39) and malignant tissues (n = 21) was also evident (P = 0.002). We also identified that whilst <it>HNF1B(C) </it>and <it>MSMB2 </it>comprised the predominant isoforms in benign tissues (90% and 98% of total <it>HNF1B </it>or <it>MSMB </it>expression)<it>, HNF1B(B) and MSMB1 </it>were predominant in malignant tissue (95% and 96% of total <it>HNF1B </it>or <it>MSMB </it>expression; P = 1.7 × 10^-7and 4 × 10^-4respectively), indicating major shifts in isoform usage.</p> <p>Conclusions</p> <p>Our results indicate that the amount or nature of mRNA transcripts expressed from the <it>LMTK2</it>, <it>HNF1B </it>and <it>MSMB </it>candidate genes is altered in prostate cancer, and provides further evidence for a role for these genes in this disorder. The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms.</p

Short and long term retention in antiretroviral care in health facilities in rural Malawi and Zimbabwe.

Despite the successful scale-up of ART services over the past years, long term retention in ART care remains a major challenge, especially in high HIV prevalence and resource-limited settings. This study analysed the short (<12 months) and long (>12 months) term retention on ART in two ART programmes in Malawi (Thyolo district) and Zimbabwe (Buhera district)

Countrywide roll-out of Xpert(®) MTB/RIF in Swaziland: the first three years of implementation.

SETTING: All 19 public health laboratories in Swaziland that had Xpert(®) MTB/RIF machines installed as part of a countrywide roll-out between June 2011 and June 2014. OBJECTIVE: To evaluate the utilisation and functionality of Xpert from 2011 to mid-2014. DESIGN: Descriptive study of Xpert implementation using routinely collected data. RESULTS: Of 48 829 Xpert tests conducted, 93% were successful: 14% detected Mycobacterium tuberculosis and 12% showed rifampicin resistance. The most common cause of unsuccessful tests was an 'Error' result (62%). Similar findings were obtained in government-supported and partner-supported laboratories. Annual utilisation of Xpert improved from 51% of maximum capacity in 2011 and 2012 to 74% in 2013 and 2014. A monitoring and supervision exercise of all Xpert testing sites in 2014 showed a generally good performance, with over 50% of laboratories achieving a ⩾80% score on most components. However, poor scores were obtained with equipment use and maintenance (6% achieving a score of ⩾80%), internal audit (19% achieving a score of ⩾80%) and process control (25% achieving a score of ⩾80%). CONCLUSION: Countrywide roll-out of Xpert in Swaziland has been successful, although operational issues have been identified and need to be resolved