p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes.

p75 neurotrophin receptor (p75NTR) belongs to the TNF-receptor superfamily and signals apoptosis in many cell settings. In human epidermis, p75NTR is mostly confined to the transit-amplifying (TA) sub-population of basal keratinocytes. Brain-derived neurotrophic factor (BDNF) or neurotrophin-4 (NT-4), which signals through p75NTR, induces keratinocyte apoptosis, whereas β-amyloid, a ligand for p75NTR, triggers caspase-3 activation to a greater extent in p75NTR transfected cells. Moreover, p75NTR co-immunoprecipitates with NRAGE, induces the phosphorylation of c-Jun N-terminal kinase (JNK) and reduces nuclear factor kappa B (NF-κB) DNA-binding activity. p75NTR also mediates pro-NGF-induced keratinocyte apoptosis through its co-receptor sortilin. Furthermore, BDNF or β-amyloid cause cell death in TA, but not in keratinocyte stem cells (KSCs) or in p75NTR silenced TA cells. p75NTR is absent in lesional psoriatic skin and p75NTR levels are significantly lower in psoriatic than in normal TA keratinocytes. The rate of apoptosis in psoriatic TA cells is significantly lower than in normal TA cells. BDNF or β-amyloid fail to induce apoptosis in psoriatic TA cells, and p75NTR retroviral infection restores BDNF- or β-amyloid-induced apoptosis in psoriatic keratinocytes. These results demonstrate that p75NTR has a pro-apoptotic role in keratinocytes and is involved in the maintenance of epidermal homeostasis

Monitoring prevention or emergence of HIV drug resistance: results of a population-based foundational survey of early warning indicators in mainland Tanzania

BACKGROUND: In Tanzania, routine individual-level testing for HIV drug resistance (HIVDR) using laboratory genotyping and phenotyping is not feasible due to resource constraints. To monitor the prevention or emergence of HIVDR at a population level, WHO developed generic strategies to be adapted by countries, which include a set of early warning indicators (EWIs). METHODS: To establish a baseline of EWIs, we conducted a retrospective longitudinal survey of 35 purposively sampled care and treatment clinics in 17 regions of mainland Tanzania. We extracted data relevant for four EWIs (ART prescribing practices, patients lost to follow-up 12 months after ART initiation, retention on first-line ART at 12 months, and ART clinic appointment keeping in the first 12 months) from the patient monitoring system on patients who initiated ART at each respective facility in 2010. We uploaded patient information into WHO HIVResNet excel-based tool to compute national and facility averages of the EWIs and tested for associations between various programmatic factors and EWI performance using Fisher’s Exact Test. RESULTS: All sampled facilities met the WHO EWI target (100%) for ART prescribing practices. However, the national averages for patients lost to follow-up 12 months after ART initiation, retention on first-line ART at 12 months, and ART clinic appointment keeping in the first 12 months fell short, at 26%, 54% and 38%, respectively, compared to the WHO targets ≤ 20%, ≥ 70%, and ≥ 80%. Clinics with fewer patients lost to follow-up 12 months after ART initiation and more patients retained on first-line-ART at 12 months were more likely to have their patients spend the longest time in the facility (including wait-time and time with providers), (p = 0.011 and 0.007, respectively). CONCLUSION: Tanzania performed very well in EWI 1a, ART prescribing practices. However, its performance in other three EWIs was far below the WHO targets. This study provides a baseline for future monitoring of EWIs in Tanzania and highlights areas for improvement in the management of ART patients in order not only to prevent emergence of HIVDR due to programmatic factors, but also to improve the quality of life for ART patients

Laser-Induced Periodic Surface Structures on Conjugated Polymers: Poly(3-hexylthiophene)

8 pags.; 11 figs.© 2015 American Chemical Society. In this work, we report on the surface patterning of semiconducting poly(3-hexylthiophene) (P3HT) thin films by means of laser-induced periodic surface structures (LIPSS). Two different laser wavelengths, 266 and 532 nm, and a broad range of fluences and number of pulses have been used in order to optimize the LIPSS morphology. Ripples period and depth can be tuned by laser parameters. In particular, the high optical absorption of P3HT at 532 nm enables the formation of well-ordered nanostructures with periodicities around 460 nm. Near edge X-ray absorption fine structure (NEXAFS) and Raman spectroscopy reveal a good chemical stability of P3HT thin films during LIPSS formation. Conducting atomic force microscopy (C-AFM) performed on the LIPSS reveals a higher electrical conduction in the trenches than in the ridge regions. Resonance Raman spectroscopy and grazing incidence wide-angle X-ray scattering (GIWAXS) indicate a loss of crystallinity of P3HT thin films during LIPSS formation, suggesting melting of the outer polymer surface. This effect produces ridges with molecular order lower than that of the original thin film. As a consequence of this transformation, the electrical conduction in the ridges becomes lower than that in the trenches.The authors gratefully acknowledge the financial support of the Spanish Ministry of Economy and Competitiveness (MINECO) through Projects MAT 2011-23455, MAT 2012-33517 and CTQ 2013-43086-P. A.R.-R. and E.R. are indebted to MINECO for a FPI (BES-2013-062620) and Ramon y Cajal (RYC-2011-08069) contracts, respectively. We thank the Swiss Light Source for beamtime at PolLux, where the NEXAFS experiments were performed. We also thank the ESRF for beamtime at BM26 where in situ GISAXS and GIWAXS experiments were carried out. We thank B. Watts for assistance in using beamline PolLux and G. Portale and W. Bras for beamline support at BM26. P. Müller-Buschbaum and S. Guo are thanked for seminal comments at the beginning of this workPeer Reviewe

In situ monitoring of laser-induced periodic surface structures formation on polymer films by grazing incidence small-angle X-ray scattering

9 pags.; 9 figs.© 2015 American Chemical Society. The formation of laser-induced periodic surface structures (LIPSS) on model spin-coated polymer films has been followed in situ by grazing incidence small-angle X-ray scattering (GISAXS) using synchrotron radiation. The samples were irradiated at different repetition rates ranging from 1 up to 10 Hz by using the fourth harmonic of a Nd:YAG laser (266 nm) with pulses of 8 ns. Simultaneously, GISAXS patterns were acquired during laser irradiation. The variation of both the GISAXS signal with the number of pulses and the LIPSS period with laser irradiation time is revealing key kinetic aspects of the nanostructure formation process. By considering LIPSS as one-dimensional paracrystalline lattice and using a correlation found between the paracrystalline disorder parameter, g, and the number of reflections observed in the GISAXS patterns, the variation of the structural order of LIPSS can be assessed. The role of the laser repetition rate in the nanostructure formation has been clarified. For high pulse repetition rates (i.e., 10 Hz), LIPSS evolve in time to reach the expected period matching the wavelength of the irradiating laser. For lower pulse repetition rates LIPSS formation is less effective, and the period of the ripples never reaches the wavelength value. Results support and provide information on the existence of a feedback mechanism for LIPSS formation in polymer films.The authors gratefully acknowledge financial support from the MINECO (MAT2011-23455, MAT2012-33517 and CTQ 2013-43086-P). E.R., I.M.-F., and A.R-R. also thank MINECO for a Ramon y Cajal contract (RYC-2011-08069) and FPI ́ fellowships (BES-2010-030074 and BES-2013-062620).Peer Reviewe

Measurement of forward photon production cross-section in proton-proton collisions at s\sqrt{s} = 13 TeV with the LHCf detector

In this paper, we report the production cross-section of forward photons in the pseudorapidity regions of $\eta\,>\,10.94$ and $8.99\,>\,\eta\,>\,8.81$, measured by the LHCf experiment with proton--proton collisions at $\sqrt{s}$ = 13 TeV. The results from the analysis of 0.191 $\mathrm{nb^{-1}}$ of data obtained in June 2015 are compared to the predictions of several hadronic interaction models that are used in air-shower simulations for ultra-high-energy cosmic rays. Although none of the models agree perfectly with the data, EPOS-LHC shows the best agreement with the experimental data among the models.Comment: 21 pages, 4 figure

Sacubitril-valsartan in heart failure and multimorbidity patients

Aims The poor control of symptoms in patients with advanced heart failure with reduced ejection function (HFrEF) can limit the functionality of patients. Sacubitril–valsartan, compared with enalapril, has been shown to reduce mortality and hospitalization, and nowadays, there is still little evidence about the improvement on functionality. The aim of our study is to analyse the improvement of the functional class and the 6 min walking test (6MWT) in patients with multiple pathologies and advanced heart failure. Methods and results From September 2016 to March 2018, 65 multimorbidity patients with severe symptomatic HFrEF were initiated to receive sacubitril–valsartan. Mean age was 78.6 ± 7.4 years, and 68% were male. The Charlson co-morbidity index was 8 points. Seventy-four per cent had New York Heart Association (NYHA) Functional Class IV. After the treatment, patients were able to achieve 55.68 m or more on 6MWT, and 91% presented an improvement in the NYHA functional class. Conclusions Sacubitril–valsartan relieves symptoms and improves functional class prognostic risk of patients with advanced HFrEF and co-morbidit

A separation of electrons and protons in the GAMMA-400 gamma-ray telescope

The GAMMA-400 gamma-ray telescope is intended to measure the fluxes of gamma rays and cosmic-ray electrons and positrons in the energy range from 100 MeV to several TeV. Such measurements concern with the following scientific goals: search for signatures of dark matter, investigation of gamma-ray point and extended sources, studies of the energy spectra of Galactic and extragalactic diffuse emission, studies of gamma-ray bursts and gamma-ray emission from the active Sun, as well as high-precision measurements of spectra of high-energy electrons and positrons, protons, and nuclei up to the knee. The main components of cosmic rays are protons and helium nuclei, whereas the part of lepton component in the total flux is ~10E-3 for high energies. In present paper, the capability of the GAMMA-400 gamma-ray telescope to distinguish electrons and positrons from protons in cosmic rays is investigated. The individual contribution to the proton rejection is studied for each detector system of the GAMMA-400 gamma-ray telescope. Using combined information from all detector systems allow us to provide the proton rejection from electrons with a factor of ~4x10E5 for vertical incident particles and ~3x10E5 for particles with initial inclination of 30 degrees. The calculations were performed for the electron energy range from 50 GeV to 1 TeV.Comment: 19 pages, 10 figures, submitted to Advances and Space Researc

CaloCube: a novel calorimeter for high-energy cosmic rays in space

In order to extend the direct observation of high-energy cosmic rays up to the PeV region, highly performing calorimeters with large geometrical acceptance and high energy resolution are required. Within the constraint of the total mass of the apparatus, crucial for a space mission, the calorimeters must be optimized with respect to their geometrical acceptance, granularity and absorption depth. CaloCube is a homogeneous calorimeter with cubic geometry, to maximise the acceptance being sensitive to particles from every direction in space; granularity is obtained by relying on small cubic scintillating crystals as active elements. Different scintillating materials have been studied. The crystal sizes and spacing among them have been optimized with respect to the energy resolution. A prototype, based on CsI(Tl) cubic crystals, has been constructed and tested with particle beams. Some results of tests with different beams at CERN are presented.Comment: Seven pages, seven pictures. Proceedings of INSTR17 Novosibirs