Low level of virological failure and drug resistance among patients receiving antiretroviral treatment under programme conditions in Maputo, Mozambique

Mexico AIDS Conference 200

Bio-Inspired Multi-Layer Spiking Neural Network Extracts Discriminative Features from Speech Signals

Spiking neural networks (SNNs) enable power-efficient implementations due to their sparse, spike-based coding scheme. This paper develops a bio-inspired SNN that uses unsupervised learning to extract discriminative features from speech signals, which can subsequently be used in a classifier. The architecture consists of a spiking convolutional/pooling layer followed by a fully connected spiking layer for feature discovery. The convolutional layer of leaky, integrate-and-fire (LIF) neurons represents primary acoustic features. The fully connected layer is equipped with a probabilistic spike-timing-dependent plasticity learning rule. This layer represents the discriminative features through probabilistic, LIF neurons. To assess the discriminative power of the learned features, they are used in a hidden Markov model (HMM) for spoken digit recognition. The experimental results show performance above 96% that compares favorably with popular statistical feature extraction methods. Our results provide a novel demonstration of unsupervised feature acquisition in an SNN

The Future Mortality of High Mortality Countries: A Model Incorporating Expert Arguments

This paper examines the future of mortality in the 65 countries still experiencing high mortality in 2010, as defined by a cutoff of 40 deaths before age five per thousand live births. Mortality declines in several countries stagnated or reversed in the last two decades of the twentieth century due mainly to HIV/AIDS. The forces underlying past mortality trends and affecting the future course of mortality are examined by reviewing the existing literature and reporting the results of the global survey and invited meeting, both involving mortality experts. The experts assessed the likelihood and weight of forces hypothesized to influence mortality. A statistical model is combined with these expert assessments to produce a set of mortality assumptions that are incorporated into the projections reported in this paper. This paper also addresses the limited availability of reliable data on age-specific mortality rates

Crystal Structures, Local Atomic Environments, and Ion Diffusion Mechanisms of Scandium-Substituted Sodium Superionic Conductor (NASICON) Solid Electrolytes

The importance of exploring new solid electrolytes for all-solid-state batteries has led to significant interest in NASICON-type materials. Here, the Sc3+-substituted NASICON compositions Na3ScxZr2-x(SiO4)2-x(PO4)1+x (termed N3) and Na2ScyZr2-y(SiO4)1-y(PO4)2+y (termed N2) (x, y = 0 – 1) are studied as model Na+-ion conducting electrolytes for solid-state batteries. The influence of Sc3+ substitution on the crystal structures and local atomic environments has been characterized by powder X-ray diffraction (XRD) and neutron powder diffraction (NPD), as well as solid-state 23Na, 31P, and 29Si nuclear magnetic resonance (NMR) spectroscopy. A phase transition between 295 and 473 K from monoclinic C2/c to rhombohedral R c is observed for the N3 compositions, while N2 compositions crystallize in a rhombohedral R c unit cell in this temperature range. Alternating current (AC) impedance spectroscopy, molecular dynamics (MD) and high temperature 23Na NMR are in good agreement, showing that with a higher Sc3+ concentration, the ionic conductivity (about 10-4 S/cm at 473 K) decreases and the activation energy for ion diffusion increases. 23Na NMR experiments indicate that the nature of the Na+-ion motion is two-dimensional on the local atomic scale of NMR though the long-range diffusion pathways are three-dimensional. In addition, a combination of MD, bond valence, maximum entropy/Rietveld and van Hove correlation methods has been used, to reveal that the Na+-ion diffusion in these NASICON materials is three-dimensional and that there is a continuous exchange of sodium between Na(1) and Na(2) sites

Structural and Mechanistic Insights into Fast Lithium-Ion Conduction in Li4SiO4-Li3PO4 Solid Electrolytes.

Solid electrolytes that are chemically stable and have a high ionic conductivity would dramatically enhance the safety and operating lifespan of rechargeable lithium batteries. Here, we apply a multi-technique approach to the Li-ion conducting system (1-z)Li4SiO4-(z)Li3PO4 with the aim of developing a solid electrolyte with enhanced ionic conductivity. Previously unidentified superstructure and immiscibility features in high-purity samples are characterized by X-ray and neutron diffraction across a range of compositions (z = 0.0-1.0). Ionic conductivities from AC impedance measurements and large-scale molecular dynamics (MD) simulations are in good agreement, showing very low values in the parent phases (Li4SiO4 and Li3PO4) but orders of magnitude higher conductivities (10(-3) S/cm at 573 K) in the mixed compositions. The MD simulations reveal new mechanistic insights into the mixed Si/P compositions in which Li-ion conduction occurs through 3D pathways and a cooperative interstitial mechanism; such correlated motion is a key factor in promoting high ionic conductivity. Solid-state (6)Li, (7)Li, and (31)P NMR experiments reveal enhanced local Li-ion dynamics and atomic disorder in the solid solutions, which are correlated to the ionic diffusivity. These unique insights will be valuable in developing strategies to optimize the ionic conductivity in this system and to identify next-generation solid electrolytes.The ALISTORE ERI and CNRS are acknowledged for supporting Y.D. through a joint Ph.D. scholarship between Picardie (France) and Bath (UK). The authors thank D. Sheptyakov (PSI, Switzerland) and M. Bianchini (ILL-Grenoble, France) for assistance with neutron diffraction experiments, and M. T. Dunstan (Cambridge, UK) for assistance with NMR experiments. Financial support from the EPSRC Energy Materials Programme (Grant EP/K016288) is gratefully acknowledged. The HPC Materials Chemistry Consortium (EP/L000202) allowed use of the ARCHER facilities. O.P. and S.E. acknowledge support from a Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2014-EF, no. 655444) and an ERASMUS+ scholarship, respectively.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b0444

FHR4-based immunoconjugates direct complement-dependent cytotoxicity and phagocytosis towards HER2-positive cancer cells

Directing selective complement activation towards tumour cells is an attractive strategy to promote their elimination. In the present work, we have generated heteromultimeric immunoconjugates that selectively activate the complement alternative pathway (AP) on tumour cells. We used the C4b-binding protein C-terminal-alpha-/beta-chain scaffold for multimerisation to generate heteromultimeric immunoconjugates displaying (a) a multivalent-positive regulator of the AP, the human factor H-related protein 4 (FHR4) with; (b) a multivalent targeting function directed against erbB2 (HER2); and (c) a monovalent enhanced GFP tracking function. Two distinct VHH targeting two different epitopes against HER2 and competing either with trastuzumab or with pertuzumab-recognising epitopes [VHH(T) or VHH(P)], respectively, were used as HER2 anchoring moieties. Optimised high-FHR4 valence heteromultimeric immunoconjugates [FHR4/VHH(T) or FHR4/VHH(P)] were selected by sequential cell cloning and a selective multistep His-Trap purification. Optimised FHR4-heteromultimeric immunoconjugates successfully overcame FH-mediated complement inhibition threshold, causing increased C3b deposition on SK-OV-3, BT474 and SK-BR3 tumour cells, and increased formation of lytic membrane attack complex densities and complement-dependent cytotoxicity (CDC). CDC varies according to the pattern expression and densities of membrane-anchored complement regulatory proteins on tumour cell surfaces. In addition, opsonised BT474 tumour cells were efficiently phagocytosed by macrophages through complement-dependent cell-mediated cytotoxicity. We showed that the degree of FHR4-multivalency within the multimeric immunoconjugates was the key element to efficiently compete and deregulate FH and FH-mediated convertase decay locally on tumour cell surface. FHR4 can thus represent a novel therapeutic molecule, when expressed as a multimeric entity and associated with an anchoring system, to locally shift the complement steady-state towards activation on tumour cell surface

Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients

Objectives To compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtype B integrase inhibitor (INI)-naive and raltegravir-treated patients. Methods Integrase sequences from 650 INI-naive patients and 84 raltegravir-treated patients were analysed. Results The T124A mutation alone and the combination T124A/L101I were more frequent in raltegravir-failing patients than in INI-naive patients (39.3% versus 24.5%, respectively, P = 0.005 for T124A and 20.2% versus 10.0%, respectively, P = 0.008 for T124A/L101I). The S153Y/F mutations were not detected in any integrase sequence (except for S153F alone, only detected in one INI-naive patient). Conclusions T124A and T124A/L101I, more frequent in raltegravir-treated patients, could have some effect on raltegravir response and their presence could play a role in the selection of other mutations conferring S/GSK1349572 resistance. The impact of raltegravir-mediated changes such as these on the virological response to S/GSK1349572 should be studied further

Nutrients limitation of primary productivity in the Southeast Pacific (BIOSOPE cruise)

Revue sans Comité de lectureInternational audienceIron is an essential nutrient involved in a variety of biological processes in the ocean, including photosynthesis, respiration and nitrogen fixation. Atmospheric deposition of aerosols is recognized as the main source of iron for the surface ocean. In high nutrient, low chlorophyll areas, it is now clearly established that iron limits phytoplankton productivity but its biogeochemical role in low nutrient, low chlorophyll environments has been poorly studied. We investigated this question in the unexplored southeast Pacific, arguably the most oligotrophic area of the global ocean. Situated far from any continental aerosol source, the atmospheric iron flux to this province is amongst the lowest of the world ocean. Here we report that, despite low dissolved iron concentrations (~0.1 nmol l-1) measured across the whole gyre (3 stations situated in the center, the western and the eastern edge), photosynthesis and primary productivity are only limited by iron availability at the border of the gyre, but not in the center. The seasonal stability of the gyre has apparently allowed for the development of populations acclimated to these extreme oligotrophic conditions. Moreover, despite clear evidence of nitrogen limitation in the central gyre, we were unable to measure nitrogen fixation in our experiments, even after iron and/or phosphate additions, and cyanobacterial nifH gene abundances were extremely low compared to the North Pacific Gyre. The South Pacific gyre is therefore unique with respect to the physiological status of its phytoplankton populations