Immune responses against hepatitis C virus genotype 3a virus-like particles in mice: A novel VLP prime-adenovirus boost strategy

Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15-20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy. (C) 2015 Elsevier Ltd. All rights reserved.

Design of a Wearable Remote Neonatal Health Monitoring Device

In this text we present the design of a wearable health monitoring device capable of remotely monitoring health parameters of neonates for the first few weeks after birth. The device is primarily aimed at continuously tracking the skin temperature to indicate the onset of hypothermia in newborns. A medical grade thermistor is responsible for temperature measurement and is directly interfaced to a microcontroller with an integrated bluetooth low energy radio. An inertial sensor is also present in the device to facilitate breathing rate measurement which has been discussed briefly. Sensed data is transferred securely over bluetooth low energy radio to a nearby gateway, which relays the information to a central database for real time monitoring. Low power optimizations at both the circuit and software levels ensure a prolonged battery life. The device is packaged in a baby friendly, water proof housing and is easily sterilizable and reusable.

Influence of recombination on acquisition and reversion of immune escape and compensatory mutations in HIV-1

Following transmission, HIV-1 adapts in the new host by acquiring mutations that allow it to escape from the host immune response at multiple epitopes. It also reverts mutations associated with epitopes targeted in the transmitting host but not in the new host. Moreover, escape mutations are often associated with additional compensatory mutations that partially recover fitness costs. It is unclear whether recombination expedites this process of multi-locus adaptation. To elucidate the role of recombination, we constructed a detailed population dynamics model that integrates viral dynamics, host immune response at multiple epitopes through cytotoxic T lymphocytes, and viral evolution driven by mutation, recombination, and selection. Using this model, we compute the expected waiting time until the emergence of the strain that has gained escape and compensatory mutations against the new host's immune response, and reverted these mutations at epitopes no longer targeted. We find that depending on the underlying fitness landscape, shaped by both costs and benefits of mutations, adaptation proceeds via distinct dominant pathways with different effects of recombination, in particular distinguishing escape and reversion. When adaptation at a single epitope is involved, recombination can substantially accelerate immune escape but minimally affects reversion. When multiple epitopes are involved, recombination can accelerate or inhibit adaptation depending on the fitness landscape. Specifically, recombination tends to delay adaptation when a purely uphill fitness landscape is accessible at each epitope, and accelerate it when a fitness valley is associated with each epitope. Our study points to the importance of recombination in shaping the adaptation of HIV-1 following its transmission to new hosts, a process central to T cell-based vaccine strategies. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.

Toward a High-Resolution Monitoring of Continental Surface Water Extent and Dynamics, at Global Scale: from GIEMS (Global Inundation Extent from Multi-Satellites) to SWOT (Surface Water Ocean Topography)

Up to now, high-resolution mapping of surface water extent from satellites has only been available for a few regions, over limited time periods. The extension of the temporal and spatial coverage was difficult, due to the limitation of the remote sensing technique e.g., the interaction of the radiation with vegetation or cloud for visible observations or the temporal sampling with the synthetic aperture radar (SAR)]. The advantages and the limitations of the various satellite techniques are reviewed. The need to have a global and consistent estimate of the water surfaces over long time periods triggered the development of a multi-satellite methodology to obtain consistent surface water all over the globe, regardless of the environments. The Global Inundation Extent from Multi-satellites (GIEMS) combines the complementary strengths of satellite observations from the visible to the microwave, to produce a low-resolution monthly dataset () of surface water extent and dynamics. Downscaling algorithms are now developed and applied to GIEMS, using high-spatial-resolution information from visible, near-infrared, and synthetic aperture radar (SAR) satellite images, or from digital elevation models. Preliminary products are available down to 500-m spatial resolution. This work bridges the gaps and prepares for the future NASA/CNES Surface Water Ocean Topography (SWOT) mission to be launched in 2020. SWOT will delineate surface water extent estimates and their water storage with an unprecedented spatial resolution and accuracy, thanks to a SAR in an interferometry mode. When available, the SWOT data will be adopted to downscale GIEMS, to produce a long time series of water surfaces at global scale, consistent with the SWOT observations.

The W-11-4A platform comprehensive strength monitoring system

A comprehensive strength monitoring system used on a fixed jacket platform is presented in this paper. The long-term monitoring of W-11-4A platform achieved. Structural responses (strain and acceleration) at selected locations, as well as associated environmental parameters, have been obtained. The emphasis of the paper is placed on the system design, and the instrumentation and operation methodology employed in the monitoring of the structural responses. The performance of the system and the characteristic results obtained during its 13-month operation are also summarized.

Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

In vivo regulation of the Vi antigen in Salmonella and induction of immune responses with an in vivo-inducible promoter.

Salmonella enterica serovar Typhi, the agent of typhoid fever in humans, expresses the surface Vi polysaccharide antigen that contributes to virulence. However, Vi expression can also be detrimental to some key steps of S. Typhi infectivity, for example, invasion, and Vi is the target of protective immune responses. We used a strain of S. Typhimurium carrying the whole Salmonella pathogenicity island 7 (SPI-7) to monitor in vivo Vi expression within phagocytic cells of mice at different times after systemic infection. We also tested whether it is possible to modulate Vi expression via the use of in vivo-inducible promoters and whether this would trigger anti-Vi antibodies through the use of Vi-expressing live bacteria. Our results show that Vi expression in the liver and spleen is downregulated with the progression of infection and that the Vi-negative population of bacteria becomes prevalent by day 4 postinfection. Furthermore, we showed that replacing the natural tviA promoter with the promoter of the SPI-2 gene ssaG resulted in sustained Vi expression in the tissues. Intravenous or oral infection of mice with a strain of S. Typhimurium expressing Vi under the control of the ssaG promoter triggered detectable levels of all IgG subclasses specific for Vi. Our work highlights that Vi is downregulated in vivo and provides proof of principle that it is possible to generate a live attenuated vaccine that induces Vi-specific antibodies after single oral administration.

Thin film monitoring with silicon bulk acoustic resonators

Abstract-This paper reports a single-crystal silicon mass sensor based on a square-plate resonant structure excited in the wine glass bulk acoustic mode at a resonant frequency of 2.065 MHz and an impressive quality factor of 4 million at 12 mtorr pressure. Mass loading on the resonator results in a linear downshift in the resonant frequency of this device, wherein the measured sensitivity is found to be 175 Hz cm2/μg. The silicon resonator is embedded in an oscillator feedback loop, which has a short-term frequency stability of 3 mHz (approximately 1.5 ppb) at an operating pressure of 3.2 mtorr, corresponding to an equivalent mass noise floor of 17 pg/cm2. Possible applications of this device include thin film monitoring and gas sensing, with the potential added benefits of scalability and integration with CMOS technology. © 2008 IEEE.

Monitoring A Micromechanical Process In Macroscale Carbon Nanotube Films And Fibers

The evaluation of mechanical properties of carbon nanotube (CNT) fibers is inherently difficult. Here, Raman scattering-a generic methodology independent of mechanical measurements-is used to determine the interbundle strength and microscopic failure process for various CNT macroarchitectures. Raman data are used to predict the moduli of CNT films and fibers, and to illustrate the influences of the twisting geometries on the fibers' mechanical performances.