Study of First-Order Thermal Sigma-Delta Architecture for Convective Accelerometers

This paper presents the study of an original closed-loop conditioning approach for fully-integrated convective inertial sensors. The method is applied to an accelerometer manufactured on a standard CMOS technology using an auto-aligned bulk etching step. Using the thermal behavior of the sensor as a summing function, a first order sigma-delta modulator is built. This "electro-physical" modulator realizes an analog-to-digital conversion of the signal. Besides the feedback scheme should improve the sensor performance.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Hepatitis C virus infection and related liver disease: the quest for the best animal model

Hepatitis C virus (HCV) is a major cause of cirrhosis and hepatocellular carcinoma (HCC) making the virus the most common cause of liver failure and transplantation. HCV is estimated to chronically affect 130 million individuals and to lead to more than 350,000 deaths per year worldwide. A vaccine is currently not available. The recently developed direct acting antivirals (DAAs) have markedly increased the efficacy of the standard of care but are not efficient enough to completely cure all chronically infected patients and their toxicity limits their use in patients with advanced liver disease, co-morbidity or transplant recipients. Because of the host restriction, which is limited to humans and non-human primates, in vivo study of HCV infection has been hampered since its discovery more than 20 years ago. The chimpanzee remains the most physiological model to study the innate and adaptive immune responses, but its use is ethically difficult and is now very restricted and regulated. The development of a small animal model that allows robust HCV infection has been achieved using chimeric liver immunodeficient mice, which are therefore not suitable for studying the adaptive immune responses. Nevertheless, these models allowed to go deeply in the comprehension of virus-host interactions and to assess different therapeutic approaches. The immunocompetent mouse models that were recently established by genetic humanization have shown an interesting improvement concerning the study of the immune responses but are still limited by the absence of the complete robust life cycle of the virus. In this review, we will focus on the relevant available animal models of HCV infection and their usefulness for deciphering the HCV life cycle and virus-induced liver disease, as well as for the development and evaluation of new therapeutics. We will also discuss the perspectives on future immunocompetent mouse models and the hurdles to their development

Ergodic vs diffusive decoherence in mesoscopic devices

We report on the measurement of phase coherence length in a high mobility two-dimensional electron gas patterned in two different geometries, a wire and a ring. The phase coherence length is extracted both from the weak localization correction in long wires and from the amplitude of the Aharonov-Bohm oscillations in a single ring, in a low temperature regime when decoherence is dominated by electronic interactions. We show that these two measurements lead to different phase coherence lengths, namely $L_{\Phi}^\mathrm{wire}\propto T^{-1/3}$ and $L_{\Phi}^\mathrm{ring}\propto T^{-1/2}$. This difference reflects the fact that the electrons winding around the ring necessarily explore the whole sample (ergodic trajectories), while in a long wire the electrons lose their phase coherence before reaching the edges of the sample (diffusive regime).Comment: LaTeX, 5 pages, 4 pdf figures ; v2: revised versio

A novel adenovirus vector for easy cloning in the E3 region downstream of the CMV promoter

The construction of expression vectors derived from the human adenovirus type 5 (Ad5), usually based on homologous recombination, is time consuming as a shuttle plasmid has to be selected before recombination with the viral genome. Here, we describe a method allowing direct cloning of a transgene in the E3 region of the Ad5 genome already containing the immediate early CMV promoter upstream of three unique restriction sites. This allowed the construction of recombinant adenoviral genomes in just one step, reducing considerably the time of selection and, of course, production of the corresponding vectors. Using this vector, we produced recombinant adenoviruses, each giving high-level expression of the transgene in the transduced cells

Experimental Test of the Numerical Renormalization Group Theory for Inelastic Scattering from Magnetic Impurities

We present measurements of the phase coherence time \tauphi in quasi one-dimensional Au/Fe Kondo wires and compare the temperature dependence of \tauphi with a recent theory of inelastic scattering from magnetic impurities (Phys. Rev. Lett. 93, 107204 (2004)). A very good agreement is obtained for temperatures down to 0.2 $T_K$. Below the Kondo temperature $T_K$, the inverse of the phase coherence time varies linearly with temperature over almost one decade in temperature.Comment: 5 pages, 3 figure

Quantum Coherence at Low Temperatures in Mesoscopic Systems: Effect of Disorder

We study the disorder dependence of the phase coherence time of quasi one-dimensional wires and two-dimensional (2D) Hall bars fabricated from a high mobility GaAs/AlGaAs heterostructure. Using an original ion implantation technique, we can tune the intrinsic disorder felt by the 2D electron gas and continuously vary the system from the semi-ballistic regime to the localized one. In the diffusive regime, the phase coherence time follows a power law as a function of diffusion coefficient as expected in the Fermi liquid theory, without any sign of low temperature saturation. Surprisingly, in the semi-ballistic regime, it becomes independent of the diffusion coefficient. In the strongly localized regime we find a diverging phase coherence time with decreasing temperature, however, with a smaller exponent compared to the weakly localized regime.Comment: 21 pages, 30 figure

Low temperature dephasing in irradiated metallic wires

We present phase coherence time measurements in quasi-one-dimensional Ag wires implanted with Ag$^{+}$ ions with an energy of $100 keV$. The measurements have been carried out in the temperature range from $100 mK$ up to $10 K$; this has to be compared with the Kondo temperature of iron in silver, i.e. $T_{K}^{Ag/Fe} \approx 4 K$, used in recent experiments on dephasing in Kondo systems\cite{mallet_prl_06,birge_prl_06}. We show that the phase coherence time is not affected by the implantation procedure, clearly proving that ion implantation process by itself \emph{does not lead to any extra dephasing} at low temperature.Comment: 4 pages, 4figure

Synergy of entry inhibitors with direct-acting antivirals uncovers novel combinations for prevention and treatment of hepatitis C

Objective: Although direct-acting antiviral agents (DAAs) have markedly improved the outcome of treatment in chronic HCV infection, there continues to be an unmet medical need for improved therapies in difficult-to-treat patients as well as liver graft infection. Viral entry is a promising target for antiviral therapy. Design: Aiming to explore the role of entry inhibitors for future clinical development, we investigated the antiviral efficacy and toxicity of entry inhibitors in combination with DAAs or other host-targeting agents (HTAs). Screening a large series of combinations of entry inhibitors with DAAs or other HTAs, we uncovered novel combinations of antivirals for prevention and treatment of HCV infection. Results: Combinations of DAAs or HTAs and entry inhibitors including CD81-, scavenger receptor class B type I (SR-BI)- or claudin-1 (CLDN1)-specific antibodies or small-molecule inhibitors erlotinib and dasatinib were characterised by a marked and synergistic inhibition of HCV infection over a broad range of concentrations with undetectable toxicity in experimental designs for prevention and treatment both in cell culture models and in human liver-chimeric uPA/SCID mice. Conclusions: Our results provide a rationale for the development of antiviral strategies combining entry inhibitors with DAAs or HTAs by taking advantage of synergy. The uncovered combinations provide perspectives for efficient strategies to prevent liver graft infection and novel interferon-free regimens

In vivo combination of human anti-envelope glycoprotein E2 and -Claudin-1 monoclonal antibodies for prevention of hepatitis C virus infection

Despite the development of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection remains a major cause for liver disease and cancer worldwide. Entry inhibitors block virus host cell entry and, therefore, prevent establishment of chronic infection and liver disease. Due to their unique mechanism of action, entry inhibitors provide an attractive antiviral strategy in organ transplantation. In this study, we developed an innovative approach in preventing HCV infection using a synergistic combination of a broadly neutralizing human monoclonal antibody (HMAb) targeting the HCV E2 protein and a host-targeting anti-claudin 1 (CLDN1) humanized monoclonal antibody. An in vivo proof-of-concept study in human liver-chimeric FRG-NOD mice proved the efficacy of the combination therapy at preventing infection by an HCV genotype 1b infectious serum. While administration of individual antibodies at lower doses only showed a delay in HCV infection, the combination therapy was highly protective. Furthermore, the combination proved to be effective in preventing infection of primary human hepatocytes by neutralization-resistant HCV escape variants selected during liver transplantation, suggesting that a combination therapy is suited for the neutralization of difficult-to-treat variants. In conclusion, our findings suggest that the combination of two HMAbs targeting different steps of virus entry improves treatment efficacy while simultaneously reducing treatment duration and costs. Our approach not only provides a clinical perspective to employ HMAb combination therapies to prevent graft re-infection and its associated liver disease but may also help to alleviate the urgent demand for organ transplants by allowing the transplantation of organs from HCV-positive donors

Hepatitis C virus infection and tight junction proteins: The ties that bind.

The hepatitis C virus (HCV) is a major cause of liver diseases ranging from liver inflammation to advanced liver diseases like cirrhosis and hepatocellular carcinoma (HCC). HCV infection is restricted to the liver, and more specifically to hepatocytes, which represent around 80% of liver cells. The mechanism of HCV entry in human hepatocytes has been extensively investigated since the discovery of the virus 30 years ago. The entry mechanism is a multi-step process relying on several host factors including heparan sulfate proteoglycan (HSPG), low density lipoprotein receptor (LDLR), tetraspanin CD81, Scavenger Receptor class B type I (SR-BI), Epidermal Growth Factor Receptor (EGFR) and Niemann-Pick C1-like 1 (NPC1L1). Moreover, in order to establish a persistent infection, HCV entry is dependent on the presence of tight junction (TJ) proteins Claudin-1 (CLDN1) and Occludin (OCLN). In the liver, tight junction proteins play a role in architecture and homeostasis including sealing the apical pole of adjacent cells to form bile canaliculi and separating the basolateral domain drained by sinusoidal blood flow. In this review, we will highlight the role of liver tight junction proteins in HCV infection, and we will discuss the potential targeted therapeutic approaches to improve virus eradication.journal articlereview2020 Jul 012020 04 05importe