The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated ...

Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act a...

This paper provides an overview of recent results for relay-delay systems. In a first section, simple examples illustrate the problems induced by delays in the synthesis of sliding mode controllers. Then, a brief overview of the existing results shows the present advances and limits in this domain. The last parts of the paper are devoted to new results: first, for systems with state delay, then...

We report the effect of serum pH and of the presence or absence of mercaptoethanol, N-acetyl-L-cysteine, monothioglycerol, ethylenediaminetetraacetate, and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetate on the activation of the human creatine kinase isoenzymes. At the serum pH giving maximal enzyme stability and minimal assay lag phase (Nealon et al., Clin. Chem. 26: 1165-116...

Abstract Less than 50% of ovarian cancer patients survive five years after diagnosis. This rate has changed little in the last 30 years, highlighting need for novel therapies. A promising strategy employs T cells engineered to target tumor-expressed proteins. Mesothelin (Msln) is overexpressed cancers, contributes malignant and invasive phenotype limited expression healthy cells, making it a ca...

The product of the LAG-3 gene is a cell surface protein with significant homology to CD4. It has been suggested that it can serve as a functional equivalent of CD4 and account for the MHC class II-restricted responses which persist in CD4-deficient mice. To test this hypothesis, we have created CD4/LAG-3 double-deficient mice by successive homologous recombinations in embryonic stem cells. Thes...

OBJECTIVES Although CD8+ T cells play a critical role in the control of HIV-1 infection,their antiviral efficacy can be limited by antigenic variation and immune exhaustion.The latter phenomenon is characterized by the upregulation of multiple inhibitory receptors, such as programmed death-1 (PD-1), CD244 and lymphocyte activation gene-3 (LAG-3), which modulate the functional capabilities of CD...

Naturally acquired immunity to malaria develops slowly, requiring several years of repeated exposure to be effective. The cellular and molecular factors underlying this observation are only partially understood. Recent studies suggest that chronic Plasmodium falciparum exposure may induce functional exhaustion of lymphocytes, potentially impeding optimal control of infection. However, it remain...

In a recent paper we presented the first adaptive control design for an ODE system with a possibly large actuator delay of unknown length. We achieved global stability under full state feedback. In this paper we generalize the design to the situation where, besides the unknown delay value, the ODE also has unknown parameters, and where trajectory tracking (rather than equilibrium regulation) is...