High levels of parasite-specific IgG1 correlate with the amicrofilaremic state in Loa loa infection

To investigate the mechanisms of protective immunity operating in Loa loa infection, 56 persons from a L. ioa-endemic village in southeast Gabon were examined over a 7-year period. The level of L. loa-specific IgG subclasses in defined parasitologic groups was compared by use of ELISA with either adult, microfilarial, or third-stage larval (L3) antigens of L. loa. With all antigen preparations, IgG1 levels were significantly higher in amicrofilaremic persons than in persons with high or low levels of microfilariae. Moreover, there was a significant negative correlation between IgG1 levels to L3 antigen and the density of microfilariae (Spearman's r(s) = -.701; P < .01). There was no correlation between density of microfilariae and levels of other IgG subclasses or of IgE. These data indicate that IgG1 may play a role in the effector mechanism(s) involved in resistance against L. loa and suggest that L3 antigens may be important in eliciting protective responses.     

Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy

The absence of reliable, robust, and non-invasive biomarkers for anti- Programmed cell death protein 1 (PD-1) immunotherapy is an urgent unmet medical need for the treatment of cancer patients. No predictive biomarkers have been established based on the direct assessment of T cell functions, the primary mechanism of action of anti-PD-1 therapy. In this study, we established a model system to test T cell functions modulated by Nivolumab using anti-CD3 monoclonal antibody (mAb)-stimulated peripheral blood mononuclear cells (PBMCs), and characterized T cell functions primarily based on the knowledge gained from retrospective observations of patients treated with anti-PD-1 immunotherapy. During a comprehensive cytokine profile assessment to identify potential biomarkers, we found that Nivolumab increases expression of T helper type 1 (Th1) associated cytokines such as interferon-γ (IFN-γ) and interleukin-2 (IL-2) in a subset of donors. Furthermore, Nivolumab increases production of Th2, Th9, and Th17 associated cytokines, as well as many proinflammatory cytokines such as IL-6 in a subset of donors. Conversely, Nivolumab treatment has no impact on T cell proliferation, expression of CD25, CD69, or Granzyme B, and only modestly increases in the expansion of regulatory T cells. Our results suggest that assessment of cytokine production using a simple PBMC-based T cell functional assay could be used as a potential predictive marker for anti-PD-1 immunotherapy.     

Low frequency noise characterization in 0.13 μm p-MOSFETs. Impact of scaled-down 0.25, 0.18 and 0.13 μm technologies on 1/f noise

This paper presents an experimental analysis of the noise measurements performed in 0.13 μm technology p-MOS transistors operating from weak to strong inversion in ohmic and saturation regimes. The 1/f noise origin is interpreted in terms of carrier number with correlated mobility fluctuations. The contribution of the access resistance noise is noticed for large overdrive voltages. The slow oxide trap density N_t(E_F) and the Coulomb scattering noise parameter α_s have been extracted. Then the 1/f noise level in the three scaled-down p-MOSFETs generations (0.25, 0.18 and 0.13 μm) is compared. The variation of the noise parameter values is discussed with respect to the technology node. The highest oxide trap density is obtained for the thinnest gate oxide. It is concluded that the oxide thinning should lead to noise reduction only if the product t_ox². N_t is taken into consideration. This trend will be significant in future scaled-down MOSFETs.