The structural dependence of the effective mass and Luttinger parameters in semiconductor quantum wells

A detailed comparison of the empirical pseudopotential method with single and multiple band calculations based on the envelope function and effective mass approximations are presented. It is shown that, in order to give agreement with the more rigorous microscopic approach of the pseudopotential method, structural dependent effective masses and Luttinger parameters must be invoked. The CdTe/Cd(1 – x)Mn(x)Te system has been employed as an example, and the first pseudopotential calculations of quantum wells and superlattices in this material are presented. It is shown that the electron, light- and heavy-hole effective masses tend towards twice their bulk values in the limit of narrow quantum wells. © 1997 American Institute of Physics

Double crystal x-ray diffraction simulations of diffusion in semiconductor microstructures

Diffusion in group IV, III-V and II-VI semiconductors is an interesting problem not only from a fundamental physics viewpoint but also in practical terms, since it could determine the useful lifetime of a device. Any attempt to control the amount of diffusion in a semiconductor device, whether it be a quantum well structure or not, requires an accurate determination of the diffusion coefficient. The present theoretical study shows that this could be achieved via x-ray diffraction studies in quantum well structures. It is demonstrated that the rocking curves of single quantum wells are not sensitive to diffusion. However the intensity of the first order satellite, which is characteristic of superlattice rocking curves, is strongly dependent upon diffusion and it is proposed that this technique could be used to measure the diffusion coefficient D. © 1998 American Institute of Physics

Kinetics of human myeloid-derived suppressor cells after blood draw

Background: Human myeloid-derived suppressor cells (MDSC) have been described as a group of immature myeloid cells which exert immunosuppressive action by inhibiting function of T lymphocytes. While there is a huge scientific interest to study these cells in multiple human diseases, the methodological approach varies substantially between published studies. This is problematic as human MDSC seem to be a sensible cell type concerning not only cryopreservation but also time point after blood draw. To date data on delayed blood processing influencing cell numbers and phenotype is missing. We therefore evaluated the kinetics of granulocytic MDSC (gMDSC) and monocytic MDSC (mMDSC) frequencies after blood draw in order to determine the best time point for analysis of this recently defined cell type. Methods: In this study, we isolated peripheral blood mononuclear cells (PBMC) of patients with HIV infection or solid tumors directly after blood draw. We then analyzed the frequencies of gMDSC and mMDSC 2, 4 and 6 h after blood draw and after an overnight rest by FACS analysis using the standard phenotypic markers. In addition, part of the cells was frozen directly after PBMC preparation and was measured after thawing. Results: gMDSC levels showed no significant difference using fresh PBMC over time with a limitation for the overnight sample. However they were massively diminished after freezing (p = 0.0001 for all subjects). In contrast, frequencies of fresh mMDSC varied over time with no difference between time point 2 and 4 h but a significantly reduction after 6 h and overnight rest (p = 0.0005 and p = 0.005 respectively). Freezing of PBMC decreased the yield of mMDSC reaching statistical significance (p = 0.04). For both MDSC subgroups, FACS analysis became more difficult over time due to less sharp divisions between populations. Conclusions: According to our data human MDSC need to be studied on fresh PBMC. gMDSC can be studied with delay, mMDSC however should be studied no later than 4 h after blood draw. These results are crucial as an increasing number of clinical trials aim at analyzing MDSC nowadays and the logistics of blood processing implies delayed sample processing in some cases

High frequencies of PMN-MDSCs are associated with low suppressive capacity in advanced stages of HIV-1 infection

Background Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are an immature cell type that inhibits the effector functions of T lymphocytes in chronic HIV infection. A well-known immunological feature of the disease course is the development of immune exhaustion, which is correlated with excessive immune activation in late-stage disease. Here, we hypothesized that immune exhaustion would also affect PMN-MDSCs in late-stage HIV-1 infection. Methods We evaluated untreated chronically HIV-infected patients (progressors, n = 10) and control groups (controllers, patients with non-small cell lung carcinoma and healthy controls, n = 16) with regard to levels of PMN-MDSCs and their inhibitory potential. Additionally, we studied CD8 T cell effector functions (interferon-gamma, TNF alpha, IL-2 and CD107) and parameters of CD8 T cell activation (CD38 and HLA-DR) and exhaustion (PD-1 and LAG-3) by flow cytometry. Plasma inflammation markers analyzed here were IL-6, IL-8, soluble CD14, highly sensitive CRP, and cystatin C. Results Coincubation experiments with isolated PMN-MDSCs led to a significant inhibition of CD8 T cell proliferation (p < 0.0001), with a significant correlation between PMN-MDSC frequency and suppressive capacity: the higher the frequency of PMN-MDSCs was, the lower the suppressive capacity (rho = 0.51, p = 0.0082). Stratifying all study subjects into subgroups with PMN-MDSC frequencies above or below 2.5% resulted in a significantly increased suppressive capacity in patients with frequencies below 2.5% (p = 0.021). While there was no correlation with the cellular activation markers CD38 and HLA-DR, high IL-8 levels were significantly associated with high PMN-MDSC frequencies (rho = 0.52, p = 0.0074) and low suppressive capacity (rho = 0.47, p = 0.019). Conclusions In this study, we demonstrate for the first time that PMN-MDSCs show limited effector functions in advanced disease stages of HIV infection. The hyperactive immune state is associated with this loss of function. However, we show an association with the proinflammatory cytokine IL-8, which is an important factor for the migration and adhesion of polymorphonuclear cells

Treatment intensification in HIV-infected Patients is associated With reduced Frequencies of regulatory T cells

In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [= 5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets. The New Era (NE) study recruited patients with primary HIV infection (PHI) or chronically HIV-infected patients with conventional ART (CHI) and applied an intensified 5-drug regimen containing maraviroc and raltegravir for several years. We compared the frequencies of the immune suppressive cells, namely, the myeloid-derived suppressor cells (MDSCs), regulatory B cells (Bregs), and regulatory T cells (Tregs), of the treatment intensification patients to the control groups, especially to the patients with conventional 3-drug ART, and analyzed the Gag/Nef-specific CD8 T cell responses. There were no differences between PHI and CHI in the NE population (p > 0.11) for any of the studied cell types. Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic myeloid-derived suppressor cell (M-MDSC), and the Breg frequencies were comparable to those of patients with a 3-drug ART. However, the Treg levels were significantly lower in the NE patients than those in 3ART-treated individuals and other control groups (p = 0.0033). The Gag/Nef-specific CD8 T cell response was broader (p = 0.0134) with a higher magnitude (p = 0.026) in the NE population than that in the patients with conventional ART. However, we did not find a correlation between the frequency of the immune suppressive cells and the interferon-gamma+ CD8 T cell response. In the treatment intensification subjects, the frequencies of the immune suppressive cells were comparable or lower than those of the conventional ART-treated subjects, with surprisingly broad HIV-specific CD8 T cell responses, suggesting a preservation of immune function with the applied treatment regimen. Interestingly, these effects were seen in both treatment intensification subpopulations and were not attributed to the start of treatment in primary infection