Ultrafast pump-probe dynamics in ZnSe-based semiconductor quantum-wells

Pump-probe experiments are used as a controllable way to investigate the properties of photoexcited semiconductors, in particular, the absorption saturation. We present an experiment-theory comparison for ZnSe quantum wells, investigating the energy renormalization and bleaching of the excitonic resonances. Experiments were performed with spin-selective excitation and above-bandgap pumping. The model, based on the semiconductor Bloch equations in the screened Hartree-Fock approximation, takes various scattering processes into account phenomenologically. Comparing numerical results with available experimental data, we explain the experimental results and find that the electron spin-flip occurs on a time scale of 30 ps.Comment: 10 pages, 9 figures. Key words: nonlinear and ultrafast optics, modeling of femtosecond pump-probe experiments, electron spin-flip tim

Nonlinear Optical Response Functions of Mott Insulators Based on Dynamical Mean Field Approximation

We investigate the nonlinear optical susceptibilities of Mott insulators with the dynamical mean field approximation. The two-photon absorption (TPA) and the third-harmonic generation (THG) spectra are calculated, and the classification by the types of coupling to external fields shows different behavior from conventional semiconductors. The direct transition terms are predominant both in the TPA and THG spectra, and the importance of taking all types of interaction with the external field into account is illustrated in connection with the THG spectrum and dcKerr effect. The dependence of the TPA and THG spectra on the Coulomb interaction indicate a scaling relation. We apply this relation to the quantitative evaluation and obtain results comparable to those of experiments.Comment: 14 pages, 12 figure

An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.

BackgroundType 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed.MethodsWe conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals.ResultsA total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed.ConclusionsTeplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.)

?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA

Combining Antigen-Based Therapy with GABA Treatment Synergistically Prolongs Survival of Transplanted ß-Cells in Diabetic NOD Mice

Antigen-based therapies (ABTs) very effectively prevent the development of type 1 diabetes (T1D) when given to young nonobese diabetic (NOD) mice, however, they have little or no ability to reverse hyperglycemia in newly diabetic NOD mice. More importantly, ABTs have not yet demonstrated an ability to effectively preserve residual ß-cells in individuals newly diagnosed with type 1 diabetes (T1D). Accordingly, there is great interest in identifying new treatments that can be combined with ABTs to safely protect ß-cells in diabetic animals. The activation of γ-aminobutyric acid (GABA) receptors (GABA-Rs) on immune cells has been shown to prevent T1D, experimental autoimmune encephalomyelitis (EAE) and rheumatoid arthritis in mouse models. Based on GABA's ability to inhibit different autoimmune diseases and its safety profile, we tested whether the combination of ABT with GABA treatment could prolong the survival of transplanted ß-cells in newly diabetic NOD mice. Newly diabetic NOD mice were untreated, or given GAD/alum (20 or 100 µg) and placed on plain drinking water, or water containing GABA (2 or 6 mg/ml). Twenty-eight days later, they received syngenic pancreas grafts and were monitored for the recurrence of hyperglycemia. Hyperglycemia reoccurred in the recipients given plain water, GAD monotherapy, GABA monotherapy, GAD (20 µg)+GABA (2 mg/ml), GAD (20 µg)+GABA (6 mg/ml) and GAD (100 µg)+GABA (6 mg/ml) about 1, 2-3, 3, 2-3, 3-8 and 10-11 weeks post-transplantation, respectively. Thus, combined GABA and ABT treatment had a synergistic effect in a dose-dependent fashion. These findings suggest that co-treatment with GABA (or other GABA-R agonists) may provide a new strategy to safely enhance the efficacy of other therapeutics designed to prevent or reverse T1D, as well as other T cell-mediated autoimmune diseases

Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD65. Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD65 autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD65, but not with control antigens, compared with placebo subjects. GAD65-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD65 enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD65-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD65 immunity

Nonlinear optics and saturation behavior of quantum dot samples under continuous wave driving

The nonlinear optical response of self-assembled quantum dots is relevant to the application of quantum dot based devices in nonlinear optics, all-optical switching, slow light and self-organization. Theoretical investigations are based on numerical simulations of a spatially and spectrally resolved rate equation model, which takes into account the strong coupling of the quantum dots to the carrier reservoir created by the wetting layer states. The complex dielectric susceptibility of the ground state is obtained. The saturation is shown to follow a behavior in between the one for a dominantly homogeneously and inhomogeneously broadened medium. Approaches to extract the nonlinear refractive index change by fringe shifts in a cavity or self-lensing are discussed. Experimental work on saturation characteristic of InGa/GaAs quantum dots close to the telecommunication O-band (1.24-1.28 mm) and of InAlAs/GaAlAs quantum dots at 780 nm is described and the first demonstration of the cw saturation of absorption in room temperature quantum dot samples is discussed in detail