Simulation of Transport and Gain in Quantum Cascade Lasers

Quantum cascade lasers can be modeled within a hierarchy of different approaches: Standard rate equations for the electron densities in the levels, semiclassical Boltzmann equation for the microscopic distribution functions, and quantum kinetics including the coherent evolution between the states. Here we present a quantum transport approach based on nonequilibrium Green functions. This allows for quantitative simulations of the transport and optical gain of the device. The division of the current density in two terms shows that semiclassical transitions are likely to dominate the transport for the prototype device of Sirtori et al. but not for a recent THz-laser with only a few layers per period. The many particle effects are extremely dependent on the design of the heterostructure, and for the case considered here, inclusion of electron-electron interaction at the Hartree Fock level, provides a sizable change in absorption but imparts only a minor shift of the gain peak.Comment: 12 pages, 5 figures included, to appear in in "Advances in Solid State Physics", ed. by B. Kramer (Springer 2003

Gain in quantum cascade lasers and superlattices: A quantum transport theory

Gain in current-driven semiconductor heterostructure devices is calculated within the theory of nonequilibrium Green functions. In order to treat the nonequilibrium distribution self-consistently the full two-time structure of the theory is employed without relying on any sort of Kadanoff-Baym Ansatz. The results are independent of the choice of the electromagnetic field if the variation of the self-energy is taken into account. Excellent quantitative agreement is obtained with the experimental gain spectrum of a quantum cascade laser. Calculations for semiconductor superlattices show that the simple 2-time miniband transport model gives reliable results for large miniband widths at room temperatureComment: 8 Pages, 4 Figures directly included, to appear in Physical Review

Anisotropy and nonlinearity in superlattices

This paper uses analytical expressions for the nonlinear optical absorption of superlattices by treating them as anisotropic media. The controllable system shows that the nonlinearities increase with anisotropy suggesting that strongly anisotropic materials such as those used for solar cells may also be useful for nonlinear optical applications

Can hibernators sense and evade fires? Olfactory acuity and locomotor performance during deep torpor.

Increased habitat fragmentation, global warming and other human activities have caused a rise in the frequency of wildfires worldwide. To reduce the risks of uncontrollable fires, prescribed burns are generally conducted during the colder months of the year, a time when in many mammals torpor is expressed regularly. Torpor is crucial for energy conservation, but the low body temperatures (T b) are associated with a decreased responsiveness and torpid animals might therefore face an increased mortality risk during fires. We tested whether hibernators in deep torpor (a) can respond to the smell of smoke and (b) can climb to avoid fires at T bs below normothermic levels. Our data show that torpid eastern pygmy-possums (Cercartetus nanus) are able to detect smoke and also can climb. All males aroused from torpor when the smoke stimulus was presented at an ambient temperature (T a) of 15 °C (T b ∼18 °C), whereas females only raised their heads. The responses were less pronounced at T a 10 °C. The first coordinated movement of possums along a branch was observed at a mean T b of 15.6 °C, and animals were even able to climb their prehensile tail when they reached a mean T b of 24.4 °C. Our study shows that hibernators can sense smoke and move at low T b. However, our data also illustrate that at T b ≤13 °C, C. nanus show decreased responsiveness and locomotor performance and highlight that prescribed burns during winter should be avoided on very cold days to allow torpid animals enough time to respond

The role of kinetic context in apparent biased agonism at GPCRs

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

AAV2-Mediated Combined Subretinal Delivery of IFN-α and IL-4 Reduces the Severity of Experimental Autoimmune Uveoretinitis

We previously showed that adeno-associated virus 2 (AAV2) mediated subretinal delivery of human interferon-alpha (IFN-α) could effectively inhibit experimental autoimmune uveoretinitis (EAU). In this study we investigated whether subretinal injection of both AVV2.IFN-α and AAV2.IL-4 had a stronger inhibition on EAU activity. B10RIII mice were subretinally injected with AAV2.IFN-α alone (1.5×107 vg), AAV2.IL-4 alone (3.55×107 vg), and AAV2.IFN-α combined with AAV2.IL-4. PBS, AAV2 vector encoding green fluorescent protein (AAV2.GFP) (5×107 vg) was subretinally injected as a control. IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically. AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α. The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone. There was no difference concerning DTH (delayed-type hypersensitivity) reaction, lymphocyte proliferation and IL-17 production among the investigated treatment groups, suggesting that local retinal gene delivery did not affect the systemic immune response

A Novel Labeling Approach Identifies Three Stability Levels of Acetylcholine Receptors in the Mouse Neuromuscular Junction In Vivo

The turnover of acetylcholine receptors at the neuromuscular junction is regulated in an activity-dependent manner. Upon denervation and under various other pathological conditions, receptor half-life is decreased., in our setup the same animals are used throughout the whole measurement period, thereby permitting a dramatic reduction of animal numbers at increased data quality. We identified three stability levels of acetylcholine receptors depending on the presence or absence of innervation: one pool of receptors with a long half-life of ∼13 days, a second with an intermediate half-life of ∼8 days, and a third with a short half-life of ∼1 day. Data were highly reproducible from animal to animal and followed simple exponential terms. The principal outcomes of these measurements were reproduced by an optical pulse-labeling assay introduced recently.A novel assay to determine kinetics of acetylcholine receptor turnover with small animal numbers is presented. Our data show that nerve activity acts on muscle acetylcholine receptor stability by at least two different means, one shifting receptor lifetime from short to intermediate and another, which further increases receptor stability to a long lifetime. We hypothesize on possible molecular mechanisms

Assessment of Blood Hemodynamics by USPIO-Induced R1 Changes in MRI of Murine Colon Carcinoma

The objective of this study is to assess whether ultrasmall superparamagnetic iron oxide (USPIO)-induced changes of the water proton longitudinal relaxation rate (R1) provide a means to assess blood hemodynamics of tumors. Two types of murine colon tumors (C26a and C38) were investigated prior to and following administration of USPIO blood-pool contrast agent with fast R1 measurements. In a subpopulation of mice, R1 was measured following administration of hydralazine, a well-known blood hemodynamic modifier. USPIO-induced R1 increase in C38 tumors (ΔR1 = 0.072 ± 0.0081 s−1) was significantly larger than in C26a tumors (ΔR1 = 0.032 ± 0.0018 s−1, N = 9, t test, P < 0.001). This was in agreement with the immunohistochemical data that showed higher values of relative vascular area (RVA) in C38 tumors than in C26a tumors (RVA = 0.059 ± 0.015 vs. 0.020 ± 0.011; P < 0.05). Following administration of hydralazine, a decrease in R1 value was observed. This was consistent with the vasoconstriction induced by the steal effect mechanism. In conclusion, R1 changes induced by USPIO are sensitive to tumor vascular morphology and to blood hemodynamics. Thus, R1 measurements following USPIO administration can give novel insight into the effects of blood hemodynamic modifiers, non-invasively and with a high temporal resolution