Microscopic theory of gain, absorption, and refractive index insemiconductor laser materials-influence of conduction-bandnonparabolicity and Coulomb-induced intersubband coupling

The influence of the conduction-band nonparabolicity and Coulomb coupling between different electronic subbands and different hole subbands on gain, absorption, and refractive index in semiconductor heterostructures is investigated. We implement these features into a fully microscopic approach. At low carrier densities, the nonparabolicity leads to a steeper increase of the absorption for increasing transition energy. In this regime, the Coulomb subband coupling allows for a shift of oscillator strength to energetically lower transitions. In the gain regime, the conduction-band nonparabolicity is shown to reduce the gain width for a given carrier density and to strongly modify the corresponding refractive index. The Coulomb coupling is especially important to determine the correct energetic position and density dependence of the gain maximum. In addition, it leads to a steeper transition from the gain to the absorptive region     

Raman oscillation with intracavity sum-frequency generation

We use a plane-wave analysis to examine a Raman oscillator containing an intracavity sum-frequency interaction that frequency sums the circulating first-order Stokes radiation with the pump radiation. We find that there is an optimum ratio between the nonlinear coupling in the Raman medium and the nonlinear coupling in the sum-frequency generator. We also find that higher order Stokes radiation should be suppressed with the optimum choice of nonlinear coupling in the sum-frequency interaction. Numerical integration of the equations containing transverse effects predicts a time-averaged power-conversion efficiency of 61.4% for conversion of 532- to 273.5-nm radiation using a CW mode-locked frequency-doubled Nd:YAG laser with Ba(NO₂) ₃ for the Raman material and CsLiB₆O₁₀ (CLBO) for the sum-frequency material     

Replacement of threonine 394 by alanine facilitates internalization and resensitization of the rat mu opioid receptor

Signaling of G protein-coupled receptors is terminated by phosphorylation of intracellular serine and threonine residues. Resensitization of these receptors requires internalization and subsequent dephosphorylation. We have recently shown that the resensitization rate of the rat micro opioid receptor (MOR) isoforms MOR1 and MOR1B is mainly determined by the amino acid composition of their alternatively spliced C-terminal tails. Upon agonist stimulation, MOR1B passes through an accelerated cycle of receptor endocytosis and reactivation, which in turn promotes a greater resistance to agonist-induced desensitization, as compared with MOR1. Given the fact that MOR1B lacks only one putative phosphorylation site (T394 of MOR1), we replaced this threonine by an alanine and stably expressed the wild-type MOR1 and its T394A mutant in mouse neuroblastoma Neuro2a cells. We show that during prolonged [D-Ala2, MePhe4, Gly5-ol]enkephalin exposure (5 h), the T394A receptor mutant desensitized at a slower rate than MOR1. In contrast, T394A is more rapidly removed from the cell surface than MOR1, as determined by flow cytometry using epitope-tagged receptors. This fast internalization was followed by immediate resensitization of T394A during 20 min of agonist removal while the wild-type MOR1 remained inactive. Similar to MOR1B, rapid internalization and reactivation of T394A may explain its delayed desensitization. These findings suggest that T394 represents a negative regulatory signal for MOR1 internalization. Furthermore, phosphorylation of this threonine residue may influence the time course of micro opioid receptor resensitization.     

Tumor-Associated Microglia/Macrophages as a Predictor for Survival in Glioblastoma and Temozolomide-Induced Changes in CXCR2 Signaling with New Resistance Overcoming Strategy by Combination Therapy

Tumor recurrence is the main challenge in glioblastoma (GBM) treatment. Gold standard therapy temozolomide (TMZ) is known to induce upregulation of IL8/CXCL2/CXCR2 signaling that promotes tumor progression and angiogenesis. Our aim was to verify the alterations on this signaling pathway in human GBM recurrence and to investigate the impact of TMZ in particular. Furthermore, a combi-therapy of TMZ and CXCR2 antagonization was established to assess the efficacy and tolerability. First, we analyzed 76 matched primary and recurrent GBM samples with regard to various histological aspects with a focus on the role of TMZ treatment and the assessment of predictors of overall survival (OS). Second, the combi-therapy with TMZ and CXCR2-antagonization was evaluated in a syngeneic mouse tumor model with in-depth immunohistological investigations and subsequent gene expression analyses. We observed a significantly decreased infiltration of tumor-associated microglia/macrophages (TAM) in recurrent tumors, while a high TAM infiltration in primary tumors was associated with a reduced OS. Additionally, more patients expressed IL8 in recurrent tumors and TMZ therapy maintained CXCL2 expression. In mice, enhanced anti-tumoral effects were observed after combi-therapy. In conclusion, high TAM infiltration predicts a survival disadvantage, supporting findings of the tumor-promoting phenotype of TAMs. Furthermore, the combination therapy seemed to be promising to overcome CXCR2-mediated resistance.     

Electronic Properties of the Interfaces Between the Wide Bandgap Organic Semiconductor Para‐Sexiphenyl and Samarium

Ultraviolet photoelectron spectroscopy was used to determine the energy level alignment at the interfaces formed by either the deposition of para‐sexiphenyl (6P) onto samarium thin films, or by growing samarium on 6P films. We find that for both cases (6P on Sm, and Sm on 6P) the interaction at the interface is weak (physisorption), and the interfacial dipole is smaller than 0.2 eV. This weak interaction enabled us to demonstrate that small morphological changes in the substrate Sm film lead to a reversal in the direction of the interfacial dipole. For native silicon oxide substrates the appearance of a photoemission signal more than 1 eV above the Fermi level is observed, and explained by the energy level alignment process for wide bandgap organic semiconductors. Additionally, we demonstrate that large lateral vacuum level shifts (ca. 1 eV) can be locally realized on an inhomogeneous sample.     

Cost performance and risk in the construction of offshore and onshore wind farms

This article investigates the risk of cost overruns and underruns occurring in the construction of 51 onshore and offshore wind farms commissioned between 2000 and 2015 in 13 countries. In total, these projects required about $39 billion in investment and reached about 11 GW of installed capacity. We use this original dataset to test six hypotheses about construction cost overruns related to (i) technological learning, (ii) fiscal control, (iii) economies of scale, (iv) configuration, (v) regulation and markets and (vi) manufacturing experience. We find that across the entire dataset, the mean cost escalation per project is 6.5% or about $63 million per windfarm, although 20 projects within the sample (39%) did not exhibit cost overruns. The majority of onshore wind farms exhibit cost underruns while for offshore wind farms the results have a larger spread. Interestingly, no significant relationship exists between the size (in total MW or per individual turbine capacity) of a windfarm and the severity of a cost overrun. Nonetheless, there is an indication that the risk increases for larger wind farms at greater distances offshore using new types of turbines and foundations. Overall, the mean cost escalation for onshore projects is 1.7% and 9.6% for offshore projects, amounts much lower than those for other energy infrastructure. Copyright © 2016 John Wiley & Sons, Ltd.     

An attempt to give nursing home residents a voice in the quality improvement process: the challenge of frailty

A model for the development of spatiotemporal receptive fields of simple cells in the visual cortex is proposed. The model is based on the 1990 hypothesis of Saul and Humphrey that the convergence of four types of input onto a cortical cell, viz. non-lagged ON and OFF inputs and lagged ON and OFF inputs, underlies the spatial and temporal structure of the receptive fields. It therefore explains both orientation and direction selectivity of simple cells. The response properties of the four types of input are described by the product of linear spatial and temporal response functions. Extending the 1994 model of one of the authors (K.D. Miller), we describe the development of spatiotemporal receptive fields as a Hebbian learning process taking into account not only spatial but also temporal correlations between the different inputs. We derive the correlation functions that drive the development both for the period before and after eye-opening and demonstrate how the joint development of orientation and direction selectivity can be understood in the framework of correlation-based learning. Our investigation is split into two parts that are presented in two papers. In the first, the model for the response properties and for the development of direction-selective receptive fields is presented. In the second paper we present simulation results that are compared with experimental data, and also provide a first analysis of our model.     

In situ analysis of metal melts in metallurgic vacuum devices by laser-induced breakdown spectroscopy

We report on rapid in situ analysis of liquid metal melts under reduced ambient pressure by laser-induced breakdown spectroscopy (LIBS) using a transportable system. LIBS denotes a method in which characteristic optical emission line intensities of excited species in laser-generated plasma plumes are used for a quantitative chemical analysis of target materials. It is a fast, noncontact method that can be carried out under various atmospheric conditions, allowing large working distances between the sample under investigation and the detection system. For these reasons, LIBS is applicable in particular for process control in metallurgy under reduced ambient pressure. This was demonstrated for two types of vacuum devices under production conditions at a steel mill. The results of these experiments, including calibration curves for Cr, Ni, and Mg in liquid steel, are presented. The influence of variations in the ambient pressure on the results of the LIBS analysis is discussed within the frame of a generalized shock-wave model for the expansion of the laser-induced plasma plume.     

Sphingosine 1-Phosphate Receptor 5 (S1P5) Knockout Ameliorates Adenine-Induced Nephropathy

S1P and its receptors have been reported to play important roles in the development of renal fibrosis. Although S1P₅ has barely been investigated so far, there are indications that it can influence inflammatory and fibrotic processes. Here, we report the role of S1P₅ in renal inflammation and fibrosis. Male S1P₅ knockout mice and wild-type mice on a C57BL/6J background were fed with an adenine-rich diet for 7 days or 14 days to induce tubulointerstitial fibrosis. The kidneys of untreated mice served as respective controls. Kidney damage, fibrosis, and inflammation in kidney tissues were analyzed by real-time PCR, Western blot, and histological staining. Renal function was assessed by plasma creatinine ELISA. The S1P₅ knockout mice had better renal function and showed less kidney damage, less proinflammatory cytokine release, and less fibrosis after 7 days and 14 days of an adenine-rich diet compared to wild-type mice. S1P₅ knockout ameliorates tubular damage and tubulointerstitial fibrosis in a model of adenine-induced nephropathy in mice. Thus, targeting S1P₅ might be a promising goal for the pharmacological treatment of kidney diseases.