Histamine modulation of glutamate release from hippocampal synaptosomes

We have discovered two substituted 4-aminopiperidine compounds having high in vitro affinity and selectivity for the human dopamine D1 receptor. Both compounds, 3-ethoxy-N-methyl-N-[1-(phenylmethyl)-4-piperidinyl]-2-pyridinylamine (U-99363E), and its 3-isopropoxy analog (U-101958), were found through a routine receptor binding screen. The determined affinities (Ki) of these compounds for the cloned human dopamine D4 receptor were 2.2 and 1.4 nM, respectively. They exhibited at least 100-fold lower affinities for dopamine D2 and for other dopaminergic, serotonergic and adrenergic receptors. Both compounds were found to antagonize quinpirole-induced mitogenesis in Chinese hamster ovary cells expressing the human dopamine D4 receptor. In spite of their poor metabolic stability and low bioavailability. U-99363E and U-101958 appear to be among the first high-affinity, highly selective dopamine D4 receptor antagonists reported, and may have utility in in vitro investigations requiring selective tagging or blockade of dopamine D4 sites.     

Growth paths for the sulfurization of Cu-rich Cu/In thin films

In-situ energy-dispersive X-ray diffraction performed at the BESSY and HASY-LAB synchrotron facilities was used to observe sulfur pressure dependent growth paths for the formation of CuInS₂ thin films from Cu-rich metallic precursors. CuInS₂ can form directly from the intermetallic phases, through binary sulfides or via CuIn₅S₈. Particular attention is given to the latter reaction sequence, typical of rapid thermal processing (RTP), with complementary EDS and SEM analysis.     

A Substantial Structural Conversion of the Native Monomer Leads to in-Register Parallel Amyloid Fibril Formation in Light-Chain Amyloidosis

Amyloid light-chain (AL) amyloidosis is a rare disease in which plasma-cell-produced monoclonal immunoglobulin light chains misfold and become deposited as fibrils in the extracellular matrix. λ6 subgroup light chains are particularly fibrillogenic, and around 25 % of amyloid-associated λ6 light chains exist as the allotypic G24R variant that renders the protein less stable. The molecular details of this process, as well as the structures of the fibrils, are unknown. We have used solid-state NMR to investigate different fibril polymorphs. The secondary structures derived from NMR predominantly show β-strands, including in former turn or helical regions, and provide a molecular basis for previously identified fibrillogenic hotspots. We have determined, by using differentially ¹⁵N:¹³C-labeled samples, that the β-strands are stacked in-register parallel in the fibrils. This supramolecular arrangement shows that the native globular folds rearrange substantially upon fibrillization, and rules out the previously hypothesized fibril formation from native monomers.     

In-situ studies of the recrystallization process of CuInS2 thin films by energy dispersive X-ray diffraction

Recrystallization processes during the sulfurization of CuInS₂ (CIS) thin films have been studied in-situ using energy dispersive X-ray diffraction (EDXRD) with synchrotron radiation. In order to observe the recrystallization isolated from other reactions occurring during film growth, Cu-poor, small grained CIS layers covered with CuS on top were heated in a vacuum chamber equipped with windows for synchrotron radiation in order to analyze the grain growth mechanism within the CIS layer. In-situ monitoring of the grain size based on diffraction line profile analysis of the CIS-112 reflection was utilized to interrupt the recrystallization process at different points. Ex-situ studies by electron backscatter diffraction (EBSD) and energy dispersive X-ray spectroscopy (EDX) performed on samples of intermediate recrystallization states reveal that during the heat treatment Cu and In interdiffuse inside the layer indicating the importance of the mobility of these two elements during CuInS₂ grain growth.     

Recrystallization of Cu(In,Ga)Se2 thin films studied by X-ray diffraction

Recrystallization is essential for the synthesis of the highest quality Cu(In,Ga)Se₂ (CIGSe) thin films for solar cell applications. Here we present a real-time study of the recrystallization of CIGSe thin films. We trigger the recrystallization by allowing diffusion of Cu into a Cu-poor CIGSe film and use synchrotron-based energy-dispersive X-ray diffraction to monitor this transition in real time. Additionally, we characterize the films by means of angle-dispersive X-ray diffraction. Before recrystallization, the X-ray diffraction patterns exhibit a signature that does not correspond to the ideal chalcopyrite structure of CIGSe. This signature can be attributed to stacking faults within the bulk of the films by modeling diffraction patterns of faulted CIGSe with the software DIFFaX. It is detected at temperatures below 650 K and is absent at temperatures above 750 K, which indicates that the faults in question were annihilated in this temperature range. This process occurs after the incorporation of Cu into the Cu-poor CIGSe lattice, which takes place in the 550–650 K temperature range.     

Blind source separation in post-nonlinear mixtures using competitive learning, Simulated annealing, and a genetic algorithm

This paper presents a new adaptive procedure for the linear and nonlinear separation of signals with nonuniform, symmetrical probability distributions, based on both simulated annealing and competitive learning methods by means of a neural network, considering the properties of the vectorial spaces of sources and mixtures, and using a multiple linearization in the mixture space. Moreover, the paper proposes the fusion of two important paradigms-genetic algorithms and the blind separation of sources in nonlinear mixtures. In nonlinear mixtures, optimization of the system parameters and, especially, the search for invertible functions is very difficult due to the existence of many local minima. The main characteristics of the methods are their simplicity and the rapid convergence experimentally validated by the separation of many kinds of signals, such as speech or biomedical data.     

MicroRNAs from Extracellular Vesicles Secreted by Bovine Embryos as Early Biomarkers of Developmental Competence

During early development, embryos secrete extracellular vesicles (EVs) that participate in embryo–maternal communication. Among other molecules, EVs carry microRNAs (miRNAs) that interfere with gene expression in target cells; miRNAs participate in embryo–maternal communication. Embryo selection based on secreted miRNAs may have an impact on bovine breeding programs. This research aimed to evaluate the size, concentration, and miRNA content of EVs secreted by bovine embryos with different developmental potential, during the compaction period (days 3.5–5). Individual culture media from in vitro–produced embryos were collected at day 5, while embryos were further cultured and classified at day 7, as G1 (conditioned-culture media by embryos arrested in the 8–16-cells stage) and G2 (conditioned-culture media by embryos that reached blastocyst stages at day 7). Collected nanoparticles from embryo conditioned culture media were cataloged as EVs by their morphology and the presence of classical molecular markers. Size and concentration of EVs from G1 were higher than EVs secreted by G2. We identified 95 miRNAs; bta-miR-103, bta-miR-502a, bta-miR-100, and bta-miR-1 were upregulated in G1, whereas bta-miR-92a, bta-miR-140, bta-miR-2285a, and bta-miR-222 were downregulated. The most significant upregulated pathways were fatty acid biosynthesis and metabolism, lysine degradation, gap junction, and signaling pathways regulating pluripotency of stem cells. The characteristics of EVs secreted by bovine embryos during the compaction period vary according to embryo competence. Embryos that reach the blastocyst stage secrete fewer and smaller vesicles. Furthermore, the loading of specific miRNAs into the EVs depends on embryo developmental competence.     

12.6% efficient CdS/Cu(In,Ga)S2-based solar cell with an open circuit voltage of 879 mV prepared by a rapid thermal process

A Cu(In,Ga)S₂-based solar cell with a confirmed efficiency of 12.6% together with an open circuit voltage of 879 mV, prepared from sputtered metals subsequently sulfurized using rapid thermal processing in sulfur vapor, is reported. The performance of the new cell is superior to those obtained previously with multi-source evaporated absorbers. We show that by carefully adjusting the temperature profile, good absorber properties could be transferred from a long process to a rapid thermal process. The improved efficiency is due to an appropriate degree of gallium diffusion toward the surface, which could be achieved despite the short sulfurization time. Absorber and solar cell characteristics are presented.     

Influence of precursor stacking on the absorber growth in Cu(In,Ga)S2 based solar cells prepared by a rapid thermal process

Rapid thermal sulfurization of metallic precursors has proven to be a successful method for the preparation of Cu(In,Ga)S₂ based solar cells. However, during the sulfurization, several problems can be encountered. Due to the difference in reaction rates between ternary sulfides, the process can result in absorbers with a layered CuInS₂/CuGaS₂ structure or slow and incomplete sulfurization that leads to samples where an unreacted Cu-Ga metallic phase remains at the back of the sample. The formation kinetics of single phase Cu(In,Ga)S₂ is a complex process which depends on several parameters. In this work, we focus on the influence of precursor stacking and investigate the growth of Cu(In,Ga)S₂ thin films using scanning electron microscopy and X-ray diffraction. It is observed that precursor alloying occurs prior to sulfurization and that the Cu(In,Ga)S₂ compound is formed by the interdiffusion of the ternary CuInS₂ and CuGaS₂ phases. Correlation between the structural properties of the precursors/absorbers and the obtained solar cells is made.     

Salmonella enterica serotypes isolated from imported frozen chicken meat in the Canary islands

To determine the prevalence of Salmonella enterica serotypes in imported frozen chicken meat, 406 samples (whole chicken, legs, and breast meat) were analyzed for Salmonella according to ISO6579 rules, serotypes were assigned, and phage typing was conducted for Salmonella serotypes Enteritidis, Typhimurium, and Heidelberg. The overall frequency of Salmonella isolation was 16.5%. By country of origin, the highest percentage of cases was found among the samples from France followed by samples from Brazil. The differences between legs and breast meat were significant. The most frequently isolated serotype of Salmonella was Enteritidis, followed by Salmonella Heidelberg, Salmonella Typhimurium, and Salmonella Virchow. By country of origin, we identified a large percentage of serotype Salmonella Enteritidis in the samples imported from Brazil. There was a greater diversity of serotypes isolated from the French samples, and Salmonella Enteritidis was not the dominant strain. In the samples from the United States, the only serotype isolated was Salmonella Kentucky, although a smaller number of samples was analyzed. The Salmonella Enteritidis phage type that prevailed in both France and Brazil was 4. Phage types 204c and 204 were identified for Salmonella Typhimurium, and phage types 8, 31, and 37 were identified for Salmonella Virchow.