Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) represents a major burden to global health, and refined vaccines are needed. Replication-deficient lymphocytic choriomeningitis virus (rLCMV)-based vaccine vectors against cytomegalovirus have proven safe for human use and elicited robust T cell responses in a large proportion of vaccine recipients. Here, we developed an rLCMV vaccine expressing the Mtb antigens TB10.4 and Ag85B. In mice, rLCMV elicited high frequencies of polyfunctional Mtb-specific CD8 and CD4 T cell responses. CD8 but not CD4 T cells were efficiently boosted upon vector re-vaccination. High-frequency responses were also observed in neonatally vaccinated mice, and co-administration of rLCMV with Expanded Program of Immunization (EPI) vaccines did not result in substantial reciprocal interference. Importantly, rLCMV immunization significantly reduced the lung Mtb burden upon aerosol challenge, resulting in improved lung ventilation. Protection was associated with increased CD8 T cell recruitment but reduced CD4 T cell infiltration upon Mtb challenge. When combining rLCMV with BCG vaccination in a heterologous prime-boost regimen, responses to the rLCMV-encoded Mtb antigens were further augmented, but protection was not significantly different from rLCMV or BCG vaccination alone. This work suggests that rLCMV may show utility for neonatal and/or adult vaccination efforts against pulmonary tuberculosis.     

Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol,Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents,and Carbonic Anhydrases I,II, VII,IX, and XII Inhibitors

A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with K_Is = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80–55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4’-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC₅₀ of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.     

Silver-Sodium Exchange in Sodium Galliosilicate Glasses

The silver-sodium interdiffusion coefficients of several glasses in the sodium galliosilicate system were determined. The compositional dependence of the interdiffusion coefficient is compared to that observed in the self-diffusion coefficients calculated from dc electrical conductivity data. The observed trends are discussed in terms of a structural model proposed for these glasses.     

Analysis of geosynthetic tubes filled with several liquids with different densities

A two dimensional model of a geosynthetic tube sitting on a rigid horizontal foundation and filled with several separated liquids with different densities is proposed. The material from which the tube is made is a special synthetic fabric which is inextensible, perfectly flexible, and leakproof. Such a model is useful for modeling a consolidations process in the tube filled with a slurry. The equilibrium equations of the model are formulated. Unknown values like the pressure on the top and bottom of the tube, the tension in the geosynthetic fabric, the length of the contact zone between the tube and the rigid foundation are searched with respect to the given perimeter, the volumes and densities of liquids. Such a problem is solved by the Newton’s method. The initial approximation is obtained by solving a simplified problem with one liquid with the average density. The problem is implemented in a MATLAB code for geosynthetic tubes filled with two, three, and four liquids with different densities. The tubes filled with two different liquids are studied in more detail. The graphs of the relations are compared with the graphs for the tube filled with the single liquid whose density is the average of the densities of the liquids. The comparison enables to discuss the influence of the consolidation process on the height, the contact zone, the pressures and the tension of the tube. The results of the proposed model for a tube filled with a single liquid are compared with another model.     

High-Temperature Hall Measurements on Cerium Dioxide Thin Films

Simultaneous Hall and conductivity measurements have been performed on sputtered polycrystalline thin films and on bulk ceramic specimens of nearly stoichiometric CeO₂ in the temperature range between 900° and 1040°C. The measurements have been performed in air using low-frequency alternating current. In the case of the bulk ceramic specimens, an upper limit for the carrier mobility of ≤0.2 cm²/(V·s) has been obtained, which is in accordance with data from the literature for bulk samples. The conductivity of the thin films (l/1Ω·m) at 1000°C) is in accordance with data from the literature for bulk ceramics. The carrier density derived from the Hall measurements (3 × 10¹⁶/cm³ at 1000°C) increases with increasing temperature, whereas the Hall mobility (4 cm²(V·s) at 1000°C) decreases with increasing temperature. These values differ from literature data for bulk ceramic specimens. The difference may be duelo the small grain diameters (∼200 nm) in the 1-μm-thick thin films.     

Escherichia coli O157 and non-O157 Shiga toxin-producing Escherichia coli in fecal samples of finished pigs at slaughter in Switzerland

Fecal samples from 630 slaughtered finisher pigs were examined by PCR to assess the shedding of Escherichia coli O157 (rfbE) and Shiga toxin-producing E. coli (STEC, stx). The proportion of positive samples was 7.5% for rfbE and 22% for stx. By colony hybridization, 31 E. coli O157 and 45 STEC strains were isolated, and these strains were further characterized by phenotypic and genotypic traits. Among E. coli O157 strains, 30 were sorbitol positive, 30 had an H type other than H7, and none harbored stx genes. Intimin (eae), enterohemolysin (ehxA), EAST1 (astA), and porcine A/E-associated protein (paa) were present in 10, 3, 26, and 6% of strains. Among them, one eae-gamma1-positive O157:H7 strain testing positive for ehxA and astA and two eae-alpha1-positive O157:H45 strains were classified as enteropathogenic E. coli (EPEC). The O157:H45 EPEC harbored the EAF plasmid and the bfpA gene, factors characteristic for typical EPEC. The isolated STEC strains (43 sorbitol positive) belonged to 11 O:H serotypes, including three previously reported in human STEC causing hemolytic uremic syndrome (O9:H-, O26:H-, and O103:H2). All but one strain harbored stx2e. The eae and ehxA genes, which are strongly correlated with human disease, were present in only one O103:H2 strain positive for stx1 and paa, whereas the astA gene was found more frequently (14 strains). High prevalence of STEC was found among finisher pigs, but according to the virulence factors the majority of these strains seem to be of low virulence.     

Eine Methode zur Quantitativen Verfolgung von Festphasenreaktionen in der Peptidsynthese

A Method for the Quantitative Control of Solid Phase Reactions in the Peptide Synthesis A quantitative control-method of partial steps of a solid phase peptide synthesis is described, based on a hydrazinolytic cleavage of protected peptides from the solid support. A separation of the peptide hydrazides by gelchromatography on sephadex G 15 in dimethylformamide and a quantitative evaluation of the hydrazide-content in the elution fractions is reported, which permits the control of the Nα-deprotection step in the same way as the evaluation of the coupling yields of the desired sequence. The new method is discussed for the example of two solid phase syntheses of the pentapeptide N-tert.-butyl-oxycarbonyl-L -valyl-S-benzyl-L -cysteinyl-L -alanyl-L - leucyl-O-benzyl-L -tyrosine hydrazide.     

Silver versus white sheet as a back reflector for microcrystalline silicon solar cells deposited on LPCVD‐ZnO electrodes of various textures

We compare the performance of two back reflector designs on the optoelectrical properties of microcrystalline silicon solar cells. The first one consists of a 5‐µm‐thick low‐pressure chemical vapor deposition (LPCVD)‐ZnO electrode combined with a white sheet; the second one incorporates an Ag reflector deposited on a thin LPCVD‐ZnO layer (with thickness below 200 nm). For this latter design, the optical loss in the nano‐rough Ag reflector can be strongly reduced by smoothing the surface of the thin underlying ZnO layer, by means of an Ar‐plasma treatment. Because of its superior lateral conductivity, the thin‐ZnO/Ag back reflector design provides a higher fill factor than the dielectric back reflector design. When decreasing the roughness of the front electrode with respect to our standard front LPCVD‐ZnO layer, the electrical cell performance is improved; in addition, the implementation of the thin‐ZnO/Ag back reflector leads to a significant relative gain in light trapping. Applying this newly optimized combination of front and back electrodes, the conversion efficiency is improved from 8.9% up to 9.4%, for cells with an active‐layer thickness of only 1.1 µm. We thereby highlight the necessity to optimize simultaneously the front and back electrodes. Copyright © 2014 John Wiley & Sons, Ltd.     

Growth and characterization of GaSb bulk crystals with low acceptor concentration

GaSb bulk single crystals with low acceptor concentration were grown from a bismuth solution by the traveling heater method. The result is isoelectronic doping by Bi which gives a variation of the opto-electronic properties as a function of grown length as well as a pronounced microscopic segregation. Photoluminescence spectra at 4K show a decrease of the natural acceptor during growth, which is confirmed by Hall measurements. The electrical properties of this isoelectronic doped GaSb are hole concentrations and mobilities of N_A − N_D = 1.7 × 10¹⁶ cm⁻³ and μ = 870 cm²Vs at room temperature and N_A-N_D = 1 × 10¹⁶ cm⁻³ and μ = 4900 cm²/Vs at 77K, respectively. The lowest p-type carrier concentration measured at 300K is N_A − N_D = 3.3 × 10¹⁵ cm⁻³