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.     

Performance of solar driven methanol–water combined ejector–absorption cycle in the Athens area

The performance of a solar driven CH₄O-H₂O combined ejector– absorption unit, operating in conjunction with intermediate temperature solar collectors in Athens, is predicted along the five months (May–September) in case of the unit working as heat pump in an industrial area. The operation of the unit and the related thermodynamics are simulated by suitable computer codes and the required local climatological data are determined by statistical processings over a considerable number of years. It is found that the heat gain factor varies in the range from 2.1330 to 2.4481 for the above period of time. The maximum HGF of about 2.4481 is obtained in July at 14.25 hrs with corresponding specific heat gain power 915 W/m². The maximum Q_gain of about 1086 W/m² is obtained in June at 12.54 hrs with corresponding HGF 2.3572. Also the maximum value of HGF was estimated by correlation of three temperatures: generator temperature (85.0°C–97.2°C), condenser temperature (43.3°C–47.6°C) and evaporator temperature (12.6°C–25.4°C).     

Synthesis of Brightly PEGylated Luminescent Magnetic Upconversion Nanophosphors for Deep Tissue and Dual MRI Imaging

A method is developed to fabricate monodispersed biocompatible Yb/Er or Yb/Tm doped β‐NaGdF₄ upconversion phosphors using polyelectrolytes to prevent irreversible particle aggregation during conversion of the precursor, Gd₂O(CO₃)₂?H₂O:Yb/Er or Yb/Tm, to β‐NaGdF₄:Yb/Er or Yb/Tm. The polyelectrolyte on the outer surface of nanophosphors also provided an amine tag for PEGylation. This method is also employed to fabricate PEGylated magnetic upconversion phosphors with Fe₃O₄ as the core and β‐NaGdF₄ as a shell. These magnetic upconversion nanophosphors have relatively high saturation magnetization (7.0 emu g^?1) and magnetic susceptibility (1.7 × 10^?2 emu g^?1 Oe^?1), providing them with large magnetophoretic mobilities. The magnetic properties for separation and controlled release in flow, their optical properties for cell labeling, deep tissue imaging, and their T₁‐ and T₂‐weighted magnetic resonance imaging (MRI) relaxivities are studied. The magnetic upconversion phosphors display both strong magnetophoresis, dual MRI imaging (r₁ = 2.9 mM^?1 s^?1, r₂ = 204 mM^?1 s^?1), and bright luminescence under 1 cm chicken breast tissue.     

An alcohol expectancy-challenge prevention program for at risk college women.

Alcohol expectancy-challenge programs are effective in changing expectancies and reducing drinking in college men (J. Darker & M. S. Goldman. 1993. 1998); however, recent evidence suggests this protocol might not be effective for women (M. E. Dunn, C. Lau, & I. Y. Cruz, 2000). This study was designed to reevaluate the effectiveness of a social/sexual expectancy-challenge intervention in college women reporting moderate to heavy alcohol use. Forty-six undergraduate women were randomly assigned to the prevention or control condition. Participants reported alcohol expectancies at pre- and posttest and monitored their drinking patterns daily for 6 weeks. The program was effective in changing some expectancies but did not reduce drinking. This further confirms differences in the mechanisms by which expectancy-challenge programs function for men and women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cat carotid body chemosensory responses to non-hypoxic stimuli are inhibited by sodium nitroprusside in situ and in vitro

We studied the effects of sodium nitroprusside, a nitric oxide donor, on the chemosensory responses to cyanide and nicotine in the cat carotid body. In situ, sodium nitroprusside infusion reduced the cyanide-evoked responses in a dose-dependent manner. In vitro, Tyrode containing nitroprusside reversibly reduced the cyanide- (by 59%) and nicotine-induced (by 45%) chemosensory responses. The present results suggest that chemosensory responses induced by cyanide and nicotine are reduced by increased nitric oxide content, similarly to the hypoxic chemosensory responses.     

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

Oxygen in coal ash: a simplified approach to the analysis of ash and mineral matter in coal

Oxygen was determined accurately in eight U.S. Bureau of Mines coal ash samples A, B, D, F, G, I, and J, NBS coal fly ash 1633 reference material, and two low-temperature ashes (LTA) from lllinois State Geological Survey. The method uses fast-neutron activation (FNA) analysis employing a dual counting and irradiation system which is essentially free from interferences. The stoichiometric balance based on analyses of the ashes performed by the USBM is calculated and summations given in oxide and element percent. Excellent agreement is found with the chemical data obtained by classical silicate analysis methods. Accurate oxygen determination for coal ash and LT-ash (or mineral matter) is important for calculation of data in the ultimate analysis of coal as such. Knowledge is required for recalculation of the data on a dry and dry-ash-free basis. The routinely used ‘oxygen by difference’ values are inadequate for accurate work. In order to determine the organic oxygen in coal one also has to correct for oxygen in mineral matter and oxygen in the water removed as moisture. The Parr formula and other methods of empirical estimation are inadequate and may be replaced in some cases by the oxygen determination. The complete data provide a quantitative basis for stoichiometric interpretation of coal analyses. It was found that the eight coal-ash samples analysed contained 45.5 ± 3% oxygen. Since these ashes represent a large variety of U.S. coals, this figure can be used as an estimate for recalculation and evaluation of the proximate and ultimate coal analyses. It is better, however, to use values actually determined in ash by the rapid fast-neutron activation method. This permits a better estimation of the sum of cations plus sulphates in the ash.     

Mechanical and barrier properties of MOCVD processed alumina coatings on Ti6Al4V titanium alloy

This study focuses on the implementation of different aluminum oxide coatings processed by metal-organic chemical vapor deposition from aluminum tri-isopropoxide on commercial Ti6Al4V titanium alloy to improve its high temperature corrosion resistance. Films grown at 350 °C and at 480 °C are amorphous and correspond to formulas AlOOH, and Al₂O₃, respectively. Those deposited at 700 °C are composed of γ-Al₂O₃ nanocrystals dispersed in a matrix of amorphous alumina. Their mechanical properties and adhesion to the substrates were investigated by indentation, scratch and micro tensile tests. Hardness and rigidity of the films increase with increasing deposition temperature. The hardness of the coatings prepared at 350 °C and 480 °C is 5.8 ± 0.7 GPa and 10.8 ± 0.8 GPa respectively. Their Young's modulus is 92 ± 8 GPa (350 °C) and 155 ± 6 GPa (480 °C). Scratch tests cause adhesive failures of the films grown at 350 °C and 480 °C whereas cohesive failure is observed for the nanocrystalline one, grown at 700 °C. Micro tensile tests show a more progressive cracking of the latter films than on the amorphous ones. The films allow maintaining good mechanical properties after corrosion with NaCl deposit during 100 h at 450 °C. After corrosion test only the film deposited at 700 °C yields an elongation at break comparable to that of the as processed samples without corrosion. The as established processing–structure–properties relation paves the way to engineer MOCVD aluminum oxide complex coatings which meet the specifications of the high temperature corrosion protection of titanium alloys with regard to the targeted applications.     

Synthesis,SAR and Unanticipated Pharmacological Profiles of Analogues of the mGluR5 Ago‐potentiator ADX‐47273

An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago‐potentiator ADX‐47273. This effort identified key substituents in the 3‐position of oxadiazole that engendered either mGluR5 ago‐potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9‐fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.