Severity of Infectious Mononucleosis (IM) Correlates with the Frequency of Crossreactive Influenza A Virus (IAV)-M1 and Epstein Barr Virus (EBV)-BMLF-1-specific CD8 T Cells

During EBV-associated IM IAV-specific crossreactive memory T cells are activated and play a role in disease severity. In HLA-A2+ IM patients, influenza M158 (IAV-M1)-specific CD8 memory T cell responses crossreacted with two different EBV lytic epitopes, BMLF1280 (17/29) and BRLF1190 (19/20). Furthermore, 11/22 IM patients demonstrated some intra-viral crossreactivity between EBV-BRLF1 and -BMLF1 responses. Disease severity of IM directly correlated with significantly increased frequencies of crossreactive IAV-M1/EBV-BMLF1, IAV-M1, and EBV-BMLF1 specific CD8 cells, and with mean viral load over the first 5 weeks of infection. Disease severity did not correlate with BRLF1 or M1/BRLF1 crossreactive responses. When severity of IM was scored and patients were assigned to either mild or severe groups, disease severity correlated with specific TCR Vb usage in IAV-M1 population suggesting that TcR selection is driving disease outcome. Consistent with IAV-M1 and EBV-BMLF1 responses driving increased immunopathology was the observation that patients with severe disease had significantly more IAV-M1 and EBV-BMLF1 cells producing IFNg/MIP1-b in response to antigen as compared to patients with mild disease. These results suggest that T cell crossreactivity impacts T cell selection and function and ultimately disease outcome. Insights on these issues are important for the intelligent design of vaccines and to develop therapeutic interventions for virally induced disease (NIHAI49320)

Epstein-Barr Virus (EBV)-lytic Cross-reactive Influenza-A (IAV) Memory CD8 T-cells in EBV Sero-negative Middle-aged Adults

EBV is a common human pathogen, which infects ~90% of people and establishes a life-long chronic infection. The clinical outcomes of acute infection can range from asymptomatic to severe immunopathology such as infectious mononucleosis (IM). However, for unknown reasons 5-10% of middle-aged adults (\u3e35 years) remain EBV-seronegative (EBV-SN) when the virus infects the vast majority of people, and is actively shed at high titers during chronic infection. Here we show that EBV-SN (ASN) HLA-A2+ middle-aged adults possess a unique IAV-M1-GIL58-66 memory CD8 T-cell response that cross-reacts with EBV lytic epitopes that differs from teenage EBV-SN (TSN) (18-19 years) and EBV-seropositive (EBV-SP) adult donors. The five tested HLA-A2+ EBV-SN middle-aged adults had a significantly increased IAV-M158-66-GIL tetramer+ CD8 frequency compared to EBV-SP donors. Upon exposure to EBV antigens in vitro both IAV-M158-66GIL/EBV-BMLF1280-288-GLC and IAV-M158-66-GIL/EBV-BRLF1109-117-YVL, functionally cross-reactive CD8+ responses could be detected in the peripheral blood of middle-aged EBV-SN donors, while only IAV-M1/EBV-YVL cross-reactive responses were detected in some teenage EBV-SN or EBV-seropositive people . Surprisingly, these IAV-M1-GIL-specific CD8 T-cells in middle-aged EBV-SN adults expanded dramatically to EBV lytic antigens and produced cytokines at high functional avidity. They lysed EBV-infected targets and showed potential (by CD103 expression) to enter mucosal epithelial tissue where infection initiates. Additionally, these cross-reactive cells had an oligo-clonal T-cell receptor repertoire different than EBV-SP donors. Taken together these data suggest that an altered cross-reactive T cell repertoire could mediate protective immunity against viral infection. Our results imply that sero-negative adults might have the ability to resist viral infection via heterologous immunity. (NIH-AI49320)

Temperature-programmed desorption of H2 from molybdenum nitride thin films

The thermal desorption of hydrogen from [beta]-Mo16N7, [gamma]-Mo2N and [delta]-MoN thin films was investigated. Hydrogen adsorption at [approximate]270 K produced two hydrogen desorption peaks, one at [approximate]370 K (designated as the [beta]1 site) and the other at [approximate]800 K (designated as the [beta]2 site). We concluded that the [beta]1 peak was due to a low-energy surface site and the [beta]2 peak to a subsurface site. Desorption from the [beta]1 state obeyed first-order kinetics. The hydrogen saturation capacity increased in the following order: [beta]-Mo16N72N. This variation in saturation coverage tracked with the nominal molybdenum atom surface density. Nitrogen also desorbed from the Mo nitride surfaces during the H2 temperature-programmed desorption experiments producing a low-temperature peak at [approximate]370 K and several high-temperature peaks in the range 500-900 K. The amount of nitrogen that desorbed increased with increasing H2 dose, suggesting a hydrogen-induced nitrogen desorption process. Hydrogen may have weakened the Mo-N bond thereby facilitating the desorption of nitrogen. We believe that the low-temperature peak was due to nitrogen bound to Mo atoms at the surface. The high-temperature peaks were probably a consequence of hydrogen that diffused into the surface altering the Mo-N bonding in the subsurface region. Thermal desorption characteristics of the Mo nitride films were similar to those of a series of bulk [gamma]-Mo2N powders that we previously investigated. Apparent energies for hydrogen desorption from the low-temperature sites were near 25 kcal/mol, and both the thin films and powders possessed high-temperature subsurface binding sites. The most striking observation was the similarity between the characters of the [delta]-MoN film and the Mo nitride powder with the highest hydrodenitrogenation activity. This similarity suggested that the high activity was due to the presence of [delta]-MoN-like structures at or near the bulk powder surface.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31475/1/0000397.pd

Surface structure and composition of high-surface-area molybdenum nitrides

The determination of surface structure is critical in elucidating structure-function relationships for catalytic materials. However, such materials often consist of active regions of very limited spatial extent, rendering conventional bulk structural characterization techniques of limited utility. In this work, we have employed high-resolution transmission electron microscopy coupled with Fourier analysis, and X-ray photoelectron spectroscopy to determine the near-surface structures and compositions of a series of molybdenum nitride catalysts. The results show the near-surface to differ both in crystal structure and composition from the bulk. The bulk structure was [gamma]-Mo2N (fcc) while the lattice structure near the surface was body-centered. Many of the materials contained nitrogen in excess of that expected for phases in the Mo-N phase diagram. As the amount of nitrogen decreased, the oxygen content increased, and the calculated lattice parameter increased. Taken together, the results suggested the presence of Mo2N3-xOx, a hypothetical primitive cubic structure, near the surface. This structure, which would produce a diffraction pattern that approximates that of a body-centered lattice, accounts for the near-surface structural and compositional properties of the high-surface-area molybdenum nitrides.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31593/1/0000522.pd

Molybdenum nitride catalysts : I. Influence of the synthesis factors on structural properties

Effects of the synthesis parameters on the structural properties of molybdenum nitride catalysts, prepared by the temperature-programmed reaction of MoO3 with NH3, have been examined. Molybdenum trioxide was heated in flowing NH3 through two linear heating segments (623 to 723 K then 723 to 973 K) with different space velocities in a 23 factorial design. The temperature limits for these heating segments were defined based on the results of in situ X-ray diffraction analysis of the gas-solid reaction. The resulting catalysts were characterized using BET surface area analysis, environmental scanning electron microscopy, ex situ X-ray diffraction, and oxygen chemisorption. The primary bulk phase present was [gamma]-Mo2N. Some of the lower surface area catalysts also contained MoO2 and Mo, but there was no evidence of nitrides other than [gamma]-Mo2N. The catalysts consisted of micrometersized, plate-like aggregates of nanometer-sized crystallites, and possessed surface areas ranging up to [approximate]140 m2/g depending on the synthesis and reduction conditions employed. Statistical analysis of the results revealed that the space velocity individually and the heating rates combined had the most significant effects on the structural properties. The production of catalysts with surface areas in excess of 50 m2/g required the use of slow heating rates during the first segment and high space velocities. We concluded that the key to producing the highest surface area Mo nitrides was channeling the reaction through HxMoO3 (x 2OyN1-y intermediates. Passivation of the materials immediately following synthesis appeared to produce an oxynitride at the surface. Reduction of the passivated materials in H2 at temperatures up to 673 K caused a significant increase in the surface area and O2 uptake. The O2 uptake for the low and medium surface area catalysts varied linearly with the BET surface area and corresponded to an O:Mo stoichiometry of approximately 1:5. The oxygen site density for the highest surface area nitride was lower than those for the lower surface area catalysts, presumably due to differing surface structures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31907/1/0000860.pd

Redes e camadas de relacionamentos na economia: metodologias para o estudo da confiança mercantil na América Portuguesa do Antigo Regime

This paper explores how far different relationship densities can be associated with varying degrees of interaction and confidence in the southern part of eighteenth-century Portuguese America. Sources include probate inventories, parish records and letters. A database focused on relationships and social interactions has been created for this purpose, and our conclusions indicate a close relationship between relationship density and trade confidenceEl objetivo de este trabajo es explorar la posibilidad de considerar las diferentes densidades de relación que estarían asociadas con diferentes grados de interacción y confianza, en la región meridional de la América portuguesa del siglo XVIII. Para llevar a cabo esta investigación, utilizamos distintas fuentes, entre ellas, los inventarios, los registros bautismales y las correspondencias. Para el estudio de este tema, ha sido creada una base de datos centrada en las relaciones e interacciones sociales. Los resultados indican una aproximación entre la densidad de las relaciones y la confianza. [pt] O objetivo deste trabalho é explorar a possibilidade de considerar as diferentes densidades de relações sociais que estariam associadas a diferentes graus de interação e confiança, tendo em conta a região meridional da América Portuguesa no final do século XVIII. Para realizar esta investigação, utilizamos fontes diversas, incluindo inventários post-mortem, registros paroquiais e correspondências. Para este estudo, foi criada uma base de dados centrada nas relações e interações sociais. Os resultados indicam uma aproximação estreita entre a densidade das relações e a confiança

Inhibition of HIF-1 alpha by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited