Induction of IL 2 receptor expression and cytotoxicity of thymocytes by stimulation with TCF1

We investigated the role of T cell cytotoxicity inducing factor 1 (TCF1) in the induction of a cytotoxic T cell response. We found that help-deficient thymocyte cultures supplied with saturating amounts of purified IL 2 did not develop CTL in a 5-day culture. The expression of cytotoxicity was dependent on the addition of TCF1 derived from the T cell hybridoma K15. TCF1 also induced proliferation of thymocytes in the presence of IL 2. Only the PNA- thymocyte subpopulation responded to TCF1 with proliferation and cytotoxicity in the presence of IL 2. The monokine IL 1 also induced proliferation in this subpopulation but failed to induce cytotoxicity. IL 1 was further distinguished from TCF1 by inhibition of IL 1-induced but not TCF1-induced proliferation by anti-IL 1 antibodies. In addition, using anti-IL 2 receptor antibodies (AMT 13), we showed that TCF1 in the presence of IL 2 substantially increased IL 2 receptor expression in thymocytes. IL 1 had the same effect on induction of IL 2 receptor expression as TCF1. Because some effects of IL 1 and TCF1 are distinct and some overlap, we discuss whether IL 1 and TCF1 induce different subsets of PNA- thymocytes

Vaccination with viral vectors expressing NP, M1 and chimeric hemagglutinin induces broad protection against influenza virus challenge in mice

Seasonal influenza virus infections cause up to half a million deaths each year, the majority of which are older adults. Annual influenza virus vaccination protects against disease, but in the event of a mismatch between the circulating strain and vaccine strain, vaccine effectiveness is severely impacted. Therefore, there is an urgent need for a vaccine that induces broad protection against drifted seasonal and emerging pandemic influenza viruses. One approach in designing such a universal influenza virus vaccine is based on targeting conserved regions of the influenza virus hemagglutinin (HA), the major glycoprotein on the surface of the virus. Using chimeric hemagglutinin constructs (cHA), the immune system can be primed to produce antibody responses against the conserved immunosubdominant stalk region rather than the variable immunodominant head region. Furthermore, replication deficient viral vectors based on Chimpanzee Adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA) virus expressing the influenza virus internal antigens, such as the nucleoprotein (NP) and the matrix protein 1 (M1), are capable of inducing strong influenza specific T cell responses in vaccinated individuals. This is another approach towards a broadly cross-protective influenza vaccine given the degree of conservation of NP and M1 across different influenza virus strains. Here, we combine these two platforms to evaluate the efficacy of a viral vector-based group 2 cHA intramuscular vaccination regime in mice to confer protection against influenza virus challenge of matched and mismatched group 2 strains. We show that vectored vaccines expressing both cHA and an NP-M1 fusion protein, in a prime-boost regimen (with different cHAs given at each vaccination), provide enhanced protection against H3N2 and H10N8 virus challenge when compared to vaccination with cHA alone or NP-M1 alone. The vaccine induced antibody responses against divergent HAs, NP, M1, and whole virus correlated with nature of administered vaccine and extent of protection seen across vaccinated groups. Influenza specific T cell responses were also increased in the vectored vaccines expressing both the cHA and the NP-M1 fusion protein. For further characterization, we are interested in looking at an optimal vaccination regimen, the possibility of an additional boost to induce cross-reactive antibodies, and the nature of the induced antibodies. Overall, these results improve our understanding of vaccination platforms capable of harnessing cellular and humoral immunity with the ultimate goal of designing a universal influenza vaccine

Determination of the angle gamma using B -> D* V modes

We propose a method to determine the angle $\gamma=arg(V_{ub})$, using the $B\to D^*V$ ($V=K^*, \rho$) modes. The $D^*$ is considered to decay to $D \pi$. An interference of the $B \to D^{*0}V$ and $B \to \bar {D^{*0}}V$ amplitudes is achieved by looking at a common final state $f$, in the subsequent decays of $D^0/\bar{D^0}$. A detailed analysis of the angular distribution, allows determination, not only of $\gamma$ and $|V_{ub}|$, but also all the hadronic amplitudes and strong phases involved. No prior knowledge of doubly Cabibbo suppressed branching ratios of $D$ are required. Large CP violating asymmetries ($\sim30$ for $\gamma=30^o$) are possible if $\bar{D^0} \to f$ is doubly Cabbibo suppressed, while $D^0 \to f$ is Cabbibo allowed, for decays of $B^+$ or $B^0$.Comment: 12 Pages Revte

Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2

Summary Uptake of apoptotic cells (ACs) by dendritic cells (DCs) and induction of a tolerogenic DC phenotype is an important mechanism for establishing peripheral tolerance to self-antigens. The receptors involved and underlying signaling pathways are not fully understood. Here, we identify Dectin-1 as a crucial tolerogenic receptor binding with nanomolar affinity to the core domain of several annexins (annexin A1, A5, and A13) exposed on ACs. Annexins bind to Dectin-1 on a site distinct from the interaction site of pathogen-derived β-glucans. Subsequent tolerogenic signaling induces selective phosphorylation of spleen tyrosine kinase (SYK), causing activation of NADPH oxidase-2 and moderate production of reactive oxygen species. Thus, mice deficient for Dectin-1 develop autoimmune pathologies (autoantibodies and splenomegaly) and generate stronger immune responses (cytotoxic T cells) against ACs. Our data describe an important immunological checkpoint system and provide a link between immunosuppressive signals of ACs and maintenance of peripheral immune tolerance

Signal-to-Noise Measurements on Irradiated CMS Tracker Detector Modules in an Electron Testbeam

The CMS experiment at the Large Hadron Collider at CERN is in the last phase of its construction. The harsh radiation environment at LHC will put strong demands in radiation hardness to the innermost parts of the detector. To assess the performance of irradiated microstrip detector modules, a testbeam was conducted at the Testbeam 22 facility of the DESY research center. The primary objective was the signal-to-noise measurement of irradiated CMS Tracker modules to ensure their functionality up to 10 years of LHC operation. The paper briefly summarises the basic setup at the facility and the hardware and software used to collect and analyse the data. Some interesting subsidiary results are shown, which confirm the expected behaviour of the detector with respect to the signal-to-noise performance over the active detector area and for different electron energies. The main focus of the paper are the results of the signal-to-noise measurements for CMS Tracker Modules which were exposed to different radiation doses

On the distortion of twin building lattices

We show that twin building lattices are undistorted in their ambient group; equivalently, the orbit map of the lattice to the product of the associated twin buildings is a quasi-isometric embedding. As a consequence, we provide an estimate of the quasi-flat rank of these lattices, which implies that there are infinitely many quasi-isometry classes of finitely presented simple groups. In an appendix, we describe how non-distortion of lattices is related to the integrability of the structural cocycle

Resolution Studies on Silicon Strip Sensors with fine Pitch

In June 2008 single-sided silicon strip sensors with 50 $\mu$m readout pitch were tested in a highly energetic pion beam at the SPS at CERN. The purpose of the test was to evaluate characteristic detector properties by varying the strip width and the number of intermediate strips. The experimental setup and first results for the spatial resolution are discussed.Comment: proceeding of the International Linear Collider Workshop 2008 (LCWS08); corrected typos, added reference for section

Ácidos grasos como marcadores de las relaciones tróficas entre el sestón, el zooplancton crustáceo y el sifonóforo Nanomia cara en Georges Basin y el cañón Oceanographer (NO Atlántico)

[EN] Fatty acid concentrations expressed as percentages of total fatty acid pools in seston, stage V copepodites of Calanus finmarchicus, adults of the euphausiid Meganyctiphanes norvegica, and the physonect siphonophore Nanomia cara were used to elucidate trophic links in Georges Basin and Oceanographer Canyon in September 2003. Seston at both locations was refractory and comprised mainly of saturated fatty acids. Phytoplankton did not contribute significantly to the fatty acid composition of seston or higher trophic levels. Only four fatty acids, i.e. 14:0, 16:0, 16:1 (n–7) and 18:1 (n–7), were transferred from seston to C. finmarchicus or M. norvegica, which suggested weak trophic interactions. Fatty acids transferred from the two species of crustaceans to N. cara included the same four fatty acids, along with three polyunsaturated fatty acids found in relatively high concentrations in both crustaceans, i.e. 20:3 (n–6), 20:5 (n–3) and 22:6 (n–3). In addition, 18:1 (n–9), which occurred in relatively high concentrations only in M. norvegica, and 18:0 and 18:2 (n–6), which were found in low concentrations in both crustaceans, also appeared to be transferred to N. cara. Overall, fatty acid trophic markers proved useful for identifying trophic links to N. cara[ES] En este estudio se utilizaron las concentraciones de ácidos grasos (expresadas como porcentajes) para identificar posibles relaciones tróficas entre el seston, el estadio V (copepoditos) de Calanus finmarchicus, los adultos del eufáusido Meganyctiphanes norvegica, y el sifonóforo fisonecto Nanomia cara en Georges Basin y el cañón submarino Oceanographer durante Septiembre de 2003. En ambos lugares el seston era muy refractario y compuesto básicamente por ácidos grasos saturados. El fitoplancton no contribuyó de forma significativa a la composición de ácidos grasos del seston o de niveles tróficos superiores. Sólo cuatro ácidos grasos [14:0, 16:0, 16:1 (n–7) y 18:1 (n–7)] se transfirieron potencialmente del seston a C. finmarchicus o M. norvegica, lo que sugiere una débil conexión trófica entre estos eslabones de la cadena. Los ácidos grasos transferidos de las dos especies de zooplancton crustáceo a N. cara incluyen los mismos descritos más arriba y otros tres ácidos grasos poliinsaturados [20:3 (n–6), 20:5 (n–3) y 22:6 (n–3)] encontrados en concentraciones relativamente elevadas en ambos crustáceos. Además, tanto el 18:1 (n–9) (encontrado en elevadas concentraciones en M. norvegica) y los 18:0 y 18:2 (n–6) (encontrados en bajas concentraciones en ambas especies de crustáceos) se transfieren a N. cara. Los ácidos grasos demuestran ser una herramienta útil para identificar conexiones tróficas en N. caraA grant to MJY from the National Science Foundation (NSF-0002493), the European Project EUROGEL, and USDA CRIS Project FLA-FAS-03978 supported this workPeer reviewe