Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes

The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype

The ICARUS Experiment, A Second-Generation Proton Decay Experiment and Neutrino Observatory at the Gran Sasso Laboratory

The final phase of the ICARUS physics program requires a sensitive mass of liquid Argon of 5000 tons or more. The T600 detector stands today as the first living proof that such large detector can be built and that liquid Argon imaging technology can be implemented on such large scales. After the successful completion of a series of technical tests to be performed at the assembly hall in Pavia, the T600 detector will be ready to be transported into the LNGS tunnel. The operation of the T600 at the LNGS will allow us (1) to develop the local infrastructure needed to operate our large detector (2) to start the handling of the underground liquid argon technology (3) to study the local background (4) to start the data taking with an initial liquid argon mass that will reach in a 5-6 year program the multi-kton goal. The T600 is to be considered as the first milestone on the road towards a total sensitive mass of 5000 tons: it is the first piece of the detector to be complemented by further modules of appropriate size and dimensions, in order to reach in a most efficient and rapid way the final design mass. In this document, we describe the physics program that will be accomplished within the first phase of the program

Observation of long ionizing tracks with the ICARUS T600 first half-module

F. Arneodo, B. Bade"ek, A. Badertscher, B. Baiboussinov, M. Baldo Ceolin, G. Battistoni, B. Bekman, P. Benetti, E. Bernardini, M. Bischofberger, A. Borio di Tigliole, R. Brunetti, A. Bueno, E. Calligarich, M. Campanelli, C. Carpanese, D. Cavalli, F. Cavanna, P. Cennini, S. Centro, A. Cesana, C. Chen, D. Chen, D.B. Chen, Y. Chen, D. Cline, Z. Dai, C. De Vecchi, A. Dabrowska, R. Dolfini*, M. Felcini, A. Ferrari, F. Ferri, Y. Ge, A. Gigli Berzolari, I. Gil-Botella, K. Graczyk, L. Grandi, K. He, J. Holeczek, X. Huang, C. Juszczak, D. Kie"czewska, J. Kisiel, T. Koz"owski, H. Kuna-Ciska", M. Laffranchi, J. Łagoda, Z. Li, F. Lu, J. Ma, M. Markiewicz, A. Martinez de la Ossa, C. Matthey, F. Mauri, D. Mazza, G. Meng, M. Messina, C. Montanari, S. Muraro, S. Navas-Concha, M. Nicoletto, G. Nurzia, S. Otwinowski, Q. Ouyang, O. Palamara, D. Pascoli, L. Periale, G. Piano Mortari, A. Piazzoli, P. Picchi, F. Pietropaolo, W. P ! o"ch"opek, T. Rancati, A. Rappoldi, G.L. Raselli, J. Rico, E. Rondio, M. Rossella, A. Rubbia, C. Rubbia, P. Sala, D. Scannicchio, E. Segreto, F. Sergiampietri, J. Sobczyk, J. Stepaniak, M. Szeptycka, M. Szleper, M. Szarska, M. Terrani, S. Ventura, C. Vignoli, H. Wang, M. W ! ojcik, J. Woo, G. Xu, Z. Xu, A. Zalewska, J. Zalipska, C. Zhang, Q. Zhang, S. Zhen, W. Zipper a INFN Laboratori Nazionali del Gran Sasso, s.s. 17bis Km 18+910, Assergi (L'Aquila), Italy b Institute of Experimental Physics, Warsaw University, Warszawa, Poland c Institute for Particle Physics, ETH H . onggerberg, Z . urich, Switzerland Dipartimento di Fisica e INFN, Universit " a di Padova, via Marzolo 8, Padova, Italy Dipartimento di Fisica e INFN, Universit " a di Milano, via Celoria 16, Milano, Italy f Institute of Physics, University of Silesia, Katowice, Poland Dipartimento di Fisica e INFN, Universit " a di Pavia, via Bassi 6, Pavia, Italy Dpto de F!isica Te ! orica y del Cosmos & C.A.F.P.E., Universidad de Granada, Avda. Severo Ochoa s/n, Granada, Spain Dipartimento di Fisica e INFN, Universit " a dell'Aquila, via Vetoio, L'Aquila, Italy CERN, CH-1211 Geneva 23, Switzerland Politecnico di Milano (CESNEF), Universit " a di Milano, via Ponzio 34/3, Milano, Ital

Measurements of primary and secondary flows in an industrial forward-curved centrifugal fan

An industrial-type centrifugal-flow fan was instrumented and tested in order to obtain a fully-detailed relative flow pattern at impeller discharge. Testing entailed investigation of both primary flows (jet-wake pattern and presence of return flows) and secondary flows (due to streamwise vorticity either from meridional curvature or rotation effects). In addition to conventional probing, a crossed hot-wire probe was employed in the tests. Ensemble-averaging the hot-wire signals made it possible to obtain the three-dimensional phase-averaged relative flow pattern at discharge by means of double positioning of the probe. Results show secondary-flow effects of appreciable magnitude interacting with primary flows (e. g. , return flow in the hub region and variations in vortex structure and wake position with variations in flowrate

Measurements of primary and secondary flows in an industrial forward-curved centrifugal fan

An industrial-type centrifugal-flow fan was instrumented and tested in order to obtain a fully-detailed relative flow pattern at impeller discharge. Testing entailed investigation of both primary flows (jet-wake pattern and presence of return flows) and secondary flows (due to streamwise vorticity either from meridional curvature or rotation effects). In addition to conventional probing, a crossed hot-wire probe was employed in the tests. Ensemble-averaging the hot-wire signals made it possible to obtain the three-dimensional phase-averaged relative flow pattern at discharge by means of double positioning of the probe. Results show secondary-flow effects of appreciable magnitude interacting with primary flows (e. g. , return flow in the hub region and variations in vortex structure and wake position with variations in flowrate