The Cyclophilin-Binding Agent Sanglifehrin A Is a Dendritic Cell Chemokine and Migration Inhibitor

Sanglifehrin A (SFA) is a cyclophilin-binding immunosuppressant but the immunobiology of action is poorly understood. We and others have reported that SFA inhibits IL-12 production and antigen uptake in dendritic cells (DC) and exhibits lower activity against lymphocytes. Here we show that SFA suppresses DC chemokine production and migration. Gene expression analysis and subsequent protein level confirmation revealed that SFA suppressed CCL5, CCL17, CCL19, CXCL9 and CXCL10 expression in human monocyte-derived DC (moDC). A systems biology analysis, Onto Express, confirmed that SFA interferes with chemokine-chemokine receptor gene expression with the highest impact. Direct comparison with the related agent cyclosporine A (CsA) and dexamethasone indicated that SFA uniquely suppresses moDC chemokine expression. Competitive experiments with a 100-fold molar excess of CsA and with N-Methyl-Val-4-cyclosporin, representing a nonimmunosuppressive derivative of CsA indicated chemokine suppression through a cyclophilin-A independent pathway. Functional assays confirmed reduced migration of CD4+ Tcells and moDCs to supernatant of SFA-exposed moDCs. Vice versa, SFA-exposed moDC exhibited reduced migration against CCL19. Moreover, SFA suppressed expression of the ectoenzyme CD38 that was reported to regulate DC migration and cytokine production. These results identify SFA as a DC chemokine and migration inhibitor and provide novel insight into the immunobiology of SFA

Observation of isotonic symmetry for enhanced quadrupole collectivity in neutron-rich 62,64,66Fe isotopes at N=40

The transition rates for the 2_{1}^{+} states in 62,64,66Fe were studied using the Recoil Distance Doppler-Shift technique applied to projectile Coulomb excitation reactions. The deduced E2 strengths illustrate the enhanced collectivity of the neutron-rich Fe isotopes up to N=40. The results are interpreted by the generalized concept of valence proton symmetry which describes the evolution of nuclear structure around N=40 as governed by the number of valence protons with respect to Z~30. The deformation suggested by the experimental data is reproduced by state-of-the-art shell calculations with a new effective interaction developed for the fpgd valence space.Comment: 4 pages, 2 figure

Identifying Boosted Objects with N-subjettiness

We introduce a new jet shape -- N-subjettiness -- designed to identify boosted hadronically-decaying objects like electroweak bosons and top quarks. Combined with a jet invariant mass cut, N-subjettiness is an effective discriminating variable for tagging boosted objects and rejecting the background of QCD jets with large invariant mass. In efficiency studies of boosted W bosons and top quarks, we find tagging efficiencies of 30% are achievable with fake rates of 1%. We also consider the discovery potential for new heavy resonances that decay to pairs of boosted objects, and find significant improvements are possible using N-subjettiness. In this way, N-subjettiness combines the advantages of jet shapes with the discriminating power seen in previous jet substructure algorithms.Comment: 26 pages, 26 figures, 2 tables; v2: references added; v3: discussion of results extende

Jet Substructure Without Trees

We present an alternative approach to identifying and characterizing jet substructure. An angular correlation function is introduced that can be used to extract angular and mass scales within a jet without reference to a clustering algorithm. This procedure gives rise to a number of useful jet observables. As an application, we construct a top quark tagging algorithm that is competitive with existing methods.Comment: 22 pages, 16 figures, version accepted by JHE

Lifetime measurements in 63^{63}Co and 65^{65}Co

Lifetimes of the $9/2^-_1$ and $3/2^-_1$ states in $^{63}$Co and the $9/2^-_1$ state in $^{65}$Co were measured using the recoil distance Doppler shift and the differential decay curve methods. The nuclei were populated by multi-nucleon transfer reactions in inverse kinematics. Gamma rays were measured with the EXOGAM Ge array and the recoiling fragments were fully identified using the large-acceptance VAMOS spectrometer. The E2 transition probabilities from the $3/2^-_1$ and $9/2^-_1$ states to the $7/2^-$ ground state could be extracted in $^{63}$Co as well as an upper limit for the $9/2^-_1\rightarrow7/2^-_1$ $B$(E2) value in $^{65}$Co. The experimental results were compared to large-scale shell-model calculations in the $pf$ and $pfg_{9/2}$ model spaces, allowing to draw conclusions on the single-particle or collective nature of the various states.Comment: 8 pages, 8 figures, 1 table, accepted for publication in Physical Review

Jet Dipolarity: Top Tagging with Color Flow

A new jet observable, dipolarity, is introduced that can distinguish whether a pair of subjets arises from a color singlet source. This observable is incorporated into the HEPTopTagger and is shown to improve discrimination between top jets and QCD jets for moderate to high pT.Comment: 8 pages, 6 figures (updated to JHEP version

Quantum stereodynamics of Li + HF reactive collisions: The role of reactants polarization on the differential cross section

A complete quantum study for the state-to-state Li + HF(v,j,m) → LiF(v′,j′,Ω′) + H reactive collisions has been performed using a wave packet method, for different initial rotational states and helicity states of the reactants. The state-to-state differential cross section has been simulated, and the polarization of products extracted. It is found that the reactivity is enhanced for nearly collinear collisions, which produces a vibrational excitation of HF, needed to overcome the late barrier. It is also found that LiF(v′ = 0) products are preferentially forward scattered, while vibrationally excited LiF(v′ = 1 and 2) are backward scattered. These results are interpreted with a simple reaction mechanism, based on the late character and bent geometry of the transition state, originating from a covalent/ionic crossing, which consists of two steps: the arrival at the transition state and the dissociation. In the first step, in order to get to the saddle point some HF vibrational excitation is required, which favors head-on collisions and therefore low values of m. In the second step a fast dissociation of H atom takes place, which is explained by the ionic Li+F -H character of the bent transition state: the FH- is repulsive making that H depart rapidly leaving a highly rotating LiF molecule. For the higher energy analyzed, where resonances slightly contribute, the orientation and alignment of product rotational states, referred to as reactants frame (with the z-axis parallel to k), are approximately constant with the scattering angle. The alignment is close to -1, showing that j′ is perpendicular to k, while starting from initial states with well defined rotational orientation, as states with pure m values, the final rotational are also oriented. It is also found that when using products frame (with the z′-axis parallel to k′) the rotational alignment and orientation of products varies a lot with the scattering angle just because the z′ axis changes from being parallel to anti-parallel to k when varying from θ = 0 to π. © the Owner Societies 2011.This work has been supported by the Ministerio de Ciencia e Innovación, under grants CSD2009-00038 (programa CONSOLIDER-INGENIO 2010 entitled “Molecular Astrophysics: the Herschel and Alma era”), FIS2010-18132, CTQ2008-02578 and CTQ2007-62898, and by Comunidad Autónoma de Madrid (CAM) under Grant No. S-0505/MAT/0303.Peer Reviewe

Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer

The degree and type of T cell infiltration influence rectal cancer prognosis regardless of classical tumor staging. We asked whether clonal expansion and tumor infiltration are restricted to selected-phenotype T cells; which clones are accessible in peripheral blood; and what the spatial distribution of their target antigens is. From five rectal cancer patients, we isolated paired tumor-infiltrating T cells (TILs) and T cells from unaffected rectum mucosa (T(UM)) using 13-parameter FACS single cell index sorting. TCRαβ sequences, cytokine, and transcription factor expression were determined with single cell sequencing. TILs and T(UM) occupied distinct phenotype compartments and clonal expansion predominantly occurred within CD8(+) T cells. Expanded TIL clones identified by paired TCRαβ sequencing and exclusively detectable in the tumor showed characteristic PD-1 and TIM-3 expression. TCRβ repertoire sequencing identified 49 out of 149 expanded TIL clones circulating in peripheral blood and 41 (84%) of these were PD-1(-) TIM-3(-). To determine whether clonal expansion of predominantly tumor-infiltrating T cell clones was driven by antigens uniquely presented in tumor tissue, selected TCRs were reconstructed and incubated with cells isolated from corresponding tumor or unaffected mucosa. The majority of clones exclusively detected in the tumor recognized antigen at both sites. In summary, rectal cancer is infiltrated with expanded distinct-phenotype T cell clones that either i) predominantly infiltrate the tumor, ii) predominantly infiltrate the unaffected mucosa, or iii) overlap between tumor, unaffected mucosa, and peripheral blood. However, the target antigens of predominantly tumor-infiltrating TIL clones do not appear to be restricted to tumor tissue

Heavy Squarks at the LHC

The LHC, with its seven-fold increase in energy over the Tevatron, is capable of probing regions of SUSY parameter space exhibiting qualitatively new collider phenomenology. Here we investigate one such region in which first generation squarks are very heavy compared to the other superpartners. We find that the production of these squarks, which is dominantly associative, only becomes rate-limited at mSquark > 4(5) TeV for L~10(100) fb-1. However, discovery of this scenario is complicated because heavy squarks decay primarily into a jet and boosted gluino, yielding a dijet-like topology with missing energy (MET) pointing along the direction of the second hardest jet. The result is that many signal events are removed by standard jet/MET anti-alignment cuts designed to guard against jet mismeasurement errors. We suggest replacing these anti-alignment cuts with a measurement of jet substructure that can significantly extend the reach of this channel while still removing much of the background. We study a selection of benchmark points in detail, demonstrating that mSquark= 4(5) TeV first generation squarks can be discovered at the LHC with L~10(100)fb-1