Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

AbstractThe expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA) termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells

Velocity-selective sublevel resonance of atoms with an array of current-carrying wires

Resonance transitions between the Zeeman sublevels of optically-polarized Rb atoms traveling through a spatially periodic magnetic field are investigated in a radio-frequency (rf) range of sub-MHz. The atomic motion induces the resonance when the Zeeman splitting is equal to the frequency at which the moving atoms feel the magnetic field oscillating. Additional temporal oscillation of the spatially periodic field splits a motion-induced resonance peak into two by an amount of this oscillation frequency. At higher oscillation frequencies, it is more suitable to consider that the resonance is mainly driven by the temporal field oscillation, with its velocity-dependence or Doppler shift caused by the atomic motion through the periodic field. A theoretical description of motion-induced resonance is also given, with emphasis on the translational energy change associated with the internal transition.Comment: 7 pages, 3 figures, final versio

Correlation structure in nondipole photoionization

The nondipole parameters that characterize the angular disribution of the photoelectrons from the 3d subshell of Cs are found to be altered qualitatively by the inclusion of correlation in the form of interchannel coupling between the $3d_{3/2}$ and $3d_{5/2}$ photoionization channels. A prominent characteristic maximum is predicted only in the parameters for $3d_{5/2}$ photoionization, while the effect for $3d_{3/2}$ is rather weak. The results are obtained within the framework of the Generalized Random Phase Approximation with Exchange (GRPAE), which in addition to the RPAE effects takes into account the rearrangement of all atomic electrons due to the creation of a 3d vacancy

Design, Commissioning and Performance of the PIBETA Detector at PSI

We describe the design, construction and performance of the PIBETA detector built for the precise measurement of the branching ratio of pion beta decay, pi+ -> pi0 e+ nu, at the Paul Scherrer Institute. The central part of the detector is a 240-module spherical pure CsI calorimeter covering 3*pi sr solid angle. The calorimeter is supplemented with an active collimator/beam degrader system, an active segmented plastic target, a pair of low-mass cylindrical wire chambers and a 20-element cylindrical plastic scintillator hodoscope. The whole detector system is housed inside a temperature-controlled lead brick enclosure which in turn is lined with cosmic muon plastic veto counters. Commissioning and calibration data were taken during two three-month beam periods in 1999/2000 with pi+ stopping rates between 1.3*E3 pi+/s and 1.3*E6 pi+/s. We examine the timing, energy and angular detector resolution for photons, positrons and protons in the energy range of 5-150 MeV, as well as the response of the detector to cosmic muons. We illustrate the detector signatures for the assorted rare pion and muon decays and their associated backgrounds.Comment: 117 pages, 48 Postscript figures, 5 tables, Elsevier LaTeX, submitted to Nucl. Instrum. Meth.

Early above- and below-ground responses of subboreal conifer seedlings to various levels of deciduous canopy removal

We examined the growth of understory conifers, following partial or complete deciduous canopy removal, in a field study established in two regions in Canada. In central British Columbia, we studied the responses of three species (Pseudotsuga menziesii var. glauca (Beissn.) Franco, Picea glauca (Moench) Voss x Picea engelmannii Parry ex Engelm., and Abies lasiocarpa (Hook.) Nutt.), and in northwestern Quebec, we studied one species (Abies balsamea (L.) Mill.). Stem and root diameter and height growth were measured 5 years before and 3 years after harvesting. Both root and stem diameter growth increased sharply following release but seedlings showed greater root growth, suggesting that in the short term, improvement in soil resource capture and transport, and presumably stability, may be more important than an increase in stem diameter and height growth. Response was strongly size dependent, which appears to reflect greater demand for soil resources as well as higher light levels and greater tree vigour before release for taller individuals. Growth ratios could not explain the faster response generally attributed to true fir species or the unusual swift response of spruces. Good prerelease vigour of spruces, presumably favoured by deciduous canopies, could explain their rapid response to release

Further studies on a hybrid cell-surface antigen associated with human chromosome 11 using a monoclonal antibody

A monoclonal antibody has been obtained that recognizes an antigen encoded by human chromosome 11. We present evidence that this monoclonal antibody recognizes the same or a similar antigenic activity as that previously called a 1 . Genetic information necessary for a 1 expression and recognition by the monoclonal antibody both map to 11p13 → 11pter. Mutants that have lost a 1 are no longer recognized by the monoclonal antibody. The macroglycolipid fraction of human erythrocyte membranes which contains the a 1 antigenic activity is able to convert antigen-negative Chinese hamster ovary cells into cells which are killed by the monoclonal antibody plus complement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45556/1/11188_2005_Article_BF01543049.pd

Cichlid biogeography: comment and review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72313/1/j.1467-2979.2004.00148.x.pd

The first Hubble diagram and cosmological constraints using superluminous supernovae

This paper has gone through internal review by the DES collaboration. It has Fermilab preprint number 19-115-AE and DES publication number 13387. We acknowledge support from EU/FP7- ERC grant 615929. RCN would like to acknowledge support from STFC grant ST/N000688/1 and the Faculty of Technology at the University of Portsmouth. LG was funded by the European Union’s Horizon 2020 Framework Programme under the Marie Skłodowska- Curie grant agreement no. 839090. This work has been partially supported by the Spanish grant PGC2018-095317-B-C21 within the European Funds for Regional Development (FEDER). Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S. National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Education Funding Council for England, the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, the Kavli Institute of Cosmological Physics at the University of Chicago, the Center for Cosmology and Astro-Particle Physics at the Ohio State University, the Mitchell Institute for Fundamental Physics and Astronomy at Texas A&M University, Financiadora de Estudos e Projetos, Fundac¸ ˜ao Carlos Chagas Filho de Amparo `a Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnol´ogico and the Minist´erio da Ciˆencia, Tecnologia e Inovac¸ ˜ao, the Deutsche Forschungsgemeinschaft, and the Collaborating Institutions in the Dark Energy Survey. The Collaborating Institutions are Argonne National Laboratory, the University of California at Santa Cruz, the University of Cambridge, Centro de Investigaciones Energ´eticas, Medioambientales y Tecnol ´ogicas-Madrid, the University of Chicago, University College London, the DES-Brazil Consortium, the University of Edinburgh, the Eidgen¨ossische Technische Hochschule (ETH) Z¨urich, Fermi NationalAccelerator Laboratory, theUniversity of Illinois atUrbana- Champaign, the Institut de Ci`encies de l’Espai (IEEC/CSIC), the Institut de F´ısica d’Altes Energies, Lawrence Berkeley National Laboratory, the Ludwig-Maximilians Universit¨at M¨unchen and the associated Excellence Cluster Universe, the University of Michigan, the National Optical Astronomy Observatory, the University of Nottingham, The Ohio State University, the University of Pennsylvania, the University of Portsmouth, SLAC National Accelerator Laboratory, Stanford University, the University of Sussex, Texas A&M University, and the OzDES Membership Consortium. Based in part on observations at Cerro Tololo Inter-American Observatory, National Optical Astronomy Observatory, which is operated by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. The DES data management system is supported by the National Science Foundation under grant numbers AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by MINECO under grants AYA2015- 71825, ESP2015-66861, FPA2015-68048, SEV-2016-0588, SEV- 2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the CERCA program of the Generalitat de Catalunya. Research leading to these results has received funding from the European Research Council under the European Union Seventh Framework Programme (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478.We acknowledge support from the Australian Research Council Centre of Excellence for All-skyAstrophysics (CAASTRO), through project number CE110001020, and the Brazilian Instituto Nacional de Ciˆencia e Tecnologia (INCT) e-Universe (CNPq grant 465376/2014-2). This paper has been authored by Fermi Research Alliance, LLC under Contract No.DE-AC02-07CH11359 with theU.S.Department of Energy, Office of Science, Office of High Energy Physics. The United States Government retains and the publisher, by accepting the paper for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this paper, or allow others to do so, for United States Government purposes.We present the first Hubble diagram of superluminous supernovae (SLSNe) out to a redshift of two, together with constraints on the matter density, M, and the dark energy equation-of-state parameter, w(≡p/ρ). We build a sample of 20 cosmologically useful SLSNe I based on light curve and spectroscopy quality cuts. We confirm the robustness of the peak–decline SLSN I standardization relation with a larger data set and improved fitting techniques than previous works. We then solve the SLSN model based on the above standardization via minimization of the χ2 computed from a covariance matrix that includes statistical and systematic uncertainties. For a spatially flat cold dark matter ( CDM) cosmological model, we find M = 0.38+0.24 −0.19, with an rms of 0.27 mag for the residuals of the distance moduli. For a w0waCDM cosmological model, the addition of SLSNe I to a ‘baseline’ measurement consisting of Planck temperature together with Type Ia supernovae, results in a small improvement in the constraints of w0 and wa of 4 per cent.We present simulations of future surveys with 868 and 492 SLSNe I (depending on the configuration used) and show that such a sample can deliver cosmological constraints in a flat CDM model with the same precision (considering only statistical uncertainties) as current surveys that use Type Ia supernovae, while providing a factor of 2–3 improvement in the precision of the constraints on the time variation of dark energy, w0 and wa. This paper represents the proof of concept for superluminous supernova cosmology, and demonstrates they can provide an independent test of cosmology in the high-redshift (z > 1) universe.EU/FP7-ERC grant 615929STFC grant ST/N000688/1Faculty of Technology at the University of PortsmouthEuropean Union’s Horizon 2020 Framework Programme under the Marie Skłodowska- Curie grant agreement no. 839090Spanish grant PGC2018-095317-B-C21 within the European Funds for Regional Development (FEDER)U.S. Department of EnergyU.S. National Science FoundationMinistry of Science and Education of SpainScience and Technology Facilities Council of the United KingdomHigher Education Funding Council for EnglandNational Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign,Kavli Institute of Cosmological Physics at the University of ChicagoCenter for Cosmology and Astro-Particle Physics at the Ohio State UniversityMitchell Institute for Fundamental Physics and Astronomy at Texas A&M University, Financiadora de Estudos e Projetos, Fundacão Carlos Chagas Filho de Amparo `a Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico and the Ministério da Ciencia, Tecnologia e InovacãoDeutsche ForschungsgemeinschaftCollaborating Institutions in the Dark Energy Survey.National Science Foundation under grant numbers AST-1138766 and AST-1536171.T MINECO under grants AYA2015- 71825, ESP2015-66861, FPA2015-68048, SEV-2016-0588, SEV- 2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union.CERCA program of the Generalitat de Catalunya.European Research Council under the European Union Seventh Framework Programme (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478.Australian Research Council Centre of Excellence for All-skyAstrophysics (CAASTRO), through project number CE110001020Brazilian Instituto Nacional de Ciˆencia e Tecnologia (INCT) e-Universe (CNPq grant 465376/2014-2)Fermi Research Alliance, LLC under Contract No.DE-AC02-07CH11359 with theU.S.Department of Energy, Office of Science, Office of High Energy Physic

Measurement of the splashback feature around SZ-selected Galaxy clusters with DES, SPT, and ACT

We present a detection of the splashback feature around galaxy clusters selected using the Sunyaev–Zel’dovich (SZ) signal. Recent measurements of the splashback feature around optically selected galaxy clusters have found that the splashback radius, rsp, is smaller than predicted by N-body simulations. A possible explanation for this discrepancy is that rsp inferred from the observed radial distribution of galaxies is affected by selection effects related to the optical cluster-finding algorithms. We test this possibility by measuring the splashback feature in clusters selected via the SZ effect in data from the South Pole Telescope SZ survey and the Atacama Cosmology Telescope Polarimeter survey. The measurement is accomplished by correlating these cluster samples with galaxies detected in the Dark Energy Survey Year 3 data. The SZ observable used to select clusters in this analysis is expected to have a tighter correlation with halo mass and to be more immune to projection effects and aperture-induced biases, potentially ameliorating causes of systematic error for optically selected clusters. We find that the measured rsp for SZ-selected clusters is consistent with the expectations from simulations, although the small number of SZ-selected clusters makes a precise comparison difficult. In agreement with previous work, when using optically selected redMaPPer clusters with similar mass and redshift distributions, rsp is ∼2σ smaller than in the simulations. These results motivate detailed investigations of selection biases in optically selected cluster catalogues and exploration of the splashback feature around larger samples of SZ-selected clusters. Additionally, we investigate trends in the galaxy profile and splashback feature as a function of galaxy colour, finding that blue galaxies have profiles close to a power law with no discernible splashback feature, which is consistent with them being on their first infall into the cluster