Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory.

PD-L1 on the surface of tumor cells binds its receptor PD-1 on effector T cells, thereby suppressing their activity. Antibody blockade of PD-L1 can activate an anti-tumor immune response leading to durable remissions in a subset of cancer patients. Here, we describe an alternative mechanism of PD-L1 activity involving its secretion in tumor-derived exosomes. Removal of exosomal PD-L1 inhibits tumor growth, even in models resistant to anti-PD-L1 antibodies. Exosomal PD-L1 from the tumor suppresses T cell activation in the draining lymph node. Systemically introduced exosomal PD-L1 rescues growth of tumors unable to secrete their own. Exposure to exosomal PD-L1-deficient tumor cells suppresses growth of wild-type tumor cells injected at a distant site, simultaneously or months later. Anti-PD-L1 antibodies work additively, not redundantly, with exosomal PD-L1 blockade to suppress tumor growth. Together, these findings show that exosomal PD-L1 represents an unexplored therapeutic target, which could overcome resistance to current antibody approaches

Final results of the tests on the resistive plate chambers for the ALICE muon arm

Abstract The trigger for the ALICE muon spectrometer will be issued by single-gap, low resistivity bakelite resistive plate chambers (RPCs). The trigger system consists of four 5.5 × 6.5 m 2 RPC planes arranged in two stations, for a total of 72 detectors. One hundred and sixteen detectors have been assembled and tested in Torino. The tests have been performed with the streamer mixture developed for heavy ion data-taking. The tests include: the detection of gas leaks and parasitic currents; the measurement of the efficiency with cosmic rays, with particular regard to the uniformity of the efficiency throughout the whole active surface, with a granularity of about 2 × 2 cm 2 ; the measurement of the dark current and of the mean and localised noise rate. All the RPCs produced have been characterised. Among them, the detectors to be finally installed in ALICE and some spare have been selected; 17% of all the produced detectors have been discarded. A short description of the test set-up is given. The results of the tests are presented, with particular regard to the performance of the selected detectors

Alignment of the ALICE Inner Tracking System with cosmic-ray tracks

37 pages, 15 figures, revised version, accepted by JINSTALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 micron in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10^5 charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.Peer reviewe

Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at $\sqrt{s} = 900$ GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region $(|\eta|<0.8)$ over the transverse momentum range $0.15<p_{\rm T}<10$ GeV/$c$. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for $|\eta|<0.8$ is $\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001$ (stat.) $\pm0.007$ (syst.) GeV/$c$ and \left_{\rm NSD}=0.489\pm0.001 (stat.) $\pm0.007$ (syst.) GeV/$c$, respectively. The data exhibit a slightly larger $\left<p_{\rm T}\right>$ than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Memristor and Translation Control in Cancer Immunology

The progression of technology in the field of cancer biology is allowing us to discover and understand novel unexplored molecular mechanism governing cancer initiation, progression and metastasis. Yet, a lot still needs to be done in order to achieve better a stable therapy for patients, including a precise personalized medicine that take into account specific genetic alterations. With this work I am providing a detailed contribution in the field of memristor, future fundamental player for the clinical diffusion of the sequencing technique, to conclude in a series of discoveries in the field of cancer immunology all based on the ribosome profiling sequencing approach. More in detail this work could be divided into three main parts: Memristor, Memristive application to RNA/DNA sequencing and cancer immunology. The first section it is focused on new advances in the field of Memristor. In particular, I present the GBCM model, the SBPI algorithm and the circuitry designed in order to implement the two features. Moreover, is presented a series of essays made to prove the efficiency of the dynamics of the perceptron. Such essays evaluate the characterization of the different impulses to the system, the learning dynamics — finding the most efficient learning strategies — and the robustness of the circuitry to various kinds of noises. The next part of this elaborate will focus on “memristive” application. In particular, I approached the study of nanopores as a novel physics system that can be effectively modelled by the usage of a series of memristive elements. Nanopores are widely used in the DNA/RNA sequencing even thought they require more implementing before become an impactful marketable device committed to low cost sequencing as shown in the “nanopore” section. During this section the memristive contribution and applications will be presented. In particular, in the last few years unbios DNA/RNA sequencing techniques have become fundamental to understand new molecular mechanism in biology. In cancer, DNA sequencing allowed scientists to discover a large number of genomic mutations promoting cellular transformation and cancer progression. Chronologically later, RNA sequencing disclose a specific and carefully controlled program in the chromatin undergoing the regulation of the transcription of specific mRNAs piloting oncologic phenotypes. In the last part of this section I will present a relatively novel sequencing technique (called ribosome profiling), and its implication in cancer immunology. This approach, by modifying the canonical RNA sequencing protocol allows to the detect the amount of ribosomes per transcripts potentially actively translating the the transcripts into proteins. In conclusion it is presented the sticking finding employing Ribosome Profiling, discovering how C-MYC contributes to the regulation of the innate immune response to protect the tumor niche from the cytotoxic activity of the CD3+ CD8+ lymphocytes