p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer

Background: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. Patients and methods: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. Results: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. Conclusions: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cance

A Cylindrical GEM Inner Tracker for the BESIII experiment at IHEP

The Beijing Electron Spectrometer III (BESIII) is a multipurpose detector that collects data provided by the collision in the Beijing Electron Positron Collider II (BEPCII), hosted at the Institute of High Energy Physics of Beijing. Since the beginning of its operation, BESIII has collected the world largest sample of J/{\psi} and {\psi}(2s). Due to the increase of the luminosity up to its nominal value of 10^33 cm-2 s-1 and aging effect, the MDC decreases its efficiency in the first layers up to 35% with respect to the value in 2014. Since BESIII has to take data up to 2022 with the chance to continue up to 2027, the Italian collaboration proposed to replace the inner part of the MDC with three independent layers of Cylindrical triple-GEM (CGEM). The CGEM-IT project will deploy several new features and innovation with respect the other current GEM based detector: the {\mu}TPC and analog readout, with time and charge measurements will allow to reach the 130 {\mu}m spatial resolution in 1 T magnetic field requested by the BESIII collaboration. In this proceeding, an update of the status of the project will be presented, with a particular focus on the results with planar and cylindrical prototypes with test beams data. These results are beyond the state of the art for GEM technology in magnetic field

May a unitary autonomic index help assess autonomic cardiac regulation in elite athletes? Preliminary observations on the national Italian Olympic committee team

Long term endurance training, as occurring in elite athletes, is associated to cardiac neural remodeling in favor of cardioprotective vagal mechanisms, resulting in resting bradycardia and augmented contribution of cardiac parasympathetic nerve activity. Autonomic assessment can be performed by way of Heart Rate Variability. This technique however provides multiple indices, and there is not yet complete agreement on their specific significance. Purpose of the study was to assess whether a rank transformation and radar plot could provide a unitary autonomic index, capable to show a correlation between intensity of individual work and quality of autonomic regulation

NLRP3 polymorphisms and response to interferon-beta in multiple sclerosis patients

Evidence exists for a potential modulation of inflammasome activity by interferon beta. Here, we investigated the roles of inflammasomes [absent in melanoma 2 (AIM2); NLR family, CARD domain containing 4 (NLRC4); NLR family, pyrin domain containing 1 and 3 (NLRP1 and NLRP3)] and related cytokines (IL1B, IL10, IL18) in the response to interferon beta in patients with relapsing-remitting multiple sclerosis. Ninety-seven patients treated with interferon beta were classified into responders and non-responders according to clinical criteria after 24 months and clinical-radiological criteria after 12 months of treatment. Messenger RNA expression levels of inflammasomes and cytokines were determined by real-time polymerase chain reaction in peripheral blood mononuclear cells collected before treatment with interferon beta. In a subgroup of patients, NLRP3 and IL1B expression was also determined after 3 months (n = 32) and 12 months (n = 20) of interferon beta treatment. A polymorphism located in the NLRP3 gene, rs35829419, was genotyped in 789 multiple sclerosis patients treated with interferon beta. Baseline mRNA expression levels for NLRP3 and IL1B were increased in peripheral blood mononuclear cells from non-responders compared to responders classified according to clinical criteria after 24 months (P = 0.02 and P = 0.001, respectively). No significant differences were observed for other inflammasomes and related cytokines. Differences in NLRP3 and IL1B expression remained significant following a clinical-radiological classification after 12 months (P = 0.007 and P = 0.02, respectively). After treatment with interferon beta, NLRP3 and IL1B expression was increased in responders but unchanged in non-responders. A trend for association was observed between rs35829419 and interferon beta response (pM-H = 0.08). These results point to a role of the NLRP3 inflammasome and its related cytokine IL1B in the response to interferon beta in patients with relapsing-remitting multiple sclerosis

High field hybrid photoinjector electron source for advanced light source applications

The production of high spectral brilliance radiation from electron beam sources depends critically on the electron beam qualities. One must obtain very high electron beam brightness, implying simultaneous high peak current and low emittance. These attributes are enabled through the use of very high field acceleration in a radio-frequency (rf) photoinjector source. Despite the high fields currently utilized, there is a limit on the achievable peak current in high brightness operation, in the range of tens of Ampere. This limitation can be overcome by the use of a hybrid standing wave/traveling wave structure; the standing wave portion provides acceleration at a high field from the photocathode, while the traveling wave part yields strong velocity bunching. This approach is explored here in a C-band scenario, at field strengths (&gt;100 MV/m) at the current state-of-the-art. It is found that one may arrive at an electron beam with many hundreds of Amperes with well-sub-micron normalized emittance. This extremely compact injector system also possesses attractive simplification of the rf distribution system by eliminating the need for an rf circulator. We explore the use of this device in a compact 400 MeV-class source, driving both inverse Compton scattering and free-electron laser radiation sources with unique, attractive properties

The PLASMONX Project for advanced beam physics experiments

The Project PLASMONX is well progressing into its design phase and has entered as well its second phase of procurements for main components. The project foresees the installation at LNF of a Ti:Sa laser system (peak power > 170 TW), synchronized to the high brightness electron beam produced by the SPARC photo-injector. The advancement of the procurement of such a laser system is reported, as well as the construction plans of a new building at LNF to host a dedicated laboratory for high intensity photon beam experiments (High Intensity Laser Laboratory). Several experiments are foreseen using this complex facility, mainly in the high gradient plasma acceleration field and in the field of mono- chromatic ultra-fast X-ray pulse generation via Thomson back-scattering. Detailed numerical simulations have been carried out to study the generation of tightly focused electron bunches to collide with laser pulses in the Thomson source: results on the emitted spectra of X-rays are presented

Building the impedance model of a real machine

A reliable impedance model of a particle accelerator can be built by combining the beam coupling impedances of all the components. This is a necessary step to be able to evaluate the machine performance limitations, identify the main contributors in case an impedance reduction is required, and study the interaction with other mechanisms such as optics nonlinearities, transverse damper, noise, space charge, electron cloud, beam-beam (in a collider). The main phases to create a realistic impedance model, and verify it experimentally, will be reviewed, highlighting the main challenges. Some examples will be presented revealing the levels of precision of machine impedance models that have been achieved

THE SNS RING DIPOLE MAGNETIC FIELD QUALITY.

The large acceptance and compact size of the Spallation Neutron Source (SNS) ring implies the use of short, large aperture dipole magnets, with significant end field errors. The SNS will contain 32 such dipoles. We report magnetic field measurements of the first 16 magnets. The end field errors have been successfully compensated by the use of iron bumps. For 1.0 GeV protons, the magnets have been shimmed to meet the 0.01% specification for rms variation of the integral field. At 1.3 GeV, the rms variation is 0.036%. The load on the corrector system at 1.3 GeV will be reduced by the use of sorting

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy