Advantages and Requirements in Time Resolving Tracking for Astroparticle Experiments in Space

A large-area, solid-state detector with single-hit precision timing measurement will enable several breakthrough experimental advances for the direct measurement of particles in space. Silicon microstrip detectors are the most promising candidate technology to instrument the large areas of the next-generation astroparticle space borne detectors that could meet the limitations on power consumption required by operations in space. We overview the novel experimental opportunities that could be enabled by the introduction of the timing measurement, concurrent with the accurate spatial and charge measurement, in Silicon microstrip tracking detectors, and we discuss the technological solutions and their readiness to enable the operations of large-area Silicon microstrip timing detectors in space

Akt/protein kinase B and endothelial nitric oxide synthase mediate muscular neovascularization induced by tissue kallikrein gene transfer

BACKGROUND: Angiogenesis gene therapy with human tissue kallikrein (hTK) has shown promise for ischemic disease. The present study was undertaken to (1) assess an optimal gene transfer modality, (2) clarify hTK angiogenic pathways, and (3) discount possible side effects. METHODS AND RESULTS: The hTK gene was transferred to murine adductors by increasing doses of an adenovirus (Ad.hTK). Heterologous protein production was evaluated by ELISA and immunohistochemistry. Structural and functional characteristics of hTK-induced neovascularization were assessed. Muscular endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF)-A mRNA and protein content were evaluated by real-time polymerase chain reaction and Western blotting. The ability of hTK to phosphorylate-activate Akt/protein kinase B (Akt-B) and VEGF receptor 2 (VEGF-R2) was also determined. Implication of the aforementioned mechanisms in Ad.hTK-induced neovascularization was challenged by blocking Akt-B with a dominant-negative Akt construct; NOS with N(G)-nitro-L-arginine methyl ester; and VEGF-A with neutralizing antibody, VEGF-R2 antagonist, or Ad carrying soluble VEGF-R1 gene. We found that 10(7) PFU Ad.hTK led to peak increases in capillary and arteriole density. Newly developed arterioles persisted for up to 8 weeks. Ad.hTK did not change microvascular permeability. Ad.hTK upregulated eNOS mRNA and protein and activated Akt-B through Ser-473 phosphorylation. Inhibitory studies documented that these biochemical events were instrumental to Ad.hTK-induced neovascularization. In contrast, Ad.hTK neither affected VEGF-A and VEGF-R2 levels nor increased VEGF-R2 phosphorylation. Consistently, Ad.hTK-induced neovascularization was not disturbed by any of the different approaches used to block VEGF-A. CONCLUSIONS: Our findings provide new information on the pathway involved in hTK-induced neoangiogenesis and represent an advancement toward clinical applications with Ad.hTK

A New Approach to Calorimetry in Space-Based Experiments for High-Energy Cosmic Rays

Precise measurements of the energy spectra and of the composition of cosmic rays in the PeV region could improve our knowledge regarding their origin, acceleration mechanism, propagation, and composition. At the present time, spectral measurements in this region are mainly derived from data collected by ground-based detectors, because of the very low particle rates at these energies. Unfortunately, these results are affected by the high uncertainties typical of indirect measurements, which depend on the complicated modeling of the interaction of the primary particle with the atmosphere. A space experiment dedicated to measurements in this energy region has to achieve a balance between the requirements of lightness and compactness, with that of a large acceptance to cope with the low particle rates. CaloCube is a four-year-old R&D project, approved and financed by the Istituto Nazionale di Fisica Nucleare (INFN) in 2014, aiming to optimize the design of a space-borne calorimeter. The large acceptance needed is obtained by maximizing the number of entrance windows, while thanks to its homogeneity and high segmentation this new detector achieves an excellent energy resolution and an enhanced separation power between hadrons and electrons. In order to optimize detector performances with respect to the total mass of the apparatus, comparative studies on different scintillating materials, different sizes of crystals, and different spacings among them have been performed making use of MonteCarlo simulations. In parallel to simulations studies, several prototypes instrumented with CsI(Tl) (Caesium Iodide, Tallium doped) cubic crystals have been constructed and tested with particle beams. Moreover, the last development of CaloCube, the Tracker-In-Calorimeter (TIC) project, financed by the INFN in 2018, is focused on the feasibility of including several silicon layers at different depths in the calorimeter in order to reconstruct the particle direction. In fact, an important requirement for γ -ray astronomy is to have a good angular resolution in order to allow precise identification of astrophysical sources in space. In respect to the traditional approach of using a tracker with passive material in front of the calorimeter, the TIC solution can save a significant amount of mass budget in a space satellite experiment, which can then be exploited to improve the acceptance and the resolution of the calorimeter. In this paper, the status of the project and perspectives for future developments are presented

Tracker-in-Calorimeter (TIC) Project: A Calorimetric New Solution for Space Experiments

A space-based detector dedicated to measurements of γ-rays and charged particles has to achieve a balance between different instrumental requirements. A good angular resolution is necessary for the γ-rays, whereas an excellent geometric factor is needed for the charged particles. The tracking reference technique of γ-ray physics is based on a pair-conversion telescope made of passive material (e.g., tungsten) coupled with sensitive layers (e.g., silicon microstrip). However, this kind of detector has a limited acceptance because of the large lever arm between the active layers, needed to improve the track reconstruction capability. Moreover, the passive material can induce fragmentation of nuclei, thus worsening charge reconstruction performances. The Tracker-In-Calorimeter (TIC) project aims to solve all these drawbacks. In the TIC proposal, the silicon sensors are moved inside a highly-segmented isotropic calorimeter with a couple of external scintillators dedicated to charge reconstruction. In principle, this configuration has a good geometrical factor, and the angle of the γ-rays can be precisely reconstructed from the lateral profile of the electromagnetic shower sampled, at different depths in the calorimeter, by silicon strips. The effectiveness of this approach has been studied with Monte Carlo simulations and validated with beam test data of a small prototype

Lung-to-Heart Nano-in-Micro Peptide Promotes Cardiac Recovery in a Pig Model of Chronic Heart Failure

Background: The lack of disease-modifying drugs is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential to act directly on cardiomyocytes. However, a strategy for effective delivery of therapeutics to the heart is lacking. Objectives: In this study, the authors sought to assess tolerability and efficacy of an inhalable lung-to-heart nano-in-micro technology (LungToHeartNIM) for cardiac-specific targeting of a mimetic peptide (MP), a first-in-class for modulating impaired L-type calcium channel (LTCC) trafficking, in a clinically relevant porcine model of HF. Methods: Heart failure with reduced ejection fraction (HFrEF) was induced in Göttingen minipigs by means of tachypacing over 6 weeks. In a setting of overt HFrEF (left ventricular ejection fraction [LVEF] 30% ± 8%), animals were randomized and treatment was started after 4 weeks of tachypacing. HFrEF animals inhaled either a dry powder composed of mannitol-based microparticles embedding biocompatible MP-loaded calcium phosphate nanoparticles (dpCaP-MP) or the LungToHeartNIM only (dpCaP without MP). Efficacy was evaluated with the use of echocardiography, invasive hemodynamics, and biomarker assessment. Results: DpCaP-MP inhalation restored systolic function, as shown by an absolute LVEF increase over the treatment period of 17% ± 6%, while reversing cardiac remodeling and reducing pulmonary congestion. The effect was recapitulated ex vivo in cardiac myofibrils from treated HF animals. The treatment was well tolerated, and no adverse events occurred. Conclusions: The overall tolerability of LungToHeartNIM along with the beneficial effects of the LTCC modulator point toward a game-changing treatment for HFrEF patients, also demonstrating the effective delivery of a therapeutic peptide to the diseased heart

Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at sNN=5.02 TeV

The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-of- flight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number

The FOOT FragmentatiOn Of Target Experiment

International audienceIn proton-therapy clinical practice a constant RBE equal to 1.1 is adopted, regardless of the demonstrated RBE variations, which depends on physical and biological parameters. Among other mechanisms, nuclear interactions might influence the proton-RBE due to secondary heavier particles produced by target fragmentation that can significantly contribute to the total dose: an un-wanted and undetermined increase of normal tissues complications probability may occur. The FOOT experiment is designed to study these processes. Target ($^{16}$O,$^{12}$C) fragmentation induced by 150 − 250 M eV proton beam will be studied via inverse kinematic approach, where $^{16}$O and $^{12}$C therapeutic beams, with the same kinetic energy per nucleon of the proton, collide on graphite and hydrocarbons target to provide the cross section on Hydrogen (to explore also the projectile fragmentation). The detector design, the performances and expected resolution results obtained form Monte Carlo study, based on the FLUKA code will be presented

Development and characterization of a Δ E-TOF detector prototype for the FOOT experiment

This paper describes the development and characterization of a ΔE-TOF detector composed of a plastic scintillator bar coupled at both ends to silicon photomultipliers. This detector is a prototype of a larger version which will be used in the FOOT (FragmentatiOn Of Target) experiment to identify the fragments produced by ion beams accelerated onto a hydrogen-enriched target. The final ΔE-TOF detector will be composed of two layers of plastic scintillator bars with orthogonal orientation and will measure, for each crossing fragment, the energy deposited in the plastic scintillator (ΔE), the time of flight (TOF), and the coordinates of the interaction position in the scintillator. To meet the FOOT experimental requirements, the detector should have energy resolution of a few percents and time resolution of 70 ps, and it should allow to discriminate multiple fragments belonging to the same event. To evaluate the achievable performances, the detector prototype was irradiated with protons of kinetic energy in the 70–230 MeV range and interacting at several positions along the bar. The measured energy resolution σΔE∕ΔE was 6–14%, after subtracting the fluctuations of the deposited energy. A time resolution σ between 120 and 180 ps was obtained with respect to a trigger detector. A spatial resolution σ of 1.9 cm was obtained for protons interacting at the center of the bar