Characterisation of AMS H35 HV-CMOS monolithic active pixel sensor prototypes for HEP applications

Monolithic active pixel sensors produced in High Voltage CMOS (HV-CMOS) technology are being considered for High Energy Physics applications due to the ease of production and the reduced costs. Such technology is especially appealing when large areas to be covered and material budget are concerned. This is the case of the outermost pixel layers of the future ATLAS tracking detector for the HL-LHC. For experiments at hadron colliders, radiation hardness is a key requirement which is not fulfilled by standard CMOS sensor designs that collect charge by diffusion. This issue has been addressed by depleted active pixel sensors in which electronics are embedded into a large deep implantation ensuring uniform charge collection by drift. Very first small prototypes of hybrid depleted active pixel sensors have already shown a radiation hardness compatible with the ATLAS requirements. Nevertheless, to compete with the present hybrid solutions a further reduction in costs achievable by a fully monolithic design is desirable. The H35DEMO is a large electrode full reticle demonstrator chip produced in AMS 350 nm HV-CMOS technology by the collaboration of Karlsruher Institut f\"ur Technologie (KIT), Institut de F\'isica d'Altes Energies (IFAE), University of Liverpool and University of Geneva. It includes two large monolithic pixel matrices which can be operated standalone. One of these two matrices has been characterised at beam test before and after irradiation with protons and neutrons. Results demonstrated the feasibility of producing radiation hard large area fully monolithic pixel sensors in HV-CMOS technology. H35DEMO chips with a substrate resistivity of 200$\Omega$ cm irradiated with neutrons showed a radiation hardness up to a fluence of $10^{15}$n$_{eq}$cm$^{-2}$ with a hit efficiency of about 99% and a noise occupancy lower than $10^{-6}$ hits in a LHC bunch crossing of 25ns at 150V

Time dynamics of background noise in geoelectrical and geochemical signals: an application in a seismic area of Southern Italy

We analyse geoelectrical and geochemical time series jointly measured by means of a multiparametric automatic station close to an anomalous fluid emission in Val d’Agri (Basilicata, Italy). The investigated area is located on Southern Apennine chain that in past and recent years was interested by destructive earthquakes. After a complete pre-processing of time series, we analyse the fluctuations triggered by the seasonal cycles and focus our attention on the possible link between geoelectrical and geochemical signals. In order to extract quantitative dynamical information from experimental time series, we detect scaling laws in power spectra that are typical fingerprints of fractional Brownian processes. After this analysis, the problem of the identification of extreme events in the time series has been approached. We consider significant anomalous patterns only when more consecutive values are above/below a fixed threshold in almost two of the time series jointly measured. We give the first preliminary results about the comparison between anomalous patterns detected in geoelectrical and geochemical parameters and the local seismic activity and, finally, analyse the implications with the earthquake prediction problem

Robust Satellite Techniques for Volcanic and Seismic Hazards Monitoring

Several satellite techniques have been proposed to monitor events related to seismic and volcanic activity. A selfadaptive approach (RAT, Robust AVHRR Techniques) has recently been proposed which seems able to recognise space-time anomalies, differently related to such events, also in the presence of highly variable contributions from atmospheric (transmittance), surface (emissivity and morphology) and observational (time/season, but also solar and satellite zenithal angles) conditions. On the basis of NOAA-AVHRR data, the RAT aprroach has already been applied to Mount Etna volcanic ash cloud monitoring in daytime, and to seismic area monitoring in Southern Italy. This paper presents the theoretical basis for the extension of RAT approach also to nighttime volcanic ash cloud detection, together with its possible implementation to lava flow monitoring. One example of successful forecasting (few days before) of a new lava vent opening during the Mount Etna eruption of July 2001 will be discussed in some detail. Progress on the use of the same approach on seismically active area monitoring will be discussed by comparison with previous results achieved on the Irpinia-Basilicata earthquake (MS = 6.9), which occurred on November 23rd 1980 in Southern Italy

Intra-articular therapy with infliximab in psoriatic arthritis: efficacy and safety in refractory monoarthritis

Objective: To evaluate efficacy and safety of intra-articular therapy (IA) with infliximab (IFX), in patients with psoriatic arthritis (PsA) and refractory monoarthritis. Methods: Four male and 1 female aged from 25 to 71 years and disease duration from 1 to 25 years, affected by PsA (CASPAR criteria) were observed . All patients were treated with immunomodulators (methotrexate, leflunomide, cyclosporin A), 3/5 with concomitant steroids, 4/5 with NSAID’s. Only 1 patient were treated with IFX 5 mg/kg IV every 6 weeks. Before the IFX injection an amount of synovial fluid was aspired from the inflamed site and the anti-TNF injection was echographic guided. Patients were evaluated at regular intervals through clinical and echographic examination and retreated in case of flare. Results: At follow-up visit after 7 days, in all patients treated with the first injection was detected total regression of the inflammation and no new inflamed synovial fluid was observed; power doppler examination shows reduction of local vascularization. Two patients experienced full remission after 6 months and only one injection, 1 patient (arthritis of the wrist) was in remission after 2 injections (3 months of interval). In 2 patients with knee arthritis and important synovial hypertrophy good results obtained after the first injection were not maintained afterwards and second injection was ineffective: these patients were evaluated for surgical intervention. Conclusions: Local injections of IFX were safe and well tolerated in all patients. The efficacy in short term was observed in all cases; our supposition is that presence of synovial hypertrophy is cause of worsening

A 50 ps resolution monolithic active pixel sensor without internal gain in SiGe BiCMOS technology

A monolithic pixelated silicon detector designed for high time resolution has been produced in the SG13G2 130 nm SiGe BiCMOS technology of IHP. This proof-of-concept chip contains hexagonal pixels of 65 µm and 130 µm side. The SiGe front-end electronics implemented provides an equivalent noise charge of 90 and 160 e- for a pixel capacitance of 70 and 220 fF, respectively, and a total time walk of less than 1 ns. Lab measurements with a 90Sr source show a time resolution of the order of 50 ps. This result is competitive with silicon technologies that integrate an avalanche gain mechanism. © 2019 CERN

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15\u201320 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801\u20133). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E \u3b3 \u2009\u2009>\u2009\u2009200\u2009keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7\u201319.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc

In vivo Diffusion Tensor Magnetic Resonance Tractography of the Sheep Brain : An Atlas of the Ovine White Matter Fiber Bundles

Diffusion Tensor Magnetic Resonance Imaging (DTI) allows to decode the mobility of water molecules in cerebral tissue, which is highly directional along myelinated fibers. By integrating the direction of highest water diffusion through the tissue, DTI Tractography enables a non-invasive dissection of brain fiber bundles. As such, this technique is a unique probe for in vivo characterization of white matter architecture. Unraveling the principal brain texture features of preclinical models that are advantageously exploited in experimental neuroscience is crucial to correctly evaluate investigational findings and to correlate them with real clinical scenarios. Although structurally similar to the human brain, the gyrencephalic ovine model has not yet been characterized by a systematic DTI study. Here we present the first in vivo sheep (ovis aries) tractography atlas, where the course of the main white matter fiber bundles of the ovine brain has been reconstructed. In the context of the EU's Horizon EDEN2020 project, in vivo brain MRI protocol for ovine animal models was optimized on a 1.5T scanner. High resolution conventional MRI scans and DTI sequences (b-value = 1,000 s/mm2, 15 directions) were acquired on ten anesthetized sheep o. aries, in order to define the diffusion features of normal adult ovine brain tissue. Topography of the ovine cortex was studied and DTI maps were derived, to perform DTI tractography reconstruction of the corticospinal tract, corpus callosum, fornix, visual pathway, and occipitofrontal fascicle, bilaterally for all the animals. Binary masks of the tracts were then coregistered and reported in the space of a standard stereotaxic ovine reference system, to demonstrate the consistency of the fiber bundles and the minimal inter-subject variability in a unique tractography atlas. Our results determine the feasibility of a protocol to perform in vivo DTI tractography of the sheep, providing a reliable reconstruction and 3D rendering of major ovine fiber tracts underlying different neurological functions. Estimation of fiber directions and interactions would lead to a more comprehensive understanding of the sheep's brain anatomy, potentially exploitable in preclinical experiments, thus representing a precious tool for veterinaries and researchers

Heterocycle-containing tranylcypromine derivatives endowed with high anti-LSD1 activity

As regioisomers/bioisosteres of 1a, a 4-phenylbenzamide tranylcypromine (TCP) derivative previously disclosed by us, we report here the synthesis and biological evaluation of some (hetero)arylbenzoylamino TCP derivatives 1b-6, in which the 4-phenyl moiety of 1a was shifted at the benzamide C3 position or replaced by 2- or 3-furyl, 2- or 3-thienyl, or 4-pyridyl group, all at the benzamide C4 or C3 position. In anti-LSD1-CoREST assay, all the meta derivatives were more effective than the para analogues, with the meta thienyl analogs 4b and 5b being the most potent (IC50 values = 0.015 and 0.005 μM) and the most selective over MAO-B (selectivity indexes: 24.4 and 164). When tested in U937 AML and prostate cancer LNCaP cells, selected compounds 1a,b, 2b, 3b, 4b, and 5a,b displayed cell growth arrest mainly in LNCaP cells. Western blot analyses showed increased levels of H3K4me2 and/or H3K9me2 confirming the involvement of LSD1 inhibition in these assays