The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli

This work is licensed under a Creative Commons Attribution 4.0 International License.Finasteride (FIN) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. FIN is clinically approved for the treatment of benign prostatic hyperplasia and male baldness; while often well-tolerated, FIN has also been shown to cause or exacerbate psychological problems in vulnerable subjects. Evidence on the psychological effects of FIN, however, remains controversial, in view of inconsistent clinical reports. Here, we tested the effects of FIN in a battery of tests aimed at capturing complementary aspects of mood regulation and stress reactivity in rats. FIN reduced exploratory, incentive, prosocial, and risk-taking behavior; furthermore, it decreased stress coping, as revealed by increased immobility in the forced-swim test (FST). This last effect was also observed in female and orchiectomized male rats, suggesting that the mechanism of action of FIN does not primarily reflect changes in gonadal steroids. The effects of FIN on FST responses were associated with a dramatic decrease in corticotropin release hormone (CRH) mRNA and adrenocorticotropic hormone (ACTH) levels. These results suggest that FIN impairs stress reactivity and reduces behavioral activation and impulsive behavior by altering the function of the hypothalamus–pituitary–adrenal (HPA) axis

Observation of γγ → ττ in proton-proton collisions and limits on the anomalous electromagnetic moments of the τ lepton

The production of a pair of τ leptons via photon–photon fusion, γγ → ττ, is observed for the f irst time in proton–proton collisions, with a significance of 5.3 standard deviations. This observation is based on a data set recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb−1. Events with a pair of τ leptons produced via photon–photon fusion are selected by requiring them to be back-to-back in the azimuthal direction and to have a minimum number of charged hadrons associated with their production vertex. The τ leptons are reconstructed in their leptonic and hadronic decay modes. The measured fiducial cross section of γγ → ττ is σfid obs = 12.4+3.8 −3.1 fb. Constraints are set on the contributions to the anomalous magnetic moment (aτ) and electric dipole moments (dτ) of the τ lepton originating from potential effects of new physics on the γττ vertex: aτ = 0.0009+0.0032 −0.0031 and |dτ| < 2.9×10−17ecm (95% confidence level), consistent with the standard model

Sviluppo del firmware per il controllo del detector ALPIDE ed implementazione su FPGA

I sensori a stato solido giocano un ruolo sempre più fondamentale nello sviluppo di detector per la fisica delle alte energie, questo grazie alla loro compattezza e bassa densità di potenza necessaria per il loro funzionamento. In questa tesi si è studiato il sensore ALPIDE (ALice PIxel DEtector) scelto dalla collaborazione ALICE per l'upgrade dell' ITS (Inner Tracking System). Tale sensore è un Monolithic Active Pixel Sensor (MAPS), ovverosia il detector e l'elettronica di front-end sono ottenuti da uno stesso blocco monolitico di silicio, questo per soddisfare i requisiti imposti da ALICE, primi fra tutti la bassa densità di potenza ed elevata risoluzione spaziale. Il lavoro di questa tesi è principalmente costituito dallo sviluppo di un firmware da implementare in un FPGA per il controllo di tale chip e fornire una semplice comunicazione con PC per l'acquisizione di dati. Sono valutate poi le performance del nuovo sistema di lettura e controllo

Isoallopregnanolone reduces tic‐like behaviours in the D1 CT

Tourette syndrome (TS) is a neuropsychiatric disorder characterised by multiple, persistent tics. These semi-voluntary motor and phonic manifestations are typically aggravated by exposure to acute stress, yet the mechanisms underlying this exacerbation remain unclear. Using a well-characterised animal model of TS, the D1CT-7 mouse, we recently showed that acute stress increases tic-like responses and causes sensorimotor gating deficits, as measured by the prepulse inhibition of the startle. We showed that these effects are promoted by the brain synthesis of the neurosteroid allopregnanolone (AP). In line with this idea, inhibition of AP synthesis by finasteride was found to suppress the tic-exacerbating effects of stress; conversely, AP administration resulted in a marked enhancement of the number of tic-like motor bursts. Given that the primary mechanism of AP is based on the positive allosteric modulation of GABA(A) receptors, in the present study, we hypothesised that the enhancement in tic-like behaviours induced by either stress or AP may be countered by isoallopregnanolone (isoAP), the natural 3 beta-epimer of AP that acts as an antagonist to the AP-binding site within GABA(A) receptors. In agreement with our hypothesis, isoAP (5-10 mg kg(-1), s.c.) dose-dependently reduced the number of tic-like behaviours induced by stress in D1CT-7 mice. These effects were comparable to those elicited by both the benchmark TS therapy haloperidol (0.3 mg kg(-1), i.p.), as well as finasteride (25 mg kg(-1), i.p.). IsoAP also countered the prepulse inhibition deficits secondary to stress in D1CT-7 mice. Finally, isoAP opposed the enhancement of tic-like behaviours induced by AP (15 mg kg(-1), i.p.). Given that isoAP is well-tolerated and has an optimal safety profile, these data suggest that this steroid may have therapeutic properties in TS.</p

Design and implementation of Neural Network based conditions for the CMS Level-1 Global Trigger upgrade for the HL-LHC

The CMS detector will be upgraded to maintain, or even improve, the physics acceptance under the harsh data taking conditions foreseen during the High-Luminosity LHC operations. In particular, the trigger system (Level-1 and High Level Triggers) will be completely redesigned to utilize detailed information from sub-detectors at the bunch crossing rate: the upgraded Global Trigger will use high-precision trigger objects to provide the Level-1 decision. Besides cut-based algorithms, novel machine-learning-based algorithms will also be included in the Global Trigger to achieve a higher selection efficiency and detect unexpected signals. Implementation of these novel algorithms is presented, focusing on how the neural network models can be optimized to ensure a feasible hardware implementation. The performance and resource usage of the optimized neural network models are discussed in detail

Adaptability and efficiency of the CMS Level-1 Global Trigger firmware implementation for Phase-2

We present details on the new Level-1 Global Trigger at CMS for the upcoming high-luminosity operation of the LHC. Our focus is on the newly developed firmware, which employs a bottom-up generic approach to enhance menu adaptability and accommodate the increase in upstream data. We also highlight our efficient pipelining strategy that ensures excellent routability at 480 MHz. Furthermore, we discuss the firmware implementation for three prototypes targeting Serenity boards, together with their current and future testing and validation endeavours