mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors

In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs and shows low expression levels in the adult cerebellar cortex. Here we found that mGlu5 receptors were heavily expressed by PCs in the early postnatal life, when mGlu1α receptors were barely detectable. The developmental decline of mGlu5 receptors coincided with the appearance of mGlu1α receptors in PCs, and both processes were associated with specular changes in CpG methylation in the corresponding gene promoters. It was the mGlu1 receptor that drove the elimination of mGlu5 receptors from PCs, as shown by data obtained with conditional mGlu1α receptor knockout mice and with targeted pharmacological treatments during critical developmental time windows. The suppressing activity of mGlu1 receptors on mGlu5 receptor was maintained in mature PCs, suggesting that expression of mGlu1α and mGlu5 receptors is mutually exclusive in PCs. These findings add complexity to the the finely tuned mechanisms that regulate PC biology during development and in the adult life and lay the groundwork for an in-depth analysis of the role played by mGlu5 receptors in PC maturation

Additive manufacturing and testing of a soft magnetic rotor for a switched reluctance motor

Additive manufacturing is acknowledged as a key enabling technology, although its adoption is still constrained to niche applications. A promising area for this technology is the production of electrical machines (EMs) and/or their main components (e.g. magnetic cores, windings, heat exchangers, etc.) due to the potential of creating lightweight, highly efficient rotating motors, suitable for applications requiring a low moment of inertia. This work investigates the readiness of metal additive manufacturing, specifically Laser Powder Bed Fusion (LPBF), applied to the field of EMs to bridge the gaps of how to use this technological approach in this field. A soft magnetic material featuring high silicon content (Fe-5.0%w.t.Si) has been developed for LPBF and a rotor has been 3D-printed for a switched reluctance machine. The printed rotor was assembled into a conventionally laminated stator and the performance of the whole machine was evaluated. Its performance was compared against an identical machine equipped with a laminated rotor of the same dimensions made of conventional non-oriented silicon steel. A comparative study was carried out through both finite element simulations and experimental tests. The efficiency of the two machines was assessed together with the principal electrical and mechanical quantities under several operating conditions

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

The usefulness of the anaerobic threshold in the assessment and prognostic evaluation of the patient with dyspnea

The anaerobic threshold (AT) is defined as the oxygen consumption level above which energy production becomes determined by anaerobic metabolism, which causes a sustained increase in lactate and metabolic acidosis. The AT, as measured by cardiopulmonary stress testing, is ubiquitously used to determine the prognosis and diagnosis of cardiovascular and respiratory diseases. This measurement can help clinicians in the functional evaluation of patients and as guidance for rehabilitation and therapy. This article reviews the pathophysiological aspects and methods of measurement of the AT during a cardiopulmonary stress test, and its clinical use in assessing cardiac and respiratory diseases

Porto-pulmonary arterial hypertension. translation of pathophysiological concepts to the bedside

Porto-pulmonary arterial hypertension (PoPAH) is a form of pulmonary arterial hypertension (PAH) that affects patients with cirrhosis, and - to a lesser extent - patients with non-cirrhotic liver diseases. Compared with other forms of PAH, PoPAH is more prevalent in male, in older subjects, and is characterized by lower mean pulmonary arterial pressure (mPAP) and lower pulmonary vascular resistance (PVR) with higher cardiac output. Despite more favorable hemodynamics and functional class, patients with PoPAH have a significantly worse survival than patients with other forms of PAH, likely because of liver-related events and therapeutic barriers to PAH-specific therapy. Furthermore, here cardiopulmonary and hepatic complications may affect treatment efficacy. These patients have been excluded from most randomized clinical trials testing PAH-specific treatments. To date, there is only one study investigating efficacy, safety, tolerability and pharmacokinetics of PAH-specific therapy in patients with PoPAH in a randomized placebo-controlled setting. In this trial the use of the endothelin1 receptor antagonist macitentan showed clear hemodynamic benefit without safety concerns. However, the drug effects on functional capacity and mortality remain unclear. Here we review the current knowledge on the pathophysiology and management of PoPAH and report a case vignette of a patient with PoPAH due to hepatorenal polycystic disease