Studio di un algoritmo lineare di ricostruzione analogica della posizione per il rivelatore a pixel di ATLAS

A detailed study of spatial resolution of Atlas pixel sensors prototypes was performed. Charge interpolation was used and allowed for a significant improvement with respect to digital resolution. A simplified algorithm for charge interpolation was developed. Its application to both unirradiated and irradiated sensors is presented and discussed

Public Credit Programmes and Firm Performance in Brazil

Credit rationing is a common phenomenon faced by firms, one that has negative implications for longâ term investments. In Brazil, public credit plays a key role in supporting firms: stateâ owned banks account for almost half of the outstanding credit. Public credit programmes aim at reducing credit restrictions, increasing competitiveness and job creation for small and medium enterprises. This article analyzes the effectiveness of the credit lines managed by two main public institutions in Brazil. Results show that access to public credit lines has a significant positive impact on firmsâ employment growth and exports, while no effect was found on wage differential. The impact on exports is driven by the increase in volumes among exporting firms rather than the probability of becoming an exporter.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138401/1/dpr12250_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138401/2/dpr12250.pd

Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M1 muscarinic receptor

Established therapy in Alzheimer’s disease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M1 muscarinic receptors found in higher concentrations in the cortex and hippocampus. Adverse effects, due to indiscriminate activation of other muscarinic receptor subtypes, are common. M1 muscarinic positive allosteric modulators/allosteric agonists such as BQCA offer an attractive solution, being exquisitely M1-selective over other muscarinic subtypes. A common difficulty with allosteric ligands is interpreting SAR, based on composite potency values derived in the presence of fixed concentration of agonist. In reality these values encompass multiple pharmacological parameters, each potentially and differentially sensitive to structural modification of the ligand. We report novel BQCA analogues which appear to augment ligand affinity for the receptor (pKB), intrinsic efficacy (τB), and both binding (α) and functional (β) cooperativity with acetylcholine. Ultimately, development of such enriched SAR surrounding allosteric modulators will provide insight into their mode of action

Mechanotransduction in human and mouse beta cell lines: reliable models to characterize novel signaling pathways controlling beta cell fate

Background and aims: Attempts to influence \u3b2-cell differentiation by engineering substrates that mimic appropriate extracellular matrix (ECM) topographies are hampered by the fact that profound details of mechanosensing/transduction complexity remain elusive. We recently demonstrated that human islets of Langerhans sense the ECM nanotopography and activate a mechanotransductive pathway, which is essential for preserving long-term \u3b2-cell differentiation and function in vitro. However, human islets of Langerhans are extremely heterogeneous and their availability for research purpose is limited. Therefore, aim of the proposed research was to investigate whether mouse and human \u3b2-cell lines might sense changes innthe ECM topography and might be used as a simplified model to dissect the molecular pathways involved in mechanotransduction. Materials and methods: We used supersonic cluster beam deposition to fabricate nanostructured substrates characterized by a quantitatively controllable ECM-like nanoroughness. Mouse \u3b2TC3 and human 1.1B4 cells were seeded on these substrates and after five days in culture, the activation of the mechanotransductive pathway was verified by means of morphological (super-resolution fluorescence microscopy), functional and proteomic techniques. Results: Quantitative immunofluorescence studies demonstrated that the cell-nanotopography interaction affects the focal adhesion structures (smaller vinculin clusters), the organization of the actin cytoskeleton (shorter actin fiber) and the nuclear architecture. Functional studies revealed that nanostructured surfaces improve the \u3b2-cell mitochondrial activity and increase the glucose-stimulated Ca2+currents and insulin release. Label-free shotgun proteomics broadly confirmed the morphological and functional studies and showed the upregulation of a number of mechanosensors and transcription factors involved in \u3b2-cell differentiation in cells grown on nanostructured substrates compared to those grown on flat standard control surfaces. Conclusion: Our data reveal that mouse and human \u3b2-cell lines sense changes in extracellular mechanical forces and activate a mechanotransductive pathway. The findings from this study will be useful to clarify the link between mechanotransduction and cell fate and to successfully engineer scaffolds in order to have functional beta cells

COVID-19 and surgical training in Italy: Residents and young consultants perspectives from the battlefield

COVID-19 is seriously affecting Italy, putting the health system under extreme pressure. Training of medical students and residents is also suffering from this with the suspension of lectures and clinical rotations. What solutions have been taken to deal with the issue

Proteomic Analysis Reveals a Mitochondrial Remodeling of βTC3 Cells in Response to Nanotopography

Recently, using cluster-assembled zirconia substrates with tailored roughness produced by supersonic cluster beam deposition, we demonstrated that \u3b2 cells can sense nanoscale features of the substrate and can translate these stimuli into a mechanotransductive pathway capable of preserveing \u3b2-cell differentiation and function in vitro in long-term cultures of human islets. Using the same proteomic approach, we now focused on the mitochondrial fraction of \u3b2TC3 cells grown on the same zirconia substrates and characterized the morphological and proteomic modifications induced by the nanostructure. The results suggest that, in \u3b2TC3 cells, mitochondria are perturbed by the nanotopography and activate a program involving metabolism modification and modulation of their interplay with other organelles. Data were confirmed in INS1E, a different \u3b2-cell model. The change induced by the nanostructure can be pro-survival and prime mitochondria for a metabolic switch to match the new cell needs