Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibroblasts and proliferation: A new potential target for antifibrotic therapy

Background: Fibrosis may be considered the hallmark of systemic sclerosis (SSc), the end stage triggered by different pathological events. Transforming growth factor-β (TGF-β) and platelet-derived growth factor BB (PDGF-BB) are profibrotic molecules modulating myofibroblast differentiation and proliferation, respectively. There is evidence linking CD248 with these two molecules, both highly expressed in patients with SSc, and suggesting that CD248 may be a therapeutic target for several diseases. The aim of this work was to evaluate the expression of CD248 in SSc skin and its ability to modulate SSc fibrotic process. Methods: After ethical approval was obtained, skin biopsies were collected from 20 patients with SSc and 10 healthy control subjects (HC). CD248 expression was investigated in the skin, as well as in bone marrow mesenchymal stem cells (MSCs) treated with TGF-β or PDGF-BB, by immunofluorescence, qRT-PCR, and Western blotting. Finally, in SSc-MSCs, the CD248 gene was silenced by siRNA. Results: Increased expression of CD248 was found in endothelial cells and perivascular stromal cells of SSc skin. In SSc-MSCs, the levels of CD248 and α-smooth muscle actin expression were significantly higher than in HC-MSCs. In both SSc- and HC-MSCs, PDGF-BB induced increased expression of Ki-67 when compared with untreated cells but was unable to modulate CD248 levels. After CD248 silencing, both TGF-β and PDGF-BB signaling were inhibited in SSc-MSCs. Conclusions: CD248 overexpression may play an important role in the fibrotic process by modulating the molecular target, leading to perivascular cells differentiation toward myofibroblasts and interfering with its expression, and thus might open a new therapeutic strategy to inhibit myofibroblast generation during SSc

Sovereign debt crisis, fiscal consolidation, and active central bankers in a monetary union

In this paper we examine global financial instability and its impact on the sovereign debts of peripheral countries in a stylized model of the European Economic and Monetary Union (EMU), where centralized and national policy authorities strategically interact. We show that active expansionary monetary policies might operate as indirect risk-sharing mechanisms that improve EMU stability and the welfare of (a part of the) member states. The European Central Bank (ECB) partially internalizes the fact that the monetary union\u2019s stability is a public good by reallocating a part of the cost of stabilizing the EMU from the periphery to the core countries. In this respect, unconventional monetary policies such as \u2018quantitative easing\u2019 are more effective than traditional monetary policies centered on ex-post interest rate adjustments. The rationale of our findings is that unconventional monetary policies decrease the cost of fiscal interventions in the peripheral countries and incentivize the consolidation of their public balance sheets; these same unconventional policies produce positive externalities but also come at a cost for central countries

Status of Salerno Laboratory (Measurements in Nuclear Emulsion)

A report on the analysis work in the Salerno Emulsion Laboratory is presented. It is related to the search for nu_mu->nu_tau oscillations in CHORUS experiment, the calibrations in the WANF (West Area Neutrino Facility) at Cern and tests and preparation for new experiments.Comment: Proc. The First International Workshop of Nuclear Emulsion Techniques (12-24 June 1998, Nagoya, Japan), 15 pages, 11 figure

A Simple Model for the Absorption of Starlight by Dust in Galaxies

We present a new model to compute the effects of dust on the integrated spectral properties of galaxies, based on an idealized prescription of the main features of the interstellar medium (ISM). The model includes the ionization of HII regions in the interiors of the dense clouds in which stars form and the influence of the finite lifetime of these clouds on the absorption of radiation. We compute the production of emission lines and the absorption of continuum radiation in the HII regions and the subsequent transfer of line and continuum radiation in the surrounding HI regions and the ambient ISM. This enables us to interpret simultaneously all the observations of a homogeneous sample of nearby UV-selected starburst galaxies, including the ratio of far-IR to UV luminosities, the ratio of Halpha to Hbeta luminosities, the Halpha equivalent width, and the UV spectral slope. We show that the finite lifetime of stellar birth clouds is a key ingredient to resolve an apparent discrepancy between the attenuation of line and continuum photons in starburst galaxies. In addition, we find that an effective absorption curve proportional to lambda^-0.7 reproduces the observed relation between the ratio of far-IR to UV luminosities and the UV spectral slope. We interpret this relation most simply as a sequence in the overall dust content of the galaxies. The shallow wavelength dependence of the effective absorption curve is compatible with the steepness of known extinction curves if the dust has a patchy distribution. In particular, we find that a random distribution of discrete clouds with optical depths similar to those in the Milky Way provides a consistent interpretation of all the observations. Our model for absorption can be incorporated easily into any population synthesis model. (abridged)Comment: To appear in the 2000 July 20 issue of the Astrophysical Journal; 19 pages with 13 embedded PS figures (emulateapj5.sty

Avolition as the core negative symptom in schizophrenia: relevance to pharmacological treatment development

Negative symptoms have long been considered a core component of schizophrenia. Modern conceptualizations of the structure of negative symptoms posit that there are at least two broad dimensions (motivation and pleasure and diminished expression) or perhaps five separable domains (avolition, anhedonia, asociality, blunted affect, alogia). The current review synthesizes a body of emerging research indicating that avolition may have a special place among these dimensions, as it is generally associated with poorer outcomes and may have distinct neurobiological mechanisms. Network analytic findings also indicate that avolition is highly central and interconnected with the other negative symptom domains in schizophrenia, and successfully remediating avolition results in global improvement in the entire constellation of negative symptoms. Avolition may therefore reflect the most critical treatment target within the negative symptom construct. Implications for targeted treatment development and clinical trial design are discussed

Application of an innovative model for the risk management of covid-19 in a multinational manufacturing company

The COVID-19 incidence in 61 manufacturing plants in Europe (EU), North America (NA) and Latin-America (LATAM) was compared with the incidence observed in the countries where the plants are located in order to evaluate the application of an innovative model for COVID-19 risk management. Firstly, a network of local and global teams was created, including an external university occupational physician team for scientific support. In July 2020, global prevention guidelines for the homogenous management of the pandemic were applied, replacing different site or regional procedures. A tool for COVID-19 monitoring was implemented to investigate the relationship between the incidence rates inside and outside the plants. In the period of May–November 2020, 565 confirmed cases (EU 330, NA 141, LATAM 94) were observed among 20,646 workers with different jobs and tasks, and in the last two months 85% EU and 70% NA cases were recorded. Only in 10% of cases was a possible internal origin of the contagion not excluded. In the EU and NA, unlike LATAM, the COVID-19 incidence rates inside the sites punctually followed the rising trend outside. In conclusion, the model, combining a global approach with the local application of the measures, maintains the sustainability in the manufacturing industry

Exterior-point Optimization for Nonconvex Learning

In this paper we present the nonconvex exterior-point optimization solver (NExOS) -- a novel first-order algorithm tailored to constrained nonconvex learning problems. We consider the problem of minimizing a convex function over nonconvex constraints, where the projection onto the constraint set is single-valued around local minima. A wide range of nonconvex learning problems have this structure including (but not limited to) sparse and low-rank optimization problems. By exploiting the underlying geometry of the constraint set, NExOS finds a locally optimal point by solving a sequence of penalized problems with strictly decreasing penalty parameters. NExOS solves each penalized problem by applying a first-order algorithm, which converges linearly to a local minimum of the corresponding penalized formulation under regularity conditions. Furthermore, the local minima of the penalized problems converge to a local minimum of the original problem as the penalty parameter goes to zero. We implement NExOS in the open-source Julia package NExOS.jl, which has been extensively tested on many instances from a wide variety of learning problems. We demonstrate that our algorithm, in spite of being general purpose, outperforms specialized methods on several examples of well-known nonconvex learning problems involving sparse and low-rank optimization. For sparse regression problems, NExOS finds locally optimal solutions which dominate glmnet in terms of support recovery, yet its training loss is smaller by an order of magnitude. For low-rank optimization with real-world data, NExOS recovers solutions with 3 fold training loss reduction, but with a proportion of explained variance that is 2 times better compared to the nuclear norm heuristic.Comment: 40 pages, 6 figure

Acquiring, archiving, analyzing and exchanging seismic data in real time at the Seismological Research Center of the OGS in Italy

After the 1976 Friuli earthquake (Ms = 6.5) in north-eastern Italy that caused about 1,000 casualties and widespread destruction in the Friuli area, the Italian government established the Centro di Ricerche Sismologiche (CRS). This is now a department of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS), and it is specifically devoted to the monitoring of the seismicity of north-eastern Italy. Since its inception, the North-East Italy Seismic Network has grown enormously. Currently, it consists of 14 broad-band and 20 short-period seismic stations, all of which are telemetered to and acquired in real time at the OGS-CRS data center in Udine. Data exchange agreements in place with other Italian, Slovenian, Austrian and Swiss seismological institutes lead to a total number of 94 seismic stations acquired in real time, which confirms that the OGS is the reference institute for seismic monitoring of north-eastern Italy. Since 2002, CRS has been using the Antelope software suite as the main tool for collecting, analyzing, archiving and exchanging seismic data. SeisComP is also used as a real-time data exchange server tool. A customized web accessible server is used to manually relocate earthquakes, and automatic procedures have been set-up for moment-tensor determination, shaking-map computation, web publishing of earthquake parametric data, waveform drumplots, state-of-health parameters, and quality checks of the station by spectra analysis. Scripts for email/SMS/fax alerting to public institutions have also been customized. Recently, a real-time seismology website was designed and set-up (http://rts.crs.inogs.it/)