Phosphorylation of human plasminogen activators and plasminogen

AbstractPlasminogen (PG), urokinase-type plasminogen activator (u-PA) and tissue-type PA (t-PA) are the main molecules involved in fibrinolysis and in many other physiological and pathological processes. In the present study we report that human t-PA, purified from human melanoma cells, and PG, purified from human plasma, both contain P-Tyr residues, as revealed by immunoblotting analyses with monoclonal anti-P-Tyr antibodies. In addition HPLC amino acid analysis of acid-hydrolyzed t-PA, PG and u-PA, shows that: (i)P-Ser and P-Tyr residues are present in t-PA; (ii)P-Thr and P-Tyr are present in PG; (iii) P-Ser, P-Thr and P-Tyr are present in u-PA. The utilization of monoclonal anti-P-Ser and anti-P-Thr antibodies in immunoblotting experiments has confirmed these data which indicate that phosphorylation is a common feature of PAs and of PG

Cyclic Plasticity and Low Cycle Fatigue of an AISI 316L Stainless Steel: Experimental Evaluation of Material Parameters for Durability Design

AISI 316L stainless steels are widely employed in applications where durability is crucial. For this reason, an accurate prediction of its behaviour is of paramount importance. In this work, the spotlight is on the cyclic response and low-cycle fatigue performance of this material, at room temperature. Particularly, the first aim of this work is to experimentally test this material and use the results as input to calibrate the parameters involved in a kinematic and isotropic nonlinear plasticity model (Chaboche and Voce). This procedure is conducted through a newly developed calibration procedure to minimise the parameter estimates errors. Experimental data are eventually used also to estimate the strain–life curve, namely the Manson–Coffin curve representing the 50% failure probability and, afterwards, the design strain–life curves (at 5% failure probability) obtained by four statistical methods (i.e., deterministic, “Equivalent Prediction Interval”, univariate tolerance interval, Owen’s tolerance interval for regression). Besides the characterisation of the AISI 316L stainless steel, the statistical methodology presented in this work appears to be an efficient tool for engineers dealing with durability problems as it allows one to select fatigue strength curves at various failure probabilities depending on the sought safety level

fem strategies for large scale thermo mechanical simulations with material non linearity

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Viscosity, Boson Peak and Elastic Moduli in the Na2O-SiO2 System

The temperature and chemical dependence of the melt viscosity are ubiquitous in the model development of the volcanic dynamics, as well as in the glass production and design. We focussed on the yet-explored relationship between the bulk and shear moduli ratio and boson peak with the melt fragility of their parental glasses. Here, we explored the extension of the observed trend by testing the conventional binary system Na2O-SiO2, thus providing new evidence supporting the link between the flow of melts and supercooled liquids and the vibrational dynamics of their parental glasses. This was accomplished by integrating new low-frequency Raman measurements and integrating data from the literature on Brillouin light scattering and viscometry. This approach allows us to feed the MYEGA equation with reliable input parameters to quantitatively predict the viscosity of the Na2O-SiO2 system from the liquid up to the glass transition

Defective Function of the Fas Apoptotic Pathway in Type 1 Diabetes Mellitus Correlates with Age at Onset

The Fas death receptor triggers lymphocyte apoptosis through an extrinsic and an intrinsic pathway involving caspase-8 and -9 respectively. Inherited defects of Fas function are displayed by a proportion of patients with Type 1 diabetes mellitus (T1DM) especially those with a second autoimmunity (T1DM-p). This study assesses activation of both pathways in Fas-resistant (FasR) patients to localize the defect. 21/28 (75%) T1DM-p, 14/50 (38%) T1DM, and 7/150 (5%) controls were FasR. Analysis of the 35 FasR patients and 20 Fas-sensitive (FasS) controls showed that caspase-9 activity was lower in T1DM-p and T1DM than in controls, whereas caspase-8 activity was lower in T1DM-p than in T1DM and the controls. Single patient analysis showed that 16/35 patients displayed defective activity of one (FasR1), whereas 19 displayed normal activity of both caspases (FasR2) Ages at onset of diabetes mellitus in T1DM and the second autoimmune disease in T1DM-p were lower in FasR than in FasS patients. All FasR1 patients developed diabetes mellitus before the age of 9 years, whereas a later onset was displayed by 26% FasR2 and 53% FasS patients. These data show that defective Fas function may involve both the extrinsic and intrinsic pathway in T1DM and severity correlates with the precocity of the autoimmune attack and its tissue polyreactivity

Thermal efficiency gains enabled by using supercritical CO2 mixtures in Concentrated Solar Power applications

Supercritical Carbon Dioxide (sCO2) power cycles have been proposed for Concentrated Solar Power (CSP) applications as a means to increase the performance and reduce the cost of state-of-the-art CSP systems. Nevertheless, the sensitivity of sCO2 systems to the usually hot ambient temperatures found in solar sites compromises the actual thermodynamic and economic gains that were originally anticipated by researchers of this innovative power cycle. In order to exploit the actual potential of sCO2 cycles, the utilization of dopants to shift the (pseudo)critical temperature of the working fluid to higher values is proposed here as a solution towards enabling exactly the same features of supercritical CO2 cycles even when ambient temperatures compromise the feasibility of the latter technology. To this end, this work explores the impact of adopting a CO2-based working mixture on the performance of a CSP power block, considering hexafluorobenzene (C6F6) and titanium tetrachloride (TiCl4) as possible dopants. Different cycle options and operating conditions are studied (250-300 bar and 550-700ºC) as well as molar fractions ranging between 10 and 25%. The results in this work confirm that CO2 blends with 15-25%(v) of the cited dopants enable efficiencies that are well in excess of 50% for minimum cycle temperatures as high as 50 or even 55ºC. It is also confirmed that, for these cycles, turbine inlet temperature and pressure hardly have any effect on the characteristics of the cycle that yields the best performance possible. In this regard, the last part of this work also shows that cycle layout should be an additional degree of freedom in the optimisation process inasmuch as the best performing layout changes depending on boundary conditions.Unión Europea SI-1900/10/201

Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience

The addition of venetoclax to hypomethylating agents (HMA-V) improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive treatment. The aim of our study was to confirm data reported in literature, in a real-life multicenter experience. We retrospectively evaluated 56 naive AML patients who received HMA-V at 8 different collaborating Hematology Units in the North-East of Italy, from September 2018 to October 2020. Patients received azacitidine or decitabine at standard dose, adding venetoclax starting from cycle 1-3. The median time-to-response was 2 cycles and composite complete remission rate (CCR) was 67.9%. Thirteen out of 38 responders (34.2%) relapsed, with a median response duration of 13.7 months. Transfusion independence (TI) was obtained in 27 (87.0%) and 28 (90.3%) out of 31 patients for red blood cells and platelets, respectively. Median OS was 12.3 months (95% CI, 8.1-16.5), and median PFS was 11.3 months (95% CI, 4.6-17.9). Cytogenetic risk was the only variable impacting on survival, while no differences were observed stratifying patients by age, bone marrow blasts, WHO classification or type of HMA. In conclusion, our real-life multicenter experience indicates that HMA-V treatment allows achieving good response rates in naive AML patients, ineligible for intensive chemotherapy

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity