Impact of data from recent clinical trials on strategies for treating patients with type 2 diabetes mellitus

Type 2 diabetes is associated with increased risk for the development of cardiovascular disease (CVD) secondary to hyperglycemia’s toxicity to blood vessels. The escalating incidence of CVD among patients with type 2 diabetes has prompted research into how lowering glycated hemoglobin (HbA1c) may improve CVD-related morbidity and mortality. Data from recent studies have shown that some patients with type 2 diabetes actually have increased mortality after achieving the lowest possible HbA1c using intensive antidiabetes treatment. Multiple factors, such as baseline HbA1c, duration of diabetes, pancreatic β-cell decline, presence of overweight/obesity, and the pharmacologic durability of antidiabetes medications influence diabetes treatment plans and therapeutic results. Hypertension and dyslipidemia are common comorbidities in patients with type 2 diabetes, which impact the risk of CVD independently of glycemic control. Consideration of all of these risk factors provides the best option for reducing morbidity and mortality in patients with type 2 diabetes. Based on the results of recent trials, the appropriate use of current antidiabetes therapies can optimize glycemic control, but use of intensive glucose-lowering therapy will need to be tailored to individual patient needs and risks

Geology of the Shakespeare quadrangle (H03), Mercury

By using images acquired by the Mercury dual imaging system (MDIS) on-board the MESSENGER spacecraft during 2008–2015 and available DTMs, a new 1:3,000,000-scale geological map of the Shakespeare quadrangle of Mercury has been compiled. The quadrangle is located between latitudes 22.5°–65.0°N and longitudes 270.0°–180.0°E and covers an area of about 5 million km2. The mapping was based on photo-interpretation performed on a reference monochromatic basemap of reflectance at 166 m/pixel resolution. The geological features were digitized within a geographic information system with a variable mapping scale between 1:300,000 and 1:600,000. This quadrangle is characterized by the occurrence of three main types of plains materials and four basin materials (pertaining to the Caloris basin), whose geologic boundaries have been here redefined compared to the previous map of the quadrangle. The stratigraphic relationships between the craters were based on three main degradation morphologies. Furthermore, previously unmapped tectonic landforms were detected and interpreted as thrusts or wrinkle ridges

Polynomial Approach for Filtering and Identification of a Class of Uncertain Systems

Abstract this paper considers the filtering and identification problems for a class of discrete-time uncertain stochastic systems that admit a finite number of linear working modes. It is shown here that this class of uncertain systems can be modeled by using a suitably defined extended system, whose state evolves according to a bilinear model. A polynomial filtering algorithm is derived for such extended system, which readily provides the polynomial estimates of both the original state and the working mode. Simulations show the effectiveness of the proposed approach and the improvements with respect to standard linear filtering algorithms

Il problema dell'interazione fluido-strutura nella modellazione del comportamento dinamico delle dighe

[IT] II problema in oggetto può essere formulato, come ben noto, a diversi livelli di complessità (e di “completezza” per quanto attiene alia rappresentatività física dei modelli proposti). Ciò è attestato dai numerosissimi contributi in proposito, a partire dal classico approccio “alla Westergaard” (v. concetto di “masse aggiunte”, Westergaard,1993) con fondo del serbatoio rígido (approccio nel quale, al livello più elementare, si assume anche I’ ipotesi di rigidità della struttura e di incomprimibilità del fluido), per arrivare alle formulazioni più recenti in cui si tiene conto, separatamente [8] o congiuntamente, della deformabilità della struttura, della comprimibilità del fluido e della deformabilità del fondo del serbatoio; formulazioni nelle quali in genere il concetto di “masse aggiunte” non è più valido (o va modificato profundamente, ad es. Rendendo tali “masse “ quantità complesse anzichè reali efunzioni della frequenza anzichè costanti). Assai spesso interessa in primo luogo identificare i modi naturali (smorzati o no) di vibrazione della diga, considerata come un sistema elástico lineare, ed in tal caso il problema è direttamente formulato in termini di oscillazioni armoniche (eventualmente con smorzamento: moto “pseudo-armonico”); la risposta ad eccilazioni non periodiche in campo lineare viene allora ricoslruita attraverso la nota tecnica dell’analisi modale.Fanelli, M.; Palumbo, P. (1998). Il problema dell'interazione fluido-strutura nella modellazione del comportamento dinamico delle dighe. Ingeniería del Agua. 5(2):51-62. https://doi.org/10.4995/ia.1998.2749SWORD516252Antes H., von Estorff, G., (1987) Analysis of absorption effects on the dynamic response of dam-reservoir systems by boundary element methods, Earthquake Eng. Str. Dyn. Vol. 15Fanelli M., (1990) Rapid preliminary analysis of arch dams: The Ritter method revisited, Dam Engineering. Vol.I, Issue 2Fanelli M., Fanelli A., (1992) Optimal proportioning of archgravity dams: the automatic generation of a simplified starting geometry, Dam Engineering. Vol.III, Issue 4Fanelli M, Fanelli A., Salvaneschi R, (1993) A neural network approach to the definition of near optimal arch dam shape, Dam Engineering, Vol. IV, Issue 2;Fanelli M., Fanelli A., Bonetti R, (1994) Non linear analysis in the preliminary evaluation of arch dam design, Hydropower & Dams. Vol.I, Issue 6Fanelli M., Fanelli A., GalimbertiC., Palumbo, P. (1995) The role of the reservoir in the selsmic analysis of concrete dams, Hydropower & Dams. Vol. 11, Issue 6Fork., Chopra A.K., (1986) Earthquake analysis of arch dams including dam-water interaction, boundary absorption and foundation flexibility, Earth-quake Eng. Str. Dyn. Vol. 14Kashiwayanagi M., Ohmachi T., (1992) Observed effects of reservoir water ondynamic characteristics of an arch dam, Proceedings. International Symposium on Arch Dams. Univ. Press, Nanjing, ChinaProceedings of the Benchmark-Workshops on Numerical Analysis of Dams: Bergamo, May 1991; Bergamo, July 1992; Paris, September 1994; Madrid, September 1996Westergaard, H.M., (1993) Water pressures on dams during earthquakes, Transactions of ASCE, Vol. 98, 41

Study of Tailor Heat Treated Blanks Using the Fourier-series-based VFM

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On a stochastic approach to model the double phosphorylation/dephosphorylation cycle

Because of the unavoidable intrinsic noise affecting biochemical processes, astochastic approach is usually preferred whenever a deterministic model givestoo rough information or, worse, may lead to erroneous qualitative behaviorsand/or quantitatively wrong results. In this work we focus on the chemicalmaster equation (CME)-based method which provides an accurate stochasticdescription of complex biochemical reaction networks in terms of the probabilitydistribution of the underlying chemical populations. Indeed, deterministic mod-els can be dealt with as first-order approximations of the average-value dynamicscoming from the stochastic CME approach. Here we investigate the double phos-phorylation/dephosphorylation cycle, a well-studied enzymatic reaction networkwhere the inherent double time scale requires one to exploit quasisteady stateapproximation (QSSA) approaches to infer qualitative and quantitative informa-tion. Within the deterministic realm, several researchers have deeply investi-gated the use of the proper QSSA, agreeing to highlight that only one type ofQSSA (the total QSSA) is able to faithfully replicate the qualitative behaviorof bistability occurrences, as well as the correct assessment of the equilibriumpoints, accordingly to the not approximated (full) model. Based on recent resultsproviding CME solutions that do not resort to Monte Carlo simulations, the pro-posed stochastic approach shows some counterintuitive facts arising when tryingto straightforwardly transfer bistability deterministic results into the stochasticrealm, and suggests how to handle such cases according to both theoretical andnumerical results

Amphiphilic CCK peptides assembled in supramolecular aggregates: structural investigations and in vitro studies

Supramolecular aggregates obtained by self-aggregation of five new cationic amphiphilic CCK8 peptides have been obtained in water solution and characterized for: (i) aggregate structure and stability; (ii) CCK8 peptide conformation and bioavailability on the external aggregate surface; and (iii) for their cell binding properties. The cationic amphiphilic CCK8 peptides self-aggregate giving a combination of liposomal and micelle structures, with radii ranging between B60 nm and B90 nm, and between B5 and B10 nm, respectively. The presence of CCK8 peptide well-exposed on the aggregate surface is demonstrated by fluorescence measurements. Peptide conformation changes in the five supramolecular aggregates: the CCK8 conformational behaviour is probably induced by the presence of three charged lysine residues close to the bioactive peptide sequence. Only aggregates in which the CCK8 peptide presents a structural arrangement similar to that found for the same peptide in DPC micelles give promising binding properties to CCK2-R receptors overexpressed by transfected A431 cells. Chemical modifications on the CCK8 N-terminus seem to play an important role in stabilizing the peptide active conformation, either when the peptide derivative is in monomeric or in aggregate form. For their easy preparation procedures and their binding properties, supramolecular aggregates based on cationic peptide amphiphiles can be considered as promising candidates for target selective drug carriers on cancer cells