Characterization of residual compressive stresses in layered ceramics by positron annihilation spectroscopy

Microstructural characterization of stress states of alumina layers subjected to residual compressive stresses was performed by positron annihilation spectroscopy (PAS). Al₂O₃–t-ZrO₂ three layered samples were appropriately designed and processed by sequential slip casting with symmetric structure. The zirconia contents inside the core layer were selected in order to generate compressive stresses of variable intensity in the outer Al₂O₃ layers. PAS results highlighted a correlation between positron annihilation parameters and microstructural changes related to the generation of residual stresses.     

Effect of the Addition of Chili Pepper Powder on Vegetable Oils Oxidative Stability

Red chili pepper represents an excellent source of functional bioactive compounds, and its use as food additive could be useful for protecting other products from spoilage. Olive oils show a limited shelf‐life due to a progressive quality deterioration linked mostly to oxidation reactions providing a loss of quality in terms of organoleptic and healthy properties. In this work, the addition of red chili pepper powder to virgin, extra‐virgin olive and sunflower oils was proved to be effective in improving their stability during 12 months of shelf‐life. Oil stability was monitored by employing the Oxitest system, based on accelerating the oxidation process. Three pepper powders of different pungency were added to the virgin olive oil samples with the aim of investigating whether capsaicinoids could be responsible for the observed effects. The strongest effect was recorded when employing the less pungent pepper showing that the protective effect could not be attributed to the capsaicinoids content. Besides, a screening on different oils demonstrated that the less stable samples received a stronger protective effect. The evaluation of a possible dose‐effect relation was also carried out pointing out that a threshold dose of about 1 % was required to record an effect. The results suggest potential perspectives in the field of food technology, as addition of a small amount of sweet pepper could be proposed to prolong food shelf‐life.     

Optimization of Diarylthiazole B‐Raf Inhibitors: Identification of a Compound Endowed with High Oral Antitumor Activity,Mitigated hERG Inhibition,and Low Paradoxical Effect

Aberrant activation of the mitogen‐activated protein kinase (MAPK)‐mediated pathway components, RAF‐MEK‐ERK, is frequently observed in human cancers and clearly contributes to oncogenesis. As part of a project aimed at finding inhibitors of B‐Raf, a key player in the MAPK cascade, we originally identified a thiazole derivative endowed with high potency and selectivity, optimal in vitro ADME properties, and good pharmacokinetic profiles in rodents, but that suffers from elevated hERG inhibitory activity. An optimization program was thus undertaken, focused mainly on the elaboration of the R¹ and R² groups of the scaffold. This effort ultimately led to N‐(4‐{2‐(1‐cyclopropylpiperidin‐4‐yl)‐4‐[3‐(2,5‐difluorobenzenesulfonylamino)‐2‐fluorophenyl]thiazol‐5‐yl}‐pyridin‐2‐yl)acetamide ( 20 ), which maintains favorable in vitro and in vivo properties, but lacks hERG liability. Besides exhibiting potent antiproliferative activity against only cell lines bearing B‐Raf V600E or V600D mutations, compound 20 also intriguingly shows a weaker “paradoxical” activation of MEK in non‐mutant B‐Raf cells than other known B‐Raf inhibitors. It also demonstrates very good efficacy in vivo against the A375 xenograft melanoma model (tumor volume inhibition >90 % at 10 mg kg^?1); it is therefore a suitable candidate for preclinical development.     

Dielectric,mechanical and transport properties of bisphenol A polycarbonate/graphene nanocomposites prepared by melt blending

Nanocomposites based on polycarbonate (PC) and different amounts of untreated graphene nanoplatelets (GnP) (from 1 to 7 wt %) were prepared by melt blending. The nanocomposites were thoroughly characterized employing the following techniques: broad band dielectric spectroscopy, thermally stimulated depolarization currents, differential scanning calorimetry, tensile testing, dynamic mechanical thermal analysis, and water vapor, carbon dioxide and oxygen permeability measurements. The presence of a MWS relaxation mode indicated the accumulation of electrical charges trapped at the interfaces of the polycarbonate with graphene 2D platelets. The addition of GnP produced nanocomposite materials with enhanced mechanical and barrier properties. The melt mixed PC/graphene nanocomposites prepared here exhibit well‐balanced properties, even though unmodified graphene nanoplatelets were used. In addition, the nanocomposites were obtained by a single extrusion process, which is easily scalable for industrial applications. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44654.     

PTEN and Other PtdIns(3,4,5)P3 Lipid Phosphatases in Breast Cancer

The phosphoinositide 3-kinase (PI3K)/AKT signalling pathway is hyperactivated in ~70% of breast cancers. Class I PI3K generates PtdIns(3,4,5)P₃ at the plasma membrane in response to growth factor stimulation, leading to AKT activation to drive cell proliferation, survival and migration. PTEN negatively regulates PI3K/AKT signalling by dephosphorylating PtdIns(3,4,5)P₃ to form PtdIns(4,5)P₂. PtdIns(3,4,5)P₃ can also be hydrolysed by the inositol polyphosphate 5-phosphatases (5-phosphatases) to produce PtdIns(3,4)P₂. Interestingly, while PTEN is a bona fide tumour suppressor and is frequently mutated/lost in breast cancer, 5-phosphatases such as PIPP, SHIP2 and SYNJ2, have demonstrated more diverse roles in regulating mammary tumourigenesis. Reduced PIPP expression is associated with triple negative breast cancers and reduced relapse-free and overall survival. Although PIPP depletion enhances AKT phosphorylation and supports tumour growth, this also inhibits cell migration and metastasis in vivo, in a breast cancer oncogene-driven murine model. Paradoxically, SHIP2 and SYNJ2 are increased in primary breast tumours, which correlates with invasive disease and reduced survival. SHIP2 or SYNJ2 overexpression promotes breast tumourigenesis via AKT-dependent and independent mechanisms. This review will discuss how PTEN, PIPP, SHIP2 and SYNJ2 distinctly regulate multiple functional targets, and the mechanisms by which dysregulation of these distinct phosphoinositide phosphatases differentially affect breast cancer progression.     

Interplay between Oxidative Stress and Metabolic Derangements in Non-Alcoholic Fatty Liver Disease: The Role of Selenoprotein P

Background: Pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) are complex and multifactorial. We investigated oxidative stress through the measurement of selenoprotein P (SeP) in serum and we explored its relation to metabolic derangements and liver damage in a group of non-diabetic NAFLD subjects. Methods: 57 NAFLD patients underwent a double-tracer oral glucose tolerance test (OGTT). Insulin resistance (IR) components were calculated at baseline as follows: hepatic-IR = (endogenous glucose production*insulin); peripheral-IR = (glucose rate of disappearance(Rd)); adipose-tissue(AT)-IR as Lipo-IR = (glycerol rate of appearance (Ra)*insulin) or AT-IR = (free fatty acids (FFAs)*insulin). The lipid and amino acid (AA) profiles were assessed by gas chromatography–mass spectrometry. SeP levels were measured by enzyme immunosorbent assay. Results: Circulating SeP correlated with insulin (r_S = 0.28), FFAs (r_S = 0.42), glucose Rd (r_S = −0.33) and glycerol Ra (r_S = −0.34); consistently, SeP levels correlated with Lipo-IR and AT-IR (r_S > 0.4). Among the AA and lipid profiles, SeP inversely correlated with serine (r_S = −0.31), glycine (r_S = −0.44) and branched chain AA (r_S = −0.32), and directly correlated with saturated (r_S = 0.41) and monounsaturated FFAs (r_S = 0.40). Hepatic steatosis and fibrosis increased in subjects with higher levels of SeP. In multivariable regression analysis, SeP was associated with the degree of hepatic fibrosis (t = 2.4, p = 0.022). Conclusions: SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD.     

Evaluation of chlorogenic acid and its metabolites as potential antioxidants for fish oils

The antioxidant effects on cod liver oil (CLO) of chlorogenic acid (CGA) and its metabolites, caffeic acid (CA) and quinic acid (QA), were investigated. All three chemicals were separately added to CLO at a concentration range of 0.001–0.080 wt‐% and tested by Rancimat. CA was the best antioxidant; its antioxidant effect was directly proportional to the dose added, but only within the concentration range of 0.005–0.050 wt‐%. QA did not show any effect on CLO oxidation, while CGA revealed itself as a weak antioxidant. Cytotoxicity was also evaluated by using murine 3T6 fibroblasts treated for 24 h with CGA, CA and QA at a concentration range of 0.1–5.0 mM. QA did not have an influence on cell proliferation, while CGA and CA showed a significant anti‐proliferative activity already at a concentration of 0.1 mM. Finally, compounds similar to the standard 8‐iso prostaglandin F_2α, called CLO‐“isoprostanes”‐like compounds, were isolated. At high temperature (100 and 110 °C) CLO‐“isoprostanes‐like” compounds did not show a relevant pro‐oxidant action on the refined olive oil to which they were added in variable amounts. On the contrary, the CLO‐“isoprostanes”‐like compounds significantly decreased the antioxidant effectiveness of CA. Indeed, at a CLO‐“isoprostanes‐like” compound dose of 300 µg, the antioxidant effectiveness of CA was halved.     

Automatic verification of concurrent systems using a formula-based compositional approach

When verifying concurrent systems, described by transition systems, state explosion is one of the most serious problems: systems are often described by transition systems with a prohibitive number of states. The primary cause of this problem is the parallel composition of interacting processes. In the recent years, compositional techniques have been developed to attack the state explosion problem. These techniques are based on dividing the verification task into simpler tasks, exploiting the natural decomposition of complex systems into processes. In this paper we present a formula-based compositional approach that allows us to deduce a property of a parallel composition of processes by checking it only on a component process. The approach can be automated and it is completely transparent to the user. Received: 17 May 2001 / 27 February 2002     

State space reduction by non-standard semantics for deadlock analysis

In recent years many techniques have been developed for automatically verifying concurrent systems and most of them are based on the representation of the concurrent system by means of a transition system. State explosion is one of the most serious problems of this approach: often the prohibitive number of states renders the verification inefficient and, in some cases, impossible.

We propose a method for reducing the state space of the transition system corresponding to a CCS process that suites deadlock analysis. The reduced transition system is generated by means of a non-standard operational semantics containing a set of rules which are, in some sense, an abstraction, preserving deadlock freeness, of the inference rules of the standard semantics. Our method does not build the standard transition system, but directly generates an abstract system with a fewer number of states, so saving memory space. We characterize a class of processes whose abstract transition system is not exponential in the number of parallel components.     

Glass Fiber Reinforced Polymer Pultruded Members: Constitutive Model and Stability Analysis

The increasingly widespread use of fiber-reinforced polymers as an alternative to conventional materials makes it necessary to formulate theoretical models which adequately evaluate the influence of the anisotropy of such composites on the structural behavior. While the cross section shapes adopted for compressed members are generally the same as in steel structures, the anisotropy which characterizes these polymers may reduce the critical loading threshold due to local buckling phenomena. A procedure to study the buckling of glass fiber reinforced polymer pultruded members by means of an homogenization approach is proposed here. A two-stage buckling model permits the determination of both global and local critical loads as explicit functions of the member geometry and its material behavior. These functions may be used for optimization of the shape of the above-mentioned members. Besides the model shows its reliability as it fits the results of experimental testson members with different slenderness ratios.