High-temperature oxidation of aluminum electroplated Fe-Mn alloys

Austenitic Mn-Al alloys (20–32 W/O Mn, 7–10 Al, 2–3 Si, 1C) were found to have satisfactory oxidation resistance up to 950°C under isothermal conditions in air. Surface enrichment of aluminum is a necessary condition for obtaining an almost pure alumina scale for uses at higher temperatures. Four different Mn-steels were Al-coated by the Capuano electroplating process. In all the steels there was an increase in the hot-oxidation resistance. The best results were obtained with steels containing both Al and Si, and this for temperatures up to 1100°C. No spalling was noticed during rapid cooling of the test pieces. Silicon was found to act as a diffusion barrier to outward iron diffusion. It appears that there is formation of a pure, thin film of alumina from the matrix which interacts with the aluminum diffusing from the superimposed, coating for the formation of good bonds.     

Adaptive course generation through learning styles representation

This paper presents an approach to automatic course generation and student modeling. The method has been developed during the European funded projects Diogene and Intraserv, focused on the construction of an adaptive e-learning platform. The aim of the platform is the automatic generation and personalization of courses, taking into account pedagogical knowledge on the didactic domain as well as statistic information on both the student’s knowledge degree and learning preferences. Pedagogical information is described by means of an innovative methodology suitable for effective and efficient course generation and personalization. Moreover, statistic information can be collected and exploited by the system in order to better describe the student’s preferences and learning performances. Learning material is chosen by the system matching the student’s learning preferences with the learning material type, following a pedagogical approach suggested by Felder and Silverman. The paper discusses how automatic learning material personalization makes it possible to facilitate distance learning access to both able-bodied and disabled people. Results from the Diogene and Intraserv evaluation are reported and discussed.     

The Synthesis and Biological Evaluation of Multifunctionalised Derivatives of Noscapine as Cytotoxic Agents

Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, is a well‐known antitussive drug that has a relatively safe in vitro toxicity profile. Noscapine is also known to possess weak anticancer efficacy, and since its discovery, efforts have been made to design derivatives with improved potency. Herein, the synthesis of a series of noscapine analogues, which have been modified in the 6′, 9′, 1 and 7‐positions, is described. In a previous study, replacement of the naturally occurring N‐methyl group in the 6′‐position with an N‐ethylaminocarbonyl was shown to promote cell‐cycle arrest and cytotoxicity against three cancer cell lines. Here, this modification has been combined with other structural changes that have previously been shown to improve anticancer activity, namely halo substitution in the 9′‐position, regioselective O‐demethylation to reveal a free phenol in the 7‐position, and reduction of the lactone to the corresponding cyclic ether in the 1‐position. The incorporation of new aryl substituents in the 9′‐position was also investigated. The study identified interesting new compounds able to induce G2/M cell‐cycle arrest and that possess cytotoxic activity against the human prostate carcinoma cell line PC3, the human breast adenocarcinoma cell line MCF‐7, and the human pancreatic epithelioid carcinoma cell line PANC‐1. In particular, the ethyl urea cyclic ether noscapinoids and a compound containing a 6′‐ethylaminocarbonyl along with 9′‐chloro, 7‐hydroxy and lactone moieties exhibited the most promising biological activities, with EC₅₀ values in the low micromolar range against all three cancer cell lines, and these derivatives warrant further investigation.     

Identification of potent human anti-IL-1RI antagonist antibodies

Interleukin-1 (IL-1) blockade by IL-1 receptor antagonist benefits some arthritis patients by reducing joint damage. This fact inspired us to develop antagonist human therapeutic antibodies against IL-1R(I) using phage libraries that display single-chain variable fragment (scFv) antibody fragments. Panning libraries against human IL-1R(I) generated 39 unique scFv-phage whose binding to IL-1R(I) was competed by IL-1 ligands. Fifteen of these scFv-phage, identified using IL-1R(I)-binding assays and dissociation rate ranking, were reformatted as scFv-Fc and IgG(4) molecules. The ease of producing antibodies in the scFv-Fc format permitted rapid identification of four lead clones (C10, C13, C14, C15) that inhibit NF-kappaB nuclear translocation induced by IL-1. Reformatting these clones as IgG(4) molecules increased their inhibition potency by 相似文献   

Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic chronic inflammation in maintenance hemodialysis patients: A multicenter longitudinal study

Chronic inflammation is widely diffuse in maintenance hemodialysis (MHD) patients and is associated with poor survival. Hemodiafiltration with endogenous reinfusion (HFR) is a dialysis technique, highly biocompatible, able to adsorb proinflammatory cytokines and to decrease amino acids and antioxidants loss. These features could be helpful in MHD patients affected by idiopathic chronic inflammation, but this issue remains to be elucidated. We performed a multicenter longitudinal study to assess the effect of the switching from bicarbonate HD to HFR in patients with serum C‐reactive Protein (CRP) > 5 mg/L coupled with albumin <4.0 g/dL in the last 6 months. We enrolled 24/176 (14%) patients, of which 20 patients were assessed at 4 months and 18 completed the study. We excluded 11 patients with evident causes of inflammation. At baseline, serum levels of CRP (18.7[7.0–39.4] mg/L) and albumin (3.5[3.3–3.7] g/dL) were significantly correlated (r = ?0.49; P = 0.028). The effect on CRP and albumin was almost evident in the first 4 months and remained stable until to eighth month. A strict correlation (R = ?0.49; 0.040) between percentage change of CRP (?35%) and albumin (+14%) after 8 months of HFR. These effects were associated with the reduction of IL‐6, IL‐1β, and TNF‐α and the increment of pre‐albumin and leptin, whereas the serum levels of Branched Chain Amino Acid (BCAA) remained unchanged. In MHD patients affected by idiopathic chronic inflammation the switching from BHD to HFR is associated with improvement of inflammation. Whether these favorable effects may modify the outcomes of these high‐risk patients needs to be confirmed by studies ad hoc.     

An integrated look at the effect of structure on nutrient bioavailability in plant foods

The true bioavailability of a nutrient being intrinsically coupled to the specific food matrix in which it occurs remains poorly considered in nutrition science. During digestion, the food matrix and, in particular, the structure of food modulate the extent and kinetics to which nutrients and bioactive compounds make themselves available for absorption. In this perspective, we describe an integrated look at the effect of structure on nutrient bioavailability in plant foods. Based on this integrated look, cell wall integrity and the particle size of the plant material during its transit in the small intestine determine the bioavailability of plant nutrients; in turn, cell wall integrity and particle size are determined by the level of oral processing and, accordingly, what subsequently escapes digestion in the upper intestine and is utilized by colon microbiota. Ultimately, the effect on nutrient digestion is linked to food structure through each step of digestion. A consideration of the structure rather than just the composition of foods opens up possibilities for the design of healthier foods. © 2018 Society of Chemical Industry     

Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt KV4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties

KCND3 encodes the voltage-gated potassium channel K_V4.3 that is highly expressed in the cerebellum, where it regulates dendritic excitability and calcium influx. Loss-of-function K_V4.3 mutations have been associated with dominant spinocerebellar ataxia (SCA19/22). By targeted NGS sequencing, we identified two novel KCND3 missense variants of the K_V4.3 channel: p.S347W identified in a patient with adult-onset pure cerebellar syndrome and p.W359G detected in a child with congenital nonprogressive ataxia. Neuroimaging showed mild cerebellar atrophy in both patients. We performed a two-electrode voltage-clamp recording of K_V4.3 currents in Xenopus oocytes: both the p.G345V (previously reported in a SCA19/22 family) and p.S347W mutants exhibited reduced peak currents by 50%, while no K+ current was detectable for the p.W359G mutant. We assessed the effect of the mutations on channel gating by measuring steady-state voltage-dependent activation and inactivation properties: no significant alterations were detected in p.G345V and p.S347W disease-associated variants, compared to controls. K_V4.3 expression studies in HEK293T cells showed 53% (p.G345V), 45% (p.S347W) and 75% (p.W359G) reductions in mutant protein levels compared with the wildtype. The present study broadens the spectrum of the known phenotypes and identifies additional variants for KCND3-related disorders, outlining the importance of SCA gene screening in early-onset and congenital ataxia.     

Analytical authentication of organic products: an overview of markers

Consumers' interest in organic foods is increasing and so is the need for robust analytical tools for their authentication. This review focuses on the most promising biomarkers/analytical approaches that are available for the authentication of organic produce. Food products have been subdivided into two groups: foods of plant origin (crops) and foods of animal origin (meat, milk and dairy products, eggs and fish). For each food category the most suitable biomarkers are presented and their potential for authentication is discussed. In the light of current knowledge, it is unlikely that the authentication of organic food products can be attained by the measurement of a single marker. Analytical approaches based on the measurement of multiple markers and/or complex chemical or physical profiles/fingerprints supported by multivariate statistical analysis seem considerably more promising in this respect. For the development of robust classification models, well‐designed experimental studies must be performed that rely on data sets that are both well balanced and of sufficient size to ensure that all relevant sources of variation for the target biomarkers are included in the reference database. Copyright © 2012 Society of Chemical Industry