OpenCOPI: middleware integration for Ubiquitous Computing

In this paper, we present OpenCOPI (Open COntext Platform Integration), a Service-Oriented Architecture-based middleware platform that supports the integration of services provided by distinct sources, ranging from services offered by simple systems to more complex services provided by context-provision middleware. OpenCOPI offers selection and composition mechanisms to, respectively, select and compose services provided by different sources, considering applications of both Quality of Service and Quality of Context requirements. It also offers an adaptation mechanism that enables to adapt the application execution due to service failures, service quality fluctuation and user mobility. OpenCOPI allows the definition of applications in a higher abstraction level by the specification of a semantic workflow that contains abstract activities. This paper illustrates the use of OpenCOPI in an application from the Gas & Oil Industry and it also shows the evaluation of the main mechanisms of OpenCOPI: the service selection, composition, adaptation and workflow execution.     

P-glycoprotein inhibitors: synthesis and in vitro evaluation of a preactivated thiomer

Abstract

The aim of this study was to synthesize the preactivated thiomer poly(acrylic acid)-cyteine-2-mercaptonicotinic acid (PAA-Cys-2MNA) and to evaluate its P-glycoprotein (P-gp) inhibitory properties. The thiomer (PAA-Cys) was synthesized by covalent immobilization of thiol groups on poly(acrylic acid) (PAA) with a molecular mass of 250?kDa followed by immobilization of 2-mercaptonicotinic acid (2MNA) to thiol groups via disulfide bond formation resulting in PAA-Cys-2MNA. P-gp inhibitory effect of this preactivated thiomer was evaluated on Caco-2 cells. Transports of rhodamine 123 at 37?°C with and without verapamil and at 4?°C were performed to evaluate P-gp function of cells. In total, 1571.81?±?156.18?µmol thiol groups were immobilized per gram of polymer that were in the next step by 99.88% preactivated. The enhancement ratios of P_app calculated from the ratio between P_app of rhodamine 123 in the presence of P-gp inhibitors and P_app of rhodamine 123 alone were 2.36, 2.09, and 1.84-fold in the presence of PAA-Cys-2MNA, PAA-Cys, and PAA, respectively. Because of its pronounced P-gp inhibitory effect, PAA-Cys-2MNA could be considered as promising macromolecular P-gp inhibitor for various drug delivery systems.     

Engineered Multifunctional Albumin‐Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin

The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection‐based delivery of insulin. Neonatal Fc receptor (FcRn)‐mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn‐targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH‐responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH‐sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn‐targeted NPs. Overall, these FcRn‐targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin.     

A symbolic summation approach to Feynman integral calculus

Given a Feynman parameter integral, depending on a single discrete variable N$N$ and a real parameter ε$\epsilon$, we discuss a new algorithmic framework to compute the first coefficients of its Laurent series expansion in ε$\epsilon$. In a first step, the integrals are expressed by hypergeometric multi-sums by means of symbolic transformations. Given this sum format, we develop new summation tools to extract the first coefficients of its series expansion whenever they are expressible in terms of indefinite nested product–sum expressions. In particular, we enhance the known multi-sum algorithms to derive recurrences for sums with complicated boundary conditions, and we present new algorithms to find formal Laurent series solutions of a given recurrence relation.     

Shear Strength of Pre-Cast Prestressed Composite Beams with Discontinuous Connections Made of Cast-in-Place Shear Keys

This work investigates the horizontal and web shear resistance of continuous and discontinuous slab-web connections in pre-cast pre-tensioned bridge systems. The beams were full scale pre-cast pre-tensioned girders and the slabs were made of ordinary reinforced concrete either cast in place, for continuous connections, or pre-cast slabs with holes spaced at 312.5 mm to be set in place, for discontinuous connections. The main variables were the connection type (continuous or discontinuous) and the ratio of the connection steel. From the test results and the numerical analysis performed, a modified stress field for the inclined compressive strut in the truss model is proposed for continuous and discontinuous slab-web connections. The analytical results obtained with the proposed modified stress field in the truss model compared well with the tests results. Design procedures for these types of elements are also discussed.     

GIUSEPPE PAGANO: A Rationalist caught between Theories and Practices of Fascist Italy

The architecture of a modern building is viewed and defined as a whole: the so-called decorative detail does not exist, only the intelligent and strictly controlled technical detail. The aesthetic basis—both social and technical at the same time—of modern architecture is reproduced in the three-dimensional composition.¹     

trans Fatty Acids in Colostrum,Mature Milk and Diet of Lactating Adolescents

The purpose of this study was to investigate the trans fatty acids (TFA) content and distribution in colostrum, mature milk, and diet of adolescent mothers, after TFA declaration in food labels became mandatory in Brazil. Participants were healthy adolescents (n 54, 15–19 years, 1–90 days postpartum) practicing exclusive breastfeeding. Milk samples were collected 3 days after delivery (colostrum) and in the third month postpartum (mature milk) by hand expression. The fatty acid composition of the milk samples was determined by gas chromatography. TFA intake corresponded to 1.23 % of total energy value. Total 18:2 TFA accounted for less than 0.5 % of the energy intake. The amount of total 18:1 TFA (mean ± SEM) was 1.9 % ± 0.14 in colostrum and 1.5 % ± 0.2 in mature milk. The total content of n‐3 PUFA was inversely correlated with the total content of 18:1 TFA in colostrum. Both in colostrum and in mature milk, vaccenic acid (11t‐18:1) was found to be the most abundant 18:1 trans isomer, followed by elaidic acid (9t‐18:1), whereas rumenic acid (9c,11t‐18:2 CLA) was the predominant 18:2 trans isomer. In conclusion, the levels of TFA of industrial sources found in the mother's diet and breast milk (colostrum and mature milk) showed a decrease in relation to those observed in studies conducted prior to the TFA labeling resolution in Brazil. However, the current low intake levels of n‐3 LCPUFA and DHA content in the milk of lactating adolescents may be insufficient for supporting adequate neurological development of the infants.     

Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans

Type 2 diabetes is characterized by impairment in insulin secretion, with an established genetic contribution. We aimed to evaluate common and low-frequency (1–5%) variants in nine genes strongly associated with insulin secretion by targeted sequencing in subjects selected from the extremes of insulin release measured by the disposition index. Collapsing data by gene and/or function, the association between disposition index and nonsense variants were significant, also after adjustment for confounding factors (OR = 0.25, 95% CI = 0.11–0.59, p = 0.001). Evaluating variants individually, three novel variants in ARAP1, IGF2BP2 and GCK, out of eight reaching significance singularly, remained associated after adjustment. Constructing a genetic risk model combining the effects of the three variants, only carriers of the ARAP1 and IGF2BP2 variants were significantly associated with a reduced probability to be in the lower, worst, extreme of insulin secretion (OR = 0.223, 95% CI = 0.105–0.473, p < 0.001). Observing a high number of normal glucose tolerance between carriers, a regression posthoc analysis was performed. Carriers of genetic risk model variants had higher probability to be normoglycemic, also after adjustment (OR = 2.411, 95% CI = 1.136–5.116, p = 0.022). Thus, in our southern European cohort, nonsense variants in all nine candidate genes showed association with better insulin secretion adjusted for insulin resistance, and we established the role of ARAP1 and IGF2BP2 in modulating insulin secretion.