Genetic Variation among Pharmacogenes in the Sardinian Population

Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians.     

Experience on Pre-Series and Series Production of LHC Dipoles Cold Masses in ASG Superconductors

In 1986 Ansaldo Magnet Dept. (now ASG Superconductors) started, in cooperation with CERN, the design activities of the first 1 m-8 T LHC prototype dipoles. After several design steps and the manufacturing of 1+3 prototype dipoles 10 m long, the final design configuration 15 m long was defined by CERN. During the following years, a very close collaboration with CERN engineers and technicians lead to define the parameters about the most critical manufacturing processes, in particular winding of s.c. cable, collaring of coils, cold mass welding and test procedures. In the meantime, installation and commissioning of all the manufacturing plants followed: winding machines, curing presses, collaring press and welding press were installed, as well as geometrical measurements stations and vacuum chamber for leak test. Finally two manufacturing halls were fully dedicated to LHC dipoles production. At the beginning of year 2002, all the manufacturing plants were coming to be operational, ready to start the large scale production of LHC cold masses: 30 pre-series, 386 series and 30 spare cold masses have been produced till May 2007, to get a total number of 446 cold masses. In this paper we summarize all the data collected during a five years production: main manufacturing data, test results and production rate are presented. Final results about tests performed at CERN in superfluid He at 1.9 K are also included as well as correlation between test result and manufacturing rate.     

A Comprehensive Bioinformatics Analysis of the Lipoxygenases Superfamily in Shewanella Woodyi Strain （Strain ATCC 519081MS32）

Sbewanella bacteria have real potential for the bioremediation of contaminated environmental and presents a differential that are three lipoxygenases described in its genome. Lipoxygenases （LOX） are a family of iron-containing enzymes that catalyze the dioxygenation of polyunsaturated fatty acids in lipids. They occur ubiquitously in plants and mammals, and only recently, they have been detected in coral, moss, fungi and a number of bacteria as well. In this work, analyzed three enzymes lipoxigenases described for Shewanella woodyi deposited in GeneBank as probable LOX gene in the Swoo_2318 S. woodyi ATCC 51908： Proteins Code （ACA86597.1） hypothetical protein, （ACA87192. I） arachidonate 15-1ipoxygenase and （AEF01209.1） arachidonate 15-1ipoxygenase precursor the strain S. woodyi DSM 12036. The bioinformatics tools tend to solve impossible problems to be addressed in the past decades. These analyses identified were the three proteins described as lipoxygenases have different secondary structures, the phosphorylation sites; the protein GRAVY （grand average of hydropathy） and protein isoelectric point are distinct. However, binding site is Fe for three lipoxygenases. This suggested that three lipoxygenases deserve special attention for work in situ, due to peculiar characteristics and still not know what is the need ofS. woodyi have in its genome three genes encoding the same protein.     

A methodology and tool environment for process analysis and reengineering

Most private and public organizations have recently turned their attention to the process by which they operate, to improve service and product quality and customer satisfaction. To support business process reengineering, methods and tools for process modeling and analysis are required. The paper presents the ARTEMIS methodology and associated tool environment for business process analysis for reengineering. In the ARTEMIS methodological framework, business processes are modeled as workflows and are analyzed according to an organizational structure perspective and an operational structure perspective. With these two perspectives, the analyst can plan reengineering interventions based on the degree of autonomy/dependency of organization units in terms of coupling, and the inter-process semantic correspondences, in terms of data and operation similarity, respectively. The ARTEMIS methodology and associated tool environment have been conceived and applied in the framework of the PROGRESS research project. In the paper, we report on a reengineering case study of this project involving the Italian Ministry of Justice.     

Bridging the gap between Graetz's and lévêque's analyses for mass/heat transfer in a channel with uniform concentration or flux at the wall

A new approximate solution which bridges the gap between the classical theories of Graetz and Lévêque for heat/mass transfer in channel flow is presented. The results include expressions, uniformly valid in the axial direction, for the mixing‐cup concentration (or temperature) profile 〈c〉 when transport towards the wall is slow (Dirichlet limit), and for the Sherwood number Sh when the wall flux can be considered uniform (Neumann limit). The technique employed provides insight into the mathematical structure of both quantities 〈c〉 (or conversion X_R) and Sh identifying explicitly the contributions from fully developed and developing behaviors, while maintaining accuracy in the transition region. Criteria to bound the different convection‐diffusion regimes are suggested, which critically systematize previous results. These results are important for model selection in the design and simulation, among others, of heat exchangers and wall‐coated microreactors where fast heterogeneous reactions occur. © 2011 American Institute of Chemical Engineers AIChE J, 58: 1880–1892, 2012     

Dipeptidyl peptidase-IV inhibitory peptides generated by tryptic hydrolysis of a whey protein concentrate rich in β-lactoglobulin

Dipeptidyl peptidase-IV (DPP-IV) is a serine protease involved in the degradation and inactivation of incretin hormones that act by stimulating glucose-dependent insulin secretion after meal ingestion. DPP-IV inhibitors have emerged as new and promising oral agents for the treatment of type 2 diabetes. The purpose of this study was to investigate the potential of β-lactoglobulin as natural source of DPP-IV inhibitory peptides. A whey protein concentrate rich in β-lactoglobulin was hydrolysed with trypsin and fractionated using a chromatographic separation at semipreparative scale. Two of the six collected fractions showed notable DPP-IV inhibitory activity. These fractions were analysed by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) to identify peptides responsible for the observed activity. The most potent fragment (IPAVF) corresponded to β-lactoglobulin f(78–82) which IC₅₀ value was 44.7 μM. The results suggest that peptides derived from β-lactoglobulin would be beneficial ingredients of foods against type 2 diabetes.     

Experimental investigation on the combustion process in a spark ignition optically accessible engine fueled with methane/hydrogen blends

The combustion process of a four-stroke optically accessible single cylinder Port Fuel Injection spark ignition (PFI SI) engine was experimentally investigated. It was fueled with two methane/hydrogen blends. The in-cylinder pressure and the related data were analyzed as indicators of the combustion quality. 2D-digital imaging measurements were performed to evaluate the flame propagation. UV–visible spectroscopy allows to characterize the combustion by means of the detection of OH* and CH*. The exhaust was characterized using conventional analyzers. For the methane/hydrogen blends the indicated data suggests an increase of the thermal efficiency and a decrease of the combustion duration with the increase of the hydrogen fraction. The optical results highlight a more homogeneous mixture that increases the combustion reaction rate and provides a more uniform and rapid flame propagation. On the other hand, high NO_x emissions were measured likely because of the higher combustion temperature due to hydrogen addition.     

Phytosterols in grapes and wine,and effects of agrochemicals on their levels

To improve the knowledge on the chemical diversity and complexity of grapevine, we investigated the plant sterol content of berry and seed tissues at pre-véraison and véraison stages in 2009 and 2010. We also assessed the effects of benzothiadiazole and chitosan elicitors on content of sterols in grapes and their levels in the corresponding experimental wines. β-Sitosterol was the most abundant component in berry tissues, in both growth stages and years, with the highest amounts in the flesh and skin at pre-véraison and véraison, respectively. Stigmasterol and campesterol were present in lower concentrations in both phenological stages and vintages. During the transition from pre-véraison to véraison, phytosterols decreased in all tissues, in both years, apart from stigmasterol in seeds. In addition, the results showed that the plant activators were more effective than conventional fungicides in rising the levels of sterols, particularly β-sitosterol, both in grapes and in microvinificates.