Performances' Estimation by Tests of Composite Material Structures With Respect to the Lay-Up Configuration and Mixing the Position of Tape and Fabric Laminae

Abstract This paper presents an estimation of performances by tests on composite material structures. In order to evaluate the effects on the structural behavior, tests changing the percentage of orientation of the fiber at 0, 45 and 90 degrees and mixing the unidirectional plies with the fabric ones have been done. Fixed the lay-up configuration and so the stacking sequence, two typology of structures have been analyzed; the first one having only unidirectional plies while the second one having a fabric ply (plain weave 0/90) in place of the top and bottom unidirectional plies. The openhole compressive strength and the filled-hole tensile strength and moduli have been characterized by test. A total of 72 specimens have been used in the test campaign. In order to well compare the test results a Performance Weight Index (PWI) has been introduced by authors in order to normalize the strength of each laminate with respect to its weight/unit of surface. Results and different laminate behaviors have been evaluated and discussed

Nat Genet

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.Comment in : Genetic differential calculus. [Nat Genet. 2015] Comment in : Scaling up phenotyping studies. [Nat Biotechnol. 2015

Understanding binding selectivity toward trypsin and factor Xa the role of aromatic interactions

A congeneric series of four bis benzamidine inhibitors sharing a dianhydrosugar isosorbide scaffold in common has been studied by crystal structure analysis and enzyme kinetics with respect to their binding to trypsin and factor amp; 8197;Xa. Within the series, aromatic interactions are an important determinant for selectivity discrimination among both serine proteases. To study the selectivity determining features in detail, we used trypsin mutants in which the original binding site is gradually substituted to finally resemble the factor amp; 8197;Xa binding pocket. The influence of these mutations has been analyzed on the binding of the closely related inhibitors. We present the crystal structures of the inhibitor complexes obtained by co crystallizing an intermediate trypsin mutant. They could be determined to a resolution of up to 1.2 amp; 8197; , and we measured the inhibitory activity Ki of each ligand against factor amp; 8197;Xa, trypsin, and the various mutants. From these data we were able to derive a detailed structure activity relationship which demonstrates the importance of aromatic interactions in protein ligand recognition and their role in modulating enzyme selectivity. Pronounced preference is experienced to accommodate the benzamidine anchor with meta topology in the S1 specificity pocket. One ligand possessing only para topology deviates strongly from the other members of the series and adopts a distinct binding mode addressing the S1 amp; 8242; site instead of the distal S3 S4 binding pocke

Estymacja właściwości użytkowych struktur z materiałów kompozytowych na podstawie testów z uwzględnieniem konfiguracji prelaminatu i przy zamianie pozycji warstwy jednokierunkowej i warstwy tkaniny

This paper presents an estimation of performances by tests on composite material structures. In order to evaluate the effects on the structural behavior, tests changing the percentage of orientation of the fiber at 0, 45 and 90 degrees and mixing the unidirectional plies with the fabric ones have been done. Fixed the lay-up configuration and so the stacking sequence, two typology of structures have been analyzed; the first one having only unidirectional plies while the second one having a fabric ply (plain weave 0/90) in place of the top and bottom unidirectional plies. The openhole compressive strength and the filled-hole tensile strength and moduli have been characterized by test. A total of 72 specimens have been used in the test campaign. In order to well compare the test results a Performance Weight Index (PWI) has been introduced by authors in order to normalize the strength of each laminate with respect to its weight/unit of surface. Results and different laminate behaviors have been evaluated and discussed.W artykule przedstawiono estymację, na podstawie testów, właściwości użytkowych struktur z materiałów kompozytowych. W celu oceny różnych wpływów na zachowanie się struktury wykonano testy przy zmiennej procentowej zawartości włókien o orientacji 0, 45 i 90° i przy zamianie pozycji warstwy jednokierunkowej i warstwy tkaniny. Przy ustalonej konfiguracji prelaminatu i takiej samej sekwencji ułożenia warstw, analizowano dwie topologie struktury, z których pierwsza miała tylko warstwy jednokierunkowe, a w drugiej była warstwa z tkaniny (splot płócienny 0/90) w miejscu warstw jednokierunkowych, górnej i dolnej. Na podstawie testu wyznaczono wytrzymałość na ściskanie próbki z otwartym otworem i wytrzymałość na rozciąganie oraz moduły przy wypełnionym otworze. W ramach badań doświadczalnych testowano ogółem 72 próbki. By prawidłowo porównać wyniki testów wprowadzono wagowy indeks osiągów (Performance Weight Index, PWI), pozwalający normalizować wytrzymałość każdego laminatu względem jego wagi na jednostkę powierzchni. Przedyskutowano i oceniono wyniki badań i zachowanie się różnych laminatów

Nuovi aspetti immunologici del trapianto di rene in eta' pediatrica = Novel immunological aspects of pediatric kidney transplantation

Pediatric kidney transplantation has been a serious challenge from the outset. The main reason lies in the immune system of children, which presents significant differences in terms of lymphocyte subpopulation distribution and alloimmune response activation from the adult immune system. These differences are greatest between neonates and adults, while they decrease in a linear and age-dependent fashion. In the past, kidney transplantation in children was a courageous initiative, given the poorer outcomes compared with adult recipients. Today, thanks to advances in therapy protocols and a better knowledge of the pediatric immune system, graft survival in pediatric patients has significantly improved and transplantation is the standard of care for the treatment of chronic organ failure in children. Moreover, there is growing interest in the field of pediatric transplantation because of the recipients' peculiar infective risk profile, the underestimated cardiovascular risk, and the necessity to identify both new non-invasive diagnostic techniques and the characteristics that make the pediatric immune system so peculiar. Acquiring new knowledge in those fields may slow down the adoption of new therapies but, on the other hand, it may represent a starting point to provide pediatric allograft recipients with diagnostic and therapeutic advantages and ultimately achieve allograft tolerance

Structural Studies on Hgr3 Orphan Receptor Ligand Prolactin-Releasing Peptide.

Prolactin-releasing peptides (PrRPs) are two novel bioactive peptides of 20 and 31 residues, dubbed respectively PrRP20 and PrRP31, isolated from bovine hypothalamic tissues as ligands of the orphan seven-transmembrane domain receptor Hgr3. The first biological activity identified for these peptides was the release of prolactin. Recent data on biological activities of PrRPs as well as on the localization of their receptors in numerous central nervous system sites suggested new potential actions of PrRPs in the regulation of the central nervous system and the possibility of identifying an alternative central role for these peptides. We describe here the synthesis and the structural characterization of the peptide PrRP20 by CD and NMR spectroscopies. A 3D model was built on the basis of the NMR data collected in a water/sodium dodecyl sulfate mixture. This system provides an amphipatic medium able to mimic the cell membrane. The main structural feature of the PrRP20 is an α-helical secondary structure spanning the 10 C-terminal residues. The conformational properties of PrRP20 are discussed in considering the sequence similarity observed between the Hgr3 and the neuropeptide Y (NPY) receptors. This similarity, together with the data showing a number of biological activities common to PrRP and NPY peptides, leads us to formulate the hypothesis that similar structural elements could exist in the ligands as well. In fact, PrRP20 and NPY are well aligned in the C-terminal portion, where they share an amphipatic α-helical secondary structure. Interestingly, the homology between the two sequences involves residues crucial for NPY biological activity. The conformational characterization of PrRP20 and the comparison with NPY are a valuable starting point for the rational design of subsequent SAR studies aimed at identifying PrRP analogues acting as either agonists or antagonists at the Hgr3 receptor. Such PrRP analogues could be useful receptorial tools able to clarify the multiple biological functions hypothesized for the PrRP receptor in the central nervous system