N-nonyloxypentyl-l-deoxynojirimycin inhibits growth, biofilm formation and virulence factors expression of Staphylococcus aureus

Staphylococcus aureus is one of the major causes of hospital-and community-associated bacterial infections throughout the world, which are difficult to treat due to the rising number of drug-resistant strains. New molecules displaying potent activity against this bacterium are urgently needed. In this study, d-and l-deoxynojirimycin (DNJ) and a small library of their N-alkyl derivatives were screened against S. aureus ATCC 29213, with the aim to identify novel candidates with inhibitory potential. Among them, N-nonyloxypentyl-l-DNJ (l-NPDNJ) proved to be the most active compound against S. aureus ATCC 29213 and its clinical isolates, with the minimum inhibitory concentration (MIC) value of 128 µg/mL. l-NPDNJ also displayed an additive effect with gentamicin and oxacillin against the gentamicin-and methicillin-resistant S. aureus isolate 00717. Sub-MIC values of l-NPDNJ affected S. aureus biofilm development in a dose-dependent manner, inducing a strong reduction in biofilm biomass. Moreover, real-time reverse transcriptase PCR analysis revealed that l-NPDNJ effectively inhibited at sub-MIC values the transcription of the spa, hla, hlb and sea virulence genes, as well as the agrA and saeR response regulator genes

Unravelling the structure of the tetrahedral metal-binding site in METP3 through an experimental and computational approach

Understanding the structural determinants for metal ion coordination in metalloproteins is a fundamental issue for designing metal binding sites with predetermined geometry and activity. In order to achieve this, we report in this paper the design, synthesis and metal binding properties of METP3, a homodimer made up of a small peptide, which self assembles in the presence of tetra-hedrally coordinating metal ions. METP3 was obtained through a redesign approach, starting from the previously developed METP molecule. The undecapeptide sequence of METP, which dimerizes to house a Cys4 tetrahedral binding site, was redesigned in order to accommodate a Cys2His2 site. The binding properties of METP3 were determined toward different metal ions. Successful assem-bly of METP3 with Co(II), Zn(II) and Cd(II), in the expected 2:1 stoichiometry and tetrahedral geometry was proven by UV-visible spectroscopy. CD measurements on both the free and metal-bound forms revealed that the metal coordination drives the peptide chain to fold into a turned conformation. Finally, NMR data of the Zn(II)-METP3 complex, together with a retrostructural analysis of the Cys-X-X-His motif in metalloproteins, allowed us to define the model structure. All the results establish the suitability of the short METP sequence for accommodating tetrahedral metal binding sites, regardless of the first coordination ligands

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

Prikaz znanja u internetu stvari: semantičko modeliranje i njegove primjene

Semantic modelling provides a potential basis for interoperating among different systems and applications in the Internet of Things (IoT). However, current work has mostly focused on IoT resource management while not on the access and utilisation of information generated by the “Things”. We present the design of a comprehensive and lightweight semantic description model for knowledge representation in the IoT domain. The design follows the widely recognised best practices in knowledge engineering and ontology modelling. Users are allowed to extend the model by linking to external ontologies, knowledge bases or existing linked data. Scalable access to IoT services and resources is achieved through a distributed, semantic storage design. The usefulness of the model is also illustrated through an IoT service discovery method.Semantičko modeliranje pruža potencijalnu osnovu za me.udjelovanje različitih sustava i aplikacija unutar interneta stvari (IoT). Međutim, postojeći radovi uglavnom su fokusirani na upravljanje IoT resursima, ali ne i pristupu i korištenju informacija koje generira “stvar”. Predstavljamo projektiranje sveobuhvatnog i laganog semantičkog opisnog modela za prikaz znanja u IoT domeni. Projektiranje slijedi široko-priznate najbolje običaje u inženjerstvu znanja i ontološkom modeliranju. Korisnicima se dopušta proširenje modela povezivanjem na eksterne ontologije, baze znanja ili postoje će povezane podatke. Skalabilni pristup IoT uslugama i resursima postiže se kroz distribuirano, semantičko projektiranje pohrane. Upotrebljivost modela tako.er je ilustrirana kroz metodu pronalaska IoT usluga

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

A sensitivity analysis on the damage detection capability of a Lamb waves based SHM system for a composite winglet

Lamb waves based Structural Health Monitoring (SHM) systems, thanks to their high sensitivity to damage detection and the ability to travel over a long distance with low power consumption, are founding increasing industrial applications, especially in the aerospace field, where airworthiness authorities require that composite materials in primary structures must remain undamaged during the in-service life. In order to tolerate damage and monitor its severity and, consequently, to repair the structure only when strictly needed, the use of SHM systems appears to be an efficient solution providing benefits for the current design practice. The continuous assessment of the structural integrity, which can be accomplished by SHM systems, can play a key-role to achieve a less-conservative design as well as to facilitate maintenance operations. This paper deals with a sensitivity analysis, based on the Finite Element (FE) theory, aimed to investigate numerically the influence of the damage orientation on the damage detection capability of a Lamb waves based SHM system arranged on a damaged Glass Fiber Reinforced Polymer composite winglet. Damage detection sensitivity has been measured by analyzing the interaction between the modelled damages and guided waves under a specific central frequency. Signals recorded at different locations by piezoelectric sensors have been compared with the baseline signals achieved under a pristine configuration of the winglet by means of a damage index. A specific trend of the considered damage index has been found out as function of the damage orientation

Adaptive wing-tip design for pollution reduction

Most of the commercial long-range aircraft are equipped with winglet to decrease the induced drag thus saving more fuel; this feature can also be found on birds, but in conventional aircraft, the winglet device is fixed. Recent projects point toward advanced smart materials and telescopic wing-tip devices to obtain an adaptive morphing shape that gives, through performances improvement, a fuel consumption and so a pollutant reduction. In order to obtain pollution reductions via high aerodynamic efficiency, the design of a telescopic inflatable variable height wing-tip device has been addressed. The span variation is pursued toward a telescopic device that is linked to an inflatable system distributed in chord and along the base of tip, ready to be extruded according to flight conditions. The performance analysis has been conducted especially to evaluate range performance, which mainly provides the relation to fuel consumption. The hinged telescopic device gives the chance of obtaining variation in winglet span according to flight condition requirements in terms of stability and aerodynamic efficiency. The solution of the inflatable system would guarantee a more comfortable arrangement of deployment system and just minor surplus of weight compared to classical winglet solutions, with all the subsequent advantages

Guided waves in a composite winglet structure: Numerical and experimental investigations

The paper deals with numerical and experimental investigations aimed to develop a Finite Element (FE) model for predicting wave propagation in a blended composite winglet. Material anisotropy, inhomogeneity, multi-layered configuration and complex geometries tend to increase the complexity of the wave propagation phenomena and consequently the development of established FE models. Moreover, even if 2D finite elements seem to be not appropriate for modelling guided waves propagation, especially for complex anisotropic structural components, they are more attractive than 3D ones, because of the computational cost saving. For this reason, part of the presented research activity is addressed to investigate the efficiency of shell finite elements in modelling guided waves propagation in a such complex structure as a winglet. The development of an efficient model depends also on the numerical characterization of the medium within which guided waves propagate through. As a consequence, preliminary simple experimental bending and modal tests have been carried out to support the material properties modelling. Subsequently, guided wave propagation FE analyses were performed and the results compared with provided experimental data. A good agreement between numerical and experimental results of the different analyses has been achieved in terms of both signal time of flight and amplitudes

Skin-spar failure detection of a composite Winglet using fbg sensors

Winglets are introduced into modern aircraft to reduce wing aerodynamic drag and to consequently optimize the fuel burn per mission. In order to be aerodynamically effective, these devices are installed at the wing tip section; this wing region is generally characterized by relevant oscillations induced by flights maneuvers and gust. The present work is focused on the validation of a continuous monitoring system based on fiber Bragg grating sensors and frequency domain analysis to detect physical condition of a skin-spar bonding failure in a composite winglet for in-service purposes. Optical fibers are used as deformation sensors. Short Time Fast Fourier Transform (STFT) analysis is applied to analyze the occurrence of structural response deviations on the base of strain data. Obtained results showed high accuracy in estimating static and dynamic deformations and great potentials in detecting structural failure occurrences