540 research outputs found
5-substituted derivatives of 6-amino-1,3-diphenyl-2-thioxo-2.3-dihydropyrimidin-4(1H9-one as a new class of potent inhibitors of interleukin 8-induced chemotaxis
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6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives as a new class of potent inhibitors of Interleukin-8-induced neutrophil chemotaxis.
No full textA series of 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives was synthesized. The compounds demonstrated to be novel, potent and selective inhibitors of Interleukin-8-induced human neutrophil chemotaxis. A SAR study was performed by varying the carbonyl function at position 5 and the chain linked to the amino group at position 6 of the scaffold. All the compounds of the series displayed inhibitory activity at nano- or picomolar concentrations against Interleukin-8-driven migration and no activity against fMLP- and C5a-induced chemotaxis. The binding tests of selected compounds on CXCR1 and CXCR2 receptors were negative. The most potent derivative showed in vivo efficacy in a mouse model of Zymosan-induced peritoniti
Defective Autophagy, Mitochondrial Clearance and Lipophagy in Niemann-Pick Type B Lymphocytes
No full textNiemann-Pick disease type A (NP-A) and type B (NP-B) are lysosomal storage diseases (LSDs) caused by sphingomyelin accumulation in lysosomes relying on reduced or absent acid sphingomyelinase. A considerable body of evidence suggests that lysosomal storage in many LSD impairs autophagy, resulting in the accumulation of poly-ubiquitinated proteins and dysfunctional mitochondria, ultimately leading to cell death. Here we test this hypothesis in a cellular model of Niemann-Pick disease type B, in which autophagy has never been studied. The basal autophagic pathway was first examined in order to evaluate its functionality using several autophagy-modulating substances such as rapamycin and nocodazole. We found that human NP-B B lymphocytes display considerable alteration in their autophagic vacuole accumulation and mitochondrial fragmentation, as well as mitophagy induction (for damaged mitochondria clearance). Furthermore, lipid traceability of intra and extra-cellular environments shows lipid accumulation in NP-B B lymphocytes and also reveals their peculiar trafficking/management, culminating in lipid microparticle extrusion (by lysosomal exocytosis mechanisms) or lipophagy. All of these features point to the presence of a deep autophagy/mitophagy alteration revealing autophagic stress and defective mitochondrial clearance. Hence, rapamycin might be used to regulate autophagy/mitophagy (at least in part) and to contribute to the clearance of lysosomal aberrant lipid storage
Adaptive optics methods in gravitational wave interferometric detectors, a perspective
No full textThe performance of present and future gravitational wave detectors is limited by fundamental
factors, such as thermal noise, seismic or newtonian noise and quantum nature of light. Besides,
technological factors impact the reach of advanced detectors in that upgrade strategies are
limited by state-of-art performances. In the realm of optics, the quantum limit to sensitivity
will be addressed by injecting higher laser power and by exploiting the capabilities of squeezed
light. In turn, technological efforts in the preparation of suitable optics able to meet more and
more demandig requirements are ongoing. Moreover, solutions to mitigate the effect of known
showstoppers such as parametric instablities are being studied.
The present day strategy to correct for residual cold defects in the core optics and to counteract
the thermal effects due to power absorption is embedded in a set of sensors and actuators
integrated in the Advanced Virgo design, the so called Thermal Compensation System (TCS).
This system is designed to be focused on the needs of high power operation of the detector,
nonetheless it is highly versatile and can deal with foreseen and unexpected issues. We discuss
the features of the TCS with emphasis on its versatility and portability to upgraded detectors; we
also present the status of the R&D activity in the Tor Vergata labs, highlighting new applications
where the methods of TCS can have a relevant impact, such as adaptive mode matching for
squeezing and damping of parametric instabilities
The dynamics of monolithic suspensions for advanced detectors: a 3-segment model
No full textIn order to reduce the suspension thermal noise, the second generation GW interferometric detectors will employ monolithic suspensions in fused silica to hold the mirrors. The fibres are produced by melting and pulling apart a fused silica rod, obtaining a long thin wire with two thicker heads. The dynamics of such a fibre is in principle different from that of a cylindrical, regular fibre, because most of the deformation energy is stored in the neck region where the diameter is variable. This is an advantage, since adjusting the neck tapering, a thermoelastic noise cancellation effect can be obtained. Therefore, a careful study of the suspensions behavior is necessary to estimate the overall noise and to optimize the control strategy. To simplify the control design, a simple three segment model for the silica fibres has been developed, fully equivalent to the beam equation at low frequencies. The model, analytically proved for a regular cylindrical fibre, can be extended to a fibre with tapered necks, provided that the equivalent bending length is suitably measured. We developed a tool to measure the position of the bending point for each fibre, thus allowing to experimentally check the validity of the model. A numerical code has been written to solve the beam equation for wires with varying diameter. This code confirms the validity of the three segment model. Moreover, it is possible to extend the solution to higher frequencies thus computing the transfer function and the energy distribution of the suspension system and estimating the thermal noise contribution
GraphDBLP: a system for analysing networks of computer scientists through graph databases
No full textThis paper presents GraphDBLP, a system that models the DBLP bibliography as a graph database for performing graph-based queries and social network analyses. GraphDBLP also enriches the DBLP data through semantic keyword similarities computed via word-embedding. In this paper, we discuss how the system was formalized as a multi-graph, and how similarity relations were identified through word2vec. We also provide three meaningful queries for exploring the DBLP community to (i) investigate author profiles by analysing their publication records; (ii) identify the most prolific authors on a given topic, and (iii) perform social network analyses over the whole community. To date, GraphDBLP contains 5+ million nodes and 24+ million relationships, enabling users to explore the DBLP data by referencing more than 3.3 million publications, 1.7 million authors, and more than 5 thousand publication venues. Through the use of word-embedding, more than 7.5 thousand keywords and related similarity values were collected. GraphDBLP was implemented on top of the Neo4j graph database. The whole dataset and the source code are publicly available to foster the improvement of GraphDBLP in the whole computer science community
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