490 research outputs found

    Classification(s) of Danielewski hypersurfaces

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    The Danielewski hypersurfaces are the hypersurfaces X Q,n in C3 {\mathbb{C}^3} defined by an equation of the form x n y = Q(x, z) where n ⩾ 1 and Q(x, z) is a polynomial such that Q(0, z) is of degree at least two. They were studied by many authors during the last twenty years. In the present article, we give their classification as algebraic varieties. We also give their classification up to automorphism of the ambient space. As a corollary, we obtain that every Danielewski hypersurface X Q,n with n ⩾ 2 admits at least two nonequivalent embeddings into $ {\mathbb{C}^3}

    Robust design optimisation of dynamical space systems

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    In this paper we present a novel approach to the optimisation of complex systems affected by epistemic uncertainty when system and uncertainty evolve dynamically with time; we propose a new modelling approach that uses Evidence Theory to capture epistemic uncertainty A system is considered which is affected by the time during the operational life (failure rate, performance degradation, function degradation, etc.). The goal is to obtain a resilient design: robust with respect to performance variability and reliable against possible partial failures of one or more components. We propose to enhance the Evidence Network Model (ENM) with time-dependent reliability functions and decompose the problem into subproblems of smaller complexity. Through this decomposition uncertainty quantification of complex systems becomes affordable for a range of real-world applications. The method is here applied to a simple resource allocation problem where the goal is to optimally position subsystems within a spacecraft [1

    Mutual visibility by luminous robots without collisions

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    We consider the Mutual Visibility problem for anonymous dimensionless robots with obstructed visibility moving in a plane: starting from distinct locations, the robots must reach, without colliding, a configuration where no three of them are collinear. We study this problem in the luminous robots model, in which each robot has a visible light that can assume colors from a fixed set. Among other results, we prove that Mutual Visibility can be solved in SSynch with 2 colors and in ASynch with 3 colors. If an adversary can interrupt and stop a robot moving to its computed destination, Mutual Visibility is still solvable in SSynch with 3 colors and, if the robots agree on the direction of one axis, also in ASynch. As a byproduct, we provide the first obstructed-visibility solutions to two classical problems for oblivious robots: collision-less convergence to a point (also known as near-gathering) and circle formation

    Digital Technologies for Transport and Mobility: Challenges, Trends and Perspectives

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    This white paper aims at presenting the ideas emerging from the different fields pertaining to transport and mobility, to describe the capacities of current state-of-the-art digital technologies and the perspectives that are expected to shape the future of transport and mobility

    Dislocation-Actuated Growth and Inhibition of Hexagonal L-Cystine Crystallization at the Molecular Level

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    Crystallization of L-cystine is a critical process in the pathogenesis of kidney stone formation in cystinuria, a disorder affecting more than 20 000 individuals in the United States alone. In an effort to elucidate the crystallization of L-cystine and the mode of action of tailored growth inhibitors that may constitute effective therapies, real-time in situ atomic force microscopy has been used to investigate the surface micromorphology and growth kinetics of the {0001} faces of L-cystine at various supersaturations and concentrations of the growth inhibitor L-cystine dimethylester (CDME). Crystal growth is actuated by screw dislocations on the {0001} L-cystine surface, producing hexagonal spiral hillocks that are a consequence of six interlacing spirals of anisotropic molecular layers. The high level of elastic stress in the immediate vicinity around the dislocation line results in a decrease in the step velocities and a corresponding increase in the spacing of steps. The kinetic curves acquired in the presence of CDME conform to the classical Cabrera–Vermilyea model. Anomalous birefringence in the {101̅0} growth sectors, combined with computational modeling, supports a high fidelity of stereospecific binding of CDME, in a unique orientation, exclusively at one of the six crystallographically unique projections on the {1010} plane

    The BaR-SPOrt Experiment

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    BaR-SPOrt (Balloon-borne Radiometers for Sky Polarisation Observations) is an experiment to measure the linearly polarized emission of sky patches at 32 and 90 GHz with sub-degree angular resolution. It is equipped with high sensitivity correlation polarimeters for simultaneous detection of both the U and Q stokes parameters of the incident radiation. On-axis telescope is used to observe angular scales where the expected polarization of the Cosmic Microwave Background (CMBP) peaks. This project shares most of the know-how and sophisticated technology developed for the SPOrt experiment onboard the International Space Station. The payload is designed to flight onboard long duration stratospheric balloons both in the Northern and Southern hemispheres where low foreground emission sky patches are accessible. Due to the weakness of the expected CMBP signal (in the range of microK), much care has been spent to optimize the instrument design with respect to the systematics generation, observing time efficiency and long term stability. In this contribution we present the instrument design, and first tests on some components of the 32 GHz radiometer.Comment: 12 pages, 10 figures, Astronomical Telescopes and Instrumentation (Polaimetry in Astronomy) Hawaii August 2002 SPIE Meetin

    RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

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    ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

    Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study

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    Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation, while only slight effects were observed in the age-matched control samples. By contrast, the addition of iron chelators on MNCs from young healthy subjects determined a decrement in the OxPhos efficiency and an increment of lactate fermentation and lipid peroxidation. In summary, MDS-MNCs display an altered energy metabolism associated with increased oxidative stress, due to iron accumulation. This condition could be partially restored by iron chelatio

    Selection and characterisation of a phage-displayed human antibody (Fab) reactive to the lung resistance-related major vault protein

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    The major vault protein is the main component on multimeric vault particles, that are likely to play an essential role in normal cell physiology and to be associated with multidrug resistance of tumour cells. In order to unravel the function of vaults and their putative contribution to multidrug resistance, specific antibodies are invaluable tools. Until now, only conventional major vault protein-reactive murine monoclonal antibodies have been generated, that are most suitable for immunohistochemical analyses. The phage display method allows for selection of human antibody fragments with potential use in clinical applications. Furthermore, cDNA sequences encoding selected antibody fragments are readily identified, facilitating various molecular targeting approaches. In order to obtain such human Fab fragments recognising major vault protein we used a large non-immunized human Fab fragment phage library. Phages displaying major vault protein-reactive Fabs were obtained through several rounds of selection on major vault protein-coated immunotubes and subsequent amplification in TG1 E coli bacteria. Eventually, one major vault protein-reactive clone was selected and further examined. The anti-major vault protein Fab was found suitable for immunohistochemical and Western blot analysis of tumour cell lines and human tissues. BIAcore analysis showed that the binding affinity of the major vault protein-reactive clone almost equalled that of the murine anti-major vault protein Mabs. The cDNA sequence of this human Fab may be exploited to generate an intrabody for major vault protein-knock out studies. Thus, this human Fab fragment should provide a valuable tool in elucidating the contribution(s) of major vault protein/vaults to normal physiology and cellular drug resistance mechanisms
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