98 research outputs found

    Control of superluminal transit through a heterogeneous medium

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    We consider pulse propagation through a two component composite medium (metal inclusions in a dielectric host) with or without cavity mirrors. We show that a very thin slab of such a medium, under conditions of localized plasmon resonance, can lead to significant superluminality with detectable levels of transmitted pulse. A cavity containing the heterogeneous medium is shown to lead to subluminal-to-superluminal transmission depending on the volume fraction of the metal inclusions. The predictions of phase time calculations are verified by explicit calculations of the transmitted pulse shapes. We also demonstrate the independence of the phase time on system width and the volume fraction under specific conditions.Comment: 21 Pages,5 Figures (Published in Journal of Modern Optics

    Targeting GSTP1-1 induces JNK activation and leads to apoptosis in cisplatin-sensitive and -resistant human osteosarcoma cell lines

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    The effect of the glutathione transferase P1-1 (GSTP1-1) targeting has been investigated in both sensitive (U-2OS) and cisplatin-resistant (U-2OS/CDDP4μg) human osteosarcoma cell lines. Despite the different enzyme’s content, inhibition of GSTP1-1 by 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) causes the activation of c-Jun N-terminal kinase (JNK) and apoptosis in both cell lines. However, different time courses of JNK activation and cell responses are observed. Whereas in the U-2OS/CDDP4μg cell line drug treatment results in an early increase of caspase activity and secondary necrosis, in the U-2OS cells it mainly causes cell cycle arrest followed by apoptosis. Thereafter, we detailed the action mechanism of NBDHEX in the U-2OS cell line. We report evidence of the interaction between GSTP1-1 and the TNF receptor associated factor 2 (TRAF2) and we demonstrate that NBDHEX is able to dissociate the GSTP1-1:TRAF2 complex. This restores the TRAF2:ASK1 signaling, thereby leading to the simultaneous and prolonged activation of JNK and p38. These mitogen-activated protein kinases (MAPKs) mediate different effects: JNK is crucial for apoptosis, whereas p38 causes an increase in the p21 level and a concomitant cell cycle arrest. Our study shows that GSTP1-1 plays an important regulatory role in TRAF signaling of osteosarcoma and discloses new features of the action mechanism of NBDHEX that suggest potentially practical consequences of these finding

    p63 isoforms regulate metabolism of cancer stem cells

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    p63 is an important regulator of epithelial development expressed in different variants containing (TA) or lacking (\u394N) the N-terminal transactivation domain. The different isoforms regulate stem-cell renewal and differentiation as well as cell senescence. Several studies indicate that p63 isoforms also play a role in cancer development; however, very little is known about the role played by p63 in regulating the cancer stem phenotype. Here we investigate the cellular signals regulated by TAp63 and \u394Np63 in a model of epithelial cancer stem cells. To this end, we used colon cancer stem cells, overexpressing either TAp63 or \u394Np63 isoforms, to carry out a proteomic study by chemical-labeling approach coupled to network analysis. Our results indicate that p63 is implicated in a wide range of biological processes, including metabolism. This was further investigated by a targeted strategy at both protein and metabolite levels. The overall data show that TAp63 overexpressing cells are more glycolytic-active than \u394Np63 cells, indicating that the two isoforms may regulate the key steps of glycolysis in an opposite manner. The mass-spectrometry proteomics data of the study have been deposited to the ProteomeXchange Consortium (http://proteomecentral. proteomexchange.org) via the PRIDE partner repository with data set identifiers PXD000769 and PXD000768

    Analysis of the RLMS Adaptive Beamforming Algorithm Implemented with Finite Precision

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    This paper studies the influence of the use of finite wordlength on the operation of the RLMS adaptive beamformingalgorithm. The convergence behavior of RLMS, based on the minimum mean square error (MSE), is analyzed for operation with finite precision. Computer simulation results verify that a wordlength of nine bits is sufficient for the RLMS algorithm to achieve performance close to that provided by full precision. The performance measures used include residual MSE, rate of convergence, error vector magnitude (EVM), and beam pattern. Based on all these measures, it is shown that the RLMS algorithm outperforms other earlier algorithms, such as least mean square (LMS), recursive least square (RLS), modified robust variable step size (MRVSS) and constrained stability LMS (CSLMS)

    NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer's disease.

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    Disarrangement in functions and quality control of mitochondria at synapses are early events in Alzheimer's disease (AD) pathobiology. We reported that a 20-22 kDa NH2-tau fragment mapping between 26 and 230 amino acids of the longest human tau isoform (aka NH2htau): (i) is detectable in cellular and animal AD models, as well in synaptic mitochondria and cerebrospinal fluids (CSF) from human AD subjects; (ii) is neurotoxic in primary hippocampal neurons; (iii) compromises the mitochondrial biology both directly, by inhibiting the ANT-1-dependent ADP/ATP exchange, and indirectly, by impairing their selective autophagic clearance (mitophagy). Here, we show that the extensive Parkin-dependent turnover of mitochondria occurring in NH2htau-expressing post-mitotic neurons plays a pro-death role and that UCHL-1, the cytosolic Ubiquitin-C-terminal hydrolase L1 which directs the physiological remodeling of synapses by controlling ubiquitin homeostasis, critically contributes to mitochondrial and synaptic failure in this in vitro AD model. Pharmacological or genetic suppression of improper mitophagy, either by inhibition of mitochondrial targeting to autophagosomes or by shRNA-mediated silencing of Parkin or UCHL-1 gene expression, restores synaptic and mitochondrial content providing partial but significant protection against the NH2htau-induced neuronal death. Moreover, in mitochondria from human AD synapses, the endogenous NH2htau is stably associated with Parkin and with UCHL-1. Taken together, our studies show a causative link between the excessive mitochondrial turnover and the NH2htau-induced in vitro neuronal death, suggesting that pathogenetic tau truncation may contribute to synaptic deterioration in AD by aberrant recruitment of Parkin and UCHL-1 to mitochondria making them more prone to detrimental autophagic clearance

    Comprehensive analysis of temporal alterations in cellular proteome of bacillus subtilis under curcumin treatment

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    Curcumin is a natural dietary compound with antimicrobial activity against various gram positive and negative bacteria. This study aims to investigate the proteome level alterations in Bacillus subtilis due to curcumin treatment and identification of its molecular/cellular targets to understand the mechanism of action. We have performed a comprehensive proteomic analysis of B. subtilis AH75 strain at different time intervals of curcumin treatment (20, 60 and 120 min after the drug exposure, three replicates) to compare the protein expression profiles using two complementary quantitative proteomic techniques, 2D-DIGE and iTRAQ. To the best of our knowledge, this is the first comprehensive longitudinal investigation describing the effect of curcumin treatment on B. subtilis proteome. The proteomics analysis revealed several interesting targets such UDP-N-acetylglucosamine 1-carboxyvinyltransferase 1, putative septation protein SpoVG and ATP-dependent Clp protease proteolytic subunit. Further, in silico pathway analysis using DAVID and KOBAS has revealed modulation of pathways related to the fatty acid metabolism and cell wall synthesis, which are crucial for cell viability. Our findings revealed that curcumin treatment lead to inhibition of the cell wall and fatty acid synthesis in addition to differential expression of many crucial proteins involved in modulation of bacterial metabolism. Findings obtained from proteomics analysis were further validated using 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) assay for respiratory activity, resazurin assay for metabolic activity and membrane integrity assay by potassium and inorganic phosphate leakage measurement. The gene expression analysis of selected cell wall biosynthesis enzymes has strengthened the proteomics findings and indicated the major effect of curcumin on cell division

    CUORE: The first bolometric experiment at the ton scale for the search for neutrino-less double beta decay

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    The Cryogenic Underground Observatory for Rare Events (CUORE) is the most massive bolometric experiment searching for neutrino-less double beta (0νββ) decay. The detector consists of an array of 988 TeO crystals (742 kg) arranged in a compact cylindrical structure of 19 towers. This paper will describe the CUORE experiment, including the cryostat, and present the detector performance during the first year of running. Additional detail will describe the effort made in improving the energy resolution in the Te 0νββ decay region of interest (ROI) and the suppression of backgrounds. A description of work to lower the energy threshold in order to give CUORE the sensitivity to search for other rare events, such as dark matter, will also be provided. 2 13

    Results from the CUORE experiment

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    Neutrinoless double beta decay (0¿ßß) is a rare, second-order nuclear transition that occurs only if neutrinos are massive Majorana particles or through new physics beyond Standard Model. This process explicitly violates the lepton number (L) by two units and, therefore, the observation of 0¿ßß would demonstrate that L is not a symmetry of nature. Combined with flavour mixing and cosmological measurements, it can provide unique contraints on neutrino mass scale and establish whether neutrinos are Dirac or Majorana particles. The Cryogenic Underground Observatory for Rare Events (CUORE) is an experiment located at the LNGS searching for 0¿ßß decay of 130Te. CUORE exploits the bolometric technique to reach high resolution around the Q-value (2527.5 keV). It consists of an array of 988 natural TeO2 cubic crystals grouped into 19 towers. With a total active mass of 742 kg (~206 kg of 130Te), CUORE is operated at very low temperature with a new 3He/4He refrigerator. Data taking started at the beginning of 2017. After a brief introduction on the detector and the way data analysis is performed, I describe CUORE first results for the search of the 0¿ßß decay that were published in March 2018

    Perspectives of lowering CUORE thresholds with Optimum Trigger

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    CUORE is a cryogenic experiment that focuses on the search of neutrinoless double beta decay in 130Te and it is located at the Gran Sasso National Laboratories. Its detector consists of 988 TeO2 crystals operating at a base temperature of ~10 mK. It is the first ton-scale bolometric experiment ever realized for this purpose. Thanks to its large target mass and ultra-low background, the CUORE detector is also suitable for the search of other rare phenomena. In particular the low energy part of the spectra is interesting for the detection of WIMP-nuclei scattering reactions. One of the most important requirements to perform these studies is represented by the achievement of a stable energy threshold lower than 10 keV. Here, the CUORE capability to accomplish this purpose using a low energy software trigger will be presented and described
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