712 research outputs found

    Pace privata e regolamentazione della vendetta in Valdinievole

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    Lot Sizing Heuristics Performance

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    Each productive system manager knows that finding the optimal trade‐off between reducing inventory and decreasing the frequency of production/ replenishment orders allows a great cut‐back in operations costs. Several authors have focused their contributions, trying to demonstrate that among the various dynamic lot sizing rules there are big differences in terms of performance, and that these differences are not negligible. In this work, eight of the best known lot sizing algorithms have been described with a unique modelling approach and have then been exhaustively tested on several different scenarios, benchmarking versus Wagner and Whitin’s optimal solution. As distinct from the contributions in the literature, the operational behaviour has been evaluated in order to determine which one is more suitable to the characteristics of each scenario

    long term administration of low doses of mycotoxins in poultry 1 residues of ochratoxin a in broilers and laying hens

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    Abstract The occurrence and amount of residues of ochratoxin A (OA) in poultry tissues and organs were investigated in a trial aimed at measuring the effects of contamination approaching the patterns more frequently found in natural situations (i.e., small doses of OA in the diet for long periods). Hubbard male broilers and laying hens were treated with an OA-contaminated feed (50 ppb) from the 14th day of age onward. Both groups were further divided into subgroups, some of which underwent continual treatment (64 and 169 days, respectively) and others that were withdrawn from administration (maximum 28 and 82 days, respectively). Determination of residues was performed by high performance liquid chromatography. Residues in liver were higher in broilers (up to 11.0 ppb) than in hens (1.5 ppb), whereas the reverse occurred in kidney (up to .8 and 5.8 ppb, respectively). Residues (.8 ppb) were also in hen thigh muscle but not in breast muscle. Residues of OA in poultry appear to be of possible public health concern. Suggestions for monitoring are given

    Picosecond Internal Dynamics of Lysozyme as Affected by Thermal Unfolding in Nonaqueous Environment

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    AbstractA neutron-scattering investigation of the internal picosecond dynamics of lysozyme solvated in glycerol as a function of temperature in the range 200–410K has been undertaken. The inelastic contribution to the measured intensity is characterized by the presence of a bump generally known as “boson peak”, clearly distinguishable at low temperature. When the temperature is increased the quasielastic component of the spectrum becomes more and more intrusive and progressively overwhelms the vibrational bump. This happens especially for T>345K when the protein goes through an unfolding process, which leads to the complete denaturation. The quasielastic term is the superposition of two components whose intensities and linewidths have been studied as a function of temperature. The slower component describes motions with characteristic times of ∼4ps corresponding to reorientations of polypeptide side chains. Both the intensity and linewidth of this kind of relaxations show two distinct regimes with a crossover in the temperature range where the melting process occurs, thus suggesting the presence of a dynamical transition correlated to the protein unfolding. Conversely the faster component might be ascribed to the local dynamics of hydrogen atoms caged by the nearest neighbors with characteristic time of ∼0.3ps

    SMN protein promotes membrane compartmentalization of ribosomal protein S6 transcript in human fibroblasts

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    Alterations of RNA homeostasis can lead to severe pathological conditions. The Survival of Motor Neuron (SMN) protein, which is reduced in Spinal Muscular Atrophy, impacts critical aspects of the RNA life cycle, such as splicing, trafficking, and translation. Increasing evidence points to a potential role of SMN in ribosome biogenesis. Our previous study revealed that SMN promotes membrane-bound ribosomal proteins (RPs), sustaining activity-dependent local translation. Here, we suggest that plasma membrane domains could be a docking site not only for RPs but also for their encoding transcripts. We have shown that SMN knockdown perturbs subcellular localization as well as translation efficiency of RPS6 mRNA. We have also shown that plasma membrane-enriched fractions from human fibroblasts retain RPS6 transcripts in an SMN-dependent manner. Furthermore, we revealed that SMN traffics with RPS6 mRNA promoting its association with caveolin-1, a key component of membrane dynamics. Overall, these findings further support the SMN-mediated crosstalk between plasma membrane dynamics and translation machinery. Importantly, our study points to a potential role of SMN in the ribosome assembly pathway by selective RPs synthesis/localization in both space and time

    The Hepatic Microcirculation in Experimental Cirrhosis a Scanning Electron Microscopy Study of Microcorrosion Casts

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    The experimental model of liver cirrhosis induced by intragastric administration of CCl4 reproduces not only the histological picture of the postnecrotic cirrhosis but also its pathophysiological features. Corrosion casts of livers affected by CCl4-induced cirrhosis show the loss of the lobular pattern. Once the cirrhosis has completely developed, the whole microvascular bed appears to be composed of groups of sinusoid nodules of diameters varying between 0.3 and 1.5 mm.. Pre- and post-sinusoidal vessels and anastomoses between the former and the latter are mainly located at the perinodular spaces. This microvascular situation modifies the normal perfusion gradient within the parenchyma. Nevertheless, it can allow a still viable function

    H3 histamine receptor-mediated activation of protein kinase calpha inhibits the growth of cholangiocarcinoma in vitro and in vivo

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    Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The D-myo-inositol 1,4,5-trisphosphate (IP(3))/Ca(2+)/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(alpha)-(-)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP(3) and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKC alpha was visualized by immunofluorescence in cell smears and immunoblotting for PKC alpha in cytosol and membrane fractions. Following knockdown of PKC alpha, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKC alpha, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP(3) levels and PKC alpha phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKC alpha expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKC alpha prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKC alpha expression was increased. RAMH inhibits cholangiocarcinoma growth by PKC alpha-dependent ERK1/2 dephosphorylation. Modulation of PKC alpha by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res 2009;7(10):1704-13

    Electron paramagnetic resonance (EPR) in medical dosimetry

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    This paper describes the fundamentals of electron paramagnetic resonance (EPR) and its application to retrospective measurements of clinically significant doses of ionizing radiation. X-band is the most widely used in EPR dosimetry because it represents a good compromise between sensitivity, sample size and water content in the sample. Higher frequency bands (e.g., W and Q) provide higher sensitivity, but they are also greatly influenced by water content. L and S bands can be used for EPR measurements in samples with high water content but they are less sensitive than X-band. Quality control for therapeutic radiation facilities using X-band EPR spectrometry of alanine is also presented

    Quasi-simultaneous INTEGRAL, SWIFT, and NuSTAR Observations of the New X-Ray Clocked Burster 1RXS J180408.9-342058

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    We report the quasi-simultaneous INTEGRAL, SWIFT, and NuSTAR observations showing spectral state transitions in the neutron star low-mass X-ray binary 1RXS J180408.9−342058 during its 2015 outburst. We present results of the analysis of high-quality broad energy band (0.8–200 keV) data in three different spectral states: high/soft, low/very-hard, and transitional state. The broadband spectra can be described in general as the sum of thermal Comptonization and reflection due to illumination of an optically thick accretion disk. During the high/soft state, blackbody emission is generated from the accretion disk and the surface of the neutron star. This emission, measured at a temperature of kT_(bb) ~ 1.2 keV, is then Comptonized by a thick corona with an electron temperature of ~2.5 keV. For the transitional and low/very-hard state, the spectra are successfully explained with emission from a double Comptonizing corona. The first component is described by thermal Comptonization of seed disk/neutron star photons (kT_(bb) ~ 1.2 keV) by a cold corona cloud with kT_e ~ 8–10 keV, while the second one originates from lower temperature blackbody photons (kT_(bb) ≤ 0.1 keV) Comptonized by a hot corona (kT_e ~ 35 keV). Finally, from NuSTAR observations, there is evidence that the source is a new clocked burster. The average time between two successive X-ray bursts corresponds to ~7.9 and ~4.0 ks when the persistent emission decreases by a factor of ~2, moving from a very hard to transitional state. The accretion rate (~4 x 10⁻⁹ M⊙ yr ⁻¹) and the decay time of the X-ray bursts longer than ~30 s suggest that the thermonuclear emission is due to mixed H/He burning triggered by thermally unstable He ignition
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