Entropic long range order in a 3D spin glass model

We uncover a new kind of entropic long range order in finite dimensional spin glasses. We study the link-diluted version of the Edwards-Anderson spin glass model with bimodal couplings (J=+/-1) on a 3D lattice. By using exact reduction algorithms, we prove that there exists a region of the phase diagram (at zero temperature and link density low enough), where spins are long range correlated, even if the ground states energy stiffness is null. In other words, in this region twisting the boundary conditions cost no energy, but spins are long range correlated by means of pure entropic effects.Comment: 15 pages, 6 figures. v3: added a phase diagram for ferromagnetically biased coupling

Application of CFD and mass-consistent models for operational wind forecasting

In the context of the San Paolo project "Wind monitoring, simulation and forecasting for the smart management and safety of port, urban and territorial system", a computational grid of Livorno City (Italy) and its surroundings at full scale has been constructed for 3D steady-state RANS simulations to be performed by the open-source code OpenFOAM. Field measurements in the same urban area have been scheduled between December 2017 and March 2018 in order to cover the entire winter season, i.e. the windiest one. The CFD results, obtained by initialising the CFD simulations with wind profiles measured through a LiDAR installed in the Port of Livorno, have been validated by means of two ultrasonic three-axial anemometers installed along a narrow canal which is located in the old city centre, about 1.5 km south-westward of the port area

Uncertainty inequalities on groups and homogeneous spaces via isoperimetric inequalities

We prove a family of $L^p$ uncertainty inequalities on fairly general groups and homogeneous spaces, both in the smooth and in the discrete setting. The crucial point is the proof of the $L^1$ endpoint, which is derived from a general weak isoperimetric inequality.Comment: 17 page

CD95/CD95L interactions and their role in autoimmunity

CD95 (Fas/Apo-1) is a broadly expressed death receptor involved in a variety of physiological and pathological apoptotic processes. Since its discovery, defects in CD95/CD95L system have been proposed as major pathogenic factors responsible for impaired immunological tolerance to self antigens and autoimmunity. Later, analysis of altered sensitivity to CD95-induced apoptosis in cells targeted by the immune response has revealed an unexpected role for CD95 and CD95L in organ-specific autoimmunity. CD95 has been shown to be expressed and functional in virtually all cell types that are target of the organ-specific autoimmune response. Here we review some of the major findings concerning the role of CD95 in autoimmunity, in dysfunctions due to increased or decreased CD95-induced apoptosis

Death in 2000 ways

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A multistate epidemic outbreak of Salmonella Goldcoast infection in humans, June 2009 to March 2010: the investigation in Italy.

After an urgent inquiry into a suspected international outbreak of Salmonella Goldcoast infection was launched by Hungary in October 2009 a nation-wide multidisciplinary investigation was carried out in Italy. The aims were to verify whether the higher than expected number of cases of S. Goldcoast infection that had occurred in Italy in the previous months were linked to the outbreak in Hungary and to determine their origin. Between June 2009 and March 2010, 79 confirmed cases of S. Goldcoast infection were identified. Of these, 17 were part of three different point-source outbreaks probably associated with the consumption of salami. Eating salami was also reported by 20 of the 39 sporadic cases that could be interviewed. Fifteen strains of S. Goldcoast isolated from the cases were typed by pulsed-field gel electrophoresis. They shared more than 90% homology with the Hungarian epidemic strain and were also highly similar to S. Goldcoast strains that had been isolated in Italy from pigs and pork-containing food items in 2009 and 2010. Although the origin of the outbreak and the common source linking the Hungarian and the Italian cases could not be definitively identified, our results suggest a possible zoonotic connection of the outbreak cases with the pork production chain

Differential Regulation of HIV-1 Clade-Specific B, C, and E Long Terminal Repeats by NF-κB and the Tat Transactivator

AbstractThe major group of human immunodeficiency viruses (HIV-1) that comprise the current global pandemic have diversified during their worldwide spread and may be divided into at least 10 distinct subtypes or clades, A through J. Subtype B predominates in North America and Europe, subtype E predominates in Southeast Asia, and subtype C predominates in sub-Saharan Africa. Functional distinctions in long terminal repeat (LTR) architecture among HIV subtypes have been identified, thus raising the possibility that regulatory divergence among the subtypes of HIV-1 has occurred. In addition to the transcriptional specificity of the HIV-1 LTR, productive HIV-1 replication is also dependent upon the viral Tat protein. Therefore, we sought to investigate whether interactions between host signaling pathways and the NF-κB regions of different HIV-1 subtypes, together with subtype-specific interactions between Tat, TAR, and cellular proteins, modulate the efficiency of HIV-1 clade-specific gene transcription. We demonstrate that the NF-κB sites of subtypes B and E both bind NF-κB-related complexes. However, the duplicated κB sites of the C subtype do not compete for NF-κB binding. Also, clade E Tat protein possesses the highest transactivation capacity, regardless of the LTR context. Furthermore, preliminary evidence suggests that the acetylation of subtype-specific Tat proteins may correlate with their transactivation efficiency

Catalytic mechanism and role of hydroxyl residues in the active site of theta class Glutathione-S-Transferases: Investigation of Ser-9 and Tyr-113 in a Glutathione S-Transferase from the australian sheep blowfly Lucilia cuprina

Abstract Spectroscopic and kinetic studies have been performed on the Australian sheep blowfly Lucilia cuprina glutathione S-transferase (Lucilia GST; EC 2.5.1.18) to clarify its catalytic mechanism. Steady state kinetics of Lucilia GST are non-Michaelian, but the quite hyperbolic isothermic binding of GSH suggests that a steady state random sequential Bi Bi mechanism is consistent with the anomalous kinetics observed. The rate-limiting step of the reaction is a viscosity-dependent physical event, and stopped-flow experiments indicate that product release is rate-limiting. Spectroscopic and kinetic data demonstrate thatLucilia GST is able to lower the pK a of the bound GSH from 9.0 to about 6.5. Based on crystallographic suggestions, the role of two hydroxyl residues, Ser-9 and Tyr-113, has been investigated. Removal of the hydroxyl group of Ser-9 by site-directed mutagenesis raises the pK a of bound GSH to about 7.6, and a very low turnover number (about 0.5% of that of wild type) is observed. This inactivation may be explained by a strong contribution of the Ser-9 hydroxyl group to the productive binding of GSH and by an involvement in the stabilization of the ionized GSH. This serine residue is highly conserved in the Theta class GSTs, so the present findings may be applicable to all of the family members. Tyr-113 appears not to be essential for the GSH activation. Stopped-flow data indicate that removal of the hydroxyl group of Tyr-113 does not change the rate-limiting step of reaction but causes an increase of the rate constants of both the formation and release of the GSH conjugate. Tyr-113 resides on α-helix 4, and its hydroxyl group hydrogen bonds directly to the hydroxyl of Tyr-105. This would reduce the flexibility of a protein region that contributes to the electrophilic substrate binding site; segmental motion of α-helix 4 possibly modulates different aspects of the catalytic mechanism of theLucilia GST

A strong glutathione S-transferase inhibitor overcomes the P-glycoprotein-mediated resistance in tumor cells - 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) triggers a caspase-dependent apoptosis in MDR1-expressing leukemia cells

The new glutathione S-transferase inhibitor 6-(7-nitro-2,1,3-benzoxadiazol- 4-ylthio)hexanol (NBDHEX) is cytotoxic toward P-glycoprotein-overexpressing tumor cell lines, i.e. CEM-VBL10, CEM-VBL100, and U-2 OS/DX580. The mechanism of cell death triggered by NBDHEX has been deeply investigated in leukemia cell lines. Kinetic data indicate a similar NBDHEX membrane permeability between multidrug resistance cells and their sensitive counterpart revealing that NBDHEX is not a substrate of the P-glycoprotein export pump. Unexpectedly, this molecule promotes a caspase-dependent apoptosis that is unusual in the P-glycoprotein-overexpressing cells. The primary event of the apoptotic pathway is the dissociation of glutathione S-transferase P1-1 from the complex with c-Jun N-terminal kinase. Interestingly, leukemia MDR1-expressing cells show lower LC50 values and a higher degree of apoptosis and caspase-3 activity than their drug-sensitive counterparts. The increased susceptibility of the multidrug resistance cells toward the NBDHEX action may be related to a lower content of glutathione S-transferase P1-1. Given the low toxicity of NBDHEX in vivo, this compound may represent an attractive basis for the selective treatment of MDR1 P-glycoproteinpositive tumors