Comparison of various lazaroid compounds for protection against ischemic liver injury

Lazaroids are a group of 21-aminosteroids that lack steroid action but have a potent cytoprotective effect by inhibiting iron-dependent lipid peroxidation. However, there have been conflicting reports on the effectiveness and potency of the various lazaroid compounds. In this study, we compared the effectiveness of three major lazaroids on warm liver ischemia in dogs using a 2-hr hepatic vascular exclusion model. The agents were given to the animals intravenously for 30 min before ischemia. The animals were divided into 5 groups: Control (n=10), no treatment; Group F (n=6), U-74006F (10 mg/kg); Group G (n=6), U-74389G (10 mg/kg); Group A1 (n=6), U-74500A (10 mg/kg); Group A2 (n=6), U-74500A (5 mg/kg). The effect of treatment was evaluated by two-week animal survival, hepatic tissue blood flow, liver function tests, blood and tissue biochemistry, and histological analyses. Animal survival in all treated groups was significantly improved compared with the control (83-100% versus 30%). Elevation of liver enzymes after reperfusion was markedly attenuated in treated groups, except for an early significant increase in Group G. Postreperfusion hepatic tissue blood flow was much higher in all treated animals (50% of the preischemic level vs. 25% in the control). Lazaroids, particularly U-74500A at 5 mg/kg (Group A2), suppressed adenine nucleotide degradation during ischemia and enhanced the resynthesis of high-energy phosphates after reperfusion. Although structural abnormalities in postreperfusion liver tissues were markedly ameliorated in all treated groups, Group A2 showed significantly less neutrophil infiltration. Liver injury from warm ischemia and reperfusion was attenuated with all lazaroid compounds, of which U-74500A at 5 mg/kg exhibited the most significant protective activity

Integrated production and inventory routing planning of oxygen supply chains

In this work, we address a production and inventory routing problem for a liquid oxygen supply chain comprising production facilities, distribution network, and distribution resources. The key decisions of the problem involve production levels of production plants, delivery schedule and routing through heterogeneous vehicles, and inventory strategies for national stock-out prevention. Due to the problem complexity, we propose a two-level hybrid solution approach that solves the problem using both exact and metaheuristic methods. At the upper level, we develop a mixed-integer linear programming (MILP) model that determines production and inventory decisions and customer allocation. In the lower level, the original problem is reduced to several multi-trip heterogeneous vehicle routing problems by fixing the optimal production, inventory, and allocation decisions and clustering customers. A well-recognised metaheuristic, guided local search method, is adapted to solve the low-level routing problems. A real-world case study in the UK illustrates the applicability and effectiveness of the proposed optimisation framework

Strained graphene structures: from valleytronics to pressure sensing

Due to its strong bonds graphene can stretch up to 25% of its original size without breaking. Furthermore, mechanical deformations lead to the generation of pseudo-magnetic fields (PMF) that can exceed 300 T. The generated PMF has opposite direction for electrons originating from different valleys. We show that valley-polarized currents can be generated by local straining of multi-terminal graphene devices. The pseudo-magnetic field created by a Gaussian-like deformation allows electrons from only one valley to transmit and a current of electrons from a single valley is generated at the opposite side of the locally strained region. Furthermore, applying a pressure difference between the two sides of a graphene membrane causes it to bend/bulge resulting in a resistance change. We find that the resistance changes linearly with pressure for bubbles of small radius while the response becomes non-linear for bubbles that stretch almost to the edges of the sample. This is explained as due to the strong interference of propagating electronic modes inside the bubble. Our calculations show that high gauge factors can be obtained in this way which makes graphene a good candidate for pressure sensing.Comment: to appear in proceedings of the NATO Advanced Research Worksho

Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1

Cell-cell junctions are an integral part of epithelia and are often disrupted in cancer cells during epithelial-to-mesenchymal transition (EMT), which is a main driver of metastatic spread. We show here that Metastasis suppressor-1 (Mtss1; Missing in Metastasis, MIM), a member of the IMD-family of proteins, inhibits cell-cell junction disassembly in wound healing or HGF-induced scatter assays by enhancing cell-cell junction strength. Mtss1 not only makes cells more resistant to cell-cell junction disassembly, but also accelerates the kinetics of adherens junction assembly. Mtss1 drives enhanced junction formation specifically by elevating Rac-GTP. Lastly, we show that Mtss1 depletion reduces recruitment of F-actin at cell-cell junctions. We thus propose that Mtss1 promotes Rac1 activation and actin recruitment driving junction maintenance. We suggest that the observed loss of Mtss1 in cancers may compromise junction stability and thus promote EMT and metastasis

First direct observation of Dirac fermions in graphite

Originating from relativistic quantum field theory, Dirac fermions have been recently applied to study various peculiar phenomena in condensed matter physics, including the novel quantum Hall effect in graphene, magnetic field driven metal-insulator-like transition in graphite, superfluid in 3He, and the exotic pseudogap phase of high temperature superconductors. Although Dirac fermions are proposed to play a key role in these systems, so far direct experimental evidence of Dirac fermions has been limited. Here we report the first direct observation of massless Dirac fermions with linear dispersion near the Brillouin zone (BZ) corner H in graphite, coexisting with quasiparticles with parabolic dispersion near another BZ corner K. In addition, we report a large electron pocket which we attribute to defect-induced localized states. Thus, graphite presents a novel system where massless Dirac fermions, quasiparticles with finite effective mass, and defect states all contribute to the low energy electronic dynamics.Comment: Nature Physics, in pres

Reach the Bottom Line of the Sbottom Search

We propose a new search strategy for directly-produced sbottoms at the LHC with a small mass splitting between the sbottom and its decayed stable neutralino. Our search strategy is based on boosting sbottoms through an energetic initial state radiation jet. In the final state, we require a large missing transverse energy and one or two b-jets besides the initial state radiation jet. We also define a few kinematic variables to further increase the discovery reach. For the case that the sbottom mainly decays into the bottom quark and the stable neutralino, we have found that even for a mass splitting as small as 10 GeV sbottoms with masses up to around 400 GeV can be excluded at the 95% confidence level with 20 inverse femtobarn data at the 8 TeV LHC.Comment: 16 pages, 6 figure

Globular Cluster Distance Determinations

The present status of the distance scale to Galactic globular clusters is reviewed. Six distance determination techniques which are deemed to be most reliable are discussed in depth. These different techniques are used to calibrate the absolute magnitude of the RR Lyrae stars. The various calibrations fall into three groups. Main sequence fitting using Hipparcos parallaxes, theoretical HB models and the RR Lyrae in the LMC all favor a bright calibration, implying a `long' globular cluster distance scale. White dwarf fitting and the astrometric distances yield a somewhat fainter RR Lyrae calibration, while the statistical parallax solution yields faint RR Lyrae stars implying a `short' distance scale to globular clusters. Various secondary distance indicators discussed all favor the long distance scale. The `long' and `short' distance scales differ by (0.31+/-0.16) mag. Averaging together all of the different distance determinations yields Mv(RR) = (0.23+/-0.04)([Fe/H] + 1.6) + (0.56+/-0.12) mag.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in pres

Direct Evidence for Dominant Bond-directional Interactions in a Honeycomb Lattice Iridate Na2IrO3

Heisenberg interactions are ubiquitous in magnetic materials and have been prevailing in modeling and designing quantum magnets. Bond-directional interactions offer a novel alternative to Heisenberg exchange and provide the building blocks of the Kitaev model, which has a quantum spin liquid (QSL) as its exact ground state. Honeycomb iridates, A2IrO3 (A=Na,Li), offer potential realizations of the Kitaev model, and their reported magnetic behaviors may be interpreted within the Kitaev framework. However, the extent of their relevance to the Kitaev model remains unclear, as evidence for bond-directional interactions remains indirect or conjectural. Here, we present direct evidence for dominant bond-directional interactions in antiferromagnetic Na2IrO3 and show that they lead to strong magnetic frustration. Diffuse magnetic x-ray scattering reveals broken spin-rotational symmetry even above Neel temperature, with the three spin components exhibiting nano-scale correlations along distinct crystallographic directions. This spin-space and real-space entanglement directly manifests the bond-directional interactions, provides the missing link to Kitaev physics in honeycomb iridates, and establishes a new design strategy toward frustrated magnetism.Comment: Nature Physics, accepted (2015