Triglyceride-rich lipoproteins prevent septic death in rats.

Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P < or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P < or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P < or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P < or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P < or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis

Fluvoxamine for aripiprazole-associated akathisia in patients with schizophrenia: a potential role of sigma-1 receptors

<p>Abstract</p> <p>Background</p> <p>Second-generation antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPSs) than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interplay of several neurotransmitter systems might play a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors are shown to regulate a number of neurotransmitter systems in the brain.</p> <p>Methods</p> <p>We report on two cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the antipsychotic drug aripiprazole.</p> <p>Results</p> <p>The global score on the Barnes Akathisia Scale in the two patients with schizophrenia treated with aripiprazole decreased after fluvoxamine monotherapy.</p> <p>Conclusion</p> <p>Doctors may wish to consider fluvoxamine as an alternative approach in treating akathisia associated with antipsychotic drugs such as aripiprazole.</p

Free Will in a Quantum World?

In this paper, I argue that Conway and Kochen’s Free Will Theorem (1,2) to the conclusion that quantum mechanics and relativity entail freedom for the particles, does not change the situation in favor of a libertarian position as they would like. In fact, the theorem more or less implicitly assumes that people are free, and thus it begs the question. Moreover, it does not prove neither that if people are free, so are particles, nor that the property people possess when they are said to be free is the same as the one particles possess when they are claimed to be free. I then analyze the Free State Theorem (2), which generalizes the Free Will Theorem without the assumption that people are free, and I show that it does not prove anything about free will, since the notion of freedom for particles is either inconsistent, or it does not concern our common understanding of freedom. In both cases, the Free Will Theorem and the Free State Theorem do not provide any enlightenment on the constraints physics can pose on free will

Scanning-probe spectroscopy of semiconductor donor molecules

Semiconductor devices continue to press into the nanoscale regime, and new applications have emerged for which the quantum properties of dopant atoms act as the functional part of the device, underscoring the necessity to probe the quantum structure of small numbers of dopant atoms in semiconductors[1-3]. Although dopant properties are well-understood with respect to bulk semiconductors, new questions arise in nanosystems. For example, the quantum energy levels of dopants will be affected by the proximity of nanometer-scale electrodes. Moreover, because shallow donors and acceptors are analogous to hydrogen atoms, experiments on small numbers of dopants have the potential to be a testing ground for fundamental questions of atomic and molecular physics, such as the maximum negative ionization of a molecule with a given number of positive ions[4,5]. Electron tunneling spectroscopy through isolated dopants has been observed in transport studies[6,7]. In addition, Geim and coworkers identified resonances due to two closely spaced donors, effectively forming donor molecules[8]. Here we present capacitance spectroscopy measurements of silicon donors in a gallium-arsenide heterostructure using a scanning probe technique[9,10]. In contrast to the work of Geim et al., our data show discernible peaks attributed to successive electrons entering the molecules. Hence this work represents the first addition spectrum measurement of dopant molecules. More generally, to the best of our knowledge, this study is the first example of single-electron capacitance spectroscopy performed directly with a scanning probe tip[9].Comment: In press, Nature Physics. Original manuscript posted here; 16 pages, 3 figures, 5 supplementary figure

Physics Opportunities of e+e- Linear Colliders

We describe the anticipated experimental program of an e+e- linear collider in the energy range 500 GeV -- 1.5 TeV. We begin with a description of current collider designs and the expected experimental environment. We then discuss precision studies of the W boson and top quark. Finally, we review the range of models proposed to explain the physics of electroweak symmetry breaking and show, for each case, the central role that the linear collider experiments will play in elucidating this physics. (to appear in Annual Reviews of Nuclear and Particle Science)Comment: 93 pages, latex + 23 figures; typos corrections + 1 reference adde

Zebrafish Mutants calamity and catastrophe Define Critical Pathways of Gene–Nutrient Interactions in Developmental Copper Metabolism

Nutrient availability is an important environmental variable during development that has significant effects on the metabolism, health, and viability of an organism. To understand these interactions for the nutrient copper, we used a chemical genetic screen for zebrafish mutants sensitive to developmental copper deficiency. In this screen, we isolated two mutants that define subtleties of copper metabolism. The first contains a viable hypomorphic allele of atp7a and results in a loss of pigmentation when exposed to mild nutritional copper deficiency. This mutant displays incompletely penetrant skeletal defects affected by developmental copper availability. The second carries an inactivating mutation in the vacuolar ATPase that causes punctate melanocytes and embryonic lethality. This mutant, catastrophe, is sensitive to copper deprivation revealing overlap between ion metabolic pathways. Together, the two mutants illustrate the utility of chemical genetic screens in zebrafish to elucidate the interaction of nutrient availability and genetic polymorphisms in cellular metabolism

Transport in topological insulator nanowires

In this chapter we review our work on the theory of quantum transport in topological insulator nanowires. We discuss both normal state properties and superconducting proximity effects, including the effects of magnetic fields and disorder. Throughout we assume that the bulk is insulating and inert, and work with a surface-only theory. The essential transport properties are understood in terms of three special modes: in the normal state, half a flux quantum along the length of the wire induces a perfectly transmitted mode protected by an effective time reversal symmetry; a transverse magnetic field induces chiral modes at the sides of the wire, with different chiralities residing on different sides protecting them from backscattering; and, finally, Majorana zero modes are obtained at the ends of a wire in a proximity to a superconductor, when combined with a flux along the wire. Some parts of our discussion have a small overlap with the discussion in the review [Bardarson and Moore, Rep. Prog. Phys., 76, 056501, (2013)]. We do not aim to give a complete review of the published literature, instead the focus is mainly on our own and directly related work.Comment: 22 pages, 8 figures; Chapter in "Topological Matter. Springer Series in Solid-State Sciences, vol 190. Springer

A Comprehensive Analysis of Electric Dipole Moment Constraints on CP-violating Phases in the MSSM

We analyze the constraints placed on individual, flavor diagonal CP-violating phases in the minimal supersymmetric extension of the Standard Model (MSSM) by current experimental bounds on the electric dipole moments (EDMs) of the neutron, Thallium, and Mercury atoms. We identify the four CP-violating phases that are individually highly constrained by current EDM bounds, and we explore how these phases and correlations among them are constrained by current EDM limits. We also analyze the prospective implications of the next generation of EDM experiments. We point out that all other CP-violating phases in the MSSM are not nearly as tightly constrained by limits on the size of EDMs. We emphasize that a rich set of phenomenological consequences is potentially associated with these generically large EDM-allowed phases, ranging from B physics, electroweak baryogenesis, and signals of CP-violation at the CERN Large Hadron Collider and at future linear colliders. Our numerical study takes into account the complete set of contributions from one- and two-loop EDMs of the electron and quarks, one- and two-loop Chromo-EDMs of quarks, the Weinberg 3-gluon operator, and dominant 4-fermion CP-odd operator contributions, including contributions which are both included and not included yet in the CPsuperH2.0 package. We also introduce an open-source numerical package, 2LEDM, which provides the complete set of two-loop electroweak diagrams contributing to the electric dipole moments of leptons and quarks.Comment: 23 pages, 11 figures; v2: references added, minor change

Holographic Conductivity in Disordered Systems

The main purpose of this paper is to holographically study the behavior of conductivity in 2+1 dimensional disordered systems. We analyze probe D-brane systems in AdS/CFT with random closed string and open string background fields. We give a prescription of calculating the DC conductivity holographically in disordered systems. In particular, we find an analytical formula of the conductivity in the presence of codimension one randomness. We also systematically study the AC conductivity in various probe brane setups without disorder and find analogues of Mott insulators.Comment: 43 pages, 28 figures, latex, references added, minor correction