Evaluation of the therapeutic potential of ant-TLR4-antibody MTS510 in experimental stroke and significa of different routes of application

Toll-like receptors (TLRs) are central sensors for the inflammatory response in ischemia-reperfusion injury. We therefore investigated whether TLR4 inhibition could be used to treat stroke in a standard model of focal cerebral ischemia. Anti-TLR4/MD2-antibody (mAb clone MTS510) blocked TLR4-induced cell activation in vitro, as reported previously. Here, different routes of MTS510 application in vivo were used to study the effects on stroke outcome up to 2d after occlusion of the middle cerebral artery (MCAO) for 45 min in adult male C57Bl/6 wild-type mice. Improved neurological performance, reduced infarct volumes, and reduced brain swelling showed that intravascular application of MTS510 had a protective effect in the model of 45 min MCAO. Evaluation of potential long-term adverse effects of anti-TLR4-mAb-treament revealed no significant deleterious effect on infarct volumes nor neurological deficit after 14d of reperfusion in a mild model of stroke (15 min MCAO). Interestingly, inhibition of TLR4 resulted in an altered adaptive immune response at 48 hours after reperfusion. We conclude that blocking TLR4 by the use of specific mAb is a promising strategy for stroke therapy. However, long-term studies with increased functional sensitivity, larger sampling sizes and use of other species are required before a clinical use could be envisaged

Combined Electroweak Analysis

Recent developments in the measurement of precision electroweak measurements are summarised, notably new results on the mass of the top quark and mass and width of the W boson. Predictions of the Standard Model are compared to the experimental results which are used to constrain the input parameters of the Standard Model, in particular the mass of the Higgs boson. The agreement between measurements and expectations from theory is discussed. Invited talk presented at the EPS HEP 2007 conference Manchester, England, July 19th to 25th, 2007Comment: 7 pages and 6 figure

The Eliashberg Function of Amorphous Metals

A connection is proposed between the anomalous thermal transport properties of amorphous solids and the low-frequency behavior of the Eliashberg function. By means of a model calculation we show that the size and frequency dependence of the phonon mean-free-path that has been extracted from measurements of the thermal conductivity in amorphous solids leads to a sizeable linear region in the Eliashberg function at small frequencies. Quantitative comparison with recent experiments gives very good agreement.Comment: 4pp., REVTeX, 1 uuencoded ps fig. Original posting had a corrupted raw ps fig appended. Published as PRB 51, 689 (1995

On the structure of the energy distribution function in the hopping regime

The impact of the dispersion of the transport coefficients on the structure of the energy distribution function for charge carriers far from equilibrium has been investigated in effective-medium approximation for model densities of states. The investigations show that two regimes can be observed in energy relaxation processes. Below a characteristic temperature the structure of the energy distribution function is determined by the dispersion of the transport coefficients. Thermal energy diffusion is irrelevant in this regime. Above the characteristic temperature the structure of the energy distribution function is determined by energy diffusion. The characteristic temperature depends on the degree of disorder and increases with increasing disorder. Explicit expressions for the energy distribution function in both regimes are derived for a constant and an exponential density of states.Comment: 16 page

History-dependent relaxation and the energy scale of correlation in the Electron-Glass

We present an experimental study of the energy-relaxation in Anderson-insulating indium-oxide films excited far from equilibrium. In particular, we focus on the effects of history on the relaxation of the excess conductance dG. The natural relaxation law of dG is logarithmic, namely dG=-log(t). This may be observed over more than five decades following, for example, cool-quenching the sample from high temperatures. On the other hand, when the system is excited from a state S_{o} in which it has not fully reached equilibrium to a state S_{n}, the ensuing relaxation law is logarithmic only over time t shorter than the time t_{w} it spent in S_{o}. For times t>t_{w} dG(t) show systematic deviation from the logarithmic dependence. It was previously shown that when the energy imparted to the system in the excitation process is small, this leads to dG=P(t/t_{w}) (simple-aging). Here we test the conjecture that `simple-aging' is related to a symmetry in the relaxation dynamics in S_{o} and S_{n}. This is done by using a new experimental procedure that is more sensitive to deviations in the relaxation dynamics. It is shown that simple-aging may still be obeyed (albeit with a modified P(t/t_{w})) even when the symmetry of relaxation in S_{o} and S_{n} is perturbed by a certain degree. The implications of these findings to the question of aging, and the energy scale associated with correlations are discussed

Cryo-Electron Tomographic Structure of an Immunodeficiency Virus Envelope Complex In Situ

The envelope glycoprotein (Env) complexes of the human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate viral entry and are a target for neutralizing antibodies. The receptor binding surfaces of Env are in large part sterically occluded or conformationally masked prior to receptor binding. Knowledge of the unliganded, trimeric Env structure is key for an understanding of viral entry and immune escape, and for the design of vaccines to elicit neutralizing antibodies. We have used cryo-electron tomography and averaging to obtain the structure of the SIV Env complex prior to fusion. Our result reveals novel details of Env organisation, including tight interaction between monomers in the gp41 trimer, associated with a three-lobed, membrane-distal gp120 trimer. A cavity exists at the gp41–gp120 trimer interface. Our model for the spike structure agrees with previously predicted interactions between gp41 monomers, and furthers our understanding of gp120 interactions within an intact spike

Tunneling anisotropic magnetoresistance in organic spin valves

We report the observation of tunneling anisotropic magnetoresistance (TAMR) in an organic spin-valve-like structure with only one ferromagnetic electrode. The device is based on a new high mobility perylene diimide-based n-type organic semiconductor. The effect originates from the tunneling injection from the LSMO contact and can thus occur even for organic layers which are too thick to support the assumption of tunneling through the layer. Magnetoresistance measurements show a clear spin-valve signal, with the typical two step switching pattern caused by the magnetocrystalline anisotropy of the epitaxial magnetic electrode.Comment: 10 pages 5 figures Paper has been rewritten, new results have been adde