Differential Conductance Measurements of MgB2-Based Josephson Junctions Below 1 Kelvin

Magnesium diboride has many intriguing characteristics, including its relatively high critical temperature and two-band nature. Most prior studies of MgB2 thin film Josephson junctions have been conducted above 2 Kelvin. We report results of sub-1 Kelvin experiments of MgB2/insulator/Pb junctions whose a-b plane is exposed for electron tunneling. By measuring differential conductance at low temperature, new details in the structure of the sigma- and pi-band gaps are observed in this data, consistent with theoretical predictions.Comment: ASC 2010 Conferenc

Branes and Calibrated Geometries

The fivebrane worldvolume theory in eleven dimensions is known to contain BPS threebrane solitons which can also be interpreted as a fivebrane whose worldvolume is wrapped around a Riemann surface. By considering configurations of intersecting fivebranes and hence intersecting threebrane solitons, we determine the Bogomol'nyi equations for more general BPS configurations. We obtain differential equations, generalising Cauchy-Riemann equations, which imply that the worldvolume of the fivebrane is wrapped around a calibrated geometry.Comment: Latex, 35 pages. References added, minor change

Evaluation of procalcitonin and CRP as sepsis markers in 74 consecutive patients admitted with prolonged febrile neutropenia

International audienceFever is a major event in critically ill patients. Its causes are difficult to identify and among them, bacterial infections must be rapidly identified and treated before sepsis reach a life threatening stage. CRP is a very sensitive marker of inflammation of whatever causes including sepsis. This is particularly crucial in immunocompromised patients. On the other hand, PCT has been extensively shown to be strongly and rapidly produced in bacterial infections only. Furthermore, PCT decreases very soon after bacterial resolution, and is thus a very useful in monitoring adequacy and efficiency of antibiotics. The utility of this marker in sever sepsis is now widely admitted

Early life stress influences acute and sensitised responses of adult mice to cocaine by interacting with GABAA α2 receptor expression

Early life stress (ELS) is known to exert long term effects on brain function, with resulting deleterious consequences for several aspects of mental health, including the development of addiction to drugs of abuse. One potential mechanism in humans is suggested by findings that ELS interacts with polymorphisms of the GABRA2 gene, encoding alpha2 subunits of GABAA receptors, to increase risk for both posttraumatic stress disorder, and vulnerability to cocaine addiction. We used a mouse model, in which the amount of material for nest building was reduced during early postnatal life, to study interactions between ELS and expression of alpha2-containing GABAA receptors in influencing cocaine-related behaviour. Breeding of parents heterozygous for deletion of alpha2 resulted in litters containing homozygous knockout (alpha2-/-), heterozygous knockout (alpha2+/-), and wildtype (alpha2+/+) offspring. Following the ELS procedure, the mice were allowed to develop to adulthood before being tested for the acute effect of cocaine on locomotor stimulation, behavioural sensitisation to repeated cocaine, and to cocaine-conditioned activity. Exposure to ELS resulted in increased acute locomotor stimulant effects of cocaine across all genotypes, with the most marked effects in alpha2-/- mice (which also showed increased activity following vehicle). Repeated cocaine administration to non-stressed mice resulted in sensitisation in alpha2+/+ and alpha2+/- mice, but, in keeping with previous findings, not in alpha2-/- mice. Prior exposure to ELS reduced sensitisation in alpha2+/+ mice, albeit not significantly, and abolished sensitisation in alpha2+/- mice. Conditioned activity was elevated following ELS in all animals, independently of genotype. Thus, while the enhanced acute effects of cocaine following ELS being most marked in alpha2-/- mice suggests a function of alpha2-containing GABAA receptors in protecting against stress, the interaction between ELS and genotype in influencing sensitisation may be more in keeping with ELS reducing expression of alpha2-containing GABAA receptors. The ability of ELS to increase cocaine-conditioned locomotor activity appears to be independent of alpha2-containing GABAA receptors

During postnatal development endogenous neurosteroids influence GABA-ergic neurotransmission of mouse cortical neurons

AbstractAs neuronal development progresses, GABAergic synaptic transmission undergoes a defined program of reconfiguration. For example, GABAA receptor (GABAAR)-mediated synaptic currents, (miniature inhibitory postsynaptic currents; mIPSCs), which initially exhibit a relatively slow decay phase, become progressively reduced in duration, thereby supporting the temporal resolution required for mature network activity. Here we report that during postnatal development of cortical layer 2/3 pyramidal neurons, GABAAR-mediated phasic inhibition is influenced by a resident neurosteroid tone, which wanes in the second postnatal week, resulting in the brief phasic events characteristic of mature neuronal signalling. Treatment of cortical slices with the immediate precursor of 5α-pregnan-3α-ol-20-one (5α3α), the GABAAR-inactive 5α-dihydroprogesterone, (5α-DHP), greatly prolonged the mIPSCs of P20 pyramidal neurons, demonstrating these more mature neurons retain the capacity to synthesize GABAAR-active neurosteroids, but now lack the endogenous steroid substrate. Previously, such developmental plasticity of phasic inhibition was ascribed to the expression of synaptic GABAARs incorporating the α1 subunit. However, the duration of mIPSCs recorded from L2/3 cortical neurons derived from α1 subunit deleted mice, were similarly under the developmental influence of a neurosteroid tone. In addition to principal cells, synaptic GABAARs of L2/3 interneurons were modulated by native neurosteroids in a development-dependent manner. In summary, local neurosteroids influence synaptic transmission during a crucial period of cortical neurodevelopment, findings which may be of importance for establishing normal network connectivity

Constraining Maximally Supersymmetric Membrane Actions

We study the recent construction of maximally supersymmetric field theory Lagrangians in three spacetime dimensions that are based on algebras with a triple product. Assuming that the algebra has a positive definite metric compatible with the triple product, we prove that the only non-trivial examples are either the well known case based on a four dimensional algebra or direct sums thereof.Comment: 11 pages, very minor changes. Reference added. Version to be published in JHE

Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer's patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability

The author's final peer reviewed version can be found by following the URI link. The Publisher's final version can be found by following the DOI link.Aims Amyloid β oligomers (AβO) are potent modulators of Alzheimer’s pathology, yet their impact on one of the earliest brain regions to exhibit signs of the condition, the locus coeruleus (LC), remains to be determined. Of particular importance is whether AβO impact the spontaneous excitability of LC neurons. This parameter determines brain‐wide noradrenaline (NA) release, and thus NA‐mediated brain functions, including cognition, emotion and immune function, which are all compromised in Alzheimer’s. Therefore, the aim of the study was to determine the expression profile of AβO in the LC of Alzheimer’s patients and to probe their potential impact on the molecular and functional correlates of LC excitability, using a mouse model of increased Aβ production (APP‐PSEN1). Methods and Results Immunohistochemistry and confocal microscopy, using AβO‐specific antibodies, confirmed LC AβO expression both intraneuronally and extracellularly in both Alzheimer’s and APP‐PSEN1 samples. Patch clamp electrophysiology recordings revealed that APP‐PSEN1 LC neuronal hyperexcitability accompanied this AβO expression profile, arising from a diminished inhibitory effect of GABA, due to impaired expression and function of the GABA‐A receptor (GABAAR) α3 subunit. This altered LC α3‐GABAAR expression profile overlapped with AβO expression in samples from both APP‐PSEN1 mice and Alzheimer’s patients. Finally, strychnine‐sensitive glycine receptors (GlyRs) remained resilient to Aβ‐induced changes and their activation reversed LC hyperexcitability. Conclusions The data suggest a close association between AβO and α3‐GABAARs in the LC of Alzheimer’s patients, and their potential to dysregulate LC activity, thereby contributing to the spectrum of pathology of the LC‐NA system in this condition

D-brane Solitons in Supersymmetric Sigma-Models

Massive D=4 N=2 supersymmetric sigma models typically admit domain wall (Q-kink) solutions and string (Q-lump) solutions, both preserving 1/2 supersymmetry. We exhibit a new static 1/4 supersymmetric `kink-lump' solution in which a string ends on a wall, and show that it has an effective realization as a BIon of the D=4 super DBI-action. It is also shown to have a time-dependent Q-kink-lump generalization which reduces to the Q-lump in a limit corresponding to infinite BI magnetic field. All these 1/4 supersymmetric sigma-model solitons are shown to be realized in M-theory as calibrated, or `Q-calibrated', M5-branes in an M-monopole background.Comment: 16 pages, 3 figures, Late