Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model.

Multiple sclerosis (MS) is characterized by central nervous system (CNS) inflammation, demyelination, and axonal degeneration. CXCL10 (IP-10), a chemokine for CXCR3+ T cells, is known to regulate T cell differentiation and migration in the periphery, but effects of CXCL10 produced endogenously in the CNS on immune cell trafficking are unknown. We created floxed cxcl10 mice and crossed them with mice carrying an astrocyte-specific Cre transgene (mGFAPcre) to ablate astroglial CXCL10 synthesis. These mice, and littermate controls, were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) to induce experimental autoimmune encephalomyelitis (EAE). In comparison to the control mice, spinal cord CXCL10 mRNA and protein were sharply diminished in the mGFAPcre/CXCL10fl/fl EAE mice, confirming that astroglia are chiefly responsible for EAE-induced CNS CXCL10 synthesis. Astroglial CXCL10 deletion did not significantly alter the overall composition of CD4+ lymphocytes and CD11b+ cells in the acutely inflamed CNS, but did diminish accumulation of CD4+ lymphocytes in the spinal cord perivascular spaces. Furthermore, IBA1+ microglia/macrophage accumulation within the lesions was not affected by CXCL10 deletion. Clinical deficits were milder and acute demyelination was substantially reduced in the astroglial CXCL10-deleted EAE mice, but long-term axon loss was equally severe in the two groups. We concluded that astroglial CXCL10 enhances spinal cord perivascular CD4+ lymphocyte accumulation and acute spinal cord demyelination in MOG peptide EAE, but does not play an important role in progressive axon loss in this MS model

Proximity induced superconductivity in indium gallium arsenide quantum wells

We report on the experimental observation of the proximity induced superconductivity in an indium gallium arsenide (In0.75Ga0.25As) quantum well. The Josephson junction was fabricated by several photo-lithographic processes on an InGaAs heterojunction and Niobium (Nb) was used as superconducting electrodes. Owing to the Andreev reflections and Andreev bound states at the Nb-In0.75Ga0.25As quantum well-Nb interfaces, the subharmonic energy gap structures (SGS) are observed at the differential conductance (dI/dV) versus voltage (V) plots when the applied source-drain bias voltages satisfy the expression VSD = 2Δ/ne. The dI/dV as a function of applied magnetic field B shows a maximum at zero B which decreases by increasing B. When decreasing B to below ±0.4 T, a hysteresis and shift of the conductance maxima close to B = 0 T are observed. Our results help to pave the way to the development of integrated coherent quantum circuitry.Authors acknowledge financial support from EPSRC grant numbers EP/M009505/1 and EP/J017671/1. K. Delfanazari is grateful to Dr. H. Asai for helpful discussions

On-Chip Andreev Devices: Hard Superconducting Gap and Quantum Transport in Ballistic Nb–In0.75Ga0.25AsQuantum-Well–Nb Josephson Junctions

A superconducting hard gap in hybrid superconductor–semiconductor devices has been found to be necessary to access topological superconductivity that hosts Majorana modes (non-Abelian excitation). This requires the formation of homogeneous and barrier-free interfaces between the superconductor and semiconductor. Here, a new platform is reported for topological superconductivity based on hybrid Nb–In$_{0.75}$Ga$_{0.25}$As-quantum-well–Nb that results in hard superconducting gap detection in symmetric, planar, and ballistic Josephson junctions. It is shown that with careful etching, sputtered Nb films can make high-quality and transparent contacts to the In$_{0.75}$Ga$_{0.25}$As quantum well, and the differential resistance and critical current measurements of these devices are discussed as a function of temperature and magnetic field. It is demonstrated that proximity-induced superconductivity in the In$_{0.75}$Ga$_{0.25}$As-quantum-well 2D electron gas results in the detection of a hard gap in four out of seven junctions on a chip with critical current values of up to 0.2 µA and transmission probabilities of >0.96. The results, together with the large g-factor and Rashba spin–orbit coupling in In$_{0.75}$Ga$_{0.25}$As quantum wells, which indeed can be tuned by the indium composition, suggest that the Nb–In$_{0.75}$Ga$_{0.25}$As–Nb system can be an excellent candidate to achieve topological phase and to realize hybrid topological superconducting devices.Authors acknowledge financial support from EPSRC grant numbers EP/M009505/1 and EP/J017671/1

Intersections of quadrics, moment-angle manifolds, and Hamiltonian-minimal Lagrangian embeddings

We study the topology of Hamiltonian-minimal Lagrangian submanifolds N in C^m constructed from intersections of real quadrics in a work of the first author. This construction is linked via an embedding criterion to the well-known Delzant construction of Hamiltonian toric manifolds. We establish the following topological properties of N: every N embeds as a submanifold in the corresponding moment-angle manifold Z, and every N is the total space of two different fibrations, one over the torus T^{m-n} with fibre a real moment-angle manifold R, and another over a quotient of R by a finite group with fibre a torus. These properties are used to produce new examples of Hamiltonian-minimal Lagrangian submanifolds with quite complicated topology.Comment: 14 pages, published version (minor changes

Stable bundles on hypercomplex surfaces

A hypercomplex manifold is a manifold equipped with three complex structures I, J, K satisfying the quaternionic relations. Let M be a 4-dimensional compact smooth manifold equipped with a hypercomplex structure, and E be a vector bundle on M. We show that the moduli space of anti-self-dual connections on E is also hypercomplex, and admits a strong HKT metric. We also study manifolds with (4,4)-supersymmetry, that is, Riemannian manifolds equipped with a pair of strong HKT-structures that have opposite torsion. In the language of Hitchin's and Gualtieri's generalized complex geometry, (4,4)-manifolds are called ``generalized hyperkaehler manifolds''. We show that the moduli space of anti-self-dual connections on M is a (4,4)-manifold if M is equipped with a (4,4)-structure.Comment: 17 pages. Version 3.0: reference adde

Correlation between centrality metrics and their application to the opinion model

In recent decades, a number of centrality metrics describing network properties of nodes have been proposed to rank the importance of nodes. In order to understand the correlations between centrality metrics and to approximate a high-complexity centrality metric by a strongly correlated low-complexity metric, we first study the correlation between centrality metrics in terms of their Pearson correlation coefficient and their similarity in ranking of nodes. In addition to considering the widely used centrality metrics, we introduce a new centrality measure, the degree mass. The m order degree mass of a node is the sum of the weighted degree of the node and its neighbors no further than m hops away. We find that the B_{n}, the closeness, and the components of x_{1} are strongly correlated with the degree, the 1st-order degree mass and the 2nd-order degree mass, respectively, in both network models and real-world networks. We then theoretically prove that the Pearson correlation coefficient between x_{1} and the 2nd-order degree mass is larger than that between x_{1} and a lower order degree mass. Finally, we investigate the effect of the inflexible antagonists selected based on different centrality metrics in helping one opinion to compete with another in the inflexible antagonists opinion model. Interestingly, we find that selecting the inflexible antagonists based on the leverage, the B_{n}, or the degree is more effective in opinion-competition than using other centrality metrics in all types of networks. This observation is supported by our previous observations, i.e., that there is a strong linear correlation between the degree and the B_{n}, as well as a high centrality similarity between the leverage and the degree.Comment: 20 page

Indirect reciprocity and the evolution of “moral signals”

Signals regarding the behavior of others are an essential element of human moral systems and there are important evolutionary connections between language and large-scale cooperation. In particular, social communication may be required for the reputation tracking needed to stabilize indirect reciprocity. Additionally, scholars have suggested that the benefits of indirect reciprocity may have been important for the evolution of language and that social signals may have coevolved with large-scale cooperation. This paper investigates the possibility of such a coevolution. Using the tools of evolutionary game theory, we present a model that incorporates primitive “moral signaling” into a simple setting of indirect reciprocity. This model reveals some potential difficulties for the evolution of “moral signals.” We find that it is possible for “moral signals” to evolve alongside indirect reciprocity, but without some external pressure aiding the evolution of a signaling system, such a coevolution is unlikely

Decoupling property of the supersymmetric Higgs sector with four doublets

In supersymmetric standard models with multi Higgs doublet fields, selfcoupling constants in the Higgs potential come only from the D-terms at the tree level. We investigate the decoupling property of additional two heavier Higgs doublet fields in the supersymmetric standard model with four Higgs doublets. In particular, we study how they can modify the predictions on the quantities well predicted in the minimal supersymmetric standard model (MSSM), when the extra doublet fields are rather heavy to be measured at collider experiments. The B-term mixing between these extra heavy Higgs bosons and the relatively light MSSM-like Higgs bosons can significantly change the predictions in the MSSM such as on the masses of MSSM-like Higgs bosons as well as the mixing angle for the two light CP-even scalar states. We first give formulae for deviations in the observables of the MSSM in the decoupling region for the extra two doublet fields. We then examine possible deviations in the Higgs sector numerically, and discuss their phenomenological implications.Comment: 26 pages, 24 figures, text sligtly modified,version to appear in Journal of High Energy Physic

Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background: The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets. Results: This work developed a novel approach, which is based on a nonlinear mathematical model, to infer genetic regulation from microarray gene expression data. By using the p53 network as a test system, we used the nonlinear model to estimate the activities of transcription factor (TF) p53 from the expression levels of its target genes, and to identify the activation/inhibition status of p53 to its target genes. The predicted top 317 putative p53 target genes were supported by DNA sequence analysis. A comparison between our prediction and the other published predictions of p53 targets suggests that most of putative p53 targets may share a common depleted or enriched sequence signal on their upstream non-coding region. Conclusions: The proposed quantitative model can not only be used to infer the regulatory relationship between TF and its down-stream genes, but also be applied to estimate the protein activities of TF from the expression levels of its target genes