Carrier transport theory for twisted bilayer graphene in the metallic regime

The mechanisms responsible for the strongly correlated insulating and superconducting phases in twisted bilayer graphene are still debated. The authors provide a theory for phonon-dominated transport that explains several experimental observations, and contrast it with the Planckian dissipation mechanism. Understanding the normal-metal state transport in twisted bilayer graphene near magic angle is of fundamental importance as it provides insights into the mechanisms responsible for the observed strongly correlated insulating and superconducting phases. Here we provide a rigorous theory for phonon-dominated transport in twisted bilayer graphene describing its unusual signatures in the resistivity (including the variation with electron density, temperature, and twist angle) showing good quantitative agreement with recent experiments. We contrast this with the alternative Planckian dissipation mechanism that we show is incompatible with available experimental data. An accurate treatment of the electron-phonon scattering requires us to go well beyond the usual treatment, including both intraband and interband processes, considering the finite-temperature dynamical screening of the electron-phonon matrix element, and going beyond the linear Dirac dispersion. In addition to explaining the observations in currently available experimental data, we make concrete predictions that can be tested in ongoing experiments

Correlation between Interleukin-4 and Interleukin-6 and auto antibodies in Systemic Lupus Erythematosus.

Background: There is a general acceptance which illustrated that auto antibodies act as a central immunological disturbance in most of the auto immune diseases, among these auto immune diseaselies the SLE Patients and Methods: Thirty five patients with SLE were compared to twenty age and sex matched, control subjects and studied for the presence of auto antibodies, plus IL-4 and IL-6 using Elisa method and immune fluorescent method (for ANA only) Results: Data showed that IL-6 detectable levels were statistically significant in patients with positive anti ds-DNA, but not significant statistically in ANA positive patients although it was detected in 24 (70.6%) of positive ANA patients, while there was no statistically significant correlation between IL- 4 detectable level and autoantibodies production. Conclusion: There is apparently a positive correlation between IL-6 and anti ds DNA production in lupus patients

Superoxide Dismutase 1 and tgSOD1G93A Mouse Spinal Cord Seed Fibrils, Suggesting a Propagative Cell Death Mechanism in Amyotrophic Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that specifically affects motor neurons and leads to a progressive and ultimately fatal loss of function, resulting in death typically within 3 to 5 years of diagnosis. The disease starts with a focal centre of weakness, such as one limb, and appears to spread to other parts of the body. Mutations in superoxide dismutase 1 (SOD1) are known to cause disease and it is generally accepted they lead to pathology not by loss of enzymatic activity but by gain of some unknown toxic function(s). Although different mutations lead to varying tendencies of SOD1 to aggregate, we suggest abnormal proteins share a common misfolding pathway that leads to the formation of amyloid fibrils.Methodology/Principal Findings: Here we demonstrate that misfolding of superoxide dismutase 1 leads to the formation of amyloid fibrils associated with seeding activity, which can accelerate the formation of new fibrils in an autocatalytic cascade. The time limiting event is nucleation to form a stable protein "seed" before a rapid linear polymerisation results in amyloid fibrils analogous to other protein misfolding disorders. This phenomenon was not confined to fibrils of recombinant protein as here we show, for the first time, that spinal cord homogenates obtained from a transgenic mouse model that overexpresses mutant human superoxide dismutase 1 (the TgSOD1(G93A) mouse) also contain amyloid seeds that accelerate the formation of new fibrils in both wildtype and mutant SOD1 protein in vitro.Conclusions/Significance: These findings provide new insights into ALS disease mechanism and in particular a mechanism that could account for the spread of pathology throughout the nervous system. This model of disease spread, which has analogies to other protein misfolding disorders such as prion disease, also suggests it may be possible to design assays for therapeutics that can inhibit fibril propagation and hence, possibly, disease progression

A comparison of in vitro properties of resting SOD1 transgenic microglia reveals evidence of reduced neuroprotective function

<p>Abstract</p> <p>Background</p> <p>Overexpression of mutant copper/zinc superoxide dismutase (<it>SOD1</it>) in rodents has provided useful models for studying the pathogenesis of amyotrophic lateral sclerosis (ALS). Microglia have been shown to contribute to ALS disease progression in these models, although the mechanism of this contribution remains to be elucidated. Here, we present the first evidence of the effects of overexpression of mutant (TG G93A) and wild type (TG WT) human <it>SOD1 </it>transgenes on a set of functional properties of microglia relevant to ALS progression, including expression of integrin β-1, spreading and migration, phagocytosis of apoptotic neuronal cell debris, and intracellular calcium changes in response to an inflammatory stimulus.</p> <p>Results</p> <p>TG SOD1 G93A but not TG SOD1 WT microglia had lower expression levels of the cell adhesion molecule subunit integrin β-1 than their NTG control cells [NTG (G93A) and NTG (WT), respectively, 92.8 ± 2.8% on TG G93A, 92.0 ± 6.6% on TG WT, 100.0 ± 1.6% on NTG (G93A), and 100.0 ± 2.7% on NTG (WT) cells], resulting in decreased spreading ability, with no effect on ability to migrate. Both TG G93A and TG WT microglia had reduced capacity to phagocytose apoptotic neuronal cell debris (13.0 ± 1.3% for TG G93A, 16.5 ± 1.9% for TG WT, 28.6 ± 1.8% for NTG (G93A), and 26.9 ± 2.8% for NTG (WT) cells). Extracellular stimulation of microglia with ATP resulted in smaller increase in intracellular free calcium in TG G93A and TG WT microglia relative to NTG controls (0.28 ± 0.02 μM for TG G93A, 0.24 ± 0.03 μM for TG WT, 0.39 ± 0.03 μM for NTG (G93A), and 0.37 ± 0.05 μM for NTG (WT) microglia).</p> <p>Conclusions</p> <p>These findings indicate that, under resting conditions, microglia from mutant <it>SOD1 </it>transgenic mice have a reduced capacity to elicit physiological responses following tissue disturbances and that higher levels of stimulatory signals, and/or prolonged stimulation may be necessary to initiate these responses. Overall, resting mutant <it>SOD1</it>-overexpressing microglia may have reduced capacity to function as sensors of disturbed tissue/cellular homeostasis in the CNS and thus have reduced neuroprotective function.</p

Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS.

Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to that of FALS-linked mutant SOD1. Our findings suggest that wild-type SOD1 can be pathogenic in SALS and identify an SOD1-dependent pathogenic mechanism common to FALS and SALS

Measurements of long-range azimuthal anisotropies and associated Fourier coefficients for pp collisions at √s=5.02 and 13 TeV and p+Pb collisions at √sNN=5.02 TeV with the ATLAS detector

ATLAS measurements of two-particle correlations are presented for √s=5.02 and 13 TeV ppcollisions and for √sNN=5.02 TeV p+Pb collisions at the LHC. The correlation functions are measured as a function of relative azimuthal angle Δϕ, and pseudorapidity separation Δη, using charged particles detected within the pseudorapidity interval |η|2, is studied using a template fitting procedure to remove a “back-to-back” contribution to the correlation function that primarily arises from hard-scattering processes. In addition to the elliptic, cos (2Δϕ), modulation observed in a previous measurement, the pp correlation functions exhibit significant cos (3Δϕ) and cos (4Δϕ) modulation. The Fourier coefficients vn, n associated with the cos (nΔϕ) modulation of the correlation functions for n=2–4 are measured as a function of charged-particle multiplicity and charged-particle transverse momentum. The Fourier coefficients are observed to be compatible with cos (nϕ) modulation of per-event single-particle azimuthal angle distributions. The single-particle Fourier coefficients vn are measured as a function of charged-particle multiplicity, and charged-particle transverse momentum for n=2–4. The integrated luminosities used in this analysis are, 64nb−1 for the √s=13 TeV pp data, 170 nb−1 for the √ s = 5.02 TeV pp data, and 28 nb−1 for the √sNN = 5.02 TeV p+Pb data

Exendin-4 Ameliorates Motor Neuron Degeneration in Cellular and Animal Models of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease. Here we hypothesized that Ex-4 may provide neuroprotective activity in ALS, and hence characterized Ex-4 actions in both cell culture (NSC-19 neuroblastoma cells) and in vivo (SOD1 G93A mutant mice) models of ALS. Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis. Additionally, in both wild-type SOD1 and mutant SOD1 (G37R) stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity. To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion. ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice. Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons. Together, our results suggest that GLP-1 receptor agonists warrant further evaluation to assess whether their neuroprotective potential is of therapeutic relevance in ALS

Top-quark mass measurement in the all-hadronic tt¯ decay channel at √s=8 TeV with the ATLAS detector

The top-quark mass is measured in the all-hadronic top-antitop quark decay channel using proton-proton collisions at a centre-of-mass energy of √s=8 TeV with the ATLAS detector at the CERN Large Hadron Collider. The data set used in the analysis corresponds to an integrated luminosity of 20.2 fb−1. The large multi-jet background is modelled using a data-driven method. The top-quark mass is obtained from template fits to the ratio of the three-jet to the dijet mass. The three-jet mass is obtained from the three jets assigned to the top quark decay. From these three jets the dijet mass is obtained using the two jets assigned to the W boson decay. The top-quark mass is measured to be 173.72 ± 0.55 (stat.) ± 1.01 (syst.) GeV

Performance of the ATLAS trigger system in 2015

During 2015 the ATLAS experiment recorded 3.8fb−1 of proton–proton collision data at a centre-of-mass energy of 13TeV. The ATLAS trigger system is a crucial component of the experiment, responsible for selecting events of interest at a recording rate of approximately 1 kHz from up to 40 MHz of collisions. This paper presents a short overview of the changes to the trigger and data acquisition systems during the first long shutdown of the LHC and shows the performance of the trigger system and its components based on the 2015 proton–proton collision data