Hidden Interactions of Sterile Neutrinos As a Probe For New Physics

Recent results from neutrino experiments show evidence for light sterile neutrinos which do not have any Standard Model interactions. In this work we study the hidden interaction of sterile neutrinos with an "MeV scale" gauge boson (the $\nu_s$HI model) with mass $M_X$ and leptonic coupling $g^\prime_l$. By performing an analysis on the $\nu_s$HI model using the data of the MINOS neutrino experiment we find that the values above $G_X/G_F=92.4$ are excluded by more than $2\sigma$ C.L., where $G_F$ is the Fermi constant and $G_X$ is the field strength of the $\nu_s$HI model. Using this model we can also probe other new physics scenarios. We find that the region allowed by the $(g-2)_\mu$ discrepancy is entirely ruled out for $M_X\lesssim 100$ MeV. Finally, the secret interaction of sterile neutrinos has been to solve a conflict between the sterile neutrinos and cosmology. It is shown here that such an interaction is excluded by MINOS for $g^\prime_s> 1.6\times10^{-2}$. This exclusion, however, does depend on the value of $g_l^{\prime}$.Comment: 11 pages, 2 figures, Improved version with new figures and further details. Accepted in PR

Signature change from Schutz's canonical quantum cosmology and its classical analogue

We study the signature change in a perfect fluid Friedmann-Robertson-Walker quantum cosmological model. In this work the Schutz's variational formalism is applied to recover the notion of time. This gives rise to a Schrodinger-Wheeler-DeWitt equation with arbitrary ordering for the scale factor. We use the eigenfunctions in order to construct wave packets and evaluate the time-dependent expectation value of the scale factor which coincides with the ontological interpretation. We show that these solutions exhibit signature transitions from a finite Euclidean to a Lorentzian domain. Moreover, such models are equivalent to a classical system where, besides the perfect fluid, a repulsive fluid is present.Comment: 15 pages, 4 figures, to appear in PR

Nano-Size Layered Manganese-Calcium Oxide as an Efficient and Biomimetic Catalyst for Water Oxidation Under Acidic Conditions: Comparable To Platinum

Inspired by Nature's catalyst, a nano-size layered manganese-calcium oxide showed a low overvoltage for water oxidation in acidic solutions, which is comparable to platinum.Institute for Advanced Studies in Basic Sciences and the National Elite FoundationUS Department of Energy, Office of Basic Energy Sciences, Division of Chemical, Geochemical and Biological Sciences DE-FG02-86ER13622, DE-FG0209ER16119Russian Foundation for Basic Research 11-04-01389a, 12-0492101a, 13-04-92711aMolecular and Cell Biology Programs of the Russian Academy of SciencesCenter for Electrochemistr

Multi-dimensional classical and quantum cosmology: Exact solutions, signature transition and stabilization

We study the classical and quantum cosmology of a $(4+d)$-dimensional spacetime minimally coupled to a scalar field and present exact solutions for the resulting field equations for the case where the universe is spatially flat. These solutions exhibit signature transition from a Euclidean to a Lorentzian domain and lead to stabilization of the internal space, in contrast to the solutions which do not undergo signature transition. The corresponding quantum cosmology is described by the Wheeler-DeWitt equation which has exact solutions in the mini-superspace, resulting in wavefunctions peaking around the classical paths. Such solutions admit parametrizations corresponding to metric solutions of the field equations that admit signature transition.Comment: 15 pages, two figures, to appear in JHE

RNA-Seq of Huntington's disease patient myeloid cells reveals innate transcriptional dysregulation associated with proinflammatory pathway activation

Innate immune activation beyond the central nervous system is emerging as a vital component of the pathogenesis of neurodegeneration. Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The systemic innate immune system is thought to act as a modifier of disease progression; however, the molecular mechanisms remain only partially understood. Here we use RNA-sequencing to perform whole transcriptome analysis of primary monocytes from thirty manifest HD patients and thirty-three control subjects, cultured with and without a proinflammatory stimulus. In contrast with previous studies that have required stimulation to elicit phenotypic abnormalities, we demonstrate significant transcriptional differences in HD monocytes in their basal, unstimulated state. This includes previously undetected increased resting expression of genes encoding numerous proinflammatory cytokines, such as IL6 Further pathway analysis revealed widespread resting enrichment of proinflammatory functional gene sets, while upstream regulator analysis coupled with Western blotting suggests that abnormal basal activation of the NFĸB pathway plays a key role in mediating these transcriptional changes. That HD myeloid cells have a proinflammatory phenotype in the absence of stimulation is consistent with a priming effect of mutant huntingtin, whereby basal dysfunction leads to an exaggerated inflammatory response once a stimulus is encountered. These data advance our understanding of mutant huntingtin pathogenesis, establish resting myeloid cells as a key source of HD immune dysfunction, and further demonstrate the importance of systemic immunity in the potential treatment of HD and the wider study of neurodegeneration

Longitudinal changes in functional connectivity of cortico-basal ganglia networks in manifests and premanifest huntington's disease

Huntington's disease (HD) is a genetic neurological disorder resulting in cognitive and motor impairments. We evaluated the longitudinal changes of functional connectivity in sensorimotor, associative and limbic cortico-basal ganglia networks. We acquired structural MRI and resting-state fMRI in three visits one year apart, in 18 adult HD patients, 24 asymptomatic mutation carriers (preHD) and 18 gender- and age-matched healthy volunteers from the TRACK-HD study. We inferred topological changes in functional connectivity between 182 regions within cortico-basal ganglia networks using graph theory measures. We found significant differences for global graph theory measures in HD but not in preHD. The average shortest path length (L) decreased, which indicated a change toward the random network topology. HD patients also demonstrated increases in degree k, reduced betweeness centrality bc and reduced clustering C. Changes predominated in the sensorimotor network for bc and C and were observed in all circuits for k. Hubs were reduced in preHD and no longer detectable in HD in the sensorimotor and associative networks. Changes in graph theory metrics (L, k, C and bc) correlated with four clinical and cognitive measures (symbol digit modalities test, Stroop, Burden and UHDRS). There were no changes in graph theory metrics across sessions, which suggests that these measures are not reliable biomarkers of longitudinal changes in HD. preHD is characterized by progressive decreasing hub organization, and these changes aggravate in HD patients with changes in local metrics. HD is characterized by progressive changes in global network interconnectivity, whose network topology becomes more random over time. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc

Predicting clinical diagnosis in Huntington's disease: An imaging polymarker.

OBJECTIVE: Huntington's disease (HD) gene carriers can be identified before clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to be useful at the level of the individual. Perfecting this prediction is integral to the search for disease modifying therapies. This study aimed to identify an imaging marker capable of reliably predicting real-life clinical diagnosis in HD. METHOD: A multivariate machine learning approach was applied to resting-state and structural magnetic resonance imaging scans from 19 premanifest HD gene carriers (preHD, 8 of whom developed clinical disease in the 5 years postscanning) and 21 healthy controls. A classification model was developed using cross-group comparisons between preHD and controls, and within the preHD group in relation to "estimated" and "actual" proximity to disease onset. Imaging measures were modeled individually, and combined, and permutation modeling robustly tested classification accuracy. RESULTS: Classification performance for preHDs versus controls was greatest when all measures were combined. The resulting polymarker predicted converters with high accuracy, including those who were not expected to manifest in that time scale based on the currently adopted statistical models. INTERPRETATION: We propose that a holistic multivariate machine learning treatment of brain abnormalities in the premanifest phase can be used to accurately identify those patients within 5 years of developing motor features of HD, with implications for prognostication and preclinical trials. Ann Neurol 2018;83:532-543.SLM is funded by a National Institute for Health Research (NIHR) Translational Research Collaboration for Rare Diseases fellowship. This research has been funded/supported by the National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. RAB is funded by the NIHR Cambridge Biomedical Research Centre and the Cambridge University NHS Foundation Trust. RED is employed on an EC Marie-Curie CIG, awarded to AH, SJT, EJ and RS receive funding from a Wellcome Collaborative Award (200181/Z/15/Z

NMDA receptor gene variations as modifiers in Huntington disease: a replication study.

Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the entire cohort. Yet, when subjects were stratified by AO subtypes, we found nominally significant evidence for an association of the GRIN2A rs1969060 variation and the GRIN2B rs1806201 variation. These findings further implicate the N-methyl D-aspartate receptor subtype genes as loci containing variation associated with AO in HD

Nanometric diamond delta doping with boron

Diamond is desired for active semiconducting device because of it high carrier mobility, high voltage breakdown resistance, and high thermal diffusivity. Exploiting diamond as a semiconductor is hampered by the lack of shallow dopants to create sufficient electronic carriers at room temperature. In this work, nanometer thick, heavily boron doped epitaxial diamond ‘delta doped’ layers have been grown on ultra smooth diamond surfaces which demonstrate p type conduction with enhanced Hall mobilities of up to 120 cm2/Vs and sheet carrier concentrations to 6 × 1013 cm–2, thus enabling a new class of active diamond electronic devices