Suppression of matching field effects by splay and pinning energy dispersion in YBa_2Cu_3O_7 with columnar defects

We report measurements of the irreversible magnetization M_i of a large number of YBa_2Cu_3O_7 single crystals with columnar defects (CD). Some of them exhibit a maximum in M_i when the density of vortices equals the density of tracks, at temperatures above 40K. We show that the observation of these matching field effects is constrained to those crystals where the orientational and pinning energy dispersion of the CD system lies below a certain threshold. The amount of such dispersion is determined by the mass and energy of the irradiation ions, and by the crystal thickness. Time relaxation measurements show that the matching effects are associated with a reduction of the creep rate, and occur deep into the collective pinning regime.Comment: 7 pages, 5 figures, submitted to Phys. Rev.

Pulsar kicks from a dark-matter sterile neutrino

We show that a sterile neutrino with mass in the 1-20 keV range and a small mixing with the electron neutrino can simultaneously explain the origin of the pulsar motions and the dark matter in the universe. An asymmetric neutrino emission from a hot nascent neutron star can be the explanation of the observed pulsar velocities. In addition to the pulsar kick mechanism based on resonant neutrino transitions, we point out a new possibility: an asymmetric off-resonant emission of sterile neutrinos. The two cases correspond to different values of the masses and mixing angles. In both cases we identify the ranges of parameters consistent with the pulsar kick, as well as cosmological constraints.Comment: 5 pages, 2 figures; final version; discussion and references adde

Model-independent extraction of ∣Vtq∣|V_{tq}| matrix elements from top-quark measurements at hadron colliders

Current methods to extract the quark-mixing matrix element $|V_{tb}|$ from single-top production measurements assume that $|V_{tb}|\gg |V_{td}|, |V_{ts}|$: top quarks decay into $b$ quarks with 100% branching fraction, s-channel single-top production is always accompanied by a $b$ quark and initial-state contributions from $d$ and $s$ quarks in the $t$-channel production of single top quarks are neglected. Triggered by a recent measurement of the ratio $R=\frac{|V_{tb}|^{2}}{|V_{td}|^{2}+|V_{ts}|^{2}+|V_{tb}|^{2}}=0.90 \pm 0.04$ performed by the D0 collaboration, we consider a $|V_{tb}|$ extraction method that takes into account non zero d- and s-quark contributions both in production and decay. We propose a strategy that allows to extract consistently and in a model-independent way the quark mixing matrix elements $|V_{td}|$, $|V_{ts}|$, and $|V_{tb}|$ from the measurement of $R$ and from single-top measured event yields. As an illustration, we apply our method to the Tevatron data using a CDF analysis of the measured single-top event yield with two jets in the final state one of which is identified as a $b$-quark jet. We constrain the $|V_{tq}|$ matrix elements within a four-generation scenario by combining the results with those obtained from direct measurements in flavor physics and determine the preferred range for the top-quark decay width within different scenarios.Comment: 36 pages, 17 figure

Neonicotinoids and their substitutes in sustainable pest control

ISBN 978-3-8047-4144-7, EASAC / FEAM REPORT (European Academies Science Advisory Council / Federation of Auropean Academies of Medicine

CSL311, a novel, potent, therapeutic monoclonal antibody for the treatment of diseases mediated by the common beta chain of the IL-3, GM-CSF and IL-5 receptors

The β common-signaling cytokines interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-5 stimulate pro-inflammatory activities of haematopoietic cells via a receptor complex incorporating cytokine-specific α and shared β common (βc, CD131) receptor. Evidence from animal models and recent clinical trials demonstrate that these cytokines are critical mediators of the pathogenesis of inflammatory airway disease such as asthma. However, no therapeutic agents, other than steroids, that specifically and effectively target inflammation mediated by all 3 of these cytokines exist. We employed phage display technology to identify and optimize a novel, human monoclonal antibody (CSL311) that binds to a unique epitope that is specific to the cytokine-binding site of the human βc receptor. The binding epitope of CSL311 on the βc receptor was defined by X-ray crystallography and site-directed mutagenesis. CSL311 has picomolar binding affinity for the human βc receptor, and at therapeutic concentrations is a highly potent antagonist of the combined activities of IL-3, GM-CSF and IL-5 on primary eosinophil survival in vitro. Importantly, CSL311 inhibited the survival of inflammatory cells present in induced sputum from human allergic asthmatic subjects undergoing allergen bronchoprovocation. Due to its high potency and ability to simultaneously suppress the activity of all 3 β common cytokines, CSL311 may provide a new strategy for the treatment of chronic inflammatory diseases where the human βc receptor is central to pathogenesis. The coordinates for the βc/CSL311 Fab complex structure have been deposited with the RCSB Protein Data Bank (PDB 5DWU).Con Panousis, Urmi Dhagat, Kirsten M. Edwards, Veronika Rayzman, Matthew P. Hardy, Hal Braley, Gail M. Gauvreau, Timothy R. Hercus, Steven Smith, Roma Sehmi, Laura McMillan, Mara Dottore, Barbara J. McClure, Louis J. Fabri, Gino Vairo, Angel F Lopez, Michael W. Parker, Andrew D. Nash, Nicholas J. Wilson, Michael J. Wilson and Catherine M. Owczare

Microwave determination of the quasiparticle scattering time in YBa2Cu3O6.95

We report microwave surface resistance (Rs) measurements on two very-high-quality YBa2Cu3O6.95 crystals which exhibit extremely low residual loss at 1.2 K (2-6 μΩ at 2 GHz), a broad, reproducible peak at around 38 K, and a rapid increase in loss, by 4 orders of magnitude, between 80 and 93 K. These data provide one ingredient in the determination of the temperature dependence of the real part of the microwave conductivity, σ1(T), and of the quasiparticle scattering time. The other necessary ingredient is an accurate knowledge of the magnitude and temperature dependence of the London penetration depth, λ(T). This is derived from published data, from microwave data of Anlage, Langley, and co-workers and from, high-quality μSR data. We infer, from a careful analysis of all available data, that λ2(0)/λ2(T) is well approximated by the simple function 1-t2, where t=T/Tc, and that the low-temperature data are incompatible with the existence of an s-wave, BCS-like gap. Combining the Rs and λ(T) data, we find that σ1(T), has a broad peak around 32 K with a value about 20 times that at Tc. Using a generalized two-fluid model, we extract the temperature dependence of the quasiparticle scattering rate which follows an exponential law, exp(T/T0), where T0≊12 K, for T between 15 and 84 K. Such a temperature dependence has previously been observed in measurements of the nuclear spin-lattice relaxation rate. Both the uncertainties in our analysis and the implications for the mechanism of high-temperature superconductivity are discussed

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele