The Role of Splayed Disorder and Channel Flow on the Dynamics of Driven 3D Vortices

We present the results of three-dimensional molecular dynamics simulations of vortices which indicate that, for B greater than the matching field, the enhanced pinning effectiveness of splayed columnar defects relative to vertical columnar defects can be explained in terms of the existence or absence of channels through which the vortices can flow without encountering defects.Comment: 2 Pages, 3 Figures, Proceedings from Houston M2S-HTSC-VI References altered, minor correction

UV and X-Ray Monitoring of AG Draconis During the 1994/1995 Outbursts

The recent 1994-1995 active phase of AG Draconis has given us for the first time the opportunity to follow the full X-ray behaviour of a symbiotic star during two successive outbursts and to compare with its quiescence X-ray emission. With \ros observations we have discovered a remarkable decrease of the X-ray flux during both optical maxima, followed by a gradual recovering to the pre-outburst flux. In the UV the events were characterized by a large increase of the emission line and continuum fluxes, comparable to the behaviour of AG Dra during the 1980-81 active phase. The anticorrelation of X-ray/UV flux and optical brightness evolution is shown to very likely be due to a temperature decrease of the hot component. Such a temperature decrease could be produced by an increased mass transfer to the burning compact object, causing it to slowly expand to about twice its original size.Comment: 12 pages postscript incl. figures, Proc. of Workshop on Supersoft X-Ray Sources, to appear in Lecture Notes in Physics vol. 472 (1996

Melting and Dimensionality of the Vortex Lattice in Underdoped YBa2Cu3O6.60

Muon spin rotation measurements of the magnetic field distribution in the vortex state of the oxygen deficient high-Tc superconductor YBa{2}Cu{3}O{6.60} reveal a vortex-lattice melting transition at much lower temperature than that in the fully oxygenated material. The transition is best described by a model in which adjacent layers of ``pancake'' vortices decouple in the liquid phase. Evidence is also found for a pinning-induced crossover from a solid 3D to quasi-2D vortex lattice, similar to that observed in the highly anisotropic superconductor Bi{2+x}Sr{2-x}CaCu{2}O{8+y}.Comment: 8 pages, 4 figures, 5 postscript file

Measurement of Cosmic-ray Muon-induced Spallation Neutrons in the Aberdeen Tunnel Underground Laboratory

AbstractMuon-induced neutrons are one of the major backgrounds to various underground experiments, such as dark matter searches, low-energy neutrino oscillation experiments and neutrino-less double beta-decay experiments. Previous experiments on the underground production rate of muon-induced neutrons were mostly carried out either at shallow sites or at very deep sites. The Aberdeen Tunnel experiment aims to measure the neutron production rate at a moderate depth of 611 meters water equivalent. Our apparatus comprises of six layers of plastic-scintillator hodoscopes for tracking the incident cosmic-ray muons, and 760 L of gadolinium-doped liquid-scintillator for both neutron production and detection targets. In this paper, we describe the design and the performance of the apparatus. The preliminary result on the measurement of neutron production rate is also presented

Developmental alterations in noxious-evoked EEG activity recorded from rat primary somatosensory cortex

Primary somatosensory cortex (S1) contains a nociceptive map that localizes potential tissue damage on the body and encodes stimulus intensity. An objective and specific biomarker of pain however is currently lacking and is urgently required for use in non-verbal clinical populations as well as in the validation of pre-clinical pain models. Here we describe studies to see if the responses of the S1 in juvenile rats are different to those in the adult. We recorded electroencephalogram (EEG) responses from S1 of lightly-anesthetized Sprague–Dawley rats at either postnatal day 21 or postnatal day 40 during the presentation of noxious (55 °C) or innocuous (30 °C) thermal stimuli applied to the plantar surface of the left hindpaw. The total EEG power across the recording period was the same in both ages after stimulation but the frequency distribution was significantly affected by age. Noxious heat evoked a significant increase in theta band (4–8 Hz) activity in adults only (P < 0.0001 compared to baseline; P < 0.0001 compared to juveniles). There were no significant differences in EEG responses to innocuous thermal stimuli. These data show that there are significant alterations in the processing of nociceptive inputs within the maturing cortex and that cortical theta activity is involved only in the adult cortical response to noxious stimulation

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine

Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01B-adjuvanted RH5.1 malaria antigen — substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society