Numerical modelling of plasticity induced by transcranial magnetic stimulation

We use neural field theory and spike-timing dependent plasticity to make a simple but biophysically reasonable model of long-term plasticity changes in the cortex due to transcranial magnetic stimulation (TMS). We show how common TMS protocols can be captured and studied within existing neural field theory. Specifically, we look at repetitive TMS protocols such as theta burst stimulation and paired-pulse protocols. Continuous repetitive protocols result mostly in depression, but intermittent repetitive protocols in potentiation. A paired pulse protocol results in depression at short (∼ 100 ms) interstimulus intervals, but potentiation for mid-range intervals. The model is sensitive to the choice of neural populations that are driven by the TMS pulses, and to the parameters that describe plasticity, which may aid interpretation of the high variability in existing experimental results. Driving excitatory populations results in greater plasticity changes than driving inhibitory populations. Modelling also shows the merit in optimizing a TMS protocol based on an individual’s electroencephalogram. Moreover, the model can be used to make predictions about protocols that may lead to improvements in repetitive TMS outcomes

A high resolution imaging detector for TeV gamma-ray astronomy

Details are presented of an atmospheric Cherenkov telescope for use in very high energy gamma-ray astronomy which consists of a cluster of 109 close-packed photomultiplier tubes at the focus of a 10 meter optical reflector. The images of the Cherenkov flashes generated both by gamma-ray and charged cosmic-ray events are digitized and recorded. Subsequent off-line analysis of the images improves the significance of the signal to noise ratio by a factor of 10 compared with non-imaging techniques

Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages Under Selection

SELECTOR is a software package for studying the evolution of multiallelic genes under balancing or positive selection while simulating complex evolutionary scenarios that integrate demographic growth and migration in a spatially explicit population framework. Parameters can be varied both in space and time to account for geographical, environmental, and cultural heterogeneity. SELECTOR can be used within an approximate Bayesian computation estimation framework. We first describe the principles of SELECTOR and validate the algorithms by comparing its outputs for simple models with theoretical expectations. Then, we show how it can be used to investigate genetic differentiation of loci under balancing selection in interconnected demes with spatially heterogeneous gene flow. We identify situations in which balancing selection reduces genetic differentiation between population groups compared with neutrality and explain conflicting outcomes observed for human leukocyte antigen loci. These results and three previously published applications demonstrate that SELECTOR is efficient and robust for building insight into human settlement history and evolution

A High Statistics Search for Ultra-High Energy Gamma-Ray Emission from Cygnus X-3 and Hercules X-1

We have carried out a high statistics (2 Billion events) search for ultra-high energy gamma-ray emission from the X-ray binary sources Cygnus X-3 and Hercules X-1. Using data taken with the CASA-MIA detector over a five year period (1990-1995), we find no evidence for steady emission from either source at energies above 115 TeV. The derived upper limits on such emission are more than two orders of magnitude lower than earlier claimed detections. We also find no evidence for neutral particle or gamma-ray emission from either source on time scales of one day and 0.5 hr. For Cygnus X-3, there is no evidence for emission correlated with the 4.8 hr X-ray periodicity or with the occurrence of large radio flares. Unless one postulates that these sources were very active earlier and are now dormant, the limits presented here put into question the earlier results, and highlight the difficulties that possible future experiments will have in detecting gamma-ray signals at ultra-high energies.Comment: 26 LaTeX pages, 16 PostScript figures, uses psfig.sty to be published in Physical Review

Before and After: Comparison of Legacy and Harmonized TCGA Genomic Data Commons’ Data

We present a systematic analysis of the effects of synchronizing a large-scale, deeply characterized, multi-omic dataset to the current human reference genome, using updated software, pipelines, and annotations. For each of 5 molecular data platforms in The Cancer Genome Atlas (TCGA)—mRNA and miRNA expression, single nucleotide variants, DNA methylation and copy number alterations—comprehensive sample, gene, and probe-level studies were performed, towards quantifying the degree of similarity between the ‘legacy’ GRCh37 (hg19) TCGA data and its GRCh38 (hg38) version as ‘harmonized’ by the Genomic Data Commons. We offer gene lists to elucidate differences that remained after controlling for confounders, and strategies to mitigate their impact on biological interpretation. Our results demonstrate that the hg19 and hg38 TCGA datasets are very highly concordant, promote informed use of either legacy or harmonized omics data, and provide a rubric that encourages similar comparisons as new data emerge and reference data evolve. Gao et al. performed a systematic analysis of the effects of synchronizing the large-scale, widely used, multi-omic dataset of The Cancer Genome Atlas to the current human reference genome. For each of the five molecular data platforms assessed, they demonstrated a very high concordance between the ‘legacy’ GRCh37 (hg19) TCGA data and its GRCh38 (hg38) version as ‘harmonized’ by the Genomic Data Commons

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

Sediment routing and basin evolution in Proterozoic to Mesozoic east Gondwana: A case study from southern Australia

Sedimentary rocks along the southern margin of Australia host an important record of the break-up history of east Gondwana, as well as fragments of a deeper geological history, which collectively help inform the geological evolution of a vast and largely underexplored region. New drilling through Cenozoic cover has allowed examination of the Cretaceous rift-related Madura Shelf sequence (Bight Basin), and identification of two new stratigraphic units beneath the shelf; the possibly Proterozoic Shanes Dam Conglomerate and the interpreted Palaeozoic southern Officer Basin unit, the Decoration Sandstone. Recognition of these new units indicates an earlier basinal history than previously known. Lithostratigraphy of the new drillcore has been integrated with that published from onshore and offshore cores to present isopach maps of sedimentary cover on the Madura Shelf. New palynological data demonstrate progression from more localised freshwater-brackish fluvio-lacustrine clastics in the early Cretaceous (Foraminisporis wonthaggiensis – Valanginian to Barremian) to widespread topography-blanketing, fully marine, glauconitic mudrocks in the mid Cretaceous (Endoceratium ludbrookiae – Albian). Geochronology and Hf-isotope geochemistry show detrital zircon populations from the Madura Shelf are comparable to those from the southern Officer Basin, as well as Cenozoic shoreline and palaeovalley sediments in the region. The detrital zircon population from the Shanes Dam Conglomerate is defined by a unimodal ~1400 Ma peak, which correlates with directly underlying crystalline basement of the Madura Province. Peak ages of ~1150 Ma and ~1650 Ma dominate the age spectra of all other samples, indicating a stable sediment reservoir through much of the Phanerozoic, with sediments largely sourced from the Albany-Fraser Orogen and Musgrave Province (directly and via multiple recycling events). The Madura Shelf detrital zircon population differs from published data for the Upper CretaceousCeduna Delta to the east, indicating significant differences in sediment provenance and routing between the Ceduna Sub-basin and central Bight Basin

On Model Checking Boolean BI

The logic of bunched implications (BI), introduced by O'Hearn and Pym, is a substructural logic which freely combines additive and multiplicative implications. Boolean BI (BBI) denotes BI with classical interpretation of additives and its model is the commutative monoid. We show that when the monoid is finitely generated and propositions are recursively defined, or the monoid is infinitely generated and propositions are restricted to generator propositions, the model checking problem is undecidable. In the case of finitely related monoid and,generator propositions. the model checking problem is EXPSPACE-complete.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000270711900021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Computer Science, Theory & MethodsEICPCI-S(ISTP)