Hyperboloidal discontinuous time-symmetric numerical algorithm with higher order jumps for gravitational self-force computations in the time domain

Within the next decade the Laser Interferometer Space Antenna (LISA) is due to be launched, providing the opportunity to extract physics from stellar objects and systems, such as \textit{Extreme Mass Ratio Inspirals}, (EMRIs) otherwise undetectable to ground based interferometers and Pulsar Timing Arrays (PTA). Unlike previous sources detected by the currently available observational methods, these sources can \textit{only} be simulated using an accurate computation of the gravitational self-force. Whereas the field has seen outstanding progress in the frequency domain, metric reconstruction and self-force calculations are still an open challenge in the time domain. Such computations would not only further corroborate frequency domain calculations and models, but also allow for full self-consistent evolution of the orbit under the effect of the self-force. Given we have \textit{a priori} information about the local structure of the discontinuity at the particle, we will show how to construct discontinuous spatial and temporal discretisations by operating on discontinuous Lagrange and Hermite interpolation formulae and hence recover higher order accuracy. In this work we demonstrate how this technique in conjunction with well-suited gauge choice (hyperboloidal slicing) and numerical (discontinuous collocation with time symmetric) methods can provide a relatively simple method of lines numerical algorithm to the problem. This is the first of a series of papers studying the behaviour of a point-particle prescribing circular geodesic motion in Schwarzschild in the \textit{time domain}. In this work we describe the numerical machinery necessary for these computations and show not only our work is capable of highly accurate flux radiation measurements but it also shows suitability for evaluation of the necessary field and it's derivatives at the particle limit

The geomorphology of Svínafellsjökull and Virkisjökull-Falljökull glacier forelands, southeast Iceland

A detailed, 1:10,500-scale, surficial geology and glacial geomorphology map of Svínafellsjökull and Virkisjökull-Falljökull glacier forelands in southeast Iceland depicts the landsystem imprint of Holocene glacier fluctuations, volcanogenic outburst floods and recent (post-1990) climate-induced rapid ice-front retreat. The map is based on field survey data in combination with 2012 airborne LiDAR data, 2009–2012 terrestrial LiDAR data and 2007 colour aerial photography. The base digital elevation model (DEM) is compiled from an ice-cap wide airborne LiDAR dataset. The mapped glacial landforms are dominated by sequences of recessional moraines laid down in the mid-Holocene, the Little Ice Age, and the last ∼100 years; the state of landform preservation generally decreasing with age. Interspersed with glaciofluvial sedimentation associated with typical ice-marginal retreat sequences is key geomorphological evidence of high-magnitude volcanogenic outburst floods (jökulhlaups) associated with the eruptions of Öraefajökull in 1362 and 1727 CE. Ice-front retreat has accelerated since c.2005 leaving a rapidly evolving buried-ice landscape in front of Virkisjökull-Falljökull – including an ice-cored esker, a large ice-floored (supraglacial) lake, and numerous actively forming kettle holes and ice caverns. This map could act as a ‘reference frame’ for geomorphologists studying the temporal evolution of glacial landform-sediment assemblages undergoing rapid change

Impact testing to determine the mechanical properties of articular cartilage in isolation and on bone

The original publication is available at www.springerlink.comNon peer reviewedPostprin

Factors associated with mobile health information seeking among Singaporean women

This study examined effects of age and social psychological factors on women’s willingness to be mobile health information seekers. A national survey of 1,878 Singaporean women was conducted to obtain information on women’s mobile phone usage, experiences of health information seeking, and appraisals of using mobile phones to seek health information. Results showed that young, middle-aged, and older women exhibited distinct mobile phone usage behaviors, health information-seeking patterns, and assessments of mobile health information seeking. Factors that accounted for their mobile information-seeking intention also varied. Data reported in this study provide insights into mobile health interventions in the future

Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers

The Genetics Core of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), formally established in 2009, aims to provide resources and facilitate research related to genetic predictors of multidimensional Alzheimer’s disease (AD)-related phenotypes. Here, we provide a systematic review of genetic studies published between 2009 and 2012 where either ADNI APOE genotype or genome-wide association study (GWAS) data were used. We review and synthesize ADNI genetic associations with disease status or quantitative disease endophenotypes including structural and functional neuroimaging, fluid biomarker assays, and cognitive performance. We also discuss the diverse analytical strategies used in these studies, including univariate and multivariate analysis, meta-analysis, pathway analysis, and interaction and network analysis. Finally, we perform pathway and network enrichment analyses of these ADNI genetic associations to highlight key mechanisms that may drive disease onset and trajectory. Major ADNI findings included all the top 10 AD genes and several of these (e.g., APOE, BIN1, CLU, CR1, and PICALM) were corroborated by ADNI imaging, fluid and cognitive phenotypes. ADNI imaging genetics studies discovered novel findings (e.g., FRMD6) that were later replicated on different data sets. Several other genes (e.g., APOC1, FTO, GRIN2B, MAGI2, and TOMM40) were associated with multiple ADNI phenotypes, warranting further investigation on other data sets. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future studies employing next-generation sequencing and convergent multi-omics approaches, and for clinical drug and biomarker development. Electronic supplementary material The online version of this article (doi:10.1007/s11682-013-9262-z) contains supplementary material, which is available to authorized users

RH5.1-CyRPA-Ripr antigen combination vaccine shows little improvement over RH5.1 in a preclinical setting

Background: RH5 is the leading vaccine candidate for the Plasmodium falciparum blood stage and has shown impact on parasite growth in the blood in a human clinical trial. RH5 binds to Ripr and CyRPA at the apical end of the invasive merozoite form, and this complex, designated RCR, is essential for entry into human erythrocytes. RH5 has advanced to human clinical trials, and the impact on parasite growth in the blood was encouraging but modest. This study assessed the potential of a protein-in-adjuvant blood stage malaria vaccine based on a combination of RH5, Ripr and CyRPA to provide improved neutralizing activity against P. falciparum in vitro. Methods: Mice were immunized with the individual RCR antigens to down select the best performing adjuvant formulation and rats were immunized with the individual RCR antigens to select the correct antigen dose. A second cohort of rats were immunized with single, double and triple antigen combinations to assess immunogenicity and parasite neutralizing activity in growth inhibition assays. Results: The DPX® platform was identified as the best performing formulation in potentiating P. falciparum inhibitory antibody responses to these antigens. The three antigens derived from RH5, Ripr and CyRPA proteins formulated with DPX induced highly inhibitory parasite neutralising antibodies. Notably, RH5 either as a single antigen or in combination with Ripr and/or CyRPA, induced inhibitory antibodies that outperformed CyRPA, Ripr. Conclusion: An RCR combination vaccine may not induce substantially improved protective immunity as compared with RH5 as a single immunogen in a clinical setting and leaves the development pathway open for other antigens to be combined with RH5 as a next generation malaria vaccine

Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans

INTRODUCTION: Genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) have been crucial in advancing the understanding of Alzheimer's disease (AD) pathophysiology. Here, we provide an update on sample collection, scientific progress and opportunities, conceptual issues, and future plans. METHODS: Lymphoblastoid cell lines and DNA and RNA samples from blood have been collected and banked, and data and biosamples have been widely disseminated. To date, APOE genotyping, genome-wide association study (GWAS), and whole exome and whole genome sequencing data have been obtained and disseminated. RESULTS: ADNI genetic data have been downloaded thousands of times, and >300 publications have resulted, including reports of large-scale GWAS by consortia to which ADNI contributed. Many of the first applications of quantitative endophenotype association studies used ADNI data, including some of the earliest GWAS and pathway-based studies of biospecimen and imaging biomarkers, as well as memory and other clinical/cognitive variables. Other contributions include some of the first whole exome and whole genome sequencing data sets and reports in healthy controls, mild cognitive impairment, and AD. DISCUSSION: Numerous genetic susceptibility and protective markers for AD and disease biomarkers have been identified and replicated using ADNI data and have heavily implicated immune, mitochondrial, cell cycle/fate, and other biological processes. Early sequencing studies suggest that rare and structural variants are likely to account for significant additional phenotypic variation. Longitudinal analyses of transcriptomic, proteomic, metabolomic, and epigenomic changes will also further elucidate dynamic processes underlying preclinical and prodromal stages of disease. Integration of this unique collection of multiomics data within a systems biology framework will help to separate truly informative markers of early disease mechanisms and potential novel therapeutic targets from the vast background of less relevant biological processes. Fortunately, a broad swath of the scientific community has accepted this grand challenge

Integrated analysis of isopentenyl pyrophosphate (IPP) toxicity in isoprenoid-producing Escherichia coli

Isopentenyl pyrophosphate (IPP) toxicity presents a challenge in engineered microbial systems since its formation is unavoidable in terpene biosynthesis. In this work, we develop an experimental platform to study IPP toxicity in isoprenol-producing Escherichia coli. We first characterize the physiological response to IPP accumulation, demonstrating that elevated IPP levels are linked to growth inhibition, reduced cell viability, and plasmid instability. We show that IPP toxicity selects for pathway "breakage", using proteomics to identify a reduction in phosphomevalonate kinase (PMK) as a probable recovery mechanism. Next, using multi-omics data, we demonstrate that endogenous E. coli metabolism is globally impacted by IPP accumulation, which slows nutrient uptake, decreases ATP levels, and perturbs nucleotide metabolism. We also observe the extracellular accumulation of IPP and present preliminary evidence that IPP can be transported by E. coli, findings that might be broadly relevant for the study of isoprenoid biosynthesis. Finally, we discover that IPP accumulation leads to the formation of ApppI, a nucleotide analog of IPP that may contribute to observed toxicity phenotypes. This comprehensive assessment of IPP stress suggests potential strategies for the alleviation of prenyl diphosphate toxicity and highlights possible engineering targets for improved IPP flux and high titer isoprenoid production