Alternatives to standard puncture initial data for binary black hole evolution

Standard puncture initial data have been widely used for numerical binary black hole evolutions despite their shortcomings, most notably the inherent lack of gravitational radiation at the initial time that is later followed by a burst of spurious radiation. We study the evolution of three alternative initial data schemes. Two of the three alternatives are based on post-Newtonian expansions that contain realistic gravitational waves. The first scheme is based on a second-order post-Newtonian expansion in Arnowitt, Deser, and Misner transverse-traceless (ADMTT) gauge that has been resummed to approach standard puncture data at the black holes. The second scheme is based on asymptotic matching of the 4-metrics of two tidally perturbed Schwarzschild solutions to a first-order post-Newtonian expansion in ADMTT gauge away from the black holes. The final alternative is obtained through asymptotic matching of the 4-metrics of two tidally perturbed Schwarzschild solutions to a second-order post-Newtonian expansion in harmonic gauge away from the black holes. When evolved, the second scheme fails to produce quasicircular orbits (and instead leads to a nearly head-on collision). This failure can be traced back to inaccuracies in the extrinsic curvature due to low order matching. More encouraging is that the latter two alternatives lead to quasicircular orbits and show gravitational radiation from the onset of the evolution, as well as a reduction of spurious radiation. Current deficiencies compared to standard punctures data include more eccentric trajectories during the inspiral and larger constraint violations, since the alternative data sets are only approximate solutions of Einstein's equations. The eccentricity problem can be ameliorated by adjusting the initial momentum parameters.Comment: 11 pages, 11 figures, 1 appendix, typos corrected, removed duplicate reference, matches published versio

Error-analysis and comparison to analytical models of numerical waveforms produced by the NRAR Collaboration

The Numerical-Relativity-Analytical-Relativity (NRAR) collaboration is a joint effort between members of the numerical relativity, analytical relativity and gravitational-wave data analysis communities. The goal of the NRAR collaboration is to produce numerical-relativity simulations of compact binaries and use them to develop accurate analytical templates for the LIGO/Virgo Collaboration to use in detecting gravitational-wave signals and extracting astrophysical information from them. We describe the results of the first stage of the NRAR project, which focused on producing an initial set of numerical waveforms from binary black holes with moderate mass ratios and spins, as well as one non-spinning binary configuration which has a mass ratio of 10. All of the numerical waveforms are analysed in a uniform and consistent manner, with numerical errors evaluated using an analysis code created by members of the NRAR collaboration. We compare previously-calibrated, non-precessing analytical waveforms, notably the effective-one-body (EOB) and phenomenological template families, to the newly-produced numerical waveforms. We find that when the binary's total mass is ~100-200 solar masses, current EOB and phenomenological models of spinning, non-precessing binary waveforms have overlaps above 99% (for advanced LIGO) with all of the non-precessing-binary numerical waveforms with mass ratios <= 4, when maximizing over binary parameters. This implies that the loss of event rate due to modelling error is below 3%. Moreover, the non-spinning EOB waveforms previously calibrated to five non-spinning waveforms with mass ratio smaller than 6 have overlaps above 99.7% with the numerical waveform with a mass ratio of 10, without even maximizing on the binary parameters.Comment: 51 pages, 10 figures; published versio

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Studies of myosin mechanics using fluorescence

Molecular fluorescence provides scientists with a wealth of information on how biological systems function at the molecular level. Through fluorescence, individual biological molecules can be tracked as they interact with other proteins, DNA, ligands, etc. and change their conformation in response to the interaction. Molecular motors such as myosin provide an ideal system for fluorescence. The multitude of currently available fluorescent techniques allow for the study of each important step required for myosin to generate directed motion along an actin filament. Several fluorescent techniques such as fluorescence resonance energy transfer (FRET), Lanthanide based resonance energy transfer (LRET), fluorescence imaging with one nanometer accuracy (FIONA), and defocused orientation and position imaging (DOPI) are all applied to specifically myosin II and myosin VI in the text below. FRET or a modified version known as LRET, allow for the measurement of angstrom level changes in the position between two fluorescent probes attached to a molecule. The advantage of LRET over FRET is that it can measure absolute distances between the two dyes as opposed to only the changes in distance between two different conformations. The anisotropy, a quantity that determines the polarization of emitted light, was measured for several lanthanide probes containing Terbium and Europium and shown to be high for Eu-DTPA (and TTHA), but near zero for Tb-DTPA (or TTHA) and when the lanthanides are excited indirectly through an antenna molecule. The fact that these probes emit un-polarized light results in the high accuracy of LRET. LRET and FRET measured the lever arm swing of smooth muscle myosin II and confirmed that there was an actin dependent state. FIONA is able to track the position of a single dye with approximately one nanometer accuracy while DOPI is able to determine the dye's orientation. Both of these techniques were used to study the motion of myosin VI and the orientation of its light chain domain (LCD) as the motor walks along actin. Despite conventional wisdom, the LCD of myosin VI did not appear to move as myosin VI took a step. Finally, preliminary single molecule FRET measurements on myosin VI are discussed.U of I Onlydissertatio

Arvind Raman

This paper outlines major challenges that we are facing in interfacing a human user with objects in the nanoworld via a haptic interface. After a review of prior efforts at haptically-enabled nanomanipulation systems, we present the current state of our nanomanipulator system. We then discuss current research issues including the direct-Z mode, force modeling, data transfer rates and the stability of the haptic interface. Results of nanomanipulation of single-walled carbon nanotubes are presented. It is our hope that the insight gained by the human user of a haptic interface to SPM will lead to scanning algorithms that can automatically adjust the SPM parameters based on the properties of the nanosample and the substrate under investigation. 1

Glioblastoma with adipocyte-like tumor cell differentiation--histological and molecular features of a rare differentiation pattern

We report on three adult patients with primary glioblastomas showing prominent adipocytic (lipomatous) differentiation, hence referred to as "glioblastomas with adipocyte-like tumor cell differentiation." Histologically, the tumors demonstrated typical features of glioblastoma but additionally contained areas consisting of glial fibrillary acidic protein (GFAP)-positive astrocytic tumor cells resembling adipocytes, that is, containing large intracellular lipid vacuoles. Comparative genomic hybridization (CGH) and focused molecular genetic analyses demonstrated gains of chromosomes 7, losses of chromosomes 9 and 10, as well as homozygous deletion of p14(ARF) in one of the tumors. The second tumor showed gains of chromosomes 3, 4, 8q and 12 as well as losses of chromosomes 10, 13, 15q, 19 and 22. In addition, this tumor carried homozygous deletions of CDKN2A and p14(ARF) as well as point mutations in the TP53 and PTEN genes. The third tumor also had a mutation in the PTEN gene. None of the tumors demonstrated EGFR, CDK4 or MDM2 amplification. Taken together, our results define a rare glioblastoma differentiation pattern and indicate that glioblastomas with adipocyte-like tumor cell differentiation share common molecular genetic features with other primary glioblastomas