Gravitational waves from binary supermassive black holes missing in pulsar observations.

This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aab1910Gravitational waves are expected to be radiated by supermassive black hole binaries formed during galaxy mergers. A stochastic superposition of gravitational waves from all such binary systems would modulate the arrival times of pulses from radio pulsars. Using observations of millisecond pulsars obtained with the Parkes radio telescope, we constrained the characteristic amplitude of this background, A(c,yr), to be <1.0 × 10(-15) with 95% confidence. This limit excludes predicted ranges for A(c,yr) from current models with 91 to 99.7% probability. We conclude that binary evolution is either stalled or dramatically accelerated by galactic-center environments and that higher-cadence and shorter-wavelength observations would be more sensitive to gravitational waves.The PPTA project was initiated with support from R.N.M.’s Australian Research Council (ARC) Federation Fellowship (grant FF0348478) and from CSIRO under that fellowship program. The PPTA project has also received support from ARC through Discovery Project grants DP0985272 and DP140102578. N.D.R.B. acknowledges support from a Curtin University research fellowship. G.H. and Y.L. are recipients of ARC Future Fellowships (respectively, grants FT120100595 and FT110100384). S.O. is supported by the Alexander von Humboldt Foundation. R.M.S. acknowledges travel support from CSIRO through a John Philip Award for excellence in early-career research. The authors declare no conflicts of interest. Data used in this analysis can be accessed via the Australian National Data Service (www.ands.org.au)

Patterns of Coral Disease across the Hawaiian Archipelago: Relating Disease to Environment

In Hawaii, coral reefs occur across a gradient of biological (host abundance), climatic (sea surface temperature anomalies) and anthropogenic conditions from the human-impacted reefs of the main Hawaiian Islands (MHI) to the pristine reefs of the northwestern Hawaiian Islands (NWHI). Coral disease surveys were conducted at 142 sites from across the Archipelago and disease patterns examined. Twelve diseases were recorded from three coral genera (Porites, Montipora, Acropora) with Porites having the highest prevalence. Porites growth anomalies (PorGAs) were significantly more prevalent within and indicative of reefs in the MHI and Porites trematodiasis (PorTrm) was significantly more prevalent within and indicative of reefs in the NWHI. Porites tissue loss syndrome (PorTLS) was also important in driving regional differences but that relationship was less clear. These results highlight the importance of understanding disease ecology when interpreting patterns of disease occurrence. PorTrm is caused by a parasitic flatworm that utilizes multiple hosts during its life cycle (fish, mollusk and coral). All three hosts must be present for the disease to occur and higher host abundance leads to higher disease prevalence. Thus, a high prevalence of PorTrm on Hawaiian reefs would be an indicator of a healthy coral reef ecosystem. In contrast, the high occurrence of PorGAs within the MHI suggests that PorGAs are related, directly or indirectly, to some environmental co-factor associated with increased human population sizes. Focusing on the three indicator diseases (PorGAs, PorTrm, PorTLS) we used statistical modeling to examine the underlying associations between disease prevalence and 14 different predictor variables (biotic and abiotic). All three diseases showed positive associations with host abundance and negative associations with thermal stress. The association with human population density differed among disease states with PorGAs showing a positive and PorTrm showing a negative association, but no significant explanatory power was offered for PorTLS

Corporate philanthropy through the lens of ethical subjectivity

The dynamic organisational processes in businesses dilute the boundaries between the individual, organisational, and societal drivers of corporate philanthropy. This creates a complex framework in which charitable project selection occurs. Using the example of European tour operators, this study investigates the mechanisms through which companies invest in charitable projects in overseas destinations. Inextricably linked to this is the increasing contestation by local communities as to how they are able to engage effectively with tourism in order to realise the benefits tourism development can bring. This research furthers such debates by exploring the processes through which tour operators facilitate community development through charitable giving. Findings show, with no formal frameworks in existence, project selection depends upon emergent strategies that connect the professional with the personal, with trust being positioned as a central driver of these informal processes. Discretionary responsibilities are reworked through business leaders’ commitment to responsible business practises and the ethical subjectivity guiding these processes

Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

Measurement of W-pair production in e+e−e^+ e^- collisions at 189 GeV

The production of W-pairs is analysed in a data samplecollected by ALEPH at a mean centre-of-mass energy of 188.6 GeV,corresponding to an integrated luminosity of 174.2 pb^-1. Crosssections are given for different topologies of W decays intoleptons or hadrons. Combining all final states and assumingStandard Model branching fractions, the total W-pair cross sectionis measured to be 15.71 +- 0.34 (stat) +- 0.18 (syst) pb.Using also the W-pair data samples collected by ALEPH at lowercentre-of-mass energies, the decay branching fraction of the W bosoninto hadrons is measured to be BR (W hadrons) = 66.97+- 0.65 (stat) +- 0.32 (syst) %, allowing a determination of theCKM matrix element |V(cs)|= 0.951 +- 0.030 (stat) +- 0.015 (syst)

Searches for neutral Higgs bosons in e+e−e^{+}e^{-} collisions at centre-of-mass energies from 192 to 202 GeV

Searches for neutral Higgs bosons are performed with the 237 pb^-1 of data collected in 1999 by the ALEPH detector at LEP, for centre-of-mass energies between 191.6 and 201.6 GeV. These searches apply to Higgs bosons within the context of the Standard Model and its minimal supersymmetric extension (MSSM) as well as to invisibly decaying Higgs bosons. No evidence of a signal is seen. A lower limit on the mass of the Standard Model Higgs boson of 107.7 GeV/c^2 at 95% confidence level is set. In the MSSM, lower limits of 91.2 and 91.6 GeV/c^2 are derived for the masses of the neutral Higgs bosons h and A, respectively. For a Higgs boson decaying invisibly and produced with the Standard Model cross section, masses below 106.4 GeV/c^2 are excluded

Altered Expression of Human Mitochondrial Branched Chain Aminotransferase in Dementia with Lewy Bodies and Vascular Dementia

© 2016, The Author(s). Cytosolic and mitochondrial human branched chain aminotransferase (hBCATc and hBCATm, respectively) play an integral role in brain glutamate metabolism. Regional increased levels of hBCATc in the CA1 and CA4 region of Alzheimer’s disease (AD) brain together with increased levels of hBCATm in frontal and temporal cortex of AD brains, suggest a role for these proteins in glutamate excitotoxicity. Glutamate toxicity is a key pathogenic feature of several neurological disorders including epilepsy associated dementia, AD, vascular dementia (VaD) and dementia with Lewy bodies (DLB). To further understand if these increases are specific to AD, the expression profiles of hBCATc and hBCATm were examined in other forms of dementia including DLB and VaD. Similar to AD, levels of hBCATm were significantly increased in the frontal and temporal cortex of VaD cases and in frontal cortex of DLB cases compared to controls, however there were no observed differences in hBCATc between groups in these areas. Moreover, multiple forms of hBCATm were observed that were particular to the disease state relative to matched controls. Real-time PCR revealed similar expression of hBCATm mRNA in frontal and temporal cortex for all cohort comparisons, whereas hBCATc mRNA expression was significantly increased in VaD cases compared to controls. Collectively our results suggest that hBCATm protein expression is significantly increased in the brains of DLB and VaD cases, similar to those reported in AD brain. These findings indicate a more global response to altered glutamate metabolism and suggest common metabolic responses that might reflect shared neurodegenerative mechanisms across several forms of dementia