Wave Propagation in Gravitational Systems: Late Time Behavior

It is well-known that the dominant late time behavior of waves propagating on a Schwarzschild spacetime is a power-law tail; tails for other spacetimes have also been studied. This paper presents a systematic treatment of the tail phenomenon for a broad class of models via a Green's function formalism and establishes the following. (i) The tail is governed by a cut of the frequency Green's function $\tilde G(\omega)$ along the $-$~Im~$\omega$ axis, generalizing the Schwarzschild result. (ii) The $\omega$ dependence of the cut is determined by the asymptotic but not the local structure of space. In particular it is independent of the presence of a horizon, and has the same form for the case of a star as well. (iii) Depending on the spatial asymptotics, the late time decay is not necessarily a power law in time. The Schwarzschild case with a power-law tail is exceptional among the class of the potentials having a logarithmic spatial dependence. (iv) Both the amplitude and the time dependence of the tail for a broad class of models are obtained analytically. (v) The analytical results are in perfect agreement with numerical calculations

Affinity purification mass spectrometry characterisation of the interactome of receptor tyrosine kinase proline-rich motifs in cancer

Receptor tyrosine kinase (RTK) overexpression is linked to the development and progression of multiple cancers. RTKs are classically considered to initiate cytoplasmic signalling pathways via ligand-induced tyrosine phosphorylation, however recent evidence points to a second tier of signalling contingent on interactions mediated by the proline-rich motif (PRM) regions of non-activated RTKs. The presence of PRMs on the C-termini of >40 % of all RTKs and the abundance of PRM-binding proteins encoded by the human genome suggests that there is likely to be a large number of previously unexplored interactions which add to the RTK intracellular interactome. Here, we explore the RTK PRM interactome and its potential significance using affinity purification mass spectrometry and in silico enrichment analyses. Peptides comprising PRM-containing C-terminal tail regions of EGFR, FGFR2 and HER2 were used as bait to affinity purify bound proteins from different cancer cell line lysates. 490 unique interactors were identified, amongst which proteins with metabolic, homeostatic and migratory functions were overrepresented. This suggests that PRMs from RTKs may sustain a diverse interactome in cancer cells. Since RTK overexpression is common in cancer, RTK PRM-derived signalling may be an important, but as yet underexplored, contributor to negative cancer outcomes including resistance to kinase inhibitors

Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study

Objectives: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics. Methods: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105–377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity. Results: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). Conclusion: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women

An Adaptable Platform for Directed Evolution in Human Cells

Therapeutic cell differentiatio

Using a breath-figure method to self-organize honeycomb-like polymeric films from dendritic side-chain polymers

In this study, we investigated various generations of waxy dendrons, dendritic side-chain polymers (varying the structure and polarity of the polymer backbone), and physical blends of dendrons with polymers for their ability to form honeycomb-like structures. Each waxy dendron comprises a focal part (possessing many hydrogen bonding sites) and a peripheral part (rich in units that undergo van der Waals interactions). Using a breath-figure process, we readily incorporated high-generation dendrons within polymer matrixes to form porous surfaces. When the high-generation waxy dendrons were grafted onto amino group - functionalized polystyrene or copolymerized with diisocyanates to form polyurethanes, the multiple long alkyl chains behaved as bristles of hydrophobic brooms, due to the presence of strong van der Waals forces. The formation of honeycomb-like patterns in the polymer films resulted from strong hydrogen bonding of the polymers to water droplets on the surfaces of substrates, with subsequent self-organization and phase separation. (C) 2011 Elsevier B.V. All rights reserved