Black holes, gravitational waves and fundamental physics: a roadmap

The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'

The in vivo performance of an enzyme-assisted self-assembled peptide/protein hydrogel

We demonstrate the distribution of the important extracellular matrix protein laminin in a novel biomaterial consisting of a hydrogel underpinned by nanofibrillar networks. These are formed by the immobilised enzyme mediated self-assembly of fmoc-L (9-fluorenylmethoxycarbonyl-tri-leucine). The peptide assembly yields nanofibrils formed of β-sheets that are locked together via π-stacking interactions. This ordering allows the localisation of the peptide sidechains on the surface, creating a hydrophobic environment. This induces the formation of bundles of these nanofibrils producing a clear hydrogel. This mechanism enables the three dimensional distribution of laminin throughout the network via supramolecular interactions. These forces favour the formation and improve the order of the network itself, as observed by spectroscopic and mechanical testing. In order to test the stability and suitability of this class of material for in vivo applications, we utilise microinjection to deliver the biomaterial under fine spatial control into a dystrophic zebrafish model organism, which lacks laminin as a result of a genetic mutation. Using confocal and transmission electron microscopy, we confirm that the biomaterial remains stable structurally, and is confined spatially to the site of injection

Depressive symptoms are associated with soluble P-selectin reactivity to acute exercise in heart failure

BACKGROUND: To determine the effects of depressive symptom severity on the circulating soluble adhesion molecule response to an acute exercise challenge in patients with heart failure (HF) compared with control subjects. METHODS: Thirty-eight male HF patients and 19 male control subjects (mean age +/- SEM: 55.5 +/- 1.9) completed the Beck Depression Inventory (BDI) before undergoing a moderate 20-minute bicycle exercise at approximately 65% to 70% VO(2peak). Plasma levels of the soluble adhesion molecules P-selectin (sP-selectin) (sCD62P) and soluble intercellular adhesion molecule-1 (sICAM-1) were determined immediately before and after and 10 minutes after exercise. RESULTS: Higher BDI scores moderated greater increases in sP-selectin levels in response to exercise over time in HF patients as compared with control subjects [F(1.8/84.5) = 3.25, p = .05]. Post hoc testing revealed that in HF patients, but not in control subjects, higher BDI scores were significantly associated with greater increases in sP-selectin levels over time in response to exercise [BDI by exercise interaction: F(1.6/49.6) = 5.67, p = .010]. Also, in HF patients, but not in control subjects, higher BDI scores were associated with higher sP-selectin levels at pre-exercise and postexercise time points [main effect BDI: F(1/31) = 4.86, p = .035]. CONCLUSIONS: Our findings suggest that in male HF patients with increasing depressive symptom severity, levels of the adhesion molecule sP-selectin are higher before and after exercise and have greater increases in response to exercise. This could have implications for acute coronary syndromes associated with exercise and thereby may impact mortality