The spherically symmetric collapse of a massless scalar field

We report on a numerical study of the spherically symmetric collapse of a self-gravitating massless scalar field. Earlier results of Choptuik(1992, 1994) are confirmed. The field either disperses to infinity or collapses to a black hole, depending on the strength of the initial data. For evolutions where the strength is close to but below the strength required to form a black hole, we argue that there will be a region close to the axis where the scalar curvature and field energy density can reach arbitrarily large levels, and which is visible to distant observersComment: 23 pages, 16 figures, uuencoded gzipped postscript This version omits 2 pages of figures. This file, the two pages of figures and the complete paper are available at ftp://ftp.damtp.cam.ac.uk/pub/gr/rsh100

The Cosmic No-Hair Theorem and the Nonlinear Stability of Homogeneous Newtonian Cosmological Models

The validity of the cosmic no-hair theorem is investigated in the context of Newtonian cosmology with a perfect fluid matter model and a positive cosmological constant. It is shown that if the initial data for an expanding cosmological model of this type is subjected to a small perturbation then the corresponding solution exists globally in the future and the perturbation decays in a way which can be described precisely. It is emphasized that no linearization of the equations or special symmetry assumptions are needed. The result can also be interpreted as a proof of the nonlinear stability of the homogeneous models. In order to prove the theorem we write the general solution as the sum of a homogeneous background and a perturbation. As a by-product of the analysis it is found that there is an invariant sense in which an inhomogeneous model can be regarded as a perturbation of a unique homogeneous model. A method is given for associating uniquely to each Newtonian cosmological model with compact spatial sections a spatially homogeneous model which incorporates its large-scale dynamics. This procedure appears very natural in the Newton-Cartan theory which we take as the starting point for Newtonian cosmology.Comment: 16 pages, MPA-AR-94-

Relativistic Elasticity

Relativistic elasticity on an arbitrary spacetime is formulated as a Lagrangian field theory which is covariant under spacetime diffeomorphisms. This theory is the relativistic version of classical elasticity in the hyperelastic, materially frame-indifferent case and, on Minkowski space, reduces to the latter in the non-relativistic limit . The field equations are cast into a first -- order symmetric hyperbolic system. As a consequence one obtains local--in--time existence and uniqueness theorems under various circumstances.Comment: 23 page

Cisplatin binding sites on human albumin

Reactions of cisplatin (cis -[PtCl2(NH3)2]) with albumin are thought to play an important role in the metabolism of this anticancer drug. They are investigated here via (i) labeling of cisplatin with 15N and use of two-dimensional 1H,15N NMR spectroscopy, (ii) comparison of natural human serum albumin with recombinant human albumin (higher homogeneity and SH content), (iii) chemical modification of Cys, Met, and His residues, (iv) reactions of bound platinum with thiourea, and (v) gel filtration chromatography. In contrast to previous reports, it is shown that the major sulfur-containing binding site involves Met and not Cys-34, and also a N ligand, in the form of an S,N macrochelate. Additional monofunctional adducts involving other Met residues and Cys-34 are also observed. During the later stages of reactions of cisplatin with albumin, release of NH3 occurs due to the strong trans influence of Met sulfur, which weakens the Pt-NH3 bonds, and protein cross-linking is observed. The consequences of these findings for the biological activity of cisplatin-albumin complexes are discussed

Theorems on existence and global dynamics for the Einstein equations

This article is a guide to theorems on existence and global dynamics of solutions of the Einstein equations. It draws attention to open questions in the field. The local-in-time Cauchy problem, which is relatively well understood, is surveyed. Global results for solutions with various types of symmetry are discussed. A selection of results from Newtonian theory and special relativity that offer useful comparisons is presented. Treatments of global results in the case of small data and results on constructing spacetimes with prescribed singularity structure or late-time asymptotics are given. A conjectural picture of the asymptotic behaviour of general cosmological solutions of the Einstein equations is built up. Some miscellaneous topics connected with the main theme are collected in a separate section.Comment: Submitted to Living Reviews in Relativity, major update of Living Rev. Rel. 5 (2002)

Community Consensus Guidelines to Support FAIR Data Standards in Clinical Research Studies in Primary Mitochondrial Disease

Primary mitochondrial diseases (PMD) are genetic disorders with extensive clinical and molecular heterogeneity where therapeutic development efforts have faced multiple challenges. Clinical trial design, outcome measure selection, lack of reliable biomarkers, and deficiencies in long-term natural history data sets remain substantial challenges in the increasingly active PMD therapeutic development space. Developing "FAIR" (findable, accessible, interoperable, reusable) data standards to make data sharable and building a more transparent community data sharing paradigm to access clinical research metadata are the first steps to address these challenges. This collaborative community effort describes the current landscape of PMD clinical research data resources available for sharing, obstacles, and opportunities, including ways to incentivize and encourage data sharing among diverse stakeholders. This work highlights the importance of, and challenges to, developing a unified system that enables clinical research structured data sharing and supports harmonized data deposition standards across clinical consortia and research groups. The goal of these efforts is to improve the efficiency and effectiveness of drug development and improve understanding of the natural history of PMD. This initiative aims to maximize the benefit for PMD patients, research, industry, and other stakeholders while acknowledging challenges related to differing needs and international policies on data privacy, security, management, and oversight

Physiological consequences of abnormal connectivity in a developmental epilepsy

Objective Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities. Methods We employed transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recording in 8 patients with epilepsy from periventricular nodular heterotopia and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions. Results Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in 1 subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone. Interpretation Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions

Theorems on existence and global dynamics for the Einstein equations

This article is a guide to theorems on existence and global dynamics of solutions of the Einstein equations. It draws attention to open questions in the field. The local in time Cauchy problem, which is relatively well understood, is surveyed. Global results for solutions with various types of symmetry are discussed. A selection of results from Newtonian theory and special relativity which offer useful comparisons is presented. Treatments of global results in the case of small data and results on constructing spacetimes with prescribed singularity structure are given. A conjectural picture of the asymptotic behaviour of general cosmological solutions of the Einstein equations is built up. Some miscellaneous topics connected with the main theme are collected in a separate section.Comment: 54 pages, submitted to Living Reviews in Relativit