Geoids in General Relativity: Geoid Quasilocal Frames

We develop, in the context of general relativity, the notion of a geoid -- a surface of constant "gravitational potential". In particular, we show how this idea naturally emerges as a specific choice of a previously proposed, more general and operationally useful construction called a quasilocal frame -- that is, a choice of a two-parameter family of timelike worldlines comprising the worldtube boundary of the history of a finite spatial volume. We study the geometric properties of these geoid quasilocal frames, and construct solutions for them in some simple spacetimes. We then compare these results -- focusing on the computationally tractable scenario of a non-rotating body with a quadrupole perturbation -- against their counterparts in Newtonian gravity (the setting for current applications of the geoid), and we compute general-relativistic corrections to some measurable geometric quantities.Comment: 24 pages, 8 figures; v2: reference added; v3: introduction clarified, reference adde

Nuclear hyaluronidase 2 drives alternative splicing of CD44 pre-mRNA to determine profibrotic or antifibrotic cell phenotype

The cell surface protein CD44 is involved in diverse physiological processes, and its aberrant function is linked to various pathologies such as cancer, immune dysregulation, and fibrosis. The diversity of CD44 biological activity is partly conferred by the generation of distinct CD44 isoforms through alternative splicing. We identified an unexpected function for the ubiquitous hyaluronan-degrading enzyme, hyaluronidase 2 (HYAL2), as a regulator of CD44 splicing. Standard CD44 is associated with fibrotic disease, and its production is promoted through serine-arginine–rich (SR) protein–mediated exon exclusion. HYAL2 nuclear translocation was stimulated by bone morphogenetic protein 7, which inhibits the myofibroblast phenotype. Nuclear HYAL2 displaced SR proteins from the spliceosome, thus enabling HYAL2, spliceosome components (U1 and U2 small nuclear ribonucleoproteins), and CD44 pre-mRNA to form a complex. This prevented double-exon splicing and facilitated the inclusion of CD44 exons 11 and 12, which promoted the accumulation of the antifibrotic CD44 isoform CD44v7/8 at the cell surface. These data demonstrate previously undescribed mechanisms regulating CD44 alternative splicing events that are relevant to the regulation of cellular phenotypes in progressive fibrosis

Dispersion enhancement and damping by buoyancy driven flows in 2D networks of capillaries

The influence of a small relative density difference on the displacement of two miscible liquids is studied experimentally in transparent 2D networks of micro channels. Both stable displacements in which the denser fluid enters at the bottom of the cell and displaces the lighter one and unstable displacements in which the lighter fluid is injected at the bottom and displaces the denser one are realized. Except at the lowest mean flow velocity U, the average $C(x,t)$ of the relative concentration satisfies a convection-dispersion equation. The dispersion coefficient is studied as function of the relative magnitude of fluid velocity and of the velocity of buoyancy driven fluid motion. A model is suggested and its applicability to previous results obtained in 3D media is discussed

Solving the subset-sum problem with a light-based device

We propose a special computational device which uses light rays for solving the subset-sum problem. The device has a graph-like representation and the light is traversing it by following the routes given by the connections between nodes. The nodes are connected by arcs in a special way which lets us to generate all possible subsets of the given set. To each arc we assign either a number from the given set or a predefined constant. When the light is passing through an arc it is delayed by the amount of time indicated by the number placed in that arc. At the destination node we will check if there is a ray whose total delay is equal to the target value of the subset sum problem (plus some constants).Comment: 14 pages, 6 figures, Natural Computing, 200

Exact Cover with light

We suggest a new optical solution for solving the YES/NO version of the Exact Cover problem by using the massive parallelism of light. The idea is to build an optical device which can generate all possible solutions of the problem and then to pick the correct one. In our case the device has a graph-like representation and the light is traversing it by following the routes given by the connections between nodes. The nodes are connected by arcs in a special way which lets us to generate all possible covers (exact or not) of the given set. For selecting the correct solution we assign to each item, from the set to be covered, a special integer number. These numbers will actually represent delays induced to light when it passes through arcs. The solution is represented as a subray arriving at a certain moment in the destination node. This will tell us if an exact cover does exist or not.Comment: 20 pages, 4 figures, New Generation Computing, accepted, 200

Individual learning on environmental vocational education and training courses does not always lead to the workplace application of knowledge and skills

YesEmpirical research on three commercial environmental vocational education and training programmes revealed distinct personal, teaching and work-based presage factors, which influenced individual learning and learning transfer to the workplace. The extent to which behaviour change and learning transfer occurred depended on a diverse range of factors, notably the workplace utility of the course; student’s level of personal commitment and position within the employing organisation; strength of the organisation’s environmental culture; level of post-course managerial/supervisory support available within the workplace; and changing workplace circumstances/priorities

Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer

Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulator ESRP2. Both ESRP2 and its close paralog ESRP1 are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including splicing switches correlating with disease progression. ESRP2 expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this, treatment with the AR antagonist bicalutamide (Casodex) induced mesenchymal splicing patterns of genes including FLNB and CTNND1. Our data reveals a new mechanism of splicing control in prostate cancer with important implications for disease progression.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

Differential expression of VEGF-Axxx isoforms is critical for development of pulmonary fibrosis

RATIONALE Fibrosis after lung injury is related to poor outcome, and idiopathic pulmonary fibrosis (IPF) can be regarded as an exemplar. Vascular endothelial growth factor (VEGF)-A has been implicated in this context, but there are conflicting reports as to whether it is a contributory or protective factor. Differential splicing of the VEGF-A gene produces multiple functional isoforms including VEGF-Aa and VEGF-Ab, a member of the inhibitory family. To date there is no clear information on the role of VEGF-A in IPF. OBJECTIVES To establish VEGF-A isoform expression and functional effects in IPF. METHODS We used tissue sections, plasma, and lung fibroblasts from patients with IPF and control subjects. In a bleomycin-induced lung fibrosis model we used wild-type MMTV mice and a triple transgenic mouse SPC-rtTATetoCreLoxP-VEGF-Ato conditionally induce VEGF-A isoform deletion specifically in the alveolar type II (ATII) cells of adult mice. MEASUREMENTS AND MAIN RESULTS IPF and normal lung fibroblasts differentially expressed and responded to VEGF-Aa and VEGF-Ab in terms of proliferation and matrix expression. Increased VEGF-Ab was detected in plasma of progressing patients with IPF. In a mouse model of pulmonary fibrosis, ATII-specific deficiency of VEGF-A or constitutive overexpression of VEGF-Ab inhibited the development of pulmonary fibrosis, as did treatment with intraperitoneal delivery of VEGF-Ab to wild-type mice. CONCLUSIONS These results indicate that changes in the bioavailability of VEGF-A sourced from ATII cells, namely the ratio of VEGF-Aa to VEGF-Ab, are critical in development of pulmonary fibrosis and may be a paradigm for the regulation of tissue repair

“Top-Down-Bottom-Up” Methodology as a Common Approach to Defining Bespoke Sets of Sustainability Assessment Criteria for the Built Environment

YesThe top-down-bottom-up (TDBU) methodology for defining bespoke sets of sustainability criteria for specific civil engineering project types is introduced and discussed. The need to define sustainability criteria for specific civil engineering project types occurs mainly in one or both of the following cases: (1) when a more comprehensive and indicative assessment of the sustainability of the project type in question is required; and/or (2) there is no readily available bespoke sustainability assessment tool, or set of criteria, for assessing the sustainability of the project type. The construction of roads, buildings, airports, tunnels, dams, flood banks, bridges, water supply, and sewage systems and their supporting systems are considered to be unique civil engineering/infrastructure project types. The normative definition of sustainable civil engineering/infrastructure projects and the framework for assessing its sustainability is defined and provided by the authors. An example of the TDBU methodology being applied to define sustainability criteria for transport noise reducing devices is presented and discussed. The end result of applying the methodology is a systematically researched and industry validated set of criteria that denotes assessing the sustainability of the civil engineering/infrastructure project type. The paper concludes that the top-down-bottom-up will support stakeholders and managers involved in assessing sustainability to consider all major research methods to define general and unique sustainability criteria to assess and so maximize sustainability