1,276 research outputs found
Integrating modes of policy analysis and strategic management practice : requisite elements and dilemmas
There is a need to bring methods to bear on public problems that are inclusive, analytic, and quick. This paper describes the efforts of three pairs of academics working from three different though complementary theoretical foundations and intervention backgrounds (i.e., ways of working) who set out together to meet this challenge. Each of the three pairs had conducted dozens of interventions that had been regarded as successful or very successful by the client groups in dealing with complex policy and strategic problems. One approach focused on leadership issues and stakeholders, another on negotiating competitive strategic intent with attention to stakeholder responses, and the third on analysis of feedback ramifications in developing policies. This paper describes the 10 year longitudinal research project designed to address the above challenge. The important outcomes are reported: the requisite elements of a general integrated approach and the enduring puzzles and tensions that arose from seeking to design a wide-ranging multi-method approach
Conformal Symmetry for General Black Holes
We show that the warp factor of a generic asymptotically flat black hole in
five dimensions can be adjusted such that a conformal symmetry emerges. The
construction preserves all near horizon properties of the black holes, such as
the thermodynamic potentials and the entropy. We interpret the geometry with
modified asymptotic behavior as the "bare" black hole, with the ambient flat
space removed. Our warp factor subtraction generalizes hidden conformal
symmetry and applies whether or not rotation is significant. We also find a
relation to standard AdS/CFT correspondence by embedding the black holes in six
dimensions. The asymptotic conformal symmetry guarantees a dual CFT description
of the general rotating black holes.Comment: 26 page
Conformal Symmetry for Black Holes in Four Dimensions
We show that the asymptotic boundary conditions of general asymptotically
flat black holes in four dimensions can be modified such that a conformal
symmetry emerges. The black holes with the asymptotic geometry removed in this
manner satisfy the equations of motion of minimal supergravity in five
dimensions. We develop evidence that a two dimensional CFT dual of general
black holes in four dimensions account for their black hole entropy.Comment: 24 pages, minor correction
GlyGly-CTERM and Rhombosortase: A C-Terminal Protein Processing Signal in a Many-to-One Pairing with a Rhomboid Family Intramembrane Serine Protease
The rhomboid family of serine proteases occurs in all domains of life. Its members contain at least six hydrophobic membrane-spanning helices, with an active site serine located deep within the hydrophobic interior of the plasma membrane. The model member GlpG from Escherichia coli is heavily studied through engineered mutant forms, varied model substrates, and multiple X-ray crystal studies, yet its relationship to endogenous substrates is not well understood. Here we describe an apparent membrane anchoring C-terminal homology domain that appears in numerous genera including Shewanella, Vibrio, Acinetobacter, and Ralstonia, but excluding Escherichia and Haemophilus. Individual genomes encode up to thirteen members, usually homologous to each other only in this C-terminal region. The domain's tripartite architecture consists of motif, transmembrane helix, and cluster of basic residues at the protein C-terminus, as also seen with the LPXTG recognition sequence for sortase A and the PEP-CTERM recognition sequence for exosortase. Partial Phylogenetic Profiling identifies a distinctive rhomboid-like protease subfamily almost perfectly co-distributed with this recognition sequence. This protease subfamily and its putative target domain are hereby renamed rhombosortase and GlyGly-CTERM, respectively. The protease and target are encoded by consecutive genes in most genomes with just a single target, but far apart otherwise. The signature motif of the Rhombo-CTERM domain, often SGGS, only partially resembles known cleavage sites of rhomboid protease family model substrates. Some protein families that have several members with C-terminal GlyGly-CTERM domains also have additional members with LPXTG or PEP-CTERM domains instead, suggesting there may be common themes to the post-translational processing of these proteins by three different membrane protein superfamilies
Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations
PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036
Evaluation of a DSGE Model of Energy in the United Kingdom Using Stationary Data
I examine the impact of energy price shock (oil prices shock and gas prices shock) on the economic activities in the United Kingdom using a dynamic stochastic general equilibrium model with a New Keynesian Philips Curve. I decomposed the changes in output caused by all of the stationary structural shocks. I found that the fall in output during the financial crisis period is driven by domestic demand shock, energy prices shock and world demand shock. I found the energy prices shock’s contribution to fall in output is temporary. Such that, the UK can borrow against such a temporary fall. This estimated model can create additional input to the policymaker’s choice of models
The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men.
A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study.
Gravitational Waves from Gravitational Collapse
Gravitational wave emission from the gravitational collapse of massive stars
has been studied for more than three decades. Current state of the art
numerical investigations of collapse include those that use progenitors with
realistic angular momentum profiles, properly treat microphysics issues,
account for general relativity, and examine non--axisymmetric effects in three
dimensions. Such simulations predict that gravitational waves from various
phenomena associated with gravitational collapse could be detectable with
advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for
publication in Living Reviews in Relativity (http://www.livingreviews.org
Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches
Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
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