5,633 research outputs found
A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli.
Metal limitation is a common situation during infection and can have profound effects on the pathogen's success. In this report, we examine the role of zinc limitation in the expression of a virulence factor in uropathogenic Escherichia coli. The pyelonephritis isolate J96 carries two hlyCABD operons that encode the RTX toxin α-hemolysin. While the coding regions of both operons are largely conserved, the upstream sequences, including the promoters, are unrelated. We show here that the two hlyCABD operons are differently regulated. The hly II operon is efficiently silenced in the presence of zinc and highly expressed when zinc is limited. In contrast, the hly I operon does not respond to zinc limitation. Genetic studies reveal that zinc-responsive regulation of the hly II operon is controlled by the Zur metalloregulatory protein. A Zur binding site was identified in the promoter sequence of the hly II operon, and we observe direct binding of Zur to this promoter region. Moreover, we find that Zur regulation of the hly II operon modulates the ability of E. coli J96 to induce a cytotoxic response in host cell lines in culture. Our report constitutes the first description of the involvement of the zinc-sensing protein Zur in directly modulating the expression of a virulence factor in bacteria
Gauge Field Formulation of Adiabatic Spin Torques
Previous calculation of spin torques for small-amplitude magnetization
dynamics around a uniformly magnetized state [J. Phys. Soc. Jpn. {\bf 75}
(2006) 113706] is extended here to the case of finite-amplitude dynamics. This
is achieved by introducing an `` adiabatic'' spin frame for conduction
electrons, and the associated SU(2) gauge field. In particular, the Gilbert
damping is shown to arise from the time variation of the spin-relaxation source
terms in this new frame, giving a new physical picture of the damping. The
present method will allow a `` first-principle'' derivation of spin torques
without any assumptions such as rotational symmetry in spin space.Comment: 4 pages, 3 figure
Spin Tunneling and Phonon-assisted Relaxation in Mn12-acetate
We present a comprehensive theory of the magnetization relaxation in a
Mn12-acetate crystal in the high-temperature regime (T>1 K), which is based on
phonon-assisted spin tunneling induced by quartic magnetic anisotropy and weak
transverse magnetic fields. The overall relaxation rate as function of the
longitudinal magnetic field is calculated and shown to agree well with
experimental data including all resonance peaks measured so far. The Lorentzian
shape of the resonances, which we obtain via a generalized master equation that
includes spin tunneling, is also in good agreement with recent data. We derive
a general formula for the tunnel splitting energy of these resonances. We show
that fourth-order diagonal terms in the Hamiltonian lead to satellite peaks. A
derivation of the effective linewidth of a resonance peak is given and shown to
agree well with experimental data. In addition, previously unknown spin-phonon
coupling constants are calculated explicitly. The values obtained for these
constants and for the sound velocity are also in good agreement with recent
data. We show that the spin relaxation in Mn12-acetate takes place via several
transition paths of comparable weight. These transition paths are expressed in
terms of intermediate relaxation times, which are calculated and which can be
tested experimentally.Comment: 18 pages, 22 EPS figures, REVTe
WISE/NEOWISE observations of Active Bodies in the Main Belt
We report results based on mid-infrared photometry of 5 active main belt
objects (AMBOs) detected by the Wide-field Infrared Survey Explorer (WISE)
spacecraft. Four of these bodies, P/2010 R2 (La Sagra), 133P/Elst-Pizarro,
(596) Scheila, and 176P/LINEAR, showed no signs of activity at the time of the
observations, allowing the WISE detections to place firm constraints on their
diameters and albedos. Geometric albedos were in the range of a few percent,
and on the order of other measured comet nuclei. P/2010 A2 was observed on
April 2-3, 2010, three months after its peak activity. Photometry of the coma
at 12 and 22 {\mu}m combined with ground-based visible-wavelength measurements
provides constraints on the dust particle mass distribution (PMD), dlogn/dlogm,
yielding power-law slope values of {\alpha} = -0.5 +/- 0.1. This PMD is
considerably more shallow than that found for other comets, in particular
inbound particle fluence during the Stardust encounter of comet 81P/Wild 2. It
is similar to the PMD seen for 9P/Tempel 1 in the immediate aftermath of the
Deep Impact experiment. Upper limits for CO2 & CO production are also provided
for each AMBO and compared with revised production numbers for WISE
observations of 103P/Hartley 2.Comment: 32 Pages, including 5 Figure
The DLV System for Knowledge Representation and Reasoning
This paper presents the DLV system, which is widely considered the
state-of-the-art implementation of disjunctive logic programming, and addresses
several aspects. As for problem solving, we provide a formal definition of its
kernel language, function-free disjunctive logic programs (also known as
disjunctive datalog), extended by weak constraints, which are a powerful tool
to express optimization problems. We then illustrate the usage of DLV as a tool
for knowledge representation and reasoning, describing a new declarative
programming methodology which allows one to encode complex problems (up to
-complete problems) in a declarative fashion. On the foundational
side, we provide a detailed analysis of the computational complexity of the
language of DLV, and by deriving new complexity results we chart a complete
picture of the complexity of this language and important fragments thereof.
Furthermore, we illustrate the general architecture of the DLV system which
has been influenced by these results. As for applications, we overview
application front-ends which have been developed on top of DLV to solve
specific knowledge representation tasks, and we briefly describe the main
international projects investigating the potential of the system for industrial
exploitation. Finally, we report about thorough experimentation and
benchmarking, which has been carried out to assess the efficiency of the
system. The experimental results confirm the solidity of DLV and highlight its
potential for emerging application areas like knowledge management and
information integration.Comment: 56 pages, 9 figures, 6 table
HCI policy and the smart city
While the idea of the ‘Smart City’ has attracted increasing attention from academia, industry, and government this interest has largely had a technical and technological focus. This paper identifies some of the important political and policy challenges facing the idea, the discourse, of a ‘smart city’ as a means to optimise HCI input into the ‘smart city’ debate. It then addresses that gap by detailing a research project that explored how experts in smart city research and development in the UK context responded to this policy challenge. Experts were asked questions regarding their prior experience with the “smart city”, their understandings of what it means for a city to be smart, and what policy potentials they've recognised in the smart city. The paper analyses and offers a synthesis of the responses collected throughout the research with the current policies concerning various smart city proximity, thereby providing a critical assessment of the values underlying the smart city. The paper aims to explore and present some of the policy possibilities for UK smart cities that are potentially useful for politicians, policy makers, planners, academics, and technology companies. I believe that these perspectives for policy development can be used to inform responsible development, spatially and socially inclusive technologies, and ultimately more resilient and liveable cities
Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families
Tourette’s Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein–protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.This study was supported by a grant from the National Institute of Mental Health (R01MH092293 to GAH and JAT) and by a grant from the New Jersey Center for Tourette Syndrome (to GAH and JAT). This study was also supported by grants from the National Institute of Mental Health (K08MH099424 to TVF) and the National Institute for Environmental Health Science (R01 ES021462 for YSK and BLL). PM has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña, and the Jaques and Gloria Gossweiler Foundation. AM has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. AM has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1, and FOR 2698). AJW received a Young Investigator Award from Tourette Association of America. IH declares that all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre
Heterogeneity in reporting on urinary outcome and cure after surgical interventions for stress urinary incontinence in adult neuro-urological patients: A systematic review
Aims: To describe all outcome parameters and definitions of cure used to report on outcome of surgical interventions for stress urinary incontinence (SUI) in neuro-urological (NU) patients. Methods: This systematic review was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The study protocol was registered and published (CRD42016033303; http://www.crd.york.ac.uk/PROSPERO). Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov were systematically searched for relevant publications until February 2017. Result
Transfer Matrices and Partition-Function Zeros for Antiferromagnetic Potts Models. V. Further Results for the Square-Lattice Chromatic Polynomial
We derive some new structural results for the transfer matrix of
square-lattice Potts models with free and cylindrical boundary conditions. In
particular, we obtain explicit closed-form expressions for the dominant (at
large |q|) diagonal entry in the transfer matrix, for arbitrary widths m, as
the solution of a special one-dimensional polymer model. We also obtain the
large-q expansion of the bulk and surface (resp. corner) free energies for the
zero-temperature antiferromagnet (= chromatic polynomial) through order q^{-47}
(resp. q^{-46}). Finally, we compute chromatic roots for strips of widths 9 <=
m <= 12 with free boundary conditions and locate roughly the limiting curves.Comment: 111 pages (LaTeX2e). Includes tex file, three sty files, and 19
Postscript figures. Also included are Mathematica files data_CYL.m and
data_FREE.m. Many changes from version 1: new material on series expansions
and their analysis, and several proofs of previously conjectured results.
Final version to be published in J. Stat. Phy
Inhibition of profibrotic microRNA-21 affects platelets and their releasate.
Fibrosis is a major contributor to organ disease for which no specific therapy is available. MicroRNA-21 (miR-21) has been implicated in the fibrogenetic response, and inhibitors of miR-21 are currently undergoing clinical trials. Here, we explore how miR-21 inhibition may attenuate fibrosis using a proteomics approach. Transfection of miR-21 mimic or inhibitor in murine cardiac fibroblasts revealed limited effects on extracellular matrix (ECM) protein secretion. Similarly, miR-21-null mouse hearts showed an unaltered ECM composition. Thus, we searched for additional explanations as to how miR-21 might regulate fibrosis. In plasma samples from the community-based Bruneck Study, we found a marked correlation of miR-21 levels with several platelet-derived profibrotic factors, including TGF-β1. Pharmacological miR-21 inhibition with an antagomiR reduced the platelet release of TGF-β1 in mice. Mechanistically, Wiskott-Aldrich syndrome protein, a negative regulator of platelet TGF-β1 secretion, was identified as a direct target of miR-21. miR-21-null mice had lower platelet and leukocyte counts compared with littermate controls but higher megakaryocyte numbers in the bone marrow. Thus, to our knowledge this study reports a previously unrecognized effect of miR-21 inhibition on platelets. The effect of antagomiR-21 treatment on platelet TGF-β1 release, in particular, may contribute to the antifibrotic effects of miR-21 inhibitors
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